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Yadav Wagley, Ping-Yee Law, Li-Na Wei, Horace H Loh
Since the discovery of mu opioid receptor (MOR) gene two decades ago, various regulatory factors have been shown to interact with the MOR promoter and modulate transcript levels. However, the majority of early transcriptional studies on MOR gene have not addressed how intracellular signaling pathways mediate extracellular modulators. In this study, we demonstrate that MOR epigenetic regulation requires multiple co-ordinated signals converged at the MOR promoter, involving mitogen-activated protein kinase (MAPK) activation and mitogen-and stress-activated protein kinase (MSK1) - similar ranges of intracellular signaling pathways that are activated by opioid agonists...
February 2, 2017: Molecular Pharmacology
Said Khelwatty, Sharadah Essapen, Izhar Bagwan, Margaret Green, Alan Seddon, Helmout Modjtahedi
Anti-EGFR mAbs cetuximab and panitumumab are routinely used for the treatment of patients with KRAS-wild type metastatic colorectal cancer (mCRC). However, in some patients their efficacy remains modest and with no clear association between the EGFR protein expression determined by PharmDx™ kit, and response to anti-EGFR therapies. Therefore, we investigated the relative expression and predictive value of wild-type EGFR (wtEGFR), mutated EGFRvIII and EGFR ligand proteins in mCRC patients treated with cetuximab...
January 31, 2017: Oncotarget
Bhuminder Singh, Graham Carpenter, Robert J Coffey
Seven ligands bind to and activate the mammalian epidermal growth factor (EGF) receptor (EGFR/ERBB1/HER1): EGF, transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN). Of these, EGF, TGFA, HBEGF, and BTC are thought to be high-affinity ligands, whereas AREG, EREG, and EPGN constitute low-affinity ligands. This focused review is meant to highlight recent studies related to actions of the individual EGFR ligands, the interesting biology that has been uncovered, and relevant advances related to ligand interactions with the EGFR...
2016: F1000Research
Jeffrey S Boyles, Shane Atwell, Zhanna Druzina, Josef G Heuer, Derrick R Witcher
Recent studies have implicated a role of the epidermal growth factor receptor (EGFR) pathway in kidney disease. Skin toxicity associated with therapeutics which completely block the EGFR pathway precludes their use in chronic dosing. Therefore, we developed antibodies which specifically neutralize the EGFR ligands TGFα (transforming growth factor-alpha) and epiregulin but not EGF (epidermal growth factor), amphiregulin, betacellulin, HB-EGF (heparin-binding epidermal growth factor), or epigen. The epitope of one such neutralizing antibody, LY3016859, was characterized in detail to elucidate the structural basis for ligand specificity...
November 2016: Protein Science: a Publication of the Protein Society
Kylie Vuong, Bruce K Armstrong, Elisabete Weiderpass, Eiliv Lund, Hans-Olov Adami, Marit B Veierod, Jennifer H Barrett, John R Davies, D Timothy Bishop, David C Whiteman, Catherine M Olsen, John L Hopper, Graham J Mann, Anne E Cust, Kevin McGeechan
IMPORTANCE: Identifying individuals at high risk of melanoma can optimize primary and secondary prevention strategies. OBJECTIVE: To develop and externally validate a risk prediction model for incident first-primary cutaneous melanoma using self-assessed risk factors. DESIGN, SETTING, AND PARTICIPANTS: We used unconditional logistic regression to develop a multivariable risk prediction model. Relative risk estimates from the model were combined with Australian melanoma incidence and competing mortality rates to obtain absolute risk estimates...
August 1, 2016: JAMA Dermatology
Andrew X Zhu, Yoon-Koo Kang, Olivier Rosmorduc, T R Jeffry Evans, Armando Santoro, Paul Ross, Edward Gane, Arndt Vogel, Michael Jeffers, Gerold Meinhardt, Carol Pena
PURPOSE: Sorafenib is the current standard therapy for advanced HCC, but validated biomarkers predicting clinical outcomes are lacking. This study aimed to identify biomarkers predicting prognosis and/or response to sorafenib, with or without erlotinib, in HCC patients from the phase 3 SEARCH trial. EXPERIMENTAL DESIGN: 720 patients were randomized to receive oral sorafenib 400 mg BID plus erlotinib 150 mg QD or placebo. Fifteen growth factors relevant to the treatment regimen and/or to HCC were measured in baseline plasma samples...
May 24, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
M Fernanda Lima-Costa, James Macinko, Juliana Vaz de Mello Mambrini, Sérgio Viana Peixoto, Alexandre Costa Pereira, Eduardo Tarazona-Santos, Antonio Luiz Pinho Ribeiro
BACKGROUND: The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual proportions of African, European and Native American genomic ancestry with T. cruzi infection and related outcomes in 1,341 participants (aged ≥ 60 years) of the Bambui (Brazil) population-based cohort study of aging...
