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  • 1
    Publication Date: 2013-01-23
    Description: Sequencing studies from several model systems have suggested that diverse and abundant small RNAs may be derived from tRNA, but the function of these molecules remains undefined. Here, we demonstrate that one such tRNA-derived fragment, cloned from human mature B cells and designated CU1276, in fact possesses the functional characteristics...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2009-05-05
    Description: Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adulthood, comprises multiple biologically and clinically distinct subtypes including germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. Gene expression profile studies have shown that its most aggressive subtype, ABC-DLBCL, is associated with constitutive activation of the NF-kappaB transcription complex. However, except for a small fraction of cases, it remains unclear whether NF-kappaB activation in these tumours represents an intrinsic program of the tumour cell of origin or a pathogenetic event. Here we show that 〉50% of ABC-DLBCL and a smaller fraction of GCB-DLBCL carry somatic mutations in multiple genes, including negative (TNFAIP3, also called A20) and positive (CARD11, TRAF2, TRAF5, MAP3K7 (TAK1) and TNFRSF11A (RANK)) regulators of NF-kappaB. Of these, the A20 gene, which encodes a ubiquitin-modifying enzyme involved in termination of NF-kappaB responses, is most commonly affected, with approximately 30% of patients displaying biallelic inactivation by mutations and/or deletions. When reintroduced in cell lines carrying biallelic inactivation of the gene, A20 induced apoptosis and cell growth arrest, indicating a tumour suppressor role. Less frequently, missense mutations of TRAF2 and CARD11 produce molecules with significantly enhanced ability to activate NF-kappaB. Thus, our results demonstrate that NF-kappaB activation in DLBCL is caused by genetic lesions affecting multiple genes, the loss or activation of which may promote lymphomagenesis by leading to abnormally prolonged NF-kappaB responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973325/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973325/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Compagno, Mara -- Lim, Wei Keat -- Grunn, Adina -- Nandula, Subhadra V -- Brahmachary, Manisha -- Shen, Qiong -- Bertoni, Francesco -- Ponzoni, Maurilio -- Scandurra, Marta -- Califano, Andrea -- Bhagat, Govind -- Chadburn, Amy -- Dalla-Favera, Riccardo -- Pasqualucci, Laura -- P01 CA092625/CA/NCI NIH HHS/ -- P01 CA092625-020003/CA/NCI NIH HHS/ -- P01 CA92625-07/CA/NCI NIH HHS/ -- R01 AI066116/AI/NIAID NIH HHS/ -- R01 AI066116-05/AI/NIAID NIH HHS/ -- R01AI066116/AI/NIAID NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 CA121852-05/CA/NCI NIH HHS/ -- U54CA121852/CA/NCI NIH HHS/ -- England -- Nature. 2009 Jun 4;459(7247):717-21. doi: 10.1038/nature07968. Epub 2009 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19412164" target="_blank"〉PubMed〈/a〉
    Keywords: Apoptosis ; Cell Line, Tumor ; DNA-Binding Proteins ; *Gene Expression Regulation, Neoplastic ; Genes/*genetics ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Lymphoma, Large B-Cell, Diffuse/*genetics/*physiopathology ; Mutation/*genetics ; NF-kappa B/antagonists & inhibitors/genetics/*metabolism ; Nuclear Proteins/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2009-12-25
    Description: The inference of transcriptional networks that regulate transitions into physiological or pathological cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness in human malignant glioma, but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here we show that reverse-engineering and an unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPbeta and STAT3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPbeta and STAT3 reprograms neural stem cells along the aberrant mesenchymal lineage, whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumour aggressiveness. In human glioma, expression of C/EBPbeta and STAT3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results show that the activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011561/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011561/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carro, Maria Stella -- Lim, Wei Keat -- Alvarez, Mariano Javier -- Bollo, Robert J -- Zhao, Xudong -- Snyder, Evan Y -- Sulman, Erik P -- Anne, Sandrine L -- Doetsch, Fiona -- Colman, Howard -- Lasorella, Anna -- Aldape, Ken -- Califano, Andrea -- Iavarone, Antonio -- 1RC2CA148308-01/CA/NCI NIH HHS/ -- P20 GM075059/GM/NIGMS NIH HHS/ -- P20GM075059/GM/NIGMS NIH HHS/ -- R01 CA085628/CA/NCI NIH HHS/ -- R01 CA101644/CA/NCI NIH HHS/ -- R01 CA109755/CA/NCI NIH HHS/ -- R01 CA127643/CA/NCI NIH HHS/ -- R01 NS061776/NS/NINDS NIH HHS/ -- R01 NS061776-01A2/NS/NINDS NIH HHS/ -- R01 NS061776-02/NS/NINDS NIH HHS/ -- R01CA085628/CA/NCI NIH HHS/ -- R01CA101644/CA/NCI NIH HHS/ -- R01CA109755/CA/NCI NIH HHS/ -- R01NS061776/NS/NINDS NIH HHS/ -- RC2 CA148308/CA/NCI NIH HHS/ -- U01 CA168426/CA/NCI NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54CA121852/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):318-25. doi: 10.1038/nature08712. Epub 2009 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20032975" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Neoplasms/diagnosis/*genetics/*pathology ; CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism ; Cell Differentiation/genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/metabolism/pathology ; Cellular Reprogramming/genetics ; Computational Biology ; *Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Glioma/diagnosis/genetics/pathology ; Humans ; Mesenchymal Stromal Cells/metabolism/pathology ; Mesoderm/*metabolism/*pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Invasiveness/genetics/pathology ; Neurons/metabolism/pathology ; Prognosis ; Reproducibility of Results ; STAT3 Transcription Factor/genetics/metabolism ; *Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2011-07-30
    Description: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162986/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162986/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agrawal, Nishant -- Frederick, Mitchell J -- Pickering, Curtis R -- Bettegowda, Chetan -- Chang, Kyle -- Li, Ryan J -- Fakhry, Carole -- Xie, Tong-Xin -- Zhang, Jiexin -- Wang, Jing -- Zhang, Nianxiang -- El-Naggar, Adel K -- Jasser, Samar A -- Weinstein, John N -- Trevino, Lisa -- Drummond, Jennifer A -- Muzny, Donna M -- Wu, Yuanqing -- Wood, Laura D -- Hruban, Ralph H -- Westra, William H -- Koch, Wayne M -- Califano, Joseph A -- Gibbs, Richard A -- Sidransky, David -- Vogelstein, Bert -- Velculescu, Victor E -- Papadopoulos, Nickolas -- Wheeler, David A -- Kinzler, Kenneth W -- Myers, Jeffrey N -- 5P50CA09700708/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA16672/CA/NCI NIH HHS/ -- CA43460/CA/NCI NIH HHS/ -- CA57345/CA/NCI NIH HHS/ -- CN43302/CN/NCI NIH HHS/ -- N01 CN043302/CN/NCI NIH HHS/ -- P50 CA097007/CA/NCI NIH HHS/ -- P50 CA097007-05/CA/NCI NIH HHS/ -- P50 DE019032/DE/NIDCR NIH HHS/ -- P50 DE019032-07/DE/NIDCR NIH HHS/ -- P50 DE019032-10/DE/NIDCR NIH HHS/ -- P50DE019032/DE/NIDCR NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-01/CA/NCI NIH HHS/ -- R37 CA043460/CA/NCI NIH HHS/ -- R37 CA043460-16/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- R37 CA057345-20/CA/NCI NIH HHS/ -- R37 DE012588/DE/NIDCR NIH HHS/ -- R37 DE012588-14/DE/NIDCR NIH HHS/ -- RC2 DE020957/DE/NIDCR NIH HHS/ -- RC2 DE020957-01/DE/NIDCR NIH HHS/ -- RC2 DE020957-02/DE/NIDCR NIH HHS/ -- RC2 DE020958/DE/NIDCR NIH HHS/ -- RC2 DE020958-02/DE/NIDCR NIH HHS/ -- RC2DE020957/DE/NIDCR NIH HHS/ -- RC2DE020958/DE/NIDCR NIH HHS/ -- T32 CA009574/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1154-7. doi: 10.1126/science.1206923. Epub 2011 Jul 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. nagrawal@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21798897" target="_blank"〉PubMed〈/a〉
    Keywords: Carcinoma/drug therapy/*genetics/virology ; Carcinoma, Squamous Cell ; Cell Cycle Proteins/*genetics ; Codon, Nonsense ; Exons ; F-Box Proteins/*genetics ; Gene Dosage ; *Genes, Tumor Suppressor ; Genes, p53 ; Head and Neck Neoplasms/drug therapy/*genetics/virology ; Humans ; INDEL Mutation ; *Mutation ; Mutation, Missense ; Neoplasms, Squamous Cell/drug therapy/*genetics/virology ; Oligonucleotide Array Sequence Analysis ; Oncogenes ; Papillomaviridae/isolation & purification ; Papillomavirus Infections/virology ; Receptor, Notch1/chemistry/*genetics ; Sequence Analysis, DNA ; Smoking ; Tobacco ; Ubiquitin-Protein Ligases/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-10-02
