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Patricia C Sanchez-Diaz, Judy C Chang, Emily S Moses, Tu Dao, Yidong Chen, Jaclyn Y Hung
Pediatric high-grade gliomas represent 8-12% of all primary tumors of the nervous system in children. Five-year survival for these pediatric aggressive tumors is poor (15-35%) indicating the need to develop better treatments for pediatric high-grade gliomas. In this work we used SF188 and SJ-GBM2 cell lines to study the function of the ubiquitin carboxyl-terminal esterase L1 (UCHL1), a deubiquitinase de-regulated in several cancers, in pediatric high-grade gliomas. UCHL1 depletion in SF188 and SJ-GBM2 glioma cells was associated with decreased cell proliferation and invasion, along with a reduced ability to grow in soft agar and to form spheres (i...
2017: PloS One
Chenglin Liu, Yu-Hang Zhang, Tao Huang, Yudong Cai
BACKGROUND: Lung adenocarcinoma is one of most threatening disease to human health. Although many efforts have been devoted to its genetic study, few researches have been focused on the transcription factors which regulate tumor initiation and progression by affecting multiple downstream gene transcription. It is proved that proper transcription factors may mediate the direct reprogramming of cancer cells, and reverse the tumorigenesis on the epigenetic and transcription levels. METHODS: In this paper, a computational method is proposed to identify the core transcription factors that can regulate as many as possible lung adenocarcinoma associated genes with as little as possible redundancy...
April 1, 2017: Artificial Intelligence in Medicine
M Kamran, Z-J Long, D Xu, S-S Lv, B Liu, C-L Wang, J Xu, E W-F Lam, Q Liu
Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies. However, little is known about its role in gastric cancer prognosis and genotoxic resistance. Here we found that AURKA was highly overexpressed in gastric cancer and inversely correlated with disease prognosis. Overexpression of AURKA exacerbated gastric cancer drug resistance through upregulating the expression of the anti-apoptotic protein Survivin...
February 20, 2017: Oncogenesis
Giuseppe Tosto, Hongjun Fu, Badri N Vardarajan, Joseph H Lee, Rong Cheng, Dolly Reyes-Dumeyer, Rafael Lantigua, Martin Medrano, Ivonne Z Jimenez-Velazquez, Mitchell S V Elkind, Clinton B Wright, Ralph L Sacco, Margaret Pericak-Vance, Lindsay Farrer, Ekaterina Rogaeva, Peter St George-Hyslop, Christiane Reitz, Richard Mayeux
OBJECTIVE: In the context of late-onset Alzheimer's disease (LOAD) over 20 genes have been identified but, aside APOE, all show small effect sizes, leaving a large part of the genetic component unexplained. Admixed populations, such as Caribbean Hispanics, can provide a valuable contribution because of their unique genetic profile and higher incidence of the disease. We aimed to identify novel loci associated with LOAD. METHODS: About 4514 unrelated Caribbean Hispanics (2451 cases and 2063 controls) were selected for genome-wide association analysis...
August 2015: Annals of Clinical and Translational Neurology
Emi Takamitsu, Motoaki Otsuka, Tatsuki Haebara, Manami Yano, Kanako Matsuzaki, Hirotsugu Kobuchi, Koko Moriya, Toshihiko Utsumi
To identify physiologically important human N-myristoylated proteins, 90 cDNA clones predicted to encode human N-myristoylated proteins were selected from a human cDNA resource (4,369 Kazusa ORFeome project human cDNA clones) by two bioinformatic N-myristoylation prediction systems, NMT-The MYR Predictor and Myristoylator. After database searches to exclude known human N-myristoylated proteins, 37 cDNA clones were selected as potential human N-myristoylated proteins. The susceptibility of these cDNA clones to protein N-myristoylation was first evaluated using fusion proteins in which the N-terminal ten amino acid residues were fused to an epitope-tagged model protein...
2015: PloS One
Yuan Liu, Travis Lear, Olivia Iannone, Sruti Shiva, Catherine Corey, Shristi Rajbhandari, Jacob Jerome, Bill B Chen, Rama K Mallampalli
Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression. Here we demonstrate that overexpression of Fbxl7 in lung epithelia decreases the protein abundance of survivin, a member of the inhibitor of apoptosis family. Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal α helix. Furthermore, both Lys-90 and Lys-91 within survivin serve as ubiquitin acceptor sites. Ectopically expressed Fbxl7 impairs mitochondrial function, whereas depletion of Fbxl7 protects mitochondria from actions of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of oxidative phosphorylation...
