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Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing

THROMBOSIS AND HAEMOSTASIS 2014年第5期112卷 992-1001页

作者： Lopez, Mercedes L. Bruges, Gustavo Crespo, Gustavo Salazar, Victor Deglesne, Pierre-Antoine Schneider, Heike Cabrera-Fuentes, Hector Schmitz, M. Lienhard Preissner, Klaus T. Inst Venezolano Invest Cient Ctr Biofis & Bioquim Caracas 1020A Venezuela Univ Giessen Inst Biochem Fac Med D-35390 Giessen Germany Hannover Med Sch Inst Biochem Hannover Germany Kazan Fed Univ Inst Fundamental Med & Biol Kazan Russia

Thrombin is essential for blood coagulation but functions also as a mediator of cellular signalling. Gene expression microarray experiments in human monocytes revealed thrombin-induced upregulation of a limited subset of genes, which are almost exclusively involved in inflammation and wound healing. Among these, the expression of F3 gene encoding for tissue factor (TF) was enhanced indicating that this physiological initiator of coagulation cascade may create a feed-forward loop to enhance blood coagulation. Activation of protease-activated receptor type 1 (PAR1) was shown to play a main role in promoting TF expression. Moreover, thrombin induced phosphorylation of ERK1/2, an event that is required for expression of thrombin-regulated genes. Thrombin also increased the expression of TF at the protein level in monocytes as evidenced by Western blot and immunostaining. Furthermore, FXa generation induced by thrombin-stimulated monocytes was abolished by a TF blocking antibody and therefore it is entirely attributable to the expression of tissue factor. This cellular activity of thrombin provides a new molecular link between coagulation, inflammation and wound healing.

关键词： Thrombin inflammation microarray technology gene expression mitogen-activated protein kinases tissue factor protease-activated receptor

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Global Molecular Effects of Tocilizumab Therapy in Rheumatoid Arthritis Synovium

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ARTHRITIS & RHEUMATOLOGY 2014年第1期66卷 15-23页

作者： Ducreux, Julie Durez, Patrick Galant, Christine Toukap, Adrien Nzeusseu Van den Eynde, Benoit Houssiau, Frederic A. Lauwerys, Bernard R. Catholic Univ Louvain B-1200 Brussels Belgium Clin Univ St Luc Brussels Belgium Ludwig Inst Canc Res Brussels Belgium de Duve Inst Brussels Belgium

Objective. To investigate the global molecular effects of tocilizumab (TCZ) in comparison with methotrexate (MTX) treatment in synovial biopsy tissue obtained from patients with previously untreated rheumatoid arthritis (RA) before therapy (T0) and 12 weeks after the initiation of therapy (T12), and to compare the results with previous gene expression data obtained in synovial biopsy tissue from adalimumab (ADA)- and rituximab (RTX)-treated patients with RA. Methods. Paired synovial biopsy samples were obtained at T0 and T12 from the affected knee of TCZ-treated RA patients and MTX-treated RA patients. Gene expression studies were performed using GeneChip Human Genome U133 Plus 2.0 microarrays, and confirmatory quantitative real-time reverse transcription-polymerase chain reaction experiments were performed on selected transcripts. The effects of TCZ and MTX on synovial cell populations and histologic characteristics were assessed by immunohistochemistry. Results. Gene expression studies showed that blockade of the interleukin-6 receptor (IL-6R) gene (IL6R) using TCZ induced a significant decrease in the expression of numerous chemokine and T cell activation genes in the RA synovium. These effects strongly correlated with the molecular effects of MTX and RTX therapy on RA synovial tissue, but differed from the molecular changes induced by ADA (decreased expression of genes involved in cell proliferation). Conclusion. The molecular similarities between the effects of TCZ, RTX, and MTX therapies in the RA synovium indicate that B cell-and IL-6-dependent pathways play synergistic roles in the pathogenesis of the disease, in particular through activation of T cell responses. Moreover, these results open perspectives for the individualization of therapeutic decisions, based on a better knowledge of the synovial molecular effects of each type of RA therapy.

