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Investigation of the Prenatal Expression Patterns of 108 Schizophrenia-Associated Genetic Loci

BIOLOGICAL PSYCHIATRY 2015年第11期77卷 E43-E51页

作者： Birnbaum, Rebecca Jaffe, Andrew E. Chen, Qiang Hyde, Thomas M. Kleinman, Joel E. Weinberger, Daniel R. Johns Hopkins Univ Sch Med Lieber Inst Brain Dev Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Dept Psychiat Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Dept Neurol Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Dept Neurosci Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Inst Med Genet Baltimore MD 21205 USA

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Optimization of an AMBER Force Field for the Artificial Nucleic Acid, LNA, and Benchmarking with NMR of L(CAAU)

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JOURNAL OF PHYSICAL CHEMISTRY B 2014年第5期118卷 1216-1228页

作者： Condon, David E. Yildirim, Ilyas Kennedy, Scott D. Mort, Brendan C. Kierzek, Ryszard Turner, Douglas H. Univ Rochester Dept Chem Rochester NY 14627 USA Northwestern Univ Dept Chem Evanston IL 60208 USA Univ Rochester Dept Biochem & Biophys Rochester NY 14642 USA Univ Rochester Ctr Integrated Res Comp Rochester NY 14627 USA Polish Acad Sci Inst Bioorgan Chem PL-61704 Poznan Poland

Locked Nucleic Acids (LNAs) are RNA analogues with an O2'-C4' methylene bridge which locks the sugar into a C3'-endo conformation. This enhances hybridization to DNA and RNA, making LNAs useful in microarrays and potential therapeutics. Here, the LNA, L(CAAU), provides a simplified benchmark for testing the ability of molecular dynamics (MD) to approximate nucleic acid properties. LNA chi torsions and partial charges were parametrized to create AMBER parm99_LNA. The revisions were tested by comparing MD predictions with AMBER parm99 and parm99_LNA against a 200 ms NOESY NMR spectrum of L(CAAU). NMR indicates an A-Form equilibrium ensemble. In 3000 ns simulations starting with an A-form structure, parm99_LNA and parm99 provide 66% and 35% agreement, respectively, with NMR NOE volumes and (3)J-couplings. In simulations of L(CAAU) starting with all chi torsions in a syn conformation, only parm99_LNA is able to repair the structure. This implies methods for parametrizing force fields for nucleic acid mimics can reasonably approximate key interactions and that parm99_LNA will improve reliability of MD studies for systems with LNA. A method for approximating chi population distribution on the basis of base to sugar NOEs is also introduced.

关键词： NUCLEIC acids NUCLEAR magnetic resonance spectroscopy MOLECULAR force constants METHYLENE group MOLECULAR hybridization microarray technology MATHEMATICAL optimization

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Examining the Interactions of the Splicing Factor MBNL1 with Target RNA Sequences via a Label-Free, Multiplex Method

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ANALYTICAL CHEMISTRY 2014年第2期86卷 1067-1075页

作者： Yadav, Amrita R. Mace, Charles R. Miller, Benjamin L. Univ Rochester Dept Phys & Astron Rochester NY 14627 USA Univ Rochester Dept Biochem & Biophys Rochester NY 14642 USA Univ Rochester Dept Biomed Engn Rochester NY 14642 USA Univ Rochester Dept Dermatol Rochester NY 14642 USA

The near-ubiquity of the involvement of RNA in crucial biological processes is accepted. It is important, therefore, to study and understand the biophysical principles that regulate the function of RNA and its interactions with other molecules (e.g., proteins and antibiotics). Methods enabling the high-throughput determination of RNA-protein binding kinetics and thermodynamics would greatly accelerate understanding of these interactions. To that end, we describe the development of a real-time biomolecular interaction analysis platform based on arrayed imaging reflectometry (AIR) for multiplex analysis of RNA-protein interactions. We demonstrate the use of aqueous AIR by measuring the binding kinetics between muscleblind-like 1 (MBNL1), a splicing regulator protein that plays a pivotal role in the Myotonic Dystrophies and Huntington's Disease, and several of its RNA targets simultaneously on a microarrayed chip. Using this approach, we observe that the kinetics of MBNL1 binding isolated CUG and repeat CUG RNA sequences (as models for "normal" and "pathogenic" RNA, respectively) are different even though their steady state binding constants are similar. The ability to compare binding kinetics between RNA sequences rapidly and easily may provide insight into the molecular basis of MBNL1-RNA binding, and more generally suggests that AIR can be a powerful tool to enable the label-free, real-time analysis of biomolecular interactions in a high-throughput format.