May 2016: PLoS Neglected Tropical Diseases
Elena Loche, Susan E Ozanne
Obesity and its related metabolic comorbidities can be inherited across generations through non-genetic mechanisms. In a recent report, Huypens et al., using an in vitro fertilization approach, provide evidence that exposure to a high-fat diet modifies egg and sperm epigenetic information, rendering the progeny more prone to obesity.
June 2016: Trends in Endocrinology and Metabolism: TEM
Weihua Wen, Lin Lu, Yuefeng He, Huirong Cheng, Fang He, Shuqiao Cao, Liang Li, Li Xiong, Tangchun Wu
Arsenic (As) metabolites could induce methylation changes of DNA and base modifications of p53, which play role in the toxicity of As. LincRNAs should play a key regulatory role in the p53 transcriptional response. There were 43 workers producing As trioxide, 36 workers who stopped exposure to As trioxide about 85 days ago, and 24 individuals as control group. Three As species in urine were measured, and primary and secondary methylation indexes, iAs%, MMA% and DMA% were calculated. RT-PCR was performed to detect the expression of 7 LincRNAs and the base modifications of exon 5, 6, 7, and 8 of p53...
February 25, 2016: Chemico-biological Interactions
M Fernanda Lima-Costa, Juliana Vaz de Mello Mambrini, Maria Lea Corrêa Leite, Sérgio Viana Peixoto, Josélia Oliveira Araújo Firmo, Antônio Ignácio de Loyola Filho, Mateus H Gouveia, Thiago P Leal, Alexandre Costa Pereira, James Macinko, Eduardo Tarazona-Santos
The study objective is to examine the role of African genome origin on baseline and 11-year blood pressure trajectories in community-based ethnoracially admixed older adults in Brazil. Data come from 1272 participants (aged ≥60 years) of the Bambui cohort study of aging during 11 years of follow-up. Outcome measures were systolic blood pressure, diastolic blood pressure, and hypertension control. Potential confounding variables were demographic characteristics, socioeconomic position (schooling and household income), and health indicators (smoking, sedentary lifestyle, high-density lipoprotein cholesterol, waist circumference, diabetes mellitus, and cardiovascular diseases), including antihypertensive drug use...
February 2016: Hypertension
M Fernanda Lima-Costa, James Macinko, Juliana Vaz de Melo Mambrini, Cibele C Cesar, Sérgio V Peixoto, Wagner C S Magalhães, Bernardo L Horta, Mauricio Barreto, Erico Castro-Costa, Josélia O A Firmo, Fernando A Proietti, Thiago Peixoto Leal, Maira R Rodrigues, Alexandre Pereira, Eduardo Tarazona-Santos
BACKGROUND: Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification. MATERIALS/METHODS: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians...
2015: PloS One
Gauri M Ugale, Nagaraj B Kalburgi, Shivaprasad Bilichodmath, Shivaraj B Warad, Mahesh S Ugale, Arati C Koregol, Shobha C Bijjargi
BACKGROUND: The host immune response to bacterial dental plaque determines periodontal disease susceptibility by increasing the secretion of inflammatory cytokines. The Epidermal Growth Factor family cytokines stimulate proliferation and keratinization of cells in dermis and oral epithelium. Epidermal Growth Factor family consists of Amphiregulin, Betacellulin, Epiregulin, Epigen, Heparin binding Epidermal Growth Factor like growth factor and transforming Growth Factor-alpha. AIM: The current study aimed to investigate expression of Betacellulin in chronic periodontitis patients with and without type 2 diabetes mellitus and thereby assessing role of betacellulin in periodontal health and disease...
November 2015: Journal of Clinical and Diagnostic Research: JCDR
Bonnie Edwards, John Lesnick, Jing Wang, Nga Tang, Carl Peters
Epigenetics continues to emerge as an important target class for drug discovery and cancer research. As programs scale to evaluate many new targets related to epigenetic expression, new tools and techniques are required to enable efficient and reproducible high-throughput epigenetic screening. Assay miniaturization increases screening throughput and reduces operating costs. Echo liquid handlers can transfer compounds, samples, reagents, and beads in submicroliter volumes to high-density assay formats using only acoustic energy-no contact or tips required...
February 2016: Journal of Laboratory Automation
G P Kononenko, A A Burkin
The distribution of mycotoxins anc unic acid in the thallus of epigenous fruticose lichens Alectoria ochroleuca; several species of the genera Cladonia, Cotraria, and Flavocetraria; foliose lichens Nephroma arcticum; and six species of the genus Peltigera were studied by mnzyme-linked immunosorbent assay. The mycotoxin content was lower in the top or apical parts of the thalli than in the basal parts and in dead areas. Differences in the distribution of usnic acid were insignificant in the majority of species, but in Cladonia stellaris and N...
