Author: "David Pot" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"David Pot"' showing total 30 results

Start Over Author "David Pot" Topic medicine

30 results on '"David Pot"'

1. SL-Cloud: A Cloud-based resource to support synthetic lethal interaction discovery [version 2; peer review: 2 approved]

Author: William Longabaugh, John Phan, Christopher J. Kemp, David Pot, Guangrong Qin, Bahar Tercan, Boris Aguilar, Taek-Kyun Kim, Ilya Shmulevich, and Nyasha Chambwe
Subjects: synthetic lethality, cloud computing, cancer genomics, cancer dependency, systems biology, functional genomics, eng, Medicine, Science
Abstract: Synthetic lethal interactions (SLIs), genetic interactions in which the simultaneous inactivation of two genes leads to a lethal phenotype, are promising targets for therapeutic intervention in cancer, as exemplified by the recent success of PARP inhibitors in treating BRCA1/2-deficient tumors. We present SL-Cloud, a new component of the Institute for Systems Biology Cancer Gateway in the Cloud (ISB-CGC), that provides an integrated framework of cloud-hosted data resources and curated workflows to enable facile prediction of SLIs. This resource addresses two main challenges related to SLI inference: the need to wrangle and preprocess large multi-omic datasets and the availability of multiple comparable prediction approaches. SL-Cloud enables customizable computational inference of SLIs and testing of prediction approaches across multiple datasets. We anticipate that cancer researchers will find utility in this tool for discovery of SLIs to support further investigation into potential drug targets for anticancer therapies.
Published: 2022
Full Text: View/download PDF

2. Domestication reduces alternative splicing expression variations in sorghum.

Author: Vincent Ranwez, Audrey Serra, David Pot, and Nathalie Chantret
Subjects: Medicine, Science
Abstract: Domestication is known to strongly reduce genomic diversity through population bottlenecks. The resulting loss of polymorphism has been thoroughly documented in numerous cultivated species. Here we investigate the impact of domestication on the diversity of alternative transcript expressions using RNAseq data obtained on cultivated and wild sorghum accessions (ten accessions for each pool). In that aim, we focus on genes expressing two isoforms in sorghum and estimate the ratio between expression levels of those isoforms in each accession. Noticeably, for a given gene, one isoform can either be overexpressed or underexpressed in some wild accessions, whereas in the cultivated accessions, the balance between the two isoforms of the same gene appears to be much more homogenous. Indeed, we observe in sorghum significantly more variation in isoform expression balance among wild accessions than among domesticated accessions. The possibility exists that the loss of nucleotide diversity due to domestication could affect regulatory elements, controlling transcription or degradation of these isoforms. Impact on the isoform expression balance is discussed. As far as we know, this is the first time that the impact of domestication on transcript isoform balance has been studied at the genomic scale. This could pave the way towards the identification of key domestication genes with finely tuned isoform expressions in domesticated accessions while being highly variable in their wild relatives.
Published: 2017
Full Text: View/download PDF

3. Transcriptome Analysis of Leaves, Flowers and Fruits Perisperm of Coffea arabica L. Reveals the Differential Expression of Genes Involved in Raffinose Biosynthesis.

Author: Suzana Tiemi Ivamoto, Osvaldo Reis, Douglas Silva Domingues, Tiago Benedito Dos Santos, Fernanda Freitas de Oliveira, David Pot, Thierry Leroy, Luiz Gonzaga Esteves Vieira, Marcelo Falsarella Carazzolle, Gonçalo Amarante Guimarães Pereira, and Luiz Filipe Protasio Pereira
Subjects: Medicine, Science
Abstract: Coffea arabica L. is an important crop in several developing countries. Despite its economic importance, minimal transcriptome data are available for fruit tissues, especially during fruit development where several compounds related to coffee quality are produced. To understand the molecular aspects related to coffee fruit and grain development, we report a large-scale transcriptome analysis of leaf, flower and perisperm fruit tissue development. Illumina sequencing yielded 41,881,572 high-quality filtered reads. De novo assembly generated 65,364 unigenes with an average length of 1,264 bp. A total of 24,548 unigenes were annotated as protein coding genes, including 12,560 full-length sequences. In the annotation process, we identified nine candidate genes related to the biosynthesis of raffinose family oligossacarides (RFOs). These sugars confer osmoprotection and are accumulated during initial fruit development. Four genes from this pathway had their transcriptional pattern validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, we identified ~24,000 putative target sites for microRNAs (miRNAs) and 134 putative transcriptionally active transposable elements (TE) sequences in our dataset. This C. arabica transcriptomic atlas provides an important step for identifying candidate genes related to several coffee metabolic pathways, especially those related to fruit chemical composition and therefore beverage quality. Our results are the starting point for enhancing our knowledge about the coffee genes that are transcribed during the flowering and initial fruit development stages.
Published: 2017
Full Text: View/download PDF

4. Genetic structure, linkage disequilibrium and signature of selection in Sorghum: lessons from physically anchored DArT markers.

Author: Sophie Bouchet, David Pot, Monique Deu, Jean-François Rami, Claire Billot, Xavier Perrier, Ronan Rivallan, Laëtitia Gardes, Ling Xia, Peter Wenzl, Andrzej Kilian, and Jean-Christophe Glaszmann
Subjects: Medicine, Science
Abstract: Population structure, extent of linkage disequilibrium (LD) as well as signatures of selection were investigated in sorghum using a core sample representative of worldwide diversity. A total of 177 accessions were genotyped with 1122 informative physically anchored DArT markers. The properties of DArTs to describe sorghum genetic structure were compared to those of SSRs and of previously published RFLP markers. Model-based (STRUCTURE software) and Neighbor-Joining diversity analyses led to the identification of 6 groups and confirmed previous evolutionary hypotheses. Results were globally consistent between the different marker systems. However, DArTs appeared more robust in terms of data resolution and bayesian group assignment. Whole genome linkage disequilibrium as measured by mean r(2) decreased from 0.18 (between 0 to 10 kb) to 0.03 (between 100 kb to 1 Mb), stabilizing at 0.03 after 1 Mb. Effects on LD estimations of sample size and genetic structure were tested using i. random sampling, ii. the Maximum Length SubTree algorithm (MLST), and iii. structure groups. Optimizing population composition by the MLST reduced the biases in small samples and seemed to be an efficient way of selecting samples to make the best use of LD as a genome mapping approach in structured populations. These results also suggested that more than 100,000 markers may be required to perform genome-wide association studies in collections covering worldwide sorghum diversity. Analysis of DArT markers differentiation between the identified genetic groups pointed out outlier loci potentially linked to genes controlling traits of interest, including disease resistance genes for which evidence of selection had already been reported. In addition, evidence of selection near a homologous locus of FAR1 concurred with sorghum phenotypic diversity for sensitivity to photoperiod.
Published: 2012
Full Text: View/download PDF

5. NCI Imaging Data Commons

Author: Andriy Fedorov, Todd Pihl, Markus D. Herrmann, Robert F. Lewis, David A. Clunie, Keyvan Farahani, Hugo J.W.L. Aerts, Steve Pieper, André Homeyer, Ulrike Wagner, William J.R. Longabaugh, David Pot, and Ron Kikinis
Subjects: Cancer Research, Radiation, Information retrieval, business.industry, Interface (computing), Cloud computing, Visualization, Metadata, DICOM, Annotation, Documentation, Oncology, DICOMweb, Medicine, Radiology, Nuclear Medicine and imaging, skin and connective tissue diseases, business
Abstract: Purpose/Objective(s) National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a cloud-based data science infrastructure. Imaging Data Commons (IDC) is a component of CRDC supported by the Cancer Moonshot™, which aims to enable access and exploration of de-identified imaging data, and to support integrated analyses with non-imaging data. IDC will interoperate with other components of CRDC, which include repositories of other types of data, such as genomics and proteomics repositories, and computational resources to perform analysis of the data. IDC builds on the strengths of the established efforts such as The Cancer Imaging Archive (TCIA) to collect and share FAIR (Findable Accessible Interoperable Reusable) imaging data. Materials/Methods IDC uses a combination of commercially available tools and capabilities provided by Google Cloud Platform (GCP) together with a range of open-source components. While the initial focus is to support clinical radiology and radiotherapy data, IDC aims to provide similar capabilities for brightfield microscopy, multi-channel immunofluorescence and other imaging modalities. Equally important is the ability to support the results of imaging data analysis, such as annotations of regions of interest in the images or various descriptors of image findings. The IDC search portal provides an interface for exploring the data, defining cohorts, and summarizing attributes of the cohort. Images can be viewed in the integrated browser-based viewer, which uses DICOMweb to access the IDC data. IDC data is public and contains no Protected Health Information (PHI). As CDRC grows, imaging datasets will be increasingly cross-linked to genomic, proteomic, and clinical data about the subjects. Results The pilot of IDC was released in October 2020, including 28 collections of the TCIA: radiology images related to The Cancer Genome Atlas (TCGA) project, and several collections prioritized to establish the capabilities of IDC in handling image-derived data. DICOM and collection-level metadata is available from the BigQuery tables, and does not require a project configured with billing. The IDC portal is available at https://portal.imagingdatacommons.cancer.gov, and integrates a customized web viewer that supports visualization of both the images and image annotations (specifically, visualization of DICOM Segmentation and Radiotherapy Structure Set is supported, including multiplanar reformatting). IDC also provides documentation and a user forum. Conclusion The IDC pilot available to the cancer research community explores the promise of cloud-hosted public imaging collections co-located with the compute resources and a growing number of tools to support data analysis. Production release of IDC is planned for Fall 2021, and will include all of the public TCIA collections, including those that contain imaging and annotation data from radiotherapy studies and clinical trials.
Published: 2021

6. Diterpenes biochemical profile and transcriptional analysis of cytochrome P450s genes in leaves, roots, flowers, and during Coffea arabica L. fruit development

Author: Thierry Leroy, David Pot, Luiz Filipe Protasio Pereira, Douglas Silva Domingues, Maria Brígida dos Santos Scholz, Leonardo M. Sakuray, Suzana Tiemi Ivamoto, Cíntia Sorane Good Kitzberger, Luiz Gonzaga Esteves Vieira, Lucia Pires Ferreira, Laboratório de Biotecnologia Vegetal, Universidade Estadual de Londrina (UEL), Laboratório de Ecofisiologia Vegetal, UMR AGAP, Universidade do Oeste Paulista (UNOESTE), Universidade Estadual Paulista (Unesp), and Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA)
Subjects: 0106 biological sciences, 0301 basic medicine, Transcription, Genetic, Physiology, Biosynthèse, Cafestol, Kahweol, Fleur, Coffea, Plant Science, Plant Roots, Coffee, 01 natural sciences, Tissu végétal, F30 - Génétique et amélioration des plantes, chemistry.chemical_compound, Cytochrome P-450 Enzyme System, Gene Expression Regulation, Plant, Gene expression, Plant defense against herbivory, Diterpénoïde, Expression des gènes, Chromatography, High Pressure Liquid, Plant Proteins, biology, food and beverages, Feuille, Coffea arabica, Composition chimique, PCR, Diterpenes, medicine.drug, Développement biologique, F60 - Physiologie et biochimie végétale, Flowers, Genes, Plant, 03 medical and health sciences, Botany, Genetics, medicine, Q04 - Composition des produits alimentaires, Genetic Association Studies, Aroma, RT-qPCR, Cytochrome P450, biology.organism_classification, Plant Leaves, 030104 developmental biology, chemistry, Fruit, biology.protein, Diterpene, U30 - Méthodes de recherche, HPLC, 010606 plant biology & botany, Racine
Abstract: Made available in DSpace on 2018-12-11T16:45:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-02-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Lipids are among the major chemical compounds present in coffee beans, and they affect the flavor and aroma of the coffee beverage. Coffee oil is rich in kaurene diterpene compounds, mainly cafestol (CAF) and kahweol (KAH), which are related to plant defense mechanisms and to nutraceutical and sensorial beverage characteristics. Despite their importance, the final steps of coffee diterpenes biosynthesis remain unknown. To understand the molecular basis of coffee diterpenes biosynthesis, we report the content dynamics of CAF and KAH in several Coffea arabica tissues and the transcriptional analysis of cytochrome P450 genes (P450). We measured CAF and KAH concentrations in leaves, roots, flower buds, flowers and fruit tissues at seven developmental stages (30–240 days after flowering - DAF) using HPLC. Higher CAF levels were detected in flower buds and flowers when compared to fruits. In contrast, KAH concentration increased along fruit development, peaking at 120 DAF. We did not detect CAF or KAH in leaves, and higher amounts of KAH than CAF were detected in roots. Using P450 candidate genes from a coffee EST database, we performed RT-qPCR transcriptional analysis of leaves, flowers and fruits at three developmental stages (90, 120 and 150 DAF). Three P450 genes (CaCYP76C4, CaCYP82C2 and CaCYP74A1) had transcriptional patterns similar to CAF concentration and two P450 genes (CaCYP71A25 and CaCYP701A3) have transcript accumulation similar to KAH concentration. These data warrant further investigation of these P450s as potential candidate genes involved in the final stages of the CAF and KAH biosynthetic pathways. Instituto Agronômico do Paraná (IAPAR) Laboratório de Biotecnologia Vegetal, CP 481 Universidade Estadual de Londrina (UEL), CP 6001 Instituto Agronômico do Paraná (IAPAR) Laboratório de Ecofisiologia Vegetal, CP 481 Centre de Coopération Internationale en Recherche Agronomique Pour le Développement (CIRAD) UMR AGAP Universidade do Oeste Paulista (UNOESTE), Rodovia Raposo Tavares, Km 572 Universidade Estadual Paulista (UNESP) Instituto de Biociências de Rio Claro, Avenida 24-A, 1515 Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA Café) Universidade Estadual Paulista (UNESP) Instituto de Biociências de Rio Claro, Avenida 24-A, 1515
Published: 2017

7. Catechol-O-methyl transferase suppresses cell invasion and interplays with MET signaling in estrogen dependent breast cancer

Author: Lucia Janacova, Michaela Stenckova, Petr Lapcik, Sarka Hrachovinova, Pavla Bouchalova, David Potesil, Roman Hrstka, Petr Müller, and Pavel Bouchal
Subjects: Medicine, Science
Abstract: Abstract Catechol-O-methyl transferase (COMT) is involved in detoxification of catechol estrogens, playing cancer-protective role in cells producing or utilizing estrogen. Moreover, COMT suppressed migration potential of breast cancer (BC) cells. To delineate COMT role in metastasis of estrogen receptor (ER) dependent BC, we investigated the effect of COMT overexpression on invasion, transcriptome, proteome and interactome of MCF7 cells, a luminal A BC model, stably transduced with lentiviral vector carrying COMT gene (MCF7-COMT). 2D and 3D assays revealed that COMT overexpression associates with decreased cell invasion (p 1, adj. p 0.58, q
Published: 2023
Full Text: View/download PDF

8. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

Author: Kelinda Tucker, Raju Kucherlapati, Ng Sam, John N. Weinstein, Lori Boice, Satish K. Tickoo, Saianand Balu, John C. Cheville, B. Arman Aksoy, Chip Stewart, Preethi H. Gunaratne, Martin L. Ferguson, Bogdan Czerniak, Christie Kovar, Theodore C. Goldstein, Mark E. Sherman, Juan M. Mosquera, Chris Sander, Yaron S.N. Butterfield, Leigh Anne Zach, Yiling Lu, Chandra Lebovitz, Gary Witkin, David Pot, Gordon Robertson, Richard A. Gibbs, James J. Hsieh, Benjamin P. Berman, Doug Voet, Kyle Chang, W. Marston Linehan, Margaret Morgan, Joan Pontius, Jodi Harr, Lihua Zhou, Joel S. Parker, David Van Den Berg, Michael B. Atkins, Sheila Reynolds, Petar Stojanov, Joel B. Nelson, Gordon B. Mills, Toni K. Choueiri, Weimin Xiao, Hye Jung E. Chun, Ronglai Shen, Rebecca Carlsen, Jennifer Brown, Tod D. Casasent, Sabina Signoretti, Jo Ellen Weaver, Phillip H. Lai, Dominique L. Berton, Patrick Plettner, Irina Ostrovnaya, Lisle E. Mose, Leslie Cope, Nils Gehlenborg, Heidi J. Sofia, Peter J. Park, Scott Morris, Hsin-Ta Wu, Fabio Vandin, Ranabir Guin, Daniel E. Carlin, Jacqueline E. Schein, Xi Liu, Nils Weinhold, Wandaliz Torres-Garcia, Cureline Olga Potapova, Daniel DiCara, Juok Cho, Steve Schumacher, Chris Wakefield, A. Rose Brannon, Susan M. Benton, Tom Bodenheimer, J. Todd Auman, Brenda Rabeno, Sharon M. Gorski, Eric E. Snyder, Divya Kalra, Brenda Ayala, Jiashan Zhang, Zhang Wei, Kyle Ellrott, Zhining Wang, Stacey Gabriel, Dominik Stoll, Daniel L. Rubin, W. Kimryn Rathmell, Eric Chuah, David Mallery, Tanja Davidsen, David Cogdell, Anders Jacobsen, John A. Demchok, Robert C. Onofrio, Anna Chu, Piotr A. Mieczkowski, Zhiyong Ding, Erin Curley, Johanna Gardner, Robert Worrell, Hailei Zhang, Jennifer C. Fisher, Donna M. Muzny, Rajiv Dhir, Walker Hale, Ari B. Kahn, Sheila Fisher, Giovanni Ciriello, Ken Burnett, Marco A. Marra, Wiam Bshara, Anil V. Parwani, Joshua M. Stuart, Richard Varhol, Kristin G. Ardlie, Han Yi, Lisa R. Trevino, Roy Tarnuzzer, Michael S. Noble, Erin Pleasance, Jesse Walsh, Leigh B. Thorne, Andy Chu, Peter W. Laird, Andrew J. Mungall, Rashmi N. Sanbhadti, Mark Backus, David A. Wheeler, Bradley A. Ozenberger, Jodi K. Maranchie, William Mallard, Jared R. Slobodan, Christine Czerwinski, Jireh Santibanez, Andrew J. Stout, Donghui Tan, Laura S. Schmidt, Junyuan Wu, Jianjiong Gao, Daniel J. Weisenberger, D. Neil Hayes, Scott Frazer, Alan P. Hoyle, Konstantin V. Fedosenko, Rehan Akbani, Todd Pihl, Rahul Vegesna, Lynda Chin, Shelley Alonso, Jeffrey G. Reid, Donna Morton, Cathy D. Vocke, R. Houston Thompson, Christopher C. Benz, Kenna R. Mills Shaw, Liming Yang, Carmelo Gaudioso, Nianxiang Zhang, Caleb F. Davis, Carrie Hirst, Shi Yan, Michael L. Blute, Barry S. Taylor, Mathew G. Soloway, Nina Thiessen, Paul T. Spellman, Deepak Srinivasan, Yongjun Zhao, Boris Reva, Wang Min, Stuart R. Jefferys, Benjamin J. Raphael, Nicholas J. Petrelli, Arash Shafiei, Lora Lewis, Eric Jonasch, David I. Heiman, Scot Waring, Richard A. Moore, Eric S. Lander, Evan O. Paull, Hoon Kim, Janae V. Simons, Stephen B. Baylin, Gad Getz, Stanley Girshik, Victor E. Reuter, Benjamin Gross, Ethan Cerami, Andrew D. Cherniack, Christine I. Smith, Christina Yau, Michael D. Topal, Peter Waltman, Jeff Boyd, Rameen Beroukhim, Angela Tam, Yingchun Liu, Peter A. Kigonya, Miruna Balasundaram, Maria J. Merino, David Haussler, Dinh Huyen, Elizabeth Buda, Michael S. Lawrence, Lin Pei, Charles M. Perou, Timothy J. Triche, Jessica Walton, Greg Eley, Tiffany Ting Liu, Joseph Paulauskis, Matthew Meyerson, Marc Ladanyi, Jaegil Kim, Katherine A. Hoadley, Huang Mei, Ilya Shmulevich, Robin J.N. Coope, Mary Iacocca, Natasja Wye, Adrian Ally, Mark A. Rubin, A. Ari Hakimi, Lori Huelsenbeck-Dill, Steven J.M. Jones, James Peterson, Mark A. Jensen, Barbara Tabak, Andrey Sivachenko, Julie Bergsten, John Eckman, Inanc Birol, Rohini Raman, Nipun Kakkar, Christina Liquori, Rileen Sinha, Dennis T. Maglinte, Lichtenstein Lee, Haiyan I. Li, William G. Kaelin, Anna K. Unruh, Noreen Dhalla, Candace Shelton, Roel G.W. Verhaak, Christopher J. Ricketts, Carrie Sougnez, Harsha Doddapaneni, Mark S. Guyer, Robert Penny, Michael F. Berger, Margi Sheth, Darlene Lee, Dimitra Tsavachidou, Chad J. Creighton, Prachi Kothiyal, Scott L. Carter, Michael Mayo, Zhu Jing, Kenneth Aldape, Corbin D. Jones, Moiz S. Bootwalla, Payal Sipahimalani, Martin Hirst, Sean P. Barletta, Kristian Cibulskis, Jerome Myers, Matthew C. Nicholls, Yidi J. Turman, Julien Baboud, Jeff Gentry, Carl Morrison, Gordon Saksena, Troy Shelton, Swapna Mahurkar, Robert A. Holt, Robert Sfeir, Shen Hui, Suzanne S. Fei, Christopher G. Wood, Candace Carter, S. Onur Sumer, Pheroze Tamboli, Yiming Zhu, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Getz, Gad Asher, Voet, Douglas, Lin, Pei, Chin, Lynda, and Lander, Eric Steven
Subjects: DNA Mutational Analysis, GRB10 Adaptor Protein, AMP-Activated Protein Kinases, Epigenesis, Genetic, PBRM1, Pentose Phosphate Pathway, Phosphatidylinositol 3-Kinases, RNA, Neoplasm, BAP1, Genome, Multidisciplinary, Genomics, Chromatin, Gene Expression Regulation, Neoplastic, DNA methylation, Signal transduction, Acetyl-CoA Carboxylase, Carcinoma, Renal Cell, Chromatin Assembly and Disassembly, Citric Acid Cycle, DNA Methylation, Gene Expression Profiling, Genome, Human, Histone-Lysine N-Methyltransferase, Humans, Metabolic Networks and Pathways, MicroRNAs, Mutation, PTEN Phosphohydrolase, Proto-Oncogene Proteins c-akt, Signal Transduction, Survival Analysis, Human, Biology, Article, Genetic, SETD2, microRNA, medicine, Neoplastic, Carcinoma, Renal Cell, medicine.disease, Clear cell renal cell carcinoma, Gene Expression Regulation, Cancer research, RNA, Neoplasm, Epigenesis
Abstract: Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
Published: 2013

9. Integrated genomic characterization of endometrial carcinoma

Author: Ding Li, Esther Elishaev, Linda Dao, Juok Cho, Alexei Protopopov, Heather Schmidt, Tod D. Casasent, Bobbie S. Gostout, P.J. DiSaia, Jacqueline E. Schein, J. Todd Auman, Jay Bowen, S. Onur Sumer, Beth Y. Karlan, Gordon Saksena, Prachi Kothiyal, Robert E. Pyatt, Theodore C. Goldstein, Lisle E. Mose, Paul J. Goodfellow, Brenda Ayala, Nilsa C. Ramirez, Thomas Barr, Payal Sipahimalani, Gordon B. Mills, Rebecca Carlsen, Linda Van Le, Andy Chu, Peter W. Laird, Russell Broaddus, Helga B. Salvesen, Sam Ng, Cyriac Kandoth, Christopher Adams, Yiling Lu, Donghui Tan, Peter White, Lori Boice, Saianand Balu, Daniel DiCara, Robert A. Holt, Christopher C. Benz, Shi Yan, Joel S. Parker, Jessica Frick, Adrian Ally, Boris Winterhoff, Pamela M. Pollock, Patrick Plettner, Ethan Cerami, Angela Tam, Katherine A. Hoadley, Melissa Hart-Kothari, Robert C. Onofrio, John N. Weinstein, Sheila Reynolds, David Haussler, Kristian Cibulskis, Charles M. Perou, Timothy J. Triche, Rehan Akbani, Jeff Roach, Michael Mayo, Ranabir Guin, W. Kimryn Rathmell, Carmen Helsel, Junyuan Wu, Will Mallard, Nandita Barnabas, Todd Pihl, Ruibin Xi, Nianxiang Zhang, David Mallery, Douglas A. Levine, Aaron D. Black, David I. Heiman, Sugy Kodeeswaran, Lynda Chin, Guoyan Liu, Mark E. Borowsky, Daniel J. Weisenberger, Yuexin Liu, Hailei Zhang, Kenna R. Mills Shaw, Anna K. Unruh, Andrew Berchuck, Michael Button, Noreen Dhalla, Bryan Hernandez, Rayna K. Matsuno, David G. Mutch, Chen Wang, Teresa R. Tabler, Yaron S.N. Butterfield, Jeff Gentry, Stuart R. Jefferys, Thomas Grossman, Kelley Kneile, Fanny Dao, Scot Waring, Barbara Tabak, Eric E. Snyder, Eric S. Lander, Richard A. Moore, David J. Dooling, David Van Den Berg, Jiabin Tang, Piotr A. Mieczkowski, Victoria Blanc, Wei Zhang, Inanc Birol, Harkness Kuck, Mathew G. Soloway, Johanna Gardner, Gary Witkin, Sahil Seth, Heidi J. Sofia, B. Arman Aksoy, Nikolaus Schultz, Marco A. Marra, Andrew D. Cherniack, D L Rotin, Anders Jacobsen, Erik Zmuda, Candace Carter, Christina Yau, Stephen C. Benz, Alexander A. Green, Michael D. Topal, Jean MacKenzie, Elena Nemirovich-Danchenko, Nicholas J. Petrelli, Dana Nicholson, Eve Shinbrot, Han Liang, Rameen Beroukhim, Charlenia Berry-Green, Kristin G. Ardlie, Joan Pontius, David Pot, Ari B. Kahn, Marc T. Goodman, Yevgeniy Antipin, Christopher Szeto, Jianhua Zhang, Ilya Shmulevich, Lori Huelsenbeck-Dill, Steven J.M. Jones, Carrie Sougnez, Kristen M. Leraas, Pei Lin, Robert A. Soslow, Erin Curley, Leigh B. Thorne, Hye Jung E. Chun, Michael S. Lawrence, Michelle O'Laughlin, Moiz S. Bootwalla, Lixing Yang, Mark A. Jensen, Rajiv Dhir, David A. Wheeler, C. Blake Gilks, Jianjiong Gao, Lisa Wise, Giovanni Ciriello, Joelle Kalicki-Veizer, Shaowu Meng, Mei Huang, Elaine R. Mardis, Faina Bogomolniy, Kai Ye, Jenny Lester, Lihua Zou, Hollie A. Harper, Robert Edwards, Ronglai Shen, Xiaojia Ren, Nils Weinhold, Harshad S. Mahadeshwar, Sandra Orsulic, Tom Bodenheimer, Zhenlin Ju, Chris Wakefield, Scott Frazer, John M. S. Bartlett, Gideon Dresdner, Hui Shen, Deepak Srinivasan, Aaron Hobensack, Cynthia McAllister, Marc Ladanyi, Tanja Davidsen, Lucinda Fulton, Michael D. McLellan, Richard K. Wilson, Zeng Dong, Olga Potapova, Sean C. Dowdy, Rui Jing, Kristin K. Zorn, Robert S. Fulton, Matti Annala, Chris Sander, Michael S. Noble, Benjamin Gross, Janae V. Simons, Phillip H. Lai, Laura Monovich, Andrew J. Mungall, Peter J. Park, Fedor Moiseenko, Liming Yang, Gad Getz, John Deardurff, Matthew Meyerson, Jeremy Parfitt, A. Gordon Robertson, Bradley M. Broom, Blaise A. Clarke, Greg Eley, Jennifer O. Fisher, Andrey Sivachenko, Narciso Olvera, Carrie Hirst, Adam M. Farkas, Karuna Garg, Wendy Winckler, Eric Chuah, Stacey Gabriel, Michael E. Carney, Stephen B. Baylin, Doug Voet, Miruna Balasundaram, Christine Czerwinski, Daphne W. Bell, Richard Varhol, Alexandra Meuter, Alan P. Hoyle, Darlene Lee, Elizabeth Buda, Li Ding, Xingzhi Song, Steven E. Schumacher, Anna L. Chu, Attila Teoman, Mary Iacocca, Semin Lee, Rileen Sinha, Itai Pashtan, Haiyan I. Li, Mikhail Abramov, Mark S. Guyer, Robert Penny, Margi Sheth, Scott L. Carter, Corbin D. Jones, Michael J. Birrer, Julie M. Gastier-Foster, D. Neil Hayes, Nathan Vanhoose, Brenda Rabeno, Raju Kucherlapati, Martin L. Ferguson, Joshua M. Stuart, Steve E. Kalloger, Mark G. Cadungog, Petar Stojanov, Tara M. Lichtenberg, Bradley A. Ozenberger, Angela Hadjipanayis, Barry S. Taylor, Boris Reva, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., and Park, Peter J.
Subjects: DNA Copy Number Variations, endocrine system diseases, ARID1A, DNA Mutational Analysis, Breast Neoplasms, Biology, medicine.disease_cause, Article, Uterine serous carcinoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, PTEN, Exome, Poly-ADP-Ribose Binding Proteins, neoplasms, 030304 developmental biology, Chromosome Aberrations, Ovarian Neoplasms, 0303 health sciences, Endometrial intraepithelial neoplasia, Multidisciplinary, Genome, Human, Microsatellite instability, DNA Polymerase II, Genomics, medicine.disease, Molecular biology, female genital diseases and pregnancy complications, Endometrial Neoplasms, 3. Good health, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Serous fluid, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, biology.protein, Female, KRAS, Signal Transduction, Transcription Factors
Abstract: We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours., National Institutes of Health (U.S.) (Grant 5U24CA143799-04), National Institutes of Health (U.S.) (Grant 5U24CA143835-04), National Institutes of Health (U.S.) (Grant 5U24CA143840-04), National Institutes of Health (U.S.) (Grant 5U24CA143843-04), National Institutes of Health (U.S.) (Grant 5U24CA143845-04), National Institutes of Health (U.S.) (Grant 5U24CA143848-04), National Institutes of Health (U.S.) (Grant 5U24CA143858-04), National Institutes of Health (U.S.) (Grant 5U24CA143866-04), National Institutes of Health (U.S.) (Grant 5U24CA143867-04), National Institutes of Health (U.S.) (Grant 5U24CA143882-04), National Institutes of Health (U.S.) (Grant 5U24CA143883-04), National Institutes of Health (U.S.) (Grant 5U24CA144025-04), National Institutes of Health (U.S.) (Grant U54HG003067-11), National Institutes of Health (U.S.) (Grant U54HG003079-10), National Institutes of Health (U.S.) (Grant U54HG003273-10)
Published: 2013