May 8, 2015: Journal of Biological Chemistry
Y Liu, T Lear, Y Zhao, J Zhao, C Zou, B B Chen, R K Mallampalli
Fbxl7, a subunit of the SCF (Skp-Cul1-F-box protein) complex induces mitotic arrest in cells; however, molecular factors that control its cellular abundance remain largely unknown. Here, we identified that an orphan F-box protein, Fbxl18, targets Fbxl7 for its polyubiquitylation and proteasomal degradation. Lys 109 within Fbxl7 is an essential acceptor site for ubiquitin conjugation by Fbxl18. An FQ motif within Fbxl7 serves as a molecular recognition site for Fbxl18 interaction. Ectopically expressed Fbxl7 induces apoptosis in Hela cells, an effect profoundly accentuated after cellular depletion of Fbxl18 protein or expression of Fbxl7 plasmids encoding mutations at either Lys 109 or within the FQ motif...
2015: Cell Death & Disease
Mariana Rodrigues-Campos, Barry J Thompson
The atypical cadherins Dachsous (Ds) and Fat (Ft) are required to control the size and shape of tissues and organs in animals. In Drosophila, a key effector of Ds and Ft is the atypical myosin Dachs, which becomes planar polarised along the proximal-distal axis in developing epithelia to regulate tissue size via the Hippo pathway and tissue shape via modulating tension at junctions. How Ds and Ft control Dachs polarisation remains unclear. Here, we identify a ubiquitin ligase, FbxL7, as a novel component of the Ds-Ft-Dachs system that is required to control the level and localisation of Dachs...
November 2014: Development
Justin A Bosch, Taryn M Sumabat, Yassi Hafezi, Brett J Pellock, Kevin D Gandhi, Iswar K Hariharan
The Drosophila protocadherin Fat (Ft) regulates growth, planar cell polarity (PCP) and proximodistal patterning. A key downstream component of Ft signaling is the atypical myosin Dachs (D). Multiple regions of the intracellular domain of Ft have been implicated in regulating growth and PCP but how Ft regulates D is not known. Mutations in Fbxl7, which encodes an F-box protein, result in tissue overgrowth and abnormalities in proximodistal patterning that phenocopy deleting a specific portion of the intracellular domain (ICD) of Ft that regulates both growth and PCP...
2014: ELife
Heung-Woo Park, Amber Dahlin, Szeman Tse, Qing Ling Duan, Brooke Schuemann, Fernando D Martinez, Stephen P Peters, Stanley J Szefler, John J Lima, Michiaki Kubo, Mayumi Tamari, Kelan G Tantisira
BACKGROUND: To date, genome-wide association studies (GWASs) of inhaled corticosteroid (ICS) response in asthmatic patients have focused primarily on lung function and exacerbations. OBJECTIVE: We hypothesized that GWAS analysis could identify novel genetic markers predicting a symptomatic response to ICSs. METHODS: We analyzed differences in asthma symptoms in response to ICSs in 124 white children from the Childhood Asthma Management Program (CAMP) trial using scores from diary cards...
March 2014: Journal of Allergy and Clinical Immunology
José Antonio Cornejo-García, Lieh-Bang Liou, Natalia Blanca-López, Inmaculada Doña, Chien-Hsiun Chen, Yi-Chun Chou, Hui-Ping Chuang, Jer-Yuarn Wu, Yuan-Tsong Chen, María Del Carmen Plaza-Serón, Cristobalina Mayorga, Rosa María Guéant-Rodríguez, Shih-Chang Lin, María José Torres, Paloma Campo, Carmen Rondón, José Julio Laguna, Javier Fernández, Jean-Louis Guéant, Gabriela Canto, Miguel Blanca, Ming Ta Michael Lee
AIM: Acute urticaria/angioedema (AUA) induced by cross-intolerance to NSAIDs is the most frequent clinical entity in hypersensitivity reactions to drugs. In this work, we conducted a genome-wide association study in Spanish and Han Chinese patients suffering from NSAID-induced AUA. MATERIALS & METHODS: A whole-genome scan was performed on a total of 232 cases (112 Spanish and 120 Han Chinese) with NSAID-induced AUA and 225 unrelated controls (124 Spanish and 101 Han Chinese)...