关键词： RNA splicing NUCLEOTIDE sequence PROTEIN binding REFLECTOMETRY microarray technology

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Synergistic effect of carbon microstructure and topography of TiO₂ nanorod arrays on hemocompatibility of carbon/TiO₂ nanorod arrays composites

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JOURNAL OF MATERIALS SCIENCE 2014年第15期49卷 5299-5308页

作者： Chen, Hong-Peng Chen, Hui-Ling Chen, Di-Hu Chen, Min Sun Yat Sen Univ State Key Lab Optoelect Mat & Technol Guangzhou 510275 Guangdong Peoples R China Guangdong Med Coll Sch Informat Engn Dongguan 523808 Peoples R China

This study systematically investigated the synergistic effect of material's surface topography and electronic structure on fibrinogen adsorption and platelet activation. Three kinds of oriented TiO2 nanorod arrays (TNA) were synthesized by the hydrothermal method by changing the growth parameters in order to adjust the surface topography and roughness. The carbon thin films with various sp(3) C contents were deposited onto the top of TNA with the DC magnetic-filtered cathodic vacuum arc deposition. The structure, the surface topography, and the roughness of TNA were characterized by X-ray diffraction, scanning electron microscopy, and atomic force microscopy, respectively. The sp(3) C content in carbon films was estimated using Raman spectroscopy. The results demonstrated that the amount of fibrinogen adsorbed on surface was influenced merely by surface topography and roughness of TNA, but independent of surface carbon coating. In addition, the platelet adhesion decreased significantly with the increase of the sp(3) C content in carbon coating at the same degree of roughness or adsorbed fibrinogen. The lowest platelet adhesion and activation was observed on the specific surface topography associated with the highest sp(3) C content in carbon coating.

关键词： FIBRINOGEN RESEARCH BLOOD platelet activation ADSORPTION (Biology) SURFACE topography microarray technology TITANIUM dioxide CARBON films MICROSTRUCTURE

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Gene Expression Analysis of Murine and Human Osteoarthritis Synovium Reveals Elevation of Transforming Growth Factor β-Responsive Genes in Osteoarthritis-Related Fibrosis

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ARTHRITIS & RHEUMATOLOGY 2014年第3期66卷 647-656页

作者： Remst, D. F. G. Blom, A. B. Vitters, E. L. Bank, R. A. van den Berg, W. B. Davidson, E. N. Blaney van der Kraan, P. M. Radboud Univ Nijmegen Med Ctr NL-6525 GA Nijmegen Netherlands Univ Groningen Univ Med Ctr Groningen NL-9713 AV Groningen Netherlands

Objective. Synovial fibrosis is a major contributor to joint stiffness in osteoarthritis (OA). Transforming growth factor beta (TGF beta), which is elevated in OA, plays a key role in the onset and persistence of synovial fibrosis. However, blocking of TGF beta in OA as a therapeutic intervention for fibrosis is not an option since TGF beta is crucial for cartilage maintenance and repair. Therefore, we undertook the present study to seek targets downstream of TGF beta for preventing OA-related fibrosis without interfering with joint homeostasis. Methods. Experiments were performed to determine whether genes involved in extracellular matrix turnover were responsive to TGF beta and were elevated in OA-related fibrosis. We analyzed gene expression in TGF beta-stimulated human OA synovial fibroblasts and in the synovium of mice with TGF beta-induced fibrosis, mice with experimental OA, and humans with end-stage OA. Gene expression was determined by microarray, low-density array, or quantitative polymerase chain reaction analysis. Results. We observed an increase in expression of procollagen genes and genes encoding collagen crosslinking enzymes under all of the OA-related fibrotic conditions investigated. Comparison of gene expression in TGF beta-stimulated human OA synovial fibroblasts, synovium from mice with experimental OA, and synovium from humans with end-stage OA revealed that the genes PLOD2, LOX, COL1A1, COL5A1, and TIMP1 were up-regulated in all of these conditions. Additionally, we confirmed that these genes were up-regulated by TGF beta in vivo in mice with TGF beta-induced synovial fibrosis. Conclusion. Most of the up-regulated genes identified in this study would be poor targets for therapy development, due to their crucial functions in the joint. However, the highly up-regulated gene PLOD2, responsible for the formation of collagen crosslinks that make collagen less susceptible to enzymatic degradation, is an attractive and promising target for interferen