10. Chemical composition in wild Ethiopian Arabica coffee accessions

Author: Natalia Ferrarezi Pagiatto, Fabrice Davrieux, Cíntia Sorane Good Kitzberger, Thierry Leroy, Pierre Charmetant, Luiz Filipe Protasio Pereira, David Pot, and Maria Brígida dos Santos Scholz
Subjects: 0106 biological sciences, Germplasm, Cafestol, Phénotype, Plant Science, 01 natural sciences, F30 - Génétique et amélioration des plantes, Plante sauvage, chemistry.chemical_compound, Diterpénoïde, Cultivar, Kahweol, Acide chlorogénique, education.field_of_study, Teneur en protéines, 04 agricultural and veterinary sciences, Coffea arabica, Composition chimique, 040401 food science, Horticulture, Caféine, saccharose, Fève de café, Génotype, medicine.drug, Teneur en glucides, F60 - Physiologie et biochimie végétale, Population, Biology, Crop, 0404 agricultural biotechnology, Variation génétique, Teneur en lipides, Botany, Genetics, medicine, education, Q04 - Composition des produits alimentaires, Genetic diversity, Amélioration des plantes, chemistry, Collection de matériel génétique, Agronomy and Crop Science, 010606 plant biology & botany
Abstract: The exploration of accessions originating from Ethiopia is one option available to increase the genetic basis of new coffee cultivars. The aim of this study was to describe the chemical composition variability of Ethiopian coffee accessions maintained in Londrina and to evaluate the year effect on that. We observed no significant interaction between the years of cultivation and the amounts of caffeine, protein, lipids, chlorogenic acids, sucrose, cafestol and kahweol, thereby suggesting that evaluations of one year were reliable to describe this collection. All compounds showed variability, but the highest variability was found in cafestol and kahweol (32.81 and 34.45 %, respectively). Significant correlations among caffeine, chlorogenic acids and protein as well as between sucrose and lipids were observed. A significant negative correlation was found between kahweol and cafestol, and kahweol had positive and negative correlation with caffeine and chlorogenic acids, respectively. Hierarchical clustering analyses identified groups in the population, and the diversity found in one crop year was similar to that for 3 years. Greater diversity of composition was observed among the Western accessions compared to the ones from the East, but no clear separation was found between the accessions of these regions. These accessions are potential sources to increase the genetic diversity to obtain new coffee cultivars.
Published: 2016

11. Evaluation of Kahweol and Cafestol in Coffee Tissues and Roasted Coffee by a New High-Performance Liquid Chromatography Methodology

Author: David Pot, Marta de Toledo Benassi, Rafael Carlos Eloy Dias, Fernanda Gonçalves Campanha, Pierre Marraccini, Lucia Pires Ferreira, and Luiz Gonzaga Esteves Vieira
Subjects: Food Handling, F60 - Physiologie et biochimie végétale, Cafestol, Coffea, Coffea canephora, High-performance liquid chromatography, chemistry.chemical_compound, Diterpénoïde, medicine, Q04 - Composition des produits alimentaires, Chromatography, High Pressure Liquid, Kahweol, Detection limit, Chromatography, Reverse-Phase, Chromatography, biology, Plant Extracts, Chemistry, Coffea arabica, Extraction (chemistry), General Chemistry, biology.organism_classification, Plant Leaves, Fruit, Diterpenes, Fève de café, HPLC, General Agricultural and Biological Sciences, Saponification, medicine.drug
Abstract: A reverse phase high-performance liquid chromatography (HPLC) method was developed for the simultaneous quantification of kahweol and cafestol in tissues of fresh fruits, leaves, and roasted coffee beans. The best resolution was obtained with isocratic elution of acetonitrile/water (55/45% v/v) and UV detection. A single sample preparation method carried out by direct saponification and extraction with organic solvent was standardized for all matrices. Good recovery (average of 99% for kahweol and 94% for cafestol), repeatability, and linearity were obtained. Detection limits of 2.3 and 3.0 mg/100 g were observed for kahweol and cafestol. The HPLC method was effective in quantifying these diterpenes in the different coffee matrices. The endosperm and perisperm of Coffea arabica cv. IAPAR 59 showed elevated amounts of kahweol as compared to the pericarp and leaves. On the other hand, cafestol was detected in all samples except in leaves from Coffea canephora cv. Apoata. (Resume d'auteur)
Published: 2009

12. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

Author: Hoadley, Katherine A., Yau, Christina, Wolf, Denise M., Cherniack, Andrew D., Tamborero, David, Sam, Ng, Leiserson, Max D. M., Niu, Beifang, Mclellan, Michael D., Uzunangelov, Vladislav, Zhang, Jiashan, Kandoth, Cyriac, Akbani, Rehan, Shen, Hui, Omberg, Larsson, Chu, Andy, Margolin, Adam A., Van'T Veer, Laura J., Lopez Bigas, Nuria, Laird, Peter W., Raphael, Benjamin J., Ding, Li, Robertson, A. Gordon, Byers, Lauren A., Mills, Gordon B., Weinstein, John N., Van Waes, Carter, Chen, Zhong, Collisson, Eric A., Benz, Christopher C, Perou, Charles M., Stuart, Joshua M., Rachel, Abbott, Scott, Abbott, Arman Aksoy, B., Kenneth, Aldape, Adrian, Ally, Samirku mar Amin, Dimitris, Anastassiou, Todd Auman, J., Baggerly, Keith A., Miruna, Balasundaram, Saianand, Balu, Baylin, Stephen B., Benz, Stephen C., Berman, Benjamin P., Brady, Bernard, Bhatt, Ami S., Inanc, Birol, Black, Aaron D., Tom, Bodenheimer, Bootwalla, Moiz S., Jay, Bowen, Ryan, Bressler, Bristow, Christopher A., Brooks, Angela N., Bradley, Broom, Elizabeth, Buda, Robert, Burton, Butterfield, Yaron S. N., Daniel, Carlin, Carter, Scott L., Casasent, Tod D., Kyle, Chang, Stephen, Chanock, Lynda, Chin, Dong Yeon Cho, Juok, Cho, Eric, Chuah, Chun, Hye Jung E., Kristian, Cibulskis, Giovanni, Ciriello, James Cle land, Melisssa, Cline, Brian, Craft, Creighton, Chad J., Ludmila, Danilova, Tanja, Davidsen, Caleb, Davis, Dees, Nathan D., Kim, Delehaunty, Demchok, John A., Noreen, Dhalla, Daniel, Dicara, Huyen, Dinh, Dobson, Jason R., Deepti, Dodda, Harshavardhan, Doddapaneni, Lawrence, Donehower, Dooling, David J., Gideon, Dresdner, Jennifer, Drummond, Andrea, Eakin, Mary, Edgerton, Eldred, Jim M., Greg, Eley, Kyle, Ellrott, Cheng, Fan, Suzanne, Fei, Ina, Felau, Scott, Frazer, Freeman, Samuel S., Jessica, Frick, Fronick, Catrina C., Ful ton, Lucinda L., Robert, Fulton, Gabriel, Stacey B., Jianjiong, Gao, Gastier Foster, Julie M., Nils, Gehlenborg, Myra, George, Gad, Getz, Richard, Gibbs, Mary, Goldman, Abel Gonzalez Perez, Benjamin, Gross, Ranabir, Guin, Preethi, Gunaratne, Angela, Hadjipanayis, Hamilton, Mark P., Hamilton, Stanley R., Leng, Han, Han, Yi, Harper, Hollie A., Psalm, Haseley, David, Haussler, Neil Hayes, D., Heiman, David I., Elena, Helman, Carmen, Helsel, Herbrich, Shelley M., Her man, James G., Toshinori, Hinoue, Carrie, Hirst, Martin, Hirst, Holt, Robert A., Hoyle, Alan P., Lisa, Iype, Anders, Jacobsen, Jeffreys, Stuart R., Jensen, Mark A., Jones, Corbin D., Jones, Steven J. M., Zhenlin, Ju, Joonil, Jung, Andre, Kahles, Ari, Kahn, Joelle Kalicki Veizer, Divya, Kalra, Krishna Latha Kanchi, Kane, David W., Hoon, Kim, Jaegil, Kim, Theo, Knijnenburg, Koboldt, Daniel C., Christie, Kovar, Roger, Kramer, Richard, Kreisberg, Raju, Kucherlapati, Marc, Ladanyi, Lander, Eric S., Larson, David E., Lawrence, Michael S., Darlene, Lee, Eunjung, Lee, Semin, Lee, William, Lee, Kjong Van Lehmann, Kalle, Leinonen, Ler aas, Kristen M., Seth, Lerner, Levine, Douglas A., Lora, Lewis, Ley, Timothy J., Haiyan I., Li, Jun, Li, Wei, Li, Han, Liang, Lichtenberg, Tara M., Jake, Lin, Ling, Lin, Pei, Lin, Wen bin Liu, Yingchun, Liu, Yuexin, Liu, Lorenzi, Philip L., Charles, Lu, Yiling, Lu, Luquette, Love lace J., Singer, Ma, Magrini, Vincent J., Mahadeshwar, Harshad S., Mardis, Elaine R., Adam, Margolin, Marra, Marco A., Michael, Mayo, Cynthia, Mcallister, Mcguire, Sean E., Mcmichael, Joshua F., James, Melott, Shaowu, Meng, Matthew, Meyerson, Mieczkowski, Piotr A., Miller, Christopher A., Miller, Martin L., Michael, Miller, Moore, Richard A., Margaret, Morgan, Donna, Morton, Mose, Lisle E., Mungall, Andrew J., Donna, Muzny, Lam, Nguyen, Noble, Michael S., Houtan, Noushmehr, Michelle, O’Laughlin, Ojesina, Akinyemi I., Tai Hsien Ou Yang, Brad, Ozenberger, Angeliki, Pantazi, Michael, Parfenov, Park, Peter J., Parker, Joel S., Evan, Paull, Chandra Sekhar Pedamallu, Todd, Pihl, Craig, Pohl, David, Pot, Alexei, Protopopov, Teresa, Przytycka, Amie Raden baugh, Ramirez, Nilsa C., Ricardo, Ramirez, Gunnar Ra, ̈ tsch, Jeffrey, Reid, Xiao jia Ren, Boris, Reva, Reynolds, Sheila M., Rhie, Suhn K., Jeffrey, Roach, Hector, Rovira, Michael, Ryan, Gordon, Saksena, Sofie, Salama, Chris, Sander, Netty, Santoso, Schein, Jacqueline E., Heather, Schmidt, Nikolaus, Schultz, Schumacher, Steven E., Jonathan, Seidman, Yasin, Senbabaoglu, Sahil, Seth, Saman tha Sharpe, Ronglai, Shen, Margi, Sheth, Yan, Shi, Ilya, Shmulevich, Silva, Grace O., Simons, Janae V., Rileen, Sinha, Payal, Sipahimalani, Smith, Scott M., Sofia, Heidi J., Artem, Sokolov, Soloway, Mathew G., Xingzhi, Song, Carrie Soug nez, Paul, Spellman, Louis, Staudt, Chip, Stewart, Petar, Stojanov, Xiaoping, Su, Onur Sumer, S., Yichao, Sun, Teresa, Swatloski, Barbara, Tabak, Angela, Tam, Donghui, Tan, Jiabin, Tang, Roy, Tarnuzzer, Taylor, Barry S., Nina, Thiessen, Ves teinn Thorsson, Timothy Triche, J. r., Van Den Berg, David J., Vandin, Fabio, Varhol, Richard J., Vaske, Charles J., Umadevi, Veluvolu, Roeland, Verhaak, Doug, Voet, Jason, Walker, Wallis, John W., Peter, Waltman, Yunhu, Wan, Min, Wang, Wenyi, Wang, Zhining, Wang, Scot, Waring, Nils, Weinhold, Weisenberger, Daniel J., Wendl, Michael C., David, Wheeler, Wilkerson, Matthew D., Wilson, Richard K., Lisa, Wise, Andrew, Wong, Chang Jiun Wu, Chia Chin Wu, Hsin Ta Wu, Junyuan, Wu, Todd, Wylie, Liu, Xi, Ruibin, Xi, Zheng, Xia, Andrew W., Xu, Yang, Da, Liming, Yang, Lixing, Yang, Yang, Yang, Jun, Yao, Rong, Yao, Kai, Ye, Ko suke Yoshihara, Yuan, Yuan, Yung, Alfred K., Travis, Zack, Dong, Zeng, Jean Claude Zenklusen, Hailei, Zhang, Jianhua, Zhang, Nianxiang, Zhang, Qunyuan, Zhang, Wei, Zhang, Wei, Zhao, Siyuan, Zheng, Jing, Zhu, Erik, Zmuda, and Lihua, Zou
Subjects: Genetics and Molecular Biology (all), Cluster Analysis, Humans, Neoplasms, Transcriptome, Biochemistry, Genetics and Molecular Biology (all), Extramural, Biochemistry, Genetics and Molecular Biology(all), Cancer, Computational biology, Disease, Biology, medicine.disease, Bioinformatics, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Article, 3. Good health, Molecular classification, TP63, CLUSTERS (ANÁLISE), medicine, Head and neck, Gene
Abstract: Summary Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.
Published: 2014

13. Signaling Inositol Polyphosphate-5-phosphatase

Author: Anne Bennett Jefferson, Lewis T. Williams, Philip W. Majerus, David Pot, and Vorachart Auethavekiat
Subjects: chemistry.chemical_classification, biology, Oculocerebrorenal syndrome, Phosphatase, Signal transducing adaptor protein, Cell Biology, medicine.disease, Biochemistry, Molecular biology, Enzyme assay, chemistry.chemical_compound, Enzyme, chemistry, biology.protein, medicine, Inositol, OCRL, Phosphatidylinositol, Molecular Biology
Abstract: An inositol polyphosphate-5-phosphatase (SIP-110) that binds the SH3 domains of the adaptor protein GRB2 was produced in Sf9 cells and characterized. SIP-110 binds to GRB2 in vitro with a stoichiometry of 1 mol of GRB2/0.7 mol of SIP-110. GRB2 binding does not affect enzyme activity implying that GRB2 serves mainly to localize SIP-110 within cells. SIP-110 hydrolyses inositol (Ins)(1,3,4,5)P4 to Ins(1,3,4)P3. The enzyme does not hydrolyze Ins(1,4,5)P3 that is a substrate for previously described 5-phosphatases nor does it hydrolyze phosphatidylinositol (PtdIns)(4,5)P2. SIP-110 also hydrolyzed PtdIns(3,4,5)P3 to PtdIns(3,4)P2 as did recombinant forms of two other 5-phosphatases designated as inositol polyphosphate-5- phosphatase II, and OCRL (the protein that is mutated in oculocerebrorenal syndrome). The inositol polyphosphate-5-phosphatase enzyme family now is represented by at least 9 distinct genes and includes enzymes that fall into 4 subfamilies based on their activities toward various 5-phosphatase substrates.
Published: 1997