关键词： METHOTREXATE THERAPEUTIC use of monoclonal antibodies ACADEMIC medical centers BIOPSY IMMUNOHISTOCHEMISTRY LONGITUDINAL method MONOCLONAL antibodies POLYMERASE chain reaction FINANCING of research RHEUMATOID arthritis STATISTICS T-test (Statistics) GENOMICS DATA analysis REVERSE transcriptase polymerase chain reaction DATA analysis software microarray technology INDIVIDUALIZED medicine DESCRIPTIVE statistics THERAPEUTIC use

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BicOverlapper 2.0: visual analysis for gene expression

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BIOINFORMATICS 2014年第12期30卷 1785-1786页

作者： Santamaria, Rodrigo Theron, Roberto Quintales, Luis Univ Salamanca Dept Comp Sci E-37008 Salamanca Spain CSIC USAL Inst Biol Func & Genom Salamanca 37007 Spain

Motivation: Systems biology demands the use of several point of views to get a more comprehensive understanding of biological problems. This usually leads to take into account different data regarding the problem at hand, but it also has to do with using different perspectives of the same data. This multifaceted aspect of systems biology often requires the use of several tools, and it is often hard to get a seamless integration of all of them, which would help the analyst to have an interactive discourse with the data. Results: Focusing on expression profiling, BicOverlapper 2.0 visualizes the most relevant aspects of the analysis, including expression data, profiling analysis results and functional annotation. It also integrates several state-of-the-art numerical methods, such as differential expression analysis, gene set enrichment or biclustering.

关键词： SYSTEMS biology GENE expression profiling COMPUTER algorithms ACQUISITION of data microarray technology

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ARTS: automated randomization of multiple traits for study design

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BIOINFORMATICS 2014年第11期30卷 1637-1639页

作者： Maienschein-Cline, Mark Lei, Zhengdeng Gardeux, Vincent Abbasi, Taimur Machado, Roberto F. Gordeuk, Victor Desai, Ankit A. Saraf, Santosh Bahroos, Neil Lussier, Yves Univ Illinois Inst Intervent Hlth Informat Ctr Res Informat Chicago IL 60612 USA Univ Illinois Dept Med Chicago IL USA Univ Illinois Dept Bioengn Chicago IL USA Univ Illinois Computat Inst Chicago IL USA Univ Illinois Argonne Natl Lab Lemont IL USA

Collecting data from large studies on high-throughput platforms, such as microarray or next-generation sequencing, typically requires processing samples in batches. There are often systematic but unpredictable biases from batch-to-batch, so proper randomization of biologically relevant traits across batches is crucial for distinguishing true biological differences from experimental artifacts. When a large number of traits are biologically relevant, as is common for clinical studies of patients with varying sex, age, genotype and medical background, proper randomization can be extremely difficult to prepare by hand, especially because traits may affect biological inferences, such as differential expression, in a combinatorial manner. Here we present ARTS (automated randomization of multiple traits for study design), which aids researchers in study design by automatically optimizing batch assignment for any number of samples, any number of traits and any batch size.

关键词： COMPUTATIONAL biology INFORMATION networks RANDOMIZATION (Statistics) HIGH throughput screening (Drug development) microarray technology GENE expression

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Advances in identification and validation of plant microRNAs and their target genes

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PHYSIOLOGIA PLANTARUM 2014年第2期152卷 203-218页

作者： Sun, Xin Zhang, Yanping Zhu, Xudong Korir, Nicholas Kibet Tao, Ran Wang, Chen Fang, Jinggui Nanjing Agr Univ Coll Hort Nanjing 210095 Jiangsu Peoples R China

Developments in the field of molecular biology and genetics, such as microarray, gene transfer and discovery of small regulatory RNAs, have led to significant advances in plant biotechnology. Among the small RNAs, microRNAs (miRNAs) have elicited much interest as key post-transcriptional regulators in eukaryotic gene expression. Advances in genome and transcriptome sequencing of plants have facilitated the generation of a huge wealth of sequence information that can find much use in the discovery of novel miRNAs and their target genes. In this review, we present an overview of the developments in the strategies and methods used to identify and study miRNAs, their target genes and the mechanisms by which these miRNAs interact with their target genes since the discovery of the first miRNA. The approaches discussed include both reverse and forward genetics. We observed that despite the availability of advanced methods, certain limitations ranging from the cost of materials, equipment and personnel to the availability of genome sequences for many plant species present a number of challenges for the development and utilization of modern scientific methods for the elucidation and development of miRNAs in many important plant species.