关键词： ACADEMIC medical centers ANIMAL experimentation IMMUNOHISTOCHEMISTRY MICE OSTEOARTHRITIS POLYMERASE chain reaction FINANCING of research STATISTICS T-test (Statistics) GENOMICS DATA analysis FIBROSIS REVERSE transcriptase polymerase chain reaction DATA analysis software microarray technology GENE expression profiling

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Direction Control of Oriented Self-Assembly for 1D, 2D, and 3D microarrays of Anisotropic Rectangular Nanoblocks

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2014年第10期136卷 3716-3719页

作者： Nakagawa, Yoshitaka Kageyama, Hiroyuki Oaki, Yuya Imai, Hiroaki Keio Univ Fac Sci & Technol Dept Appl Chem Kohoku Ku Yokohama Kanagawa 2238522 Japan

Micrometric linear chains (1D arrays), monolayers (2D arrays), and superstructures (3D arrays) of anisotropic Mn3O4 nanocuboids were selectively produced by oriented self-assembly through evaporation of a dispersion. The ID arrays were basically formed on a substrate via oriented self-assembly of the rectangular crystals in the < 100 > direction. The 2D and 3D microarrays were obtained by adjusting the particle concentration of the dispersion. The [001] direction of tetragonal crystal was controlled to be parallel and perpendicular to the substrate by changing the polarity of the medium.

关键词： MOLECULAR self-assembly ANISOTROPIC crystals DISPERSION (Atmospheric chemistry) PARTICLE concentration (Atmospheric chemistry) MANGANESE RESEARCH MAGNETIC anisotropy microarray technology

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Alignment, Morphology and Defect Control of Vertically Aligned ZnO Nanorod Array: Competition between "Surfactant" and "Stabilizer" Roles of the Amine Species and Its Photocatalytic Properties

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CRYSTAL GROWTH & DESIGN 2014年第6期14卷 2873-2879页

作者： Ranjith, Kugalur Shanmugam Pandian, Ramanathaswamy McGlynn, Enda Kumar, Ramasamy Thangavelu Rajendra Bharathiar Univ Dept Phys Adv Mat & Devices Lab Coimbatore 641046 Tamil Nadu India Indira Gandhi Ctr Atom Res Surface & Nanosci Div Mat Sci Grp Kalpakkam 603102 Tamil Nadu India Dublin City Univ Sch Phys Sci Natl Ctr Plasma Sci & Technol Dublin 9 Ireland Bharathiar Univ Dept Nanosci & Technol Coimbatore 641046 Tamil Nadu India

We demonstrate effective control of the morphology, defect content and vertical alignment of ZnO nanorod (NR) arrays grown by a solution method by simply varying the hexarnine concentration during growth. We show that the amine acts both as a growth 'stabilizer' and 'surfactant' and controls both Zn release for ZnO formation and caps non-polar planes, respectively. Competition between these 'stabilizer' and 'surfactant' roles facilitates morphology, alignment and defect content control of 1D ZnO NR arrays. Well aligned, prismatic, defect (Zn interstitial) controlled ZnO NR arrays grown with a 1M amine concentration show higher photocatalytic degradation of Methylene Blue dye solutions under UV irradiation. Shallow donor zinc interstitials readily supply electrons which may increase the space charge near the nano-catalyst surface. The increased band bending associated with the interfacial electric field in the space charge region photogenerated carriers and thus enhance the photocatalytic performance. Understanding 1D ZnO NR arrays holds great promise for tailoring ZnO NR functionalities for various may then better facilitate the separation of the role of amine in the solution growth of potential applications.

关键词： CRYSTAL morphology ZINC oxide NANORODS microarray technology SURFACE active agents AMINES PHOTOCATALYSIS

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Deciphering the Regulon of Streptomyces coelicolor AbrC3, a Positive Response Regulator of Antibiotic Production

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APPLIED AND ENVIRONMENTAL MICROBIOLOGY 2014年第8期80卷 2417-2428页

作者： Rico, Sergio Santamaria, Ramon I. Yepes, Ana Rodriguez, Hector Laing, Emma Bucca, Giselda Smith, Colin P. Diaz, Margarita Univ Salamanca CSIC Dept Genet & Microbiol IBFG E-37008 Salamanca Spain Univ Wurzburg IMIB D-97070 Wurzburg Germany Univ Surrey Fac Hlth & Med Sci Dept Microbial & Cellular Sci Guildford GU2 5XH Surrey England