14. Comprehensive molecular characterization of urothelial bladder carcinoma

Author: Elizabeth Buda, Nikolaus Schultz, Donghui Tan, Pat Swanson, Xingzhi Song, Jennifer Owens, Carmelo Gaudioso, Liming Yang, Kenna R. Mills Shaw, Sophie C. Egea, John N. Weinstein, Lihua Zou, Dmitry A. Gordenin, Gad Getz, Stuart R. Jefferys, Wiam Bshara, David Haussler, Ari B. Kahn, Mary Iacocca, Brady Bernard, Charles M. Perou, Leigh B. Thorne, Kimberly R. Christ, Eric S. Lander, Yunhu Wan, Timothy J. Triche, Dong Zeng, Bogdan Czerniak, Wenbin Liu, Jianhua Zhang, David Mallery, B. Arman Aksoy, Lynn M. Herbert, Hailei Zhang, Jennifer DiPiero, Tod D. Casasent, Sugy Kodeeswaran, Daniel DiCara, Jacqueline E. Schein, Scott L. Carter, Umadevi Veluvolu, John M. S. Bartlett, Theresa M. Koppie, Ji Yeon Yang, Ronglai Shen, Yingchun Liu, Daniel J. Weisenberger, Ranabir Guin, Myra M. George, Marc Ladanyi, J. Todd Auman, Moiz S. Bootwalla, Shaowu Meng, Mark S. Soloway, Tatjana Antic, Greg Eley, Hikmat Al-Ahmadie, Carolyn M. Hutter, Jonathan G. Seidman, Corbin D. Jones, Lori Boice, Xiaoping Su, Jay Bowen, Raju Kucherlapati, Hui Shen, Benjamin Gross, Reanne Bowlby, Lawrence A. Donehower, Phan Thi Hanh, David J. McConkey, Saianand Balu, Jiexin Zhang, Tina Wong, Juok Cho, Alexei Protopopov, Carolyn L. Smith, Yuexin Liu, Angeliki Pantazi, Jason R. Gee, Xuan Van Le, Ricardo Ramirez, Ami S. Bhatt, Samuel S. Freeman, Jaegil Kim, Bui Duc Phu, Michael Ittman, Charles C. Guo, Carmen Gomez-Fernandez, Norm D. Smith, S. Onur Sumer, Bradley A. Ozenberger, Paul M. Weinberger, George E. Sandusky, Troy Shelton, Seth P. Lerner, Charles Saller, Nicholas J. Petrelli, Nguyen Van Bang, Sahil Seth, Richard A. Gibbs, Lisle E. Mose, Aaron D. Black, Yair Lotan, Carrie Sougnez, Jessie Au, Martin L. Ferguson, Ashley Marie Regazzi, Matthew Meyerson, Joel B. Nelson, Natasja Wye, Daniel E. Carlin, Nils Weinhold, Tom Bodenheimer, Nilsa C. Ramirez, Michael Ryan, Anders Jacobsen, Eric J. Burks, Lee Lichtenstein, Erin Curley, Angela Hadjipanayis, Nils Gehlenborg, Hector Rovira, Bernard Kohl, Jean C. Zenklusen, Travis Sullivan, Margaret Morgan, Rajiv Dhir, Julie M. Gastier-Foster, Gary D. Steinberg, Mathew G. Soloway, Nina Thiessen, Jianjiong Gao, Lisa Wise, Barry S. Taylor, Gordon Saksena, Hui Yao, David Van Den Berg, Jiabin Tang, Robert Penny, Nguyen Viet Tien, Jeffrey R. Gingrich, Jing Zhu, Ronald L. Hrebinko, Dick Kreisberg, Pei Lin, Christopher A. Bristow, Andrey Sivachenko, Andy Chu, Peter W. Laird, Thomas Barr, Junyuan Wu, Robert A. Holt, Harshad S. Mahadeshwar, Piotr A. Mieczkowski, Steven A. Roberts, Victor E. Reuter, Jeffrey S. Damrauer, Roni J. Bollag, Chad J. Creighton, Johanna Gardner, Michael Parfenov, Qiang Li, Phillip H. Lai, Thomas C. Motter, Alireza Moinzadeh, Jodi K. Maranchie, Christopher C. Benz, Lynda Chin, Angela Tam, Margi Sheth, David B. Solit, Erik Zmuda, Lixing Yang, Peter J. Park, Marco A. Marra, Katherine A. Hoadley, Eila C. Skinner, Scott Frazer, Roy Tarnuzzer, Heidi J. Sofia, Bradley M. Broom, Zhining Wang, David I. Heiman, Sebrina A Tello, Lori Huelsenbeck-Dill, Steven J.M. Jones, Antonia H. Holway, Ilana Rebecca Garcia-Grossman, Merce Jorda, Roeland Verhaak, Ilya Shmulevich, W.K. Rathmell, Bernard H. Bochner, Scot Waring, Kenneth Aldape, Richard A. Moore, Toshinori Hinoue, Carrie Hirst, Mark A. Jensen, Payal Kapur, Andrew D. Cherniack, Dean F. Bajorin, Evano Paull, Cheryl M. Lewis, William Y. Kim, Giovanni Ciriello, David C. Fargo, Gordon B. Mills, Michael S. Noble, Stephanie Weaver, Whitney D. McClenden, Benjamin Davies, Payal Sipahimalani, Vina Alexopoulou, Bo Peng, Stephen B. Baylin, Michael Mayo, Rameen Beroukhim, Boris Reva, Anil V. Parwani, Joshua M. Stuart, David J. Kwiatkowski, Stacey B. Gabrie, Janae V. Simons, Rehan Akbani, Todd Pihl, Nianxiang Zhang, Suzie Carter, Michael S. Lawrence, Carmen Helsel, Carl Morrison, Xiaojia Ren, Jeffrey Roach, Peter H. O'Donnell, Miruna Balasundaram, Yevgeniy Antipin, Gideon Dresdner, Cynthia McAllister, Tanja Davidsen, Brenda Rabeno, Jolanta Bondaruk, Kristian Cibulskis, Chip Stewart, Matthew D. Wilkerson, Jonathan E. Rosenberg, Brian D. Robinson, Patricia Castro, Wei Zhang, Chandra Sekhar Pedamallu, Allison Beaver, Andrew Wei Xu, Adrian Ally, Andrea Sorcini, Andrew J. Mungall, Katherine Tarvin, Christine Czerwinski, Petar Stojanov, Philip L. Lorenzi, Alan P. Hoyle, Jay Engel, Tara M. Lichtenberg, D. Neil Hayes, John A. Demchok, Eric Chuah, Benjamin Hanf, Deepak Srinivasan, Donna E. Hansel, Noreen Dhalla, Zhenlin Ju, Leszek J. Klimczak, Trevor J. Pugh, Richard Thorp, A. Gordon Robertson, Darlene Lee, Steven E. Schumacher, Semin Lee, Sheldon I. Bastacky, Rileen Sinha, Haiyan I. Li, William Lee, Sam Ng, Joel S. Parker, Sheila Reynolds, Teresa R. Tabler, Yaron S.N. Butterfield, David Pot, Chris Sander, Wenyi Wang, Weiguo Jian, Le Quang Vinh, Netty Santoso, Doug Voet, and Joonil Jung
Subjects: Metastatic Urothelial Carcinoma, Invasive urothelial carcinoma, Virus Integration, Down-Regulation, Disease, Bioinformatics, Malignancy, Article, Phosphatidylinositol 3-Kinases, Cancer genome, medicine, Carcinoma, Humans, Molecular Targeted Therapy, RNA, Messenger, Urothelial carcinoma, Multidisciplinary, business.industry, TOR Serine-Threonine Kinases, Cell Cycle, Creative commons, medicine.disease, Chromatin, 3. Good health, Gene Expression Regulation, Neoplastic, MicroRNAs, Oxidative Stress, Urinary Bladder Neoplasms, business, Protein Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
Published: 2013