    Description: The genome-wide identification of pairs of interacting proteins is an important step in the elucidation of cell regulatory mechanisms. Much of our present knowledge derives from high-throughput techniques such as the yeast two-hybrid assay and affinity purification, as well as from manual curation of experiments on individual systems. A variety of computational approaches based, for example, on sequence homology, gene co-expression and phylogenetic profiles, have also been developed for the genome-wide inference of protein-protein interactions (PPIs). Yet comparative studies suggest that the development of accurate and complete repertoires of PPIs is still in its early stages. Here we show that three-dimensional structural information can be used to predict PPIs with an accuracy and coverage that are superior to predictions based on non-structural evidence. Moreover, an algorithm, termed PrePPI, which combines structural information with other functional clues, is comparable in accuracy to high-throughput experiments, yielding over 30,000 high-confidence interactions for yeast and over 300,000 for human. Experimental tests of a number of predictions demonstrate the ability of the PrePPI algorithm to identify unexpected PPIs of considerable biological interest. The surprising effectiveness of three-dimensional structural information can be attributed to the use of homology models combined with the exploitation of both close and remote geometric relationships between proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482288/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482288/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Qiangfeng Cliff -- Petrey, Donald -- Deng, Lei -- Qiang, Li -- Shi, Yu -- Thu, Chan Aye -- Bisikirska, Brygida -- Lefebvre, Celine -- Accili, Domenico -- Hunter, Tony -- Maniatis, Tom -- Califano, Andrea -- Honig, Barry -- CA082683/CA/NCI NIH HHS/ -- CA121852/CA/NCI NIH HHS/ -- DK057539/DK/NIDDK NIH HHS/ -- GM030518/GM/NIGMS NIH HHS/ -- GM094597/GM/NIGMS NIH HHS/ -- R01 CA082683/CA/NCI NIH HHS/ -- R01 DK057539/DK/NIDDK NIH HHS/ -- R01 GM030518/GM/NIGMS NIH HHS/ -- R01 NS043915/NS/NINDS NIH HHS/ -- R01NS043915/NS/NINDS NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 GM094597/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Oct 25;490(7421):556-60. doi: 10.1038/nature11503. Epub 2012 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023127" target="_blank"〉PubMed〈/a〉
    Keywords: *Algorithms ; Animals ; Bayes Theorem ; Brain/metabolism ; Cadherins/metabolism ; High-Throughput Screening Assays ; Humans ; Matrix Attachment Region Binding Proteins/metabolism ; Mice ; Models, Molecular ; PPAR gamma/metabolism ; Phylogeny ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping/*methods ; *Protein Interaction Maps ; Protein Kinases/chemistry/metabolism ; Proteins/*chemistry/*metabolism ; Proteome/chemistry/metabolism ; Proteomics/*methods ; ROC Curve ; Reproducibility of Results ; Saccharomyces cerevisiae/chemistry/metabolism ; Suppressor of Cytokine Signaling Proteins/metabolism ; Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-03-29
    Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-01-07
    Description: Mechanisms that maintain cancer stem cells are crucial to tumour progression. The ID2 protein supports cancer hallmarks including the cancer stem cell state. HIFalpha transcription factors, most notably HIF2alpha (also known as EPAS1), are expressed in and required for maintenance of cancer stem cells (CSCs). However, the pathways that are engaged by ID2 or drive HIF2alpha accumulation in CSCs have remained unclear. Here we report that DYRK1A and DYRK1B kinases phosphorylate ID2 on threonine 27 (Thr27). Hypoxia downregulates this phosphorylation via inactivation of DYRK1A and DYRK1B. The activity of these kinases is stimulated in normoxia by the oxygen-sensing prolyl hydroxylase PHD1 (also known as EGLN2). ID2 binds to the VHL ubiquitin ligase complex, displaces VHL-associated Cullin 2, and impairs HIF2alpha ubiquitylation and degradation. Phosphorylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2alpha ubiquitylation. In glioblastoma, ID2 positively modulates HIF2alpha activity. Conversely, elevated expression of DYRK1 phosphorylates Thr27 of ID2, leading to HIF2alpha destabilization, loss of glioma stemness, inhibition of tumour growth, and a more favourable outcome for patients with glioblastoma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Sang Bae -- Frattini, Veronique -- Bansal, Mukesh -- Castano, Angelica M -- Sherman, Dan -- Hutchinson, Keino -- Bruce, Jeffrey N -- Califano, Andrea -- Liu, Guangchao -- Cardozo, Timothy -- Iavarone, Antonio -- Lasorella, Anna -- R01CA101644/CA/NCI NIH HHS/ -- R01CA131126/CA/NCI NIH HHS/ -- R01CA178546/CA/NCI NIH HHS/ -- R01NS061776/NS/NINDS NIH HHS/ -- England -- Nature. 