May 2015: Izvestiia Akademii Nauk. Seriia Biologicheskaia
Kathleen Brannen-Donnelly, Annette S Engel
Unchanging physicochemical conditions and nutrient sources over long periods of time in cave and karst subsurface habitats, particularly aquifers, can support stable ecosystems, termed autochthonous microbial endokarst communities (AMEC). AMEC existence is unknown for other karst settings, such as epigenic cave streams. Conceptually, AMEC should not form in streams due to faster turnover rates and seasonal disturbances that have the capacity to transport large quantities of water and sediment and to change allochthonous nutrient and organic matter sources...
2015: Frontiers in Microbiology
Fernanda S G Kehdy, Mateus H Gouveia, Moara Machado, Wagner C S Magalhães, Andrea R Horimoto, Bernardo L Horta, Rennan G Moreira, Thiago P Leal, Marilia O Scliar, Giordano B Soares-Souza, Fernanda Rodrigues-Soares, Gilderlanio S Araújo, Roxana Zamudio, Hanaisa P Sant Anna, Hadassa C Santos, Nubia E Duarte, Rosemeire L Fiaccone, Camila A Figueiredo, Thiago M Silva, Gustavo N O Costa, Sandra Beleza, Douglas E Berg, Lilia Cabrera, Guilherme Debortoli, Denise Duarte, Silvia Ghirotto, Robert H Gilman, Vanessa F Gonçalves, Andrea R Marrero, Yara C Muniz, Hansi Weissensteiner, Meredith Yeager, Laura C Rodrigues, Mauricio L Barreto, M Fernanda Lima-Costa, Alexandre C Pereira, Maíra R Rodrigues, Eduardo Tarazona-Santos
While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil...
July 14, 2015: Proceedings of the National Academy of Sciences of the United States of America
Kevin Cheeseman, Jonathan B Weitzman
The epigenetics of host-pathogen interactions is emerging as an interesting angle from which to study how parasites have evolved sophisticated strategies to manipulate host gene transcription and protein expression. In this review, we discuss the application of an operational framework to investigate the host cell signalling pathways that are induced by intracellular parasites and the epigenomic consequences in the host nucleus. To illustrate this conceptual approach, we have focused on examples from two eukaryotic intracellular parasites of the apicomplexa phylum: Theileria and Toxoplasma...
August 2015: Cellular Microbiology
Amy Doerner, Rebecca Scheck, Alanna Schepartz
Binding of transforming growth factor α (TGF-α) to the epidermal growth factor receptor (EGFR) extracellular domain is encoded through the formation of a unique antiparallel coiled coil within the juxtamembrane segment. This new coiled coil is an "inside-out" version of the coiled coil formed in the presence of epidermal growth factor (EGF). A third, intermediary coiled-coil interface is formed in the juxtamembrane region when EGFR is stimulated with betacellulin. The seven growth factors that activate EGFR in mammalian systems (EGF, TGF-α, epigen, epiregulin, betacellulin, heparin-binding EGF, and amphiregulin) fall into distinct categories in which the structure of the coiled coil induced within the juxtamembrane region correlates with cell state...
June 18, 2015: Chemistry & Biology
Tiphaine C Martin, Idil Yet, Pei-Chien Tsai, Jordana T Bell
BACKGROUND: Epigenome-wide association scans (EWAS) are an increasingly powerful and widely-used approach to assess the role of epigenetic variation in human complex traits. However, this rapidly emerging field lacks dedicated visualisation tools that can display features specific to epigenetic datasets. RESULT: We developed coMET, an R package and online tool for visualisation of EWAS results in a genomic region of interest. coMET generates a regional plot of epigenetic-phenotype association results and the estimated DNA methylation correlation between CpG sites (co-methylation), with further options to visualise genomic annotations based on ENCODE data, gene tracks, reference CpG-sites, and user-defined features...
April 28, 2015: BMC Bioinformatics
M Fernanda Lima-Costa, Laura C Rodrigues, Maurício L Barreto, Mateus Gouveia, Bernardo L Horta, Juliana Mambrini, Fernanda S G Kehdy, Alexandre Pereira, Fernanda Rodrigues-Soares, Cesar G Victora, Eduardo Tarazona-Santos
Brazil never had segregation laws defining membership of an ethnoracial group. Thus, the composition of the Brazilian population is mixed, and its ethnoracial classification is complex. Previous studies showed conflicting results on the correlation between genome ancestry and ethnoracial classification in Brazilians. We used 370,539 Single Nucleotide Polymorphisms to quantify this correlation in 5,851 community-dwelling individuals in the South (Pelotas), Southeast (Bambui) and Northeast (Salvador) Brazil. European ancestry was predominant in Pelotas and Bambui (median = 85...
2015: Scientific Reports
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