关键词： MOLECULAR biology microarray technology GENETIC transformation PLANT biotechnology MICRORNA genetics PLANT species

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Cryptic chromosome abnormalities in a patient with mixed phenotype acute leukemia

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LEUKEMIA & LYMPHOMA 2014年第3期55卷 680-682页

作者： Ning, Yi Slovak, Marilyn L. Schultz, Roger A. Gojo, Ivana Baer, Maria R. Johns Hopkins Univ Dept Pathol Baltimore MD 21287 USA Sonora Quest Labs Palo Verde Lab Tempe AZ USA PerkinElmer Inc Signature Genom Labs Spokane WA USA Johns Hopkins Med Sidney Kimmel Comprehens Canc Ctr Baltimore MD USA Univ Maryland Sch Med Dept Med Baltimore MD 21201 USA Univ Maryland Sch Med Greenebaum Canc Ctr Baltimore MD 21201 USA

The article presents a case study of a 75-year-old man who was diagnosed with T-lymphoblastic leukemia. It states that the use of giemsa banding-based karyotype analysis of a bone marrow sample found a 7q deletion and submicroscopic deletions in 4q including the genes TET2, CENPE, and NFKB1. It mentions that the TET2 gene is believed to be a tumor suppressor gene while the 7q deletion was an interstitial deletion. It comments on the benefits of combining microarray analysis with karyotyping.

关键词： LYMPHOBLASTIC leukemia KARYOTYPES BONE marrow DELETION mutation ANTIONCOGENES GENES microarray technology

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In Vitro Effects of Extracts of Extra Virgin Olive Oil on Human Colon Cancer Cells

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NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL 2014年第7期66卷 1228-1236页

作者： Pampaloni, Barbara Mavilia, Carmelo Fabbri, Sergio Romani, Annalisa Ieri, Francesca Tanini, Annalisa Tonelli, Francesco Brandi, Maria Luisa Univ Florence Dept Surg & Translat Med I-50139 Florence Italy Univ Florence DISIA Dept Stat PHYTOLAB I-50139 Florence Italy

The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular diseases, and some types of cancer. Recent interest has been focused on the biological activity of phenolic compounds present in extra virgin olive oils (EVOOs). Both in vivo and in vitro studies have shown that EVOO components have positive effects on metabolic parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet function, and antimicrobial activity. We have investigated the possible interactions between 2 extracts of extra virgin olive oil and estrogen receptor beta (ER beta) in an in vitro model of colon cancer. The qualification and quantification of the components of the 2 samples tested showed that phenolic compounds-hydroxytyrosol, secoiridoids, and lignans-are the major represented compounds. EVOO extracts were tested on a colon cancer cell line engineered to overexpress ER beta (HCT8-beta 8). By using custom made Oligo microarray, gene expression profiles of colon cancer cells challenged with EVOO-T extracts when compared with those of cells exposed to 17 beta-estradiol (17 beta-E2). This study demonstrated that the EVOO extracts tested showed an antiproliferative effect on colon cancer cells through the interaction with estrogen-dependent signals involved in tumor cell growth. Specifically, the ability of EVOO extracts to inhibit cell proliferation was superimposable to the activation of the ER beta receptor, similar to what was observed after 17 beta-E2 challenge.

关键词： OLIVE RNA physiology THERAPEUTIC use of olive oil COLON tumors PREVENTION ACADEMIC medical centers BIOLOGICAL assay CELL culture CELL physiology NUTRITION PHENOLS PLANT extracts DATA analysis microarray technology DESCRIPTIVE statistics IN vitro studies THERAPEUTIC use

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Taking striping up a notch

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PIGMENT CELL & MELANOMA RESEARCH 2014年第5期27卷 688-689页

作者： Goda, Makoto Kelsh, Robert N. Hashimoto, Hisashi

The article provides an analysis of several research works done to identify molecular basis for pigment pattern formation in animals. Topics discussed include use of reaction-diffusion system, use of microarray analysis to reveal mediators between xanthophores and melanophores and tests to reveal melanophore survival related to Delta?Notch signal. It mentions the role played by xanthophores in promoting melanophore survival.

关键词： ANIMAL coloration RESEARCH REACTION-diffusion equations microarray technology XANTHOPHORES MELANOPHORES

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Recording From Over 1,000 Cells: A New Toy in Place for Epilepsy Research?

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EPILEPSY CURRENTS 2014年第2期14卷 95-96页

作者： Stacey, William

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Putting things in order

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2014年第46期111卷 16236-16237页

作者： Sun, Ning Zhao, Hongyu Yale Univ Sch Publ Hlth Dept Biostat New Haven CT 06520 USA

The author discusses the study which identifies gene pairs with correlated expression patterns from high-throughput microarray data. The author believes that the study provides great computational efficiency and elegant results in incorporating dependencies in statistical inference, and under two specific alternative hypotheses. He adds that the proposed measures in the study can be extended to increase power against other and to consider the inference of conditional independence.

关键词： INFERENTIAL statistics RESEARCH methodology GENE expression GENETIC research NUMERICAL calculations microarray technology

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