15. Comprehensive molecular profiling of lung adenocarcinoma

Author: Amie Radenbaugh, Noreen Dhalla, Christina Williamson, Charles Saller, James Suh, Ramaswamy Govindan, Travis I. Zack, Paul T. Spellman, Daniel DiCara, Harvey I. Pass, Deepak Srinivasan, William G. Richards, Robert J. Cerfolio, Igor Letovanec, A. Gordon Robertson, Gabriel Sica, Chad J. Creighton, Hendrik Dienemann, Jeffrey A. Borgia, Boris Reva, Bryan F. Meyers, Yiling Lu, Nikolaus Schultz, Christopher I. Amos, Dante Trusty, Carmelo Gaudioso, Michael Meister, James T. Robinson, Lihua Zou, James Shin, Jeremy Parfitt, Darlene Lee, Junyuan Wu, Carl Morrison, Scott L. Carter, Giovanni Ciriello, Nils Weinhold, Elena Nemirovich-Danchenko, Andrew Wei Xu, Christopher G. Maher, Lori Boice, Irina Zaytseva, Dennis A. Wigle, Kenna R. Mills Shaw, Matthew G. Soloway, Matthew Meyerson, Peng Chieh Chen, Frank Schneider, Troy Shelton, Douglas Voet, Steven E. Schumacher, D L Rotin, Saianand Balu, Stuart R. Jefferys, Tom Bodenheimer, Bradley A. Ozenberger, Eric S. Lander, Edward Gabrielson, Konstantin V. Fedosenko, Rehan Akbani, William D. Travis, Ari B. Kahn, Marcin Imielinski, Jacqueline E. Schein, Thomas L. Bauer, Kai Ye, Samuel A. Yousem, Robert C. Onofrio, Thomas Muley, Ayesha S. Bryant, Michael K. Asiedu, Monique Albert, Pei Lin, Corbin D. Jones, Edwina Duhig, Jean C. Zenklusen, Lucinda Fulton, Christina Yau, J. Todd Auman, Leigh B. Thorne, Elena Helman, Richard T. Cheney, William Lee, Patrick K. Kimes, Juok Cho, Alexei Protopopov, Wenbin Liu, Lee Lichtenstein, Jing Wang, Lixing Yang, W. Kimryn Rathmell, Jo Ellen Weaver, David A. Wheeler, Leslie Cope, Mark A. Watson, Heidi J. Sofia, Angeliki Pantazi, Ronglai Shen, Jeffrey Roach, Eric A. Collisson, Patrick Kwok Shing Ng, Angela Hadjipanayis, Peter S. Hammerman, David Van Den Berg, Kwun M. Fong, Nils Gehlenborg, Natasha Rekhtman, William K. Funkhouser, D. Neil Hayes, Harshad S. Mahadeshwar, Semin Lee, Martin Peifer, David Mallery, Piotr A. Mieczkowski, Ranabir Guin, Madhusmita Behera, Philipp A. Schnabel, Jill M. Siegfried, Carmen Gomez-Fernandez, Johanna Gardner, Lynn M. Herbert, Hailei Zhang, Robert S. Fulton, Travis Sullivan, Sahil Seth, Sam Ng, Chandra Sekhar Pedamallu, Barry S. Taylor, Venkatraman E. Seshan, Valerie W. Rusch, Jinze Liu, Daniel P. Raymond, Jianjiong Gao, Nathan A. Pennell, Marco A. Marra, Jan F. Prins, Payal Sipahimalani, Janae V. Simons, Joel S. Parker, Rileen Sinha, Lindy Hunter, Raju Kucherlapati, Dennis T. Maglinte, Fedor Moiseenko, Eric E. Snyder, Roy Tarnuzzer, Beverly Lee, James Stephen Marron, Kristian Cibulskis, Jerome Myers, Haiyan I. Li, Robert Penny, Hartmut Juhl, Richard K. Wilson, Zhining Wang, Eran Hodis, Carrie Sougnez, Jiabin Tang, William Mallard, Bryan Hernandez, Liming Yang, Jennifer Brown, Gad Getz, Farhad Kosari, Catrina Fronick, Juliann Chmielecki, Jianhua Zhang, Suresh S. Ramalingam, Michael Parfenov, Peter J. Park, Tanja Davidsen, Philip H. Lai, Jeff Boyd, Dang Huy Quoc Thinh, Harmanjatinder S. Sekhon, Malcolm V. Brock, Mark Pool, Margi Sheth, Kimberly M. Rieger-Christ, Michael J. Liptay, E. Getz, S. Onur Sumer, Ian A. Yang, B. Arman Aksoy, Douglas B. Flieder, Bradley M. Broom, Carrie Hirst, Solange Peters, Joshua M. Stuart, Khurram Z. Khan, Scott Morris, Donghui Tan, Andrew J. Mungall, Ming-Sound Tsao, Gordon B. Mills, Stephen B. Baylin, Rebecca Carlsen, Sanja Dacic, Julien Baboud, Brenda Rabeno, Richard A. Hajek, Lauren Averett Byers, Yaron S.N. Butterfield, Miruna Balasundaram, Chip Stewart, Katherine Tarvin, Peter B. Illei, James G. Herman, David J. Kwiatkowski, Andy Chu, David Haussler, Natasja Wye, Charles M. Perou, Peter W. Laird, Timothy J. Triche, Yan Shi, Jill P. Mesirov, Angela N. Brooks, Lori Huelsenbeck-Dill, Steven J.M. Jones, Antonia H. Holway, Lixia Diao, Anthony A. Gal, David G. Beer, Angela Tam, Ashley H. Salazar, Mark A. Jensen, Robert A. Holt, Katherine A. Hoadley, John A. Demchok, Sandra McDonald, Chandra Goparaju, David Pot, Belinda E. Clarke, Gordon Robertson, Michael C. Wendl, Helga Thorvaldsdottir, Kristen Rogers, Joshua D. Campbell, Chris Sander, Rayleen V. Bowman, Marc Danie Nazaire, Michael Mayo, Olga Voronina, Ludmila Danilova, Paul Zippile, Netty Santoso, John V. Heymach, Matthew D. Wilkerson, John Eckman, Morgan Windsor, Cureline Oleg Dolzhanskiy, Nina Thiessen, Mara Rosenberg, Gideon Dresdner, Levi A. Garraway, Eric Chuah, Richard Varhol, Elizabeth Buda, Li Ding, Alice H. Berger, Xingzhi Song, John M. S. Bartlett, Michael D. McLellan, Olga Potapova, Joseph Paulauskis, Igor Jurisica, Benjamin Gross, Jaegil Kim, John N. Weinstein, Kevin Lau, Christopher R. Cabanski, Philip Bonomi, Michael S. Noble, Maureen F. Zakowski, George E. Sandusky, Mary Iacocca, Eric J. Burks, Erin Curley, Lynda Chin, Rajiv Dhir, Singer Ma, Sophie C. Egea, Umadevi Veluvolu, Sugy Kodeeswaran, Christopher A. Miller, Moiz S. Bootwalla, Daniel J. Weisenberger, Shaowu Meng, Mei Huang, Elaine R. Mardis, Gordon Saksena, Nicholas J. Petrelli, Yvonne Owusu-Sarpong, Christopher C. Benz, Bernard Kohl, Jingchun Zhu, David I. Heiman, Carol Farver, Scot Waring, Richard A. Moore, Darshan Singh, Andrew D. Cherniack, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Marc Ladanyi, Stacey Gabriel, Christine Czerwinski, Alan P. Hoyle, Cancer Genome Atlas Research Network, Collisson, E. A., Campbell, J.D., Brooks, A.N., Berger, A.H., Lee, W., Chmielecki, J., Beer, D.G., Cope, L., Creighton, C.J., Danilova, L., Ding, L., Getz, G., Hammerman, P.S., Hayes, D.N., Hernandez, B., Herman, J.G., Heymach, J.V., Jurisica, I., Kucherlapati, R., Kwiatkowski, D., Ladanyi, M., Robertson, G., Schultz, N., Shen, R., Sinha, R., Sougnez, C., Tsao, M.S., Travis, W.D., Weinstein, J.N., Wigle, D.A., Wilkerson, M.D., Chu, A., Cherniack, A.D., Hadjipanayis, A., Rosenberg, M., Weisenberger, D.J., Laird, P.W., Radenbaugh, A., Ma, S., Stuart, J.M., Averett Byers, L., Baylin, S.B., Govindan, R., Meyerson, M., Gabriel, S.B., Cibulskis, K., Kim, J., Stewart, C., Lichtenstein, L., Lander, E.S., Lawrence, M.S., Kandoth, C., Fulton, R., Fulton, L.L., McLellan, M.D., Wilson, R.K., Ye, K., Fronick, C.C., Maher, C.A., Miller, C.A., Wendl, M.C., Cabanski, C., Mardis, E., Wheeler, D., Balasundaram, M., Butterfield, Y.S., Carlsen, R., Chuah, E., Dhalla, N., Guin, R., Hirst, C., Lee, D., Li, H.I., Mayo, M., Moore, R.A., Mungall, A.J., Schein, J.E., Sipahimalani, P., Tam, A., Varhol, R., Robertson, A., Wye, N., Thiessen, N., Holt, R.A., Jones, S.J., Marra, M.A., Imielinski, M., Onofrio, R.C., Hodis, E., Zack, T., Helman, E., Sekhar Pedamallu, C., Mesirov, J., Saksena, G., Schumacher, S.E., Carter, S.L., Garraway, L., Beroukhim, R., Lee, S., Mahadeshwar, H.S., Pantazi, A., Protopopov, A., Ren, X., Seth, S., Song, X., Tang, J., Yang, L., Zhang, J., Chen, P.C., Parfenov, M., Wei Xu, A., Santoso, N., Chin, L., Park, P.J., Hoadley, K.A., Auman, J.T., Meng, S., Shi, Y., Buda, E., Waring, S., Veluvolu, U., Tan, D., Mieczkowski, P.A., Jones, C.D., Simons, J.V., Soloway, M.G., Bodenheimer, T., Jefferys, S.R., Roach, J., Hoyle, A.P., Wu, J., Balu, S., Singh, D., Prins, J.F., Marron, J.S., Parker, J.S., Perou, C.M., Liu, J., Maglinte, D.T., Lai, P.H., Bootwalla, M.S., Van Den Berg, D.J., Triche, T., Cho, J., DiCara, D., Heiman, D., Lin, P., Mallard, W., Voet, D., Zhang, H., Zou, L., Noble, M.S., Gehlenborg, N., Thorvaldsdottir, H., Nazaire, M.D., Robinson, J., Aksoy, B.A., Ciriello, G., Taylor, B.S., Dresdner, G., Gao, J., Gross, B., Seshan, V.E., Reva, B., Sumer, S.O., Weinhold, N., Sander, C., Ng, S., Zhu, J., Benz, C.C., Yau, C., Haussler, D., Spellman, P.T., Kimes, P.K., Broom, B.M., Wang, J., Lu, Y., Kwok Shing Ng, P., Diao, L., Liu, W., Amos, C.I., Akbani, R., Mills, G.B., Curley, E., Paulauskis, J., Lau, K., Morris, S., Shelton, T., Mallery, D., Gardner, J., Penny, R., Saller, C., Tarvin, K., Richards, W.G., Cerfolio, R., Bryant, A., Raymond, D.P., Pennell, N.A., Farver, C., Czerwinski, C., Huelsenbeck-Dill, L., Iacocca, M., Petrelli, N., Rabeno, B., Brown, J., Bauer, T., Dolzhanskiy, O., Potapova, O., Rotin, D., Voronina, O., Nemirovich-Danchenko, E., Fedosenko, K.V., Gal, A., Behera, M., Ramalingam, S.S., Sica, G., Flieder, D., Boyd, J., Weaver, J., Kohl, B., Huy Quoc Thinh, D., Sandusky, G., Juhl, H., Duhig, E., Illei, P., Gabrielson, E., Shin, J., Lee, B., Rodgers, K., Trusty, D., Brock, M.V., Williamson, C., Burks, E., Rieger-Christ, K., Holway, A., Sullivan, T., Asiedu, M.K., Kosari, F., Rekhtman, N., Zakowski, M., Rusch, V.W., Zippile, P., Suh, J., Pass, H., Goparaju, C., Owusu-Sarpong, Y., Bartlett, J.M., Kodeeswaran, S., Parfitt, J., Sekhon, H., Albert, M., Eckman, J., Myers, J.B., Cheney, R., Morrison, C., Gaudioso, C., Borgia, J.A., Bonomi, P., Pool, M., Liptay, M.J., Moiseenko, F., Zaytseva, I., Dienemann, H., Meister, M., Schnabel, P.A., Muley, T.R., Peifer, M., Gomez-Fernandez, C., Herbert, L., Egea, S., Huang, M., Thorne, L.B., Boice, L., Hill Salazar, A., Funkhouser, W.K., Rathmell, W.K., Dhir, R., Yousem, S.A., Dacic, S., Schneider, F., Siegfried, J.M., Hajek, R., Watson, M.A., McDonald, S., Meyers, B., Clarke, B., Yang, I.A., Fong, K.M., Hunter, L., Windsor, M., Bowman, R.V., Peters, S., Letovanec, I., Khan, K.Z., Jensen, M.A., Snyder, E.E., Srinivasan, D., Kahn, A.B., Baboud, J., Pot, D.A., Mills Shaw, K.R., Sheth, M., Davidsen, T., Demchok, J.A., Wang, Z., Tarnuzzer, R., Zenklusen, J.C., Ozenberger, B.A., Sofia, H.J., Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.
Subjects: Male, Lung Neoplasms, Adenocarcinoma/genetics, Adenocarcinoma/pathology, Cell Cycle Proteins/genetics, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genomics, Humans, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Molecular Typing, Mutation/genetics, Oncogenes/genetics, Sex Factors, Transcriptome/genetics, Adenocarcinoma of Lung, Cell Cycle Proteins, Biology, Adenocarcinoma, Exon, Germline mutation, microRNA, Adenocarcinoma of the lung, medicine, Gene, Multidisciplinary, Oncogene, Oncogenes, medicine.disease, MET Exon 14 Skipping Mutation, Molecular biology, 3. Good health, Mutation, Transcriptome
Abstract: Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
Published: 2013

16. Concurrent electrophysiological recording and cognitive testing in a rodent touchscreen environment

Author: Brian D. Kangas, Ann M. Iturra-Mena, Mykel A. Robble, Oanh T. Luc, David Potter, Stefanie Nickels, Jack Bergman, William A. Carlezon, and Diego A. Pizzagalli
Subjects: Medicine, Science
Abstract: Abstract Challenges in therapeutics development for neuropsychiatric disorders can be attributed, in part, to a paucity of translational models capable of capturing relevant phenotypes across clinical populations and laboratory animals. Touch-sensitive procedures are increasingly used to develop innovative animal models that better align with testing conditions used in human participants. In addition, advances in electrophysiological techniques have identified neurophysiological signatures associated with characteristics of neuropsychiatric illness. The present studies integrated these methodologies by developing a rat flanker task with electrophysiological recordings based on reverse-translated protocols used in human electroencephalogram (EEG) studies of cognitive control. Various touchscreen-based stimuli were evaluated for their ability to efficiently gain stimulus control and advance to flanker test sessions. Optimized stimuli were then examined for their elicitation of prototypical visual evoked potentials (VEPs) across local field potential (LFP) wires and EEG skull screws. Of the stimuli evaluated, purple and green photographic stimuli were associated with efficient training and expected flanker interference effects. Orderly stimulus-locked outcomes were also observed in VEPs across LFP and EEG recordings. These studies along with others verify the feasibility of concurrent electrophysiological recordings and rodent touchscreen-based cognitive testing and encourage future use of this integrated approach in therapeutics development.
Published: 2021
Full Text: View/download PDF

17. Comprehensive genomic characterization of squamous cell lung cancers

Author: Charles J. Vaske, Ying Du, Theodore C. Goldstein, Ping Yang, Yufeng Liu, Bryan Hernandez, Daniel R. Zerbino, Kenneth H. Buetow, Khurram Z. Khan, Semin Lee, Martin Peifer, Kristin G. Ardlie, James G. Herman, Sanja Dacic, Ashley Hill, Christopher Szeto, Jianjiong Gao, Singer Ma, Peng Chieh Chen, Carl F. Schaefer, David G. Beer, Kerstin David, Brent W. Zanke, Karen Mungall, Beverly Lee, Daniel DiCara, Kristen Rogers, Rui Jing, Christina Liquori, Carrie Sougnez, Ron Bose, Brian O'Connor, Piotr A. Mieczkowski, Scott L. Carter, Andy Chu, Peter W. Laird, David J. Kwiatkowski, R. Craig Cason, Marie Christine Aubry, Rileen Sinha, Dennis T. Maglinte, Chad J. Creighton, Howard H. Sussman, Jill M. Siegfried, Laura A.L. Dillon, Agnes Viale, Marco A. Marra, Stephen E. Schumacher, Dennis A. Wigle, Yongjun Zhao, Robert C. Onofrio, Heidi J. Sofia, Ranabir Guin, Lori Boice, Ling Li, Mark Backus, Pei Lin, Prachi Kothiyal, Jan F. Prins, Lauren Averett Byers, Haiyan I. Li, An He, Ka Ming Nip, Chang-Jiun Wu, Peter Dolina, James A. Robinson, Saianand Balu, Collisson E, Jinze Liu, Nicholas D. Socci, Erin Pleasance, Joan Pontius, Christina Yau, Eric E. Snyder, Shaowu Meng, Mei Huang, Aaron McKenna, Corbin D. Jones, Carl Morrison, Malcolm V. Brock, Chris Wakefield, Jared R. Slobodan, Ethan Cerami, Angela Tam, Jane Peterson, Michael D. Topal, Jacob M. Kaufman, Elena Helman, Richard T. Cheney, Dominik Stoll, Cristiane M. Ida, Dante Trusty, Peter S. Hammerman, Yevgeniy Antipin, D. Neil Hayes, Anders Jacobsen, Anna K. Unruh, Noreen Dhalla, Candace Shelton, Peter Waltman, Chris Sander, Zhining Wang, Derek Y. Chiang, Elizabeth J. Thomson, Vonn Walter, JoEllen Weaver, Elena Nemirovich-Danchenko, Jacqueline E. Schein, Bradley M. Broom, Sandra C. Tomaszek, Peter A. Kigonya, Tod D. Casasent, Ari B. Kahn, Joanne Yi, Kyle Ellrott, John M. S. Bartlett, Payal Sipahimalani, William D. Travis, Douglas Voet, Sean P. Barletta, Elizabeth Chun, J. Todd Auman, Ludmila Danilova, Katherine A. Hoadley, Marcin Imielinski, Ramaswamy Govindan, David P. Carbone, Leigh B. Thorne, David A. Wheeler, Carrie Hirst, Barbara Tabak, Sugy Kodeeswaran, Ijeoma A. Azodo, James Stephen Marron, Michael S. Noble, Jianjua John Zhang, Paul K. Paik, Deepak Srinivasan, Boris Reva, B. Arman Aksoy, Kristian Cibulskis, Douglas B. Flieder, Fei Pan, Daniel J. Weisenberger, Ronglai Shen, Jinhua Zhang, Nils Weinhold, Harman Sekhon, David Van Den Berg, Mark S. Guyer, Robert Penny, Hartmut Juhl, Marc Danie Nazaire, Yiqun Zhang, Eric A. Collisson, Robin J.N. Coope, Tom Bodenheimer, Richard Thorp, Junyuan Wu, Matthew Meyerson, Nguyen Phi Hung, Jerome Myers, Artem Sokolov, Yidi J. Turman, Thomas Muley, Stephen B. Baylin, Anisha Gulabani, A. Gordon Robertson, Lynda Chin, Eric Chuah, Richard Varhol, Margi Sheth, Janae V. Simons, Nils Gehlenborg, Tanja Davidsen, Psalm Haseley, Miruna Balasundaram, Olga Potapova, Spring Yingchun Liu, W. Kimryn Rathmell, Bizhan Bandarchi-Chamkhaleh, Wendy Winckler, David Mallery, Nicholas J. Petrelli, Nicole Todaro, Alex E. Lash, James Shin, Travis Brown, Igor Jurisica, Benjamin Gross, Hailei Zhang, Nikolaus Schultz, Kenna R. Mills Shaw, Nam Pho, William Pao, Darlene Lee, Zhen Fan, Troy Shelton, Yan Shi, Shelley Alonso, Carmelo Gaudioso, Peter B. Illei, Stuart R. Jefferys, Maureen F. Zakowski, Marian Rutledge, Bruce E. Johnson, Andrew J. Mungall, Eric S. Lander, Matthew G. Soloway, Michael Mayo, Christopher G. Maher, John V. Heymach, Lihua Zou, Dominique L. Berton, Nina Thiessen, Gary K. Scott, Anna L. Chu, Richard A. Hajek, Ming-Sound Tsao, Liming Yang, Qianxing Mo, Nguyen Van Bang, Martin Hirst, John Eckman, Erin Curley, Rajiv Dhir, Gad Getz, Stanley Girshik, Xuan Van Le, Jeff Boyd, Roman K. Thomas, Konstantin V. Fedosenko, Juok Cho, Alexei Protopopov, Nguyen Viet Tien, Lixing Yang, Laetitia Borsu, Steven J.M. Jones, Matthew D. Wilkerson, Mark Sherman, Andrew Crenshaw, Doug Voet, Elizabeth Buda, Jennifer Brown, Yaron S.N. Butterfield, Rehan Akbani, Todd Pihl, Ruibin Xi, Nianxiang Zhang, Jessica Walton, Ricardo Ramirez, Lisle E. Mose, Leslie Cope, Greg Eley, Mark A. Jensen, John N. Weinstein, Li Ding, Li-Wei Chang, Matthew C. Nicholls, Peter J. Park, Bui Duc Phu, Christopher R. Cabanski, Bernard Kohl, Julien Baboud, Joseph Paulauskis, David Pot, Gordon Robertson, Jingchun Zhu, John A. Demchok, Eunjung Lee, Giovanni Ciriello, Mary Iacocca, Gordon Saksena, Jesse Walsh, Yupu Liang, William K. Funkhouser, Rashmi N. Sanbhadti, Sam Ng, Venkatraman E. Seshan, Valerie W. Rusch, Robert A. Holt, Robert Sfeir, Jung E. Hye-Chun, Kai Wang, Helga Thorvaldsdottir, Huy V. Nguyen, Christopher Wilks, Brian Craft, Donghui Tan, David Haussler, Charles M. Perou, Timothy J. Triche, Christopher C. Benz, Scot Waring, Peggy Yena, Richard A. Moore, Darshan Singh, Andrew D. Cherniack, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Stacey Gabriel, Martha Hatfield, Christine Czerwinski, Alan P. Hoyle, Marc Ladanyi, Joshua M. Stuart, Andrey Sivachenko, Jacqueline D. Palchik, Thomas Zeng, Inanc Birol, Rohini Raman, Ijeoma Azodo, Jianhua Zhang, Adam B. Olshen, Bradley A. Ozenberger, Angela Hadjipanayis, Sachet A. Shukla, Barry S. Taylor, John M. Greene, Jill P. Mesirov, Petar Stojanov, Raju Kucherlapati, Richard Corbett, Farhad Kosari, Martin L. Ferguson, Natasha Rekhtman, Keith A. Baggerly, Scott Morris, Brenda Rabeno, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., and Park, Peter J.
Subjects: Lung Neoplasms, Squamous Differentiation, DNA Mutational Analysis, Adenocarcinoma of Lung, Biology, Adenocarcinoma, Article, Phosphatidylinositol 3-Kinases, Gefitinib, Mutation Rate, CDKN2A, Carcinoma, medicine, Humans, Molecular Targeted Therapy, Lung cancer, Multidisciplinary, Genome, Human, Gene Expression Profiling, Genes, p16, Genomics, medicine.disease, Genes, p53, Gene expression profiling, Gene Expression Regulation, Neoplastic, Mutation, Cancer research, Carcinoma, Squamous Cell, Gene Deletion, medicine.drug, Necitumumab, Signal Transduction
Abstract: Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers., National Institutes of Health (U.S.) (Grant U24 CA126561), National Institutes of Health (U.S.) (Grant U24 CA126551), National Institutes of Health (U.S.) (Grant U24 CA126554), National Institutes of Health (U.S.) (Grant U24 CA126543), National Institutes of Health (U.S.) (Grant U24 CA126546), National Institutes of Health (U.S.) (Grant U24 CA126563), National Institutes of Health (U.S.) (Grant U24 CA126544), National Institutes of Health (U.S.) (Grant U24 CA143845), National Institutes of Health (U.S.) (Grant U24 CA143858), National Institutes of Health (U.S.) (Grant U24 CA144025), National Institutes of Health (U.S.) (Grant U24 CA143882), National Institutes of Health (U.S.) (Grant U24 CA143866), National Institutes of Health (U.S.) (Grant U24 CA143867), National Institutes of Health (U.S.) (Grant U24 CA143848), National Institutes of Health (U.S.) (Grant U24 CA143840), National Institutes of Health (U.S.) (Grant U24 CA143835), National Institutes of Health (U.S.) (Grant U24 CA143799), National Institutes of Health (U.S.) (Grant U24 CA143883), National Institutes of Health (U.S.) (Grant U24 CA143843), National Institutes of Health (U.S.) (Grant U54 HG003067), National Institutes of Health (U.S.) (Grant U54 HG003079), National Institutes of Health (U.S.) (Grant U54 HG003273)
Published: 2012