2016 Jan 14;529(7585):172-7. doi: 10.1038/nature16475. Epub 2016 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics, Columbia University Medical Center, New York 10032, USA. ; Department of Systems Biology, Columbia University Medical Center, New York 10032, USA. ; Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York 10032, USA. ; Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York 10014, USA. ; Department of Neurosurgery, Columbia University Medical Center, New York 10032, USA. ; Department of Neurology, Columbia University Medical Center, New York 10032, USA. ; Department of Pathology, Columbia University Medical Center, New York 10032, USA. ; Department of Pediatrics, Columbia University Medical Center, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26735018" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Cullin Proteins/metabolism ; Glioblastoma/*metabolism/*pathology ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism ; Inhibitor of Differentiation Protein 2/*metabolism ; Male ; Mice ; Neoplastic Stem Cells/*metabolism/pathology ; Oxygen/metabolism ; Phosphorylation ; Phosphothreonine/metabolism ; Protein Binding ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism ; Ubiquitination ; Von Hippel-Lindau Tumor Suppressor Protein/*antagonists & inhibitors/metabolism ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 50 (1985), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The kinetics of starch gelatinization in potatoes was determined by a dynamic DSC method. The results were verified by an isothermal method. Experiments were carried out on small portions of potato tissue, thus assuring that the gelatinization conditions obtained were representative of the sum of the processes occurring on thermal treatment of potatoes. The rate constants were calculated and two activation energies were found for different temperature ranges. At temperatures below 67.5°C gelatinization was not complete, even for long reaction times. A reaction mechanism is proposed, assuming a semi-cooperative process where the gelatinization of the amorphous regions of the granule acts as a reaction “promoter” of the crystalline zones.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 48 (1983), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A model of heat and mass transfer with simultaneous chemical reaction is proposed for analyzing the influence of operating variables on the reducing sugar content at the surface of blanched potatoes. This content is partially responsible for the color of the finished product. The involved parameters (potato thermal conductivity, heat transfer coefficient of the system and kinetic constants for overall reaction of reducing sugar generation) were evaluated in separate experiments. The apparent diffusion coefficient of reducing sugars in potatoes was the only parameter obtained from blanching experiments. Temperature and concentration profiles and effect of blanching temperature on surface reducing sugar content are analyzed using the developed model. The possible underestimation of the diffusion coefficient when simultaneous starch hydrolysis is not taken into account is also considered.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 69 (2004), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : The effect of freezing low-moisture Mozzarella before ripening on cheese microstructure and its relationship with caseins degradation and viscoelastic properties were analyzed, and results were compared with refrigerated control samples. Soluble and nonprotein nitrogen contents increased with ripening time although more rapidly in the samples that were frozen before ripening. Scanning electron microscopy (SEM) showed that freezing modified cheese microstructure due to ice formation; ice crystals weakened the casein matrix. Dynamic rheological tests were performed at 50 °C using oscillatory rheometry G’increased with frequency and was higher for refrigerated than for samples frozen before ripening, at the same ripening times; G’diminished as aging time increased, although more rapidly for the samples frozen before ripening.
    Type of Medium: Electronic Resource
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