The atypical two-component system (TCS) AbrC1/C2/C3 (encoded by SCO4598, SCO4597, and SCO4596), comprising two histidine kinases (HKs) and a response regulator (RR), is crucial for antibiotic production in Streptomyces coelicolor and for morphological differentiation under certain nutritional conditions. In this study, we demonstrate that deletion of the RR-encoding gene, abrC3 (SCO4596), results in a dramatic decrease in actinorhodin (ACT) and undecylprodiginine (RED) production and delays morphological development. In contrast, the overexpression of abrC3 in the parent strain leads to a 33% increase in ACT production in liquid medium. Transcriptomic analysis and chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis of the Delta abrC3 mutant and the parent strain revealed that AbrC3 directly controls ACT production by binding to the actII-ORF4 promoter region;this was independently verified by in vitro DNA-binding assays. This binding is dependent on the sequence 5'-GAASGSGRMS-3'. In contrast, the regulation of RED production is not due to direct binding of AbrC3 to either the redZ or redD promoter region. This study also revealed other members of the AbrC3 regulon: AbrC3 is a positive autoregulator which also binds to the promoter regions of SCO0736, bdtA (SCO3328), absR1 (SCO6992), and SCO6809. The direct targets share the 10-base consensus binding sequence and may be responsible for some of the phenotypes of the Delta abrC3 mutant. The identification of the AbrC3 regulon as part of the complex regulatory network governing antibiotic production widens our knowledge regarding TCS involvement in control of antibiotic synthesis and may contribute to the rational design of new hyperproducer host strains through genetic manipulation of such systems.

关键词： REGULONS STREPTOMYCES coelicolor ACTINORHODIN DNA-binding proteins microarray technology

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Overview of research on Bombyx mori microRNA

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JOURNAL OF INSECT SCIENCE 2014年第Paper133期14卷 1-13页

作者： Wang, Xin Tang, Shun-ming Shen, Xing-jia Jiangsu Univ Sci & Technol Minist Agr Key Lab Silkworm & Mulberry Genet Improvement Zhenjiang City 212018 Jiangsu Peoples R China

MicroRNAs (miRNAs) constitute some of the most significant regulatory factors involved at the post-transcriptional level after gene expression, contributing to the modulation of a large number of physiological processes such as development, metabolism, and disease occurrence. This review comprehensively and retrospectively explores the literature investigating silkworm, Bombyx mori L. (Lepidoptera: Bombicidae), miRNAs published to date, including discovery, identification, expression profiling analysis, target gene prediction, and the functional analysis of both miRNAs and their targets. It may provide experimental considerations and approaches for future study of miRNAs and benefit elucidation of the mechanisms of miRNAs involved in silkworm developmental processes and intracellular activities of other unknown non-coding RNAs.

关键词： expression profiling analysis microarray technology prediction review silkworm target gene

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The ABC Transporter ABCG1 Is Required for Suberin Formation in Potato Tuber Periderm

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PLANT CELL 2014年第8期26卷 3403-3415页

作者： Landgraf, Ramona Smolka, Ulrike Altmann, Simone Eschen-Lippold, Lennart Senning, Melanie Sonnewald, Sophia Weigel, Benjamin Frolova, Nadezhda Strehmel, Nadine Hause, Gerd Scheel, Dierk Boettcher, Christoph Rosahl, Sabine Leibniz Inst Plant Biochem Dept Stress & Dev Biol D-06120 Halle Saale Germany Univ Erlangen Nurnberg Dept Biol D-91058 Erlangen Germany Leibniz Inst Plant Biochem Dept Bioorgan Chem D-06120 Halle Saale Germany Univ Halle Wittenberg Bioctr D-06120 Halle Saale Germany

The lipid biopolymer suberin plays a major role as a barrier both at plant-environment interfaces and in internal tissues, restricting water and nutrient transport. In potato (Solanum tuberosum), tuber integrity is dependent on suberized periderm. Using microarray analyses, we identified ABCG1, encoding an ABC transporter, as a gene responsive to the pathogen-associated molecular pattern Pep-13. Further analyses revealed that ABCG1 is expressed in roots and tuber periderm, as well as in wounded leaves. Transgenic ABCG1-RNAi potato plants with downregulated expression of ABCG1 display major alterations in both root and tuber morphology, whereas the aerial part of the ABCG1-RNAi plants appear normal. The tuber periderm and root exodermis show reduced suberin staining and disorganized cell layers. Metabolite analyses revealed reduction of esterified suberin components and hyperaccumulation of putative suberin precursors in the tuber periderm of RNA interference plants, suggesting that ABCG1 is required for the export of suberin components.

关键词： SUBERIN PERIDERMIUM POTATO tuberworm POTATO diseases & pests ATP-binding cassette transporters GENE expression in plants PLANT genetics microarray technology

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