18. Comprehensive molecular characterization of human colon and rectal cancer

Author: Donghui Tan, Nils Gehlenborg, Robert S. Fulton, Pat Swanson, Pei Lin, Chang-Jiun Wu, Piotr A. Mieczkowski, David Haussler, Marco A. Marra, Stephen E. Schumacher, Bernard Kohl, Jingchun Zhu, Lucinda Fulton, Charles M. Perou, Timothy J. Triche, Madhumati Gundapuneni, Mark Backus, Eve Shinbrot, Yonghong Xiao, Xuan Van Le, Liming Yang, Gad Getz, Stanley Girshik, Jessica Walton, Barbara Tabak, Greg Eley, Brian O'Connor, Larissa K. Temple, Saianand Balu, Eric A. Collisson, Tanja Davidsen, Elizabeth Buda, Janae V. Simons, Anisha Gulabani, Joseph Willis, Tod D. Casasent, Scott Morris, Doug Voat, Jireh Santibanez, Jennifer Drummond, Li Ding, Nicholas J. Petrelli, Andrew J. Mungall, Michael Mayo, Aaron D. Black, Gerald C. Chu, Elizabeth N. Medina, Huy V. Nguyen, Aaron E. Cozen, Yongjun Zhao, Hui Shen, Christopher Szeto, Brenda Rabeno, Martin Hirst, Bogumil Kaczkowski, Lisle E. Mose, Lora Lewis, Brian Craft, Joseph Paulauskis, Ari B. Kahn, Andy Chu, Peter W. Laird, Benjamin Gross, Matthew D. Wilkerson, Raju Kucherlapati, Matthew C. Nicholls, David Van Den Berg, Vesteinn Thorsson, Richard W. Park, Ethan Cerami, David A. Wheeler, Laura A.L. Dillon, Angela Tam, Julien Baboud, Kim D. Delehaunty, Katherine A. Hoadley, Ranabir Guin, Donna M. Muzny, Gordon Saksena, Shaowu Meng, Richard Kreisberg, Kenneth H. Buetow, Rajiv Dhir, Inanc Birol, Timo Erkkilä, Martin L. Ferguson, Robert A. Holt, Elaine R. Mardis, Aaron McKenna, Rohini Raman, Robert Sfeir, Mark Sherman, Andrew Crenshaw, J. Zachary Sanborn, Spring Yingchun Liu, Yuan Qing Wu, Jane Peterson, Eric E. Snyder, Lisa Iype, John N. Weinstein, Helga Thorvaldsdottir, Adam J. Bass, Dominik Stoll, Brady Bernard, Steven J.M. Jones, Peter Dolina, Julie M. Gastier-Foster, Jared R. Slobodan, Mark A. Jensen, Jacqueline E. Schein, Christie Kovar, Anders Jacobsen, Stephen C. Benz, J. Todd Auman, Juinhua Zhang, Peter Fielding, Paul T. Spellman, Jacqueline D. Palchik, Jay Bowen, Thomas Zeng, Douglas Voet, Arnulf Dörner, Joshua M. Stuart, Ryan Demeter, Theodore C. Goldstein, Keith A. Baggerly, Jorma J. de Ronde, Deepak Srinivasan, Boris Reva, Robert E. Pyatt, Andrew Kaufman, Timothy A. Chan, Alexei Protopopov, William G. Richards, Daniel R. Zerbino, Brenda Ayala, Martin R. Weiser, Psalm Haseley, Margaret Morgan, Mary Iacocca, Thomas Robinson, Chad J. Creighton, Dominique L. Berton, Da Yang, Peng Chieh Chen, Carl F. Schaefer, Peter White, Fred Denstman, Giovanni Ciriello, Matthew N. Bainbridge, Heidi J. Sofia, Irene Newsham, Jill P. Mesirov, Ling Li, Benjamin P. Berman, Daniel J. Weisenberger, Garrett M. Nash, Jason Walker, Nina Thiessen, Narayanan Sathiamoorthy, James A. Robinson, Petar Stojanov, Todd Wylie, Derek Y. Chiang, Kristin G. Ardlie, Jianjiong Gao, Lisa Wise, Bradley A. Ozenberger, Jeffrey G. Reid, Angela Hadjipanayis, Sachet A. Shukla, Barry S. Taylor, John M. Greene, Eric Chuah, Richard Varhol, Lisa R. Trevino, Charles J. Vaske, Ying Du, Arthur P. Goldberg, Rui Jing, Jon Whitmore, Joan Pontius, Yevgeniy Antipin, Kyle Ellrott, Nilsa C. Ramirez, Tom Bodenheimer, Junyuan Wu, Lynda Chin, Scott L. Carter, Hailei Zhang, Ryan Bressler, Adam Norberg, Stacey Gabriel, Martha Hatfield, Jonathan G. Seidman, Corbin D. Jones, Huyen Dinh, D. Neil Hayes, Christine Czerwinski, Gerald R. Fowler, Mark S. Guyer, Robert Penny, Alan P. Hoyle, Hartmut Juhl, Catrina Fronick, Margi Sheth, Christopher C. Benz, Scot Waring, Peggy Yena, Richard A. Moore, Darshan Singh, Toshinori Hinoue, Yaron S.N. Butterfield, Andrew D. Cherniack, Maria C. Mariano, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Marc Ladanyi, Anna K. Unruh, Noreen Dhalla, Candace Shelton, Gary Witkin, Andrey Sivachenko, David Pot, Michael J. Zinner, Richard Thorp, Jan F. Prins, Eunjung Lee, A. Gordon Robertson, Wendy Winckler, Efsevia Vakiani, Chris Wakefield, Alex H. Ramos, Semin Lee, Zhining Wang, Sam Ng, Lihua Zhou, Christina Liquori, Rileen Sinha, Dennis T. Maglinte, Michael S. Noble, Haiyan I. Li, B. Arman Aksoy, Preethi H. Gunaratne, Michael Meyers, Daniel C. Koboldt, Lawrence A. Donehower, Darlene Lee, Jake Lin, Gary K. Scott, Hye Jung E. Chun, Sheila Reynolds, Anna L. Chu, Rehan Akbani, Todd Pihl, Ruibin Xi, Charles S. Fuchs, Nianxiang Zhang, Stanley R. Hamilton, Bradley M. Broom, Wei Zhang, Chris Sander, Marc Danie Nazaire, Carrie Hirst, Stephen B. Baylin, Joel E. Tepper, Kyle Chang, Miruna Balasundaram, Jen Brown, Yan Shi, Matthew G. Soloway, Richard A. Gibbs, Richard K. Wilson, Peter J. Park, Zhaoshi Zeng, John A. Demchok, Jesse Walsh, Rashmi N. Sanbhadti, Troy Shelton, Lixing Yang, Prachi Kothiyal, Monica M. Bertagnolli, Sean P. Barletta, Kristian Cibulskis, Yidi J. Turman, Nikolaus Schultz, Min Wang, Shelley Alonso, Carsten Zornig, P. Paty, Elizabeth J. Thomson, Peter A. Kigonya, Fei Pan, Yuexin Liu, Matthew Meyerson, Kenna R. Mills Shaw, Nam Pho, Stuart R. Jefferys, Daniel DiCara, Robert C. Onofrio, Erin Pleasance, Eric S. Lander, David J. Dooling, Christina Yau, Michael D. Topal, David B. Solit, Christopher Wilks, Ilya Shmulevich, Robin J.N. Coope, Ronglai Shen, Jose G. Guillem, R. Craig Cason, Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.
Subjects: DNA Copy Number Variations, Colorectal cancer, Biology, medicine.disease_cause, MLH1, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Mutation Rate, microRNA, medicine, Humans, Exome, 030304 developmental biology, 0303 health sciences, Multidisciplinary, POLD1, Rectal Neoplasms, Gene Expression Profiling, Microsatellite instability, Sequence Analysis, DNA, DNA Methylation, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, DNA methylation, Colonic Neoplasms, Mutation, Cancer research, KRAS
Abstract: To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ε (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression., National Institutes of Health (U.S.) (Grant U24CA143799), National Institutes of Health (U.S.) (Grant U24CA143835), National Institutes of Health (U.S.) (Grant U24CA143840), National Institutes of Health (U.S.) (Grant U24CA143843), National Institutes of Health (U.S.) (Grant U24CA143845), National Institutes of Health (U.S.) (Grant U24CA143848), National Institutes of Health (U.S.) (Grant U24CA143858), National Institutes of Health (U.S.) (Grant U24CA143866), National Institutes of Health (U.S.) (Grant U24CA143867), National Institutes of Health (U.S.) (Grant U24CA143882), National Institutes of Health (U.S.) (Grant U24CA143883), National Institutes of Health (U.S.) (Grant U24CA144025), National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U54HG003079), National Institutes of Health (U.S.) (Grant U54HG003273)
Published: 2011

19. Text-mining of PubMed abstracts by natural language processing to create a public knowledge base on molecular mechanisms of bacterial enteropathogens

Author: Jon Whitmore, Guy Plunkett, Thomas Hampton, Nicole T. Perna, Jeremy D. Glasner, Matthew Shaker, Mila Ramos-Santacruz, John M. Greene, Sam Zaremba, Joel Fedorko, Panna Shetty, and David Pot
Subjects: Salmonella, PubMed, Databases, Factual, Relational database, Interface (Java), Computer science, Abstracting and Indexing, Information Storage and Retrieval, Scientific literature, Gene mutation, computer.software_genre, medicine.disease_cause, lcsh:Computer applications to medicine. Medical informatics, Bacterial Physiological Phenomena, Biochemistry, Field (computer science), Database, User-Computer Interface, Text mining, Enterobacteriaceae, Structural Biology, medicine, Escherichia coli, lcsh:QH301-705.5, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Molecular Biology, Natural Language Processing, Internet, business.industry, Applied Mathematics, Search engine indexing, Computational Biology, Computer Science Applications, Information extraction, ComputingMethodologies_PATTERNRECOGNITION, lcsh:Biology (General), lcsh:R858-859.7, Database Management Systems, Identification (biology), Artificial intelligence, business, computer, Natural language processing
Abstract: Background The Enteropathogen Resource Integration Center (ERIC; http://www.ericbrc.org) has a goal of providing bioinformatics support for the scientific community researching enteropathogenic bacteria such as Escherichia coli and Salmonella spp. Rapid and accurate identification of experimental conclusions from the scientific literature is critical to support research in this field. Natural Language Processing (NLP), and in particular Information Extraction (IE) technology, can be a significant aid to this process. Description We have trained a powerful, state-of-the-art IE technology on a corpus of abstracts from the microbial literature in PubMed to automatically identify and categorize biologically relevant entities and predicative relations. These relations include: Genes/Gene Products and their Roles; Gene Mutations and the resulting Phenotypes; and Organisms and their associated Pathogenicity. Evaluations on blind datasets show an F-measure average of greater than 90% for entities (genes, operons, etc.) and over 70% for relations (gene/gene product to role, etc). This IE capability, combined with text indexing and relational database technologies, constitute the core of our recently deployed text mining application. Conclusion Our Text Mining application is available online on the ERIC website http://www.ericbrc.org/portal/eric/articles. The information retrieval interface displays a list of recently published enteropathogen literature abstracts, and also provides a search interface to execute custom queries by keyword, date range, etc. Upon selection, processed abstracts and the entities and relations extracted from them are retrieved from a relational database and marked up to highlight the entities and relations. The abstract also provides links from extracted genes and gene products to the ERIC Annotations database, thus providing access to comprehensive genomic annotations and adding value to both the text-mining and annotations systems.
Published: 2008

20. A New Asset for Pathogen Informatics – the Enteropathogen Resource Integration Center (ERIC), an NIAID Bioinformatics Resource Center for Biodefense and Emerging/Re-emerging Infectious Disease