November 2013: Pharmacogenomics
Yi Zhang, Jack W Kent, Michael Olivier, Omar Ali, Diana Cerjak, Ulrich Broeckel, Reham M Abdou, Thomas D Dyer, Anthony Comuzzie, Joanne E Curran, Melanie A Carless, David L Rainwater, Harald H H Göring, John Blangero, Ahmed H Kissebah
BACKGROUND: Metabolic syndrome (MetS) is an aberration associated with increased risk for cancer and inflammation. Adiponectin, an adipocyte-produced abundant protein hormone, has countering effect on the diabetogenic and atherogenic components of MetS. Plasma levels of adiponectin are negatively correlated with onset of cancer and cancer patient mortality. We previously performed microsatellite linkage analyses using adiponectin as a surrogate marker and revealed two QTLs on chr5 (5p14) and chr14 (14q13)...
2013: BMC Medical Genomics
N Forde, G B Duffy, P A McGettigan, J A Browne, J P Mehta, A K Kelly, N Mansouri-Attia, O Sandra, B J Loftus, M A Crowe, T Fair, J F Roche, P Lonergan, A C O Evans
The aims of this study were to 1) identify the earliest transcriptional response of the bovine endometrium to the presence of the conceptus (using RNAseq), 2) investigate if these genes are regulated by interferon tau (IFNT) in vivo, and 3) determine if they are predictive of the pregnancy status of postpartum dairy cows. RNAseq identified 459 differentially expressed genes (DEGs) between pregnant and cyclic endometria on day 16. Quantitative real-time PCR analysis of selected genes revealed PARP12, ZNFX1, HERC6, IFI16, RNF213, and DDX58 expression increased in pregnant compared with cyclic endometria on day 16 and were directly upregulated by intrauterine infusion of IFNT in vivo for 2 h (P < 0...
August 17, 2012: Physiological Genomics
Shinuk Kim, Mark Kon, Charles DeLisi
BACKGROUND: Molecular markers based on gene expression profiles have been used in experimental and clinical settings to distinguish cancerous tumors in stage, grade, survival time, metastasis, and drug sensitivity. However, most significant gene markers are unstable (not reproducible) among data sets. We introduce a standardized method for representing cancer markers as 2-level hierarchical feature vectors, with a basic gene level as well as a second level of (more stable) pathway markers, for the purpose of discriminating cancer subtypes...
2012: Biology Direct
Tiffany A Coon, Jennifer R Glasser, Rama K Mallampalli, Bill B Chen
Aurora family kinases play pivotal roles in several steps during mitosis. Specifically, Aurora A kinase is an important regulator of bipolar mitotic spindle formation and chromosome segregation. Like other members of the Aurora family, Aurora A kinase is also regulated by post-translational modifications. Here, we show that a previously undescribed E3 ligase component belonging to the SCF (Skp-Cullin1-F-box protein) E3 ligase family, SCFFBXL7, impairs cell proliferation by mediating Aurora A polyubiquitination and degradation...
February 15, 2012: Cell Cycle
Xianshu Wang, V Shane Pankratz, Zachary Fredericksen, Robert Tarrell, Mary Karaus, Lesley McGuffog, Paul D P Pharaoh, Bruce A J Ponder, Alison M Dunning, Susan Peock, Margaret Cook, Clare Oliver, Debra Frost, Olga M Sinilnikova, Dominique Stoppa-Lyonnet, Sylvie Mazoyer, Claude Houdayer, Frans B L Hogervorst, Maartje J Hooning, Marjolijn J Ligtenberg, Amanda Spurdle, Georgia Chenevix-Trench, Rita K Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Susan M Domchek, Katherine L Nathanson, Timothy R Rebbeck, Christian F Singer, Daphne Gschwantler-Kaulich, Catherina Dressler, Anneliese Fink, Csilla I Szabo, Michal Zikan, Lenka Foretova, Kathleen Claes, Gilles Thomas, Robert N Hoover, David J Hunter, Stephen J Chanock, Douglas F Easton, Antonis C Antoniou, Fergus J Couch
Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs), additional risk modifiers for BRCA1 and BRCA2 may be identified from promising signals discovered in breast cancer GWAS. A total of 350 SNPs identified as candidate breast cancer risk factors (P < 1 x 10(-3)) in two breast cancer GWAS studies were genotyped in 3451 BRCA1 and 2006 BRCA2 mutation carriers from nine centers...
July 15, 2010: Human Molecular Genetics
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