Author: Jeremy D. Glasner, Michael Rusch, Lorie Shaull, Matthew Shaker, Jon Whitmore, Yu Qiu, Bob Mau, Eric Neeno-Eckwall, Thomas Hampton, Guy Plunkett, Valerie Burland, Chuan Shi, Frederick R. Blattner, Nicole T. Perna, Panna Shetty, Paul Liss, Mary Wong, John M. Greene, David Pot, Sam Zaremba, Brad Anderson, and Eric L. Cabot
Subjects: Comparative genomics, Biodefense, Yersinia Infections, biology, business.industry, education, Poison control, Genome project, Bioinformatics, biology.organism_classification, Infectious disease (medical specialty), parasitic diseases, Emerging infectious disease, Medicine, business, Yersinia enterocolitica
Abstract: ERIC (Enteropathogen Resource Information Center) is one of the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers for Biodefense and Emerging/Re-emerging Infectious Disease. ERIC serves as a comprehensive information resource for five related pathogens: Yersinia enterocolitica, Yersinia pestis, diarrheagenic E. coli, Shigella spp., and Salmonella spp. ERIC integrates genomics, proteomics, biochemical and microbiological information to facilitate the interpretation and understanding of ERIC pathogens and select related non-pathogens for the advancement of diagnostics, therapeutics, and vaccines. ERIC (www.ericbrc.org) is evolving to provide state-of-the-art analysis tools and data types, such as genome sequencing, comparative genomics, genome polymorphisms, gene expression, proteomics, and pathways as well as expertly curated community genome annotation. Genome sequence and genome annotation data and a variety of analysis and tools for eight strains of Yersinia enterocolitica and Yersinia pestis pathogens (Yersinia pestis biovars Mediaevalis KIM, Mediaevalis 91001, Orientalis CO92, Orientalis IP275, Antiqua Angola, Antiqua Antiqua, Antiqua Nepal516, and Yersinia enterocolitica 8081) and two strains of Yersinia pseudotuberculosis (Yersinia pseudotuberculosis IP32953 and IP31758) are currently available through the ERIC portal. ERIC seeks to maintain a strong collaboration with the scientific community so that we can continue to identify and incorporate the latest research data, tools, and training to best meet the current and future needs of the enteropathogen research community. All tools and data developed under this NIAID contract will be freely available. Please contact info@ericbrc.org for more information.
Published: 2007

21. A quantitative trait locus analysis of natural genetic variation for Drosophila melanogaster oxidative stress survival

Author: David Pot, Sergey V. Nuzhdin, Stephen D. Kachman, Lawrence G. Harshman, and Yue Wang
Subjects: Male, medicine.disease_cause, Animals, Genetically Modified, Inbred strain, Genetics (clinical), media_common, Genetics, Ovule, Likelihood Functions, Sex Characteristics, biology, Age Factors, Longevity, Chromosome Mapping, food and beverages, Drosophila melanogaster, Natural population growth, Drosophila, Female, Animals, Inbred Strains, Biotechnology, Locus des caractères quantitatifs, media_common.quotation_subject, Quantitative Trait Loci, Quantitative trait locus, Stress, Quantitative Trait, Heritable, Variation génétique, Analyse quantitative, Genetic variation, medicine, Animals, L50 - Physiologie et biochimie animales, Oxydation, Molecular Biology, Ovum, Probability, Population Density, Genetic Variation, biology.organism_classification, L10 - Génétique et amélioration des animaux, Survival Analysis, Oxidative Stress, Fertility, Expression quantitative trait loci, Oxidative stress
Abstract: Little is known about natural genetic variation for survival under oxidative stress conditions or whether genetic variation for oxidative stress survival is associated with that for life-history traits. We have investigated survival in a high-oxygen environment at 2 adult densities using a set of recombinant inbred lines (RILs) isolated from a natural population of Drosophila melanogaster. Female and male oxidative stress survival was highly correlated. Quantitative trait loci (QTLs) for oxidative stress survival were identified on both autosomes. These QTLs were sometimes sex or density specific but were most often not. QTLs were identified that colocalize to the same region of the genome as longevity in other studies using the same set of RILs. We also determined early-age egg production and found QTLs for this trait, but there was no support for an association between oxidative stress survival and egg production.
Published: 2006

22. Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs

Author: Kateřina Hanáková, Ondřej Bernatík, Marek Kravec, Miroslav Micka, Jitender Kumar, Jakub Harnoš, Petra Ovesná, Petra Paclíková, Matěj Rádsetoulal, David Potěšil, Konstantinos Tripsianes, Lukáš Čajánek, Zbyněk Zdráhal, and Vítězslav Bryja
Subjects: Dishevelled, DVL3, Phosphorylation, Kinase, Mass spectrometry, CK1, Medicine, Cytology, QH573-671
Abstract: Abstract Background Dishevelled (DVL) is an essential component of the Wnt signaling cascades. Function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose phosphorylation generates complex barcodes underlying diverse DVL3 functions. In order to dissect the role of DVL phosphorylation we analyzed the phosphorylation of human DVL3 induced by previously reported (CK1ε, NEK2, PLK1, CK2α, RIPK4, PKCδ) and newly identified (TTBK2, Aurora A) DVL kinases. Methods Shotgun proteomics including TiO2 enrichment of phosphorylated peptides followed by liquid chromatography tandem mass spectrometry on immunoprecipitates from HEK293T cells was used to identify and quantify phosphorylation of DVL3 protein induced by 8 kinases. Functional characterization was performed by in-cell analysis of phospho-mimicking/non-phosphorylatable DVL3 mutants and supported by FRET assays and NMR spectroscopy. Results We used quantitative mass spectrometry and calculated site occupancies and quantified phosphorylation of > 80 residues. Functional validation demonstrated the importance of CK1ε-induced phosphorylation of S268 and S311 for Wnt-3a-induced β-catenin activation. S630–643 cluster phosphorylation by CK1, NEK2 or TTBK2 is essential for even subcellular distribution of DVL3 when induced by CK1 and TTBK2 but not by NEK2. Further investigation showed that NEK2 utilizes a different mechanism to promote even localization of DVL3. NEK2 triggered phosphorylation of PDZ domain at S263 and S280 prevents binding of DVL C-terminus to PDZ and promotes an open conformation of DVL3 that is more prone to even subcellular localization. Conclusions We identify unique phosphorylation barcodes associated with DVL function. Our data provide an example of functional synergy between phosphorylation in structured domains and unstructured IDRs that together dictate the biological outcome. Video Abtract. Graphical abstract
Published: 2019
Full Text: View/download PDF

23. RNF43 inhibits WNT5A-driven signaling and suppresses melanoma invasion and resistance to the targeted therapy

Author: Tomasz Radaszkiewicz, Michaela Nosková, Kristína Gömöryová, Olga Vondálová Blanářová, Katarzyna Anna Radaszkiewicz, Markéta Picková, Ráchel Víchová, Tomáš Gybeľ, Karol Kaiser, Lucia Demková, Lucia Kučerová, Tomáš Bárta, David Potěšil, Zbyněk Zdráhal, Karel Souček, and Vítězslav Bryja
Subjects: RNF43, WNT5A, melanoma, ROR1, VANGL1, BRAF V600E, Medicine, Science, Biology (General), QH301-705.5
Abstract: RNF43 is an E3 ubiquitin ligase and known negative regulator of WNT/β-catenin signaling. We demonstrate that RNF43 is also a regulator of noncanonical WNT5A-induced signaling in human cells. Analysis of the RNF43 interactome using BioID and immunoprecipitation showed that RNF43 can interact with the core receptor complex components dedicated to the noncanonical Wnt pathway such as ROR1, ROR2, VANGL1, and VANGL2. RNF43 triggers VANGL2 ubiquitination and proteasomal degradation and clathrin-dependent internalization of ROR1 receptor and inhibits ROR2 activation. These activities of RNF43 are physiologically relevant and block pro-metastatic WNT5A signaling in melanoma. RNF43 inhibits responses to WNT5A, which results in the suppression of invasive properties of melanoma cells. Furthermore, RNF43 prevented WNT5A-assisted development of resistance to BRAF V600E and MEK inhibitors. Next, RNF43 acted as melanoma suppressor and improved response to targeted therapies in vivo. In line with these findings, RNF43 expression decreases during melanoma progression and RNF43-low patients have a worse prognosis. We conclude that RNF43 is a newly discovered negative regulator of WNT5A-mediated biological responses that desensitizes cells to WNT5A.
Published: 2021
Full Text: View/download PDF

24. Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments.

Author: Shelli Schomaker, David Potter, Roscoe Warner, Jane Larkindale, Nicholas King, Amy C Porter, Jane Owens, Lindsay Tomlinson, John-Michael Sauer, Kent Johnson, and Jiri Aubrecht
Subjects: Medicine, Science
Abstract: Serum activities of alanine and aspartate aminotransferases (ALT and AST) are used as gold standard biomarkers for the diagnosis of hepatocellular injury. Since ALT and AST lack liver specificity, the diagnosis of the onset of hepatocellular injury in patients with underlying muscle impairments is severely limited. Thus, we evaluated the potential of glutamate dehydrogenase (GLDH) as a liver specific alternative biomarker of hepatocellular injury. In our study, serum GLDH in subjects with Duchene muscular dystrophy (DMD) was equivalent to serum GLDH in age matched healthy subjects, while serum ALT was increased 20-fold in DMD subjects. Furthermore, serum GLDH in 131 subjects with variety of muscle impairments was similar to serum GLDH of healthy subjects while serum ALT corelated with serum creatine kinase, a widely accepted biomarker of muscle impairment. In addition, significant elevations of ALT, AST, and CK were observed in a case of a patient with rhabdomyolysis, while serum GLDH stayed within the normal range until the onset of hypoxia-induced liver injury. In a mouse model of DMD (DMDmdx), serum GLDH but not serum ALT clearly correlated with the degree of acetaminophen-induced liver injury. Taken together, our data support the utility of serum GLDH as a liver-specific biomarker of liver injury that has a potential to improve diagnosis of hepatocellular injury in patients with underlying muscle impairments. In drug development, GLDH may have utility as a biomarker of drug induced liver injury in clinical trials of new therapies to treat muscle diseases such as DMD.
Published: 2020
Full Text: View/download PDF

25. Laser capture microdissection in combination with mass spectrometry: Approach to characterization of tissue-specific proteomes of Eudiplozoon nipponicum (Monogenea, Polyopisthocotylea).

Author: Pavel Roudnický, David Potěšil, Zbyněk Zdráhal, Milan Gelnar, and Martin Kašný
Subjects: Medicine, Science
Abstract: Eudiplozoon nipponicum (Goto, 1891) is a hematophagous monogenean ectoparasite which inhabits the gills of the common carp (Cyprinus carpio). Heavy infestation can lead to anemia and in conjunction with secondary bacterial infections cause poor health and eventual death of the host. This study is based on an innovative approach to protein localization which has never been used in parasitology before. Using laser capture microdissection, we dissected particular areas of the parasite body without contaminating the samples by surrounding tissue and in combination with analysis by mass spectrometry obtained tissue-specific proteomes of tegument, intestine, and parenchyma of our model organism, E. nipponicum. We successfully verified the presence of certain functional proteins (e.g. cathepsin L) in tissues where their presence was expected (intestine) and confirmed that there were no traces of these proteins in other tissues (tegument and parenchyma). Additionally, we identified a total of 2,059 proteins, including 72 peptidases and 33 peptidase inhibitors. As expected, the greatest variety was found in the intestine and the lowest variety in the parenchyma. Our results are significant on two levels. Firstly, we demonstrated that one can localize all proteins in one analysis and without using laboratory animals (antibodies for immunolocalization of single proteins). Secondly, this study offers the first complex proteomic data on not only the E. nipponicum but within the whole class of Monogenea, which was from this point of view until recently neglected.
Published: 2020
Full Text: View/download PDF

26. Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation

Author: Erin A Bassett, Nicholas Tokarew, Ema A Allemano, Chantal Mazerolle, Katy Morin, Alan J Mears, Brian McNeill, Randy Ringuette, Charles Campbell, Sheila Smiley, Neno T Pokrajac, Adrian M Dubuc, Vijay Ramaswamy, Paul A Northcott, Marc Remke, Philippe P Monnier, David Potter, Kim Paes, Laura L Kirkpatrick, Kenneth J Coker, Dennis S Rice, Carol Perez-Iratxeta, Michael D Taylor, and Valerie A Wallace
Subjects: Medulloblastoma, Patched, Hedgehog, Norrin, Frizzled4, stroma, Medicine, Science, Biology (General), QH301-705.5
Abstract: The tumor microenvironment is a critical modulator of carcinogenesis; however, in many tumor types, the influence of the stroma during preneoplastic stages is unknown. Here we explored the relationship between pre-tumor cells and their surrounding stroma in malignant progression of the cerebellar tumor medulloblastoma (MB). We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch+/− mouse model. Loss of Norrin/Fzd4-mediated signalling in endothelial cells, either genetically or by short-term blockade, increases the frequency of pre-tumor lesions and creates a tumor-permissive microenvironment at the earliest, preneoplastic stages of MB. This pro-tumor stroma, characterized by angiogenic remodelling, is associated with an accelerated transition from preneoplasia to malignancy. These data expose a stromal component that regulates the earliest stages of tumorigenesis in the cerebellum, and a novel role for the Norrin/Fzd4 axis as an endogenous anti-tumor signal in the preneoplastic niche.
Published: 2016
Full Text: View/download PDF

27. Sprouty2 in the dorsal hippocampus regulates neurogenesis and stress responsiveness in rats.

Author: Antonia L Dow, Tiffany V Lin, Elena H Chartoff, David Potter, Donna L McPhie, Ashlee V Van't Veer, Allison T Knoll, Kristen N Lee, Rachael L Neve, Tarun B Patel, Dost Ongur, Bruce M Cohen, and William A Carlezon
Subjects: Medicine, Science
Abstract: Both the development and relief of stress-related psychiatric conditions such as major depression (MD) and post-traumatic stress disorder (PTSD) have been linked to neuroplastic changes in the brain. One such change involves the birth of new neurons (neurogenesis), which occurs throughout adulthood within discrete areas of the mammalian brain, including the dorsal hippocampus (HIP). Stress can trigger MD and PTSD in humans, and there is considerable evidence that it can decrease HIP neurogenesis in laboratory animals. In contrast, antidepressant treatments increase HIP neurogenesis, and their efficacy is eliminated by ablation of this process. These findings have led to the working hypothesis that HIP neurogenesis serves as a biomarker of neuroplasticity and stress resistance. Here we report that local alterations in the expression of Sprouty2 (SPRY2), an intracellular inhibitor of growth factor function, produces profound effects on both HIP neurogenesis and behaviors that reflect sensitivity to stressors. Viral vector-mediated disruption of endogenous Sprouty2 function (via a dominant negative construct) within the dorsal HIP of adult rats stimulates neurogenesis and produces signs of stress resilience including enhanced extinction of conditioned fear. Conversely, viral vector-mediated elevation of SPRY2 expression intensifies the behavioral consequences of stress. Studies of these manipulations in HIP primary cultures indicate that SPRY2 negatively regulates fibroblast growth factor-2 (FGF2), which has been previously shown to produce antidepressant- and anxiolytic-like effects via actions in the HIP. Our findings strengthen the relationship between HIP plasticity and stress responsiveness, and identify a specific intracellular pathway that could be targeted to study and treat stress-related disorders.
Published: 2015
Full Text: View/download PDF

28. Large-Scale Variations in Lumber Value Recovery of Yellow Birch and Sugar Maple in Quebec, Canada.

Author: Mariana Hassegawa, Filip Havreljuk, Rock Ouimet, David Auty, David Pothier, and Alexis Achim
Subjects: Medicine, Science
Abstract: Silvicultural restoration measures have been implemented in the northern hardwoods forests of southern Quebec, Canada, but their financial applicability is often hampered by the depleted state of the resource. To help identify sites most suited for the production of high quality timber, where the potential return on silvicultural investments should be the highest, this study assessed the impact of stand and site characteristics on timber quality in sugar maple (Acer saccharum Marsh.) and yellow birch (Betula alleghaniensis Britt.). For this purpose, lumber value recovery (LVR), an estimate of the summed value of boards contained in a unit volume of round wood, was used as an indicator of timber quality. Predictions of LVR were made for yellow birch and sugar maple trees contained in a network of more than 22000 temporary sample plots across the Province. Next, stand-level variables were selected and models to predict LVR were built using the boosted regression trees method. Finally, the occurrence of spatial clusters was verified by a hotspot analysis. Results showed that in both species LVR was positively correlated with the stand age and structural diversity index, and negatively correlated with the number of merchantable stems. Yellow birch had higher LVR in areas with shallower soils, whereas sugar maple had higher LVR in regions with deeper soils. The hotspot analysis indicated that clusters of high and low LVR exist across the province for both species. Although it remains uncertain to what extent the variability of LVR may result from variations in past management practices or in inherent site quality, we argue that efforts to produce high quality timber should be prioritized in sites where LVR is predicted to be the highest.
Published: 2015
Full Text: View/download PDF

29. Comprehensive molecular portraits of human breast tumours

Author: Julie M. Gastier-Foster, Nguyen Van Bang, Christopher Szeto, Daoud Meerzaman, Nguyen Viet Tien, Richard K. Wilson, Jennifer Brown, Singer Ma, Andrew H. Beck, Sam Ng, Phillip H. Lai, Peter J. Park, Khurram Z. Khan, Gordon B. Mills, Joel S. Parker, Li Ding, Ying Hu, Jill P. Mesirov, Rebecca Carlsen, Kevin P. White, Benjamin P. Berman, Michael C. Adams, Laura A.L. Dillon, Jake Lin, Giovanni Ciriello, Simeen Malik, Moiz S. Bootwalla, Sheila Reynolds, Petar Stojanov, B. Arman Aksoy, Jerry Usary, Mei Huang, Andrzej Mackiewicz, Prachi Kothiyal, Keith A. Baggerly, Hann Hsiang Chao, Timo Erkkilä, Elaine R. Mardis, Nils Gehlenborg, Bradley M. Broom, Tara M. Lichtenberg, Jeff Gentry, Payal Sipahimalani, Chris Wakefield, Zhining Wang, Anna Chu, Konstanty Korski, Michael S. Noble, Lawrence A. Donehower, Pavana Anur, Janita Thusberg, Rohit Bhargava, Chris Sander, Lori Boice, Juok Cho, Charles Saller, Sophie C. Egea, Marc Danie Nazaire, Heather Schmidt, Bui Duc Phu, Hye Jung E. Chun, Bradley A. Ozenberger, Robert S. Fulton, Carrie Hirst, Stephen B. Baylin, Miruna Balasundaram, Peter White, Fergus J. Couch, Saianand Balu, Christina Yau, Yevgeniy Antipin, Jacek J. Brzeziński, Rehan Akbani, Todd Pihl, Ari B. Kahn, Nianxiang Zhang, Sean P. Barletta, Mary Iacocca, Kelly Daily, Wiam Bshara, Marc Ladanyi, Michael D. Topal, Huy Nguyen, Theodore C. Goldstein, Tari A. King, Bernard Kohl, Jingchun Zhu, Wiktoria Maria Suchorska, Xuan Van Le, Wei Zhang, Yan Shi, Marta Bogusz-Czerniewicz, Barry S. Taylor, Li-Wei Chang, Matthew C. Nicholls, Julien Baboud, Honorata Tatka, Doug Voet, Vesteinn Thorsson, Richard W. Park, Aaron D. Black, Pawel Murawa, Leonid Kvecher, Raju Kucherlapati, Colleen Mitchell, Wei Zhao, Leigh B. Thorne, Artem Sokolov, Modesto Patangan, Yidi J. Turman, Teresa R. Tabler, Kyle Ellrott, Yaron S.N. Butterfield, Gordon Saksena, Ronglai Shen, Yaqin Chen, Olga Voronina, Candace Carter, Yiling Lu, Cynthia McAllister, Thomas Stricker, Chunqing Luo, Dominique L. Berton, Thomas Barr, Robert A. Holt, Christopher Wilks, David Van Den Berg, Robert Sfeir, Ilya Shmulevich, Ranabir Guin, Nilsa C. Ramirez, Hollie A. Harper, John A. Demchok, Matthew J. Ellis, David Haussler, Katherine A. Hoadley, Eric Chuah, Richard J. Mural, Charles M. Perou, Timothy J. Triche, Steven J.M. Jones, Mark A. Jensen, Jeffrey R. Marks, Hanna Perz, Rashmi N. Sanbhadti, Robin J.N. Coope, Brian Craft, Andy Chu, Peter W. Laird, Eric E. Snyder, Chunhua Yan, Martin L. Ferguson, Junyuan Wu, Richard Varhol, Daniel J. Weisenberger, Yongjun Zhao, Ewa Leporowska, Ashley Hill, Katie Tarvin, M. Teresiak, David Pot, Nguyen Phi Hung, Helga Thorvaldsdottir, Erik Zmuda, Spring Yingchun Liu, Melissa Hart-Kothari, Joshua M. Stuart, Caroline Larson, Erin Pleasance, Nikolaus Schultz, Matthew Ibbs, Hubert Stoppler, Joelle Kalicki-Veizer, Andrey Sivachenko, Christopher C. Benz, Dawid Murawa, Swapna Mahurkar, Nicholas J. Petrelli, Lynda Chin, Juinhua Zhang, Pei Lin, Michael Mayo, Wilma L. Lingle, Julian Malicki, Robin Brookens, Ethan Cerami, Angela Tam, Shelley Alonso, Carmelo Gaudioso, Dominik Stoll, Anders Jacobsen, Stephen C. Benz, Mark S. Guyer, Wendy Winckler, Roel R.G. Verhaak, Chang-Jiun Wu, Raktim Sinha, Xiaping He, Nina Thiessen, Craig D. Shriver, Kenna R. Mills Shaw, Heidi J. Sofia, Martin Hirst, Stuart R. Jefferys, Robert Penny, Adam Brufsky, Kristen M. Leraas, Joshua F. McMichael, Brenda Rabeno, Inanc Birol, David J. Dooling, Peggy Yena, Richard A. Moore, Andrew D. Cherniack, Lucinda Fulton, Jessica K. Booker, Lihua Zou, Rileen Sinha, Michael D. Iglesia, Dennis T. Maglinte, Rohini Raman, Evan O. Paull, Rameen Beroukhim, Oleg Dolzhansky, Grace O. Silva, Jiashan Zhang, Witold Kycler, Janae V. Simons, Anisha Gulabani, Michael S. Lawrence, Peter Fielding, Huynh Quyet Thang, Peter A. Kigonya, Myra M. George, Jay Bowen, Haiyan I. Li, Robert E. Pyatt, Margi Sheth, Stacey Gabriel, Ana M. Gonzalez-Angulo, Hui Shen, Andrew J. Mungall, Carmen Gomez-Fernandez, Liming Yang, Hai Hu, Radoslaw Łaźniak, Olufunmilayo I. Olopade, Christine Czerwinski, Richard A. Hajek, Michael D. McLellan, Arash Shafiei, Matthew Meyerson, Gad Getz, Stanley Girshik, Cheng Fan, Shuying Liu, Olga Potapova, Alan P. Hoyle, Mia Grifford, Daniel C. Koboldt, Jacqueline D. Palchik, Jessica Walton, Greg Eley, Jamie Leigh Campbell, Thomas Zeng, Mikhail Abramov, Benjamin Gross, Brenda Deyarmin, Maciej Wiznerowicz, Natasja Wye, Ron Bose, Darlene Lee, Carl Morrison, Albert J. Kovatich, Andrew Crenshaw, Jessica Frick, John N. Weinstein, Adrian Ally, Nam H. Pho, Brady Bernard, Scott L. Carter, Gary K. Scott, Steven E. Schumacher, Barbara Tabak, D. Neil Hayes, Robert C. Onofrio, Sean D. Mooney, Mary D. Dyer, Mark Gerken, Erin Curley, Rajiv Dhir, Anna K. Unruh, Noreen Dhalla, Candace Shelton, Kevin R. Coombes, Richard Thorp, George E. Sandusky, A. Gordon Robertson, Marco A. Marra, Roy Tarnuzzer, Mark Backus, Aleix Prat, Kristin G. Ardlie, Daniel Di Cara, Richard Kreisberg, Kenneth H. Buetow, Jacqueline E. Schein, J. Todd Auman, Jianjiong Gao, Lisa Wise, Ling Li, James A. Robinson, Jonathan S. Berg, Tod D. Casasent, James N. Ingle, Brenda Ayala, Xiaolong Meng, Boris Reva, Rui Jing, Mark D. Pegram, Arkadiusz Spychała, Joan Pontius, Jeffrey A. Hooke, Daniel E. Carlin, Nils Weinhold, Jared R. Slobodan, Tom Bodenheimer, Wenbin Liu, Christopher K. Wong, W. Kimryn Rathmell, David Mallery, Paul T. Spellman, Hailei Zhang, Ryan Bressler, Deepak Srinivasan, Lisle E. Mose, Bryan Hernandez, Stella Somiari, Chad J. Creighton, Howard H. Sussman, Frederic Waldman, Matthew G. Soloway, and Universitat de Barcelona
Subjects: Proteomics, Oncologia, DNA Mutational Analysis, Genes, BRCA1, Retinoblastoma Protein, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Breast cancer, Exome, RNA, Neoplasm, Exome sequencing, Oligonucleotide Array Sequence Analysis, Ovarian Neoplasms, Genetics, 0303 health sciences, Multidisciplinary, Triple Negative Breast Neoplasms, Genomics, 3. Good health, Gene Expression Regulation, Neoplastic, Receptors, Estrogen, Oncology, 030220 oncology & carcinogenesis, Female, DNA Copy Number Variations, Class I Phosphatidylinositol 3-Kinases, Protein Array Analysis, MAP Kinase Kinase Kinase 1, Breast Neoplasms, GATA3 Transcription Factor, Biology, Article, Càncer de mama, Genetic Heterogeneity, 03 medical and health sciences, medicine, Humans, RNA, Messenger, 030304 developmental biology, MicroRNA sequencing, Genome, Human, Genetic heterogeneity, Gene Expression Profiling, Cancer, DNA Methylation, Genes, erbB-2, Genes, p53, medicine.disease, Claudin-Low, Expressió gènica, MicroRNAs, Genòmica, Mutation, Gene expression, Genes, Neoplasm
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

30. Keratinocyte migration in the developing eyelid requires LIMK2.

Author: Dennis S Rice, Gwenn M Hansen, Feng Liu, Mike J Crist, Matthew M Newhouse, David Potter, Nianhua Xu, Alejandro Abuin, Peter J Vogel, and Brian P Zambrowicz
Subjects: Medicine, Science
Abstract: In vitro studies have identified LIMK2 as a key downstream effector of Rho GTPase-induced changes in cytoskeletal organization. LIMK2 is phosphorylated and activated by Rho associated coiled-coil kinases (ROCKs) in response to a variety of growth factors. The biochemical targets of LIMK2 belong to a family of actin binding proteins that are potent modulators of actin assembly and disassembly. Although numerous studies have suggested that LIMK2 regulates cell morphology and motility, evidence supportive of these functions in vivo has remained elusive. In this study, a knockout mouse was created that abolished LIMK2 biochemical activity resulting in a profound inhibition of epithelial sheet migration during eyelid development. In the absence of LIMK2, nascent eyelid keratinocytes differentiate and acquire a pre-migratory phenotype but the leading cells fail to nucleate filamentous actin and remain immobile causing an eyes open at birth (EOB) phenotype. The failed nucleation of actin was associated with significant reductions in phosphorylated cofilin, a major LIMK2 biochemical substrate and potent modulator of actin dynamics. These results demonstrate that LIMK2 activity is required for keratinocyte migration in the developing eyelid.
Published: 2012
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

30 results on '"David Pot"'

1. SL-Cloud: A Cloud-based resource to support synthetic lethal interaction discovery [version 2; peer review: 2 approved]

2. Domestication reduces alternative splicing expression variations in sorghum.

3. Transcriptome Analysis of Leaves, Flowers and Fruits Perisperm of Coffea arabica L. Reveals the Differential Expression of Genes Involved in Raffinose Biosynthesis.

4. Genetic structure, linkage disequilibrium and signature of selection in Sorghum: lessons from physically anchored DArT markers.

5. NCI Imaging Data Commons

6. Diterpenes biochemical profile and transcriptional analysis of cytochrome P450s genes in leaves, roots, flowers, and during Coffea arabica L. fruit development

7. Catechol-O-methyl transferase suppresses cell invasion and interplays with MET signaling in estrogen dependent breast cancer

8. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

9. Integrated genomic characterization of endometrial carcinoma

10. Chemical composition in wild Ethiopian Arabica coffee accessions

11. Evaluation of Kahweol and Cafestol in Coffee Tissues and Roasted Coffee by a New High-Performance Liquid Chromatography Methodology

12. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

13. Signaling Inositol Polyphosphate-5-phosphatase

14. Comprehensive molecular characterization of urothelial bladder carcinoma

15. Comprehensive molecular profiling of lung adenocarcinoma

16. Concurrent electrophysiological recording and cognitive testing in a rodent touchscreen environment

17. Comprehensive genomic characterization of squamous cell lung cancers

18. Comprehensive molecular characterization of human colon and rectal cancer

19. Text-mining of PubMed abstracts by natural language processing to create a public knowledge base on molecular mechanisms of bacterial enteropathogens

20. A New Asset for Pathogen Informatics – the Enteropathogen Resource Integration Center (ERIC), an NIAID Bioinformatics Resource Center for Biodefense and Emerging/Re-emerging Infectious Disease

21. A quantitative trait locus analysis of natural genetic variation for Drosophila melanogaster oxidative stress survival

22. Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs

23. RNF43 inhibits WNT5A-driven signaling and suppresses melanoma invasion and resistance to the targeted therapy

24. Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments.

25. Laser capture microdissection in combination with mass spectrometry: Approach to characterization of tissue-specific proteomes of Eudiplozoon nipponicum (Monogenea, Polyopisthocotylea).

26. Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation

27. Sprouty2 in the dorsal hippocampus regulates neurogenesis and stress responsiveness in rats.

28. Large-Scale Variations in Lumber Value Recovery of Yellow Birch and Sugar Maple in Quebec, Canada.

29. Comprehensive molecular portraits of human breast tumours

30. Keratinocyte migration in the developing eyelid requires LIMK2.

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

30 results on '"David Pot"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources