WorldWideScience

Sample records for global methylation status

  1. Maternal global methylation status and risk of congenital heart diseases

    van Driel, Lydi M. J. W.; de Jonge, Robert; Helbing, Willem A.; van Zelst, Bertrand D.; Ottenkamp, Jaap; Steegers, Eric A. P.; Steegers-Theunissen, Regine P. M.

    2008-01-01

    OBJECTIVE: To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring. METHODS: As part of a case-control study in the

  2. Using a medium-throughput comet assay to evaluate the global DNA methylation status of single cells

    Lewies, Angélique; Van Dyk, Etresia; Wentzel, Johannes F.; Pretorius, Pieter J.

    2014-01-01

    The comet assay is a simple and cost effective technique, commonly used to analyze and quantify DNA damage in individual cells. The versatility of the comet assay allows introduction of various modifications to the basic technique. The difference in the methylation sensitivity of the isoschizomeric restriction enzymes HpaII and MspI are used to demonstrate the ability of the comet assay to measure the global DNA methylation level of individual cells when using cell cultures. In the experiments described here, a medium-throughput comet assay and methylation sensitive comet assay are combined to produce a methylation sensitive medium-throughput comet assay to measure changes in the global DNA methylation pattern in individual cells under various growth conditions. PMID:25071840

  3. Global DNA methylation analysis using methyl-sensitive amplification polymorphism (MSAP).

    Yaish, Mahmoud W; Peng, Mingsheng; Rothstein, Steven J

    2014-01-01

    DNA methylation is a crucial epigenetic process which helps control gene transcription activity in eukaryotes. Information regarding the methylation status of a regulatory sequence of a particular gene provides important knowledge of this transcriptional control. DNA methylation can be detected using several methods, including sodium bisulfite sequencing and restriction digestion using methylation-sensitive endonucleases. Methyl-Sensitive Amplification Polymorphism (MSAP) is a technique used to study the global DNA methylation status of an organism and hence to distinguish between two individuals based on the DNA methylation status determined by the differential digestion pattern. Therefore, this technique is a useful method for DNA methylation mapping and positional cloning of differentially methylated genes. In this technique, genomic DNA is first digested with a methylation-sensitive restriction enzyme such as HpaII, and then the DNA fragments are ligated to adaptors in order to facilitate their amplification. Digestion using a methylation-insensitive isoschizomer of HpaII, MspI is used in a parallel digestion reaction as a loading control in the experiment. Subsequently, these fragments are selectively amplified by fluorescently labeled primers. PCR products from different individuals are compared, and once an interesting polymorphic locus is recognized, the desired DNA fragment can be isolated from a denaturing polyacrylamide gel, sequenced and identified based on DNA sequence similarity to other sequences available in the database. We will use analysis of met1, ddm1, and atmbd9 mutants and wild-type plants treated with a cytidine analogue, 5-azaC, or zebularine to demonstrate how to assess the genetic modulation of DNA methylation in Arabidopsis. It should be noted that despite the fact that MSAP is a reliable technique used to fish for polymorphic methylated loci, its power is limited to the restriction recognition sites of the enzymes used in the genomic

  4. Global DNA methylation of ischemic stroke subtypes.

    Carolina Soriano-Tárraga

    Full Text Available Ischemic stroke (IS, a heterogeneous multifactorial disorder, is among the leading causes of mortality and long-term disability in the western world. Epidemiological data provides evidence for a genetic component to the disease, but its epigenetic involvement is still largely unknown. Epigenetic mechanisms, such as DNA methylation, change over time and may be associated with aging processes and with modulation of the risk of various pathologies, such as cardiovascular disease and stroke. We analyzed 2 independent cohorts of IS patients. Global DNA methylation was measured by luminometric methylation assay (LUMA of DNA blood samples. Univariate and multivariate regression analyses were used to assess the methylation differences between the 3 most common IS subtypes, large-artery atherosclerosis (LAA, small-artery disease (SAD, and cardio-aortic embolism (CE. A total of 485 IS patients from 2 independent hospital cohorts (n = 281 and n = 204 were included, distributed across 3 IS subtypes: LAA (78/281, 59/204, SAD (97/281, 53/204, and CE (106/281, 89/204. In univariate analyses, no statistical differences in LUMA levels were observed between the 3 etiologies in either cohort. Multivariate analysis, adjusted by age, sex, hyperlipidemia, and smoking habit, confirmed the lack of differences in methylation levels between the analyzed IS subtypes in both cohorts. Despite differences in pathogenesis, our results showed no global methylation differences between LAA, SAD, and CE subtypes of IS. Further work is required to establish whether the epigenetic mechanism of methylation might play a role in this complex disease.

  5. Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome

    Iriyama, Chisako [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Tomita, Akihiro, E-mail: atomita@med.nagoya-u.ac.jp [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Hoshino, Hideaki; Adachi-Shirahata, Mizuho [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Furukawa-Hibi, Yoko; Yamada, Kiyofumi [Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Nagoya (Japan); Kiyoi, Hitoshi; Naoe, Tomoki [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Circulating DNAs (CDs) can be used to detect genetic/epigenetic abnormalities in MDS. Black-Right-Pointing-Pointer Epigenetic changes can be detected more sensitively when using plasma DNA than PBMNC. Black-Right-Pointing-Pointer Mutation ratio in CDs may reflect the ratio in stem cell population in bone marrow. Black-Right-Pointing-Pointer Using CDs can be a safer alternate strategy compared to bone marrow aspiration. -- Abstract: Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several genetic/epigenetic abnormalities are deeply associated with the pathogenesis of MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS cells for evaluating their genetic/epigenetic abnormalities, BM aspiration is difficult to perform repeatedly to obtain serial samples because of pain and safety concerns. Here, we report that circulating cell-free DNAs from plasma and serum of patients with MDS can be used to detect genetic/epigenetic abnormalities. The plasma DNA concentration was found to be relatively high in patients with higher blast cell counts in BM, and accumulation of DNA fragments from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB) samples from patients treated with hypomethylating agents, global methylation analysis using bisulfite pyrosequencing was performed at the specific CpG sites of the LINE-1 promoter. The results confirmed a decrease of the methylation percentage after treatment with azacitidine (days 3-9) using DNAs from plasma, serum, and PB mono-nuclear cells (PBMNC). Plasma DNA tends to show more rapid change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2 gene mutation in DNAs from plasma, serum, and BM cells was quantitated by pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum DNA showed almost equivalent level with that in the CD34+/38- stem cell population in BM. These data suggest that genetic

  6. Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome

    Iriyama, Chisako; Tomita, Akihiro; Hoshino, Hideaki; Adachi-Shirahata, Mizuho; Furukawa-Hibi, Yoko; Yamada, Kiyofumi; Kiyoi, Hitoshi; Naoe, Tomoki

    2012-01-01

    Highlights: ► Circulating DNAs (CDs) can be used to detect genetic/epigenetic abnormalities in MDS. ► Epigenetic changes can be detected more sensitively when using plasma DNA than PBMNC. ► Mutation ratio in CDs may reflect the ratio in stem cell population in bone marrow. ► Using CDs can be a safer alternate strategy compared to bone marrow aspiration. -- Abstract: Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several genetic/epigenetic abnormalities are deeply associated with the pathogenesis of MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS cells for evaluating their genetic/epigenetic abnormalities, BM aspiration is difficult to perform repeatedly to obtain serial samples because of pain and safety concerns. Here, we report that circulating cell-free DNAs from plasma and serum of patients with MDS can be used to detect genetic/epigenetic abnormalities. The plasma DNA concentration was found to be relatively high in patients with higher blast cell counts in BM, and accumulation of DNA fragments from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB) samples from patients treated with hypomethylating agents, global methylation analysis using bisulfite pyrosequencing was performed at the specific CpG sites of the LINE-1 promoter. The results confirmed a decrease of the methylation percentage after treatment with azacitidine (days 3–9) using DNAs from plasma, serum, and PB mono-nuclear cells (PBMNC). Plasma DNA tends to show more rapid change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2 gene mutation in DNAs from plasma, serum, and BM cells was quantitated by pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum DNA showed almost equivalent level with that in the CD34+/38- stem cell population in BM. These data suggest that genetic/epigenetic analyses using PB circulating DNA can be a safer and painless alternative to using BM

  7. Transgenerational epigenetics: Inheritance of global cytosine methylation and methylation-related epigenetic markers in the shrub Lavandula latifolia.

    Herrera, Carlos M; Alonso, Conchita; Medrano, Mónica; Pérez, Ricardo; Bazaga, Pilar

    2018-04-01

    The ecological and evolutionary significance of natural epigenetic variation (i.e., not based on DNA sequence variants) variation will depend critically on whether epigenetic states are transmitted from parents to offspring, but little is known on epigenetic inheritance in nonmodel plants. We present a quantitative analysis of transgenerational transmission of global DNA cytosine methylation (= proportion of all genomic cytosines that are methylated) and individual epigenetic markers (= methylation status of anonymous MSAP markers) in the shrub Lavandula latifolia. Methods based on parent-offspring correlations and parental variance component estimation were applied to epigenetic features of field-growing plants ('maternal parents') and greenhouse-grown progenies. Transmission of genetic markers (AFLP) was also assessed for reference. Maternal parents differed significantly in global DNA cytosine methylation (range = 21.7-36.7%). Greenhouse-grown maternal families differed significantly in global methylation, and their differences were significantly related to maternal origin. Methylation-sensitive amplified polymorphism (MSAP) markers exhibited significant transgenerational transmission, as denoted by significant maternal variance component of marker scores in greenhouse families and significant mother-offspring correlations of marker scores. Although transmission-related measurements for global methylation and MSAP markers were quantitatively lower than those for AFLP markers taken as reference, this study has revealed extensive transgenerational transmission of genome-wide global cytosine methylation and anonymous epigenetic markers in L. latifolia. Similarity of results for global cytosine methylation and epigenetic markers lends robustness to this conclusion, and stresses the value of considering both types of information in epigenetic studies of nonmodel plants. © 2018 Botanical Society of America.

  8. The impact of endurance exercise on global and AMPK gene-specific DNA methylation

    King-Himmelreich, Tanya S.; Schramm, Stefanie; Wolters, Miriam C.; Schmetzer, Julia; Möser, Christine V.; Knothe, Claudia [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany); Resch, Eduard [Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project Group for Translational Medicine & Pharmacology (TMP), 60596, Frankfurt/Main (Germany); Peil, Johannes [Sports Clinic, Bad Nauheim, MCI GmbH, In der Aue 30-32, 61231, Bad Nauheim (Germany); Geisslinger, Gerd [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany); Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project Group for Translational Medicine & Pharmacology (TMP), 60596, Frankfurt/Main (Germany); Niederberger, Ellen, E-mail: e.niederberger@em.uni-frankfurt.de [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany)

    2016-05-27

    Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of the AMPK promoter, we determined the AMPK methylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as well as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes. Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in the AMPKα2 gene. These regulations were associated with a reduced AMPKα2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status to AMPK expression. Taken together, these results suggest that exercise influences AMPKα2 gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repress AMPKα2 gene expression. -- Highlights: •AMPK gene methylation increases after moderate endurance exercise in humans and mice. •AMPKα mRNA and protein decrease after moderate endurance exercise in mice. •Global DNA methylation is not affected under the same conditions.

  9. The impact of endurance exercise on global and AMPK gene-specific DNA methylation

    King-Himmelreich, Tanya S.; Schramm, Stefanie; Wolters, Miriam C.; Schmetzer, Julia; Möser, Christine V.; Knothe, Claudia; Resch, Eduard; Peil, Johannes; Geisslinger, Gerd; Niederberger, Ellen

    2016-01-01

    Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of the AMPK promoter, we determined the AMPK methylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as well as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes. Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in the AMPKα2 gene. These regulations were associated with a reduced AMPKα2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status to AMPK expression. Taken together, these results suggest that exercise influences AMPKα2 gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repress AMPKα2 gene expression. -- Highlights: •AMPK gene methylation increases after moderate endurance exercise in humans and mice. •AMPKα mRNA and protein decrease after moderate endurance exercise in mice. •Global DNA methylation is not affected under the same conditions.

  10. Comparison of methods for quantification of global DNA methylation in human cells and tissues.

    Sofia Lisanti

    Full Text Available DNA methylation is a key epigenetic modification which, in mammals, occurs mainly at CpG dinucleotides. Most of the CpG methylation in the genome is found in repetitive regions, rich in dormant transposons and endogenous retroviruses. Global DNA hypomethylation, which is a common feature of several conditions such as ageing and cancer, can cause the undesirable activation of dormant repeat elements and lead to altered expression of associated genes. DNA hypomethylation can cause genomic instability and may contribute to mutations and chromosomal recombinations. Various approaches for quantification of global DNA methylation are widely used. Several of these approaches measure a surrogate for total genomic methyl cytosine and there is uncertainty about the comparability of these methods. Here we have applied 3 different approaches (luminometric methylation assay, pyrosequencing of the methylation status of the Alu repeat element and of the LINE1 repeat element for estimating global DNA methylation in the same human cell and tissue samples and have compared these estimates with the "gold standard" of methyl cytosine quantification by HPLC. Next to HPLC, the LINE1 approach shows the smallest variation between samples, followed by Alu. Pearson correlations and Bland-Altman analyses confirmed that global DNA methylation estimates obtained via the LINE1 approach corresponded best with HPLC-based measurements. Although, we did not find compelling evidence that the gold standard measurement by HPLC could be substituted with confidence by any of the surrogate assays for detecting global DNA methylation investigated here, the LINE1 assay seems likely to be an acceptable surrogate in many cases.

  11. renewables 2011 - Global status report

    Sawin, Janet L.; Martinot, Eric; Barnes, Douglas; Martinot, Eric; McCrone, Angus; Roussell, Jodie; Sawin, Janet L.; Sims, Ralph; Sonntag-O'Brien, Virginia; Adib, Rana; Skeen, Jonathan; Musolino, Evan; Riahi, Lily; Mastny, Lisa

    2011-01-01

    Changes in renewable energy markets, investments, industries, and policies have been so rapid in recent years that perceptions of the status of renewable energy can lag years behind the reality. This report captures that reality and provides a unique overview of renewable energy worldwide as of early 2011. The report covers both current status and key trends; by design, it does not provide analysis or forecast the future. Global energy consumption rebounded in 2010 after an overall downturn in 2009. Renewable energy, which experienced no downturn in 2009, continued to grow strongly in all end-use sectors - power, heat and transport - and supplied an estimated 16% of global final energy consumption. Renewable energy accounted for approximately half of the estimated 194 gigawatts (GW) of new electric capacity added globally during the year. Renewables delivered close to 20% of global electricity supply in 2010, and by early 2011 they comprised one quarter of global power capacity from all sources. In several countries, renewables represent a rapidly growing share of total energy supply, including heat and transport

  12. Renewables 2013. Global Status Report

    Sawin, J. L. [and others

    2013-07-01

    Renewable energy markets, industries, and policy frameworks have evolved rapidly in recent years. The Renewables Global Status Report provides a comprehensive and timely overview of renewable energy market, industry, investment, and policy developments worldwide. It relies on the most recent data available, provided by many contributors and researchers from around the world, all of which is brought together by a multi-disciplinary authoring team. The report covers recent developments, current status, and key trends; by design, it does not provide analysis or forecasts. This latest Renewables Global Status Report saw: a shift in investment patterns that led to a global decrease in clean energy investment; continuing growth in installed capacity due to significant technology cost reductions and increased investment in developing countries; renewables progressively supplementing established electricity systems, demonstrating that the implementation of suitable policies can enable the successful integration of higher shares of variable renewables; and the emergence of integrated policy approaches that link energy efficiency measures with the implementation of renewable energy technologies.

  13. Differential DNA methylation patterns define status epilepticus and epileptic tolerance.

    Miller-Delaney, Suzanne F C; Das, Sudipto; Sano, Takanori; Jimenez-Mateos, Eva M; Bryan, Kenneth; Buckley, Patrick G; Stallings, Raymond L; Henshall, David C

    2012-02-01

    Prolonged seizures (status epilepticus) produce pathophysiological changes in the hippocampus that are associated with large-scale, wide-ranging changes in gene expression. Epileptic tolerance is an endogenous program of cell protection that can be activated in the brain by previous exposure to a non-harmful seizure episode before status epilepticus. A major transcriptional feature of tolerance is gene downregulation. Here, through methylation analysis of 34,143 discrete loci representing all annotated CpG islands and promoter regions in the mouse genome, we report the genome-wide DNA methylation changes in the hippocampus after status epilepticus and epileptic tolerance in adult mice. A total of 321 genes showed altered DNA methylation after status epilepticus alone or status epilepticus that followed seizure preconditioning, with >90% of the promoters of these genes undergoing hypomethylation. These profiles included genes not previously associated with epilepsy, such as the polycomb gene Phc2. Differential methylation events generally occurred throughout the genome without bias for a particular chromosomal region, with the exception of a small region of chromosome 4, which was significantly overrepresented with genes hypomethylated after status epilepticus. Surprisingly, only few genes displayed differential hypermethylation in epileptic tolerance. Nevertheless, gene ontology analysis emphasized the majority of differential methylation events between the groups occurred in genes associated with nuclear functions, such as DNA binding and transcriptional regulation. The present study reports select, genome-wide DNA methylation changes after status epilepticus and in epileptic tolerance, which may contribute to regulating the gene expression environment of the seizure-damaged hippocampus.

  14. Global status of hydrogen research

    Lakeman, J.B.; Browning, D.J.

    2001-07-01

    This report surveys the global status of hydrogen research and identifies technological barriers to the implementation of a global hydrogen economy. It is concluded that there will be a 30 year transition phase to the full implementation of the hydrogen economy. In this period, hydrogen will be largely produced by the reformation of hydrocarbons, particularly methane. It will be necessary to ensure that any carbonaceous oxides (and other unwanted species) formed as by-products will be trapped and not released into the atmosphere. Following the transition phase, hydrogen should be largely produced from renewable energy sources using some form of water cracking, largely electrolysis. Target performances and costs are identified for key technologies. The status of hydrogen research in the UK is reviews and it is concluded that the UK does not have a strategy for the adoption of the hydrogen economy, nor does it have a coherent and co-ordinated research and development strategy addressing barriers to the hydrogen economy. Despite this fact, because of the long transition phase, it is still possible for the UK to formulate a coherent strategy and make a significant contribution to the global implementation of the hydrogen economy, as there are still unresolved technology issues. The report concludes with a number of recommendations. (Author)

  15. EG-15THE METHYLATION STATUS OF MGMT IN MEDULLOBLASTOMA

    Shimizu, Yuzaburo; Kurimoto, Tomoko; Kondo, Akihide; Arai, Hajime

    2014-01-01

    BACKGROUND: Medulloblastoma is a highly malignant brain tumor in childhood. Some studies reported that alkylating chemotherapeutic drugs are effective agents in the treatment of patients with medulloblastoma. O6-methylguanine-DNA methyltransferase (MGMT) is one of the DNA repair enzymes and plays a significant role in tumor resistance to alkylating agents. Low MGMT expression or MGMT promoter methylation have been found to be associated with favorable outcomes in malignant glioma patients treated with alkylating agents such as temozolomide. However, impact of MGMT status on clinical outcomes in medulloblastoma patients is not fully evaluated. OBJECTIVE: The objective of this study is to investigate the association between MGMT status and the response for chemotherapy in pediatric patients with medulloblastoma. METHODS: Patients with medulloblastoma treated at our institution between 1995 and 2012 were reviewed retrospectively. Relevant clinical information including current disease status, tumor response to chemotherapy was obtained from the hospital charts. To evaluate the MGMT status, we performed bisulfite sequencing analysis to determine the methylation status of the MGMT promoter. RESULTS: Tumor material and detailed clinical information were available in 22 patients. Of them, 13 patients were alive (11 in CR), seven died of disease and two were lost to follow up. Five patients were with dissemination at diagnosis. We succeeded to evaluate both the MGMT status of tumors and the number of methylation sites in MGMT promoter. CONCLUSIONS: We studied the prognostic value of MGMT promoter methylation in medulloblastoma children.

  16. Renewables 2007 - Global status report

    Martinot, Eric; Mastny, Lisa; Rosbotham, Lyle; Suding, Paul; Sonntag-O'Brien, Virginia; Lempp, Philippe

    2007-01-01

    In 2007, more than $100 billion was invested in new renewable energy capacity, manufacturing plants, and research and development-a true global milestone. Yet perceptions lag behind the reality of renewable energy because change has been so rapid in recent years. This report captures that reality and provides an overview of the status of renewable energy worldwide in 2007. The report covers trends in markets, investments, industries, policies, and rural (off-grid) renewable energy. (By design, the report does not provide analysis, discuss current issues, or forecast the future.) Many of the trends reflect increasing significance relative to conventional energy

  17. Maternal Methyl-Group Donor Intake and Global DNA (HydroxyMethylation before and during Pregnancy

    Sara Pauwels

    2016-08-01

    Full Text Available It is still unclear to which extent methyl-group intake during pregnancy can affect maternal global DNA (hydroxylmethylation. Pregnancy methylation profiling and its link with methyl-group intake in a healthy population could enhance our understanding of the development of pregnancy related disorders. One hundred forty-eight women were enrolled in the MANOE (MAternal Nutrition and Offspring’s Epigenome study. Thiry-four women were enrolled before pregnancy and 116 during the first trimester of pregnancy. Global DNA (hydroxymethylation in blood using LC-MS/MS and dietary methyl-group intake (methionine, folate, betaine, and choline using a food-frequency questionnaire were estimated pre-pregnancy, during each trimester, and at delivery. Global DNA (hydroxymethylation levels were highest pre-pregnancy and at weeks 18–22 of pregnancy. We observed a positive relation between folic acid and global DNA methylation (p = 0.04 and hydroxymethylation (p = 0.04. A high intake of methionine pre-pregnancy and in the first trimester showed lower (hydroxymethylation percentage in weeks 11–13 and weeks 18–22, respectively. Choline and betaine intake in the first weeks was negatively associated with hydroxymethylation. Women with a high intake of these three methyl groups in the second and third trimester showed higher hyrdoxymethylation/methylation levels in the third trimester. To conclude, a time trend in DNA (hydroxymethylation was found and women with higher methyl-group intake showed higher methylation in the third trimester, and not in earlier phases of pregnancy.

  18. Renewables 2012 - Global status report

    Sawin, Janet L.; Bhattacharya, Sribas Chandra; Galan, Ernesto Macias; McCrone, Angus; Moomaw, William R.; Sims, Ralph; Sonntag-O'Brien, Virginia; Sverrisson, Freyr; Chawla, Kanika; Adib, Rana; Musolino, Evan; Mastny, Lisa; Skeen, Jonathan; Martinot, Eric; Hinrichs-Rahlwes, Rainer

    2012-01-01

    Renewable energy markets and policy frameworks have evolved rapidly in recent years. This report provides a comprehensive and timely overview of renewable energy market, industry, investment, and policy developments worldwide. It relies on the most recent data available, provided by a network of more than 400 contributors and researchers from around the world, all of which is brought together by a multi-disciplinary authoring team. The report covers recent developments, current status, and key trends; by design, it does not provide analysis or forecast the future. As such, this report and subsequent editions will serve as a benchmark for measuring global progress in the deployment of renewable energy, which is of particular interest in this International Year of Sustainable Energy for All. UN Secretary-General Ban Ki-moon has marked the occasion with a new global initiative, Sustainable Energy for All, which seeks to mobilise global action on three inter-linked objectives to be achieved by 2030: universal access to modern energy services, improved rates of energy efficiency, and expanded use of renewable energy sources

  19. Delivery type not associated with global methylation at birth

    Virani Shama

    2012-06-01

    Full Text Available Abstract Background Birth by cesarean delivery (CD as opposed to vaginal delivery (VD is associated with altered health outcomes later in life, including respiratory disorders, allergies and risk of developing type I diabetes. Epigenetic gene regulation is a proposed mechanism by which early life exposures affect later health outcomes. Previously, type of delivery has been found to be associated with differences in global methylation levels, but the sample sizes have been small. We measured global methylation in a large birth cohort to identify whether type of delivery is associated with epigenetic changes. Methods DNA was isolated from cord blood collected from the University of Michigan Women’s & Children Hospital and bisulfite-converted. The Luminometric Methylation Assay (LUMA and LINE-1 methylation assay were run on all samples in duplicate. Results Global methylation data at CCGG sites throughout the genome, as measured by LUMA, were available from 392 births (52% male; 65% CD, and quantitative methylation levels at LINE-1 repetitive elements were available for 407 births (52% male; 64% CD. LUMA and LINE-1 methylation measurements were negatively correlated in this population (Spearman’s r = −0.13, p =0.01. LUMA measurements were significantly lower for total CD and planned CD, but not emergency CD when compared to VD (median VD = 74.8, median total CD = 74.4, p = 0.03; median planned CD = 74.2, p = 0.02; median emergency CD = 75.3, p = 0.39. However, this association did not persist when adjusting for maternal age, maternal smoking and infant gender. Furthermore, total CD deliveries, planned CD and emergency CD deliveries were not associated with LINE-1 measurements as compared to VD (median VD = 82.2, median total CD = 81.9, p = 0.19; median planned CD = 81.9, p = 0.19; median emergency CD = 82.1, p = 0.52. This lack of association held when adjusting for maternal age

  20. Residual Deep Convolutional Neural Network Predicts MGMT Methylation Status.

    Korfiatis, Panagiotis; Kline, Timothy L; Lachance, Daniel H; Parney, Ian F; Buckner, Jan C; Erickson, Bradley J

    2017-10-01

    Predicting methylation of the O6-methylguanine methyltransferase (MGMT) gene status utilizing MRI imaging is of high importance since it is a predictor of response and prognosis in brain tumors. In this study, we compare three different residual deep neural network (ResNet) architectures to evaluate their ability in predicting MGMT methylation status without the need for a distinct tumor segmentation step. We found that the ResNet50 (50 layers) architecture was the best performing model, achieving an accuracy of 94.90% (+/- 3.92%) for the test set (classification of a slice as no tumor, methylated MGMT, or non-methylated). ResNet34 (34 layers) achieved 80.72% (+/- 13.61%) while ResNet18 (18 layers) accuracy was 76.75% (+/- 20.67%). ResNet50 performance was statistically significantly better than both ResNet18 and ResNet34 architectures (p deep neural architectures can be used to predict molecular biomarkers from routine medical images.

  1. Renewables 2010 - Global status report

    Sawin, Janet L.; Martinot, Eric; Sonntag-O'Brien, Virginia; McCrone, Angus; Roussell, Jodie; Barnes, Douglas; Flavin, Christopher; Mastny, Lisa; Kraft, Diana; Wang, Shannon; Ellenbeck, Saskia; Ilieva, Lili; Griebenow, Christof; Adib, Rana; Lempp, Philippe; Welker, Bettina

    2010-01-01

    Changes in renewable energy markets, investments, industries, and policies have been so rapid in recent years that perceptions of the status of renewable energy can lag years behind the reality. This report captures that reality and provides a unique overview of renewable energy worldwide as of early 2010. The report covers both current status and key trends. By design, the report does not provide analysis, discuss current issues, or forecast the future. Many of the trends reflect the increasing significance of renewable energy relative to conventional energy sources (including coal, gas, oil, and nuclear). By 2010, renewable energy had reached a clear tipping point in the context of global energy supply. Renewables comprised fully one quarter of global power capacity from all sources and delivered 18 percent of global electricity supply in 2009. In a number of countries, renewables represent a rapidly growing share of total energy supply-including heat and transport. The share of households worldwide employing solar hot water heating continues to increase and is now estimated at 70 million households. And investment in new renewable power capacity in both 2008 and 2009 represented over half of total global investment in new power generation. Trends reflect strong growth and investment across all market sectors-power generation, heating and cooling, and transport fuels. Grid-connected solar PV has grown by an average of 60 percent every year for the past decade, increasing 100-fold since 2000. During the past five years from 2005 to 2009, consistent high growth year-after-year marked virtually every other renewable technology. During those five years, wind power capacity grew an average of 27 percent annually, solar hot water by 19 percent annually, and ethanol production by 20 percent annually. Biomass and geothermal for power and heat also grew strongly. Much more active policy development during the past several years culminated in a significant policy milestone

  2. Renewables 2014. Global status report 2014

    Sawin, Janet L.; Sverrisson, Freyr; Chawla, Kanika; Lins, Christine; Adib, Rana; Hullin, Martin; Leitner, Sarah; Mazzaccaro, Stefano; Murdock, Hannah; Williamson, Laura E.; Wright, Glen; McCrone, Angus; Musolino, Evan; Mastny, Lisa; Lily Riahi; Sims, Ralph; Jonathan Skeen; Sverrisson, Freyr; Martinot, Eric

    2014-01-01

    The Renewables Global Status Report provides a comprehensive and timely overview of renewable energy market, industry, investment, and policy developments worldwide. It enables policy-makers, industry, investors, and civil society to make informed decisions. The report covers recent developments, current status, and key trends; by design, it does not provide analysis or forecast. The Renewables Global Status Report relies on up-to-date renewable energy data, provided by an international network of more than 500 contributors, researchers, and authors

  3. Global DNA methylation responses to low dose radiation exposure

    Newman, M.R.; Ormsby, R.J.; Blyth, B.J.; Sykes, P.J.; Bezak, E.

    2011-01-01

    Full text: High radiation doses cause breaks in the DNA which are considered the critical lesions in initiation of radiation-induced cancer. However, at very low radiation doses relevant for the general public, the induction of such breaks will be rare, and other changes to the DNA such as DNA methylation which affects gene expression may playa role in radiation responses. We are studying global DNA methylation after low dose radiation exposure to determine if low dose radiation has short- and/or long-term effects on chromatin structure. We developed a sensitive high resolution melt assay to measure the levels of DNA methylation across the mouse genome by analysing a stretch of DNA sequence within Long Interspersed Nuclear Elements-I (LINE I) that comprise a very large proportion of the mouse and human genomes. Our initial results suggest no significant short-term or longterm) changes in global NA methylation after low dose whole-body X-radiation of 10 J1Gyor 10 mGy, with a significant transient increase in NA methylation observed I day after a high dose of I Gy. If the low radiation doses tested are inducing changes in bal DNA methylation, these would appear to be smaller than the variation observed between the sexes and following the general stress of the sham-irradiation procedure itself. This research was funded by the Low Dose Radiation Research Program, Biological and Environmental Research, US DOE, Grant DE-FG02-05ER64104 and MN is the recipient of the FMCF/BHP Dose Radiation Research Scholarship.

  4. Relationship between methylation status of vitamin D-related genes, vitamin D levels, and methyl-donor biochemistry

    Emma Louise Beckett

    2016-12-01

    Full Text Available Vitamin D is known for its role in the regulation of gene expression via the vitamin D receptor, a nuclear transcription factor. More recently, a role for vitamin D in regulating DNA methylation has been identified as an additional mechanism of modulation of gene expression. How methylation status influences vitamin D metabolism and response pathways is not yet clear. Therefore, we aimed to assess the relationship between plasma 25-hydroxycholecalciferol (25(OHD and the methylation status of vitamin D metabolism enzyme genes (CYP2R1, CYP27B1 and CYP24A1 and the vitamin D receptor gene (VDR. This analysis was conducted in the context of dietary vitamin D, and background methyl donor related biochemistry, with adjustment for several dietary and lifestyle variables. Percentage methylation at CpG sites was assessed in peripheral blood cells using methylation sensitive and dependent enzymes and qPCR. Standard analytical techniques were used to determine plasma 25(OHD and homocysteine, and serum folate and B12, with the relationship to methylation status assessed using multi-variable regression analysis. CYP2R1 and VDR methylation were found to be independent predictors of plasma 25(OHD, when adjusted for vitamin D intake and other lifestyle variables. CYP24A1 was related to plasma 25(OHD directly, but not in the context of vitamin D intake. Methyl-group donor biochemistry was associated with the methylation status of some genes, but did not alter the relationship between methylation and plasma 25(OHD. Modulation of methylation status of CYP2R1, CYP24A1 and VDR in response to plasma 25(OHD may be part of feedback loops involved in maintaining vitamin D homeostasis, and may explain a portion of the variance in plasma 25(OHD levels in response to intake and sun exposure. Methyl-group donor biochemistry, while a potential independent modulator, did not alter this effect.

  5. No effect of folic acid supplementation on global DNA methylation in men and women with moderately elevated homocysteine.

    Audrey Y Jung

    Full Text Available A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n = 105 or placebo treatment (n = 111 for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference = 0.008, 95%CI = -0.05,0.07, P = 0.79. There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n = 70, baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes.ClinicalTrials.gov NCT00110604.

  6. No effect of folic acid supplementation on global DNA methylation in men and women with moderately elevated homocysteine.

    Jung, Audrey Y; Smulders, Yvo; Verhoef, Petra; Kok, Frans J; Blom, Henk; Kok, Robert M; Kampman, Ellen; Durga, Jane

    2011-01-01

    A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n = 105) or placebo treatment (n = 111) for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference = 0.008, 95%CI = -0.05,0.07, P = 0.79). There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n = 70), baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes.ClinicalTrials.gov NCT00110604.

  7. Methylation status regulates lipoprotein lipase expression in chronic lymphocytic leukemia.

    Abreu, Cecilia; Moreno, Pilar; Palacios, Florencia; Borge, Mercedes; Morande, Pablo; Landoni, Ana Inés; Gabus, Raul; Dighiero, Guillermo; Giordano, Mirta; Gamberale, Romina; Oppezzo, Pablo

    2013-08-01

    Among different prognostic factors in chronic lymphocytic leukemia (CLL), we previously demonstrated that lipoprotein lipase (LPL) is associated with an unmutated immunoglobulin profile and clinical poor outcome. Despite the usefulness of LPL for CLL prognosis, its functional role and the molecular mechanism regulating its expression are still open questions. Interaction of CLL B-cells with the tissue microenvironment favors disease progression by promoting malignant B-cell growth. Since tissue methylation can be altered by environmental factors, we investigated the methylation status of the LPL gene and the possibility that overexpression could be associated with microenvironment signals. Our results show that a demethylated state of the LPL gene is responsible for its anomalous expression in unmutated CLL cases and that this expression is dependent on microenvironment signals. Overall, this work proposes that an epigenetic mechanism, triggered by the microenvironment, regulates LPL expression in CLL disease.

  8. Renewables 2005. Global status report

    2005-01-01

    This report provides an overview of the status of renewable energy worldwide in 2005. It covers markets, investments, industries, policies, and rural (off-grid) renewable energy in developing countries. By design, the report does not provide analysis, recommendations, or conclusions. An extensive research and review process over several months involving more than 100 researchers and contributors has kept inaccuracies to a minimum. REN21 sees this report as the beginning of an active exchange of views and information. This report reveals some surprising facts about renewable energy, many reflecting strong growth trends and increasing significance relative to conventional energy. (au)

  9. Renewables 2005. Global status report

    NONE

    2005-07-01

    This report provides an overview of the status of renewable energy worldwide in 2005. It covers markets, investments, industries, policies, and rural (off-grid) renewable energy in developing countries. By design, the report does not provide analysis, recommendations, or conclusions. An extensive research and review process over several months involving more than 100 researchers and contributors has kept inaccuracies to a minimum. REN21 sees this report as the beginning of an active exchange of views and information. This report reveals some surprising facts about renewable energy, many reflecting strong growth trends and increasing significance relative to conventional energy. (au)

  10. Renewables 2005 - Global status report

    Martinot, Eric

    2005-01-01

    This report provides an overview of the status of renewable energy worldwide in 2005. It covers markets, investments, industries, policies, and rural (off-grid) renewable energy in developing countries. By design, the report does not provide analysis, recommendations, or conclusions. An extensive research and review process over several months involving more than 100 researchers and contributors has kept inaccuracies to a minimum. REN21 sees this report as the beginning of an active exchange of views and information. This report reveals some surprising facts about renewable energy, many reflecting strong growth trends and increasing significance relative to conventional energy

  11. Renewables 2012. Global Status Report

    Sawin, J. L. [and others

    2012-08-15

    Renewable energy markets and policy frameworks have evolved rapidly in recent years. This report provides a comprehensive and timely overview of renewable energy market, industry, investment, and policy developments worldwide. It relies on the most recent data available, provided by a network of more than 400 contributors and researchers from around the world, all of which is brought together by a multi-disciplinary authoring team. The report covers recent developments, current status, and key trends; by design, it does not provide analysis or forecast the future.

  12. Renewables 2017 Global Status Report

    Sawin, Janet L.; Sverrisson, Freyr; Seyboth, Kristin; Adib, Rana; Murdock, Hannah E.; Lins, Christine; Edwards, Isobel; Hullin, Martin; Nguyen, Linh H.; Prillianto, Satrio S.; Satzinger, Katharina; Appavou, Fabiani; Brown, Adam; Chernyakhovskiy, Ilya; Logan, Jeffrey; Milligan, Michael; Zinaman, Owen; Epp, Baerbel; Huber, Lon; Lyons, Lorcan; Nowak, Thomas; Otte, Pia; Skeen, Jonathan; Sovacool, Benjamin; Witkamp, Bert; Musolino, Evan; Brown, Adam; Williamson, Laura E.; Ashworth, Lewis; Mastny, Lisa

    2017-01-01

    Renewable energy technologies increase their hold across developing and emerging economies throughout the year The year 2016 saw several developments and ongoing trends that all have a bearing on renewable energy, including the continuation of comparatively low global fossil fuel prices; dramatic price declines of several renewable energy technologies; and a continued increase in attention to energy storage. For the third consecutive year, global energy-related carbon dioxide emissions from fossil fuels and industry were nearly flat in 2016, due largely to declining coal use worldwide but also due to improvements in energy efficiency and to increasing use of renewable energy. As of 2015, renewable energy provided an estimated 19.3% of global final energy consumption, and growth in capacity and production continued in 2016. The power sector experienced the greatest increases in renewable energy capacity in 2016, whereas the growth of renewables in the heating and cooling and transport sectors was comparatively slow. Most new renewable energy capacity is installed in developing countries, and largely in China, the single largest developer of renewable power and heat over the past eight years. In 2016, renewable energy spread to a growing number of developing and emerging economies, some of which have become important markets. For the more than 1 billion people without access to electricity, distributed renewable energy projects, especially those in rural areas far from the centralised grid, offer important and often cost-effective options to provide such access. The renewable energy sector employed 9.8 million people in 2016, an increase of 1.1% over 2015. By technology, solar PV and biofuels provided the largest numbers of jobs. Employment shifted further towards Asia, which accounted for 62% of all renewable energy jobs (not including large-scale hydropower), led by China. The development of community renewable energy projects continued in 2016, but the pace of

  13. Refined global methyl halide budgets with respect to rapeseed (Brassica napus) by life-cycle measurements

    Jiao, Y.; Acdan, J.; Xu, R.; Deventer, M. J.; Rhew, R. C.

    2017-12-01

    A precise quantification of global methyl halide budgets is needed to evaluate the ozone depletion potential of these compounds and to predict future changes of stratospheric ozone. However, the global budgets of methyl halides are not balanced between currently identified and quantified sources and sinks. Our study re-evaluated the methyl bromide budget from global cultivated rapeseed (Brassica napus) through life-cycle flux measurements both in the greenhouse and in the field, yielding a methyl bromide emission rate that scales globally to 1.0 - 1.2 Gg yr-1. While this indicates a globally significant source, it is much smaller than the previously widely cited value of 5 - 6 Gg yr-1(Mead et al., 2008), even taking into account the near tripling of annual global yield of rapeseed since the previous evaluation was conducted. Our study also evaluated the methyl chloride and methyl iodide emission levels from rapeseed, yielding emission rates that scale to 5.4 Gg yr-1 for methyl chloride and 1.8 Gg yr-1 of methyl iodide. The concentrations of the methyl donor SAM (S-adenosyl methionine) and the resultant product SAH (S-Adenosyl-L-homocysteine) were also analyzed to explore their role in biogenic methyl halide formation. Halide gradient incubations showed that the magnitude of methyl halide emissions from rapeseed is highly correlated to soil halide levels, thus raising the concern that the heterogeneity of soil halide contents geographically should be considered when extrapolating to global budget.

  14. Global status report on violence prevention, 2014

    Butchart, A.; Mikton, C.

    2014-01-01

    The Global status report on violence prevention 2014, which reflects data from 133 countries, is the first report of its kind to assess national efforts to address interpersonal violence, namely child maltreatment, youth violence, intimate partner and sexual violence, and elder abuse.\\ud \\ud Jointly published by WHO, the United Nations Development Programme, and the United Nations Office on Drugs and Crime, the report reviews the current status of violence prevention efforts in countries, and...

  15. Aquaculture: global status and trends

    Bostock, John; McAndrew, Brendan; Richards, Randolph; Jauncey, Kim; Telfer, Trevor; Lorenzen, Kai; Little, David; Ross, Lindsay; Handisyde, Neil; Gatward, Iain; Corner, Richard

    2010-01-01

    Aquaculture contributed 43 per cent of aquatic animal food for human consumption in 2007 (e.g. fish, crustaceans and molluscs, but excluding mammals, reptiles and aquatic plants) and is expected to grow further to meet the future demand. It is very diverse and, contrary to many perceptions, dominated by shellfish and herbivorous and omnivorous pond fish either entirely or partly utilizing natural productivity. The rapid growth in the production of carnivorous species such as salmon, shrimp and catfish has been driven by globalizing trade and favourable economics of larger scale intensive farming. Most aquaculture systems rely on low/uncosted environmental goods and services, so a critical issue for the future is whether these are brought into company accounts and the consequent effects this would have on production economics. Failing that, increased competition for natural resources will force governments to allocate strategically or leave the market to determine their use depending on activities that can extract the highest value. Further uncertainties include the impact of climate change, future fisheries supplies (for competition and feed supply), practical limits in terms of scale and in the economics of integration and the development and acceptability of new bio-engineering technologies. In the medium term, increased output is likely to require expansion in new environments, further intensification and efficiency gains for more sustainable and cost-effective production. The trend towards enhanced intensive systems with key monocultures remains strong and, at least for the foreseeable future, will be a significant contributor to future supplies. Dependence on external feeds (including fish), water and energy are key issues. Some new species will enter production and policies that support the reduction of resource footprints and improve integration could lead to new developments as well as reversing decline in some more traditional systems. PMID:20713392

  16. Aquaculture: global status and trends.

    Bostock, John; McAndrew, Brendan; Richards, Randolph; Jauncey, Kim; Telfer, Trevor; Lorenzen, Kai; Little, David; Ross, Lindsay; Handisyde, Neil; Gatward, Iain; Corner, Richard

    2010-09-27

    Aquaculture contributed 43 per cent of aquatic animal food for human consumption in 2007 (e.g. fish, crustaceans and molluscs, but excluding mammals, reptiles and aquatic plants) and is expected to grow further to meet the future demand. It is very diverse and, contrary to many perceptions, dominated by shellfish and herbivorous and omnivorous pond fish either entirely or partly utilizing natural productivity. The rapid growth in the production of carnivorous species such as salmon, shrimp and catfish has been driven by globalizing trade and favourable economics of larger scale intensive farming. Most aquaculture systems rely on low/uncosted environmental goods and services, so a critical issue for the future is whether these are brought into company accounts and the consequent effects this would have on production economics. Failing that, increased competition for natural resources will force governments to allocate strategically or leave the market to determine their use depending on activities that can extract the highest value. Further uncertainties include the impact of climate change, future fisheries supplies (for competition and feed supply), practical limits in terms of scale and in the economics of integration and the development and acceptability of new bio-engineering technologies. In the medium term, increased output is likely to require expansion in new environments, further intensification and efficiency gains for more sustainable and cost-effective production. The trend towards enhanced intensive systems with key monocultures remains strong and, at least for the foreseeable future, will be a significant contributor to future supplies. Dependence on external feeds (including fish), water and energy are key issues. Some new species will enter production and policies that support the reduction of resource footprints and improve integration could lead to new developments as well as reversing decline in some more traditional systems.

  17. The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.

    Fumiharu Ohka

    Full Text Available Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4 have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ, and even low grade gliomas (LGGs, WHO grade 2 eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the O(6-methylguanine-DNA methyltransferase (MGMT that is the main determinant of resistance to TMZ, recent studies suggested that MGMT promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that MGMT promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of MGMT promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1 IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2 LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3 LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4 higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.

  18. Renewables 2013. Global status report 2013

    Sawin, Janet L.; Chawla, Kanika; Riahi, Lily; Adib, Rana; Skeen, Jonathan; Chavez, Sandra; Skeen, Jonathan; Hinrichs-Rahlwes, Rainer; Macias Galan, Ernesto; McCrone, Angus; Musolino, Evan; Mastny, Lisa; Sims, Ralph; Sonntag-O'Brien, Virginia; Sverrisson, Freyr; Martinot, Eric

    2013-01-01

    Renewable energy markets, industries, and policy frameworks have evolved rapidly in recent years. The Renewables Global Status Report provides a comprehensive and timely overview of renewable energy market, industry, investment, and policy developments worldwide. It relies on the most recent data available, provided by a network of more than 500 contributors and researchers from around the world, all of which is brought together by a multi-disciplinary authoring team. The report covers recent developments, current status, and key trends; by design, it does not provide analysis or forecasts

  19. Global DNA methylation and oxidative stress biomarkers in workers exposed to metal oxide nanoparticles

    Liou, Saou-Hsing; Wu, Wei-Te; Liao, Hui-Yi [National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China); Chen, Chao-Yu; Tsai, Cheng-Yen; Jung, Wei-Ting [Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan (China); Lee, Hui-Ling, E-mail: huilinglee3573@gmail.com [Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan (China)

    2017-06-05

    Highlights: • Global methylation and oxidative DNA damage levels in nanomaterial handling workers were assessed. • 8-isoprostane in exhaled breath condensate of workers exposed to nanoparticles was higher. • 8-OHdG was negatively correlated with global methylation. • Exposure to metal oxide nanoparticles may lead to global methylation and DNA oxidative damage. - Abstract: This is the first study to assess global methylation, oxidative DNA damage, and lipid peroxidation in workers with occupational exposure to metal oxide nanomaterials (NMs). Urinary and white blood cell (WBC) 8-hydroxydeoxyguanosine (8-OHdG), and exhaled breath condensate (EBC) 8-isoprostane were measured as oxidative stress biomarkers. WBC global methylation was measured as an epigenetic alteration. Exposure to TiO{sub 2}, SiO{sub 2,} and indium tin oxide (ITO) resulted in significantly higher oxidative biomarkers such as urinary 8-OHdG and EBC 8-isoprostane. However, significantly higher WBC 8-OHdG and lower global methylation were only observed in ITO handling workers. Significant positive correlations were noted between WBC and urinary 8-OHdG (Spearman correlation r = 0.256, p = 0.003). Furthermore, a significant negative correlation was found between WBC 8-OHdG and global methylation (r = −0.272, p = 0.002). These results suggest that exposure to metal oxide NMs may lead to global methylation, DNA oxidative damage, and lipid peroxidation.

  20. Variation of global DNA methylation levels with age and in autistic children.

    Tsang, Shui-Ying; Ahmad, Tanveer; Mat, Flora W K; Zhao, Cunyou; Xiao, Shifu; Xia, Kun; Xue, Hong

    2016-09-23

    The change in epigenetic signatures, in particular DNA methylation, has been proposed as risk markers for various age-related diseases. However, the course of variation in methylation levels with age, the difference in methylation between genders, and methylation-disease association at the whole genome level is unclear. In the present study, genome-wide methylation levels in DNA extracted from peripheral blood for 2116 healthy Chinese in the 2-97 age range and 280 autistic trios were examined using the fluorescence polarization-based genome-wide DNA methylation quantification method developed by us. Genome-wide or global DNA methylation levels proceeded through multiple phases of variation with age, consisting of a steady increase from age 2 to 25 (r = 0.382) and another rise from age 41 to 55 to reach a peak level of ~80 % (r = 0.265), followed by a sharp decrease to ~40 % in the mid-1970s (age 56 to 75; r = -0.395) and leveling off thereafter. Significant gender effect in methylation levels was observed only for the 41-55 age group in which methylation in females was significantly higher than in males (p = 0.010). In addition, global methylation level was significantly higher in autistic children than in age-matched healthy children (p < 0.001). The multiphasic nature of changes in global methylation levels with age was delineated, and investigation into the factors underlying this profile will be essential to a proper understanding of the aging process. Furthermore, this first report of global hypermethylation in autistic children also illustrates the importance of age-matched controls in characterization of disease-associated variations in DNA methylation.

  1. Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women

    Iwasaki Motoki

    2012-07-01

    Full Text Available Abstract Background Although global hypomethylation of leukocyte DNA has been associated with an increased risk of several sites of cancer, including breast cancer, determinants of global methylation level among healthy individuals remain largely unexplored. Here, we examined whether postmenopausal endogenous sex hormones were associated with the global methylation level of leukocyte DNA. Methods A cross-sectional study was conducted using the control group of a breast cancer case–control study in Nagano, Japan. Subjects were postmenopausal women aged 55 years or over who provided blood samples. We measured global methylation level of peripheral blood leukocyte DNA by luminometric methylation assay; estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate, testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex-hormone binding globulin by immunoradiometric assay. A linear trend of association between methylation and hormone levels was evaluated by regression coefficients in a multivariable liner regression model. A total of 185 women were included in the analyses. Results Mean global methylation level (standard deviation was 70.3% (3.1 and range was from 60.3% to 79.2%. Global methylation level decreased 0.27% per quartile category for estradiol and 0.39% per quartile category for estrone while it increased 0.41% per quartile category for bioavailable estradiol. However, we found no statistically significant association of any sex hormone level measured in the present study with global methylation level of leukocyte DNA. Conclusions Our findings suggest that endogenous sex hormones are not major determinants of the global methylation level of leukocyte DNA.

  2. A high-throughput and sensitive method to measure Global DNA Methylation: Application in Lung Cancer

    Mamaev Sergey

    2008-08-01

    Full Text Available Abstract Background Genome-wide changes in DNA methylation are an epigenetic phenomenon that can lead to the development of disease. The study of global DNA methylation utilizes technology that requires both expensive equipment and highly specialized skill sets. Methods We have designed and developed an assay, CpGlobal, which is easy-to-use, does not utilize PCR, radioactivity and expensive equipment. CpGlobal utilizes methyl-sensitive restriction enzymes, HRP Neutravidin to detect the biotinylated nucleotides incorporated in an end-fill reaction and a luminometer to measure the chemiluminescence. The assay shows high accuracy and reproducibility in measuring global DNA methylation. Furthermore, CpGlobal correlates significantly with High Performance Capillary Electrophoresis (HPCE, a gold standard technology. We have applied the technology to understand the role of global DNA methylation in the natural history of lung cancer. World-wide, it is the leading cause of death attributed to any cancer. The survival rate is 15% over 5 years due to the lack of any clinical symptoms until the disease has progressed to a stage where cure is limited. Results Through the use of cell lines and paired normal/tumor samples from patients with non-small cell lung cancer (NSCLC we show that global DNA hypomethylation is highly associated with the progression of the tumor. In addition, the results provide the first indication that the normal part of the lung from a cancer patient has already experienced a loss of methylation compared to a normal individual. Conclusion By detecting these changes in global DNA methylation, CpGlobal may have a role as a barometer for the onset and development of lung cancer.

  3. Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B12.

    Jill A McKay

    Full Text Available Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA and gene specific (IGF2, ZNT5, IGFBP3 DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B(12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B(12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032 and inversely with ZNT5 methylation (rho = -0.13, p = 0.017. Methylation of the IGFBP3 locus correlated inversely with infant vitamin B(12 concentration (rho = -0.16, p = 0.007, whilst global DNA methylation correlated inversely with maternal vitamin B(12 concentrations (rho = 0.18, p = 0.044. Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ(2 = 8.82, p = 0.003 and maternal MTHFR 677C>T genotype with IGF2 methylation (χ(2 = 2.77, p = 0.006. These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B(12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for

  4. The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma.

    Mansour S Al-Moundhri

    Full Text Available BACKGROUND: Epigenetics, particularly DNA methylation, has recently been elucidated as important in gastric cancer (GC initiation and progression. We investigated the clinical and prognostic importance of whole blood global and site-specific DNA methylation in GC. METHODS: Genomic DNA was extracted from the peripheral blood of 105 Omani GC patients at diagnosis. DNA methylation was quantified by pyrosequencing of global DNA and specific gene promoter regions at 5 CpG sites for CDH1, 7 CpG sites for p16, 4 CpG sites for p53, and 3 CpG sites for RUNX3. DNA methylation levels in patients were categorized into low, medium, and high tertiles. Associations between methylation level category and clinicopathological features were evaluated using χ(2 tests. Survival analyses were carried out using the Kaplan-Meier method and log rank test. A backward conditional Cox proportional hazards regression model was used to identify independent predictors of survival. RESULTS: Older GC patients had increased methylation levels at specific CpG sites within the CDH1, p53, and RUNX-3 promoters. Male gender was significantly associated with reduced global and increased site-specific DNA methylation levels in CDH1, p16, and p53 promoters. Global DNA low methylation level was associated with better survival on univariate analysis. Patients with high and medium methylation vs. low methylation levels across p16 promoter CpG sites, site 2 in particular, had better survival. Multivariate analysis showed that global DNA hypermethylation was a significant independent predictor of worse survival (hazard ratio (HR = 2.0, 95% CI: 1.1-3.8; p = 0.02 and high methylation mean values across p16 promoter sites 1-7 were associated with better survival with HR of 0.3 (95% CI, 0.1-0.8; p = 0.02 respectively. CONCLUSIONS: Analysis of global and site-specific DNA methylation in peripheral blood by pyrosequencing provides quantitative DNA methylation values that may serve as important

  5. Glucose Tolerance, MTHFR C677T and NOS3 G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals

    Tandi E. Matsha

    2016-01-01

    Full Text Available The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28% individuals had T2DM of which 97 (17.2% were screen-detected cases. Another 119 (21.1% had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9% had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p≤0.033 and in screen-detected diabetes compared to known diabetes on treatment (p=0.019. There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p>0.999. In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β=0.943; 95% CI: 0.286 to 1.560. The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control.

  6. Glucose Tolerance, MTHFR C677T and NOS3 G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals

    Mutize, Tinashe; Erasmus, Rajiv T.

    2016-01-01

    The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p ≤ 0.033) and in screen-detected diabetes compared to known diabetes on treatment (p = 0.019). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p > 0.999). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β = 0.943; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control. PMID:27990443

  7. Alterations of global histone H4K20 methylation during prostate carcinogenesis

    Behbahani Turang E

    2012-03-01

    Full Text Available Abstract Background Global histone modifications have been implicated in the progression of various tumour entities. Our study was designed to assess global methylation levels of histone 4 lysine 20 (H4K20me1-3 at different stages of prostate cancer (PCA carcinogenesis. Methods Global H4K20 methylation levels were evaluated using a tissue microarray in patients with clinically localized PCA (n = 113, non-malignant prostate disease (n = 27, metastatic hormone-naive PCA (mPCA, n = 30 and castration-resistant PCA (CRPC, n = 34. Immunohistochemistry was performed to assess global levels of H4K20 methylation levels. Results Similar proportions of the normal, PCA, and mPCA prostate tissues showed strong H4K20me3 staining. CRPC tissue analysis showed the weakest immunostaining levels of H4K20me1 and H4K20me2, compared to other prostate tissues. H4K20me2 methylation levels indicated significant differences in examined tissues except for normal prostate versus PCA tissue. H4K20me1 differentiates CRPC from other prostate tissues. H4K20me1 was significantly correlated with lymph node metastases, and H4K20me2 showed a significant correlation with the Gleason score. However, H4K20 methylation levels failed to predict PSA recurrence after radical prostatectomy. Conclusions H4K20 methylation levels constitute valuable markers for the dynamic process of prostate cancer carcinogenesis.

  8. MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas

    Korfiatis, Panagiotis; Kline, Timothy L.; Erickson, Bradley J., E-mail: bje@mayo.edu [Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905 (United States); Coufalova, Lucie [Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905 (United States); Department of Neurosurgery of First Faculty of Medicine, Charles University in Prague, Military University Hospital, Prague 128 21 (Czech Republic); International Clinical Research Center, St. Anne’s University Hospital Brno, Brno 656 91 (Czech Republic); Lachance, Daniel H. [Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905 (United States); Parney, Ian F. [Department of Neurologic Surgery, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905 (United States); Carter, Rickey E. [Department of Health Sciences Research, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905 (United States); Buckner, Jan C. [Department of Medical Oncology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905 (United States)

    2016-06-15

    Purpose: Imaging biomarker research focuses on discovering relationships between radiological features and histological findings. In glioblastoma patients, methylation of the O{sup 6}-methylguanine methyltransferase (MGMT) gene promoter is positively correlated with an increased effectiveness of current standard of care. In this paper, the authors investigate texture features as potential imaging biomarkers for capturing the MGMT methylation status of glioblastoma multiforme (GBM) tumors when combined with supervised classification schemes. Methods: A retrospective study of 155 GBM patients with known MGMT methylation status was conducted. Co-occurrence and run length texture features were calculated, and both support vector machines (SVMs) and random forest classifiers were used to predict MGMT methylation status. Results: The best classification system (an SVM-based classifier) had a maximum area under the receiver-operating characteristic (ROC) curve of 0.85 (95% CI: 0.78–0.91) using four texture features (correlation, energy, entropy, and local intensity) originating from the T2-weighted images, yielding at the optimal threshold of the ROC curve, a sensitivity of 0.803 and a specificity of 0.813. Conclusions: Results show that supervised machine learning of MRI texture features can predict MGMT methylation status in preoperative GBM tumors, thus providing a new noninvasive imaging biomarker.

  9. MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas

    Korfiatis, Panagiotis; Kline, Timothy L.; Erickson, Bradley J.; Coufalova, Lucie; Lachance, Daniel H.; Parney, Ian F.; Carter, Rickey E.; Buckner, Jan C.

    2016-01-01

    Purpose: Imaging biomarker research focuses on discovering relationships between radiological features and histological findings. In glioblastoma patients, methylation of the O 6 -methylguanine methyltransferase (MGMT) gene promoter is positively correlated with an increased effectiveness of current standard of care. In this paper, the authors investigate texture features as potential imaging biomarkers for capturing the MGMT methylation status of glioblastoma multiforme (GBM) tumors when combined with supervised classification schemes. Methods: A retrospective study of 155 GBM patients with known MGMT methylation status was conducted. Co-occurrence and run length texture features were calculated, and both support vector machines (SVMs) and random forest classifiers were used to predict MGMT methylation status. Results: The best classification system (an SVM-based classifier) had a maximum area under the receiver-operating characteristic (ROC) curve of 0.85 (95% CI: 0.78–0.91) using four texture features (correlation, energy, entropy, and local intensity) originating from the T2-weighted images, yielding at the optimal threshold of the ROC curve, a sensitivity of 0.803 and a specificity of 0.813. Conclusions: Results show that supervised machine learning of MRI texture features can predict MGMT methylation status in preoperative GBM tumors, thus providing a new noninvasive imaging biomarker.

  10. Quantitative global and gene-specific promoter methylation in relation to biological properties of neuroblastomas

    Kiss Nimrod B

    2012-09-01

    Full Text Available Abstract Background In this study we aimed to quantify tumor suppressor gene (TSG promoter methylation densities levels in primary neuroblastoma tumors and cell lines. A subset of these TSGs is associated with a CpG island methylator phenotype (CIMP in other tumor types. Methods The study panel consisted of 38 primary tumors, 7 established cell lines and 4 healthy references. Promoter methylation was determined by bisulphate Pyrosequencing for 14 TSGs; and LINE-1 repeat element methylation was used as an indicator of global methylation levels. Results Overall mean TSG Z-scores were significantly increased in cases with adverse outcome, but were unrelated to global LINE-1 methylation. CIMP with hypermethylation of three or more gene promoters was observed in 6/38 tumors and 7/7 cell lines. Hypermethylation of one or more TSG (comprising TSGs BLU, CASP8, DCR2, CDH1, RASSF1A and RASSF2 was evident in 30/38 tumors. By contrast only very low levels of promoter methylation were recorded for APC, DAPK1, NORE1A, P14, P16, TP73, PTEN and RARB. Similar involvements of methylation instability were revealed between cell line models and neuroblastoma tumors. Separate analysis of two proposed CASP8 regulatory regions revealed frequent and significant involvement of CpG sites between exon 4 and 5, but modest involvement of the exon 1 region. Conclusions/significance The results highlight the involvement of TSG methylation instability in neuroblastoma tumors and cell lines using quantitative methods, support the use of DNA methylation analyses as a prognostic tool for this tumor type, and underscore the relevance of developing demethylating therapies for its treatment.

  11. Fatty Acid Methyl Esters and Solutol HS 15 Confer Neuroprotection After Focal and Global Cerebral Ischemia

    Lin, Hung Wen; Saul, Isabel; Gresia, Victoria L.; Neumann, Jake T.; Dave, Kunjan R.; Perez-Pinzon, Miguel A.

    2013-01-01

    We previously showed that palmitic methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Soluto...

  12. Methylation Status of miR-182 Promoter in Lung Cancer Cell Lines

    Yongwen LI

    2015-05-01

    Full Text Available Background and objective It has been proven that the abnormal expression of miR-182 was related to the occurrence and development of tumors. The aim of this study is to explore the relationship between the methylation of miR-182 promoter and its expression in lung cancer cell lines. Methods Real-time quantitative PCR and methylation-specific PCR were used to detect the expression level of miR-182 and its promoter methylation status in five lung cancer cell lines (A549, L9981, NL9980, 95C and 95D. DNA sequencing was used to confirm the methylation results. Results The level of miR-182 expression significantly differs among these lung cancer cell lines. The highly metastatic human lung cancer cell lines, namely, A549 and L9981, demonstrate a relatively lower expression level of miR-182 compared with the lowly metastatic human lung cancer cell line 95C. Methylation-specific PCR and DNA sequencing assay results indicate that these lung cancer cell lines present different levels of miR-182 promoter methylation, and the highest methylation level is observed in A549 cells. Furthermore, the expression of miR-182 in these cell lines significantly increases when treated with 10 μM 5’-Aza-dC. Conclusion DNA methylation occurs in the miR-182 promoter region in lung cancer cell lines. This methylation can regulate the expression level of miR-182. Further study must be conducted to explore the function of miR-182 promoter methylation in lung cancer occurrence and development.

  13. No Effect of Folic Acid Supplementation on Global DNA Methylation in Men and Women with Moderately Elevated Homocysteine

    Jung, A.Y.; Smulders, Y.; Verhoef, P.; Kok, F.J.; Blom, H.; Kok, R.M.; Kampman, E.; Durga, J.

    2011-01-01

    A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg

  14. No effect of folic acid supplementation on global DNA methylation in men and women with moderately elevated homocysteine

    Jung, A.Y.; Smulders, Y.; Verhoef, P.; Kok, F.J.; Blom, H.J.; Kok, R.M.; Kampman, E.; Durga, J.

    2011-01-01

    A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg

  15. Renewables global status report - 2009 Update

    Sawin, Janet L.; Martinot, Eric; Mastny, Lisa; Lempp, Philippe; Sonntag-O'Brien, Virginia; Lempp, Philippe; Foulon, Samia; Roussell, Jodie; Welker, Bettina

    2009-01-01

    Since 2004, when the Renewables Global Status Report was first launched, many indicators of renewable energy have shown dramatic gains. Annual renewable energy investment has increased fourfold to reach $120 billion in 2008. In the four years from end-2004 to end-2008, solar photovoltaic (PV) capacity increased six-fold to more than 16 gigawatts (GW), wind power capacity increased 250 percent to 121 GW, and total power capacity from new renewables increased 75 percent to 280 GW, including significant gains in small hydro, geothermal, and biomass power generation. During the same period, solar heating capacity doubled to 145 gigawatts-thermal (GWth), while bio-diesel production increased six-fold to 12 billion liters per year and ethanol production doubled to 67 billion liters per year. Annual percentage gains for 2008 were even more dramatic. Wind power grew by 29 percent and grid-tied solar PV by 70 percent. The capacity of utility-scale solar PV plants (larger than 200 kilowatts) tripled during 2008, to 3 GW. Solar hot water grew by 15 percent, and annual ethanol and bio-diesel production both grew by 34 percent. Heat and power from biomass and geothermal sources continued to grow, and small hydro increased by about 8 percent. Many leadership changes and milestones in renewable energy markets and policy took place in 2008. The United States became the leader in new capacity investment with $24 billion invested, or 20 percent of global total investment. The United States also led in added and total wind power capacity, surpassing long-time wind power leader Germany. Spain added 2.6 GW of solar PV, representing a full half of global grid-tied installations and a fivefold increase over Spain's 2007 additions. China doubled its wind power capacity for the fifth year in a row, moving into fourth place worldwide. Another significant milestone was that for the first time, both the United States and the European Union added more power capacity from renewables than

  16. Subsets of microsatellite-unstable colorectal cancers exhibit discordance between the CpG island methylator phenotype and MLH1 methylation status.

    Kim, Jung H; Rhee, Ye-Y; Bae, Jeong-M; Kwon, Hyeong-J; Cho, Nam-Y; Kim, Mi J; Kang, Gyeong H

    2013-07-01

    Although the presence of MLH1 methylation in microsatellite-unstable colorectal cancer generally indicates involvement of the CpG island methylator phenotype (CIMP) in the development of the tumor, these two conditions do not always correlate. A minority of microsatellite-unstable colorectal cancers exhibit discordance between CIMP and MLH1 methylation statuses. However, the clinicopathological features of such microsatellite-unstable colorectal cancers with discrepant MLH1 methylation and CIMP statuses remain poorly studied. Microsatellite-unstable colorectal cancers (n=220) were analyzed for CIMP and MLH1 methylation statuses using the MethyLight assay. Based on the combinatorial CIMP and MLH1 methylation statuses, the microsatellite-unstable colorectal cancers were grouped into four subtypes (CIMP-high (CIMP-H) MLH1 methylation-positive (MLH1m+), CIMP-H MLH1 methylation-negative, CIMP-low/0 (CIMP-L/0) MLH1m+, and CIMP-L/0 MLH1 methylation-negative), which were compared in terms of their associations with clinicopathological and molecular features. The CIMP-L/0 MLH1 methylation-negative and CIMP-H MLH1m+ subtypes were predominant, comprising 63.6 and 24.1% of total microsatellite-unstable colorectal cancers, respectively. The discordant subtypes, CIMP-H MLH1 methylation-negative and CIMP-L/0 MLH1m+, were found in 5 and 7% of microsatellite-unstable colorectal cancers, respectively. The CIMP-H MLH1 methylation-negative subtype exhibited elevated incidence rates in male patients and was associated with larger tumor size, more frequent loss of MSH2 expression, increased frequency of KRAS mutation, and advanced cancer stage. The CIMP-L/0 MLH1m+ subtype was associated with onset at an earlier age, a predominance of MLH1 loss, and earlier cancer stage. None of the CIMP-L/0 MLH1m+ subtype patients succumbed to death during the follow-up. Our findings suggest that the discordant subtypes of colorectal cancers exhibit distinct clinicopathological and molecular features

  17. Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

    Ozden, Sibel, E-mail: stopuz@istanbul.edu.tr [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Turgut Kara, Neslihan [Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul (Turkey); Sezerman, Osman Ugur [Department of Biostatistics and Medical Informatics, Acibadem University, Istanbul (Turkey); Durasi, İlknur Melis [Biological Sciences and Bioengineering, Faculty of Engineering and Natural Sciences, Sabancı University, Istanbul (Turkey); Chen, Tao [Department of Toxicology, School of Public Health, Soochow University, Suzhou (China); Demirel, Goksun; Alpertunga, Buket [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Chipman, J. Kevin [School of Biosciences, The University of Birmingham, Birmingham (United Kingdom); Mally, Angela [Department of Toxicology, University of Würzburg, Würzburg (Germany)

    2015-12-01

    Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

  18. Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

    Ozden, Sibel; Turgut Kara, Neslihan; Sezerman, Osman Ugur; Durasi, İlknur Melis; Chen, Tao; Demirel, Goksun; Alpertunga, Buket; Chipman, J. Kevin; Mally, Angela

    2015-01-01

    Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

  19. Methylation status and protein expression of RASSF1A in breast cancer patients.

    Hagrass, Hoda A; Pasha, Heba F; Shaheen, Mohamed A; Abdel Bary, Eman H; Kassem, Rasha

    2014-01-01

    Recently genetics and epigenetics alterations have been found to be characteristic of malignancy and hence can be used as targets for detection of neoplasia. RAS association domain family protein 1A (RASSF1A) gene hypermethylation has been a subject of interest in recent researches on cancer breast patients. The aim of the present study was to evaluate whether RASSF1A methylation status and RASSF1A protein expression are associated with the major clinico-pathological parameters. One hundred and twenty breast cancer Egyptian patients and 100-control subjects diagnosed with benign lesions of the breast were enrolled in this study. We evaluated RASSF1A methylation status in tissue and serum samples using Methyl specific PCR together with RASSF1A protein expression in tissues by immunohistochemistry. Results were studied in relation to known prognostic clinicopathological features in breast cancer. Frequency of RASSF1A methylation in tissues and serum were 70 and 63.3 % respectively and RASSF1A protein expression showed frequency of 46.7 %. There was an association between RASSF1A methylation in tissues, serum and loss of protein expression in tissues with invasive carcinoma, advanced stage breast cancer, L.N. metastasis, ER/PR and HER2 negativity. RASSF1A methylation in serum showed high degree of concordance with methylation in tissues (Kappa = 0.851, P < 0.001). RASSF1A hypermethylation in tissues and serum and its protein expression may be a valid, reliable and sensitive tool for detection and follow up of breast cancer patients.

  20. Arabidopsis phyllotaxis is controlled by the methyl-esterification status of cell-wall pectins.

    Peaucelle, Alexis; Louvet, Romain; Johansen, Jorunn N; Höfte, Herman; Laufs, Patrick; Pelloux, Jérome; Mouille, Grégory

    2008-12-23

    Plant organs are produced from meristems in a characteristic pattern. This pattern, referred to as phyllotaxis, is thought to be generated by local gradients of an information molecule, auxin. Some studies propose a key role for the mechanical properties of the cell walls in the control of organ outgrowth. A major cell-wall component is the linear alpha-1-4-linked D-GalAp pectic polysaccharide homogalacturonan (HG), which plays a key role in cell-to-cell cohesion. HG is deposited in the cell wall in a highly (70%-80%) methyl-esterified form and is subsequently de-methyl-esterified by pectin methyl-esterases (PME, EC 3.1.1.11). PME activity is itself regulated by endogenous PME inhibitor (PMEI) proteins. PME action modulates cell-wall-matrix properties and plays a role in the control of cell growth. Here, we show that the formation of flower primordia in the Arabidopsis shoot apical meristem is accompanied by the de-methyl-esterification of pectic polysaccharides in the cell walls. In addition, experimental perturbation of the methyl-esterification status of pectins within the meristem dramatically alters the phyllotactic pattern. These results demonstrate that regulated de-methyl-esterification of pectins is a key event in the outgrowth of primordia and possibly also in phyllotactic patterning.

  1. Renewables global status report - 2006 Update

    Martinot, Eric; Mastny, Lisa; Rosbotham, Lyle; Suding, Paul; Lempp, Philippe

    2006-01-01

    This update covers major changes since mid-2005 when the Renewables 2005 Global Status Report was written. Background and further information is contained in the original report, available at www.ren21.net. Record investment in new renewable energy capacity occurred in 2005-$38 billion, up from $30 billion in 2004. Germany and China were the investment leaders, with about $7 billion each, followed by the United States, Spain, Japan, and India.Wind power registered the second highest added capacity, almost as much as large hydropower, with existing capacity growing 24 percent to reach 59 gigawatts (GW). Biomass power production saw 50-100 percent increases in annual production in several countries in 2004. High growth rates also occurred in bio-diesel (85 percent increase in annual production) and grid-connected solar PV (55 percent increase in existing capacity). Solar hot water existing capacity grew by 23 percent in China and reached record levels across Europe as well. And construction began in the United States and Spain on the world's first utility-scale solar thermal power plants in 20 years. Country leadership changed or broadened in several areas. Germany leapt ahead of Japan in grid-connected solar PV, adding 600 megawatts (MW) in one year to achieve a higher cumulative capacity. The United States was the leader in wind power additions for the first time since 1992, while at the same time India's existing capacity surpassed wind pioneer Denmark. Ten countries added over 300 MW of wind, up from five countries that did so in 2004. India passed Japan in total renewable power capacity. In ethanol, U.S. production caught up to Brazil, long the world's leading producer, and three new European Union (EU) countries became producers. In bio-diesel, nine new EU countries became producers. The renewables industry captured investors' attention, as the number of renewable energy companies or divisions with market valuations greater than $40 million

  2. Methyl-Donor and Cofactor Nutrient Intakes in the First 2–3 Years and Global DNA Methylation at Age 4: A Prospective Cohort Study

    Taylor, Rachael M.; Smith, Roger; Collins, Clare E.; Mossman, David; Wong-Brown, Michelle W.; Chan, Eng-Cheng; Evans, Tiffany-Jane; Attia, John R.; Smith, Tenele; Butler, Trent

    2018-01-01

    Background: During the early postnatal period, the impact of nutrition on DNA methylation has not been well studied in humans. The aim was to quantify the relationship between one-carbon metabolism nutrient intake during the first three years of life and global DNA methylation levels at four years. Design: Childhood dietary intake was assessed using infant feeding questionnaires, food frequency questionnaires, 4-day weighed food records and 24-h food records. The dietary records were used to estimate the intake of methionine, folate, vitamins B2, B6 and B12 and choline. The accumulative nutrient intake specific rank from three months to three years of age was used for analysis. Global DNA methylation (%5-methyl cytosines (%5-mC)) was measured in buccal cells at four years of age, using an enzyme-linked immunosorbent assay (ELISA) commercial kit. Linear regression models were used to quantify the statistical relationships. Results: Data were collected from 73 children recruited from the Women and their Children’s Health (WATCH) study. No association was found between one-carbon metabolism nutrient intake and global DNA methylation levels (P 0.05). Global DNA methylation levels in males were significantly higher than in females (median %5-mC: 1.82 vs. 1.03, males and females respectively, (P 0.05)). Conclusion: No association was found between the intake of one-carbon metabolism nutrients during the early postnatal period and global DNA methylation levels at age four years. Higher global DNA methylation levels in males warrants further investigation. PMID:29495543

  3. Methyl-Donor and Cofactor Nutrient Intakes in the First 2–3 Years and Global DNA Methylation at Age 4: A Prospective Cohort Study

    Rachael M. Taylor

    2018-02-01

    Full Text Available Background: During the early postnatal period, the impact of nutrition on DNA methylation has not been well studied in humans. The aim was to quantify the relationship between one-carbon metabolism nutrient intake during the first three years of life and global DNA methylation levels at four years. Design: Childhood dietary intake was assessed using infant feeding questionnaires, food frequency questionnaires, 4-day weighed food records and 24-h food records. The dietary records were used to estimate the intake of methionine, folate, vitamins B2, B6 and B12 and choline. The accumulative nutrient intake specific rank from three months to three years of age was used for analysis. Global DNA methylation (%5-methyl cytosines (%5-mC was measured in buccal cells at four years of age, using an enzyme-linked immunosorbent assay (ELISA commercial kit. Linear regression models were used to quantify the statistical relationships. Results: Data were collected from 73 children recruited from the Women and their Children’s Health (WATCH study. No association was found between one-carbon metabolism nutrient intake and global DNA methylation levels (P > 0.05. Global DNA methylation levels in males were significantly higher than in females (median %5-mC: 1.82 vs. 1.03, males and females respectively, (P < 0.05. Conclusion: No association was found between the intake of one-carbon metabolism nutrients during the early postnatal period and global DNA methylation levels at age four years. Higher global DNA methylation levels in males warrants further investigation.

  4. Whole-genome DNA methylation status associated with clinical PTSD measures of OIF/OEF veterans

    Hammamieh, R; Chakraborty, N; Gautam, A; Muhie, S; Yang, R; Donohue, D; Kumar, R; Daigle, B J; Zhang, Y; Amara, D A; Miller, S-A; Srinivasan, S; Flory, J; Yehuda, R; Petzold, L; Wolkowitz, O M; Mellon, S H; Hood, L; Doyle, F J; Marmar, C; Jett, M

    2017-01-01

    Emerging knowledge suggests that post-traumatic stress disorder (PTSD) pathophysiology is linked to the patients’ epigenetic changes, but comprehensive studies examining genome-wide methylation have not been performed. In this study, we examined genome-wide DNA methylation in peripheral whole blood in combat veterans with and without PTSD to ascertain differentially methylated probes. Discovery was initially made in a training sample comprising 48 male Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans with PTSD and 51 age/ethnicity/gender-matched combat-exposed PTSD-negative controls. Agilent whole-genome array detected ~5600 differentially methylated CpG islands (CpGI) annotated to ~2800 differently methylated genes (DMGs). The majority (84.5%) of these CpGIs were hypermethylated in the PTSD cases. Functional analysis was performed using the DMGs encoding the promoter-bound CpGIs to identify networks related to PTSD. The identified networks were further validated by an independent test set comprising 31 PTSD+/29 PTSD− veterans. Targeted bisulfite sequencing was also used to confirm the methylation status of 20 DMGs shown to be highly perturbed in the training set. To improve the statistical power and mitigate the assay bias and batch effects, a union set combining both training and test set was assayed using a different platform from Illumina. The pathways curated from this analysis confirmed 65% of the pool of pathways mined from training and test sets. The results highlight the importance of assay methodology and use of independent samples for discovery and validation of differentially methylated genes mined from whole blood. Nonetheless, the current study demonstrates that several important epigenetically altered networks may distinguish combat-exposed veterans with and without PTSD. PMID:28696412

  5. Characterization of the Methylation Status of Pax7 and Myogenic Regulator Factors in Cell Myogenic Differentiation.

    Chao, Zhe; Zheng, Xin-Li; Sun, Rui-Ping; Liu, Hai-Long; Huang, Li-Li; Cao, Zong-Xi; Deng, Chang-Yan; Wang, Feng

    2016-07-01

    Epigenetic processes in the development of skeletal muscle have been appreciated for over a decade. DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Up to now, the importance of epigenetic marks in the regulation of Pax7 and myogenic regulatory factors (MRFs) expression is far less explored. In the present study, semi-quantitative the real-time polymerase chain reaction (RT-PCR) analyses showed MyoD and Myf5 were expressed in activated and quiescent C2C12 cells. MyoG was expressed in a later stage of myogenesis. Pax7 was weakly expressed in differentiated C2C12 cells. To further understand the regulation of expression of these genes, the DNA methylation status of Pax7, MyoD, and Myf5 was determined by bisulfite sequencing PCR. During the C2C12 myoblasts fusion process, the changes of promoter and exon 1 methylation of Pax7, MyoD, and Myf5 genes were observed. In addition, an inverse relationship of low methylation and high expression was found. These results suggest that DNA methylation may be an important mechanism regulating Pax7 and MRFs transcription in cell myogenic differentiation.

  6. Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA.

    J Richard Pilsner

    Full Text Available BACKGROUND: An emerging body of evidence indicates that early-life arsenic (As exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. OBJECTIVE: The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. DESIGN: Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs, maternal blood As (mbAs and cord blood As (cbAs. Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. RESULTS: In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1 and Q2 vs. Q4; p = 0.06 and 0.04, respectively. Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58 but negative among female newborns (N = 43; tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively and for the association between maternal uAs and LINE-1 (p = 0.07. Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05. CONCLUSIONS: These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm

  7. Assessment of global DNA methylation in the first trimester fetal tissues exposed to maternal cigarette smoking

    Fa, Svetlana; Larsen, Trine Vilsbøll; Bilde, Katrine

    2016-01-01

    to exposures with an epigenetic impact. We have assessed the influence of maternal cigarette smoking during the first trimester for fetal global DNA methylation. METHODS AND RESULTS: We analyzed the human fetal intestines and livers as well as the placentas from the first trimester pregnancies. Global DNA......AIMS: Maternal cigarette smoking during pregnancy increases the risk of negative health consequences for the exposed child. Epigenetic mechanisms constitute a likely link between the prenatal exposure to maternal cigarette smoking and the increased risk in later life for diverse pathologies....... Maternal smoking induces gene-specific DNA methylation alterations as well as global DNA hypermethylation in the term placentas and hypomethylation in the cord blood. Early pregnancy represents a developmental time where the fetal epigenome is remodeled and accordingly can be expected to be highly prone...

  8. Association between serum organochlorines and global methylation level of leukocyte DNA among Japanese women: a cross-sectional study

    Itoh, Hiroaki [Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113–8421 Japan (Japan); Iwasaki, Motoki, E-mail: moiwasak@ncc.go.jp [Epidemiology Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104–0045 Japan (Japan); Kasuga, Yoshio [Department of Surgery, Nagano Matsushiro General Hospital, 183 Matsushiro, Matsushiro-cho, Nagano City, Nagano Prefecture 381–1231 Japan (Japan); Yokoyama, Shiro; Onuma, Hiroshi [Department of Breast and Thyroid Surgery, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano City, Nagano Prefecture 380–8582 Japan (Japan); Nishimura, Hideki [Department of Respiratory Surgery and Breast Surgery, Nagano Municipal Hospital, 1333–1 Tomitake, Nagano City, Nagano Prefecture 381–8551 Japan (Japan); Kusama, Ritsu [Department of Surgery, Hokushin General Hospital, 1-5-63 Nishi, Nakano City, Nagano Prefecture 383–8505 Japan (Japan); Yoshida, Teruhiko [Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104–0045 Japan (Japan); Yokoyama, Kazuhito [Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113–8421 Japan (Japan); Tsugane, Shoichiro [Dierctor Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104–0045 Japan (Japan)

    2014-08-15

    While the global methylation level of leukocyte DNA may be a suitable biomarker for cancer risk, the level may be influenced by multiple factors, both environmental and host-related, one of which is exposure to environmental pollutants. To date, three epidemiologic studies have examined associations between serum organochlorine levels and global DNA methylation level, but their findings are not fully consistent, and the associations thus require confirmation in other well-characterized populations. We tested the association between organochlorine exposure and the global DNA methylation level of leukocytes in Japanese women. We conducted a cross-sectional study using the control group of a breast cancer case–control study in Japan. Subjects were 403 Japanese women who provided blood samples. Serum polychlorinated biphenyls (PCBs) and nine pesticide-related organochlorines were measured by gas chromatography isotope-dilution high-resolution mass spectrometry. Further, global methylation level of peripheral leukocyte DNA among 399 women was measured by luminometric methylation assay. Linear trends in the association between methylation and quartile levels of organochlorines were evaluated by regression coefficients in a multivariable linear regression model. We found significant inverse associations between the global methylation level in leukocyte DNA and many of the organochlorine levels measured. Global methylation level was significantly decreased by 0.33–0.83% per quartile category for serum o,p′-dichlorodiphenyltrichloroethane (o,p′-DDT), p,p′-DDT, p,p′-dichlorodiphenyldichloroethylene, trans-nonachlor, oxychlordane, hexachlorobenzene, β-hexachlorocyclohexane, PCB17, PCB52/69, PCB74, PCB114, and PCB183. Serum organochlorine levels were inversely associated with the global methylation level of leukocyte DNA in a relatively large sample of Japanese women. - Highlights: • Many serum organochlorine pesticides were inversely associated with the global

  9. DGKI methylation status modulates the prognostic value of MGMT in glioblastoma patients treated with combined radio-chemotherapy with temozolomide.

    Amandine Etcheverry

    Full Text Available Consistently reported prognostic factors for glioblastoma (GBM are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status.399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1 and MGMT-methylated patients (population 2. Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2.The nomogram-based stratification of the cohort identified two risk groups (high/low with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram.Our results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future.

  10. DGKI methylation status modulates the prognostic value of MGMT in glioblastoma patients treated with combined radio-chemotherapy with temozolomide.

    Etcheverry, Amandine; Aubry, Marc; Idbaih, Ahmed; Vauleon, Elodie; Marie, Yannick; Menei, Philippe; Boniface, Rachel; Figarella-Branger, Dominique; Karayan-Tapon, Lucie; Quillien, Veronique; Sanson, Marc; de Tayrac, Marie; Delattre, Jean-Yves; Mosser, Jean

    2014-01-01

    Consistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status. 399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2. The nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram. Our results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future.

  11. Highly efficient PCR assay to discriminate allelic DNA methylation status using whole genome amplification

    Ito Takashi

    2011-06-01

    Full Text Available Abstract Background We previously developed a simple method termed HpaII-McrBC PCR (HM-PCR to discriminate allelic methylation status of the genomic sites of interest, and successfully applied it to a comprehensive analysis of CpG islands (CGIs on human chromosome 21q. However, HM-PCR requires 200 ng of genomic DNA to examine one target site, thereby precluding its application to such samples that are limited in quantity. Findings We developed HpaII-McrBC whole-genome-amplification PCR (HM-WGA-PCR that uses whole-genome-amplified DNA as the template. HM-WGA-PCR uses only 1/100th the genomic template material required for HM-PCR. Indeed, we successfully analyzed 147 CGIs by HM-WGA-PCR using only ~300 ng of DNA, whereas previous HM-PCR study had required ~30 μg. Furthermore, we confirmed that allelic methylation status revealed by HM-WGA-PCR is identical to that by HM-PCR in every case of the 147 CGIs tested, proving high consistency between the two methods. Conclusions HM-WGA-PCR would serve as a reliable alternative to HM-PCR in the analysis of allelic methylation status when the quantity of DNA available is limited.

  12. LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes

    Turcot Valérie

    2012-07-01

    Full Text Available Abstract Background Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT of severely obese subjects with (MetS+ versus without (MetS- metabolic syndrome (MetS. Long interspersed nuclear element 1 (LINE-1 elements DNA methylation levels (%meth in blood, a marker of global DNA methylation, have recently been associated with fasting glucose, blood lipids, heart diseases and stroke. Aim To test whether LINE-1%meth levels in VAT are associated with MetS phenotypes and whether they can predict MetS risk in severely obese individuals. Methods DNA was extracted from VAT of 34 men (MetS-: n = 14, MetS+: n = 20 and 152 premenopausal women (MetS-: n = 84; MetS+: n = 68 undergoing biliopancreatic diversion for the treatment of obesity. LINE-1%meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA. Results The mean LINE-1%meth in VAT was of 75.8% (SD = 3.0%. Multiple linear regression analyses revealed that LINE-1%meth was negatively associated with fasting glucose levels (β = -0.04; P = 0.03, diastolic blood pressure (β =  -0.65; P = 0.03 and MetS status (β = -0.04; P = 0.004 after adjustments for the effects of age, sex, waist circumference (except for MetS status and smoking. While dividing subjects into quartiles based on their LINE-1%meth (Q1 to Q4: lower %meth to higher %meth levels, greater risk were observed in the first (Q1: odds ratio (OR = 4.37, P = 0.004 and the second (Q2: OR = 4.76, P = 0.002 quartiles compared to Q4 (1.00 when adjusting for age, sex and smoking. Conclusions These results suggest that lower global DNA methylation, assessed by LINE-1 repetitive elements methylation analysis, would be associated with a greater risk for MetS in the presence of obesity.

  13. The Prognostic Roles of Gender and O6-Methylguanine-DNA Methyltransferase Methylation Status in Glioblastoma Patients: The Female Power.

    Franceschi, Enrico; Tosoni, Alicia; Minichillo, Santino; Depenni, Roberta; Paccapelo, Alexandro; Bartolini, Stefania; Michiara, Maria; Pavesi, Giacomo; Urbini, Benedetta; Crisi, Girolamo; Cavallo, Michele A; Tosatto, Luigino; Dazzi, Claudio; Biasini, Claudia; Pasini, Giuseppe; Balestrini, Damiano; Zanelli, Francesca; Ramponi, Vania; Fioravanti, Antonio; Giombelli, Ermanno; De Biase, Dario; Baruzzi, Agostino; Brandes, Alba A

    2018-04-01

    Clinical and molecular factors are essential to define the prognosis in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of surgical resection are the most relevant prognostic factors. Our investigation of the role of gender in predicting prognosis shows a slight survival advantage for female patients. We performed a prospective evaluation of the Project of Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors in patients with GBM who received standard treatment. A total of 169 patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively. MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival was longer in the methylated females compared with the methylated males (P = 0.028) but was not significantly different between the unmethylated females and the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT methylation status considered together (methylated females vs. methylated males; hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017), age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI, 0.948-0.982; P factor. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Blood global DNA methylation is decreased in non-severe chronic obstructive pulmonary disease (COPD) patients.

    Zinellu, Angelo; Sotgiu, Elisabetta; Fois, Alessandro G; Zinellu, Elisabetta; Sotgia, Salvatore; Ena, Sara; Mangoni, Arduino A; Carru, Ciriaco; Pirina, Pietro

    2017-10-01

    Alterations in global DNA methylation have been associated with oxidative stress (OS). Since chronic obstructive pulmonary disease (COPD) is characterized by increased oxidative stress we aimed to evaluate the levels of global DNA methylation in this patient group. We assessed methylcytosine (mCyt) levels in DNA from blood collected in 43 COPD patients (29 with mild and 14 with moderate disease) and 43 age- and sex-matched healthy controls. DNA methylation was significantly lower in COPD patients vs. controls (4.20 ± 0.18% mCyt vs. 4.29 ± 0.18% mCyt, p = 0.02). Furthermore, DNA methylation in COPD patients with moderate disease was significantly lower than that in patients with mild disease (4.14 ± 0.15% mCyt vs. 4.23 ± 0.19% mCyt, p COPD (crude OR = 0.06, 95% CI 0.00 to 0.67, p = 0.023). This relationship remained significant after adjusting for several confounders (OR 0.03, 95% CI 0.00 to 0.67; p = 0.028). Receiver operating characteristics (ROC) curve analysis demonstrated the area under the curve of mCyt was 0.646, with 46.6% sensitivity and 79.1% specificity for presence of COPD. There were no significant correlations between methylation and OS indices. The presence and severity of COPD is associated with progressively lower DNA methylation in blood. However, this epigenetic alteration seems independent of oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.

    Cuyàs, E; Fernández-Arroyo, S; Verdura, S; García, R Á-F; Stursa, J; Werner, L; Blanco-González, E; Montes-Bayón, M; Joven, J; Viollet, B; Neuzil, J; Menendez, J A

    2018-02-15

    The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.

  16. The development and validation of EpiComet-Chip, a modified high-throughput comet assay for the assessment of DNA methylation status.

    Townsend, Todd A; Parrish, Marcus C; Engelward, Bevin P; Manjanatha, Mugimane G

    2017-08-01

    DNA damage and alterations in global DNA methylation status are associated with multiple human diseases and are frequently correlated with clinically relevant information. Therefore, assessing DNA damage and epigenetic modifications, including DNA methylation, is critical for predicting human exposure risk of pharmacological and biological agents. We previously developed a higher-throughput platform for the single cell gel electrophoresis (comet) assay, CometChip, to assess DNA damage and genotoxic potential. Here, we utilized the methylation-dependent endonuclease, McrBC, to develop a modified alkaline comet assay, "EpiComet," which allows single platform evaluation of genotoxicity and global DNA methylation [5-methylcytosine (5-mC)] status of single-cell populations under user-defined conditions. Further, we leveraged the CometChip platform to create an EpiComet-Chip system capable of performing quantification across simultaneous exposure protocols to enable unprecedented speed and simplicity. This system detected global methylation alterations in response to exposures which included chemotherapeutic and environmental agents. Using EpiComet-Chip on 63 matched samples, we correctly identified single-sample hypermethylation (≥1.5-fold) at 87% (20/23), hypomethylation (≥1.25-fold) at 100% (9/9), with a 4% (2/54) false-negative rate (FNR), and 10% (4/40) false-positive rate (FPR). Using a more stringent threshold to define hypermethylation (≥1.75-fold) allowed us to correctly identify 94% of hypermethylation (17/18), but increased our FPR to 16% (7/45). The successful application of this novel technology will aid hazard identification and risk characterization of FDA-regulated products, while providing utility for investigating epigenetic modes of action of agents in target organs, as the assay is amenable to cultured cells or nucleated cells from any tissue. Environ. Mol. Mutagen. 58:508-521, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Sociology in Global Environmental Governance? Neoliberalism, Protectionism and the Methyl Bromide Controversy in the Montreal Protocol

    Brian J. Gareau

    2017-10-01

    Full Text Available Sociological studies of global agriculture need to pay close attention to the protectionist aspects of neoliberalism at the global scale of environmental governance. With agri-food studies in the social sciences broadening interrogations of the impact of neoliberalism on agri-food systems and their alternatives, investigating global environmental governance (GEG will help reveal its impacts on the global environment, global science/knowledge, and the potential emergence of ecologically sensible alternatives. It is argued here that as agri-food studies of neoliberalism sharpen the focus on these dimensions the widespread consequences of protectionism of US agri-industry in GEG will become better understood, and the solutions more readily identifiable. This paper illustrates how the delayed phase out of the toxic substance methyl bromide in the Montreal Protocol exemplifies the degree to which the US agri-industry may be protected at the global scale of environmental governance, thus prolonging the transition to ozone-friendly alternatives. Additionally, it is clear that protectionism has had a significant impact on the dissemination and interpretation of science/knowledge of methyl bromide and its alternatives. Revealing the role that protectionism plays more broadly in the agriculture/environmental governance interface, and its oftentimes negative impacts on science and potential alternatives, can shed light on how protectionism can be made to serve ends that are at odds with environmental protection.

  18. Global Status Report on Violence Prevention 2014.

    Mikton, Christopher R; Butchart, Alexander; Dahlberg, Linda L; Krug, Etienne G

    2016-05-01

    Interpersonal violence affects millions of people worldwide, often has lifelong consequences, and is gaining recognition as an important global public health problem. There has been no assessment of measures countries are taking to address it. This report aims to assess such measures and provide a baseline against which to track future progress. In each country, with help from a government-appointed National Data Coordinator, representatives from six to ten sectors completed a questionnaire before convening in a consensus meeting to decide on final country data; 133 of 194 (69%) WHO Member States participated. The questionnaire covered data, plans, prevention measures, and victim services. Data were collected between November 2012 and June 2014, and analyzed between June and October 2014. Global and country-level homicides for 2000-2012 were also calculated for all 194 Members. Worldwide, 475,000 people were homicide victims in 2012 and homicide rates declined by 16% from 2000 to 2012. Data on fatal and, in particular, non-fatal forms of violence are lacking in many countries. Each of the 18 types of surveyed prevention programs was reported to be implemented in a third of the 133 participating countries; each law was reported to exist in 80% of countries, but fully enforced in just 57%; and each victim service was reported to be in place in just more than half of the countries. Although many countries have begun to tackle violence, serious gaps remain, and public health researchers have a critical role to play in addressing them. Copyright © 2016. Published by Elsevier Inc.

  19. Global Status Report on Violence Prevention 2014

    Mikton, Christopher R.; Butchart, Alexander; Dahlberg, Linda L.; Krug, Etienne G.

    2018-01-01

    Introduction Interpersonal violence affects millions of people worldwide, often has lifelong consequences, and is gaining recognition as an important global public health problem. There has been no assessment of measures countries are taking to address it. This report aims to assess such measures and provide a baseline against which to track future progress. Methods In each country, with help from a government-appointed National Data Coordinator, representatives from six to ten sectors completed a questionnaire before convening in a consensus meeting to decide on final country data; 133 of 194 (69%) WHO Member States participated. The questionnaire covered data, plans, prevention measures, and victim services. Data were collected between November 2012 and June 2014, and analyzed between June and October 2014. Global and country-level homicides for 2000–2012 were also calculated for all 194 Members. Results Worldwide, 475,000 people were homicide victims in 2012 and homicide rates declined by 16% from 2000 to 2012. Data on fatal and, in particular, non-fatal forms of violence are lacking in many countries. Each of the 18 types of surveyed prevention programs was reported to be implemented in a third of the 133 participating countries; each law was reported to exist in 80% of countries, but fully enforced in just 57%; and each victim service was reported to be in place in just more than half of the countries. Conclusions Although many countries have begun to tackle violence, serious gaps remain, and public health researchers have a critical role to play in addressing them. PMID:26689979

  20. Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells.

    Babu Swathy

    Full Text Available Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects.SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study.Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in

  1. Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells.

    Swathy, Babu; Banerjee, Moinak

    2017-01-01

    Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study. Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in neurotransmission

  2. Global DNA methylation synergistically regulates the nuclear and mitochondrial genomes in glioblastoma cells.

    Sun, Xin; Johnson, Jacqueline; St John, Justin C

    2018-05-02

    Replication of mitochondrial DNA is strictly regulated during differentiation and development allowing each cell type to acquire its required mtDNA copy number to meet its specific needs for energy. Undifferentiated cells establish the mtDNA set point, which provides low numbers of mtDNA copy but sufficient template for replication once cells commit to specific lineages. However, cancer cells, such as those from the human glioblastoma multiforme cell line, HSR-GBM1, cannot complete differentiation as they fail to enforce the mtDNA set point and are trapped in a 'pseudo-differentiated' state. Global DNA methylation is likely to be a major contributing factor, as DNA demethylation treatments promote differentiation of HSR-GBM1 cells. To determine the relationship between DNA methylation and mtDNA copy number in cancer cells, we applied whole genome MeDIP-Seq and RNA-Seq to HSR-GBM1 cells and following their treatment with the DNA demethylation agents 5-azacytidine and vitamin C. We identified key methylated regions modulated by the DNA demethylation agents that also induced synchronous changes to mtDNA copy number and nuclear gene expression. Our findings highlight the control exerted by DNA methylation on the expression of key genes, the regulation of mtDNA copy number and establishment of the mtDNA set point, which collectively contribute to tumorigenesis.

  3. High resolution melt curve analysis based on methylation status for human semen identification.

    Fachet, Caitlyn; Quarino, Lawrence; Karnas, K Joy

    2017-03-01

    A high resolution melt curve assay to differentiate semen from blood, saliva, urine, and vaginal fluid based on methylation status at the Dapper Isoform 1 (DACT1) gene was developed. Stains made from blood, saliva, urine, semen, and vaginal fluid were obtained from volunteers and DNA was isolated using either organic extraction (saliva, urine, and vaginal fluid) or Chelex ® 100 extraction (blood and semen). Extracts were then subjected to bisulfite modification in order to convert unmethylated cytosines to uracil, consequently creating sequences whose amplicons have melt curves that vary depending on their initial methylation status. When primers designed to amplify the promoter region of the DACT1 gene were used, DNA from semen samples was distinguishable from other fluids by a having a statistically significant lower melting temperature. The assay was found to be sperm-significant since semen from a vasectomized man produced a melting temperature similar to the non-semen body fluids. Blood and semen stains stored up to 5 months and tested at various intervals showed little variation in melt temperature indicating the methylation status was stable during the course of the study. The assay is a more viable method for forensic science practice than most molecular-based methods for body fluid stain identification since it is time efficient and utilizes instrumentation common to forensic biology laboratories. In addition, the assay is advantageous over traditional presumptive chemical methods for body fluid identification since results are confirmatory and the assay offers the possibility of multiplexing which may test for multiple body fluids simultaneously.

  4. Epigenetic factors in cancer risk: effect of chemical carcinogens on global DNA methylation pattern in human TK6 cells.

    Ali M Tabish

    Full Text Available In the current study, we assessed the global DNA methylation changes in human lymphoblastoid (TK6 cells in vitro in response to 5 direct and 10 indirect-acting genotoxic agents. TK6 cells were exposed to the selected agents for 24 h in the presence and/or absence of S9 metabolic mix. Liquid chromatography-mass spectrometry was used for quantitative profiling of 5-methyl-2'-deoxycytidine. The effect of exposure on 5-methyl-2'-deoxycytidine between control and exposed cultures was assessed by applying the marginal model with correlated residuals on % global DNA methylation data. We reported the induction of global DNA hypomethylation in TK6 cells in response to S9 metabolic mix, under the current experimental settings. Benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene induced global DNA hypomethylation in TK6 cells. Furthermore, we showed that dose did not have an effect on global DNA methylation in TK6 cells. In conclusion we report changes in global DNA methylation as an early event in response to agents traditionally considered as genotoxic.

  5. Global Status Report on Local Renewable Energy Policies

    Martinot, Eric; Yamashita, Noriaki; Tan, Vincent; Irie, Risa; Van Staden, Maryke; Zimmermann, Monika

    2011-01-01

    This report complements the REN21 Renewables Global Status Report by providing more detailed information at the city and local levels about policies and activities to promote renewable energy. It is intended to facilitate dialogue and illuminate pathways for future policies and actions at the local level. This 'working draft' version is intended to solicit comments and additional information

  6. Sleep quality and methylation status of selected tumor suppressor genes among nurses and midwives.

    Bukowska-Damska, Agnieszka; Reszka, Edyta; Kaluzny, Pawel; Wieczorek, Edyta; Przybek, Monika; Zienolddiny, Shanbeh; Peplonska, Beata

    2018-01-01

    Chronic sleep restriction may affect metabolism, hormone secretion patterns and inflammatory responses. Limited reports suggest also epigenetic effects, such as changes in DNA methylation profiles. The study aims to assess the potential association between poor sleep quality or sleep duration and the levels of 5-methylcytosine in the promoter regions of selected tumor suppressor genes. A cross-sectional study was conducted on 710 nurses and midwives aged 40-60 years. Data from interviews regarding sleep habits and potential confounders were used. The methylation status of tumor suppressor genes was determined via qMSP reactions using DNA samples derived from leucocytes. No significant findings were observed in the total study population or in the two subgroups of women stratified by the current system of work. A borderline significance association was observed between a shorter duration of sleep and an increased methylation level in CDKN2A among day working nurses and midwives. Further studies are warranted to explore this under-investigated topic.

  7. Epigenetic contribution to successful polyploidizations: variation in global cytosine methylation along an extensive ploidy series in Dianthus broteri (Caryophyllaceae).

    Alonso, Conchita; Balao, Francisco; Bazaga, Pilar; Pérez, Ricardo

    2016-11-01

    Polyploidization is a significant evolutionary force in plants which involves major genomic and genetic changes, frequently regulated by epigenetic factors. We explored whether natural polyploidization in Dianthus broteri complex resulted in substantial changes in global DNA cytosine methylation associated to ploidy. Global cytosine methylation was estimated by high-performance liquid chromatography (HPLC) in 12 monocytotypic populations with different ploidies (2×, 4×, 6×, 12×) broadly distributed within D. broteri distribution range. The effects of ploidy level and local variation on methylation were assessed by generalized linear mixed models (GLMMs). Dianthus broteri exhibited a higher methylation percent (˜33%) than expected by its monoploid genome size and a large variation among study populations (range: 29.3-35.3%). Global methylation tended to increase with ploidy but did not significantly differ across levels due to increased variation within the highest-order polyploidy categories. Methylation varied more among hexaploid and dodecaploid populations, despite such cytotypes showing more restricted geographic location and increased genetic relatedness than diploids and tetraploids. In this study, we demonstrate the usefulness of an HPLC method in providing precise and genome reference-free global measure of DNA cytosine methylation, suitable to advance current knowledge of the roles of this epigenetic mechanism in polyploidization processes. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  8. Evaluation of promoter methylation status of MLH1 gene in Iranian patients with colorectal tumors and adenoma polyps.

    Zarandi, Ashkan; Irani, Shiva; Savabkar, Sanaz; Chaleshi, Vahid; Ghavideldarestani, Maryam; Mirfakhraie, Reza; Khodadoostan, Mahsa; Nazemalhosseini-Mojarad, Ehsan; Asadzadeh Aghdaei, Hamid

    2017-01-01

    The aim of this study was to evaluate the methylation status of the promoter region of MLH1 gene in colorectal cancer (CRC) and its precursor lesions as well as elucidate its association with various clinicopathological characteristics among Iranian population. Epigenetic silencing of mismatch repair genes, such as MLH1 , by methylation of CpG islands of their promoter region has been proved to be an important mechanism in colorectal carcinogenesis. Fifty colorectal cancer and polyp tissue samples including 13 Primary colorectal tumor and 37 Adenoma polyp samples were enrolled in this study. Methylation-specific polymerase chain reaction (MSP) was performed to find the frequency of MLH1 Promoter Methylation. Promoter methylation of MLH1 gene was detected in 5 out of 13 tumor tissues and 4 out of 37 adenoma polyp. The frequency of MLH1 methylation in tumor samples was significantly higher compared to that in polyp tissues (P= 0.026). No significant association was observed between MLH1 promoter methylation and clinicopathological characteristics of the patients. The frequency of  MLH1  promoter methylation in CRC and colon polyp was 18%. Our findings indicated that methylation of MLH1 promoter region alone cannot be considered as a biomarker for early detection of CRC.

  9. Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs

    Ma, Jing; Chen, Xi; Liu, Yanan; Xie, Qunhui; Sun, Yawen; Chen, Jingshan; Leng, Ling; Yan, Huan; Zhao, Bin; Tang, Naijun

    2015-01-01

    Ancestral TCDD exposure could induce epigenetic transgenerational phenotypes, which may be mediated in part by imprinted gene inheritance. The aim of our study was to evaluate the transgenerational effects of ancestral TCDD exposure on the imprinted gene insulin-like growth factor-2 (Igf2) in rat somatic tissue. TCDD was administered daily by oral gavage to groups of F0 pregnant SD rats at dose levels of 0 (control), 200 or 800 ng/kg bw during gestation day 8–14. Animal transgenerational model of ancestral exposure to TCDD was carefully built, avoiding sibling inbreeding. Hepatic Igf2 expression of the TCDD male progeny was decreased concomitantly with hepatic damage and increased activities of serum hepatic enzymes both in the F1 and F3 generation. Imprinted Control Region (ICR) of Igf2 manifested a hypermethylated pattern, whereas methylation status in the Differentially Methylated Region 2 (DMR2) showed a hypomethylated manner in the F1 generation. These epigenetic alterations in these two regions maintained similar trends in the F3 generation. Meanwhile, the expressions of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) changed in a non-monotonic manner both in the F1 and F3 generation. This study provides evidence that ancestral TCDD exposure may promote epigenetic transgenerational alterations of imprinted gene Igf2 in adult somatic tissue. - Highlights: • Ancestral TCDD exposure induces epigenetic transgenerational inheritance. • Ancestral TCDD exposure affects methylation status in ICR and DMR2 region of Igf2. • DNMTs play a role in TCDD induced epigenetic transgenerational changes of Igf2.

  10. Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs

    Ma, Jing; Chen, Xi; Liu, Yanan [Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China); Xie, Qunhui [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Sun, Yawen; Chen, Jingshan; Leng, Ling; Yan, Huan [Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China); Zhao, Bin, E-mail: binzhao@rcees.ac.cn [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Tang, Naijun, E-mail: tangnaijun@tijmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China)

    2015-12-01

    Ancestral TCDD exposure could induce epigenetic transgenerational phenotypes, which may be mediated in part by imprinted gene inheritance. The aim of our study was to evaluate the transgenerational effects of ancestral TCDD exposure on the imprinted gene insulin-like growth factor-2 (Igf2) in rat somatic tissue. TCDD was administered daily by oral gavage to groups of F0 pregnant SD rats at dose levels of 0 (control), 200 or 800 ng/kg bw during gestation day 8–14. Animal transgenerational model of ancestral exposure to TCDD was carefully built, avoiding sibling inbreeding. Hepatic Igf2 expression of the TCDD male progeny was decreased concomitantly with hepatic damage and increased activities of serum hepatic enzymes both in the F1 and F3 generation. Imprinted Control Region (ICR) of Igf2 manifested a hypermethylated pattern, whereas methylation status in the Differentially Methylated Region 2 (DMR2) showed a hypomethylated manner in the F1 generation. These epigenetic alterations in these two regions maintained similar trends in the F3 generation. Meanwhile, the expressions of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) changed in a non-monotonic manner both in the F1 and F3 generation. This study provides evidence that ancestral TCDD exposure may promote epigenetic transgenerational alterations of imprinted gene Igf2 in adult somatic tissue. - Highlights: • Ancestral TCDD exposure induces epigenetic transgenerational inheritance. • Ancestral TCDD exposure affects methylation status in ICR and DMR2 region of Igf2. • DNMTs play a role in TCDD induced epigenetic transgenerational changes of Igf2.

  11. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain

    Nguyen, AnhThu; Rauch, Tibor A.; Pfeifer, Gerd P.; Hu, Valerie W.

    2010-01-01

    Autism is currently considered a multigene disorder with epigenetic influences. To investigate the contribution of DNA methylation to autism spectrum disorders, we have recently completed large-scale methylation profiling by CpG island microarray analysis of lymphoblastoid cell lines derived from monozygotic twins discordant for diagnosis of autism and their nonautistic siblings. Methylation profiling revealed many candidate genes differentially methylated between discordant MZ twins as well as between both twins and nonautistic siblings. Bioinformatics analysis of the differentially methylated genes demonstrated enrichment for high-level functions including gene transcription, nervous system development, cell death/survival, and other biological processes implicated in autism. The methylation status of 2 of these candidate genes, BCL-2 and retinoic acid-related orphan receptor alpha (RORA), was further confirmed by bisulfite sequencing and methylation-specific PCR, respectively. Immunohistochemical analyses of tissue arrays containing slices of the cerebellum and frontal cortex of autistic and age- and sex-matched control subjects revealed decreased expression of RORA and BCL-2 proteins in the autistic brain. Our data thus confirm the role of epigenetic regulation of gene expression via differential DNA methylation in idiopathic autism, and furthermore link molecular changes in a peripheral cell model with brain pathobiology in autism.—Nguyen, A., Rauch, T. A., Pfeifer, G. P., Hu, V. W. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. PMID:20375269

  12. Fluorescence-labeled methylation-sensitive amplified fragment length polymorphism (FL-MS-AFLP) analysis for quantitative determination of DNA methylation and demethylation status.

    Kageyama, Shinji; Shinmura, Kazuya; Yamamoto, Hiroko; Goto, Masanori; Suzuki, Koichi; Tanioka, Fumihiko; Tsuneyoshi, Toshihiro; Sugimura, Haruhiko

    2008-04-01

    The PCR-based DNA fingerprinting method called the methylation-sensitive amplified fragment length polymorphism (MS-AFLP) analysis is used for genome-wide scanning of methylation status. In this study, we developed a method of fluorescence-labeled MS-AFLP (FL-MS-AFLP) analysis by applying a fluorescence-labeled primer and fluorescence-detecting electrophoresis apparatus to the existing method of MS-AFLP analysis. The FL-MS-AFLP analysis enables quantitative evaluation of more than 350 random CpG loci per run. It was shown to allow evaluation of the differences in methylation level of blood DNA of gastric cancer patients and evaluation of hypermethylation and hypomethylation in DNA from gastric cancer tissue in comparison with adjacent non-cancerous tissue.

  13. Determination of DNA methylation associated with Acer rubrum (red maple) adaptation to metals: analysis of global DNA modifications and methylation-sensitive amplified polymorphism.

    Kim, Nam-Soo; Im, Min-Ji; Nkongolo, Kabwe

    2016-08-01

    Red maple (Acer rubum), a common deciduous tree species in Northern Ontario, has shown resistance to soil metal contamination. Previous reports have indicated that this plant does not accumulate metals in its tissue. However, low level of nickel and copper corresponding to the bioavailable levels in contaminated soils in Northern Ontario causes severe physiological damages. No differentiation between metal-contaminated and uncontaminated populations has been reported based on genetic analyses. The main objective of this study was to assess whether DNA methylation is involved in A. rubrum adaptation to soil metal contamination. Global cytosine and methylation-sensitive amplified polymorphism (MSAP) analyses were carried out in A. rubrum populations from metal-contaminated and uncontaminated sites. The global modified cytosine ratios in genomic DNA revealed a significant decrease in cytosine methylation in genotypes from a metal-contaminated site compared to uncontaminated populations. Other genotypes from a different metal-contaminated site within the same region appear to be recalcitrant to metal-induced DNA alterations even ≥30 years of tree life exposure to nickel and copper. MSAP analysis showed a high level of polymorphisms in both uncontaminated (77%) and metal-contaminated (72%) populations. Overall, 205 CCGG loci were identified in which 127 were methylated in either outer or inner cytosine. No differentiation among populations was established based on several genetic parameters tested. The variations for nonmethylated and methylated loci were compared by analysis of molecular variance (AMOVA). For methylated loci, molecular variance among and within populations was 1.5% and 13.2%, respectively. These values were low (0.6% for among populations and 5.8% for within populations) for unmethylated loci. Metal contamination is seen to affect methylation of cytosine residues in CCGG motifs in the A. rubrum populations that were analyzed.

  14. Socioeconomic status is associated with global diabetes prevalence.

    Xu, Zhiye; Yu, Dan; Yin, Xueyao; Zheng, Fenping; Li, Hong

    2017-07-04

    The incidence of diabetes is increasing globally. We investigated the relationship between diabetes prevalence and patient socioeconomic status across multiple countries. We searched PubMed to identify population-based surveys reporting diabetes prevalence between 1990 and May 2016. Search results were filtered, and Human Development Index (HDI) values from the United Nations Development Programme were used to assess socioeconomic status for a given nation. Our analysis included 45 national surveys from 32 countries. Diabetes prevalence was positively correlated with national HDI (r = 0.421 P = 0.041) in developing countries, and negatively correlated with HDI (r = -0.442 P = 0.045) in developed countries. Diabetes prevalence trends were the same in women and men, although men were associated with increased diabetes risk in developed countries (r = 0.459 P = 0.048). Thus, diabetes prevalence rises with increasing HDI in developing countries, and this is reversed in developed countries. Ours is the first study to investigate the relationship between diabetes and socioeconomic status at global level using HDI values. These results will aid in evaluating global diabetes prevalence and risk with respect to patient socioeconomic status, and will be useful in the development of policies that help reduce disease incidence.

  15. Evaluation of Global Genomic DNA Methylation in Human Whole Blood by Capillary Electrophoresis UV Detection

    Angelo Zinellu

    2017-01-01

    Full Text Available Alterations in global DNA methylation are implicated in various pathophysiological processes. The development of simple and quick, yet robust, methods to assess DNA methylation is required to facilitate its measurement and interpretation in clinical practice. We describe a highly sensitive and reproducible capillary electrophoresis method with UV detection for the separation and detection of cytosine and methylcytosine, after formic acid hydrolysis of DNA extracted from human whole blood. Hydrolysed samples were dried and resuspended with water and directly injected into the capillary without sample derivatization procedures. The use of a run buffer containing 50 mmol/L BIS-TRIS propane (BTP phosphate buffer at pH 3.25 and 60 mmol/L sodium acetate buffer at pH 3.60 (4 : 1, v/v allowed full analyte identification within 11 min. Precision tests indicated an elevated reproducibility with an interassay CV of 1.98% when starting from 2 μg of the extracted DNA. The method was successfully tested by measuring the DNA methylation degree both in healthy volunteers and in reference calf thymus DNA.

  16. Axin gene methylation status correlates with radiosensitivity of lung cancer cells

    Yang, Lian-He; Stoecker, Maggie; Wang, Endi; Xu, Ke; Wang, En-Hua; Han, Yang; Li, Guang; Xu, Hong-Tao; Jiang, Gui-Yang; Miao, Yuan; Zhang, Xiu-Peng; Zhao, Huan-Yu; Xu, Zheng-Fan

    2013-01-01

    We previously reported that Axin1 (Axin) is down-regulated in many cases of lung cancer, and X-ray irradiation increased Axin expression and inhibited lung cancer cells. The mechanisms, however, were not clear. Four lung cancer cell lines were used to detect the methylation status of Axin with or without X-ray treatment. Real-time PCR was used to quantify the expression of Axin, and western blot analysis was applied to measure protein levels of Axin, β-catenin, Cyclin D1, MMP-7, DNMTS, MeCP2 and acetylated histones. Flow cytometric analysis, colony formation assay, transwell assay and xenograft growth experiment were used to study the biological behavior of the cells with hypermethylated or unmethylated Axin gene after X-ray treatment. Hypermethylated Axin gene was detected in 2 of 4 cell lines, and it correlated inversely with Axin expression. X-ray treatment significantly up-regulated Axin expression in H446 and H157 cells, which possess intrinsic hypermethylation of the Axin gene (P<0.01), but did not show up-regulation in LTE and H460 cells, which have unmethylated Axin gene. 2Gy X-ray significantly reduced colony formation (from 71% to 10.5%) in H157 cells, while the reduction was lower in LTE cells (from 71% to 20%). After X-ray irradiation, xenograft growth was significantly decreased in H157 cells (from 1.15 g to 0.28 g) in comparison with LTE cells (from 1.06 g to 0.65 g). Significantly decreased cell invasiveness and increased apoptosis were also observed in H157 cells treated with X-ray irradiation (P<0.01). Down-regulation of DNMTs and MeCP2 and up-regulation of acetylated histones could be detected in lung cancer cells. X-ray-induced inhibition of lung cancer cells may be mediated by enhanced expression of Axin via genomic DNA demethylation and histone acetylation. Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor

  17. Spatially explicit trends in the global conservation status of vertebrates.

    Rodrigues, Ana S L; Brooks, Thomas M; Butchart, Stuart H M; Chanson, Janice; Cox, Neil; Hoffmann, Michael; Stuart, Simon N

    2014-01-01

    The world's governments have committed to preventing the extinction of threatened species and improving their conservation status by 2020. However, biodiversity is not evenly distributed across space, and neither are the drivers of its decline, and so different regions face very different challenges. Here, we quantify the contribution of regions and countries towards recent global trends in vertebrate conservation status (as measured by the Red List Index), to guide action towards the 2020 target. We found that>50% of the global deterioration in the conservation status of birds, mammals and amphibians is concentrated in nations (e.g. Cook Islands, Fiji, Mauritius, Seychelles, and Tonga), have achieved net improvements. Per capita wealth does not explain these patterns, with two of the richest countries - United States and Australia - fairing conspicuously poorly. Different countries were affected by different combinations of threats. Reducing global rates of biodiversity loss will require investment in the regions and countries with the highest responsibility for the world's biodiversity, focusing on conserving those species and areas most in peril and on reducing the drivers with the highest impacts.

  18. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

    2011-01-01

    Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

  19. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    Lagerstedt Kristina

    2011-06-01

    Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

  20. Sleep quality and methylation status of core circadian rhythm genes among nurses and midwives.

    Bukowska-Damska, Agnieszka; Reszka, Edyta; Kaluzny, Pawel; Wieczorek, Edyta; Przybek, Monika; Zienolddiny, Shanbeh; Peplonska, Beata

    2017-01-01

    ABSTARCT Poor sleep quality or sleep restriction is associated with sleepiness and concentration problems. Moreover, chronic sleep restriction may affect metabolism, hormone secretion patterns and inflammatory responses. Limited recent reports suggest a potential link between sleep deprivation and epigenetic effects such as changes in DNA methylation profiles. The aim of the present study was to assess the potential association between poor sleep quality or sleep duration and the levels of 5-methylcytosine in the promoter regions of PER1, PER2, PER3, BMAL1, CLOCK, CRY1 CRY2 and NPAS2 genes, taking into account rotating night work and chronotype as potential confounders or modifiers. A cross-sectional study was conducted on 710 nurses and midwives (347 working on rotating nights and 363 working only during the day) aged 40-60 years. Data from in-person interviews about sleep quality, chronotype and potential confounders were used. Sleep quality and chronotype were assessed using Pittsburgh Sleep Quality Questionnaire (PSQI) and Morningness-Eveningness Questionnaire (MEQ), respectively. Morning blood samples were collected. The methylation status of the circadian rhythm genes was determined via quantitative methylation-specific real-time PCR assays (qMSP) reactions using DNA samples derived from leucocytes. The proportional odds regression model was fitted to quantify the relationship between methylation index (MI) as the dependent variable and sleep quality or sleep duration as the explanatory variable. Analyses were carried out for the total population as well as for subgroups of women stratified by the current system of work (rotating night shift/day work) and chronotype (morning type/intermediate type/evening type). A potential modifying effect of the system of work or the chronotype was examined using the likelihood ratio test. No significant findings were observed in the total study population. Subgroup analyses revealed two statistically significant

  1. Global revolution: a status report on renewable energy worldwide

    Martinot, Eric

    2005-01-01

    With at least 48 countries around the world having some type of renewable energy promotion policy, and increasingly favourable economics, renewables are seeing strong growth and increasing significance. In 2004, global investment in renewables reached US$30 billion. More than 1.7 million people are directly employed by the industry and the 180 GW of installed renewables represents 4% of global capacity. The author discusses the state of renewables in 2005, based on the Just-released 'Renewables 2005 Global Status Report' which was sponsored by the REN21 Renewable Energy Policy Network and involved over 100 collaborators, under the headings: investment trends; industry and market trends; policies to promote renewable energy. (UK)

  2. Global sea-to-air flux climatology for bromoform, dibromomethane and methyl iodide

    F. Ziska

    2013-09-01

    Full Text Available Volatile halogenated organic compounds containing bromine and iodine, which are naturally produced in the ocean, are involved in ozone depletion in both the troposphere and stratosphere. Three prominent compounds transporting large amounts of marine halogens into the atmosphere are bromoform (CHBr3, dibromomethane (CH2Br2 and methyl iodide (CH3I. The input of marine halogens to the stratosphere has been estimated from observations and modelling studies using low-resolution oceanic emission scenarios derived from top-down approaches. In order to improve emission inventory estimates, we calculate data-based high resolution global sea-to-air flux estimates of these compounds from surface observations within the HalOcAt (Halocarbons in the Ocean and Atmosphere database (https://halocat.geomar.de/. Global maps of marine and atmospheric surface concentrations are derived from the data which are divided into coastal, shelf and open ocean regions. Considering physical and biogeochemical characteristics of ocean and atmosphere, the open ocean water and atmosphere data are classified into 21 regions. The available data are interpolated onto a 1°×1° grid while missing grid values are interpolated with latitudinal and longitudinal dependent regression techniques reflecting the compounds' distributions. With the generated surface concentration climatologies for the ocean and atmosphere, global sea-to-air concentration gradients and sea-to-air fluxes are calculated. Based on these calculations we estimate a total global flux of 1.5/2.5 Gmol Br yr−1 for CHBr3, 0.78/0.98 Gmol Br yr−1 for CH2Br2 and 1.24/1.45 Gmol Br yr−1 for CH3I (robust fit/ordinary least squares regression techniques. Contrary to recent studies, negative fluxes occur in each sea-to-air flux climatology, mainly in the Arctic and Antarctic regions. "Hot spots" for global polybromomethane emissions are located in the equatorial region, whereas methyl iodide emissions are enhanced in the

  3. Differences in global DNA methylation of testicular seminoma are not associated with changes in histone modifications, clinical prognosis, BRAF mutations or gene expression

    Pedersen, Louise Holm; Nielsen, John E; Daugaard, Gedske

    2016-01-01

    -seminomas. It is well established from e.g. melanoma, colorectal and thyroid cancer that a methylated phenotype can be correlated to prognosis and can be related to BRAF mutations. In the present study we investigated the global methylation level in 67 seminomas and classified them as hypo-methylated, intermediate...

  4. Effect of Exposure to 900 MHz GSM Mobile Phone Radiofrequency Radiation on Estrogen Receptor Methylation Status in Colon Cells of Male Sprague Dawley Rats

    Mokarram, P.; Sheikhi, M.; Mortazavi, S.M.J.; Saeb, S.; Shokrpour, N.

    2017-01-01

    Background: Over the past several years, the rapidly increasing use of mobile phones has raised global concerns about the biological effects of exposure to radiofrequency (RF) radiation. Numerous studies have shown that exposure to electromagnetic fields (EMFs) can be associated with effects on the nervous, endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of genetic diversity, the onset and progression of cancer can be controlled by epigenetic mechanisms such as gene promoter methylation. There are extensive studies on the epigenetic changes of the tumor suppressor genes as well as the identification of methylation biomarkers in colorectal cancer. Some studies have revealed that genetic changes can be induced by exposure to RF radiation. However, whether or not RF radiation is capable of inducing epigenetic alteration has not been clarified yet. To date, no study has been conducted on the effect of radiation on epigenetic alterations in colorectal cancer (CRC). Several studies have also shown that methylation of estrogen receptor α (ERα), MYOD, MGMT, SFRP2 and P16 play an important role in CRC. It can be hypothesized that RF exposure can be a reason for the high incidence of CRC in Iran. This study aimed to investigate whether epigenetic pattern of ERα is susceptible to RF radiation and if RF radiation can induce radioadaptive response as epigenetic changes after receiving the challenge dose (γ-ray). Material and Method: 40 male Sprague-Dawley rats were divided into 4 equal groups (Group I: exposure to RF radiation of a GSM cell phone for 4 hours and sacrificed after 24 hours; Group II: RF exposure for 4 hours, exposure to Co-60 gamma radiation (3 Gy) after 24 hours and sacrificed after 72 hrs; Group III: only 3Gy gamma radiation; Group 4: control group). DNA from colon tissues was extracted to evaluate the methylation status by methylation specific PCR. Results: Our finding showed that exposure to GSM cell phone RF radiation was

  5. Effect of Exposure to 900 MHz GSM Mobile Phone Radiofrequency Radiation on Estrogen Receptor Methylation Status in Colon Cells of Male Sprague Dawley Rats

    Mokarram P.

    2017-03-01

    Full Text Available Background: Over the past several years, the rapidly increasing use of mobile phones has raised global concerns about the biological effects of exposure to radiofrequency (RF radiation. Numerous studies have shown that exposure to electromagnetic fields (EMFs can be associated with effects on the nervous, endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of genetic diversity, the onset and progression of cancer can be controlled by epigenetic mechanisms such as gene promoter methylation. There are extensive studies on the epigenetic changes of the tumor suppressor genes as well as the identification of methylation biomarkers in colorectal cancer. Some studies have revealed that genetic changes can be induced by exposure to RF radiation. However, whether or not RF radiation is capable of inducing epigenetic alteration has not been clarified yet. To date, no study has been conducted on the effect of radiation on epigenetic alterations in colorectal cancer (CRC. Several studies have also shown that methylation of estrogen receptor α (ERα, MYOD, MGMT, SFRP2 and P16 play an important role in CRC. It can be hypothesized that RF exposure can be a reason for the high incidence of CRC in Iran. This study aimed to investigate whether epigenetic pattern of ERα is susceptible to RF radiation and if RF radiation can induce radioadaptive response as epigenetic changes after receiving the challenge dose (γ-ray. Material and Method: 40 male Sprague-Dawley rats were divided into 4 equal groups (Group I: exposure to RF radiation of a GSM cell phone for 4 hours and sacrificed after 24 hours; Group II: RF exposure for 4 hours, exposure to Co-60 gamma radiation (3 Gy after 24 hours and sacrificed after 72 hrs; Group III: only 3Gy gamma radiation; Group 4: control group. DNA from colon tissues was extracted to evaluate the methylation status by methylation specific PCR. Results: Our finding showed that exposure to GSM cell phone RF

  6. Identifying Key Proteins in Hg Methylation Pathways of Desulfovibrio by Global Proteomics, Final Technical Report

    Summers, Anne O. [Univ. of Georgia, Athens, GA (United States). Dept. of Microbiology; Miller, Susan M. [Univ. of California, San Francisco, CA (United States). Dept. of Pharmaceutical Chemistry; Wall, Judy [Univ. of Missouri, Columbia, MO (United States). Dept. of Biochemistry; Lipton, Mary [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-06-18

    Elemental mercury, Hg(0) is a contaminant at many DOE sites, especially at Oak Ridge National Laboratory (ORNL) where the spread of spilled Hg and its effects on microbial populations have been monitored for decades. To explore the microbial interactions with Hg, we have devised a global proteomic approach capable of directly detecting Hg-adducts of proteins. This technique developed in the facultative anaerobe, Escherichia coli, allows us to identify the proteins most vulnerable to acute exposure to organomercurials phenyl- and ethyl-mercury (as surrogates for the highly neurotoxic methyl-Hg) (Polacco, et al, 2011). We have found >300 such proteins in all metabolic functional groups and cellular compartments; most are highly conserved and can serve as markers for acute Hg exposure (Zink, et al. 2016, in preparation). We have also discovered that acute Hg exposure severely disrupts thiol, iron and redox homeostases, and electrolyte balance (LaVoie, et al., 2015) Thus, we proposed to bring these techniques to bear on the central problem of identifying the cellular proteins involved in bacterial uptake and methylation of mercury and its release from the cell.

  7. Quantifying the global cellular thiol-disulfide status

    Hansen, Rosa E; Roth, Doris; Winther, Jakob R

    2009-01-01

    It is widely accepted that the redox status of protein thiols is of central importance to protein structure and folding and that glutathione is an important low-molecular-mass redox regulator. However, the total cellular pools of thiols and disulfides and their relative abundance have never been...... determined. In this study, we have assembled a global picture of the cellular thiol-disulfide status in cultured mammalian cells. We have quantified the absolute levels of protein thiols, protein disulfides, and glutathionylated protein (PSSG) in all cellular protein, including membrane proteins. These data...... cell types. However, when cells are exposed to a sublethal dose of the thiol-specific oxidant diamide, PSSG levels increase to >15% of all protein cysteine. Glutathione is typically characterized as the "cellular redox buffer"; nevertheless, our data show that protein thiols represent a larger active...

  8. Age-associated decrease in global DNA methylation in patients with major depression

    Tseng PT

    2014-11-01

    results support a decrease in global DNA methylation associated with age in patients with severe depression. Further studies are needed to clarify the role of the methylation level as a disease marker of depression and whether antidepressant treatment changes the methylation profiles. Keywords: 5-methylcytosine, 5-hydroxymethylcytosine, antidepressant, mood disorder, gene modification, epigenetic

  9. In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.

    Bekim Sadikovic

    Full Text Available Genetic and epigenetic changes contribute to deregulation of gene expression and development of human cancer. Changes in DNA methylation are key epigenetic factors regulating gene expression and genomic stability. Recent progress in microarray technologies resulted in developments of high resolution platforms for profiling of genetic, epigenetic and gene expression changes. OS is a pediatric bone tumor with characteristically high level of numerical and structural chromosomal changes. Furthermore, little is known about DNA methylation changes in OS. Our objective was to develop an integrative approach for analysis of high-resolution epigenomic, genomic, and gene expression profiles in order to identify functional epi/genomic differences between OS cell lines and normal human osteoblasts. A combination of Affymetrix Promoter Tilling Arrays for DNA methylation, Agilent array-CGH platform for genomic imbalance and Affymetrix Gene 1.0 platform for gene expression analysis was used. As a result, an integrative high-resolution approach for interrogation of genome-wide tumour-specific changes in DNA methylation was developed. This approach was used to provide the first genomic DNA methylation maps, and to identify and validate genes with aberrant DNA methylation in OS cell lines. This first integrative analysis of global cancer-related changes in DNA methylation, genomic imbalance, and gene expression has provided comprehensive evidence of the cumulative roles of epigenetic and genetic mechanisms in deregulation of gene expression networks.

  10. Physiological differences and changes in global DNA methylation levels in Agave angustifolia Haw. albino variant somaclones during the micropropagation process.

    Duarte-Aké, Fátima; Castillo-Castro, Eduardo; Pool, Felipe Barredo; Espadas, Francisco; Santamaría, Jorge M; Robert, Manuel L; De-la-Peña, Clelia

    2016-12-01

    Global DNA methylation changes caused by in vitro conditions are associated with the subculturing and phenotypic variation in Agave angustifolia Haw. While the relationship between the development of albinism and in vitro culture is well documented, the role of epigenetic processes in this development leaves some important questions unanswered. During the micropropagation of Agave angustifolia Haw., we found three different phenotypes, green (G), variegated (V) and albino (A). To understand the physiological and epigenetic differences among the somaclones, we analyzed several morphophysiological parameters and changes in the DNA methylation patterns in the three phenotypes during their in vitro development. We found that under in vitro conditions, the V plantlets maintained their CAM photosynthetic capacity, while the A variant showed no pigments and lost its CAM photosynthetic ability. Epigenetic analysis revealed that global DNA methylation increased in the G phenotype during the first two subcultures. However, after that time, DNA methylation levels declined. This hypomethylation correlated with the appearance of V shoots in the G plantlets. A similar correlation occurred in the V phenotype, where an increase of 2 % in the global DNA methylation levels was correlated with the generation of A shoots in the V plantlets. This suggests that an "epigenetic stress memory" during in vitro conditions causes a chromatin shift that favors the generation of variegated and albino shoots.

  11. Human Papillomavirus 16, 18, 31 and 45 viral load, integration and methylation status stratified by cervical disease stage

    Marongiu, Luigi; Godi, Anna; Parry, John V; Beddows, Simon

    2014-01-01

    Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45. Samples singly infected with HPV16 (n = 226), HPV18 (n = 32), HPV31 (n = 75) or HPV45 (n = 29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3’L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample. Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2–26.1; p < 0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0–6.8; p = 0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8–18.0; p < 0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31. This

  12. The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes in a population of healthy adults in South Australia

    Nair-Shalliker, Visalini, E-mail: visalinin@nswcc.org.au [Cancer Research Division, Cancer Council New South Wales (Australia); Dhillon, Varinderpal [CSIRO Food and Nutritional Sciences (Australia); Clements, Mark [Department of Medical Epidemiology and Biostatistics, Karolinska Institutet (Sweden); Armstrong, Bruce K. [Sydney School of Public Health, University of Sydney (Australia); Fenech, Michael [CSIRO Food and Nutritional Sciences (Australia)

    2014-07-15

    Highlights: • Solar UV exposure is positively correlated with LINE 1 hypomethylation. • This was observed in human peripheral blood lymphocytes. • There was no evident effect modification by serum vitamin D (25OHD) levels. • This was observed in a population of healthy adults from South Australia. - Abstract: Background: There is a positive association between solar UV exposure and micronucleus frequency in peripheral blood lymphocytes (PBL) and this association may be stronger when serum vitamin D (25(OH)D) levels are insufficient (<50 nmol/L). Micronucleus formation can result from global hypomethylation of DNA repeat sequences. The aim of this analysis was to evaluate the relationship between solar UV exposure and methylation pattern in LINE-1 repetitive elements in PBL DNA and to see if serum 25(OH)D levels modify it. Method: Personal solar UV exposure was estimated from hours of outdoor exposure over 6 weeks recalled at the time of blood collection in 208 male and female participants living in South Australia. Methylation in LINE-1 repetitive elements was assessed in PBL using pyrosequencing. Results: Methylation in LINE-1 decreased with increasing solar UV exposure (% decrease = 0.5% per doubling of sUV; 95%CI: −0.7 to −0.2 p{sub value} = 0.00003). Although there was no correlation between LINE-1 methylation and micronucleus frequency, there was a 4.3% increase (95%CI: 0.6–8.1 p-value = 0.02) in nucleoplasmic bridges and a 4.3% increase in necrosis (CI: 1.9–6.8 p-value = 0.0005) for every 1% increase in LINE-1 methylation. Serum 25(OH)D was not associated with DNA methylation; or did it modify the association of solar UV with DNA methylation. Conclusion: Exposure to solar UV radiation may reduce DNA methylation in circulating lymphocytes. This association does not appear to be influenced or mediated by vitamin D status.

  13. Amyloid protein-mediated differential DNA methylation status regulates gene expression in Alzheimer’s disease model cell line

    Sung, Hye Youn; Choi, Eun Nam; Ahn Jo, Sangmee; Oh, Seikwan; Ahn, Jung-Hyuck

    2011-01-01

    Highlights: ► Genome-wide DNA methylation pattern in Alzheimer’s disease model cell line. ► Integrated analysis of CpG methylation and mRNA expression profiles. ► Identify three Swedish mutant target genes; CTIF, NXT2 and DDR2 gene. ► The effect of Swedish mutation on alteration of DNA methylation and gene expression. -- Abstract: The Swedish mutation of amyloid precursor protein (APP-sw) has been reported to dramatically increase beta amyloid production through aberrant cleavage at the beta secretase site, causing early-onset Alzheimer’s disease (AD). DNA methylation has been reported to be associated with AD pathogenesis, but the underlying molecular mechanism of APP-sw-mediated epigenetic alterations in AD pathogenesis remains largely unknown. We analyzed genome-wide interplay between promoter CpG DNA methylation and gene expression in an APP-sw-expressing AD model cell line. To identify genes whose expression was regulated by DNA methylation status, we performed integrated analysis of CpG methylation and mRNA expression profiles, and identified three target genes of the APP-sw mutant; hypomethylated CTIF (CBP80/CBP20-dependent translation initiation factor) and NXT2 (nuclear exporting factor 2), and hypermethylated DDR2 (discoidin domain receptor 2). Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored mRNA expression of these three genes, implying methylation-dependent transcriptional regulation. The profound alteration in the methylation status was detected at the −435, −295, and −271 CpG sites of CTIF, and at the −505 to −341 region in the promoter of DDR2. In the promoter region of NXT2, only one CpG site located at −432 was differentially unmethylated in APP-sw cells. Thus, we demonstrated the effect of the APP-sw mutation on alteration of DNA methylation and subsequent gene expression. This epigenetic regulatory mechanism may contribute to the pathogenesis of AD.

  14. Status of the globally threatened forest birds of northeast Brazil

    Glauco Alves Pereira

    2014-01-01

    Full Text Available The Atlantic Forest of northeast Brazil hosts a unique biota which is among the most threatened in the Neotropics. Near-total conversion of forest habitat to sugar cane monocultures has left the region's endemic forest-dependent avifauna marooned in a few highly-fragmented and degraded forest remnants. Here we summarise the current status of 16 globally threatened species based on surveys conducted over the last 11 years. We found a bleak situation for most of these species and consider that three endemics: Glaucidium mooreorum (Pernambuco Pygmy-owl, Cichlocolaptes mazarbarnetti (Cryptic Treehunter and Philydor novaesi (Alagoas Foliage-gleaner are most likely globally extinct. Some positive news can, however, be reported for both Leptodon forbesi (White-collared Kite and Synallaxis infuscata (Pinto's Spinetail which may warrant re-evaluation of their respective red list statuses. We outline a road map to prioritise conservation interventions in the region directed at preventing the extinction of this suite of threatened bird species and their companion biota.

  15. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status

    P. Bady (Pierre); D. Sciuscio (Davide); A.C. Diserens; J. Bloch (Jocelyne); M.J. van den Bent (Martin); C. Marosi (Christine); P-Y. Dietrich (Pierre Yves); M. Weller (Michael); L. Mariani (Luigi); F.L. Heppner (Frank ); D.R. Mcdonald (David ); D. Lacombe (Denis); R. Stupp (Roger); M. Delorenzi (Mauro); M.E. Hegi (Monika)

    2012-01-01

    textabstractThe methylation status of the O6-methylguanine- DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of

  16. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status

    Friso, Simonetta; Choi, Sang-Woon; Girelli, Domenico; Mason, Joel B.; Dolnikowski, Gregory G.; Bagley, Pamela J.; Olivieri, Oliviero; Jacques, Paul F.; Rosenberg, Irwin H.; Corrocher, Roberto; Selhub, Jacob

    2002-01-01

    DNA methylation, an essential epigenetic feature of DNA that modulates gene expression and genomic integrity, is catalyzed by methyltransferases that use the universal methyl donor S-adenosyl-l-methionine. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate (5-methylTHF), the methyl donor for synthesis of methionine from homocysteine and precursor of S-adenosyl-l-methionine. In the present study we sought to determine the effect of folate status on genomic DNA methylation with an emphasis on the interaction with the common C677T mutation in the MTHFR gene. A liquid chromatography/MS method for the analysis of nucleotide bases was used to assess genomic DNA methylation in peripheral blood mononuclear cell DNA from 105 subjects homozygous for this mutation (T/T) and 187 homozygous for the wild-type (C/C) MTHFR genotype. The results show that genomic DNA methylation directly correlates with folate status and inversely with plasma homocysteine (tHcy) levels (P < 0.01). T/T genotypes had a diminished level of DNA methylation compared with those with the C/C wild-type (32.23 vs.62.24 ng 5-methylcytosine/μg DNA, P < 0.0001). When analyzed according to folate status, however, only the T/T subjects with low levels of folate accounted for the diminished DNA methylation (P < 0.0001). Moreover, in T/T subjects DNA methylation status correlated with the methylated proportion of red blood cell folate and was inversely related to the formylated proportion of red blood cell folates (P < 0.03) that is known to be solely represented in those individuals. These results indicate that the MTHFR C677T polymorphism influences DNA methylation status through an interaction with folate status. PMID:11929966

  17. Methylation status of the APC and RASSF1A promoter in cell-free circulating DNA and its prognostic role in patients with colorectal cancer.

    Matthaios, Dimitrios; Balgkouranidou, Ioanna; Karayiannakis, Anastasios; Bolanaki, Helen; Xenidis, Nikolaos; Amarantidis, Kyriakos; Chelis, Leonidas; Romanidis, Konstantinos; Chatzaki, Aikaterini; Lianidou, Evi; Trypsianis, Grigorios; Kakolyris, Stylianos

    2016-07-01

    DNA methylation is the most frequent epigenetic alteration. Using methylation-specific polymerase chain reaction (MSP), the methylation status of the adenomatous polyposis coli ( APC ) and Ras association domain family 1 isoform A ( RASSF1A ) genes was examined in cell-free circulating DNA from 155 plasma samples obtained from patients with early and advanced colorectal cancer (CRC). APC and RASSF1A hypermethylation was frequently observed in both early and advanced disease, and was significantly associated with a poorer disease outcome. The methylation status of the APC and RASSF1A promoters was investigated in cell-free DNA of patients with CRC. Using MSP, the promoter methylation status of APC and RASSF1A was examined in 155 blood samples obtained from patients with CRC, 88 of whom had operable CRC (oCRC) and 67 had metastatic CRC (mCRC). The frequency of APC methylation in patients with oCRC was 33%. Methylated APC promoter was significantly associated with older age (P=0.012), higher stage (P=0.014) and methylated RASSF1A status (P=0.050). The frequency of APC methylation in patients with mCRC was 53.7%. In these patients, APC methylation was significantly associated with methylated RASSF1A status (P=0.016). The frequency of RASSF1A methylation in patients with oCRC was 25%. Methylated RASSF1A in oCRC was significantly associated with higher stage (P=0.021). The frequency of RASSF1A methylation in mCRC was 44.8%. Methylated RASSF1A in mCRC was associated with moderate differentiation (P=0.012), high levels of carcinoembryonic antigen (P=0.023) and methylated APC status (P=0.016). Patients with an unmethylated APC gene had better survival in both early (81±5 vs. 27±4 months, PAPC . Patients with an unmethylated RASSF1A gene had better survival in both early (71±6 vs. 46±8 months, PAPC and RASSF1A promoter methylation status and survival may be indicative of a prognostic role for these genes in CRC, which requires additional testing in larger studies.

  18. Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia.

    Lin, Hung Wen; Saul, Isabel; Gresia, Victoria L; Neumann, Jake T; Dave, Kunjan R; Perez-Pinzon, Miguel A

    2014-02-01

    We previously showed that palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Solutol HS15, a clinically approved excipient because it possesses similar fatty acid compositions as PAME/SAME. Asphyxial cardiac arrest (ACA, 6 min) was performed 30 min after PAME/SAME treatment (0.02 mg/kg, IV). Solutol HS15 (2 ml/kg, IP) was injected chronically for 14 days (once daily). Histopathology of hippocampal CA1 neurons was assessed 7 days after ACA. For focal ischemia experiments, PAME, SAME, or Solutol HS15 was administered following reperfusion after 2 h of middle cerebral artery occlusion (MCAO). 2,3,5-Triphenyltetrazolium staining of the brain was performed 24 h after MCAO and the infarct volume was quantified. Following ACA, the number of surviving hippocampal neurons was enhanced by PAME-treated (68%), SAME-treated (69%), and Solutol-treated HS15 (68%) rats as compared to ACA only-treated groups. Infarct volume was decreased by PAME (83%), SAME (68%), and Solutol HS15 (78%) as compared to saline (vehicle) in MCAO-treated animals. PAME, SAME, and Solutol HS15 provide robust neuroprotection in both paradigms of ischemia. This may prove therapeutically beneficial since Solutol HS15 is already administered as a solublizing agent to patients. With proper timing and dosage, administration of Solutol HS15 and PAME/SAME can be an effective therapy against cerebral ischemia.

  19. Epigenetics in type 1 diabetes: TNFa gene promoter methylation status in Chilean patients with type 1 diabetes mellitus.

    Arroyo-Jousse, Viviana; Garcia-Diaz, Diego F; Codner, Ethel; Pérez-Bravo, Francisco

    2016-12-01

    TNF-α is a pro-inflammatory cytokine that is involved in type 1 diabetes (T1D) pathogenesis. The TNFa gene is subject of epigenetic regulation in which folate and homocysteine are important molecules because they participate in the methionine cycle where the most important methyl group donor (S-adenosylmethionine) is formed. We investigated whether TNFa gene promoter methylation status in T1D patients was related to blood folate, homocysteine and TNF-α in a transversal case-control study. We studied T1D patients (n 25, mean=13·7 years) and healthy control subjects (n 25, mean=31·1 years), without T1D and/or other autoimmune diseases or direct family history of these diseases. A blood sample was obtained for determination of serum folate, plasma homocysteine and TNF-α concentrations. Whole blood was used for the extraction of DNA to determine the percentage of methylation by real-time PCR and melting-curve analysis. Results are expressed as means and standard deviations for parametric variables and as median (interquartile range) for non-parametric variables. T1D patients showed a higher TNFa gene promoter methylation (39·2 (sd 19·5) %) when compared with control subjects (25·4 (sd 13·7) %) (P=0·008). TNFa gene promoter methylation was positively associated only with homocysteine levels in T1D patients (r 0·55, P=0·007), but not in control subjects (r -0·122, P=0·872). To our knowledge, this is the first work that reports the methylation status of the TNFa gene promoter and its relationship with homocysteine metabolism in Chilean T1D patients without disease complications.

  20. Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex.

    Maral Tajerian

    Full Text Available Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC, and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with abnormal behavior and pathological gene expression in the central nervous system. DNA methylation might also be involved in mediating the pathologies associated with chronic pain in the brain. We therefore tested a whether alterations in DNA methylation are found in the brain long after chronic neuropathic pain is induced in the periphery using the spared nerve injury modal and b whether these injury-associated changes are reversible by interventions that reverse the pathologies associated with chronic pain. Six months following peripheral nerve injury, abnormal sensory thresholds and increased anxiety were accompanied by decreased global methylation in the PFC and the amygdala but not in the visual cortex or the thalamus. Environmental enrichment attenuated nerve injury-induced hypersensitivity and reversed the changes in global PFC methylation. Furthermore, global PFC methylation correlated with mechanical and thermal sensitivity in neuropathic mice. In summary, induction of chronic pain by peripheral nerve injury is associated with epigenetic changes in the brain. These changes are detected long after the original injury, at a long distance from the site of injury and are reversible with environmental manipulation. Changes in brain structure and

  1. Euthanasia: Global Scenario and Its Status in India.

    Shekhawat, Raghvendra Singh; Kanchan, Tanuj; Setia, Puneet; Atreya, Alok; Krishan, Kewal

    2018-04-01

    The legal and moral validity of euthanasia has been questioned in different situations. In India, the status of euthanasia is no different. It was the Aruna Ramachandra Shanbaug case that got significant public attention and led the Supreme Court of India to initiate detailed deliberations on the long ignored issue of euthanasia. Realising the importance of this issue and considering the ongoing and pending litigation before the different courts in this regard, the Ministry of Health and Family Welfare, Government of India issued a public notice on May 2016 that invited opinions from the citizens and the concerned stakeholders on the proposed draft bill entitled The Medical Treatment of Terminally Ill Patients (Protection of Patients and Medical Practitioners) Bill. Globally, only a few countries have legislation with discreet and unambiguous guidelines on euthanasia. The ongoing developments have raised a hope of India getting a discreet law on euthanasia in the future.

  2. LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

    Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

    2017-01-02

    Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

  3. Invasive Fetal Therapy: Global Status and Local Development

    Ming Chen

    2004-12-01

    Full Text Available There are few congenital anomalies that can be treated in utero, despite the rapid development of fetal medicine. The number of available antenatal treatments is growing with the advance of supplementary tools, especially ultrasound and endoscopy. Disorders involving accumulation of excessive fluid in the amniotic cavity (polyhydramnios, chest (hydrothorax, abdomen (ascites and urinary system (obstructive uropathy are regularly treated using aspiration or shunt drainage under ultrasound monitoring. Electrolyte solutions or concentrated blood component supplements are used to treat oligohydramnios (amnioinfusion and amniopatch and fetal anemia (fetal transfusion. Placental tumor (chorioangioma and fetal tumors (cystic hygroma and sacrococcygeal teratoma are also successfully treated by antenatal injection of medications. Fetoscopic procedures, especially obstetric endoscopy, are now used regularly in North America, Europe, Australasia and Japan after the validity was established in the treatment of twin-twin transfusion syndrome when compared with traditional amnioreduction. However, most procedures involving surgical fetoscopy or open fetal surgery remain experimental. Their validity and efficacy are not confirmed in a number of fetal diseases for which they were claimed to be effective. A brief review of the global status and history of invasive fetal therapy is given, and its status in Taiwan is also described. Future development in this field relies on greater understanding of the basic physiology and pathology of the diseases involved, as well as on the progress of sophisticated instrumentation.

  4. Global Status of Nuclear Power: Prospects and Challenges

    Tayobeka, B. M.

    2010-01-01

    Global energy requirements and the share of electricity in total energy consumption are increasing rapidly, and the contribution of nuclear power is projected to increase significantly. Out of the 29 countries currently using nuclear power for electricity generation, 22 intend to allow new plants to be built, and, of those, the majority are actively supporting the increased use of nuclear power, some by providing incentives. Most of these countries are expected to build reactors with a generating capacity of over 1000 MW(e). Only three countries continue to have a policy to phase out the use of nuclear energy in the future by not replacing existing operating nuclear power plants and with no consideration of the option of new nuclear plants.In addition, a growing number of countries are expressing interest in introducing nuclear power. Of the more than 60 countries that have expressed such an interest in recent years, over 20 are actively considering nuclear power programmes to meet their energy needs and the others have expressed interest in understanding the issues associated with the introduction of nuclear power.The drivers for rising expectations for nuclear power include: growing energy demand, concern over national energy supply security, the increasingly volatile price of fossil fuels and global environmental concerns. The drivers appear to be the same for countries expanding existing nuclear programmes and those seeking to introduce programmes. The projections made by different international organizations indicate a significant growth in the use of nuclear power. The IAEA projections indicate a world total for nuclear electrical generating capacity of between 445 and 543 GW(e) by 2020 and between 511 and 807 GW(e) by 2030. This paper takes a detailed look into the global status of nuclear power, highlighting challenges and prospects of the technology going into the next century.(author).

  5. New Measurements of Methyl Ethyl Ketone (MEK) Photolysis Rates and Their Relevance to Global Oxidative Capacity

    Brewer, J.; Ravishankara, A. R.; Mellouki, A.; Fischer, E. V.; Kukui, A.; Véronique, D.; Ait-helal, W.; Leglise, J.; Ren, Y.

    2017-12-01

    Methyl ethyl ketone (MEK) is one of the most abundant ketones in the atmosphere. MEK can be emitted directly into the atmosphere from both anthropogenic and natural sources, and it is also formed during the gas-phase oxidation of volatile organic compounds (VOCs). MEK is lost via reaction with OH, photolysis and deposition to the surface. Similar to the other atmospheric ketones, the photolysis of MEK may represent a source of HOx (OH + HO2) radicals in the upper troposphere. The degradation of MEK also leads to the atmospheric formation of acetaldehyde and formaldehyde. This work presents a new analysis of the temperature dependence of MEK photolysis cross-sections and a quantification of MEK photolysis rates under surface pressures using the CNRS HELIOS outdoor atmospheric chamber (Chambre de simulation atmosphérique à irradiation naturelle d'Orléans; http://www.era-orleans.org/ERA-TOOLS/helios-project.html). Additionally, we use the GEOS-Chem 3-D CTM (version 10-01, www.geos-chem.org) to investigate the impact of these newly measured rates and cross-sections on the global distribution and seasonality of MEK, as well as its importance to the tropospheric oxidative capacity.

  6. Welsh Slate: A Candidate for Global Heritage Stone Status

    Horak, Jana; Hughes, Terry; Lott, Graham

    2013-04-01

    Slate is the iconic stone of Wales, and has a temporal and geographic record of usage such that it is considered worthy of consideration for Global Heritage Stone status. The reputation of Welsh slate is built on the quality and durability of the stone, enabling it to be used in a wide range of contexts from industrial roofing, through domestic housing to higher prestige buildings. Although metamorphic slates are present in several across Wales, the highest quality roofing material was extracted from just two areas in north-west Wales; the Cambrian Slate Belt, around Bethesda to Nantlle, working purple and green slates of the Llanberis Slate Formation and a second area to the south around Blaenau Ffestiniog - the Ordovician Slate Belt - which works grey slates of the Nant Francon Supergroup. These two areas are considered to form the core of the Welsh Slate Province. Welsh slate has been extracted for at least 2000 years, as evidenced by their presence as roofing slates in Roman forts in North Wales dating from 77AD. Slates from medieval churches and castles in north Wales indicate extraction continued throughout this period. In the 16th century exportation of Welsh slate commenced, initially limited to Ireland and those parts of England where it could be transported by boat. The second half of 18th century saw the first major expansion of the industry, facilitated by improved road transportation and some mechanisation, and subsequently in the 1830s by repeal of punitive boat taxes: production increased substantially through the late 19th century supported by the introduction of steam railways, and both production and exports peaked around 1900. The industry is still active today, although on a much reduced scale, with an estimate of around 20% of output being exported. Considerable reserves of this high quality slate resource remain in North Wales and it is important to ensure that they are protected to maintain continuity of supply to the heritage sector and are

  7. 5-azacytidine promotes microspore embryogenesis initiation by decreasing global DNA methylation, but prevents subsequent embryo development in rapeseed and barley

    María-Teresa eSolís

    2015-06-01

    Full Text Available Microspores are reprogrammed by stress in vitro towards embryogenesis. This process is an important tool in breeding to obtain double-haploid plants. DNA methylation is a major epigenetic modification that changes in differentiation and proliferation. We have shown changes in global DNA methylation during microspore reprogramming. 5-Azacytidine (AzaC cannot be methylated and leads to DNA hypomethylation. AzaC is a useful demethylating agent to study DNA dynamics, with a potential application in microspore embryogenesis. This work analyzes the effects of short and long AzaC treatments on microspore embryogenesis initiation and progression in two species, the dicot Brassica napus and the monocot Hordeum vulgare. This involved the quantitative analyses of proembryo and embryo production, the quantification of DNA methylation, 5mdC immunofluorescence and confocal microscopy, and the analysis of chromatin organization (condensation/ decondensation by light and electron microscopy. Four days of AzaC treatments (2.5 µM increased embryo induction, response associated with a decrease of DNA methylation, modified 5mdC and heterochromatin patterns compared to untreated embryos. By contrast, longer AzaC treatments diminished embryo production. Similar effects were found in both species, indicating that DNA demethylation promotes microspore reprogramming, totipotency acquisition and embryogenesis initiation, while embryo differentiation requires de novo DNA methylation and is prevented by AzaC. This suggests a role for DNA methylation in the repression of microspore reprogramming and possibly totipotency acquisition.Results provide new insights into the role of epigenetic modifications in microspore embryogenesis and suggest a potential benefit of inhibitors, such as AzaC, to improve the process efficiency in biotechnology and breeding programs.

  8. How Global Science has yet to Bridge Global Differences - A Status Report of the IUGS Taskforce on Global Geoscience Workforce

    Keane, C. M.; Gonzales, L. M.

    2010-12-01

    The International Union of Geological Sciences, with endorsement by UNESCO, has established a taskforce on global geosciences workforce and has tasked the American Geological Institute to take a lead. Springing from a session on global geosciences at the IGC33 in Oslo, Norway, the taskforce is to address three issues on a global scale: define the geosciences, determine the producers and consumers of geoscientists, and frame the understandings to propose pathways towards improved global capacity building in the geosciences. With the combination of rapid retirements in the developed world, and rapid economic expansion and impact of resource and hazard issues in the developing world, the next 25 years will be a dynamic time for the geosciences. However, to date there has been little more than a cursory sense of who and what the geosciences are globally and whether we will be able to address the varied needs and issues in the developed and the developing worlds. Based on prior IUGS estimates, about 50% of all working geoscientists reside in the Unites States, and the US was also producing about 50% of all new geosciences graduate degrees globally. Work from the first year of the taskforce has elucidated the immense complexity of the issue of defining the geosciences, as it bring is enormous cultural and political frameworks, but also shed light on the status of the geosciences in each country. Likewise, this leads to issues of who is actually producing and consuming geoscience talent, and whether countries are meeting domestic demand, and if not, is external talent available to import. Many US-based assumptions about the role of various countries in the geosciences’ global community of people, namely China and India, appear to have been misplaced. In addition, the migration of geoscientists between countries raised enormous questions about what is nationality and if there is an ideal ‘global geoscientist.’ But more than anything, the taskforce is revealing clear

  9. Decreased expression level of BER genes in Alzheimer's disease patients is not derivative of their DNA methylation status.

    Sliwinska, Agnieszka; Sitarek, Przemysław; Toma, Monika; Czarny, Piotr; Synowiec, Ewelina; Krupa, Renata; Wigner, Paulina; Bialek, Katarzyna; Kwiatkowski, Dominik; Korycinska, Anna; Majsterek, Ireneusz; Szemraj, Janusz; Galecki, Piotr; Sliwinski, Tomasz

    2017-10-03

    Neurodegeneration in Alzheimer's disease can be caused by accumulation of oxidative DNA damage resulting from altered expression of genes involved in the base excision repair system (BER). Promoter methylation can affect the profile of BER genes expression. Decreased expression of BER genes was observed in the brains of AD patients. The aim of our study was to compare the expression and methylation profiles of six genes coding for proteins involved in BER, namely: hOGG1, APE1, MUTYH, NEIL1, PARP1 and XRCC1, in the peripheral blood cells of AD patients and healthy volunteers. The study consisted of 100 persons diagnosed with Alzheimer's disease according to DSM-IV criteria, and 110 healthy volunteers. DNA and total RNA were isolated from venous blood cells. Promoter methylation profiles were obtained by High Resolution Melting (HRM) analysis of bisulfide converted DNA samples. Real-time PCR with TaqMan probes was employed for gene expression analysis. APE1, hOGG1, MUTYH, PARP1 and NEIL1 were significantly (pgenes. The methylation status of promoters is not associated with downregulation of BER genes. Our results show that downregulation of BER genes detected in peripheral blood samples could reflect the changes occurring in the brain of patients with AD, and may be a useful biomarker of this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method

    Rundle-Thiele, Dayle [Centre for Clinical Research, University of Queensland, Brisbane, Queensland (Australia); Day, Bryan; Stringer, Brett [Brain Cancer Research Unit, Queensland Institute of Medical Research, Brisbane, Queensland (Australia); Fay, Michael [Department of Radiation Oncology, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia); Martin, Jennifer [Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales (Australia); Jeffree, Rosalind L [Department of Neurosurgery, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia); Thomas, Paul [Queensland PET Service, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia); Bell, Christopher [Centre for Clinical Research, University of Queensland, Brisbane, Queensland (Australia); Salvado, Olivier [CSIRO Digital Productivity Flagship, CSIRO, Herston, Queensland (Australia); Gal, Yaniv [Centre for Medical Diagnostic Technologies in Queensland, University of Queensland, Brisbane, Queensland (Australia); Coulthard, Alan [Discipline of Medical Imaging, University of Queensland, St Lucia, Queensland (Australia); Department of Medical Imaging, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia); Crozier, Stuart [Centre for Medical Diagnostic Technologies in Queensland, University of Queensland, Brisbane, Queensland (Australia); Rose, Stephen, E-mail: stephen.rose@csiro.au [CSIRO Digital Productivity Flagship, CSIRO, Herston, Queensland (Australia); Centre for Clinical Research, University of Queensland, Brisbane, Queensland (Australia)

    2015-06-15

    Accurate knowledge of O{sup 6}-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC. We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC within contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods. A strong trend between a measure of ‘minimum ADC’ and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the ‘low ADC’ component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246). This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.

  11. Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method

    Rundle-Thiele, Dayle; Day, Bryan; Stringer, Brett; Fay, Michael; Martin, Jennifer; Jeffree, Rosalind L; Thomas, Paul; Bell, Christopher; Salvado, Olivier; Gal, Yaniv; Coulthard, Alan; Crozier, Stuart; Rose, Stephen

    2015-01-01

    Accurate knowledge of O 6 -methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC. We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC within contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods. A strong trend between a measure of ‘minimum ADC’ and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the ‘low ADC’ component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246). This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling

  12. The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo

    Flores-Sierra, José; Arredondo-Guerrero, Martín; Cervantes-Paz, Braulio

    2016-01-01

    the epigenome. Methods: Based on these considerations, we asked whether the tFA elaidic acid (EA; tC18:1) has any effects on global DNA methylation and the transcriptome in cultured human THP-1 monocytes, and whether the progeny of EA-supplemented dams during either pregnancy or lactation in mice (n = 20 per...... of 3 months. Conclusion: We document that global DNA hypermethylation is a specific and consistent response to EA in cell culture and in mice, and that EA may exert long-term effects on the epigenome following maternal exposure....

  13. Status of Early-Career Academic Cardiology: A Global Perspective.

    Tong, Carl W; Madhur, Meena S; Rzeszut, Anne K; Abdalla, Marwah; Abudayyeh, Islam; Alexanderson, Erick; Buber, Jonathan; Feldman, Dmitriy N; Gopinathannair, Rakesh; Hira, Ravi S; Kates, Andrew M; Kessler, Thorsten; Leung, Steve; Raj, Satish R; Spatz, Erica S; Turner, Melanie B; Valente, Anne Marie; West, Kristin; Sivaram, Chittur A; Hill, Joseph A; Mann, Douglas L; Freeman, Andrew M

    2017-10-31

    Early-career academic cardiologists, who many believe are an important component of the future of cardiovascular care, face myriad challenges. The Early Career Section Academic Working Group of the American College of Cardiology, with senior leadership support, assessed the progress of this cohort from 2013 to 2016 with a global perspective. Data consisted of accessing National Heart, Lung, and Blood Institute public information, data from the American Heart Association and international organizations, and a membership-wide survey. Although the National Heart, Lung, and Blood Institute increased funding of career development grants, only a small number of early-career American College of Cardiology members have benefited as funding of the entire cohort has decreased. Personal motivation, institutional support, and collaborators continued to be positive influential factors. Surprisingly, mentoring ceased to correlate positively with obtaining external grants. The totality of findings suggests that the status of early-career academic cardiologists remains challenging; therefore, the authors recommend a set of attainable solutions. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. The global status of insect resistance to neonicotinoid insecticides.

    Bass, Chris; Denholm, Ian; Williamson, Martin S; Nauen, Ralf

    2015-06-01

    The first neonicotinoid insecticide, imidacloprid, was launched in 1991. Today this class of insecticides comprises at least seven major compounds with a market share of more than 25% of total global insecticide sales. Neonicotinoid insecticides are highly selective agonists of insect nicotinic acetylcholine receptors and provide farmers with invaluable, highly effective tools against some of the world's most destructive crop pests. These include sucking pests such as aphids, whiteflies, and planthoppers, and also some coleopteran, dipteran and lepidopteran species. Although many insect species are still successfully controlled by neonicotinoids, their popularity has imposed a mounting selection pressure for resistance, and in several species resistance has now reached levels that compromise the efficacy of these insecticides. Research to understand the molecular basis of neonicotinoid resistance has revealed both target-site and metabolic mechanisms conferring resistance. For target-site resistance, field-evolved mutations have only been characterized in two aphid species. Metabolic resistance appears much more common, with the enhanced expression of one or more cytochrome P450s frequently reported in resistant strains. Despite the current scale of resistance, neonicotinoids remain a major component of many pest control programmes, and resistance management strategies, based on mode of action rotation, are of crucial importance in preventing resistance becoming more widespread. In this review we summarize the current status of neonicotinoid resistance, the biochemical and molecular mechanisms involved, and the implications for resistance management. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Global methylation silencing of clustered proto-cadherin genes in cervical cancer: serving as diagnostic markers comparable to HPV

    Wang, Kai-Hung; Lin, Cuei-Jyuan; Liu, Chou-Jen; Liu, Dai-Wei; Huang, Rui-Lan; Ding, Dah-Ching; Weng, Ching-Feng; Chu, Tang-Yuan

    2015-01-01

    Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome-wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 as controls. Twelve members of clustered proto-cadherin (PCDH) genes were collectively methylated and silenced, which were validated in cancer cells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% (P < 10 −25 ), and 2.8%, 24.2%, 50.6%, and 94.7% (P < 10 −29 ), respectively. In diagnosis of CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 from cervical scraping had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.8%, 80.3%, 73%, and 81.8%, respectively. Testing of this combination from cervical scraping is equally sensitive but more specific than human papillomavirus (HPV) test in diagnosis of CIN2 or more severe lesions. The study disclosed a collective methylation of PCDH genes in cancer of cervix and other sites. At least two of them can be promising diagnostic markers for cervical cancer noninferior to HPV

  16. Characterization of Timed Changes in Hepatic Copper Concentrations, Methionine Metabolism, Gene Expression, and Global DNA Methylation in the Jackson Toxic Milk Mouse Model of Wilson Disease

    Anh Le

    2014-05-01

    Full Text Available Background: Wilson disease (WD is characterized by hepatic copper accumulation with progressive liver damage to cirrhosis. This study aimed to characterize the toxic milk mouse from The Jackson Laboratory (Bar Harbor, ME, USA (tx-j mouse model of WD according to changes over time in hepatic copper concentrations, methionine metabolism, global DNA methylation, and gene expression from gestational day 17 (fetal to adulthood (28 weeks. Methods: Included liver histology and relevant biochemical analyses including hepatic copper quantification, S-adenosylmethionine (SAM and S-adenosylhomocysteine (SAH liver levels, qPCR for transcript levels of genes relevant to methionine metabolism and liver damage, and DNA dot blot for global DNA methylation. Results: Hepatic copper was lower in tx-j fetuses but higher in weanling (three weeks and adult tx-j mice compared to controls. S-adenosylhomocysteinase transcript levels were significantly lower at all time points, except at three weeks, correlating negatively with copper levels and with consequent changes in the SAM:SAH methylation ratio and global DNA methylation. Conclusion: Compared to controls, methionine metabolism including S-adenosylhomocysteinase gene expression is persistently different in the tx-j mice with consequent alterations in global DNA methylation in more advanced stages of liver disease. The inhibitory effect of copper accumulation on S-adenosylhomocysteinase expression is associated with progressively abnormal methionine metabolism and decreased methylation capacity and DNA global methylation.

  17. Global Framework for Climate Services (GFCS): status of implementation

    Lucio, Filipe

    2014-05-01

    The GFCS is a global partnership of governments and UN and international agencies that produce and use climate information and services. WMO, which is leading the initiative in collaboration with UN ISDR, WHO, WFP, FAO, UNESCO, UNDP and other UN and international partners are pooling their expertise and resources in order to co-design and co-produce knowledge, information and services to support effective decision making in response to climate variability and change in four priority areas (agriculture and fod security, water, health and disaster risk reduction). To address the entire value chain for the effective production and application of climate services the GFCS main components or pillars are being implemented, namely: • User Interface Platform — to provide ways for climate service users and providers to interact to identify needs and capacities and improve the effectiveness of the Framework and its climate services; • Climate Services Information System — to produce and distribute climate data, products and information according to the needs of users and to agreed standards; • Observations and Monitoring - to generate the necessary data for climate services according to agreed standards; • Research, Modelling and Prediction — to harness science capabilities and results and develop appropriate tools to meet the needs of climate services; • Capacity Building — to support the systematic development of the institutions, infrastructure and human resources needed for effective climate services. Activities are being implemented in various countries in Africa, the Caribbean and South pacific Islands. This paper will provide details on the status of implementation of the GFCS worldwider.

  18. Global DNA methylation in earthworms: A candidate biomarker of epigenetic risks related to the presence of metals/metalloids in terrestrial environments

    Maldonado Santoyo, Maria; Rodriguez Flores, Crescencio; Lopez Torres, Adolfo; Wrobel, Kazimierz [Department of Chemistry, University of Guanajuato, L de Retana No 5, 36000 Guanajuato (Mexico); Wrobel, Katarzyna, E-mail: katarzyn@quijote.ugto.mx [Department of Chemistry, University of Guanajuato, L de Retana No 5, 36000 Guanajuato (Mexico)

    2011-10-15

    In this work, possible relationships between global DNA methylation and metal/metalloid concentrations in earthworms have been explored. Direct correlation was observed between soil and tissue As, Se, Sb, Zn, Cu, Mn, Ag, Co, Hg, Pb (p < 0.05). Speciation results obtained for As and Hg hint at the capability of earthworms for conversion of inorganic element forms present in soil to methylated species. Inverse correlation was observed between the percentage of methylated DNA cytosines and total tissue As, As + Hg, As + Hg + Se + Sb ({beta} = -0.8456, p = 0.071; {beta} = -0.9406, p = 0.017; {beta} = -0.9526, p = 0.012 respectively), as well as inorganic As + Hg ({beta} = -0.8807, p = 0.049). It was concluded that earthworms would be particularly helpful as bioindicators of elements undergoing in vivo methylation and might also be used to assess the related risk of epigenetic changes in DNA methylation. - Graphical abstract: Display Omitted Highlights: > Several metals and metalloids contribute to epigenetic gene regulation. > As, Hg, Se, Sb inversely correlated with global DNA methylation in earthworms. > Biomethylation of the above elements in worms suggested. > Elements biomethylation apparently competes with DNA methylation. > DNA methylation a biomarker of epigenetic risks related to soil metals/metalloids. - Biomethylation of As, Hg in earthworms versus DNA methylation - a candidate biomarker of epigenetic risks related to the presence of metals/metalloids in soil.

  19. The global Landsat archive: Status, consolidation, and direction

    Wulder, Michael A.; White, Joanne C.; Loveland, Thomas; Woodcock, Curtis; Belward, Alan; Cohen, Warren B.; Fosnight, Eugene A.; Shaw, Jerad; Masek, Jeffery G.; Roy, David P.

    2016-01-01

    Landsat data coverage, resulting in an enhanced capacity for mapping, monitoring change, and capturing historic conditions. Although future missions can be planned and implemented, the past cannot be revisited, underscoring the value and enhanced significance of historical Landsat data and the LGAC initiative. The aim of this paper is to report the current status of the global USGS Landsat archive, document the existing and anticipated contributions of LGAC to the archive, and characterize the current acquisitions of Landsat-7 and Landsat-8. Landsat-8 is adding data to the archive at an unprecedented rate as nearly all terrestrial images are now collected. We also offer key lessons learned so far from the LGAC initiative, plus insights regarding other critical elements of the Landsat program looking forward, such as acquisition, continuity, temporal revisit, and the importance of continuing to operationalize the Landsat program.

  20. Clinical Neuropathology practice news 1-2014: Pyrosequencing meets clinical and analytical performance criteria for routine testing of MGMT promoter methylation status in glioblastoma

    Preusser, Matthias; Berghoff, Anna S.; Manzl, Claudia; Filipits, Martin; Weinhäusel, Andreas; Pulverer, Walter; Dieckmann, Karin; Widhalm, Georg; Wöhrer, Adelheid; Knosp, Engelbert; Marosi, Christine; Hainfellner, Johannes A.

    2014-01-01

    Testing of the MGMT promoter methylation status in glioblastoma is relevant for clinical decision making and research applications. Two recent and independent phase III therapy trials confirmed a prognostic and predictive value of the MGMT promoter methylation status in elderly glioblastoma patients. Several methods for MGMT promoter methylation testing have been proposed, but seem to be of limited test reliability. Therefore, and also due to feasibility reasons, translation of MGMT methylation testing into routine use has been protracted so far. Pyrosequencing after prior DNA bisulfite modification has emerged as a reliable, accurate, fast and easy-to-use method for MGMT promoter methylation testing in tumor tissues (including formalin-fixed and paraffin-embedded samples). We performed an intra- and inter-laboratory ring trial which demonstrates a high analytical performance of this technique. Thus, pyrosequencing-based assessment of MGMT promoter methylation status in glioblastoma meets the criteria of high analytical test performance and can be recommended for clinical application, provided that strict quality control is performed. Our article summarizes clinical indications, practical instructions and open issues for MGMT promoter methylation testing in glioblastoma using pyrosequencing. PMID:24359605

  1. Prognostic role of APC and RASSF1A promoter methylation status in cell free circulating DNA of operable gastric cancer patients.

    Balgkouranidou, I; Matthaios, D; Karayiannakis, A; Bolanaki, H; Michailidis, P; Xenidis, N; Amarantidis, K; Chelis, L; Trypsianis, G; Chatzaki, E; Lianidou, E S; Kakolyris, S

    2015-08-01

    Gastric carcinogenesis is a multistep process including not only genetic mutations but also epigenetic alterations. The best known and more frequent epigenetic alteration is DNA methylation affecting tumor suppressor genes that may be involved in various carcinogenetic pathways. The aim of the present study was to investigate the methylation status of APC promoter 1A and RASSF1A promoter in cell free DNA of operable gastric cancer patients. Using methylation specific PCR, we examined the methylation status of APC promoter 1A and RASSF1A promoter in 73 blood samples obtained from patients with gastric cancer. APC and RASSF1A promoters were found to be methylated in 61 (83.6%) and 50 (68.5%) of the 73 gastric cancer samples examined, but in none of the healthy control samples (p APC promoter and elevated CEA (p = 0.033) as well as CA-19.9 (p = 0.032) levels, was noticed. The Kaplan-Meier estimates of survival, significantly favored patients with a non-methylated APC promoter status (p = 0.008). No other significant correlations between APC and RASSF1A methylation status and different tumor variables examined was observed. Serum RASSF1A and APC promoter hypermethylation is a frequent epigenetic event in patients with early operable gastric cancer. The observed correlations between APC promoter methylation status and survival as well as between a hypermethylated RASSF1A promoter and nodal positivity may be indicative of a prognostic role for those genes in early operable gastric cancer. Additional studies, in a larger cohort of patients are required to further explore whether these findings could serve as potential molecular biomarkers of survival and/or response to specific treatments. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. DNA Methylation Status of the Interspersed Repetitive Sequences for LINE-1, Alu, HERV-E, and HERV-K in Trabeculectomy Specimens from Glaucoma Eyes

    Sunee Chansangpetch

    2018-01-01

    Full Text Available Background/Aims. Epigenetic mechanisms via DNA methylation may be related to glaucoma pathogenesis. This study aimed to determine the global DNA methylation level of the trabeculectomy specimens among patients with different types of glaucoma and normal subjects. Methods. Trabeculectomy sections from 16 primary open-angle glaucoma (POAG, 12 primary angle-closure glaucoma (PACG, 16 secondary glaucoma patients, and 10 normal controls were assessed for DNA methylation using combined-bisulfite restriction analysis. The percentage of global methylation level of the interspersed repetitive sequences for LINE-1, Alu, HERV-E, and HERV-K were compared between the 4 groups. Results. There were no significant differences in the methylation for LINE-1 and HERV-E between patients and normal controls. For the Alu marker, the methylation was significantly lower in all types of glaucoma patients compared to controls (POAG 52.19% versus control 52.83%, p=0.021; PACG 51.50% versus control, p=0.005; secondary glaucoma 51.95% versus control, p=0.014, whereas the methylation level of HERV-K was statistically higher in POAG patients compared to controls (POAG 49.22% versus control 48.09%, p=0.017. Conclusions. The trabeculectomy sections had relative DNA hypomethylation of Alu in all glaucoma subtypes and relative DNA hypermethylation of HERV-K in POAG patients. These methylation changes may lead to the fibrotic phenotype in the trabecular meshwork.

  3. DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia.

    Borssén, Magnus; Haider, Zahra; Landfors, Mattias; Norén-Nyström, Ulrika; Schmiegelow, Kjeld; Åsberg, Ann E; Kanerva, Jukka; Madsen, Hans O; Marquart, Hanne; Heyman, Mats; Hultdin, Magnus; Roos, Göran; Forestier, Erik; Degerman, Sofie

    2016-07-01

    Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y ) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD ≥0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making. © 2016 Wiley Periodicals, Inc.

  4. Global analysis of the protection status of the world's forests

    Schmitt, Christine B.; Burgess, Neil David; Coad, Lauren

    2009-01-01

    This study presents a global analysis of forest cover and forest protection. An updated Global Forest Map (using MODIS2005) provided a current assessment of forest cover within 20 natural forest types. This map was overlaid onto WWF realms and ecoregions to gain additional biogeographic information...... on forest distribution. Using the 2008 World Database on Protected Areas, percentage forest cover protection was calculated globally, within forest types, realms and ecoregions, and within selected areas of global conservation importance. At the 10% tree cover threshold, global forest cover was 39 million...... km2. Of this, 7.7% fell within protected areas under IUCN management categories I-IV. With the inclusion of IUCN categories V and VI, the level of global forest protection increased to 13.5%. Percentage forest protection (IUCN I-IV) varied greatly between realms from 5.5% (Palearctic) to 13...

  5. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status.

    Bady, Pierre; Sciuscio, Davide; Diserens, Annie-Claire; Bloch, Jocelyne; van den Bent, Martin J; Marosi, Christine; Dietrich, Pierre-Yves; Weller, Michael; Mariani, Luigi; Heppner, Frank L; Mcdonald, David R; Lacombe, Denis; Stupp, Roger; Delorenzi, Mauro; Hegi, Monika E

    2012-10-01

    The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of pathogenetic and epigenetic features of this intriguingly distinct behavior requires accurate MGMT classification to assess high throughput molecular databases. Promoter methylation-mediated gene silencing is strongly dependent on the location of the methylated CpGs, complicating classification. Using the HumanMethylation450 (HM-450K) BeadChip interrogating 176 CpGs annotated for the MGMT gene, with 14 located in the promoter, two distinct regions in the CpG island of the promoter were identified with high importance for gene silencing and outcome prediction. A logistic regression model (MGMT-STP27) comprising probes cg12434587 [corrected] and cg12981137 provided good classification properties and prognostic value (kappa = 0.85; log-rank p CIMP) positive tumors was found in glioblastomas from The Cancer Genome Atlas than in low grade and anaplastic glioma cohorts, while in CIMP-negative gliomas MGMT was classified as methylated in approximately 50 % regardless of tumor grade. The proposed MGMT-STP27 prediction model allows mining of datasets derived on the HM-450K or HM-27K BeadChip to explore effects of distinct epigenetic context of MGMT methylation suspected to modulate treatment resistance in different tumor types.

  6. Constitutional and somatic methylation status of DMRH19 and KvDMR in Wilms tumor patients

    Leila C.A. Cardoso

    2012-01-01

    Full Text Available The most frequent epigenetic alterations in Wilms tumor (WT occur at WT2, assigned to 11p15. WT2 consists of two domains: telomeric domain 1 (DMRH19 that contains the IGF2 gene and an imprinted maternally expressed transcript (H19 and centromeric domain 2 (KvDMR that contains the genes KCNQ1, KCNQ1OT1 and CDKN1C. In this work, we used pyrosequencing and MS-MLPA to compare the methylation patterns of DMRH19/KvDMR in blood and tumor samples from 40 WT patients. Normal constitutional KvDMR methylation indicated that most of the epigenetic alterations in WT occur at DMRH19. Constitutional DMRH19 hypermethylation (HM DMRH19 was observed in two patients with Beckwith-Wiedemann syndrome. Pyrosequencing and MS-MLPA showed HM DMRH19 in 28/34 tumor samples: 16/34 with isolated HM DMRH19 and 12/34 with concomitant HM DMRH19 and KvDMR hypomethylation, indicating paternal uniparental disomy. With the exception of one blood sample, the MS-MLPA and pyrosequencing findings were concordant. Diffuse or focal anaplasia was present in five tumor samples and was associated with isolated somatic HM DMRH19 in four of them. Constitutional 11p15 methylation abnormalities were present in 5% of the samples and somatic abnormalities in the majority of tumors. Combined analysis of DMRH19/KvDMR by pyrosequencing and MS-MLPA is beneficial for characterizing epigenetic anomalies in WT, and MS-MLPA is useful and reliable for estimation of DNA methylation in a clinical setting.

  7. Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer.

    Saadallah-Kallel, Amana; Abdelmaksoud-Dammak, Rania; Triki, Mouna; Charfi, Slim; Khabir, Abdelmajid; Sallemi-Boudawara, Tahia; Mokdad-Gargouri, Raja

    2017-08-01

    Aberrant DNA methylation of CpG islands occurred frequently in CRC and associated with transcriptional silencing of key genes. In this study, the CIMP combined with MLH1 or p16 INK4a methylation status was determined in CRC patients and correlated with clinicopathological parameters and overall survival. Our data showed that CIMP+ CRCs were identified in 32.9% of cases and that CACNAG1 is the most frequently methylated promoter. When we combined the CIMP with the MLH1 or the p16 INK4a methylation status, we found that CIMP-/MLH1-U (37.8%) and CIMP-/p16 INK4a -U (35.4%) tumors were the most frequent among the four subtypes. Statistical analysis showed that tumor location, lymphovascular invasion, TNM stage, and MSI differed among the group of patients. Kaplan-Meier analyses revealed differences in overall survival according to the CIMP combined with MLH1 or p16 INK4a methylation status. In a multivariate analysis, CIMP/MLH1 and CIMP/p16 INK4a methylation statuses were predictive of prognosis, and the OS was longer for patients with tumors CIMP-/MLH1-M, as well as CIMP-/p16 INK4a -M. Furthermore, DNMT1 is significantly overexpressed in tumors than in normal tissues as well as in CIMP+ than CIMP- tumors. Our results suggest that tumor classification based on the CIMP status combined with MLH1 or p16 INK4a methylation is useful to predict prognosis in CRC patients.

  8. Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.

    Metcalf, Alexander M; Spurdle, Amanda B

    2014-03-01

    Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

  9. Status of research on Drosophila ananassae at global level

    Extensive research work on D. ananassae has been done by numerous researchers per- taining to .... sae has been most extensively utilized for various kinds of studies at global .... ananassae for quantitative and qualitative analyses of acces-.

  10. Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression

    Laura Bordoni

    2015-11-01

    Full Text Available Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM, a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. Through gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Thirty-three percent of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Further studies are however needed to elucidate the molecular mechanisms, but, despite this, an intergenerational PERM-induced damage on progenies has been identified for the first time.

  11. Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes

    Jufvas, ?sa; Sj?din, Simon; Lundqvist, Kim; Amin, Risul; Vener, Alexander V; Str?lfors, Peter

    2013-01-01

    BACKGROUND: Epidemiological evidence indicates yet unknown epigenetic mechanisms underlying a propensity for overweight and type 2 diabetes. We analyzed the extent of methylation at lysine 4 and lysine 9 of histone H3 in primary human adipocytes from 43 subjects using modification-specific antibodies. RESULTS: The level of lysine 9 dimethylation was stable, while adipocytes from type 2 diabetic and non-diabetic overweight subjects exhibited about 40% lower levels of lysine 4 dimethylation com...

  12. 5-Azacytidine combined with 2,4-D improves somatic embryogenesis of Acca sellowiana (O. Berg) Burret by means of changes in global DNA methylation levels.

    Fraga, Hugo P F; Vieira, Leila N; Caprestano, Clarissa A; Steinmacher, Douglas A; Micke, Gustavo A; Spudeit, Daniel A; Pescador, Rosete; Guerra, Miguel P

    2012-12-01

    DNA methylation is an epigenetic regulatory mechanism of gene expression which can be associated with developmental phases and in vitro morphogenetic competence in plants. The present work evaluated the effects of 5-azacytidine (AzaC) and 2,4-dichlorophenoxyacetic acid (2,4-D) on Acca sellowiana somatic embryogenesis (SE) and global DNA methylation levels by high-performance liquid chromatography mass spectrometry (HPLC/MS/MS). 2,4-D-free treatments revealed no somatic embryo formation in both accessions tested. Treatments supplemented with 2,4-D pulse plus AzaC in the culture medium resulted in increased embryo formation. In AzaC-free treatment, HPLC/MS/MS analysis showed a gradual increase in methylation levels in cultures of both accessions tested during SE induction. Treatment with AzaC and 2,4-D-free resulted in a marked decrease in methylation for both accessions, ranging from 37.6 to 20.8 %. In treatment with 2,4-D and AzaC combined, the 85 accession showed increasing global methylation levels. Otherwise, the 101X458 accession, in the same treatment, showed a decrease between 10 and 20 days, followed by an increase after 30 days (39.5, 36.2 and 41.6 %). These results indicate that 2,4-D pulse combined with AzaC improves SE induction. However, the conversion phase showed that although positively influencing SE induction, AzaC had a dysregulatory effect on the stage of autotrophic plant formation, resulting in significantly lower conversion rates. The results suggest that DNA methylation dramatically influences SE in Acca sellowiana, and global DNA methylation dynamics are related to morphogenetic response. 5-Azacytidine combined with 2,4-D increases the number of Acca sellowiana somatic embryos. Global DNA methylation is directly affected by these compounds.

  13. Methyl-Deficient Diets and Risks of Breast Cancer Among African-American Women: A Case-Control Study by Methylation Status of the ER Gene

    Zhu, Kangmin

    2001-01-01

    This is the final report of our case-control study testing the hypothesis that methyl-deficient diets are more likely to be related to breast cancer with methylated CpG islands of the estrogen-receptor (ER) gene...

  14. Generation of Five Human Lactoferrin Transgenic Cloned Goats Using Fibroblast Cells and Their Methylation Status of Putative Differential Methylation Regions of IGF2R and H19 Imprinted Genes

    Sun, Yanyan; Zhang, Yanli; Wang, Ziyu; Song, Yang; Wang, Feng

    2013-01-01

    Background Somatic cell nuclear transfer (SCNT) is a promising technique to produce transgenic cloned mammalian, including transgenic goats which may produce Human Lactoferrin (hLF). However, success percentage of SCNT is low, because of gestational and neonatal failure of transgenic embryos. According to the studies on cattle and mice, DNA methylation of some imprinted genes, which plays a vital role in the reprogramming of embryo in NT maybe an underlying mechanism. Methodology/Principal Findings Fibroblast cells were derived from the ear of a two-month-old goat. The vector expressing hLF was constructed and transfected into fibroblasts. G418 selection, EGFP expression, PCR, and cell cycle distribution were applied sequentially to select transgenic cells clones. After NT and embryo transfer, five transgenic cloned goats were obtained from 240 cloned transgenic embryos. These transgenic goats were identified by 8 microsatellites genotyping and southern blot. Of the five transgenic goats, 3 were lived after birth, while 2 were dead during gestation. We compared differential methylation regions (DMR) pattern of two paternally imprinted genes (H19 and IGF2R) of the ear tissues from the lived transgenic goats, dead transgenic goats, and control goats from natural reproduction. Hyper-methylation pattern appeared in cloned aborted goats, while methylation status was relatively normal in cloned lived goats compared with normal goats. Conclusions/Significance In this study, we generated five hLF transgenic cloned goats by SCNT. This is the first time the DNA methylation of lived and dead transgenic cloned goats was compared. The results demonstrated that the methylation status of DMRs of H19 and IGF2R were different in lived and dead transgenic goats and therefore this may be potentially used to assess the reprogramming status of transgenic cloned goats. Understanding the pattern of gene imprinting may be useful to improve cloning techniques in future. PMID:24204972

  15. Propofol effectively inhibits lithium-pilocarpine- induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

    Wang, Henglin; Wang, Zhuoqiang; Mi, Weidong; Zhao, Cong; Liu, Yanqin; Wang, Yongan; Sun, Haipeng

    2012-01-01

    Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine. The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior, electroencephalography and 24-hour survival rate. Propofol (12.5–100 mg/kg) improved status epilepticus in a dose-dependent manner, and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection. Western blot results showed that, 24 hours after induction of status epilepticus, the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus. Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels, but not the increase in N-methyl-D-aspartate receptor 2A subunit levels. The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine. This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures. PMID:25737709

  16. Global status of fish-borne zoonotic trematodiasis in humans

    Hung, Nguyen Manh; Madsen, Henry; Fried, Bernard

    2013-01-01

    ) are listed. Some trematodes, which are highly pathogenic for humans such as Clonorchis sinensis, Opisthorchis viverrini, O. felineus are discussed in detail, i.e. infection status in humans in endemic areas, clinical aspects, symptoms and pathology of disease caused by these flukes. Other liver fluke species...

  17. The Diverse World of Early Childhood. Global Status Report.

    Neugebauer, Roger

    2002-01-01

    Examines demographic information about the status of young children around the world. Graphs nations with the largest populations of young children and highest percentage of their populations composed of young children in comparison to the aged, the percentage of regional populations under age 5 and over 64, and birth and infant mortality rates.…

  18. Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats.

    Asmita Kulkarni

    Full Text Available Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12 are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12 deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12 deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12 lowers plasma and placental DHA levels (p<0.05 and reduces global DNA methylation levels (p<0.05. When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.

  19. Utility of 5-Methylcytosine Immunohistochemical Staining to Assess Global DNA Methylation and Its Prognostic Impact in MDS Patients

    Chandra, Dinesh; Tyagi, Seema; Singh, Jasdeep; Deka, Roopam; Manivannan, Prabhu; Mishra, Pravas; Pati, Hara Prasad; Saxena, Renu

    2017-12-29

    Background: DNA methylation plays a vital role in the pathogenesis of the myelodysplastic syndrome (MDS), a heterogeneous group of clonal hematopoietic stem cell (HSC) disorders. It is reported to be an independent prognostic factor affecting overall survival (OS). Our aim was to analyze the role of global DNA methylation using an anti-5-methylcytosine (5-MC) antibody by immunohistochemistry (IHC) of bone marrow biopsy (BM Bx) specimens in MDS patients, assessing correlations with various clinical and biological prognostic factors. Material and methods: A total of 59 MDS cases, classified as per the World Health Organization (WHO) 2008 guidelines, were evaluated over a period of 4 years. Clinical data were retrieved from departmental case records and anti-5-MC expression was analyzed with formalin fixed paraffin embedded sections of BM Bx specimens of MDS patients and controls. Results: The median age at diagnosis was 52 years (15-85years). Patients were categorized into low risk (59%) and high risk (41%) according to International Prognostic Scoring System (IPSS). The median follow-up time was 10 months (1 to 37 months). We generated a methylation score (M-score) using anti-5-MC and with the derived cut-off of 30.5 from the receiver operator curve (ROC), there was a significant difference between the two groups in the percentage of BM blasts (p=0.01), WHO sub-type (p=0.01), IPSS (p=0.004), progression to AML (p=0.04) on univariate analysis. Interestingly, patients showing a high M-score (M-score ≥ 30.5) demonstrated a significantly shorter OS and progression to AML. However, on multivariate analysis, only BM blasts (p=0.01) and IPSS (p=0.02) remained independent variables for progression to AML and OS respectively. Conclusion: Immunostaining with anti-5-MC antibody with BM Bx samples is a simple and cost effective technique to detect global methylation, a powerful tool to predict overall survival in patients with MDS. Creative Commons Attribution License

  20. The status and challenge of global fire modelling

    Hantson, Stijn; Arneth, Almut; Harrison, Sandy P.; Kelley, Douglas I.; Prentice, I. Colin; Rabin, Sam S.; Archibald, Sally; Mouillot, Florent; Arnold, Steve R.; Artaxo, Paulo; Bachelet, Dominique; Ciais, Philippe; Forrest, Matthew; Friedlingstein, Pierre; Hickler, Thomas; Kaplan, Jed O.; Kloster, Silvia; Knorr, Wolfgang; Lasslop, Gitta; Li, Fang; Mangeon, Stephane; Melton, Joe R.; Meyn, Andrea; Sitch, Stephen; Spessa, Allan; van der Werf, Guido R.; Voulgarakis, Apostolos; Yue, Chao

    2016-06-01

    Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. We indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.

  1. The status of adolescent medicine: Building a global adolescent workforce

    Lee, Lana; Upadhya, Krishna K; Matson, Pamela; Adger, Hoover; Trent, Maria E

    2016-01-01

    Remarkable public health achievements to reduce infant and child mortality and improve the health and well-being of children worldwide have successfully resulted in increased survival and a growing population of young people aged 10–24 years. Population trends indicate that the current generation of 1.8 billion young people is the largest in history, but there is a scarcity of dedicated resources available to effectively meet the health needs of adolescents and young adults worldwide. Growing recognition of the pivotal roles young people play in the cultures, societies, and countries in which they live has spurred an expanding global movement to address the needs of this special population. Building an effective global workforce of highly-skilled adolescent health professionals who understand the unique biological, psychological, behavioral, social, and environmental factors that impact the health of adolescents is a critical step in addressing the health needs of the growing cohort of young people. In this review, we aim to: 1) Define a global assessment of the health needs for adolescents around the world; 2) Describe examples of current training programs and requirements in Adolescent Medicine; 3) Identify existing gaps and barriers to develop an effective adolescent health workforce; and 4) Develop a call for targeted actions to build capacity of the adolescent health workforce, broaden culturally relevant research and evidence-based intervention strategies, and reinforce existing interdisciplinary global networks of youth advocates and adolescent health professionals to maximize the opportunities for training, research, and care delivery. PMID:26167974

  2. Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas

    Xiang, Shengyan; Liu, Zhaojun; Zhang, Baozhen; Zhou, Jing; Zhu, Bu-Dong; Ji, Jiafu; Deng, Dajun

    2010-01-01

    Alu methylation is correlated with the overall level of DNA methylation and recombination activity of the genome. However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized. This information is useful for understanding natural status of Alu in the genome and helpful for developing an optimal assay to quantify Alu hypomethylation. Bisulfite clone sequencing was carried out in 14 human gastric samples initially. A Cac8I COBRA-DHPLC assay was developed to detect methylated-Alu proportion in cell lines and 48 paired gastric carcinomas and 55 gastritis samples. DHPLC data were statistically interpreted using SPSS version 16.0. From the results of 427 Alu bisulfite clone sequences, we found that only 27.2% of CpG sites within Alu elements were preserved (4.6 of 17 analyzed CpGs, A ~ Q) and that 86.6% of remaining-CpGs were methylated. Deamination was the main reason for low preservation of methylation targets. A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). Comethylation of the sites H and J were used as an indicator of the proportion of methylated-Alu in a Cac8I COBRA-DHPLC assay. Validation studies showed that hypermethylation or hypomethylation of Alu elements in human cell lines could be detected sensitively by the assay after treatment with 5-aza-dC and M.SssI, respectively. The proportion of methylated-Alu copies in gastric carcinomas (3.01%) was significantly lower than that in the corresponding normal samples (3.19%) and gastritis biopsies (3.23%). Most Alu CpG sites are deaminated in the genome. 27% of Alu CpG sites represented in our amplification products. 87% of the remaining CpG sites are methylated. Alu hypomethylation in primary gastric carcinomas could be detected with the Cac8I COBRA-DHPLC assay quantitatively

  3. UVB irradiation does not directly induce detectable changes of DNA methylation in human keratinocytes [v1; ref status: indexed, http://f1000r.es/np

    Christoph Lahtz

    2013-02-01

    Full Text Available Unprotected exposure to UVB radiation from the sun and the resulting DNA damage are thought to be responsible for physiological changes in the skin and for a variety of skin cancers, including basal cell and squamous cell carcinoma and malignant melanoma. Although the mutagenic effects of UVB have been well documented and studied mechanistically, there is only limited information as to whether UV light may also be responsible for inducing epigenetic changes in the genome of exposed cells. DNA methylation is a stable epigenetic modification involved in gene control. To study the effects of UVB radiation on DNA methylation, we repeatedly exposed normal human keratinocytes to a UVB light source. After a recovery period, we analyzed global DNA methylation patterns in the irradiated and control cells using the methylated-CpG island recovery assay (MIRA method in combination with high-resolution microarrays. Bioinformatics analysis revealed only a limited number of possible differences between UVB-exposed and control cells. However, these minor apparent changes could not be independently confirmed by bisulfite sequencing-based approaches. This study reveals that UVB irradiation of keratinocytes has no recognizable global effect on DNA methylation patterns and suggests that changes in DNA methylation, as observed in skin cancers, are not immediate consequences of human exposure to solar UVB irradiation.

  4. Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat

    Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il [Hebrew University Hadassah Medical School, Jerusalem (Israel); Guillemin, Claire [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Neeman-azulay, Meytal; Weinstein-Fudim, Liza [Hebrew University Hadassah Medical School, Jerusalem (Israel); Stodgell, Christopher J.; Miller, Richard K. [Department of Obstetrics and Gynecology, University of Rochester, Rochester (United States); Szyf, Moshe [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Ornoy, Asher [Hebrew University Hadassah Medical School, Jerusalem (Israel)

    2014-05-01

    Fetal Growth Restriction (FGR) is a leading cause for long term morbidity. The Cohen diabetic sensitive rats (CDs), originating from Wistar, develop overt diabetes when fed high sucrose low copper diet (HSD) while the original outbred Sabra strain do not. HSD induced FGR and fetal oxidative stress, more prominent in the CDs, that was alleviated more effectively by copper than by the anti-oxidant vitamins C and E. Our aim was to evaluate the impact of copper or the anti-oxidant Tempol on placental size, protein content, oxidative stress, apoptosis and total DNA methylation. Animals were mated following one month of HSD or regular chow diet and supplemented throughout pregnancy with either 0, 1 or 2 ppm of copper sulfate or Tempol in their drinking water. Placental weight on the 21st day of pregnancy decreased in dams fed HSD and improved upon copper supplementation. Placental/fetal weight ratio increased among the CDs. Protein content decreased in Sabra but increased in CDs fed HSD. Oxidative stress biochemical markers improved upon copper supplementation; immunohistochemistry for oxidative stress markers was similar between strains and diets. Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. Placental global DNA methylation was decreased only among the CDs dams fed HSD. We conclude that FGR in this model is associated with smaller placentae, reduced DNA placental methylation, and increased oxidative stress that normalized with copper supplementation. DNA hypomethylation makes our model a unique method for investigating genes associated with growth, oxidative stress, hypoxia and copper. - Highlights: • Sensitive Cohen diabetic rats (CDs) had small placentae and growth restricted fetuses. • CDs dams fed high sucrose low copper diet had placental global DNA hypomethylation. • Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. • Oxidative stress parameters improved by Tempol and resolved by copper

  5. Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat

    Ergaz, Zivanit; Guillemin, Claire; Neeman-azulay, Meytal; Weinstein-Fudim, Liza; Stodgell, Christopher J.; Miller, Richard K.; Szyf, Moshe; Ornoy, Asher

    2014-01-01

    Fetal Growth Restriction (FGR) is a leading cause for long term morbidity. The Cohen diabetic sensitive rats (CDs), originating from Wistar, develop overt diabetes when fed high sucrose low copper diet (HSD) while the original outbred Sabra strain do not. HSD induced FGR and fetal oxidative stress, more prominent in the CDs, that was alleviated more effectively by copper than by the anti-oxidant vitamins C and E. Our aim was to evaluate the impact of copper or the anti-oxidant Tempol on placental size, protein content, oxidative stress, apoptosis and total DNA methylation. Animals were mated following one month of HSD or regular chow diet and supplemented throughout pregnancy with either 0, 1 or 2 ppm of copper sulfate or Tempol in their drinking water. Placental weight on the 21st day of pregnancy decreased in dams fed HSD and improved upon copper supplementation. Placental/fetal weight ratio increased among the CDs. Protein content decreased in Sabra but increased in CDs fed HSD. Oxidative stress biochemical markers improved upon copper supplementation; immunohistochemistry for oxidative stress markers was similar between strains and diets. Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. Placental global DNA methylation was decreased only among the CDs dams fed HSD. We conclude that FGR in this model is associated with smaller placentae, reduced DNA placental methylation, and increased oxidative stress that normalized with copper supplementation. DNA hypomethylation makes our model a unique method for investigating genes associated with growth, oxidative stress, hypoxia and copper. - Highlights: • Sensitive Cohen diabetic rats (CDs) had small placentae and growth restricted fetuses. • CDs dams fed high sucrose low copper diet had placental global DNA hypomethylation. • Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. • Oxidative stress parameters improved by Tempol and resolved by copper

  6. Global statistics on addictive behaviours: 2014 status report.

    Gowing, Linda R; Ali, Robert L; Allsop, Steve; Marsden, John; Turf, Elizabeth E; West, Robert; Witton, John

    2015-06-01

    Addictive behaviours are among the greatest scourges on humankind. It is important to estimate the extent of the problem globally and in different geographical regions. Such estimates are available, but there is a need to collate and evaluate these to arrive at the best available synthetic figures. Addiction has commissioned this paper as the first of a series attempting to do this. Online sources of global, regional and national information on prevalence and major harms relating to alcohol use, tobacco use, unsanctioned psychoactive drug use and gambling were identified through expert review and assessed. The primary data sources located were the websites of the World Health Organization (WHO), the United Nations Office on Drugs and Crime (UNODC) and the Alberta Gambling Research Institute. Summary statistics were compared with recent publications on the global epidemiology of addictive behaviours. An estimated 4.9% of the world's adult population (240 million people) suffer from alcohol use disorder (7.8% of men and 1.5% of women), with alcohol causing an estimated 257 disability-adjusted life years lost per 100 000 population. An estimated 22.5% of adults in the world (1 billion people) smoke tobacco products (32.0% of men and 7.0% of women). It is estimated that 11% of deaths in males and 6% of deaths in females each year are due to tobacco. Of 'unsanctioned psychoactive drugs', cannabis is the most prevalent at 3.5% globally, with each of the others at gambling are not possible, but in countries where it has been assessed the prevalence is estimated at 1.5%. Tobacco and alcohol use are by far the most prevalent addictive behaviours and cause the large majority of the harm. However, the quality of data on prevalence and addiction-related harms is mostly low, and comparisons between countries and regions must be viewed with caution. There is an urgent need to review the quality of data on which global estimates are made and coordinate efforts to arrive at

  7. The MTHFR 677TT genotype and folate intake interact to lower global leukocyte DNA methylation in young Mexican American women.

    Axume, Juan; Smith, Steven S; Pogribny, Igor P; Moriarty, David J.; Caudill., Marie A.

    2007-01-01

    DNA methylation is an epigenetic feature that is associated with X chromosome inactivation, genomic imprinting, transcriptional silencing of genes and genomic stability. Folate provides a labile source of methyl groups which may be used for cellular methylation reactions including DNA methylation. The methylenetetrahydrofolate reductase (MTHFR) 677C→T variant is an important determinant of folate nutriture and may influence DNA methylation. This study sought to assess the influence of the MTH...

  8. Evaluation of perioperative nutritional status with subjective global assessment method in patients undergoing gastrointestinal cancer surgery.

    Erdim, Aylin; Aktan, Ahmet Özdemir

    2017-01-01

    This study was designed to evaluate the perioperative nutritional status of patients undergoing surgery for gastrointestinal cancer using Subjective Global Assessment and surgeon behavior on nutritional support. We recruited 100 patients undergoing surgery for gastrointestinal cancer in one university and two state teaching hospitals. Subjective Global Assessment was administered to evaluate preoperative and postoperative nutritional status. Fifty-two patients in the state hospitals (Group 1) and 48 in the university hospital were assessed. Anthropometric and biochemical measurements were performed. Changes in preoperative Subjective Global Assessment scores and scores at the time of discharge and types of nutritional support were compared. Subjective Global Assessment-B was regarded as moderate and Subjective Global Assessment-C as heavy malnutrition. Ten patients had Subjective Global Assessment-B and 29 had Subjective Global Assessment-C malnutrition in Group 1 and nine had Subjective Global Assessment-B and 31 had Subjective Global Assessment-C malnutrition in Group 2 during preoperative assessment. Respective numbers in postoperative assessment were 12 for Subjective Global Assessment-B and 30 for Subjective Global Assessment-C in Group 1 and 14 for Subjective Global Assessment-B and 26 for Subjective Global Assessment-C in Group 2. There was no difference between two groups. Nutritional methods according to Subjective Global Assessment evaluation in pre- and postoperative periods were not different between the groups. This study demonstrated that the malnutrition rate is high among patients scheduled for gastrointestinal cancer surgery and the number of surgeons were inadequate to provide perioperative nutritional support. Both university and state hospitals had similar shortcomings. Subjective Global Assessment is an easy and reliable test and if utilized will be helpful to detect patients requiring nutritional support.

  9. 1-Methyl-4-phenylpyridinium-induced alterations of glutathione status in immortalized rat dopaminergic neurons

    Drechsel, Derek A.; Liang, L.-P.; Patel, Manisha

    2007-01-01

    Decreased glutathione levels associated with increased oxidative stress are a hallmark of numerous neurodegenerative diseases, including Parkinson's disease. GSH is an important molecule that serves as an anti-oxidant and is also a major determinant of cellular redox environment. Previous studies have demonstrated that neurotoxins can cause changes in reduced and oxidized GSH levels; however, information regarding steady state levels remains unexplored. The goal of this study was to characterize changes in cellular GSH levels and its regulatory enzymes in a dopaminergic cell line (N27) following treatment with the Parkinsonian toxin, 1-methyl-4-phenylpyridinium (MPP + ). Cellular GSH levels were initially significantly decreased 12 h after treatment, but subsequently recovered to values greater than controls by 24 h. However, oxidized glutathione (GSSG) levels were increased 24 h following treatment, concomitant with a decrease in GSH/GSSG ratio prior to cell death. In accordance with these changes, ROS levels were also increased, confirming the presence of oxidative stress. Decreased enzymatic activities of glutathione reductase and glutamate-cysteine ligase by 20-25% were observed at early time points and partly account for changes in GSH levels after MPP + exposure. Additionally, glutathione peroxidase activity was increased 24 h following treatment. MPP + treatment was not associated with increased efflux of glutathione to the medium. These data further elucidate the mechanisms underlying GSH depletion in response to the Parkinsonian toxin, MPP +

  10. Global Precipitation Measurement (GPM) Mission: Overview and Status

    Hou, Arthur Y.

    2012-01-01

    The Global Precipitation Measurement (GPM) Mission is an international satellite mission specifically designed to unify and advance precipitation measurements from a constellation of research and operational microwave sensors. NASA and JAXA will deploy a Core Observatory in 2014 to serve as a reference satellite to unify precipitation measurements from the constellation of sensors. The GPM Core Observatory will carry a Ku/Ka-band Dual-frequency Precipitation Radar (DPR) and a conical-scanning multi-channel (10-183 GHz) GPM Microwave Radiometer (GMI). The DPR will be the first dual-frequency radar in space to provide not only measurements of 3-D precipitation structures but also quantitative information on microphysical properties of precipitating particles. The DPR and GMI measurements will together provide a database that relates vertical hydrometeor profiles to multi-frequency microwave radiances over a variety of environmental conditions across the globe. This combined database will be used as a common transfer standard for improving the accuracy and consistency of precipitation retrievals from all constellation radiometers. For global coverage, GPM relies on existing satellite programs and new mission opportunities from a consortium of partners through bilateral agreements with either NASA or JAXA. Each constellation member may have its unique scientific or operational objectives but contributes microwave observations to GPM for the generation and dissemination of unified global precipitation data products. In addition to the DPR and GMI on the Core Observatory, the baseline GPM constellation consists of the following sensors: (1) Special Sensor Microwave Imager/Sounder (SSMIS) instruments on the U.S. Defense Meteorological Satellite Program (DMSP) satellites, (2) the Advanced Microwave Scanning Radiometer-2 (AMSR-2) on the GCOM-W1 satellite of JAXA, (3) the Multi-Frequency Microwave Scanning Radiometer (MADRAS) and the multi-channel microwave humidity sounder

  11. Conservation and restoration of mangroves: Global status, perspectives, and prognosis

    Romañach, Stephanie; DeAngelis, Donald L.; Koh, Hock Lye; Li, Yuhong; Teh, Su Yean; Barizan, Raja Sulaiman Raja; Zhai, Lu

    2018-01-01

    Mangrove forests provide critical services around the globe to both human populations and the ecosystems they occupy. However, losses of mangrove habitat of more than 50% have been recorded in some parts of the world, and these losses are largely attributable to human activities. The importance of mangroves and the threats to their persistence have long been recognized, leading to actions taken locally, by national governments, and through international agreements for their protection. In this review, we explore the status of mangrove forests as well as efforts to protect them. We examine threats to the persistence of mangroves, consequences, and potential solutions for effective conservation. We present case studies from disparate regions of the world, showing that the integration of human livelihood needs in a manner that balances conservation goals can present solutions that could lead to long-term sustainability of mangrove forests throughout the world.

  12. Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.

    Crescenti, Anna; Solà, Rosa; Valls, Rosa M; Caimari, Antoni; Del Bas, Josep M; Anguera, Anna; Anglés, Neus; Arola, Lluís

    2013-01-01

    DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, pcocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process. Clinicaltrials.govNCT00511420 and NCT00502047.

  13. Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.

    Anna Crescenti

    Full Text Available DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs, methylenetetrahydrofolate reductase (MTHFR, and methionine synthase reductase (MTRR genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001. Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process.Clinicaltrials.govNCT00511420 and NCT00502047.

  14. Global status of nuclear power and the needed human resources

    Bernido, Corazon C.

    2009-01-01

    According to projections of the OECD/IEA, the world energy demand will expand by 45% from now until 2030, with coal accounting for more than a third of the overall rise. To reduce greenhouse gases and mitigate climate change, many countries are resorting to renewables and nuclear power. Some statistics about nuclear energy in the global energy mix and about nuclear power plants worldwide, as well as the energy situation in the country are presented. According to sources from the Department of Energy on the Philippine Energy Plan, nuclear power is a long-term energy option and will likely enter the energy mix by 2025. Preparation of the infrastructure for nuclear power has to start ten to fifteen years before the first plant comes online. The needed human resources, the education and training required are present. (Author)

  15. Global DNA Methylation in the Chestnut Blight Fungus Cryphonectria parasitica and Genome-Wide Changes in DNA Methylation Accompanied with Sectorization

    Kum-Kang So

    2018-02-01

    Full Text Available Mutation in CpBck1, an ortholog of the cell wall integrity mitogen-activated protein kinase kinase kinase (MAPKKK of Saccharomyces cerevisiae, in the chestnut blight fungus Cryphonectria parasitica resulted in a sporadic sectorization as culture proceeded. The progeny from the sectored area maintained the characteristics of the sector, showing a massive morphogenetic change, including robust mycelial growth without differentiation. Epigenetic changes were investigated as the genetic mechanism underlying this sectorization. Quantification of DNA methylation and whole-genome bisulfite sequencing revealed genome-wide DNA methylation of the wild-type at each nucleotide level and changes in DNA methylation of the sectored progeny. Compared to the wild-type, the sectored progeny exhibited marked genome-wide DNA hypomethylation but increased methylation sites. Expression analysis of two DNA methyltransferases, including two representative types of DNA methyltransferase (DNMTase, demonstrated that both were significantly down-regulated in the sectored progeny. However, functional analysis using mutant phenotypes of corresponding DNMTases demonstrated that a mutant of CpDmt1, an ortholog of RID of Neurospora crassa, resulted in the sectored phenotype but the CpDmt2 mutant did not, suggesting that the genetic basis of fungal sectorization is more complex. The present study revealed that a mutation in a signaling pathway component resulted in sectorization accompanied with changes in genome-wide DNA methylation, which suggests that this signal transduction pathway is important for epigenetic control of sectorization via regulation of genes involved in DNA methylation.

  16. Examination of DNA methylation status of the ELOVL2 marker may be useful for human age prediction in forensic science.

    Zbieć-Piekarska, Renata; Spólnicka, Magdalena; Kupiec, Tomasz; Makowska, Żanetta; Spas, Anna; Parys-Proszek, Agnieszka; Kucharczyk, Krzysztof; Płoski, Rafał; Branicki, Wojciech

    2015-01-01

    Age estimation in forensic investigations may complement the prediction of externally visible characteristics and the inference of biogeographical ancestry, thus allowing a better description of an unknown individual. Multiple CpG sites that show linear correlation between age and degree of DNA methylation have been identified in the human genome, providing a selection of candidates for age prediction. In this study, we optimized an assay based on bisulfite conversion and pyrosequencing of 7 CpG sites located in the ELOVL2 gene. Examination of 303 blood samples collected from individuals aged 2-75 years allowed selection of the most informative site, explaining 83% of variation in age. The final linear regression model included two CpG sites in ELOVL2 and enabled age prediction with R(2)=0.859, prediction error=6.85 and mean absolute deviation MAD=5.03. Examination of a testing set of 124 blood samples (MAD=5.75) showed that 68.5% of samples were correctly predicted, assuming that chronological and predicted ages matched ± 7 years. It was found that the ELOVL2 methylation status in bloodstains had not changed significantly after 4 weeks of storage in room temperature conditions. Analysis of 45 bloodstains deposited on tissue paper after 5, 10 and 15 years of storage in room conditions indicated that although a gradual decrease of positive PCR results was observed, the general age prediction success rate remained similar and equaled 60-78%. The obtained results show that the ELOVL2 locus provides a very good source of information about human chronological age based on analysis of blood, including bloodstains, and it may constitute a powerful and reliable predictor in future forensic age estimation models. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. DNA methylation levels associated with race and childhood asthma severity.

    Chan, Marcia A; Ciaccio, Christina E; Gigliotti, Nicole M; Rezaiekhaligh, Mo; Siedlik, Jacob A; Kennedy, Kevin; Barnes, Charles S

    2017-10-01

    Asthma is a common chronic childhood disease worldwide. Socioeconomic status, genetic predisposition and environmental factors contribute to its incidence and severity. A disproportionate number of children with asthma are economically disadvantaged and live in substandard housing with potential indoor environmental exposures such as cockroaches, dust mites, rodents and molds. These exposures may manifest through epigenetic mechanisms that can lead to changes in relevant gene expression. We examined the association of global DNA methylation levels with socioeconomic status, asthma severity and race/ethnicity. We measured global DNA methylation in peripheral blood of children with asthma enrolled in the Kansas City Safe and Healthy Homes Program. Inclusion criteria included residing in the same home for a minimum of 4 days per week and total family income of less than 80% of the Kansas City median family income. DNA methylation levels were quantified by an immunoassay that assessed the percentage of 5-methylcytosine. Our results indicate that overall, African American children had higher levels of global DNA methylation than children of other races/ethnicities (p = 0.029). This difference was more pronounced when socioeconomic status and asthma severity were coupled with race/ethnicity (p = 0.042) where low-income, African American children with persistent asthma had significantly elevated methylation levels relative to other races/ethnicities in the same context (p = 0.006, Hedges g = 1.14). Our study demonstrates a significant interaction effect among global DNA methylation levels, asthma severity, race/ethnicity, and socioeconomic status.

  18. Dietary Chromium Restriction of Pregnant Mice Changes the Methylation Status of Hepatic Genes Involved with Insulin Signaling in Adult Male Offspring.

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-01-01

    Maternal undernutrition is linked with an elevated risk of diabetes mellitus in offspring regardless of the postnatal dietary status. This is also found in maternal micro-nutrition deficiency, especial chromium which is a key glucose regulator. We investigated whether maternal chromium restriction contributes to the development of diabetes in offspring by affecting DNA methylation status in liver tissue. After being mated with control males, female weanling 8-week-old C57BL mice were fed a control diet (CON, 1.19 mg chromium/kg diet) or a low chromium diet (LC, 0.14 mg chromium/kg diet) during pregnancy and lactation. After weaning, some offspring were shifted to the other diet (CON-LC, or LC-CON), while others remained on the same diet (CON-CON, or LC-LC) for 29 weeks. Fasting blood glucose, serum insulin, and oral glucose tolerance test was performed to evaluate the glucose metabolism condition. Methylation differences in liver from the LC-CON group and CON-CON groups were studied by using a DNA methylation array. Bisulfite sequencing was carried out to validate the results of the methylation array. Maternal chromium limitation diet increased the body weight, blood glucose, and serum insulin levels. Even when switched to the control diet after weaning, the offspring also showed impaired glucose tolerance and insulin resistance. DNA methylation profiling of the offspring livers revealed 935 differentially methylated genes in livers of the maternal chromium restriction diet group. Pathway analysis identified the insulin signaling pathway was the main process affected by hypermethylated genes. Bisulfite sequencing confirmed that some genes in insulin signaling pathway were hypermethylated in livers of the LC-CON and LC-LC group. Accordingly, the expression of genes in insulin signaling pathway was downregulated. There findings suggest that maternal chromium restriction diet results in glucose intolerance in male offspring through alterations in DNA methylation which

  19. Dietary Chromium Restriction of Pregnant Mice Changes the Methylation Status of Hepatic Genes Involved with Insulin Signaling in Adult Male Offspring.

    Qian Zhang

    Full Text Available Maternal undernutrition is linked with an elevated risk of diabetes mellitus in offspring regardless of the postnatal dietary status. This is also found in maternal micro-nutrition deficiency, especial chromium which is a key glucose regulator. We investigated whether maternal chromium restriction contributes to the development of diabetes in offspring by affecting DNA methylation status in liver tissue. After being mated with control males, female weanling 8-week-old C57BL mice were fed a control diet (CON, 1.19 mg chromium/kg diet or a low chromium diet (LC, 0.14 mg chromium/kg diet during pregnancy and lactation. After weaning, some offspring were shifted to the other diet (CON-LC, or LC-CON, while others remained on the same diet (CON-CON, or LC-LC for 29 weeks. Fasting blood glucose, serum insulin, and oral glucose tolerance test was performed to evaluate the glucose metabolism condition. Methylation differences in liver from the LC-CON group and CON-CON groups were studied by using a DNA methylation array. Bisulfite sequencing was carried out to validate the results of the methylation array. Maternal chromium limitation diet increased the body weight, blood glucose, and serum insulin levels. Even when switched to the control diet after weaning, the offspring also showed impaired glucose tolerance and insulin resistance. DNA methylation profiling of the offspring livers revealed 935 differentially methylated genes in livers of the maternal chromium restriction diet group. Pathway analysis identified the insulin signaling pathway was the main process affected by hypermethylated genes. Bisulfite sequencing confirmed that some genes in insulin signaling pathway were hypermethylated in livers of the LC-CON and LC-LC group. Accordingly, the expression of genes in insulin signaling pathway was downregulated. There findings suggest that maternal chromium restriction diet results in glucose intolerance in male offspring through alterations in DNA

  20. Current global status of carotid artery stent placement.

    Wholey, M H; Wholey, M; Bergeron, P; Diethrich, E B; Henry, M; Laborde, J C; Mathias, K; Myla, S; Roubin, G S; Shawl, F; Theron, J G; Yadav, J S; Dorros, G; Guimaraens, J; Higashida, R; Kumar, V; Leon, M; Lim, M; Londero, H; Mesa, J; Ramee, S; Rodriguez, A; Rosenfield, K; Teitelbaum, G; Vozzi, C

    1998-05-01

    Our purpose was to review the current status of carotid artery stent placement throughout the world. Surveys were sent to major interventional centers in Europe, North and South America, and Asia. Information from peer-reviewed journals was also included and supplemented the survey. The survey asked various questions regarding the patients enrolled, procedure techniques, and results of carotid stenting, including complications and restenosis. Of the centers which were sent surveys, 24 responded. The total number of endovascular carotid stent procedures that have been performed worldwide to date included 2,048 cases, with a technical success of 98.6%. Complications that occurred during carotid stent placement or within a 30-day period following placement were recorded. Overall, there were 63 minor strokes, with a rate of occurrence of 3.08%. The total number of major strokes was 27, for a rate of 1.32%. There were 28 deaths within a 30-day postprocedure period, resulting in a mortality rate of 1.37%. Restenosis rates of carotid stenting have been 4.80% at 6 mo. Endovascular stent treatment of carotid artery atherosclerotic disease is growing as an alternative to vascular surgery, especially for patients that are at high risk for standard carotid endarterectomy. The periprocedural risks for major and minor strokes and death are generally acceptable at this early stage of development.

  1. Global status of recycling waste solar panels: A review.

    Xu, Yan; Li, Jinhui; Tan, Quanyin; Peters, Anesia Lauren; Yang, Congren

    2018-05-01

    With the enormous growth in the development and utilization of solar-energy resources, the proliferation of waste solar panels has become problematic. While current research into solar panels has focused on how to improve the efficiency of the production capacity, the dismantling and recycling of end-of-life (EOL) panels are seldom considered, as can be seen, for instance, in the lack of dedicated solar-panel recycling plants. EOL solar-panel recycling can effectively save natural resources and reduce the cost of production. To address the environmental conservation and resource recycling issues posed by the huge amount of waste solar panels regarding environmental conservation and resource recycling, the status of the management and recycling technologies for waste solar panels are systemically reviewed and discussed in this article. This review can provide a quantitative basis to support the recycling of PV panels, and suggests future directions for public policy makers. At present, from the technical aspect, the research on solar panel recovery is facing many problems, and we need to further develop an economically feasible and non-toxic technology. The research on solar photovoltaic panels' management at the end of life is just beginning in many countries, and there is a need for further improvement and expansion of producer responsibility. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Global Framework for Climate Services (GFCS): status of implementation

    Lucio, Filipe

    2015-04-01

    The World Climate Conference-3 (Geneva 2009) unanimously decided to establish the Global Framework for Climate Services (GFCS), a UN-led initiative spearheaded by WMO to guide the development and application of science-based climate information and services in support of decision-making in climate sensitive sectors. By promoting science-based decision-making, the GFCS is empowering governments, communities and companies to build climate resilience, reduce vulnerabilities and adapt to impacts. The initial priority areas of GFCS are Agriculture and Food Security; Disaster Risk Reduction; Health; and Water Resources. The implementation of GFCS is well underway with a governance structure now fully established. The governance structure of GFCS includes the Partner Advisory Committee (PAC), which is GFCS's stakeholder engagement mechanism. The membership of the PAC allows for a broad participation of stakeholders. The European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT), the European Commission (EC), the Food and Agriculture Organization of the UN (FAO), the Global Water Partnership (GWP), the International Federation of Red Cross and Red Crescent Societies (IFRC), the International Union of Geodesy and Geophysics (IUGG), United Nations Environment Programme (UNEP), the United Nations Institute for Training and Research (UNITAR), the World Business Council for Sustainable Development (WBCSD), the World Food Programme (WFP) and WMO have already joined the PAC. Activities are being implemented in various countries in Africa, the Caribbean, Asia and Pacific Small Islands Developing States through flagship projects and activities in the four priority areas of GFCS to enable the development of a Proof of Concept. The focus at national level is on strengthening institutional capacities needed for development of capacities for co-design and co-production of climate services and their application in support of decision-making in climate sensitive

  3. Optimal estimation of the surface fluxes of methyl chloride using a 3-D global chemical transport model

    X. Xiao

    2010-06-01

    Full Text Available Methyl chloride (CH3Cl is a chlorine-containing trace gas in the atmosphere contributing significantly to stratospheric ozone depletion. Large uncertainties in estimates of its source and sink magnitudes and temporal and spatial variations currently exist. GEIA inventories and other bottom-up emission estimates are used to construct a priori maps of the surface fluxes of CH3Cl. The Model of Atmospheric Transport and Chemistry (MATCH, driven by NCEP interannually varying meteorological data, is then used to simulate CH3Cl mole fractions and quantify the time series of sensitivities of the mole fractions at each measurement site to the surface fluxes of various regional and global sources and sinks. We then implement the Kalman filter (with the unit pulse response method to estimate the surface fluxes on regional/global scales with monthly resolution from January 2000 to December 2004. High frequency observations from the AGAGE, SOGE, NIES, and NOAA/ESRL HATS in situ networks and low frequency observations from the NOAA/ESRL HATS flask network are used to constrain the source and sink magnitudes. The inversion results indicate global total emissions around 4100 ± 470 Gg yr−1 with very large emissions of 2200 ± 390 Gg yr−1 from tropical plants, which turn out to be the largest single source in the CH3Cl budget. Relative to their a priori annual estimates, the inversion increases global annual fungal and tropical emissions, and reduces the global oceanic source. The inversion implies greater seasonal and interannual oscillations of the natural sources and sink of CH3Cl compared to the a priori. The inversion also reflects the strong effects of the 2002/2003 globally widespread heat waves and droughts on global emissions from tropical plants, biomass burning and salt marshes, and on the soil sink.

  4. Global Conservation of Protein Status between Cell Lines and Xenografts

    Julian Biau

    2016-08-01

    Full Text Available Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a xenograft model beforehand. We studied a selection of 89 protein markers of interest in 14 human cell cultures and respective subcutaneous xenografts using the reverse-phase protein array technology. We specifically focused on proteins and posttranslational modifications involved in DNA repair, PI3K pathway, apoptosis, tyrosine kinase signaling, stress, cell cycle, MAPK/ERK signaling, SAPK/JNK signaling, NFκB signaling, and adhesion/cytoskeleton. Using hierarchical clustering, most cell culture-xenograft pairs cluster together, suggesting a global conservation of protein signature. Particularly, Akt, NFkB, EGFR, and Vimentin showed very stable protein expression and phosphorylation levels highlighting that 4 of 10 pathways were highly correlated whatever the model. Other proteins were heterogeneously conserved depending on the cell line. Finally, cell line models with low Akt pathway activation and low levels of Vimentin gave rise to more reliable xenograft models. These results may be useful for the extrapolation of cell culture experiments to in vivo models in novel targeted drug discovery.

  5. Estimated Glomerular Filtration Rate; Laboratory Implementation and Current Global Status.

    Miller, W Greg; Jones, Graham R D

    2018-01-01

    In 2002, the Kidney Disease Outcomes Quality Initiative guidelines for identifying and treating CKD recommended that clinical laboratories report estimated glomerular filtration rate (eGFR) with every creatinine result to assist clinical practitioners to identify people with early-stage CKD. At that time, the original Modification of Diet in Renal Disease (MDRD) Study equation based on serum creatinine measurements was recommended for calculating eGFR. Because the MDRD Study equation was developed using a nonstandardized creatinine method, a Laboratory Working Group of the National Kidney Disease Education program was formed and implemented standardized calibration traceability for all creatinine methods from global manufacturers by approximately 2010. A modified MDRD Study equation for use with standardized creatinine was developed. The Chronic Kidney Disease Epidemiology Collaboration developed a new equation in 2009 that was more accurate than the MDRD Study equation at values above 60 mL/min/1.73 m 2 . As of 2017, reporting eGFR with creatinine is almost universal in many countries. A reference system for cystatin C became available in 2010, and manufacturers are in the process to standardize cystatin C assays. Equations for eGFR based on standardized cystatin C alone and with creatinine are now available from the Chronic Kidney Disease Epidemiology Collaboration and other groups. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  6. Overview of the status and global strategy for neonicotinoids.

    Jeschke, Peter; Nauen, Ralf; Schindler, Michael; Elbert, Alfred

    2011-04-13

    In recent years, neonicotinoid insecticides have been the fastest growing class of insecticides in modern crop protection, with widespread use against a broad spectrum of sucking and certain chewing pests. As potent agonists, they act selectively on insect nicotinic acetylcholine receptors (nAChRs), their molecular target site. The discovery of neonicotinoids can be considered as a milestone in insecticide research and greatly facilitates the understanding of functional properties of the insect nAChRs. In this context, the crystal structure of the acetylcholine-binding proteins provides the theoretical foundation for designing homology models of the corresponding receptor ligand binding domains within the nAChRs, a useful basis for virtual screening of chemical libraries and rational design of novel insecticides acting on these practically relevant channels. Because of the relatively low risk for nontarget organisms and the environment, the high target specificity of neonicotinoid insecticides, and their versatility in application methods, this important class has to be maintained globally for integrated pest management strategies and insect resistance management programs. Innovative concepts for life-cycle management, jointly with the introduction of generic products, have made neonicotinoids the most important chemical class for the insecticide market.

  7. Global and National Socioeconomic Disparities in Obesity, Overweight, and Underweight Status

    Spencer Moore

    2010-01-01

    Results. Globally, 6.7% was underweight, 25.7% overweight, and 8.9% obese. Underweight status was least (5.8% and obesity (9.3% most prevalent in the richest quintile. There was variability between countries, with a tendency for lower-income quintiles to be at increased risk for underweight and reduced risk for obesity. Conclusion. International policies may require flexibility in addressing cross-national differences in the socio-economic covariates of BMI status.

  8. The global smoking epidemic: a history and status report.

    Proctor, Robert N

    2004-05-01

    The World Health Organization estimates that tobacco causes approximately 5 million deaths annually worldwide, a number expected to double by 2025. Cigarette consumption grew from only a few billion per year in 1900 to present values of approximately 5.5 trillion worldwide. Historical causes for the rise of smoking include the invention of flue curing, safety matches, and cigarette rolling machines, but also the distribution of cigarettes to soldiers during World War I, mass marketing, the failure of governments to limit consumption, and the duplicitous denial of hazards by manufacturers. Cancers of the lip, throat, and tongue were linked to tobacco as early as the 18th century, but a lung cancer hazard from smoking was not suspected until the first decade of the 20th century. Epidemiologic evidence began to emerge in the 1920s, and by the 1950s, the causal link with cigarette smoking was well established. Epidemiologic studies, animal experiments, and studies demonstrating pathologic changes in lung tissues at autopsy were 3 pivotal sources of evidence. However, the tobacco industry refused to concede the reality of tobacco hazards until the late 1990s. Instead, the industry sought to target physicians and others with its message of "no proof," using subtle techniques of deception, including the funding of spurious research, duplicitous press releases, propaganda efforts directed at physicians, and the employment of historians to construct exculpatory narratives. The World Health Organization's Framework Convention on Tobacco Control promises to standardize global tobacco control measures, including policies to limit smuggling. Effective means of reducing tobacco use include counter-advertising, increased taxation, smoke-free workplace legislation, and litigation against the industry.

  9. A refined, rapid and reproducible high resolution melt (HRM-based method suitable for quantification of global LINE-1 repetitive element methylation

    Tse M Yat

    2011-12-01

    Full Text Available Abstract Background The methylation of DNA is recognized as a key mechanism in the regulation of genomic stability and evidence for its role in the development of cancer is accumulating. LINE-1 methylation status represents a surrogate measure of genome-wide methylation. Findings Using high resolution melt (HRM curve analysis technology, we have established an in-tube assay that is linear (r > 0.9986 with a high amplification efficiency (90-105%, capable of discriminating between partcipant samples with small differences in methylation, and suitable for quantifying a wide range of LINE-1 methylation levels (0-100%--including the biologically relevant range of 50-90% expected in human DNA. We have optimized this procedure to perform using 2 μg of starting DNA and 2 ng of bisulfite-converted DNA for each PCR reaction. Intra- and inter-assay coefficients of variation were 1.44% and 0.49%, respectively, supporting the high reproducibility and precision of this approach. Conclusions In summary, this is a completely linear, quantitative HRM PCR method developed for the measurement of LINE-1 methylation. This cost-efficient, refined and reproducible assay can be performed using minimal amounts of starting DNA. These features make our assay suitable for high throughput analysis of multiple samples from large population-based studies.

  10. Recurrence in oral and pharyngeal cancer is associated with quantitative MGMT promoter methylation

    Taioli, Emanuela; Ragin, Camille; Wang, Xiao-hong; Chen, Jiangying; Langevin, Scott M; Brown, Ashley R; Gollin, Susanne M; Garte, Seymour; Sobol, Robert W

    2009-01-01

    Biomarkers that predict clinical response, tumor recurrence or patient survival are severely lacking for most cancers, particularly for oral and pharyngeal cancer. This study examines whether gene-promoter methylation of tumor DNA correlates with survival and recurrence rates in a population of patients with oral or pharyngeal cancer. The promoter methylation status of the DNA repair gene MGMT and the tumor suppressor genes CDKN2A and RASSF1 were evaluated by methylation-specific PCR in 88 primary oral and pharyngeal tumors and correlated with survival and tumor recurrence. Quantitative MGMT methylation was also assessed. 29.6% of the tumors presented with MGMT methylation, 11.5% with CDKN2A methylation and 12.1% with RASSF1 methylation. MGMT promoter methylation was significantly associated with poorer overall and disease-free survival. No differences in methylation status of MGMT and RASSF1 with HPV infection, smoking or drinking habits were observed. A significant inverse trend with the amount of MGMT methylation and overall and disease-free survival was observed (p trend = 0.002 and 0.001 respectively). These results implicate MGMT promoter methylation as a possible biomarker for oral and pharyngeal cancer prognosis. The critical role of MGMT in DNA repair suggests that defective DNA repair may be correlative in the observed association between MGMT promoter methylation and tumor recurrence. Follow-up studies should include further quantitative MSP-PCR measurement, global methylation profiling and detailed analysis of downstream DNA repair genes regulated by promoter methylation

  11. Fabricated World Class: Global University League Tables, Status Differentiation and Myths of Global Competition

    David, Matthew

    2016-01-01

    UK media coverage of global university league tables shows systematic bias towards the Russell Group, although also highlighting tensions within its membership. Coverage positions UK "elite" institutions between US superiority and Asian ascent. Coverage claims that league table results warrant UK university funding reform. However,…

  12. Japanese Global Precipitation Measurement (GPM) mission status and application of satellite-based global rainfall map

    Kachi, Misako; Shimizu, Shuji; Kubota, Takuji; Yoshida, Naofumi; Oki, Riko; Kojima, Masahiro; Iguchi, Toshio; Nakamura, Kenji

    2010-05-01

    As accuracy of satellite precipitation estimates improves and observation frequency increases, application of those data to societal benefit areas, such as weather forecasts and flood predictions, is expected, in addition to research of precipitation climatology to analyze precipitation systems. There is, however, limitation on single satellite observation in coverage and frequency. Currently, the Global Precipitation Measurement (GPM) mission is scheduled under international collaboration to fulfill various user requirements that cannot be achieved by the single satellite, like the Tropical Rainfall Measurement Mission (TRMM). The GPM mission is an international mission to achieve high-accurate and high-frequent rainfall observation over a global area. GPM is composed of a TRMM-like non-sun-synchronous orbit satellite (GPM core satellite) and constellation of satellites carrying microwave radiometer instruments. The GPM core satellite carries the Dual-frequency Precipitation Radar (DPR), which is being developed by the Japan Aerospace Exploration Agency (JAXA) and the National Institute of Information and Communications Technology (NICT), and microwave radiometer provided by the National Aeronautics and Space Administration (NASA). Development of DPR instrument is in good progress for scheduled launch in 2013, and DPR Critical Design Review has completed in July - September 2009. Constellation satellites, which carry a microwave imager and/or sounder, are planned to be launched around 2013 by each partner agency for its own purpose, and will contribute to extending coverage and increasing frequency. JAXA's future mission, the Global Change Observation Mission (GCOM) - Water (GCOM-W) satellite will be one of constellation satellites. The first generation of GCOM-W satellite is scheduled to be launched in 2011, and it carries the Advanced Microwave Scanning Radiometer 2 (AMSR2), which is being developed based on the experience of the AMSR-E on EOS Aqua satellite

  13. Global DNA methylation is altered by neoadjuvant chemoradiotherapy in rectal cancer and may predict response to treatment - A pilot study.

    Tsang, J S

    2014-07-28

    In rectal cancer, not all tumours display a response to neoadjuvant treatment. An accurate predictor of response does not exist to guide patient-specific treatment. DNA methylation is a distinctive molecular pathway in colorectal carcinogenesis. Whether DNA methylation is altered by neoadjuvant treatment and a potential response predictor is unknown. We aimed to determine whether DNA methylation is altered by neoadjuvant chemoradiotherapy (CRT) and to determine its role in predicting response to treatment.

  14. Skin score correlates with global DNA methylation and GSTO1 A140D polymorphism in arsenic-affected population of Eastern India.

    Majumder, Moumita; Dasgupta, Uma B; Guha Mazumder, D N; Das, Nilansu

    2017-07-01

    Arsenic is a potent environmental toxicant causing serious public health concerns in India, Bangladesh and other parts of the world. Gene- and promoter-specific hypermethylation has been reported in different arsenic-exposed cell lines, whereas whole genome DNA methylation study suggested genomic hypo- and hypermethylation after arsenic exposure in in vitro and in vivo studies. Along with other characteristic biomarkers, arsenic toxicity leads to typical skin lesions. The present study demonstrates significant correlation between severities of skin manifestations with their whole genome DNA methylation status as well as with a particular polymorphism (Ala 140 Asp) status in arsenic metabolizing enzyme Glutathione S-transferase Omega-1 (GSTO1) in arsenic-exposed population of the district of Nadia, West Bengal, India.

  15. Case–control study of HLA-G promoter methylation status, HPV infection and cervical neoplasia in Curitiba, Brazil: a pilot analysis

    Gillio-Tos, Anna; Carvalho, Newton S; Maestri, Carlos A; Lacerda, Hadriano M; Zugna, Daniela; Richiardi, Lorenzo; Merletti, Franco; Bicalho, Maria da Graça; Fiano, Valentina; Grasso, Chiara; Tarallo, Valentina; De Marco, Laura; Trevisan, Morena; Xavier, MarinaBarbaradeSousa; Slowik, Renata

    2012-01-01

    The causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hypotheses. The tolerogenic protein HLA-G has shown aberrant expression in a variety of cancers, which has been suggested as a mechanism for tumor escape from immunosurveillance. In the present study we evaluate the role of epigenetic modification (promoter de-methylation) of the HLA-G gene on susceptibility to HPV infection and development of high-grade cervical lesions. A case–control study was carried out in Curitiba, Brazil, between February and June 2010. A total of 789 women aged 15–47 years were recruited: 510 controls with normal cervical cytology, and 279 cases with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2, N = 150) or grade 3 (CIN3, N = 129). All women were administered a questionnaire by interview, which collected information on demographic and lifestyle factors, and a cervical sample was collected. HPV DNA detection was performed by GP5+/GP6+ primer-mediated PCR. HPV-positive samples were genotyped by multiplex PCR. A pilot analysis of HLA-G promoter methylation was carried out in a subset of the study population (96 cases and 76 controls) by pyrosequencing. HLA-G methylation and HPV infection status of cases and controls were compared, and confounding factors were computed by t Student and non-parametric Wilcoxon tests. Comparison of HLA-G methylation between cases and controls was assessed by the Bonferroni correction. The association of HLA-G methylation with CIN2/3 was evaluated by logistic regression. HPV prevalence was 19.6% in controls and 94.3% in CIN2/3 cases. HPV16, 31, 33, 35 and 18 were the most prevalent types. Methylation analysis of seven CpGs in the HLA-G promoter did not reveal any spontaneous de-methylation

  16. The Effects of Lycopene on the Methylation of the GSTP1 Promoter and Global Methylation in Prostatic Cancer Cell Lines PC3 and LNCaP

    Li-Juan Fu

    2014-01-01

    Full Text Available DNA (cytosine-5- methylation silencing of GSTP1 function occurs in prostate adenocarcinoma (PCa. Previous studies have shown that there is an inverse relationship between dietary lycopene intake and the risk of PCa. However, it is unknown whether lycopene reactivates the tumor suppressor gene glutathioneS-transferase-π (GSTP1 by demethylation of the hypermethylated CpGs that act to silence the GSTP1 promoter. Here, we demonstrated that lycopene treatment significantly decreased the methylation levels of the GSTP1 promoter and increased the mRNA and protein levels of GSTP1 in an androgen-independent PC-3 cell line. In contrast, lycopene treatment did not demethylate the GSTP1 promoter or increase GSTP1 expression in the androgen-dependent LNCaP cell line. DNA methyltransferase (DNMT 3A protein levels were downregulated in PC-3 cells following lycopene treatment; however, DNMT1 and DNMT3B levels were unchanged. Furthermore, the long interspersed element (LINE-1 and short interspersed element ALU were not demethylated when treated by lycopene. In LNCaP cells, lycopene treatment did not affect any detected DNMT protein expression, and the methylation levels of LINE-1 and ALU were decreased. These results indicated that the protective effect of lycopene on the prostate is different between androgen-dependent and androgen-independent derived PCa cells. Further, in vivo studies should be conducted to confirm these promising results and to evaluate the potential role of lycopene in the protection of the prostate.

  17. Global DNA methylation in earthworms: a candidate biomarker of epigenetic risks related to the presence of metals/metalloids in terrestrial environments.

    Santoyo, María Maldonado; Flores, Crescencio Rodríguez; Torres, Adolfo Lopez; Wrobel, Kazimierz; Wrobel, Katarzyna

    2011-10-01

    In this work, possible relationships between global DNA methylation and metal/metalloid concentrations in earthworms have been explored. Direct correlation was observed between soil and tissue As, Se, Sb, Zn, Cu, Mn, Ag, Co, Hg, Pb (p< 0.05). Speciation results obtained for As and Hg hint at the capability of earthworms for conversion of inorganic element forms present in soil to methylated species. Inverse correlation was observed between the percentage of methylated DNA cytosines and total tissue As, As + Hg, As + Hg + Se + Sb (β = -0.8456, p = 0.071; β = -0.9406, p = 0.017; β = -0.9526, p = 0.012 respectively), as well as inorganic As + Hg (β = -0.8807, p = 0.049). It was concluded that earthworms would be particularly helpful as bioindicators of elements undergoing in vivo methylation and might also be used to assess the related risk of epigenetic changes in DNA methylation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Methylation status of imprinted genes DLK1-GTL2, MEST (PEG1), ZAC (PLAGL1), and LINE-1 elements in spermatozoa of normozoospermic men, unlike H19 imprinting control regions, is not associated with idiopathic recurrent spontaneous miscarriages.

    Ankolkar, Mandar; Salvi, Vinita; Warke, Himangi; Vundinti, Babu Rao; Balasinor, N H

    2013-05-01

    To study methylation aberrations in spermatozoa at developmentally important imprinted regions to ascertain their role in early embryo loss in idiopathic recurrent spontaneous miscarriages (RSM). Case-control study. Academic research setting at National Institute for Research in Reproductive Health, Parel, Mumbai. Male partners of couples with a history of RSM and male partners of couples with proven fertility (control group). None. DNA methylation levels at imprinting control regions of DLK1-GTL2, MEST (PEG1), and ZAC (PLAGL1) by Epityper Massarray and global methylation levels as measured by LINE-1 methylation and anti-5-methyl cytosine antibody in spermatozoa of 23 men in control group and 23 men in RSM group. We did not observe any aberration in the total methylation levels in any of the imprinted genes or global methylation analyzed. Our results indicate that paternal methylation aberrations at imprinting control regions of DLK1-GTL2, MEST (PEG1), and ZAC (PLAGL1) and global methylation levels are not associated with idiopathic RSM and may not be good epigenetic markers (unlike the H-19 imprinting control region) for diagnosis of idiopathic RSM. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. The global childhood obesity epidemic and the association between socio-economic status and childhood obesity

    Wang, Youfa; Lim, Hyunjung

    2012-01-01

    This paper describes the current prevalence and time trends of childhood obesity worldwide, and the association between childhood obesity and socio-economic status (SES). Childhood obesity has become a global public health crisis. The prevalence is highest in western and industrialized countries, but still low in some developing countries. The prevalence also varies by age and gender. The WHO Americas and eastern Mediterranean regions had higher prevalence of overweight and obesity (30–40%) t...

  20. [Effect of total glucosides of peony on expression and DNA methylation status of ITGAL gene in CD4(+) T cells of systemic lupus erythematosus].

    Zhao, Ming; Liang, Gongping; Luo, Shuangyan; Lu, Qianjin

    2012-05-01

    To investigate the effect of total glucosides of peony (TGP) on expression and DNA methylation status of ITGAL gene (CD11a) in CD4(+) T cells from patients with systemic lupus erythematosus (SLE). CD4(+) T cells were isolated by positive selection using CD4 beads. CD4(+) T cells were treated by TGP at 0, 62.5, 312.5 and 1562.5 mg/L for 48 h. The MTT method was used to assess cell viability; mRNA expression level was measured by realtime-PCR; protein level of CD11a was measured by flow cytometric analysis; DNA methylation status was assayed by bisulfite sequencing. No significant change in cell viability was found in CD4(+) T cells among the different concentration groups (P>0.05). Compared with control, the mRNA and protein levels of ITGAL were down-regulated significantly in SLE CD4(+) T cells treated with TGP (1562.5 mg/L) (PTGP (1562.5 mg/L) treated CD4(+) T cells compared with control group (PTGP can repress CD11a gene expression through enhancing DNA methylation of ITGAL promoter in CD4(+) T cells from patients with SLE. This observation represents a preliminary step in understanding the mechanism of TGP in SLE therapy.

  1. Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation.

    Benton, Michael G; Somasundaram, Swetha; Glasner, Jeremy D; Palecek, Sean P

    2006-12-01

    One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

  2. Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation

    Glasner Jeremy D

    2006-12-01

    Full Text Available Abstract Background One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS and gamma radiation. Results Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1 are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Conclusion Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

  3. Application of machine learning methods to histone methylation ChIP-Seq data reveals H4R3me2 globally represses gene expression

    2010-01-01

    Background In the last decade, biochemical studies have revealed that epigenetic modifications including histone modifications, histone variants and DNA methylation form a complex network that regulate the state of chromatin and processes that depend on it including transcription and DNA replication. Currently, a large number of these epigenetic modifications are being mapped in a variety of cell lines at different stages of development using high throughput sequencing by members of the ENCODE consortium, the NIH Roadmap Epigenomics Program and the Human Epigenome Project. An extremely promising and underexplored area of research is the application of machine learning methods, which are designed to construct predictive network models, to these large-scale epigenomic data sets. Results Using a ChIP-Seq data set of 20 histone lysine and arginine methylations and histone variant H2A.Z in human CD4+ T-cells, we built predictive models of gene expression as a function of histone modification/variant levels using Multilinear (ML) Regression and Multivariate Adaptive Regression Splines (MARS). Along with extensive crosstalk among the 20 histone methylations, we found H4R3me2 was the most and second most globally repressive histone methylation among the 20 studied in the ML and MARS models, respectively. In support of our finding, a number of experimental studies show that PRMT5-catalyzed symmetric dimethylation of H4R3 is associated with repression of gene expression. This includes a recent study, which demonstrated that H4R3me2 is required for DNMT3A-mediated DNA methylation--a known global repressor of gene expression. Conclusion In stark contrast to univariate analysis of the relationship between H4R3me2 and gene expression levels, our study showed that the regulatory role of some modifications like H4R3me2 is masked by confounding variables, but can be elucidated by multivariate/systems-level approaches. PMID:20653935

  4. Global Proteome Response to Deletion of Genes Related to Mercury Methylation and Dissimilatory Metal Reduction Reveals Changes in Respiratory Metabolism in Geobacter sulfurreducens PCA.

    Qian, Chen; Johs, Alexander; Chen, Hongmei; Mann, Benjamin F; Lu, Xia; Abraham, Paul E; Hettich, Robert L; Gu, Baohua

    2016-10-07

    Geobacter sulfurreducens PCA can reduce, sorb, and methylate mercury (Hg); however, the underlying biochemical mechanisms of these processes and interdependent metabolic pathways remain unknown. In this study, shotgun proteomics was used to compare global proteome profiles between wild-type G. sulfurreducens PCA and two mutant strains: a ΔhgcAB mutant, which is deficient in two genes known to be essential for Hg methylation and a ΔomcBESTZ mutant, which is deficient in five outer membrane c-type cytochromes and thus impaired in its ability for dissimilatory metal ion reduction. We were able to delineate the global response of G. sulfurreducens PCA in both mutants and identify cellular networks and metabolic pathways that were affected by the loss of these genes. Deletion of hgcAB increased the relative abundances of proteins implicated in extracellular electron transfer, including most of the c-type cytochromes, PilA-C, and OmpB, and is consistent with a previously observed increase in Hg reduction in the ΔhgcAB mutant. Deletion of omcBESTZ was found to significantly increase relative abundances of various methyltransferases, suggesting that a loss of dissimilatory reduction capacity results in elevated activity among one-carbon (C1) metabolic pathways and thus increased methylation. We show that G. sulfurreducens PCA encodes only the folate branch of the acetyl-CoA pathway, and proteins associated with the folate branch were found at lower abundance in the ΔhgcAB mutant strain than the wild type. This observation supports the hypothesis that the function of HgcA and HgcB is linked to C1 metabolism through the folate branch of the acetyl-CoA pathway by providing methyl groups required for Hg methylation.

  5. Mutations in TET2 and DNMT3A genes are associated with changes in global and gene-specific methylation in acute myeloid leukemia.

    Ponciano-Gómez, Alberto; Martínez-Tovar, Adolfo; Vela-Ojeda, Jorge; Olarte-Carrillo, Irma; Centeno-Cruz, Federico; Garrido, Efraín

    2017-10-01

    Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia. Peripheral blood samples from 110 untreated patients with acute myeloid leukemia and 15 healthy control individuals were collected. Global 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from peripheral blood leukocytes were measured by using the MethylFlashTM Quantification kits. DNMT3A and TET2 expression levels were evaluated by real-time quantitative polymerase chain reaction. The R882A hotspot of DNMT3A and exons 6-10 of TET2 were amplified by polymerase chain reaction and sequenced using the Sanger method. Methylation patterns of 16 gene promoters were evaluated by pyrosequencing after treating DNA with sodium bisulfite, and their transcriptional products were measured by real-time quantitative polymerase chain reaction.Here, we demonstrate altered levels of 5-methylcytosine and 5-hydroxymethylcytosine and highly variable transcript levels of DNMT3A and TET2 in peripheral blood leukocytes from acute myeloid leukemia patients. We found a mutation prevalence of 2.7% for DNMT3A and 11.8% for TET2 in the Mexican population with this disease. The average overall survival of acute myeloid leukemia patients with DNMT3A mutations was only 4 months. In addition, we showed that mutations in DNMT3A and TET2 may cause irregular DNA methylation patterns and transcriptional expression levels in 16 genes known to be involved in acute myeloid leukemia pathogenesis

  6. CpG Methylation Analysis—Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics

    Sepulveda, Antonia R.; Jones, Dan; Ogino, Shuji; Samowitz, Wade; Gulley, Margaret L.; Edwards, Robin; Levenson, Victor; Pratt, Victoria M.; Yang, Bin; Nafa, Khedoudja; Yan, Liying; Vitazka, Patrick

    2009-01-01

    Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics. PMID:19541921

  7. Methylation in hepatocellular carcinoma

    Regina M. Santella

    2007-02-01

    epigenetic aberrations as DNA isolated from an individual's tumor. The process by which tumor DNA is released into circulating blood is unclear but may result from accelerated necrosis, apoptosis or other processes. p53 mutation and p16 promoter hypermethylation have been detected in paired tumor and plasma of HCC cases. More recently, we investigated promoter hypermethylation in DNA isolated from the serum of HCC patients who provided repeated blood samples prior to diagnosis and controls enrolled in a cancer screen program in Taiwan. Among cases, aberrant methylation was found in serum DNA one to nine years before clinical HCC diagnosis. RASSF1A had the highest frequency of hypermethylation with 70% of cases having at least one positive sample compared to 44% for p16 and 22% for p15. For the controls, promoter hypermethylation was found in 6 and 4% of subjects for RASSF1A and p16, respectively; none had methylation of p15. An ROC curve that included clinical risk factors (age, HBsAg status, anti-HCV status, smoking, alcohol status and hypermethylation biomarkers gave an overall predictive accuracy of 89% with sensitivity and specificity 84% and 94%, respectively. The analysis of epigenetic changes on RASSF1A, p16 and p15 tumor suppressor genes in serum DNA may be a valuable biomarkers for early detection in populations at high risk of HCC. In addition, the area of global hypomethylation remains largely unexplored in HCC.

  8. DNA Methylation in Peripheral Blood Cells of Pigs Cloned by Somatic Cell Nuclear Transfer

    Gao, Fei; Li, Shengting; Lin, Lin

    2011-01-01

    To date, the genome-wide DNA methylation status of cloned pigs has not been investigated. Due to the relatively low success rate of pig cloning by somatic cell nuclear transfer, a better understanding of the epigenetic reprogramming and the global methylation patterns associated with development...... in cloned pigs is required. In this study we applied methylation-specific digital karyotyping tag sequencing by Solexa technology and investigated the genome-wide DNA methylation profiles of peripheral blood cells in cloned pigs with normal phenotypes in comparison with their naturally bred controls....... In the result, we found that globally there was no significant difference of DNA methylation patterns between the two groups. Locus-specifically, some genes involved in embryonic development presented a generally increased level of methylation. Our findings suggest that in cloned pigs with normal phenotypes...

  9. Measuring global trends in the status of biodiversity: red list indices for birds.

    Stuart H M Butchart

    2004-12-01

    Full Text Available The rapid destruction of the planet's biodiversity has prompted the nations of the world to set a target of achieving a significant reduction in the rate of loss of biodiversity by 2010. However, we do not yet have an adequate way of monitoring progress towards achieving this target. Here we present a method for producing indices based on the IUCN Red List to chart the overall threat status (projected relative extinction risk of all the world's bird species from 1988 to 2004. Red List Indices (RLIs are based on the number of species in each Red List category, and on the number changing categories between assessments as a result of genuine improvement or deterioration in status. The RLI for all bird species shows that their overall threat status has continued to deteriorate since 1988. Disaggregated indices show that deteriorations have occurred worldwide and in all major ecosystems, but with particularly steep declines in the indices for Indo-Malayan birds (driven by intensifying deforestation of the Sundaic lowlands and for albatrosses and petrels (driven by incidental mortality in commercial longline fisheries. RLIs complement indicators based on species population trends and habitat extent for quantifying global trends in the status of biodiversity. Their main weaknesses are that the resolution of status changes is fairly coarse and that delays may occur before some status changes are detected. Their greatest strength is that they are based on information from nearly all species in a taxonomic group worldwide, rather than a potentially biased subset. At present, suitable data are only available for birds, but indices for other taxonomic groups are in development, as is a sampled index based on a stratified sample from all major taxonomic groups.

  10. Nutritional status of patients treated with radiotherapy as determined by subjective global assessment

    Koom, Woong Sub; Keum, Ki Chang [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Ahn, Seung Do [Dept. of Radiation Oncology, Asan Medical Center, Seoul (Korea, Republic of); and others

    2012-09-15

    The purpose of this prospective multi-institutional study was to evaluate the nutritional status of patients undergoing radiotherapy (RT) for treatment of head and neck, lung, or gastrointestinal cancer. A total of 1,000 patients were enrolled in this study at seven different hospitals in Seoul, Korea between October 2009 and May 2010. The nutritional status of patients after receiving 3 weeks of RT was evaluated using subjective global assessment (SGA). The nutritional status of each patient was rated as well nourished (A), moderately malnourished (B), or severely malnourished (C). The mean age of patients in this study was 59.4 {+-} 11.9 years, and the male to female ratio was 7:3. According to the SGA results, 60.8%, 34.5%, and 4.7% of patients were classified as A, B, or C, respectively. The following criteria were significantly associated with malnutrition (SGA B or C; p < 0.001): loss of subcutaneous fat or muscle wasting (odds ratio [OR], 11.473); increased metabolic demand/stress (OR, 8.688); ankle, sacral edema, or ascites (OR, 3.234); and weight loss 5% (OR, 2.299). SGA was applied successfully to assess the nutritional status of most patients. The prevalence of malnutrition in a radiation oncology department was 39.2%. The results of this study serve as a basis for implementation of nutrition intervention to patients being treated at radiation oncology departments.

  11. Nutritional status of patients treated with radiotherapy as determined by subjective global assessment

    Koom, Woong Sub; Keum, Ki Chang; Ahn, Seung Do

    2012-01-01

    The purpose of this prospective multi-institutional study was to evaluate the nutritional status of patients undergoing radiotherapy (RT) for treatment of head and neck, lung, or gastrointestinal cancer. A total of 1,000 patients were enrolled in this study at seven different hospitals in Seoul, Korea between October 2009 and May 2010. The nutritional status of patients after receiving 3 weeks of RT was evaluated using subjective global assessment (SGA). The nutritional status of each patient was rated as well nourished (A), moderately malnourished (B), or severely malnourished (C). The mean age of patients in this study was 59.4 ± 11.9 years, and the male to female ratio was 7:3. According to the SGA results, 60.8%, 34.5%, and 4.7% of patients were classified as A, B, or C, respectively. The following criteria were significantly associated with malnutrition (SGA B or C; p < 0.001): loss of subcutaneous fat or muscle wasting (odds ratio [OR], 11.473); increased metabolic demand/stress (OR, 8.688); ankle, sacral edema, or ascites (OR, 3.234); and weight loss 5% (OR, 2.299). SGA was applied successfully to assess the nutritional status of most patients. The prevalence of malnutrition in a radiation oncology department was 39.2%. The results of this study serve as a basis for implementation of nutrition intervention to patients being treated at radiation oncology departments.

  12. Molecular characterization of HOXC8 gene and methylation status analysis of its exon 1 associated with the length of cashmere fiber in Liaoning cashmere goat.

    Bai, Wen L; Wang, Jiao J; Yin, Rong H; Dang, Yun L; Wang, Ze Y; Zhu, Yu B; Cong, Yu Y; Deng, Liang; Guo, Dan; Wang, Shi Q; Yang, Shu H; Xue, Hui L

    2017-02-01

    Homeobox protein Hox-C8 (HOXC8) is a member of Hox family. It is expressed in the dermal papilla of the skin and is thought to be associated with the hair inductive capacity of dermal papilla cells. In the present study, we isolated and characterized a full-length open reading frame of HOXC8 cDNA from the skin tissue of Liaoning cashmere goat, as well as, established a phylogenetic relationship of goat HOXC8 with that of other species. Also, we investigated the effect of methylation status of HOXC8 exon 1 at anagen secondary hair follicle on the cashmere fiber traits in Liaoning cashmere goat. The sequence analysis indicated that the obtained cDNA was 1134-bp in length containing a complete ORF of 729-bp. It encoded a peptide of 242 amino acid residues in length. The structural analysis indicated that goat HOXC8 contained a typical homeobox domain. The phylogenetic analysis revealed that Capra hircus HOXC8 had a closer genetic relationship with that of Ovis aries, followed by Bos Taurus and Bubalus bubalis. The methylation analysis suggested that the methylation degree of HOXC8 exon 1 in anagen secondary hair follicle might be involved in regulating the growth of cashmere fiber in Liaoning cashmere goat. Our results provide new evidence for understanding the molecular structural and evolutionary characteristics of HOXC8 in Liaoning cashmere goat, as well as, for further insight into the role of methylation degree of HOXC8 exon 1 regulates the growth of cashmere fiber in goat.

  13. Evaluation of folate receptor 1 (FOLR1) mRNA expression, its specific promoter methylation and global DNA hypomethylation in type I and type II ovarian cancers

    Notaro, Sara; Reimer, Daniel; Fiegl, Heidi; Schmid, Gabriel; Wiedemair, Annamarie; Rössler, Julia; Marth, Christian; Zeimet, Alain Gustave

    2016-01-01

    In this retrospective study we evaluated the respective correlations and clinical relevance of FOLR1 mRNA expression, FOLR1 promoter specific methylation and global DNA hypomethylation in type I and type II ovarian cancer. Two hundred fifty four ovarian cancers, 13 borderline tumours and 60 samples of healthy fallopian epithelium and normal ovarian epithelium were retrospectively analysed for FOLR1 expression with RT-PCR. FOLR1 DNA promoter methylation and global DNA hypomethylation (measured by means of LINE1 DNA hypomethylation) were evaluated with MethyLight technique. No correlation between FOLR1 mRNA expression and its specific promoter DNA methylation was found neither in type I nor in type II cancers, however, high FOLR1 mRNA expression was found to be correlated with global DNA hypomethylation in type II cancers (p = 0.033). Strong FOLR1 mRNA expression was revealed for Grades 2-3, FIGO stages III-IV, residual disease > 0, and serous histotype. High FOLR1 expression was found to predict increased platinum sensitivity in type I cancers (odds ratio = 3.288; 1.256-10.75; p = 0.020). One-year survival analysis showed in type I cancers an independent better outcome for strong expression of FOLR1 in FIGO stage III and IV. For the entire follow up period no significant independent outcome for FOLR1 expression was revealed. In type I cancers LINE 1 DNA hypomethylation was found to exhibit a worse PFS and OS which were confirmed to be independent in multivariate COX regression model for both PFS (p = 0.026) and OS (p = 0.012). No correlations were found between FOLR1 expression and its specific promoter methylation, however, high FOLR1 mRNA expression was associated with DNA hypomethylation in type II cancers. FOLR1 mRNA expression did not prove to predict clinical outcome in type II cancers, although strong FOLR1 expression generally denotes ovarian cancers with highly aggressive phenotype. In type I cancers, however, strong FOLR1 expression has been found to be a

  14. Technological Innovation and Competitiveness in The Global Economy: India's Changing Status and Its Implications

    Bala Subrahmanya Mungila Hillemane

    2013-09-01

    Full Text Available   This paper probes the changing innovation status and resultant competitiveness in the context of global economy and questions the recent ranking improvements of India on the basis of hard economic facts. This paper has made use of secondary data comprising innovation indices and competitiveness rankings published by international organizations and reputed business schools from time to time since 1996 to analyze the changing status of India internationally. Later, using secondary data on key macro-economic variables published by the Government of India, the recent ranking of India is closely examined as well as recent steps taken by the government of India to improve competitiveness is elaborated. The study throws light on the changing but improving innovation dimensions and competitiveness ranking of India since 1996 till 2010. From nowhere India emerges and occupies the second slot, after China, in the global competitiveness ranking. But hard core macro-economic variables do not justify India’s elevation to the top in any way. Given this, the study throws light on the recent policy measures announced by the Government of India and its implications as well as policy imperatives.

  15. Molecular Features and Methylation Status in Early Onset (≤40 Years Colorectal Cancer: A Population Based, Case-Control Study

    Giulia Magnani

    2015-01-01

    Full Text Available Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%. KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02. Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

  16. The DNA methylation status alteration of two steroidogenic genes in gonads of rare minnow after bisphenol A exposure.

    Zhang, Ting; Liu, Yan; Chen, Hong; Gao, Jiancao; Zhang, Yingying; Yuan, Cong; Wang, Zaizhao

    2017-08-01

    Both cytochrome P450c17 (CYP17A1) and P-450 side chain cleavage (CYP11A1) play important roles in steroid biosynthesis. According to our previous studies, bisphenol A (BPA) could regulate the mRNA expression of cyp17a1 and cyp11a1 in rare minnow Gobiocypris rarus. However, the potential mechanism of the regulation is barely understood. In the present study, aiming to explore how BPA affects the mRNA expression of cyp17a1 and cyp11a1 in testes and ovaries of G. rarus, we firstly cloned 340-bp fragment of 5' flanking region of cyp11a1 and then detected the methylation level of CpG loci involved in 5' flanking of cyp11a1 and cyp17a1 and their mRNA expression levels. Results showed that exposure to BPA significantly increased serum estradiol (E2) and 11-ketotesterone (11-KT) concentrations. Ovarian mRNA expression of cyp17a1 and cyp11a1 were significantly decreased after BPA exposure 7- for and 14-days. However, transcriptions of testicular cyp17a1 and cyp11a1 were significantly increased and decreased respectively after BPA treatment for 14days. The DNA methylation levels of cyp17a1 were decreased in ovaries on day 7 and increased in ovaries and decreased in testes respectively on day 14. The methylation levels of cyp11a1 were increased in ovaries on day 7 and both ovaries and testes on day 14. There were a significant correlation between DNA methylation at specific CpG loci and cyp17a1 and cyp11a1 genes transcription levels. In conclusion, the CpG loci methylation in 5' flanking region appears to involve in the regulation of mRNA expression of cyp17a1 and cyp11a1 mediated by BPA. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The status and prospects of renewable energy for combating global warming

    Arent, Douglas J., E-mail: doug.arent@nrel.gov; Wise, Alison; Gelman, Rachel

    2011-07-15

    Reducing anthropogenic greenhouse gas (GHG) emissions in material quantities, globally, is a critical element in limiting the impacts of global warming. GHG emissions associated with energy extraction and use are a major component of any strategy addressing climate change mitigation. Non-emitting options for electrical power and liquid transportation fuels are increasingly considered key components of an energy system with lower overall environmental impacts. Renewable energy technologies (RETs) as well as biofuels technologies have been accelerating rapidly during the past decades, both in technology performance and cost-competitiveness - and they are increasingly gaining market share. These technology options offer many positive attributes, but also have unique cost/benefit trade-offs, such as land-use competition for bioresources and variability for wind and solar electric generation technologies. This paper presents a brief summary of status, recent progress, some technological highlights for RETs and biofuels, and an analysis of critical issues that must be addressed for RETs to meet a greater share of the global energy requirements and lower GHG emissions.

  18. The status and prospects of renewable energy for combating global warming

    Arent, Douglas J.; Wise, Alison; Gelman, Rachel

    2011-01-01

    Reducing anthropogenic greenhouse gas (GHG) emissions in material quantities, globally, is a critical element in limiting the impacts of global warming. GHG emissions associated with energy extraction and use are a major component of any strategy addressing climate change mitigation. Non-emitting options for electrical power and liquid transportation fuels are increasingly considered key components of an energy system with lower overall environmental impacts. Renewable energy technologies (RETs) as well as biofuels technologies have been accelerating rapidly during the past decades, both in technology performance and cost-competitiveness - and they are increasingly gaining market share. These technology options offer many positive attributes, but also have unique cost/benefit trade-offs, such as land-use competition for bioresources and variability for wind and solar electric generation technologies. This paper presents a brief summary of status, recent progress, some technological highlights for RETs and biofuels, and an analysis of critical issues that must be addressed for RETs to meet a greater share of the global energy requirements and lower GHG emissions.

  19. The Status Quo and Developing Trend Analysis of Global Carbon Finance

    Liu Qian; Wang Yao

    2011-01-01

    This paper gives a systematic view of the new trends of global carbon finance innovation under the challenge of global climate change and in the process of transition to achieve economic growth from "high carbon" to 'low carbon', covering the following aspects: the structure, status quo and developing trend of global carbon market. The paper discusses the innovation in financial organization and service systems and governments' overall guidance and policy support, and draws the conclusion that the world is undergoing massive changes with governments actively responding to carbon finance to embrace the tremendous opportunities for clean energy and climate change in financial industry. To seize the opportunity, a complete and overall carbon finance system of China should be put in the top of the agenda. Given the current tasks of energy conservation and pollution reduction and the growing demand for capital input, China needs to construct an clear of policy guidance, a diversified financia service system, and a multi-approach carbon finance system to intensify and widen the participation of financial industry, to expand financing channels for sustainable economy and spread risks, and finally, work out an inexpensive solution to the realization of China's low carbon target.

  20. Food Insecurity and Mental Health Status: A Global Analysis of 149 Countries.

    Jones, Andrew D

    2017-08-01

    This study sought to determine the association of individual-level food insecurity (FI) with mental health status across all global regions. Cross-sectional data were analyzed in 2016 from the 2014 Gallup World Poll, a series of globally implemented, nationally representative surveys. FI was assessed using the Food Insecurity Experience Scale Survey Module for Individuals, an eight-question psychometric scale reporting individuals' experiences of FI. Individual-level composite indices of mental health, the Negative Experience Index and Positive Experience Index (0-100 scale), were calculated based on responses to five questions of respondents' recent negative and positive experiences, respectively, associated with depression and mental distress. The prevalence of any FI ranged from 18.3% in East Asia to 76.1% in Sub-Saharan Africa. In global analyses (149 countries) using adjusted multiple regression analyses, FI was associated in a dose-response fashion with poorer scores on the mental health indices (coefficient [95% CI]: Negative Experience Index: mild FI, 10.4 [9.5, 11.2]; moderate FI, 17.7 [16.4, 19.0]; severe FI, 24.5 [22.7, 26.3]; Positive Experience Index: mild FI, -8.3 [-9.3, -7.4]; moderate FI, -12.6 [-13.8, -11.3]; severe FI, -16.2 [-17.9, -14.5]). Within-region analyses (11 regions) consistently demonstrated the same trends. FI is associated with poorer mental health and specific psychosocial stressors across global regions independent of SES. The numerous pathways via which FI may contribute to common mental disorders, and the broad social implications of FI linked to cultural norms and self-efficacy, may contribute to the cross-cultural consistency of the findings. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  1. MECP2 promoter methylation and X chromosome inactivation in autism.

    Nagarajan, Raman P; Patzel, Katherine A; Martin, Michelle; Yasui, Dag H; Swanberg, Susan E; Hertz-Picciotto, Irva; Hansen, Robin L; Van de Water, Judy; Pessah, Isaac N; Jiang, Ruby; Robinson, Wendy P; LaSalle, Janine M

    2008-06-01

    Epigenetic mechanisms have been proposed to play a role in the etiology of autism. This hypothesis is supported by the discovery of increased MECP2 promoter methylation associated with decreased MeCP2 protein expression in autism male brain. To further understand the influence of female X chromosome inactivation (XCI) and neighboring methylation patterns on aberrant MECP2 promoter methylation in autism, multiple methylation analyses were peformed on brain and blood samples from individuals with autism. Bisulfite sequencing analyses of a region 0.6 kb upstream of MECP2 in brain DNA samples revealed an abrupt transition from a highly methylated region in both sexes to a region unmethylated in males and subject to XCI in females. Chromatin immunoprecipitation analysis demonstrated that the CCTC-binding factor (CTCF) bound to this transition region in neuronal cells, consistent with a chromatin boundary at the methylation transition. Male autism brain DNA samples displayed a slight increase in methylation in this transition region, suggesting a possible aberrant spreading of methylation into the MECP2 promoter in autism males across this boundary element. In addition, autistic female brain DNA samples showed evidence for aberrant MECP2 promoter methylation as an increase in the number of bisulfite sequenced clones with undefined XCI status for MECP2 but not androgen receptor (AR). To further investigate the specificity of MECP2 methylation alterations in autism, blood DNA samples from females and mothers of males with autism were also examined for XCI skewing at AR, but no significant increase in XCI skewing was observed compared to controls. These results suggest that the aberrant MECP2 methylation in autism brain DNA samples is due to locus-specific rather than global X chromosome methylation changes.

  2. Controlling the HIV/AIDS epidemic: current status and global challenges

    Thorsten eDemberg

    2012-08-01

    Full Text Available This review provides an overview of the current status of the global HIV pandemic and strategies to bring it under control. It updates numerous preventive approaches including behavioral interventions, male circumcision, pre- and post-exposure prophylaxis, vaccines, and microbicides. The manuscript summarizes current anti-retroviral treatment options, their impact in the western world, and difficulties faced by emerging and resource-limited nations in providing and maintaining appropriate treatment regimens. Current clinical and pre-clinical approaches towards a cure for HIV are described, including new drug compounds that target viral reservoirs and gene therapy approaches aimed at altering susceptibility to HIV infection. Recent progress in vaccine development is summarized, including novel approaches and new discoveries.

  3. Assessing Global Marine Biodiversity Status within a Coupled Socio-Ecological Perspective

    Selig, Elizabeth R.; Longo, Catherine; Halpern, Benjamin S.; Best, Benjamin D.; Hardy, Darren; Elfes, Cristiane T.; Scarborough, Courtney; Kleisner, Kristin M.; Katona, Steven K.

    2013-01-01

    People value the existence of a variety of marine species and habitats, many of which are negatively impacted by human activities. The Convention on Biological Diversity and other international and national policy agreements have set broad goals for reducing the rate of biodiversity loss. However, efforts to conserve biodiversity cannot be effective without comprehensive metrics both to assess progress towards meeting conservation goals and to account for measures that reduce pressures so that positive actions are encouraged. We developed an index based on a global assessment of the condition of marine biodiversity using publically available data to estimate the condition of species and habitats within 151 coastal countries. Our assessment also included data on social and ecological pressures on biodiversity as well as variables that indicate whether good governance is in place to reduce them. Thus, our index is a social as well as ecological measure of the current and likely future status of biodiversity. As part of our analyses, we set explicit reference points or targets that provide benchmarks for success and allow for comparative assessment of current conditions. Overall country-level scores ranged from 43 to 95 on a scale of 1 to 100, but countries that scored high for species did not necessarily score high for habitats. Although most current status scores were relatively high, likely future status scores for biodiversity were much lower in most countries due to negative trends for both species and habitats. We also found a strong positive relationship between the Human Development Index and resilience measures that could promote greater sustainability by reducing pressures. This relationship suggests that many developing countries lack effective governance, further jeopardizing their ability to maintain species and habitats in the future. PMID:23593188

  4. Present status of Tomari No.3 unit construction and efforts for preventing global warming

    Ouchi, Tamotsu; Sakai, Ichiro; Makino, Takeshi

    2009-01-01

    Hokkaido Electric Power Company, Inc. (HEPCO) supplies electricity to almost all area of Hokkaido. Its service area accounts for about one-fifth of Japan's area, on the other hand, the population of the service area only accounts for 4.4% of the nation. This means Hokkaido's nature is precious, and one of HEPCO's missions is to protect such environment, with providing stable electricity. Therefore, nuclear power, which does not emit greenhouse effect gas for generation, is becoming more important. HEPCO's operating nuclear power stations are Tomari No.1 unit and No.2 unit. Their generation capacity is 579 MW respectively. Now, No.3 unit is under construction. Its generation capacity is 912 MW and it will be operational in December 2009. In Hokkaido, about one fourth of electricity is now produced by nuclear power, however, after Tomari No.3 is completed, more than 40% of electricity will be produced by nuclear. So, Tomari No.3 unit will contribute stable supply of electricity in the first half of 21st century and prevent global warming in Hokkaido. This paper describes the present status of Tomari No.3 unit construction with major specifications and our efforts to prevent global warming. (author)

  5. Present status of Tomari No.3 unit construction and efforts for preventing global warming

    Ouchi, Tamotsu

    2008-01-01

    Hokkaido Electric Power Company, Inc. (HEPCO) supplies electricity to almost all area of Hokkaido. Its service area accounts for about one-fifth of Japan's area, on the other hand, the population of the service area only accounts for 4.4% of the nation. This means Hokkaido's nature is precious, and one of HEPCO's missions is to protect such environment, with providing stable electricity. Therefore, nuclear power, which does not emit greenhouse effect gas for generation, is becoming more important. HEPCO's operating nuclear power stations are Tomari No.1 unit and No.2 unit. Their generation capacity is 579 MW respectively. Now, No.3 unit is under construction. Its generation capacity is 912 MW and it will be operational in December 2009. In Hokkaido, about one fourth of electricity is now produced by nuclear power, however, after Tomari No.3 is completed, about 40% of electricity will be produced by nuclear. So, Tomari No.3 unit will contribute stable supply of electricity in the first half of 21st century and prevent global warming in Hokkaido. This paper describes the present status of Tomari No.3 unit construction with major specifications and our efforts to prevent global warming. (author)

  6. The global childhood obesity epidemic and the association between socio-economic status and childhood obesity

    Wang, Youfa; Lim, Hyunjung

    2015-01-01

    This paper describes the current prevalence and time trends of childhood obesity worldwide, and the association between childhood obesity and socio-economic status (SES). Childhood obesity has become a global public health crisis. The prevalence is highest in western and industrialized countries, but still low in some developing countries. The prevalence also varies by age and gender. The WHO Americas and eastern Mediterranean regions had higher prevalence of overweight and obesity (30–40%) than the European (20–30%), south-east Asian, western Pacific, and African regions (10–20% in the latter three). A total of 43 million children (35 million in developing countries) were estimated to be overweight or obese; 92 million were at risk of overweight in 2010. The global overweight and obesity prevalence has increased dramatically since 1990, for example in preschool-age children, from approximately 4% in 1990 to 7% in 2010. If this trend continues, the prevalence may reach 9% or 60 million people in 2020. The obesity–SES association varies by gender, age, and country. In general, SES groups with greater access to energy-dense diets (low-SES in industrialized countries and high-SES in developing countries) are at increased risk of being obese than their counterparts. PMID:22724639

  7. THE GLOBAL TANDEM-X DEM: PRODUCTION STATUS AND FIRST VALIDATION RESULTS

    M. Huber

    2012-07-01

    Full Text Available The TanDEM-X mission will derive a global digital elevation model (DEM with satellite SAR interferometry. Two radar satellites (TerraSAR-X and TanDEM-X will map the Earth in a resolution and accuracy with an absolute height error of 10m and a relative height error of 2m for 90% of the data. In order to fulfill the height requirements in general two global coverages are acquired and processed. Besides the final TanDEM-X DEM, an intermediate DEM with reduced accuracy is produced after the first coverage is completed. The last step in the whole workflow for generating the TanDEM-X DEM is the calibration of remaining systematic height errors and the merge of single acquisitions to 1°x1° DEM tiles. In this paper the current status of generating the intermediate DEM and first validation results based on GPS tracks, laser scanning DEMs, SRTM data and ICESat points are shown for different test sites.

  8. DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia

    Borssén, Magnus; Haider, Zahra; Landfors, Mattias

    2016-01-01

    . In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T......: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD ≥0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ...... regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. CONCLUSIONS: CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further...

  9. Gene transcription profiles, global DNA methylation and potential transgenerational epigenetic effects related to Zn exposure history in Daphnia magna

    Vandegehuchte, Michiel B.; De Coninck, Dieter; Vandenbrouck, Tine; De Coen, Wim M.; Janssen, Colin R.

    2010-01-01

    A reduced level of DNA methylation has recently been described in both Zn-exposed and non-exposed offspring of Daphnia magna exposed to Zn. The hypothesis examined in this study is that DNA hypomethylation has an effect on gene transcription. A second hypothesis is that accumulative epigenetic effects can affect gene transcription in non-exposed offspring from parents with an exposure history of more than one generation. Transcriptional gene regulation was studied with a cDNA microarray. In the exposed and non-exposed hypomethylated daphnids, a large proportion of common genes were similarly up- or down-regulated, indicating a possible effect of the DNA hypomethylation. Two of these genes can be mechanistically involved in DNA methylation reduction. The similar transcriptional regulation of two and three genes in the F 0 and F 1 exposed daphnids on one hand and their non-exposed offspring on the other hand, could be the result of a one-generation temporary transgenerational epigenetic effect, which was not accumulative. - Zn-induced DNA hypomethylation is related to gene transcription in Daphnia magna and Zn exposure potentially induced limited temporary transgenerational effects on gene transcription.

  10. Parenting, Socioeconomic Status Risk, and Later Young Adult Health: Exploration of Opposing Indirect Effects via DNA Methylation

    Beach, Steven R. H.; Lei, Man-Kit; Brody, Gene H.; Kim, Sangjin; Barton, Allen W.; Dogan, Meesha V.; Philibert, Robert A.

    2016-01-01

    A sample of 398 African American youth, residing in rural counties with high poverty and unemployment, were followed from ages 11 to 19. Protective parenting was associated with better health, whereas elevated socioeconomic status (SES) risk was associated with poorer health at age 19. Genome-wide epigenetic variation assessed in young adulthood…

  11. Intrauterine Reprogramming of the Polycystic Ovary Syndrome: Evidence from a Pilot Study of Cord Blood Global Methylation Analysis

    Luca Lambertini

    2017-12-01

    Full Text Available Polycystic ovary syndrome (PCOS affects 5–15% of women. PCOS is a heterogeneous disorder displaying endocrine, metabolic, and reproductive dysfunction and cardiovascular risk manifestations. Evidence of heritability exists, but only a portion of the genetic transmission has been identified by genome-wide association studies and linkage studies, suggesting epigenetic phenomena may play a role. Evidence implicates intrauterine influences in the genesis of PCOS. This was a pilot study that aimed at identifying an epigenetic PCOS reprogramming signature by profiling the methylation of the DNA extracted from umbilical cord blood (UCB from 12 subjects undergoing in vitro fertilization. Six subjects were anovulatory PCOS women diagnosed by Rotterdam criteria and six ovulatory non-PCOS women matched for age and body mass index. UCB was collected at delivery of the placenta; the DNA was extracted and submitted to methylation analysis. A differential methylation picture of prevalent hypomethylation affecting 918 genes was detected. Of these, 595 genes (64.8% carried single or multiple hypomethylated CpG dinucleotides and 323 genes (35.2% single or multiple hypermethylated CpG dinucleotides. The Ingenuity Pathway Analysis (IPA online platform enlisted 908 of the 918 input genes and clustered 794 of them into 21 gene networks. Key features of the primary networks scored by IPA included carbohydrate and lipid metabolism, neurotransmitter signaling, cardiovascular system development and function, glycosaminoglycan signaling regulation and control of amino acid biosynthesis. Central to the network activities were genes controlling hormonal regulation (ESR1, mitochondrial activity (APP, PARK2, and glucose metabolism (INS. Regulatory pathways such as G-protein coupled receptor signaling, inositol metabolism, and inflammatory response were also highlighted. These data suggested the existence of a putative “PCOS epigenomic superpathway” with three main

  12. Proceedings of the 2015 international summit on fibropapillomatosis: Global status, trends, and population impacts

    Hargrove, Stacy A.; Work, Thierry M.; Brunson, Shandell; Foley, Allen M.; Balazs, George H.

    2016-01-01

    The 2015 International Summit on Fibropapillomatosis (FP) was convened in Honolulu, Hawaii June 11-14, 2015. Scientists from around the world were invited to present results from sea turtle monitoring and research programs as they relate to the global status, trends, and population impacts of FP on green turtles. The participants engaged in discussions that resulted in the following conclusions: 1.Globally, FP has long been present in wild sea turtle populations the earliest mention was in the late 1800s in the Florida Keys. 2.FP primarily affects medium-sized immature turtles in coastal foraging pastures. 3.Expression of FP differs across ocean basins and to some degree within basins. Turtles in the Southeast US, Caribbean, Brazil, and Australia rarely have oral tumors (inside the mouth cavity), whereas they are common and often severe in Hawaii. Internal tumors (on vital organs) occur in the Atlantic and Hawaii, but only rarely in Australia. Liver tumors are common in Florida but not in Hawaii. 4.Recovery from FP through natural processes, when the affliction is not severe, has been documented in wild populations globally. 5.FP causes reduced survivorship, but documented mortality rates in Australia and Hawaii are low. The mortality impact of FP is not currently exceeding population growth rates in some intensively monitored populations (e.g., Florida, Hawaii) as evidenced by increasing nesting trends despite the incidence of FP in immature foraging populations. 6.Pathogens, hosts, and potential disease and environmental cofactors have the capacity to change; while we are having success now, there needs to be continued monitoring to detect changes in the distribution, occurrence, and severity of the disease. 7.While we do not have clear evidence to provide the direct link, globally, the preponderance of sites with a high frequency of FP tumors are areas with some degree of degradation resulting from altered watersheds. Watershed management and responsible coastal

  13. Alkylating agent methyl methanesulfonate (MMS) induces a wave of global protein hyperacetylation: Implications in cancer cell death

    Lee, Min-Young; Kim, Myoung-Ae; Kim, Hyun-Ju; Bae, Yoe-Sik; Park, Joo-In; Kwak, Jong-Young; Chung, Jay H.; Yun, Jeanho

    2007-01-01

    Protein acetylation modification has been implicated in many cellular processes but the direct evidence for the involvement of protein acetylation in signal transduction is very limited. In the present study, we found that an alkylating agent methyl methanesulfonate (MMS) induces a robust and reversible hyperacetylation of both cytoplasmic and nuclear proteins during the early phase of the cellular response to MMS. Notably, the acetylation level upon MMS treatment was strongly correlated with the susceptibility of cancer cells, and the enhancement of MMS-induced acetylation by histone deacetylase (HDAC) inhibitors was shown to increase the cellular susceptibility. These results suggest protein acetylation is important for the cell death signal transduction pathway and indicate that the use of HDAC inhibitors for the treatment of cancer is relevant

  14. Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia.

    Magnus Borssén

    Full Text Available BACKGROUND: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. DESIGN AND METHODS: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43 using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32. RESULTS: Based on CpG island methylator phenotype (CIMP, T-ALL samples were subgrouped as CIMP+ (high methylation and CIMP- (low methylation. CIMP- T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. CONCLUSIONS: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.

  15. Anti-N-Methyl-d-Aspartate Receptor Encephalitis as an Unusual Cause of Altered Mental Status in the Emergency Department.

    Weaver, Michael; Griffey, Richard T

    2016-08-01

    Anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis is a newly identified form of encephalitis whose incidence is on the rise. Awareness of this condition and symptom recognition are key to early diagnosis and prompt treatment, which may alter the course of the disease. A 35-year-old woman presented to our Emergency Department (ED) with lethargy, bizarre behavior, agitation, confusion, memory deficits, and word-finding difficulties. Her symptoms and evaluation were potentially consistent with a primary psychiatric disorder, but the absence of frank psychosis and presence of neurologic features related to memory and cognition prompted other considerations. In the ED we performed a lumbar puncture, and in addition to routine studies, ordered anti-NMDAR antibody screening. The screening studies returned positive, leading to treatment with glucocorticoids and intravenous immune globulin and resulting in improvement to near baseline function. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although anti-NMDAR encephalitis is relatively uncommon, reports of this previously unrecognized condition are increasing, with an unclear true incidence of disease. Emergency providers should consider this diagnosis in their differential for patients presenting with new neuropsychiatric symptoms, particularly in young women. Prompt treatment leads to near complete neurologic recovery in 75% of patients, whereas delays in diagnosis and treatment may be associated with worse outcomes including death. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Clinical global assessment of nutritional status as predictor of mortality in chronic kidney disease patients.

    Dai, Lu; Mukai, Hideyuki; Lindholm, Bengt; Heimbürger, Olof; Barany, Peter; Stenvinkel, Peter; Qureshi, Abdul Rashid

    2017-01-01

    The value of subjective global assessment (SGA) as nutritional assessor of protein-energy wasting (PEWSGA) in chronic kidney disease (CKD) patients depends on its mortality predictive capacity. We investigated associations of PEWSGA with markers of nutritional status and all-cause mortality in CKD patients. In 1031 (732 CKD1-5 non-dialysis and 299 dialysis) patients, SGA and body (BMI), lean (LBMI) and fat (FBMI) body mass indices, % handgrip strength (% HGS), serum albumin, and high sensitivity C-reactive protein (hsCRP) were examined at baseline. The five-year all-cause mortality predictive strength of baseline PEWSGA and during follow-up were investigated. PEWSGA was present in 2% of CKD1-2, 16% of CKD3-4, 31% of CKD5 non-dialysis and 44% of dialysis patients. Patients with PEWSGA (n = 320; 31%) had higher hsCRP and lower BMI, LBMI, FBMI, %HGS and serum albumin. But, using receiver operating characteristics-derived cutoffs, these markers could not classify (by kappa statistic) or explain variations of (by multinomial logistic regression analysis) presence of PEWSGA. In generalized linear models, SGA independently predicted mortality after adjustments of multiple confounders (RR: 1.17; 95% CI: 1.11-1.23). Among 323 CKD5 patients who were re-assessed after median 12.6 months, 222 (69%) remained well-nourished, 37 (11%) developed PEWSGA de novo, 40 (12%) improved while 24 (8%) remained with PEWSGA. The latter independently predicted mortality (RR: 1.29; 95% CI: 1.13-1.46). SGA, a valid assessor of nutritional status, is an independent predictor of all-cause mortality both in CKD non-dialysis and dialysis patients that outperforms non-composite nutritional markers as prognosticator.

  17. Identification of Differentially Methylated Sites with Weak Methylation Effects

    Hong Tran

    2018-02-01

    Full Text Available Deoxyribonucleic acid (DNA methylation is an epigenetic alteration crucial for regulating stress responses. Identifying large-scale DNA methylation at single nucleotide resolution is made possible by whole genome bisulfite sequencing. An essential task following the generation of bisulfite sequencing data is to detect differentially methylated cytosines (DMCs among treatments. Most statistical methods for DMC detection do not consider the dependency of methylation patterns across the genome, thus possibly inflating type I error. Furthermore, small sample sizes and weak methylation effects among different phenotype categories make it difficult for these statistical methods to accurately detect DMCs. To address these issues, the wavelet-based functional mixed model (WFMM was introduced to detect DMCs. To further examine the performance of WFMM in detecting weak differential methylation events, we used both simulated and empirical data and compare WFMM performance to a popular DMC detection tool methylKit. Analyses of simulated data that replicated the effects of the herbicide glyphosate on DNA methylation in Arabidopsis thaliana show that WFMM results in higher sensitivity and specificity in detecting DMCs compared to methylKit, especially when the methylation differences among phenotype groups are small. Moreover, the performance of WFMM is robust with respect to small sample sizes, making it particularly attractive considering the current high costs of bisulfite sequencing. Analysis of empirical Arabidopsis thaliana data under varying glyphosate dosages, and the analysis of monozygotic (MZ twins who have different pain sensitivities—both datasets have weak methylation effects of <1%—show that WFMM can identify more relevant DMCs related to the phenotype of interest than methylKit. Differentially methylated regions (DMRs are genomic regions with different DNA methylation status across biological samples. DMRs and DMCs are essentially the same

  18. Assessing nutritional status in cancer: role of the Patient-Generated Subjective Global Assessment.

    Jager-Wittenaar, Harriët; Ottery, Faith D

    2017-09-01

    The Scored Patient-Generated Subjective Global Assessment (PG-SGA) is used internationally as the reference method for proactive risk assessment (screening), assessment, monitoring and triaging for interventions in patients with cancer. This review aims to explain the rationale behind and data supporting the PG-SGA, and to provide an overview of recent developments in the utilization of the PG-SGA and the PG-SGA Short Form. The PG-SGA was designed in the context of a paradigm known as 'anabolic competence'. Uniquely, the PG-SGA evaluates the patient's status as a dynamic rather than static process. The PG-SGA has received new attention, particularly as a screening instrument for nutritional risk or deficit, identifying treatable impediments and guiding patients and professionals in triaging for interdisciplinary interventions. The international use of the PG-SGA indicates a critical need for high-quality and linguistically validated translations of the PG-SGA. As a 4-in-1 instrument, the PG-SGA can streamline clinic work flow and improve the quality of interaction between the clinician and the patient. The availability of multiple high-quality language versions of the PG-SGA enables the inclusion of the PG-SGA in international multicenter studies, facilitating meta-analysis and benchmarking across countries.

  19. Global ex-situ crop diversity conservation and the Svalbard Global Seed Vault: assessing the current status.

    Ola T Westengen

    Full Text Available Ex-situ conservation of crop diversity is a global concern, and the development of an efficient and sustainable conservation system is a historic priority recognized in international law and policy. We assess the completeness of the safety duplication collection in the Svalbard Global Seed Vault with respect to data on the world's ex-situ collections as reported by the Food and Agriculture Organization of the United Nations. Currently, 774,601 samples are deposited at Svalbard by 53 genebanks. We estimate that more than one third of the globally distinct accessions of 156 crop genera stored in genebanks as orthodox seeds are conserved in the Seed Vault. The numbers of safety duplicates of Triticum (wheat, Sorghum (sorghum, Pennisetum (pearl millet, Eleusine (finger millet, Cicer (chickpea and Lens (lentil exceed 50% of the estimated numbers of distinct accessions in global ex-situ collections. The number of accessions conserved globally generally reflects importance for food production, but there are significant gaps in the safety collection at Svalbard in some genera of high importance for food security in tropical countries, such as Amaranthus (amaranth, Chenopodium (quinoa, Eragrostis (teff and Abelmoschus (okra. In the 29 food-crop genera with the largest number of accessions stored globally, an average of 5.5 out of the ten largest collections is already represented in the Seed Vault collection or is covered by existing deposit agreements. The high coverage of ITPGRFA Annex 1 crops and of those crops for which there is a CGIAR mandate in the current Seed Vault collection indicates that existence of international policies and institutions are important determinants for accessions to be safety duplicated at Svalbard. As a back-up site for the global conservation system, the Seed Vault plays not only a practical but also a symbolic role for enhanced integration and cooperation for conservation of crop diversity.

  20. Global ex-situ crop diversity conservation and the Svalbard Global Seed Vault: assessing the current status.

    Westengen, Ola T; Jeppson, Simon; Guarino, Luigi

    2013-01-01

    Ex-situ conservation of crop diversity is a global concern, and the development of an efficient and sustainable conservation system is a historic priority recognized in international law and policy. We assess the completeness of the safety duplication collection in the Svalbard Global Seed Vault with respect to data on the world's ex-situ collections as reported by the Food and Agriculture Organization of the United Nations. Currently, 774,601 samples are deposited at Svalbard by 53 genebanks. We estimate that more than one third of the globally distinct accessions of 156 crop genera stored in genebanks as orthodox seeds are conserved in the Seed Vault. The numbers of safety duplicates of Triticum (wheat), Sorghum (sorghum), Pennisetum (pearl millet), Eleusine (finger millet), Cicer (chickpea) and Lens (lentil) exceed 50% of the estimated numbers of distinct accessions in global ex-situ collections. The number of accessions conserved globally generally reflects importance for food production, but there are significant gaps in the safety collection at Svalbard in some genera of high importance for food security in tropical countries, such as Amaranthus (amaranth), Chenopodium (quinoa), Eragrostis (teff) and Abelmoschus (okra). In the 29 food-crop genera with the largest number of accessions stored globally, an average of 5.5 out of the ten largest collections is already represented in the Seed Vault collection or is covered by existing deposit agreements. The high coverage of ITPGRFA Annex 1 crops and of those crops for which there is a CGIAR mandate in the current Seed Vault collection indicates that existence of international policies and institutions are important determinants for accessions to be safety duplicated at Svalbard. As a back-up site for the global conservation system, the Seed Vault plays not only a practical but also a symbolic role for enhanced integration and cooperation for conservation of crop diversity.

  1. Renewables 2018 - Global status report. A comprehensive annual overview of the state of renewable energy. Advancing the global renewable energy transition - Highlights of the REN21 Renewables 2018 Global Status Report in perspective

    Sawin, Janet L.; Sverrisson, Freyr; Rutovitz, Jay; Dwyer, Scott; Teske, Sven; Murdock, Hannah E.; Adib, Rana; Guerra, Flavia; Murdock, Hannah E.; Blanning, Linh H.; Guerra, Flavia; Hamirwasia, Vibhushree; Misra, Archita; Satzinger, Katharina; Williamson, Laura E.; Lie, Mimi; Nilsson, Anna; Aberg, Emma; Weckend, Stephanie; Wuester, Henning; Ferroukhi, Rabia; Garcia, Celia; Khalid, Arslan; Renner, Michael; Taylor, Michael; Epp, Barbel; Seyboth, Kristin; Skeen, Jonathan; Kamiya, George; Munuera, Luis; Appavou, Fabiani; Brown, Adam; Kondev, Bozhil; Musolino, Evan; Brown, Adam; Mastny, Lisa; Arris, Lelani

    2018-06-01

    REN21's Renewables 2018 Global Status Report presents developments and trends through the end of 2017, as well as observed trends from early 2018 where available. Renewable power accounted for 70% of net additions to global power generating capacity in 2017, the largest increase in renewable power capacity in modern history, according to REN21's Renewables 2018 Global Status Report (GSR). But the heating, cooling and transport sectors - which together account for about four-fifths of global final energy demand - continue to lag far behind the power sector. The GSR, published today, is the most comprehensive annual overview of the state of renewable energy worldwide. New solar photovoltaic (PV) capacity reached record levels: Solar PV additions were up 29% relative to 2016, to 98 GW. More solar PV generating capacity was added to the electricity system than net capacity additions of coal, natural gas and nuclear power combined. Wind power also drove the uptake of renewables with 52 GW added globally. Investment in new renewable power capacity was more than twice that of net, new fossil fuel and nuclear power capacity combined, despite large, ongoing subsidies for fossil fuel generation. More than two-thirds of investments in power generation were in renewables in 2017, thanks to their increasing cost-competitiveness - and the share of renewables in the power sector is expected to only continue to rise. Investment in renewables was regionally concentrated: China, Europe and the United States accounted for nearly 75% of global investment in renewables in 2017. However, when measured per unit of gross domestic product (GDP), the Marshall Islands, Rwanda, the Solomon Islands, Guinea Bissau, and many other developing countries are investing as much as or more in renewables than developed and emerging economies. Both energy demand and energy-related CO 2 emissions rose substantially for the first time in four years. Energy-related CO 2 emissions rose by 1

  2. Atmospheric concentrations and trends of poly- and perfluoroalkyl substances (PFAS) and volatile methyl siloxanes (VMS) over 7 years of sampling in the Global Atmospheric Passive Sampling (GAPS) network.

    Rauert, Cassandra; Shoieb, Mahiba; Schuster, Jasmin K; Eng, Anita; Harner, Tom

    2018-07-01

    Poly- and per-fluoroalkyl substances (PFAS) and volatile methyl siloxanes (VMS) were monitored at 21 sites in the Global Atmospheric Passive Sampling (GAPS) Network. Atmospheric concentrations previously reported from 2009 were compared to concentrations measured at these sites in 2013 and 2015, to assess trends over 7 years of monitoring. Concentrations of the fluorotelomer alcohols (FTOHs) and fluorinated sulfonamides and sulfonamidoethanols (FOSAs and FOSEs) were stable at these sites from 2009 to 2015 with no significant difference (p > 0.05) in concentrations. Elevated concentrations of all the neutral PFAS were detected at the urban sites as compared to the polar/background sites. The perfluorosulfonic acids (PFSAs), meanwhile, saw a significant increase (p  0.05). Concentrations of the PFSAs and the PFCAs were similar at all location types, showing the global reach of these persistent compounds. Concentrations of the cyclic VMS (cVMS) were at least an order of magnitude higher than the linear VMS (lVMS) and the PFAS. Octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6) saw a weak significant increase in concentrations from 2009 to 2013 (p < 0.05), however, hexamethylcyclotrisiloxane (D3) had a strong significant decrease in concentrations from 2009 to 2015 (p < 0.01). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Socioeconomic status and tobacco consumption among adolescents: a multilevel analysis of Argentina's Global Youth Tobacco Survey.

    Linetzky, Bruno; Mejia, Raul; Ferrante, Daniel; De Maio, Fernando G; Diez Roux, Ana V

    2012-09-01

    The relationship between poverty and tobacco consumption among adolescents has not been extensively studied, and what evidence exists has come almost entirely from developed countries. Moreover, the impact of contextual factors--such as school-level poverty--remains unclear. We obtained information about smoking behavior from the Global Youth Tobacco Survey in Argentina in 2007. School-level characteristics were derived by matching schools to census areas from the 2001 Census. Additional school-level information was obtained from the Ministry of Education. Random intercept models were used to evaluate the associations of school-level variables (poverty in the census area of the school, school receipt of social assistance, and public or private status) with current smoking, intention to quit, secondhand smoke exposure outside the home, support for smoke-free laws, purchase of single cigarettes among smokers, and susceptibility to smoking in 5 years among nonsmokers. After controlling for age and sex, students attending schools receiving social assistance were more likely to smoke (odds ratio [OR] 1.35, 95% CI 1.02-1.80) and to purchase loose cigarettes (OR 1.66, 95% CI 1.08-2.54), whereas school poverty was significantly associated with secondhand smoke exposure (OR 1.27, 95% CI 1.04-1.58). This study shows that an association exists between unfavorable contextual school characteristics and tobacco consumption and related measures among youth in Argentina. Efforts to prevent smoking may need to address the school-level factors that place youth at higher risk.

  4. The impact of hereditary multiple exostoses on quality of life, satisfaction, global health status, and pain.

    D'Ambrosi, Riccardo; Ragone, Vincenza; Caldarini, Camilla; Serra, Nicola; Usuelli, Federico Giuseppe; Facchini, Renato Mario

    2017-02-01

    The aim of the study was to evaluate quality of life (QOL), global health status, pain, and level of satisfaction in patients with hereditary multiple exostoses (HME), and to correlate the association between the severity of diseases and age, sex, number of surgical procedures, and number of exostoses. The data of 50 patients with HME were retrospectively evaluated and recorded. QOL was evaluated with the Short-Form Health Survey (SF-12) questionnaire, the 12-Item General Health Questionnaire (GHQ-12), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF); intensity of pain was measured using the visual analogue scale (VAS). The association of age, gender, pain, quality of life, number of exostoses, and number of surgical procedures were evaluated and correlated. Mean number of exostoses in our patient's cohort resulted 18.12 ± 8.60, and every patient underwent to a mean of 5.62 ± 5.74 surgical procedures for the exostoses. Mean VAS resulted 5.16 ± 2.90. Considering SF-12, mental (MCS) and physical (PCS) component resulted, respectively, 45.36 ± 10.76 and 38.73 ± 11.09, while GHQ-12 and Q-LES-Q-SF were 15.48 ± 4.70 and 45.28 ± 9.55, respectively. We found a significant positive correlation between the number of exostoses and the number of surgical procedures (p life as measured by the MCS and PCS scores similar to the disability associated with osteoarthritis in the mental component and tumors or diabetes as regards the physical component. Moreover, we found no difference in patients' quality of life as regards number of exostoses, age, and surgical procedure, but we found that women have a worse response as regards the psychological side than men.

  5. The Global Precipitation Measurement (GPM) Mission: Overview and U.S. Status

    Hou, Arthur Y.; Azarbarzin, Ardeshir A.; Kakar, Ramesh K.; Neeck, Steven

    2011-01-01

    -track scanning humidity sounders on operational satellites such as the National Polar-orbiting Operational Environmental Satellite System (NPOESS) Preparatory Project (NPP), POES, the NASA/NOAA Joint Polar Satellite System (JPSS), and EUMETSAT MetOp satellites. Data from Chinese and Russian microwave radiometers may also become available through international collaboration under the auspices of the Committee on Earth Observation Satellites (CEOS) and Group on Earth Observations (GEO). The current generation of global rainfall products combines observations from a network of uncoordinated satellite missions using a variety of merging techniques. Relative to current data products, GPM's "nextgeneration" precipitation products will be characterized by: (1) more accurate instantaneous precipitation estimate (especially for light rain and cold-season solid precipitation), (2) more frequent sampling by an expanded constellation of microwave radiometers including operational humidity sounders over land, (3) intercalibrated microwave brightness temperatures from constellation radiometers within a unified framework, and (4) physical-based precipitation retrievals from constellation radiometers using a common a priori hydrometeor database constrained by combined radar/radiometer measurements provided by the GPM Core Observatory. An overview of the GPM mission concept, the U.S. GPM program status and updates on international science collaborations on GPM will be presented.

  6. Double-labelling immunohistochemistry for MGMT and a “cocktail” of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours

    2013-01-01

    Background Our aim was to develop a new protocol for MGMT immunohistochemistry with good agreement between observers and good correlation with molecular genetic tests of tumour methylation. We examined 40 primary brain tumours (30 glioblastomas and 10 oligodendroglial tumours) with our new technique, namely double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumour antigens (CD34, CD45 and CD68). We compared the results with single-labelling immunohistochemistry for MGMT and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA, a recognised molecular genetic technique which we applied as the gold-standard for the methylation status). Results Double-labelling immunohistochemistry for MGMT produced a visual separation of tumourous and non-tumourous elements on the same histological slide, making it quick and easy to determine whether tumour cell nuclei were MGMT-positive or MGMT-negative (and thereby infer the methylation status of the tumour). We found good agreement between observers (kappa 0.76) and within observer (kappa 0.84). Furthermore, double-labelling showed good specificity (80%), sensitivity (73.33%), positive predictive value (PPV, 83.33%) and negative predictive value (NPV, 68.75%) compared to MS-MLPA. Double-labelling was quicker and easier to assess than single-labelling and it outperformed quantitative computerised image analysis of MGMT single-labelling in terms of sensitivity, specificity, PPV and NPV. Conclusions Double-labelling immunohistochemistry for MGMT and a cocktail of non-tumourous elements provides a "one look" method for determining whether tumour cell nuclei are MGMT-positive or MGMT-negative. This can be used to infer the methylation status of the tumour. There is good observer agreement and good specificity, sensitivity, PPV and NPV compared to a molecular gold-standard. PMID:24252243

  7. Double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours.

    Burke, Elinor; Grobler, Mariana; Elderfield, Kay; Bond, Frances; Crocker, Matthew; Taylor, Rohan; Bridges, Leslie R

    2013-06-10

    Our aim was to develop a new protocol for MGMT immunohistochemistry with good agreement between observers and good correlation with molecular genetic tests of tumour methylation. We examined 40 primary brain tumours (30 glioblastomas and 10 oligodendroglial tumours) with our new technique, namely double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumour antigens (CD34, CD45 and CD68). We compared the results with single-labelling immunohistochemistry for MGMT and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA, a recognised molecular genetic technique which we applied as the gold-standard for the methylation status). Double-labelling immunohistochemistry for MGMT produced a visual separation of tumourous and non-tumourous elements on the same histological slide, making it quick and easy to determine whether tumour cell nuclei were MGMT-positive or MGMT-negative (and thereby infer the methylation status of the tumour). We found good agreement between observers (kappa 0.76) and within observer (kappa 0.84). Furthermore, double-labelling showed good specificity (80%), sensitivity (73.33%), positive predictive value (PPV, 83.33%) and negative predictive value (NPV, 68.75%) compared to MS-MLPA. Double-labelling was quicker and easier to assess than single-labelling and it outperformed quantitative computerised image analysis of MGMT single-labelling in terms of sensitivity, specificity, PPV and NPV. Double-labelling immunohistochemistry for MGMT and a cocktail of non-tumourous elements provides a "one look" method for determining whether tumour cell nuclei are MGMT-positive or MGMT-negative. This can be used to infer the methylation status of the tumour. There is good observer agreement and good specificity, sensitivity, PPV and NPV compared to a molecular gold-standard.

  8. Aberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients.

    Laing, M E

    2010-08-01

    Changes in genomic DNA methylation associated with cancer include global DNA hypomethylation and gene-specific hyper- or hypomethylation. We have previously identified a genetic variant in the MTHFR gene involved in the methylation pathway which confers risk for the development of squamous cell carcinoma (SCC) in renal transplant patients. This genetic variant has also been discovered to confer SCC risk in nontransplant patients with low folate status.

  9. Influence of adjunctive classical homeopathy on global health status and subjective wellbeing in cancer patients - A pragmatic randomized controlled trial.

    Frass, Michael; Friehs, Helmut; Thallinger, Christiane; Sohal, Narinderjit Kaur; Marosi, Christine; Muchitsch, Ilse; Gaertner, Katharina; Gleiss, Andreas; Schuster, Ernst; Oberbaum, Menachem

    2015-06-01

    The use of complementary and alternative medicine has increased over the past decade. The aim of this study was to evaluate whether homeopathy influenced global health status and subjective wellbeing when used as an adjunct to conventional cancer therapy. In this pragmatic randomized controlled trial, 410 patients, who were treated by standard anti-neoplastic therapy, were randomized to receive or not receive classical homeopathic adjunctive therapy in addition to standard therapy. The study took place at the Medical University Vienna, Department of Medicine I, Clinical Division of Oncology. The main outcome measures were global health status and subjective wellbeing as assessed by the patients. At each of three visits (one baseline, two follow-up visits), patients filled in two different questionnaires. 373 patients yielded at least one of three measurements. The improvement of global health status between visits 1 and 3 was significantly stronger in the homeopathy group by 7.7 (95% CI 2.3-13.0, p=0.005) when compared with the control group. A significant group difference was also observed with respect to subjective wellbeing by 14.7 (95% CI 8.5-21.0, p<0.001) in favor of the homeopathic as compared with the control group. Control patients showed a significant improvement only in subjective wellbeing between their first and third visits. Results suggest that the global health status and subjective wellbeing of cancer patients improve significantly when adjunct classical homeopathic treatment is administered in addition to conventional therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Transcriptome analysis of an mvp mutant reveals important changes in global gene expression and a role for methyl jasmonate in vernalization and flowering in wheat.

    Diallo, Amadou Oury; Agharbaoui, Zahra; Badawi, Mohamed A; Ali-Benali, Mohamed Ali; Moheb, Amira; Houde, Mario; Sarhan, Fathey

    2014-06-01

    The einkorn wheat mutant mvp-1 (maintained vegetative phase 1) has a non-flowering phenotype caused by deletions including, but not limited to, the genes CYS, PHYC, and VRN1. However, the impact of these deletions on global gene expression is still unknown. Transcriptome analysis showed that these deletions caused the upregulation of several pathogenesis-related (PR) and jasmonate-responsive genes. These results suggest that jasmonates may be involved in flowering and vernalization in wheat. To test this hypothesis, jasmonic acid (JA) and methyl jasmonate (MeJA) content in mvp and wild-type plants was measured. The content of JA was comparable in all plants, whereas the content of MeJA was higher by more than 6-fold in mvp plants. The accumulation of MeJA was also observed in vernalization-sensitive hexaploid winter wheat during cold exposure. This accumulation declined rapidly once plants were deacclimated under floral-inductive growth conditions. This suggests that MeJA may have a role in floral transition. To confirm this result, we treated vernalization-insensitive spring wheat with MeJA. The treatment delayed flowering with significant downregulation of both TaVRN1 and TaFT1 genes. These data suggest a role for MeJA in modulating vernalization and flowering time in wheat. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  11. Methylation-Sensitive Amplification Length Polymorphism (MS-AFLP) Microarrays for Epigenetic Analysis of Human Genomes.

    Alonso, Sergio; Suzuki, Koichi; Yamamoto, Fumiichiro; Perucho, Manuel

    2018-01-01

    Somatic, and in a minor scale also germ line, epigenetic aberrations are fundamental to carcinogenesis, cancer progression, and tumor phenotype. DNA methylation is the most extensively studied and arguably the best understood epigenetic mechanisms that become altered in cancer. Both somatic loss of methylation (hypomethylation) and gain of methylation (hypermethylation) are found in the genome of malignant cells. In general, the cancer cell epigenome is globally hypomethylated, while some regions-typically gene-associated CpG islands-become hypermethylated. Given the profound impact that DNA methylation exerts on the transcriptional profile and genomic stability of cancer cells, its characterization is essential to fully understand the complexity of cancer biology, improve tumor classification, and ultimately advance cancer patient management and treatment. A plethora of methods have been devised to analyze and quantify DNA methylation alterations. Several of the early-developed methods relied on the use of methylation-sensitive restriction enzymes, whose activity depends on the methylation status of their recognition sequences. Among these techniques, methylation-sensitive amplification length polymorphism (MS-AFLP) was developed in the early 2000s, and successfully adapted from its original gel electrophoresis fingerprinting format to a microarray format that notably increased its throughput and allowed the quantification of the methylation changes. This array-based platform interrogates over 9500 independent loci putatively amplified by the MS-AFLP technique, corresponding to the NotI sites mapped throughout the human genome.

  12. Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer.

    White-Al Habeeb, Nicole M A; Ho, Linh T; Olkhov-Mitsel, Ekaterina; Kron, Ken; Pethe, Vaijayanti; Lehman, Melanie; Jovanovic, Lidija; Fleshner, Neil; van der Kwast, Theodorus; Nelson, Colleen C; Bapat, Bharati

    2014-09-15

    Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2'-deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

  13. Globalization

    Tulio Rosembuj

    2006-12-01

    Full Text Available There is no singular globalization, nor is the result of an individual agent. We could start by saying that global action has different angles and subjects who perform it are different, as well as its objectives. The global is an invisible invasion of materials and immediate effects.

  14. Globalization

    Tulio Rosembuj

    2006-01-01

    There is no singular globalization, nor is the result of an individual agent. We could start by saying that global action has different angles and subjects who perform it are different, as well as its objectives. The global is an invisible invasion of materials and immediate effects.

  15. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 1 - Overview of Global Status and Research Needs.

    Knight-Jones, T J D; Robinson, L; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    The Global Foot-and-mouth disease (FMD) Research Alliance periodically reviews the state of FMD research to assess progress and to identify new priorities. In this supplement we provide an update of global FMD research, comprising (i) this overview paper, which includes background information with key findings, and papers covering (ii) epidemiology, wildlife and economics, (iii) vaccines, (iv) diagnostics, (v) biotherapeutics and disinfectants, (vi) immunology and (vii) pathogenesis and molecular biology. FMD research publications were reviewed (2011-2015) and activity updates were obtained from 33 FMD research institutes from around the world. Although a continual threat, FMD has been effectively controlled in much of the world using existing tools. However, control remains a challenge in most developing countries, where little has been done to understand the ongoing burden of FMD. More research is needed to support control in endemically infected countries, particularly robust field studies. Traditional FMD vaccines have several limitations including short duration and spectrum of protection, cold chain requirements, and the costs and biosecurity risks associated with vaccine production. Significant progress has been made in the development of novel vaccine candidates, particularly in the use of recombinant vaccines and virus-like particles as an alternative to traditional inactivated whole virus vaccines. Continued investment is needed to turn these developments into improved vaccines produced at scale. Increased knowledge of cellular and mucosal immunity would benefit vaccine development, as would further advances in our ability to enhance vaccine capsid stability. Developments in molecular biology and phylogenetics underlie many of the recent advances in FMD research, including improved vaccines and diagnostics, and improved understanding of FMD epidemiology. Tools for genetic analyses continue to become both more powerful and more affordable enabling them to

  16. Histone Lysine Methylation and Neurodevelopmental Disorders

    Jeong-Hoon Kim

    2017-06-01

    Full Text Available Methylation of several lysine residues of histones is a crucial mechanism for relatively long-term regulation of genomic activity. Recent molecular biological studies have demonstrated that the function of histone methylation is more diverse and complex than previously thought. Moreover, studies using newly available genomics techniques, such as exome sequencing, have identified an increasing number of histone lysine methylation-related genes as intellectual disability-associated genes, which highlights the importance of accurate control of histone methylation during neurogenesis. However, given the functional diversity and complexity of histone methylation within the cell, the study of the molecular basis of histone methylation-related neurodevelopmental disorders is currently still in its infancy. Here, we review the latest studies that revealed the pathological implications of alterations in histone methylation status in the context of various neurodevelopmental disorders and propose possible therapeutic application of epigenetic compounds regulating histone methylation status for the treatment of these diseases.

  17. Global health training and international clinical rotations during residency: current status, needs, and opportunities.

    Drain, Paul K; Holmes, King K; Skeff, Kelley M; Hall, Thomas L; Gardner, Pierce

    2009-03-01

    Increasing international travel and migration have contributed to globalization of diseases. Physicians today must understand the global burden and epidemiology of diseases, the disparities and inequities in global health systems, and the importance of cross-cultural sensitivity. To meet these needs, resident physicians across all specialties have expressed growing interest in global health training and international clinical rotations. More residents are acquiring international experience, despite inadequate guidance and support from most accreditation organizations and residency programs. Surveys of global health training, including international clinical rotations, highlight the benefits of global health training as well as the need for a more coordinated approach. In particular, international rotations broaden a resident's medical knowledge, reinforce physical examination skills, and encourage practicing medicine among underserved and multicultural populations. As residents recognize these personal and professional benefits, a strong majority of them seek to gain international clinical experience. In conclusion, with feasible and appropriate administrative steps, all residents can receive global health training and be afforded the accreditation and programmatic support to participate in safe international rotations. The next steps should address accreditation for international rotations and allowance for training away from continuity clinics by residency accreditation bodies, and stipend and travel support for six or more weeks of call-free elective time from residency programs.

  18. Globalization

    Andru?cã Maria Carmen

    2013-01-01

    The field of globalization has highlighted an interdependence implied by a more harmonious understanding determined by the daily interaction between nations through the inducement of peace and the management of streamlining and the effectiveness of the global economy. For the functioning of the globalization, the developing countries that can be helped by the developed ones must be involved. The international community can contribute to the institution of the development environment of the gl...

  19. Sociodemographic, disease status, and illness perceptions predictors of global self-ratings of health and quality of life among those with coronary heart disease

    Aalto, Anna-Mari; Aro, Arja R; Weinman, John

    2006-01-01

    This one-year follow-up study (n = 130 at baseline, n =2745 at follow-up, aged 45-74 years) examined the relationship of patients' perceptions of coronary heart disease (CHD) and illness-related factors with global health status and global quality of life (QOL) ratings. The independent variables...... were CHD history (myocardial infarction, revascularisation), CHD severity (use of nitrates, CHD risk factors and co-morbidities) and illness perceptions. In multivariate regression analysis, CHD history and severity explained 13% of variance in global health status and 8% in global QOL ratings...... at the baseline. Illness perceptions increased the share of explained variance by 18% and 16% respectively. In the follow-up, illness perceptions explained a significant but modest share of variance in change in health status and QOL when baseline health status and QOL and CHD severity were adjusted for more...

  20. Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1).

    Nwaobi, Sinifunanya E; Olsen, Michelle L

    2015-09-26

    DNA methylation serves to regulate gene expression through the covalent attachment of a methyl group onto the C5 position of a cytosine in a cytosine-guanine dinucleotide. While DNA methylation provides long-lasting and stable changes in gene expression, patterns and levels of DNA methylation are also subject to change based on a variety of signals and stimuli. As such, DNA methylation functions as a powerful and dynamic regulator of gene expression. The study of neuroepigenetics has revealed a variety of physiological and pathological states that are associated with both global and gene-specific changes in DNA methylation. Specifically, striking correlations between changes in gene expression and DNA methylation exist in neuropsychiatric and neurodegenerative disorders, during synaptic plasticity, and following CNS injury. However, as the field of neuroepigenetics continues to expand its understanding of the role of DNA methylation in CNS physiology, delineating causal relationships in regards to changes in gene expression and DNA methylation are essential. Moreover, in regards to the larger field of neuroscience, the presence of vast region and cell-specific differences requires techniques that address these variances when studying the transcriptome, proteome, and epigenome. Here we describe FACS sorting of cortical astrocytes that allows for subsequent examination of a both RNA transcription and DNA methylation. Furthermore, we detail a technique to examine DNA methylation, methylation sensitive high resolution melt analysis (MS-HRMA) as well as a luciferase promoter assay. Through the use of these combined techniques one is able to not only explore correlative changes between DNA methylation and gene expression, but also directly assess if changes in the DNA methylation status of a given gene region are sufficient to affect transcriptional activity.

  1. A global, cross cultural study examining the relationship between employee health risk status and work performance metrics.

    Howarth, Ana; Quesada, Jose; Mills, Peter R

    2017-01-01

    Health risk assessments (HRA) are used by many organisations as a basis for developing relevant and targeted employee health and well-being interventions. However, many HRA's have a western-centric focus and therefore it is unclear whether the results can be directly extrapolated to those from non-western countries. More information regarding the differences in the associations between country status and health risks is needed along with a more global perspective of employee health risk factors and well-being overall. Therefore we aimed to i) quantify and compare associations for a number of health risk factors based on country status, and then ii) explore which characteristics can aid better prediction of well-being levels and in turn workplace productivity globally. Online employee HRA data collected from 254 multi-national companies, for the years 2013 through 2016 was analysed (n = 117,274). Multiple linear regression models were fitted, adjusting for age and gender, to quantify associations between country status and health risk factors. Separate regression models were used to assess the prediction of well-being measures related to productivity. On average, the developing countries were comprised of younger individuals with lower obesity rates and markedly higher job satisfaction compared to their developed country counterparts. However, they also reported higher levels of anxiety and depression, a greater number of health risks and lower job effectiveness. Assessment of key factors related to productivity found that region of residency was the biggest predictor of presenteeism and poor pain management was the biggest predictor of absenteeism. Clear differences in health risks exist between employees from developed and developing countries and these should be considered when addressing well-being and productivity in the global workforce.

  2. Why do results conflict regarding the prognostic value of the methylation status in colon cancers? the role of the preservation method

    Tournier Benjamin

    2012-01-01

    Full Text Available Abstract Background In colorectal carcinoma, extensive gene promoter hypermethylation is called the CpG island methylator phenotype (CIMP. Explaining why studies on CIMP and survival yield conflicting results is essential. Most experiments to measure DNA methylation rely on the sodium bisulfite conversion of unmethylated cytosines into uracils. No study has evaluated the performance of bisulfite conversion and methylation levels from matched cryo-preserved and Formalin-Fixed Paraffin Embedded (FFPE samples using pyrosequencing. Methods Couples of matched cryo-preserved and FFPE samples from 40 colon adenocarcinomas were analyzed. Rates of bisulfite conversion and levels of methylation of LINE-1, MLH1 and MGMT markers were measured. Results For the reproducibility of bisulfite conversion, the mean of bisulfite-to-bisulfite standard deviation (SD was 1.3%. The mean of run-to-run SD of PCR/pyrosequencing was 0.9%. Of the 40 DNA couples, only 67.5%, 55.0%, and 57.5% of FFPE DNA were interpretable for LINE-1, MLH1, and MGMT markers, respectively, after the first analysis. On frozen samples the proportion of well converted samples was 95.0%, 97.4% and 87.2% respectively. For DNA showing a total bisulfite conversion, 8 couples (27.6% for LINE-1, 4 couples (15.4% for MLH1 and 8 couples (25.8% for MGMT displayed significant differences in methylation levels. Conclusions Frozen samples gave reproducible results for bisulfite conversion and reliable methylation levels. FFPE samples gave unsatisfactory and non reproducible bisulfite conversions leading to random results for methylation levels. The use of FFPE collections to assess DNA methylation by bisulfite methods must not be recommended. This can partly explain the conflicting results on the prognosis of CIMP colon cancers.

  3. Methylation profiling in individuals with Russell-Silver syndrome.

    Peñaherrera, Maria S; Weindler, Susanne; Van Allen, Margot I; Yong, Siu-Li; Metzger, Daniel L; McGillivray, Barbara; Boerkoel, Cornelius; Langlois, Sylvie; Robinson, Wendy P

    2010-02-01

    Russell-Silver syndrome (RSS) is a heterogeneous disorder associated with pre- and post-natal growth restriction and relative macrocephaly. Involvement of imprinted genes on both chromosome 7 and 11p15.5 has been reported. To further characterize the role of epimutations in RSS we evaluated the methylation status at both 11p15.5 imprinting control regions (ICRs): ICR1 associated with H19/IGF2 expression and ICR2 (KvDMR1) associated with CDKN1C expression in a series of 35 patients with RSS. We also evaluated methylation at the promoter regions of other imprinted genes involved in growth such as PLAGL1 (6q24), GCE (7q21), and PEG10 (7q21) in this series of 35 patients with RSS. Thirteen of the 35 patient samples, but none of 22 controls, showed methylation levels at ICR1 that were more than 2 SD below the mean for controls. Three RSS patients were highly methylated at the SCGE promoter, all of which were diagnosed with upd(7)mat. To identify further potential global methylation changes in RSS patients, a subset of 22 patients were evaluated at 1505 CpG sites by the Illumina GoldenGate methylation array. Among the few CpG sites displaying a significant difference between RSS patients and controls, was a CpG associated with the H19 promoter. No other sites associated with known imprinted genes were identified as abnormally methylated in RSS patients by this approach. While the association of hypomethylation of the H19/IGF2 ICR1 is clear, the continuous distribution of methylation values among the patients and controls complicates the establishment of clear cut-offs for clinical diagnosis. Copyright 2010 Wiley-Liss, Inc.

  4. Late-occurring chromosome aberrations and global DNA methylation in hematopoietic stem/progenitor cells of CBA/CaJ mice exposed to silicon ({sup 28}Si) ions

    Rithidech, Kanokporn Noy, E-mail: kanokporn.rithidech@stonybrookmedicine.edu [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Honikel, Louise M. [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Reungpathanaphong, Paiboon [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Applied Radiation and Isotopes, Faculty of Sciences, Kasetsart University, Chatuchuck, Bangkok 10900 (Thailand); Tungjai, Montree [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Radiologic Technology, Faculty of Associated Medical Sciences, Center of Excellence for Molecular Imaging, Chiang Mai University, Chiang Mai 50200 (Thailand); Jangiam, Witawat [Pathology Department, Stony Brook University, Stony Brook, NY 11794-8691 (United States); Department of Chemical Engineering, Faculty of Engineering, Burapha University, Chonburi 20131 (Thailand); Whorton, Elbert B. [StatCom, PO Box 3041, Galveston, TX 77551 (United States)

    2015-11-15

    Highlights: • Late-occurring chromosome aberrations were found in HSPCs of exposed CBA/CaJ mice. • A dose-dependent reduction in the level of global 5hmC was detected in HSPCs. • There is a link between reduced global 5hmC levels and genomic instability in vivo. • The level of global 5hmC is a better marker of radiation exposure than that of 5mC. - Abstract: Although myeloid leukemia (ML) is one of the major health concerns from exposure to space radiation, the risk prediction for developing ML is unsatisfactory. To increase the reliability of predicting ML risk, a much improved understanding of space radiation-induced changes in the target cells, i.e. hematopoietic stem/progenitor cells (HSPCs), is important. We focused on the in vivo induction of late-occurring damage in HSPCs of mice exposed to {sup 28}Si ions since such damage is associated with radiation-induced genomic instability (a key event of carcinogenesis). We gave adult male CBA/CaJ mice, known to be sensitive to radiation-induced ML, a whole-body exposure (2 fractionated exposures, 15 days apart, that totaled each selected dose, delivered at the dose-rate of 1 cGy/min) to various doses of 300 MeV/n {sup 28}Si ions, i.e. 0 (sham controls), 0.1, 0.25, or 0.5 Gy. At 6 months post-irradiation, we collected bone marrow cells from each mouse (five mice per treatment-group) for obtaining the myeloid-lineage of HSPC-derived clones for analyses. We measured the frequencies of late-occurring chromosome aberrations (CAs), using the genome-wide multicolor fluorescence in situ hybridization method. The measurement of CAs was coupled with the characterization of the global DNA methylation patterns, i.e. 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). A dose-dependent increase in the frequencies of CAs was detected (Analysis of Variance or ANOVA, p < 0.01), indicating the induction of genomic instability after exposure of mice to 300 MeV/n {sup 28}Si ions. Slight increases in the levels of 5m

  5. Methyl donor supplementation blocks the adverse effects of maternal high fat diet on offspring physiology.

    Jesselea Carlin

    Full Text Available Maternal consumption of a high fat diet during pregnancy increases the offspring risk for obesity. Using a mouse model, we have previously shown that maternal consumption of a high fat (60% diet leads to global and gene specific decreases in DNA methylation in the brain of the offspring. The present experiments were designed to attempt to reverse this DNA hypomethylation through supplementation of the maternal diet with methyl donors, and to determine whether methyl donor supplementation could block or attenuate phenotypes associated with maternal consumption of a HF diet. Metabolic and behavioral (fat preference outcomes were assessed in male and female adult offspring. Expression of the mu-opioid receptor and dopamine transporter mRNA, as well as global DNA methylation were measured in the brain. Supplementation of the maternal diet with methyl donors attenuated the development of some of the adverse effects seen in offspring from dams fed a high fat diet; including weight gain, increased fat preference (males, changes in CNS gene expression and global hypomethylation in the prefrontal cortex. Notable sex differences were observed. These findings identify the importance of balanced methylation status during pregnancy, particularly in the context of a maternal high fat diet, for optimal offspring outcome.

  6. Global Status of DDT and Its Alternatives for Use in Vector Control to Prevent Disease

    Berg, van den H.

    2009-01-01

    Objective - I review the status of dichlorodiphenyltrichloroethane (DDT), used for disease vector control, along with current evidence on its benefits and risks in relation to the available alternatives. Data sources and extraction - Contemporary data on DDT use were largely obtained from

  7. Multiple drivers of decline in the global status of freshwater crayfish (Decapoda:Astacidea)

    Nadia I. Richman; Monika Böhm; Susan B. Adams; Fernando Alvarez; Elizabeth A. Bergey; John J. S. Bunn; Quinton Burnham; Jay Cordeiro; Jason Coughran; Keith A. Crandall; Kathryn L. Dawkins; Robert J. DiStefano; Niall E. Doran; Lennart Edsman; Arnold G. Eversole; Leopold Füreder; James M. Furse; Francesca Gherardi; Premek Hamr; David M. Holdich; Pierre Horwitz; Kerrylyn Johnston; Clive M. Jones; Julia P. G. Jones; Robert L. Jones; Thomas G. Jones; Tadashi Kawai; Susan Lawler; Marilu López-Mejía; Rebecca M. Miller; Carlos Pedraza-Lara; Julian D. Reynolds; Alastair M. M. Richardson; Mark B. Schultz; Guenter A. Schuster; Peter J. Sibley; Catherine Souty-Grosset; Christopher A. Taylor; Roger F. Thoma; Jerry Walls; Todd S. Walsh; Ben Cohen

    2015-01-01

    Rates of biodiversity loss are higher in freshwater ecosystems than in most terrestrial or marine ecosystems, making freshwater conservation a priority. However, prioritization methods are impeded by insufficient knowledge on the distribution and conservation status of freshwater taxa, particularly invertebrates. We evaluated the extinction risk of the world’s 590...

  8. Preliminary results of the global audit of treatment of refractory status epilepticus.

    Ferlisi, M; Hocker, S; Grade, M; Trinka, E; Shorvon, S

    2015-08-01

    The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015. Published by Elsevier Inc.

  9. The status and prospects of the debate upon the global warming and nuclear power

    Yim, C. Y.

    2001-01-01

    Possible climate change caused by global warming becomes one of the most serious challenges that mankind shall tackle in 21 st century. Nuclear power, which doesn't emit any greenhouse gas during the generation of electricity, is a promising solution to mitigate the global warming. However, there are still debates about the role of nuclear power related to the subjects such as safety, radioactive waste management and nuclear proliferation risk in the international climate change talks. This paper introduces on-going negotiation focused on the nuclear power and then, gives some prospects on the future negotiations. Finally the brief analysis of their impacts on domestic nuclear industry is carried out

  10. Relative expression of rRNA transcripts and 45S rDNA promoter methylation status are dysregulated in tumors in comparison with matched-normal tissues in breast cancer.

    Karahan, Gurbet; Sayar, Nilufer; Gozum, Gokcen; Bozkurt, Betul; Konu, Ozlen; Yulug, Isik G

    2015-06-01

    Ribosomal RNA (rRNA) expression, one of the most important factors regulating ribosome production, is primarily controlled by a CG-rich 45 S rDNA promoter. However, the DNA methylation state of the 45 S rDNA promoter, as well as its effect on rRNA gene expression in types of human cancers is controversial. In the present study we analyzed the methylation status of the rDNA promoter (-380 to +53 bp) as well as associated rRNA expression levels in breast cancer cell lines and breast tumor-normal tissue pairs. We found that the aforementioned regulatory region was extensively methylated (74-96%) in all cell lines and in 68% (13/19 tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18 S, 28 S, 5.8 S and 45 S external transcribed spacer (45 S ETS) greatly varied in the breast cancer cell lines regardless of their methylation status. Analyses of rRNA transcript expression levels in the breast tumor and normal matched tissues showed no significant difference when normalized with TBP. On the other hand, using the geometric mean of the rRNA expression values (GM-rRNA) as reference enabled us to identify significant changes in the relative expression of rRNAs in the tissue samples. We propose GM-rRNA normalization as a novel strategy to analyze expression differences between rRNA transcripts. Accordingly, the 18S rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio was significantly lower in breast tumor samples than this ratio in the matched normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated with the 45 S rDNA promoter methylation level in the normal breast tissue samples, yet not in the breast tumors. Significant correlations observed between the expression levels of rRNA transcripts in the normal samples were lost in the tumor samples. We showed that the expression of rRNA transcripts may not be based solely on promoter methylation. Carcinogenesis may cause dysregulation of the correlation

  11. The global carbon nation: Status of CO2 capture, storage and utilization

    Kocs, Elizabeth A.

    2017-07-01

    As the world transitions toward cleaner and more sustainable energy generation, Carbon Capture and Sequestration/Storage (CCS) plays an essential role in the portfolio of technologies to help reduce global greenhouse gas (GHG) emissions. The projected increase in population size and its resulting increase in global energy consumption, for both transportation and the electricity grid —the largest emitters of greenhouse gases, will continue to add to current CO2 emissions levels during this transition. Since eighty percent of today's global energy continues to be generated by fossil fuels, a shift to low-carbon energy sources will take many decades. In recent years, shifting to renewables and increasing energy efficiencies have taken more importance than deploying CCS. Together, this triad —renewables, energy efficiency, and CCS— represent a strong paradigm for achieving a carbon-free world. Additionally, the need to accelerate CCS in developing economies like China and India are of increasing concern since migration to renewables is unlikely to occur quickly in those countries. CCS of stationary sources, accounting for only 20% reduction in emissions, as well as increasing efficiency in current systems are needed for major reductions in emissions. A rising urgency for fifty to eighty percent reduction of CO2 emissions by 2050 and one hundred percent reduction by 2100 makes CCS all that more critical in the transition to a cleaner-energy future globally.

  12. The global carbon nation: Status of CO2 capture, storage and utilization

    Kocs Elizabeth A.

    2017-01-01

    Full Text Available As the world transitions toward cleaner and more sustainable energy generation, Carbon Capture and Sequestration/Storage (CCS plays an essential role in the portfolio of technologies to help reduce global greenhouse gas (GHG emissions. The projected increase in population size and its resulting increase in global energy consumption, for both transportation and the electricity grid —the largest emitters of greenhouse gases, will continue to add to current CO2 emissions levels during this transition. Since eighty percent of today’s global energy continues to be generated by fossil fuels, a shift to low-carbon energy sources will take many decades. In recent years, shifting to renewables and increasing energy efficiencies have taken more importance than deploying CCS. Together, this triad —renewables, energy efficiency, and CCS— represent a strong paradigm for achieving a carbon-free world. Additionally, the need to accelerate CCS in developing economies like China and India are of increasing concern since migration to renewables is unlikely to occur quickly in those countries. CCS of stationary sources, accounting for only 20% reduction in emissions, as well as increasing efficiency in current systems are needed for major reductions in emissions. A rising urgency for fifty to eighty percent reduction of CO2 emissions by 2050 and one hundred percent reduction by 2100 makes CCS all that more critical in the transition to a cleaner-energy future globally.

  13. Zinc sulfate contributes to promote telomere length extension via increasing telomerase gene expression, telomerase activity and change in the TERT gene promoter CpG island methylation status of human adipose-derived mesenchymal stem cells.

    Raheleh Farahzadi

    Full Text Available The use of mesenchymal stem cells (MSCs for cell therapy and regenerative medicine has received widespread attention over the past few years, but their application can be complicated by factors such as reduction in proliferation potential, the senescent tendency of the MSCs upon expansion and their age-dependent decline in number and function. It was shown that all the mentioned features were accompanied by a reduction in telomerase activity and telomere shortening. Furthermore, the role of epigenetic changes in aging, especially changes in promoter methylation, was reported. In this study, MSCs were isolated from the adipose tissue with enzymatic digestion. In addition, immunocytochemistry staining and flow cytometric analysis were performed to investigate the cell-surface markers. In addition, alizarin red-S, sudan III, toluidine blue, and cresyl violet staining were performed to evaluate the multi-lineage differentiation of hADSCs. In order to improve the effective application of MSCs, these cells were treated with 1.5 × 10-8 and 2.99 × 10-10 M of ZnSO4 for 48 hours. The length of the absolute telomere, human telomerase reverse transcriptase (hTERT gene expression, telomerase activity, the investigation of methylation status of the hTERT gene promoter and the percentage of senescent cells were analyzed with quantitative real-time PCR, PCR-ELISA TRAP assay, methylation specific PCR (MSP, and beta-galactosidase (SA-β-gal staining, respectively. The results showed that the telomere length, the hTERT gene expression, and the telomerase activity had significantly increased. In addition, the percentage of senescent cells had significantly decreased and changes in the methylation status of the CpG islands in the hTERT promoter region under treatment with ZnSO4 were seen. In conclusion, it seems that ZnSO4 as a proper antioxidant could improve the aging-related features due to lengthening of the telomeres, increasing the telomerase gene expression

  14. Genome-wide screening identifies Plasmodium chabaudi-induced modifications of DNA methylation status of Tlr1 and Tlr6 gene promoters in liver, but not spleen, of female C57BL/6 mice.

    Al-Quraishy, Saleh; Dkhil, Mohamed A; Abdel-Baki, Abdel Azeem S; Delic, Denis; Santourlidis, Simeon; Wunderlich, Frank

    2013-11-01

    Epigenetic reprogramming of host genes via DNA methylation is increasingly recognized as critical for the outcome of diverse infectious diseases, but information for malaria is not yet available. Here, we investigate the effect of blood-stage malaria of Plasmodium chabaudi on the DNA methylation status of host gene promoters on a genome-wide scale using methylated DNA immunoprecipitation and Nimblegen microarrays containing 2,000 bp oligonucleotide features that were split into -1,500 to -500 bp Ups promoters and -500 to +500 bp Cor promoters, relative to the transcription site, for evaluation of differential DNA methylation. Gene expression was analyzed by Agilent and Affymetrix microarray technology. Challenging of female C57BL/6 mice with 10(6) P. chabaudi-infected erythrocytes resulted in a self-healing outcome of infections with peak parasitemia on day 8 p.i. These infections induced organ-specific modifications of DNA methylation of gene promoters. Among the 17,354 features on Nimblegen arrays, only seven gene promoters were identified to be hypermethylated in the spleen, whereas the liver exhibited 109 hyper- and 67 hypomethylated promoters at peak parasitemia in comparison with non-infected mice. Among the identified genes with differentially methylated Cor-promoters, only the 7 genes Pigr, Ncf1, Klkb1, Emr1, Ndufb11, and Tlr6 in the liver and Apol6 in the spleen were detected to have significantly changed their expression. Remarkably, the Cor promoter of the toll-like receptor Tlr6 became hypomethylated and Tlr6 expression increased by 3.4-fold during infection. Concomitantly, the Ups promoter of the Tlr1 was hypermethylated, but Tlr1 expression also increased by 11.3-fold. TLR6 and TLR1 are known as auxillary receptors to form heterodimers with TLR2 in plasma membranes of macrophages, which recognize different pathogen-associated molecular patterns (PAMPs), as, e.g., intact 3-acyl and sn-2-lyso-acyl glycosylphosphatidylinositols of P. falciparum

  15. A global audit of the status and trends of Arctic and Northern Hemisphere goose populations

    Schmutz, Joel A.; Fox, Anthony D.; Leafloor, James O.

    2018-01-01

    This report attempts to review the abundance, status and distribution of natural wild goose populations in the northern hemisphere. The report comprises three parts that 1) summarise key findings from the study and the methodology and analysis applied; 2) contain the individual accounts for each of the 68 populations included in this report; and 3) provide the datasets compiled for this study which will be made accessible on the Arctic Biodiversity Data Service.

  16. The variation in the health status of immigrants and Italians during the global crisis and the role of socioeconomic factors.

    Petrelli, Alessio; Di Napoli, Anteo; Rossi, Alessandra; Costanzo, Gianfranco; Mirisola, Concetta; Gargiulo, Lidia

    2017-06-12

    The effects of the recent global economic and financial crisis especially affected the most vulnerable social groups. Objective of the study was to investigate variation of self-perceived health status in Italians and immigrants during the economic global crisis, focusing on demographic and socioeconomic factors. Through a cross-sectional design we analyzed the national sample of multipurpose surveys "Health conditions and use of health services" (2005 and 2013) conducted by the Italian National Institute of Statistics (ISTAT). Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, derived from SF-12 questionnaire, were assumed as study outcome, dichotomizing variables distribution at 1 st quartile. Prevalence rate ratios (PRR) were estimated through log-binomial regression models, stratified by citizenship and gender, evaluating the association between PCS and MCS with surveys' year, adjusting for age, educational level, employment status, self-perceived economic resources, smoking habits, body mass index. From 2005 to 2013 the proportion of people not employed or reporting scarce/insufficient economic resources increased, especially among men, in particular immigrants. Compared with 2005 we observed in 2013 among Italians a significant lower probability of worse PCS (PRR = 0.96 both for males and females), while no differences were observed among immigrants; a higher probability of worse MCS was observed, particularly among men (Italians: PRR = 1.26;95%CI:1.22-1.29; immigrants: PRR = 1.19;95%CI:1.03-1.38). Self-perceived scarce/insufficient economic resources were strongly and significantly associated with worse PCS and MCS for all subgroups. Lower educational level was strongly associated with worse PCS in Italians and slightly associated with worse MCS for all subgroups. Being not employed was associated with worse health status, especially mental health among men. Our findings support the hypothesis that economic global crisis

  17. Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells

    Katja Zappe

    2018-01-01

    Full Text Available Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l and high (4.5 g/l glucose cell culture condition. Malondialdehyde (MDA as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1 and the DNA methyltransferase 1 (DNMT1 as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H2O2-induced oxidative stress. Thereby, 10 μM vitamin E proved to be more efficient than did 50 μM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.

  18. China's "energy revolution": measuring the status quo, modelling regional dynamics and assessing global impacts

    Mischke, Peggy

    As the world's largest economy in transition, China plays a growing role in global energy markets, clean technology deployment and climate change negotiations. The Chinese president Xi Jinping called in June 2014 for an “energy revolution” of the country’s “energy production and consumption habits......, expanded and applied in this regard. The theories underlying this research are stemming from various scientific disciplines, such as energy and power engineering, macro- and energy-economics, and power project finance. Cross-cutting aspects are the harmonization of Chinese and international energy...... top-down and bottom-up global energy planning tools to model future regional dynamics of China's energy sector; and (v) an assessment of electricity generation costs of the first operational concentrated solar power technologies in China. The results of this thesis are relevant for a broad scientific...

  19. WMO statement on the status of the global climate in 1997

    NONE

    1998-12-31

    The brochure gives a summary of global climate during 1996, from information provided by the Climate Prediction Center in the United States with inputs from other climate centres around the world. The 1997 global mean surface temperature anomaly, 0.43{degree}C above the 1961-90 base-period mean temperature, was the highest since records began in 1860. One major contributing factor was the El Nino Southern Oscillation (ENSO) episode with temperatures in the tropical belt being the second highest in the historical record. ENSO resulted in increased rainfall in the central and eastern aquatorical pacific. In Indonesia, low rainfall from March to December and drought conditions by July and August contributed to uncontrolled wildfires in rainforests of Sumatra and Borneo resulting in widespread smoke pollution. The booklet is provided through the Climate Change Detection Project of the World Climate Data and Monitoring Programme (WCDMP). 10 figs.

  20. Data Storage and Management for Global Research Data Infrastructures - Status and Perspectives

    Erwin Laure

    2013-07-01

    Full Text Available In the vision of Global Research Data Infrastructures (GRDIs, data storage and management plays a crucial role. A successful GRDI will require a common globally interoperable distributed data system, formed out of data centres, that incorporates emerging technologies and new scientific data activities. The main challenge is to define common certification and auditing frameworks that will allow storage providers and data communities to build a viable partnership based on trust. To achieve this, it is necessary to find a long-term commitment model that will give financial, legal, and organisational guarantees of digital information preservation. In this article we discuss the state of the art in data storage and management for GRDIs and point out future research directions that need to be tackled to implement GRDIs.

  1. Estimating the global conservation status of more than 15,000 Amazonian tree species

    ter Steege, H.; et al., [Unknown; Duivenvoorden, J.F.

    2015-01-01

    Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened ...

  2. Current Status and Future Perspective in the Globalization of Traditional Chinese Medicines

    Wan-Ying Wu; Wen-Zhi Yang; Jin-Jun Hou; De-An Guo

    2015-01-01

    Globalization of traditional Chinese medicines started around 1996, which was initiated by the Chinese government. However, substantial progress was only achieved in recent years including the adoption of TCM quality monographs in the western pharmacopoeias (United States Pharmacopoeia and European Pharmacopoeia) and registration in main stream drug regulatory agencies such as US Food and Drug Administration (FDA) and European Medicines Agency (EMA). So far, several TCM herbal quality monogra...

  3. The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring

    Soubry A

    2011-10-01

    Full Text Available Abstract In utero exposures to environmental factors may result in persistent epigenetic modifications affecting normal development and susceptibility to chronic diseases in later life. We explored the relationship between exposure of the growing fetus to maternal depression or antidepressants and DNA methylation at two differentially methylated regions (DMRs of the imprinted Insulin-like Growth Factor 2 (IGF2 gene. Aberrant DNA methylation at the IGF2 and neighboring H19 DMRs has been associated with deregulated IGF2 expression, childhood cancers and several chronic diseases during adulthood. Our study population is comprised of pregnant mothers and their newborns (n = 436, as part of the Newborn Epigenetics Study (NEST. A standardized questionnaire was completed and medical record data were abstracted to ascertain maternal depression and antidepressive drug use. DMR methylation levels in umbilical cord blood leukocytes were quantified using pyrosequencing. From the 436 newborns, laboratory data were obtained for 356 individuals at the IGF2 DMRs, and for 411 individuals at the H19 DMRs; about half of each group was African American or Caucasian. While overall no association between depression and methylation profiles was found, we observed a significant hypermethylation of the H19 DMRs in newborns of African American (n = 177 but not Caucasian (n = 168 mothers who reported the use of antidepressive drugs during pregnancy (β = +6.89, p = 0.01. Of note, our data reveal a race-independent association between smoking during pregnancy and methylation at the IGF2 DMR (+3.05%, p = 0.01. In conclusion, our findings suggest a race-dependent response related to maternal use of antidepressants at one of the IGF2 DMRs in the offspring.

  4. Globalization

    Plum, Maja

    Globalization is often referred to as external to education - a state of affair facing the modern curriculum with numerous challenges. In this paper it is examined as internal to curriculum; analysed as a problematization in a Foucaultian sense. That is, as a complex of attentions, worries, ways...... of reasoning, producing curricular variables. The analysis is made through an example of early childhood curriculum in Danish Pre-school, and the way the curricular variable of the pre-school child comes into being through globalization as a problematization, carried forth by the comparative practices of PISA...

  5. Globalization

    F. Gerard Adams

    2008-01-01

    The rapid globalization of the world economy is causing fundamental changes in patterns of trade and finance. Some economists have argued that globalization has arrived and that the world is “flat†. While the geographic scope of markets has increased, the author argues that new patterns of trade and finance are a result of the discrepancies between “old†countries and “new†. As the differences are gradually wiped out, particularly if knowledge and technology spread worldwide, the t...

  6. The Fine LINE: Methylation Drawing the Cancer Landscape

    Isabelle R. Miousse

    2015-01-01

    Full Text Available LINE-1 (L1 is the most abundant mammalian transposable element that comprises nearly 20% of the genome, and nearly half of the mammalian genome has stemmed from L1-mediated mobilization. Expression and retrotransposition of L1 are suppressed by complex mechanisms, where the key role belongs to DNA methylation. Alterations in L1 methylation may lead to aberrant expression of L1 and have been described in numerous diseases. Accumulating evidence clearly indicates that loss of global DNA methylation observed in cancer development and progression is tightly associated with hypomethylation of L1 elements. Significant progress achieved in the last several years suggests that such parameters as L1 methylation status can be potentially utilized as clinical biomarkers for determination of the disease stage and in predicting the disease-free survival in cancer patients. In this paper, we summarize the current knowledge on L1 methylation, with specific emphasis given to success and challenges on the way of introduction of L1 into clinical practice.

  7. Childhood socioeconomic status and risk in early family environments: predictors of global sleep quality in college students.

    Counts, Cory J; Grubin, Fiona C; John-Henderson, Neha A

    2018-06-01

    Low socioeconomic status (SES) in childhood associates with poor sleep quality in adulthood. Separately, childhood family environments shape health into adulthood. Here, we investigated whether these early life factors independently or interactively inform global sleep quality in college students. Cross-sectional. College students at a state university (N = 391). As a measure of childhood SES, we asked participants to consider their families' socioeconomic standing relative to the rest of the society during their childhood. We used the Risky Family questionnaire to measure adversity and the presence of warmth and affection in the family environment during childhood, and the Pittsburgh Sleep Quality Index as a measure of current global sleep quality. We used linear regressions adjusting for age and sex to examine relationships between childhood SES, risk in childhood family environments, and global sleep quality. Lower childhood SES and greater risk in childhood family environments independently predicted poor sleep quality. Importantly, in low-risk family environments, there was no significant difference in sleep quality as a function of childhood SES. However, students who were from low childhood SES backgrounds who also reported high levels of risk in their early family environments had the worst sleep quality. Findings highlight the importance of considering socioeconomic and family environments in childhood as informants of sleep quality across the lifespan. Compromised sleep quality in college students could affect academic performance and health over time. Copyright © 2018 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

  8. Global mHealth policy arena: status check and future directions.

    Malvey, Donna M; Slovensky, Donna J

    2017-01-01

    In this review, we examine an important piece of the mHealth puzzle that has received scant attention-health policy. The question is whether health policy ultimately will serve to unite nations in advancing global mHealth or, as Mars and Scott suggested in 2010, keep nations isolated and ultimately making their policy decisions in "eHealth silos". Such a non-collaborative approach seriously hampers the potential for using mobile health technologies to deliver health care across borders, assuring individuals access to affordable, convenient, and quality healthcare in underserved regions. From a global perspective, mHealth policy review is difficult as some important policies may be subsumed in comprehensive planning and strategy documents. Political, environmental, economic, organizational, and technology disparities across nations represent a significant impediment to developing mHealth products and services that can be deployed globally. To date, there is modest evidence that such challenges are being addressed. Even though payers can encourage adoption of mHealth with financial incentives for use, it appears that payment or reimbursement tends to be a roadblock for almost all nations, whether they are emerging or developed. If payment for mHealth services is not guaranteed, business models will not be sustainable and providers will have fewer opportunities for scalability. Furthermore, because mHealth policies typically are subject to some type of government scrutiny and oversight, many product developers and entrepreneurs may turn elsewhere for their investments. Global resource scarcity also challenges optimal mHealth deployment, and governments seek to ensure improved population health outcomes as return on their mHealth investments. Unfortunately, such justification is difficult as evaluation methods simply have not kept pace with mHealth technology capability. Requisite measurement tools are sorely lacking when it comes to evaluating efficacy of m

  9. Renewables 2015 global status report - Annual Reporting on Renewables: Ten years of excellence

    Sawin, Janet L.; Sverrisson, Freyr; Rickerson, Wilson; Lins, Christine; Williamson, Laura E.; Adib, Rana; Murdock, Hannah E.; Musolino, Evan; Hullin, Martin; Reith, Ayla; Valero, Alana; Mastny, Lisa; Petrichenko, Ksenia; Seyboth, Kristin; Skeen, Jonathan; Sovacool, Benjamin; Wouters, Frank; Martinot, Eric

    2015-01-01

    Renewable energy continued to grow in 2014 against the backdrop of increasing global energy consumption, particularly in developing countries, and a dramatic decline in oil prices during the second half of the year. Despite rising energy use, for the first time in four decades, global carbon emissions associated with energy consumption remained stable in 2014 while the global economy grew; this stabilisation has been attributed to increased penetration of renewable energy and to improvements in energy efficiency. Globally, there is growing awareness that increased deployment of renewable energy (and energy efficiency) is critical for addressing climate change, creating new economic opportunities, and providing energy access to the billions of people still living without modern energy services. Although discussion is limited to date, renewables also are an important element of climate change adaptation, improving the resilience of existing energy systems and ensuring delivery of energy services under changing climatic conditions. Renewable energy provided an estimated 19.1% of global final energy consumption in 2013, and growth in capacity and generation continued to expand in 2014. Heating capacity grew at a steady pace, and the production of bio-fuels for transport increased for the second consecutive year, following a slowdown in 2011-2012. The most rapid growth, and the largest increase in capacity, occurred in the power sector, led by wind, solar PV, and hydropower. Growth has been driven by several factors, including renewable energy support policies and the increasing cost-competitiveness of energy from renewable sources. In many countries, renewables are broadly competitive with conventional energy sources. At the same time, growth continues to be tempered by subsidies to fossil fuels and nuclear power, particularly in developing countries. Although Europe remained an important market and a centre for innovation, activity continued to shift towards other

  10. Methylation-Specific PCR Unraveled

    Sarah Derks

    2004-01-01

    Full Text Available Methylation‐specific PCR (MSP is a simple, quick and cost‐effective method to analyze the DNA methylation status of virtually any group of CpG sites within a CpG island. The technique comprises two parts: (1 sodium bisulfite conversion of unmethylated cytosine's to uracil under conditions whereby methylated cytosines remains unchanged and (2 detection of the bisulfite induced sequence differences by PCR using specific primer sets for both unmethylated and methylated DNA. This review discusses the critical parameters of MSP and presents an overview of the available MSP variants and the (clinical applications.

  11. Application of liquid chromatography/electrospray ionization ion trap tandem mass spectrometry for the evaluation of global nucleic acids: methylation in garden cress under exposure to CuO nanoparticles.

    Alcazar Magana, Armando; Wrobel, Kazimierz; Corrales Escobosa, Alma Rosa; Wrobel, Katarzyna

    2016-01-15

    A full understanding of the biological impact of nanomaterials demands analytical procedures suitable for the detection/quantification of epigenetic changes that occur in the exposed organisms. Here, the effect of CuO nanoparticles (NPs) on global methylation of nucleic acids in Lepidium sativum was evaluated by liquid chromatography/ion trap mass spectrometry. Enhanced selectivity toward cytosine-containing nucleosides was achieved by using their proton-bound dimers formed in positive electrospray ionization (ESI(+)) as precursor ions for multiple reaction monitoring (MRM) quantification based on one or two ion transitions. Plants were exposed to CuO NPs (0-1000 mg L(-1)); nucleic acid extracts were washed with bathocuproine disulfate; nucleosides were separated on a Luna C18 column coupled via ESI(+) to an AmaZon SL mass spectrometer (Bruker Daltonics). Cytidine, 2´-deoxycytidine, 5-methylcytidine, 5-methyl-2´-deoxycytidine and 5-hydroxymethyl-2´-deoxycytidine were quantified by MRM based on MS(3) ([2M+H](+)/[M+H](+)/[M+H-132](+) or [M+H-116](+)) and MS(2) ([2M+H](+)/[M+H](+) ). Bathocuproine disulfate, added as Cu(I) complexing agent, allowed for elimination of [2M+Cu](+) adducts from the mass spectra. Poorer instrumental detection limits were obtained for MS(3) (20-120 fmol) as compared to MS(2) (9.0-41 fmol); however, two ion transitions helped to eliminate matrix effects in plant extracts. The procedure was tested by analyzing salmon sperm DNA (Sigma) and applied for the evaluation of DNA and RNA methylation in plants; in the absence of NPs, 13.03% and 0.92% methylated cytosines were found in DNA and RNA, respectively; for NPs concentration >50 mg L(-1), DNA hypomethylation was observed with respect to unexposed plants. RNA methylation did not present significant changes upon plant exposure; 5-hydroxymethyl-2´-deoxycytidine was not detected in any sample. The MRM quantification proposed here of cytosine-containing nucleosides using their proton-bound homo

  12. The global status of freshwater fish age validation studies and a prioritization framework for future research

    Pope, Kevin L.; Hamel, Martin J.; Pegg, Mark A.; Spurgeon, Jonathan J.

    2016-01-01

    Age information derived from calcified structures is commonly used to estimate recruitment, growth, and mortality for fish populations. Validation of daily or annual marks on age structures is often assumed, presumably due to a lack of general knowledge concerning the status of age validation studies. Therefore, the current status of freshwater fish age validation studies was summarized to show where additional effort is needed, and increase the accessibility of validation studies to researchers. In total, 1351 original peer-reviewed articles were reviewed from freshwater systems that studied age in fish. Periodicity and age validation studies were found for 88 freshwater species comprising 21 fish families. The number of age validation studies has increased over the last 30 years following previous calls for more research; however, few species have validated structures spanning all life stages. In addition, few fishes of conservation concern have validated ageing structures. A prioritization framework, using a combination of eight characteristics, is offered to direct future age validation studies and close the validation information gap. Additional study, using the offered prioritization framework, and increased availability of published studies that incorporate uncertainty when presenting research results dealing with age information are needed.

  13. Exposure to 3,3',5-triiodothyronine affects histone and RNA polymerase II modifications, but not DNA methylation status, in the regulatory region of the Xenopus laevis thyroid hormone receptor βΑ gene.

    Kasai, Kentaro; Nishiyama, Norihito; Izumi, Yushi; Otsuka, Shunsuke; Ishihara, Akinori; Yamauchi, Kiyoshi

    2015-11-06

    Thyroid hormones (THs) play a critical role in amphibian metamorphosis, during which the TH receptor (TR) gene, thrb, is upregulated in a tissue-specific manner. The Xenopus laevis thrb gene has 3 TH response elements (TREs) in the 5' flanking regulatory region and 1 TRE in the exon b region, around which CpG sites are highly distributed. To clarify whether exposure to 3,3',5-triiodothyronine (T3) affects histone and RNA polymerase II (RNAPII) modifications and the level of DNA methylation in the 5' regulatory region, we conducted reverse transcription-quantitative polymerase chain reaction, bisulfite sequencing and chromatin immunoprecipitation assay using X. laevis cultured cells and premetamorphic tadpoles treated with or without 2 nM T3. Exposure to T3 increased the amount of the thrb transcript, in parallel with enhanced histone H4 acetylation and RNAPII recruitment, and probably phosphorylation of RNAPII at serine 5, in the 5' regulatory and exon b regions. However, the 5' regulatory region remained hypermethylated even with exposure to T3, and there was no significant difference in the methylation status between DNAs from T3-untreated and -treated cultured cells or tadpole tissues. Our results demonstrate that exposure to T3 induced euchromatin-associated epigenetic marks by enhancing histone acetylation and RNAPII recruitment, but not by decreasing the level of DNA methylation, in the 5' regulatory region of the X. laevis thrb gene. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Incidence and mortality of lung cancer: global trends and association with socioeconomic status.

    Wong, Martin C S; Lao, Xiang Qian; Ho, Kin-Fai; Goggins, William B; Tse, Shelly L A

    2017-10-30

    We examined the correlation between lung cancer incidence/mortality and country-specific socioeconomic development, and evaluated its most recent global trends. We retrieved its age-standardized incidence rates from the GLOBOCAN database, and temporal patterns were assessed from global databases. We employed simple linear regression analysis to evaluate their correlations with Human Development Index (HDI) and Gross Domestic Product (GDP) per capita. The average annual percent changes (AAPC) of the trends were evaluated from join-point regression analysis. Country-specific HDI was strongly correlated with age-standardized incidence (r = 0.70) and mortality (r = 0.67), and to a lesser extent GDP (r = 0.24 to 0.55). Among men, 22 and 30 (out of 38 and 36) countries showed declining incidence and mortality trends, respectively; whilst among women, 19 and 16 countries showed increasing incidence and mortality trends, respectively. Among men, the AAPCs ranged from -2.8 to -0.6 (incidence) and -3.6 to -1.1 (mortality) in countries with declining trend, whereas among women the AAPC range was 0.4 to 8.9 (incidence) and 1 to 4.4 (mortality) in countries with increasing trend. Among women, Brazil, Spain and Cyprus had the greatest incidence increase, and all countries in Western, Southern and Eastern Europe reported increasing mortality. These findings highlighted the need for targeted preventive measures.

  15. Present status of research activities relating global warming problems in Japan (mainly MITI and relating organizations)

    Yokoyama, O.

    1993-12-31

    Japanese government has issued action program so called {open_quotes}Action Program to Arrest Global Warming{close_quotes} for preventing global warming at Oct., 1990. According to the program, CO{sub 2} emission should be stabilized on a per capita basis in the year 2000 and beyond at about same level as in 2000 by introducing several methods such as energy conservation, improvement of energy using efficiency, expanding use of renewable energy and so on. The basic concept, target and methods are summarized. At the same time, MITI published so called {open_quotes}New Earth 21{close_quotes} project which aims remedying the earth environment modified by human activities since industrial innovation began at about 200 years ago in coming 100 years. This plan proposed yearly step of research development of technology for mitigating CO{sub 2} emission. According to the MITI`s plan, 15 institutions belonging to AIST have carrying research for developing technology of reducing emission of CO{sub 2} and other greenhouse gases, with cooperation of other research organizations such as RITE (research Institute of Innovative Technology for Earth) and NEDO (New Energy and Industrial Technology Developing Organization). Time schedule of the research development by The New Earth 21 project is summarized in Table 2. Now, in Japan, many national institutions and universities, research works relating reduction and mitigation of GHG are carried out according to this guideline.

  16. Estimating the global conservation status of more than 15,000 Amazonian tree species

    ter Steege, Hans; Pitman, Nigel C. A.; Killeen, Timothy J.; Laurance, William F.; Peres, Carlos A.; Guevara, Juan Ernesto; Salomão, Rafael P.; Castilho, Carolina V.; Amaral, Iêda Leão; de Almeida Matos, Francisca Dionízia; de Souza Coelho, Luiz; Magnusson, William E.; Phillips, Oliver L.; de Andrade Lima Filho, Diogenes; de Jesus Veiga Carim, Marcelo; Irume, Mariana Victória; Martins, Maria Pires; Molino, Jean-François; Sabatier, Daniel; Wittmann, Florian; López, Dairon Cárdenas; da Silva Guimarães, José Renan; Mendoza, Abel Monteagudo; Vargas, Percy Núñez; Manzatto, Angelo Gilberto; Reis, Neidiane Farias Costa; Terborgh, John; Casula, Katia Regina; Montero, Juan Carlos; Feldpausch, Ted R.; Honorio Coronado, Euridice N.; Montoya, Alvaro Javier Duque; Zartman, Charles Eugene; Mostacedo, Bonifacio; Vasquez, Rodolfo; Assis, Rafael L.; Medeiros, Marcelo Brilhante; Simon, Marcelo Fragomeni; Andrade, Ana; Camargo, José Luís; Laurance, Susan G. W.; Nascimento, Henrique Eduardo Mendonça; Marimon, Beatriz S.; Marimon, Ben-Hur; Costa, Flávia; Targhetta, Natalia; Vieira, Ima Célia Guimarães; Brienen, Roel; Castellanos, Hernán; Duivenvoorden, Joost F.; Mogollón, Hugo F.; Piedade, Maria Teresa Fernandez; Aymard C., Gerardo A.; Comiskey, James A.; Damasco, Gabriel; Dávila, Nállarett; García-Villacorta, Roosevelt; Diaz, Pablo Roberto Stevenson; Vincentini, Alberto; Emilio, Thaise; Levis, Carolina; Schietti, Juliana; Souza, Priscila; Alonso, Alfonso; Dallmeier, Francisco; Ferreira, Leandro Valle; Neill, David; Araujo-Murakami, Alejandro; Arroyo, Luzmila; Carvalho, Fernanda Antunes; Souza, Fernanda Coelho; do Amaral, Dário Dantas; Gribel, Rogerio; Luize, Bruno Garcia; Pansonato, Marcelo Petrati; Venticinque, Eduardo; Fine, Paul; Toledo, Marisol; Baraloto, Chris; Cerón, Carlos; Engel, Julien; Henkel, Terry W.; Jimenez, Eliana M.; Maas, Paul; Mora, Maria Cristina Peñuela; Petronelli, Pascal; Revilla, Juan David Cardenas; Silveira, Marcos; Stropp, Juliana; Thomas-Caesar, Raquel; Baker, Tim R.; Daly, Doug; Paredes, Marcos Ríos; da Silva, Naara Ferreira; Fuentes, Alfredo; Jørgensen, Peter Møller; Schöngart, Jochen; Silman, Miles R.; Arboleda, Nicolás Castaño; Cintra, Bruno Barçante Ladvocat; Valverde, Fernando Cornejo; Di Fiore, Anthony; Phillips, Juan Fernando; van Andel, Tinde R.; von Hildebrand, Patricio; Barbosa, Edelcilio Marques; de Matos Bonates, Luiz Carlos; de Castro, Deborah; de Sousa Farias, Emanuelle; Gonzales, Therany; Guillaumet, Jean-Louis; Hoffman, Bruce; Malhi, Yadvinder; de Andrade Miranda, Ires Paula; Prieto, Adriana; Rudas, Agustín; Ruschell, Ademir R.; Silva, Natalino; Vela, César I. A.; Vos, Vincent A.; Zent, Eglée L.; Zent, Stanford; Cano, Angela; Nascimento, Marcelo Trindade; Oliveira, Alexandre A.; Ramirez-Angulo, Hirma; Ramos, José Ferreira; Sierra, Rodrigo; Tirado, Milton; Medina, Maria Natalia Umaña; van der Heijden, Geertje; Torre, Emilio Vilanova; Vriesendorp, Corine; Wang, Ophelia; Young, Kenneth R.; Baider, Claudia; Balslev, Henrik; de Castro, Natalia; Farfan-Rios, William; Ferreira, Cid; Mendoza, Casimiro; Mesones, Italo; Torres-Lezama, Armando; Giraldo, Ligia Estela Urrego; Villarroel, Daniel; Zagt, Roderick; Alexiades, Miguel N.; Garcia-Cabrera, Karina; Hernandez, Lionel; Huamantupa-Chuquimaco, Isau; Milliken, William; Cuenca, Walter Palacios; Pansini, Susamar; Pauletto, Daniela; Arevalo, Freddy Ramirez; Sampaio, Adeilza Felipe; Valderrama Sandoval, Elvis H.; Gamarra, Luis Valenzuela

    2015-01-01

    Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened plant species on Earth by 22%. We show that the trends observed in Amazonia apply to trees throughout the tropics, and we predict that most of the world’s >40,000 tropical tree species now qualify as globally threatened. A gap analysis suggests that existing Amazonian protected areas and indigenous territories will protect viable populations of most threatened species if these areas suffer no further degradation, highlighting the key roles that protected areas, indigenous peoples, and improved governance can play in preventing large-scale extinctions in the tropics in this century. PMID:26702442

  17. Global status of and prospects for protection of terrestrial geophysical diversity.

    Sanderson, Eric W; Segan, Daniel B; Watson, James E M

    2015-06-01

    Conservation of representative facets of geophysical diversity may help conserve biological diversity as the climate changes. We conducted a global classification of terrestrial geophysical diversity and analyzed how land protection varies across geophysical diversity types. Geophysical diversity was classified in terms of soil type, elevation, and biogeographic realm and then compared to the global distribution of protected areas in 2012. We found that 300 (45%) of 672 broad geophysical diversity types currently meet the Convention on Biological Diversity's Aichi Target 11 of 17% terrestrial areal protection, which suggested that efforts to implement geophysical diversity conservation have a substantive basis on which to build. However, current protected areas were heavily biased toward high elevation and low fertility soils. We assessed 3 scenarios of protected area expansion and found that protection focused on threatened species, if fully implemented, would also protect an additional 29% of geophysical diversity types, ecoregional-focused protection would protect an additional 24%, and a combined scenario would protect an additional 42%. Future efforts need to specifically target low-elevation sites with productive soils for protection and manage for connectivity among geophysical diversity types. These efforts may be hampered by the sheer number of geophysical diversity facets that the world contains, which makes clear target setting and prioritization an important next step. © 2015 Society for Conservation Biology.

  18. Current Status and Future Perspective in the Globalization of Traditional Chinese Medicines

    Wan-Ying Wu

    2015-01-01

    Full Text Available Globalization of traditional Chinese medicines started around 1996, which was initiated by the Chinese government. However, substantial progress was only achieved in recent years including the adoption of TCM quality monographs in the western pharmacopoeias (United States Pharmacopoeia and European Pharmacopoeia and registration in main stream drug regulatory agencies such as US Food and Drug Administration (FDA and European Medicines Agency (EMA. So far, several TCM herbal quality monographs were adopted by the United States Pharmacopoeia including Chinese Salvia, Ganoderma lucidum and Panax notoginseng, etc. Over 45 TCM quality monographs were recorded in the European Pharmacopoeia with 20 more in progress. After the successful registration of the first TCM product named Diao Xin Xue Kang as traditional medicine via the Medicines Evaluation Board of the Netherlands, several other TCM herbal products are in the registration process in several European member states. So far, there has been still not any TCM product authorized as a drug by the FDA regardless of a few TCM products in phase III or phase II clinical trials. This review summarizes the progress made in the globalization of traditional Chinese medicines in recent years and future issues in this regard.

  19. Anaerobic digestion for bioenergy production: Global status, environmental and techno-economic implications, and government policies.

    Vasco-Correa, Juliana; Khanal, Sami; Manandhar, Ashish; Shah, Ajay

    2018-01-01

    Anaerobic digestion (AD) is a mature technology that can transform organic matter into a bioenergy source - biogas (composed mainly of methane and carbon dioxide), while stabilizing waste. AD implementation around the world varies significantly, from small-scale household digesters in developing countries to large farm-scale or centralized digesters in developed countries. These differences in the implementation of AD technology are due to a complex set of conditions, including economic and environmental implications of the AD technology, and stimulus provided by a variety of polices and incentives related to agricultural systems, waste management, and renewable energy production. This review explores the current status of the AD technology worldwide and some of the environmental, economic and policy-related drivers that have shaped the implementation of this technology. The findings show that the regulations and incentives have been the primary factor influencing the steady growth of this technology, in both developing and developed countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Status report on the USGS component of the Global Seismographic Network

    Gee, L. S.; Bolton, H. F.; Derr, J.; Ford, D.; Gyure, G.; Hutt, C. R.; Ringler, A.; Storm, T.; Wilson, D.

    2010-12-01

    As recently as four years ago, the average age of a datalogger in the portion of the Global Seismographic Network (GSN) operated by the United States Geological Survey (USGS) was 16 years - an eternity in the lifetime of computers. The selection of the Q330HR in 2006 as the “next generation” datalogger by an Incorporated Research Institutions for Seismology (IRIS) selection committee opened the door for upgrading the GSN. As part of the “next generation” upgrades, the USGS is replacing a single Q680 system with two Q330HRs and a field processor to provide the same capability. The functionality includes digitizing, timing, event detection, conversion into miniSEED records, archival of miniSEED data on the ASP and telemetry of the miniSEED data using International Deployment of Accelerometers (IDA) Authenticated Disk Protocol (IACP). At many sites, Quanterra Balers are also being deployed. The Q330HRs feature very low power consumption (which will increase reliability) and higher resolution than the Q680 systems. Furthermore, this network-wide upgrade provides the opportunity to correct known station problems, standardize the installation of secondary sensors and accelerometers, replace the feedback electronics of STS-1 sensors, and perform checks of absolute system sensitivity and sensor orientation. The USGS upgrades began with ANMO in May, 2008. Although we deployed Q330s at KNTN and WAKE in the fall of 2007 (and in the installation of the Caribbean network), these deployments did not include the final software configuration for the GSN upgrades. Following this start, the USGS installed six additional sites in FY08. With funding from the American Recovery and Reinvestment Act and the USGS GSN program, 14 stations were upgraded in FY09. Twenty-one stations are expected to be upgraded in FY10. These systematic network-wide upgrades will improve the reliability and data quality of the GSN, with the end goal of providing the Earth science community high

  1. DNA methylation

    Williams, Kristine; Christensen, Jesper; Helin, Kristian

    2012-01-01

    DNA methylation is involved in key cellular processes, including X-chromosome inactivation, imprinting and transcriptional silencing of specific genes and repetitive elements. DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. The recent...... discovery that the three members of the TET protein family can convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) has provided a potential mechanism leading to DNA demethylation. Moreover, the demonstration that TET2 is frequently mutated in haematopoietic tumours suggests that the TET...... proteins are important regulators of cellular identity. Here, we review the current knowledge regarding the function of the TET proteins, and discuss various mechanisms by which they contribute to transcriptional control. We propose that the TET proteins have an important role in regulating DNA methylation...

  2. Present status of seawater desalination and problems of nuclear utilization. Aiming at coping with global shortage of water

    2006-07-01

    With recent global population increase and economic and life level improvement, water demand increases tremendously and in 2025 water scarcity will occur in almost the half of countries and regions in the world. Nuclear desalination is highly expected to cope with this issue. The Japan Atomic Industrial Forum (JAIF) established special committee on seawater desalination problems to discuss possibilities of nuclear desalination introduction. Present status of seawater desalination and problems of nuclear utilization were reviewed and the committee recommended the necessity of establishing medium and long-term plan on international business development of nuclear desalination and also the start of basic research on problems of nuclear utilization such as technical and institutional limits and efficient applicability of nuclear energy. (T. Tanaka)

  3. Renewable energy from wind and sun. Status quo and development perspectives at the global level

    Graichen, Patrick; Grotewold, Lars; Kordowski, Klaus; Wesemann, Philipp

    2015-01-01

    The global market for renewable energy technologies has experienced strong growth since the year 2000. In 2013 newly installed electricity production plants based on renewable energy for the first time outnumbered the aggregate of newly installed plants based on coal, gas or nuclear energy. In more and more parts of the world, wind and solar energy plants are becoming the most cost-effective means of electricity production. As renewable energy resources begin to claim significant shares in the energy mix they also become more system-relevant, resulting in a need for more investment as well as regulatory changes. Due to their specific features (high capital intensity, low incremental costs, fluctuating electricity production), and in spite of the marked decline in costs, wind and solar energy are still dependent on proactive policies in support of renewable energy.

  4. A Status Report on the Global Research in Microbial Metabolic Engineering

    Joe, Min Ho; Lim, Sang Yong; Kim, Dong Ho

    2008-09-15

    Biotechnology industry is now a global 'Mega-Trend' and metabolic engineering technology has important role is this area. Therefore, many countries has made efforts in this field to produce top value added bio-products efficiently using microorganisms. It has been applied to increase the production of chemicals that are already produced by the host organism, to produce desired chemical substances from less expensive feedstock, and to generate products that are new to the host organism. Recent experimental advances, the so-called '-omics' technologies, mainly functional genomics, proteomics and metabolomics, have enabled wholesale generation of new genomic, transcriptomic, proteomic, and metabolomic data. This report provides the insights of the integrated view of metabolism generated by metabolic engineering for biotechnological applications of microbial metabolic engineering.

  5. A Status Report on the Global Research in Microbial Metabolic Engineering

    Joe, Min Ho; Lim, Sang Yong; Kim, Dong Ho

    2008-09-01

    Biotechnology industry is now a global 'Mega-Trend' and metabolic engineering technology has important role is this area. Therefore, many countries has made efforts in this field to produce top value added bio-products efficiently using microorganisms. It has been applied to increase the production of chemicals that are already produced by the host organism, to produce desired chemical substances from less expensive feedstock, and to generate products that are new to the host organism. Recent experimental advances, the so-called '-omics' technologies, mainly functional genomics, proteomics and metabolomics, have enabled wholesale generation of new genomic, transcriptomic, proteomic, and metabolomic data. This report provides the insights of the integrated view of metabolism generated by metabolic engineering for biotechnological applications of microbial metabolic engineering

  6. A Status Report on the Global Research in Microbial Metabolic Engineering

    Joe, Min Ho; Lim, Sang Yong; Kim, Dong Ho

    2008-09-15

    Biotechnology industry is now a global 'Mega-Trend' and metabolic engineering technology has important role is this area. Therefore, many countries has made efforts in this field to produce top value added bio-products efficiently using microorganisms. It has been applied to increase the production of chemicals that are already produced by the host organism, to produce desired chemical substances from less expensive feedstock, and to generate products that are new to the host organism. Recent experimental advances, the so-called '-omics' technologies, mainly functional genomics, proteomics and metabolomics, have enabled wholesale generation of new genomic, transcriptomic, proteomic, and metabolomic data. This report provides the insights of the integrated view of metabolism generated by metabolic engineering for biotechnological applications of microbial metabolic engineering.

  7. Current status of alcohol marketing policy--an urgent challenge for global governance.

    Casswell, Sally

    2012-03-01

    To review research literature and available information on the extent and impacts of marketing, current policy response and the interests engaged in the policy debate in order to inform recommendations for policy change on alcohol marketing. Relevant literature, including systematic reviews and publicly available information (websites and participant observation) is reviewed and synthesized. Alcohol marketing has expanded markedly in the past 50 years and, while there remains uncertainty about the impact across the population, there is now clear evidence of its impact on the consumption of young people. Few countries have effective policy in place restricting alcohol marketing, and there is a lack of an international response to alcohol marketing which crosses national boundaries. The protection of alcohol marketing has been a major focus for vested interest groups and this has affected governmental response at national and international levels. There has been a lack of non-governmental organization engagement. The policy response to tobacco marketing provides a clear contrast to that of alcohol marketing policy and provides a model for alcohol marketing policy. The global exposure of young people to alcohol marketing requires an urgent policy response. The Framework Convention on Tobacco Control provides an appropriate model for global governance to control alcohol marketing. There are extant examples of national level legislation achieving comprehensive bans with France's Loi Evin providing a feasible model. Resources from philanthropic organizations to allow non-governmental organization engagement are urgently required, as is engagement by the governmental sector independent of commercial influence. © 2012 The Author, Addiction © 2012 Society for the Study of Addiction.

  8. Antismoking messages and current cigarette smoking status in Somaliland: results from the Global Youth Tobacco Survey 2004

    Muula Adamson S

    2008-05-01

    Full Text Available Abstract Background Tobacco is a leading cause of death globally. There are limited reports on current cigarette smoking prevalence and its associated-antismoking messages among adolescents in conflict zones of the world. We, therefore, conducted secondary analysis of data to estimate the prevalence of current cigarette smoking, and to determine associations of antismoking messages with smoking status. Methods We used data from the Somaliland Global Youth Tobacco Survey (GYTS of 2004 to estimate the prevalence of smoking. We also assessed whether being exposed to anti-smoking media, education and having discussed with family members on the harmful effects of smoking were associated with smoking. Logistic regression analysis was used to assess these associations. Current smoking was defined as having reported smoking cigarettes, even a single puff, in the last 30 days preceding the survey (main outcome. Results Altogether 1563 adolescents participated in the survey. However, 1122 had data on the main outcome. Altogether, 15.8% of the respondents reported having smoked cigarettes (10.3% among males, and 11.1% among females. Factors that were associated with reported non-smoking were: discussing harmful effects of smoking cigarettes with their family members (OR = 0.61, 95% CI 0.52, 0.71; being taught that smoking makes teeth yellow, causes wrinkles and smokers smell badly (OR = 0.62, 95% CI 0.52, 0.74; being taught that people of the respondent's age do not smoke (OR = 0.81, 95% CI 0.69, 0.95; and having reported that religious organizations discouraged young people smoking (OR = 0.70, 95% CI 0.60, 0.82. However, exposure to a lot many antismoking messages at social gatherings was associated with smoking. Exposure to antismoking print media was not associated with smoking status. Conclusion A combination of school and home based antismoking interventions may be effective in controlling adolescent smoking in Somaliland.

  9. Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C

    Liu, Xi-yu; Li, Hong

    2017-01-01

    Aims. Latent autoimmune diabetes in adults (LADA) is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods. Blood CD4+ T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results. Reduced global H3 lysine 9 methylation was observed in LADA patients’ CD4+ T lymphocytes, compared to healthy controls (P < 0.05). H3 l...

  10. Assessment of Nutritional Status of Nepalese Hemodialysis Patients by Anthropometric Examinations and Modified Quantitative Subjective Global Assessment

    Arun Sedhain

    2015-01-01

    Full Text Available Objective To assess the nutritional status of patients on maintenance hemodialysis by using modified quantitative subjective global assessment (MQSGA and anthropometric measurements. Method We Conducted a cross sectional descriptive analytical study to assess the nutritional status of fifty four patients with chronic kidney disease undergoing maintenance hemodialysis by using MQSGA and different anthropometric and laboratory measurements like body mass index (BMI, mid-arm circumference (MAC, mid-arm muscle circumference (MAMC, triceps skin fold (TSF and biceps skin fold (BSF, serum albumin, C-reactive protein (CRP and lipid profile in a government tertiary hospital at Kathmandu, Nepal. Results Based on MQSGA criteria, 66.7% of the patients suffered from mild to moderate malnutrition and 33.3% were well nourished. None of the patients were severely malnourished. CRP was positive in 56.3% patients. Serum albumin, MAC and BMI were (mean + SD 4.0 + 0.3 mg/dl, 22 + 2.6 cm and 19.6 ± 3.2 kg/m 2 respectively. MQSGA showed negative correlation with MAC ( r = −0.563; P = < 0.001, BMI ( r = −0.448; P = < 0.001, MAMC ( r = −0.506; P = < .0001, TSF ( r = −0.483; P = < .0002, and BSF ( r = −0.508; P = < 0.0001. Negative correlation of MQSGA was also found with total cholesterol, triglyceride, LDL cholesterol and HDL cholesterol without any statistical significance. Conclusion Mild to moderate malnutrition was found to be present in two thirds of the patients undergoing hemodialysis. Anthropometric measurements like BMI, MAC, MAMC, BSF and TSF were negatively correlated with MQSGA. Anthropometric and laboratory assessment tools could be used for nutritional assessment as they are relatively easier, cheaper and practical markers of nutritional status.

  11. The effect of thiopurine drugs on DNA methylation in relation to TPMT expression.

    Hogarth, L A; Redfern, C P F; Teodoridis, J M; Hall, A G; Anderson, H; Case, M C; Coulthard, S A

    2008-10-15

    The thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well-established agents for the treatment of leukaemia but their main modes of action are controversial. Thiopurine methyltransferase (TPMT) metabolises thiopurine drugs and influences their cytotoxic activity. TPMT, like DNA methyltransferases (DNMTs), transfers methyl groups from S-adenosylmethionine (SAM) and generates S-adenosylhomocysteine (SAH). Since SAM levels are dependent on de novo purine synthesis (DNPS) and the metabolic products of 6-TG and 6-MP differ in their ability to inhibit DNPS, we postulated that 6-TG compared to 6-MP would have differential effects on changes in SAM and SAH levels and global DNA methylation, depending on TPMT status. To test this hypothesis, we used a human embryonic kidney cell line with inducible TPMT. Although changes in SAM and SAH levels occurred with each drug, decrease in global DNA methylation more closely reflected a decrease in DNMT activity. Inhibition was influenced by TPMT for 6-TG, but not 6-MP. The decrease in global methylation and DNMT activity with 6-MP, or with 6-TG when TPMT expression was low, were comparable to 5-aza-2'-deoxycytidine. However, this was not reflected in changes in methylation at the level of an individual marker gene (MAGE1A). The results suggest that a non-TPMT metabolised metabolite of 6-MP and 6-TG and the TPMT-metabolised 6-MP metabolite 6-methylthioguanosine 5'-monophosphate, contribute to a decrease in DNMT levels and global DNA methylation. As demethylating agents have shown promise in leukaemia treatment, inhibition of DNA methylation by the thiopurine drugs may contribute to their cytotoxic affects.

  12. Wp specific methylation of highly proliferated LCLs

    Park, Jung-Hoon; Jeon, Jae-Pil; Shim, Sung-Mi; Nam, Hye-Young; Kim, Joon-Woo; Han, Bok-Ghee; Lee, Suman

    2007-01-01

    The epigenetic regulation of viral genes may be important for the life cycle of EBV. We determined the methylation status of three viral promoters (Wp, Cp, Qp) from EBV B-lymphoblastoid cell lines (LCLs) by pyrosequencing. Our pyrosequencing data showed that the CpG region of Wp was methylated, but the others were not. Interestingly, Wp methylation was increased with proliferation of LCLs. Wp methylation was as high as 74.9% in late-passage LCLs, but 25.6% in early-passage LCLs. From two Burkitt's lymphoma cell lines, Wp specific hypermethylation was also found (>80%). Interestingly, the expression of EBNA2 gene which located directly next to Wp was associated with its methylation. Our data suggested that Wp specific methylation may be important for the indicator of the proliferation status of LCLs, and the epigenetic viral gene regulation of EBNA2 gene by Wp should be further defined possibly with other biological processes

  13. Current status and future projections of LNG demand and supplies: A global prospective

    Kumar, Satish; Kwon, Hyouk-Tae; Choi, Kwang-Ho; Hyun Cho, Jae; Lim, Wonsub; Moon, Il

    2011-01-01

    An unceasing growth of gas consumption in domestic households, industry, and power plants has gradually turned natural gas into a major source of energy. Main drivers in this development are the technical and economic advantages of natural gas. It is a clean, versatile, and easily controllable fuel. On this basis, natural gas is often considered the form of energy that will be the 'bridging fuel' to a sustainable energy system, sometime after 2050. Unlike other main sources of energy, such as oil and coal, gas is not traded on an actual world market. This paper provides an overview on demand and supplies of natural gas (LNG) in the past as a function of gas prices, gas technology (gas sweetening, liquefaction, shipping and re-gasification), and gas market and how they have changed recently. It also discusses the likely developments in global LNG demand for the period to the year 2030. - Highlights: → This study provides an overview on demand and supplies of LNG in the past and future. → Outlook for LNG demand in Asia pacific region is very robust. → In past decade the shale gas production in USA has increased fivefold. → The future of European gas supply depends largely on the geopolitical environments. → Within the gas sector LNG is playing an ever increasing role in gas transportation.

  14. Assessment of nutritional status using abridged scored patient-generated subjective global assessment in cancer patient.

    Shahvazi, Simin; Onvani, Shokouh; Heydari, Marziyeh; Mehrzad, Valiollah; Nadjarzadeh, Azadeh; Fallahzadeh, Hosseyn

    2017-01-01

    Malnutrition is a common problem among cancer patients, usually occurs due to poor appetite, low food intake, and changes in body metabolism. The aim of this study is to determine the prevalence of malnutrition in patients receiving chemotherapy on an outpatient basis. This cross-sectional study conducted on 300 cancer patients referred to hospital. The prevalence of malnutrition among patients was assessed using the abridged scored patient-generated subjective global assessment (abPG-SGA) standard questionnaire. Moreover, patient's weight and 24 h dietary recall were measured. Descriptive statistics were used to present characteristics of patients and dietary recalls. For revealing the correlation, Spearman correlation was used. The average abPG-SGA score was 7.6 (standard deviation [SD] = 5.4) and 60.7% of patients were malnourished and required nutritional intervention. Patients mean age and mean duration of illness were 54.2 (SD = 14.7(years, 25 months, respectively. The most common complaint of patients included fatigue (51.3%), anorexia (43.3%), and dry mouth (41%). Reduction in food intake in past month was reported by 41.7% of patients. According to the high prevalence of cancers and increasing growth of them in recent years with regard to outpatient treatment development for cancer patients, using the abPG-SGA standard questionnaire by nutritionist or nurses can be effective to detect malnourished patients and reduce complications caused by disease.

  15. Production and trading of biomass for energy - An overview of the global status

    Heinimoe, J.; Junginger, M.

    2009-01-01

    The markets for industrially used biomass for energy purposes are developing rapidly toward being international commodity markets. Determining international traded biomass volumes for energy purposes is difficult, for several reasons, such as challenges regarding the compilation of statistics on the topic. While for some markets (pellets and ethanol) separate overviews exist, no comprehensive statistics and summaries aggregating separate biomass streams are available. The aim of this paper is to summarise trade volumes for various biomasses used for energy and to review the challenges related to measurement of internationally traded volumes of biofuels. International trade of solid and liquid biofuels was estimated to be about 0.9 EJ for 2006. Indirect trade of biofuels thorough trading of industrial roundwood and material byproducts comprises the largest proportion of trading, having a share of about 0.6 EJ. The remaining amount consisted of products that are traded directly for energy purposes, with ethanol, wood pellets, and palm oil being the most important commodities. In 2004-2006, the direct trade of biofuels increased 60%, whereas indirect trade has been almost constant. When compared to current global energy use of biomass (about 50 EJ yr -1 ) and to the long-term theoretical trading potential between the major regions of the world (80-150 EJ yr -1 ), the development of international trade of biomass for energy purposes is in its initial stage, but it is expected to continue to grow rapidly. (author)

  16. Global Inequalities in Cervical Cancer Incidence and Mortality are Linked to Deprivation, Low Socioeconomic Status, and Human Development.

    Singh, Gopal K; Azuine, Romuladus E; Siahpush, Mohammad

    2012-01-01

    This study examined global inequalities in cervical cancer incidence and mortality rates as a function of cross-national variations in the Human Development Index (HDI), socioeconomic factors, Gender Inequality Index (GII), and healthcare expenditure. Age-adjusted incidence and mortality rates were calculated for women in 184 countries using the 2008 GLOBOCAN database, and incidence and mortality trends were analyzed using the WHO cancer mortality database. Log-linear regression was used to model annual trends, while OLS and Poisson regression models were used to estimate the impact of socioeconomic and human development factors on incidence and mortality rates. Cervical cancer incidence and mortality rates varied widely, with many African countries such as Guinea, Zambia, Comoros, Tanzania, and Malawi having at least 10-to-20-fold higher rates than several West Asian, Middle East, and European countries, including Iran, Saudi Arabia, Syria, Egypt, and Switzerland. HDI, GII, poverty rate, health expenditure per capita, urbanization, and literacy rate were all significantly related to cervical cancer incidence and mortality, with HDI and poverty rate each explaining >52% of the global variance in mortality. Both incidence and mortality rates increased in relation to lower human development and higher gender inequality levels. A 0.2 unit increase in HDI was associated with a 20% decrease in cervical cancer risk and a 33% decrease in cervical cancer mortality risk. The risk of a cervical cancer diagnosis increased by 24% and of cervical cancer death by 42% for a 0.2 unit increase in GII. Higher health expenditure levels were independently associated with decreased incidence and mortality risks. Global inequalities in cervical cancer are clearly linked to disparities in human development, social inequality, and living standards. Reductions in cervical cancer rates are achievable by reducing inequalities in socioeconomic conditions, availability of preventive health

  17. Global Inequalities in Cervical Cancer Incidence and Mortality are Linked to Deprivation, Low Socioeconomic Status, and Human Development

    Gopal K. Singh, PhD

    2012-11-01

    Full Text Available Objective: This study examined global inequalities in cervical cancer incidence and mortality rates as a function of cross-national variations in the Human Development Index (HDI, socioeconomic factors, Gender Inequality Index (GII, and healthcare expenditure.Methods: Age-adjusted incidence and mortality rates were calculated for women in 184 countries using the 2008 GLOBOCAN database, and incidence and mortality trends were analyzed using the WHO cancer mortality database. Log-linear regression was used to model annual trends, while OLS and Poisson regression models were used to estimate the impact of socioeconomic and human development factors on incidence and mortality rates.Results: Cervical cancer incidence and mortality rates varied widely, with many African countries such as Guinea, Zambia, Comoros, Tanzania, and Malawi having at least 10-to-20-fold higher rates than several West Asian, Middle East, and European countries, including Iran, Saudi Arabia, Syria, Egypt, and Switzerland. HDI, GII, poverty rate, health expenditure per capita, urbanization, and literacy rate were all significantly related to cervical cancer incidence and mortality, with HDI and poverty rate each explaining >52% of the global variance in mortality. Both incidence and mortality rates increased in relation to lower human development and higher gender inequality levels. A 0.2 unit increase in HDI was associated with a 20% decrease in cervical cancer risk and a 33% decrease in cervical cancer mortality risk. The risk of a cervical cancer diagnosis increased by 24% and of cervical cancer death by 42% for a 0.2 unit increase in GII. Higher health expenditure levels were independently associated with decreased incidence and mortality risks.Conclusions and Public Health Implications: Global inequalities in cervical cancer are clearly linked to disparities in human development, social inequality, and living standards. Reductions in cervical cancer rates are achievable by

  18. Health policy and systems research training: global status and recommendations for action

    Tancred, Tara M; Schleiff, Meike; Peters, David H

    2016-01-01

    Abstract Objective To investigate the characteristics of health policy and systems research training globally and to identify recommendations for improvement and expansion. Methods We identified institutions offering health policy and systems research training worldwide. In 2014, we recruited participants from identified institutions for an online survey on the characteristics of the institutions and the courses given. Survey findings were explored during in-depth interviews with selected key informants. Findings The study identified several important gaps in health policy and systems research training. There were few courses in central and eastern Europe, the Middle East, North Africa or Latin America. Most (116/152) courses were instructed in English. Institutional support for courses was often lacking and many institutions lacked the critical mass of trained individuals needed to support doctoral and postdoctoral students. There was little consistency between institutions in definitions of the competencies required for health policy and systems research. Collaboration across disciplines to provide the range of methodological perspectives the subject requires was insufficient. Moreover, the lack of alternatives to on-site teaching may preclude certain student audiences such as policy-makers. Conclusion Training in health policy and systems research is important to improve local capacity to conduct quality research in this field. We provide six recommendations to improve the content, accessibility and reach of training. First, create a repository of information on courses. Second, establish networks to support training. Third, define competencies in health policy and systems research. Fourth, encourage multidisciplinary collaboration. Fifth, expand the geographical and language coverage of courses. Finally, consider alternative teaching formats. PMID:27429488

  19. Global coverage of cetacean line-transect surveys: status quo, data gaps and future challenges.

    Kristin Kaschner

    Full Text Available Knowledge of abundance, trends and distribution of cetacean populations is needed to inform marine conservation efforts, ecosystem models and spatial planning. We compiled a geo-spatial database of published data on cetacean abundance from dedicated visual line-transect surveys and encoded >1100 abundance estimates for 47 species from 430 surveys conducted worldwide from 1975-2005. Our subsequent analyses revealed large spatial, temporal and taxonomic variability and gaps in survey coverage. With the exception of Antarctic waters, survey coverage was biased toward the northern hemisphere, especially US and northern European waters. Overall, <25% of the world's ocean surface was surveyed and only 6% had been covered frequently enough (≥ 5 times to allow trend estimation. Almost half the global survey effort, defined as total area (km(2 covered by all survey study areas across time, was concentrated in the Eastern Tropical Pacific (ETP. Neither the number of surveys conducted nor the survey effort had increased in recent years. Across species, an average of 10% of a species' predicted range had been covered by at least one survey, but there was considerable variation among species. With the exception of three delphinid species, <1% of all species' ranges had been covered frequently enough for trend analysis. Sperm whales emerged from our analyses as a relatively data-rich species. This is a notoriously difficult species to survey visually, and we use this as an example to illustrate the challenges of using available data from line-transect surveys for the detection of trends or for spatial planning. We propose field and analytical methods to fill in data gaps to improve cetacean conservation efforts.

  20. Methylated genes as new cancer biomarkers.

    Duffy, M J

    2012-02-01

    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

  1. The DNA methylation status of MyoD and IGF-I genes are correlated with muscle growth during different developmental stages of Japanese flounder (Paralichthys olivaceus).

    Huang, Yajuan; Wen, Haishen; Zhang, Meizhao; Hu, Nan; Si, Yufeng; Li, Siping; He, Feng

    2018-05-01

    Many genes related to muscle growth modulate myoblast proliferation and differentiation and promote muscle hypertrophy. MyoD is a myogenic determinant that contributes to myoblast determination, and insulin-like growth factor 1 (IGF-I) interacts with MyoD to regulate muscle hypertrophy and muscle mass. In this study, we aimed to assess DNA methylation and mRNA expression patterns of MyoD and IGF-I during different developmental stages of Japanese flounder, and to examine the relationship between MyoD and IGF-I gene. DNA and RNA were extracted from muscles, and DNA methylation of MyoD and IGF-I promoter and exons was detected by bisulfite sequencing. The relative expression of MyoD and IGF-I was measured by quantitative polymerase chain reaction. IGF-I was measured by radioimmunoassay. Interestingly, the lowest expression of MyoD and IGF-I emerged at larva stage, and the mRNA expression was negatively associated with methylation. We hypothesized that many skeletal muscle were required to complete metamorphosis; thus, the expression levels of MyoD and IGF-I genes increased from larva stage and then decreased. The relative expression levels of MyoD and IGF-I exhibited similar patterns, suggesting that MyoD and IGF-I regulated muscle growth through combined effects. Changes in the concentrations of IGF-I hormone were similar to those of IGF-I gene expression. Our results the mechanism through which MyoD and IGF-I regulate muscle development and demonstrated that MyoD interacted with IGF-I to regulate muscle growth during different developmental stages. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors

    Schernhammer Eva S

    2010-05-01

    Full Text Available Abstract Background Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. LINE-1 (L1 retrotransposon constitutes a substantial portion of the human genome, and LINE-1 methylation correlates with global DNA methylation status. LINE-1 hypomethylation in colon cancer has been strongly associated with poor prognosis. However, whether LINE-1 hypomethylators constitute a distinct cancer subtype remains uncertain. Recent evidence for concordant LINE-1 hypomethylation within synchronous colorectal cancer pairs suggests the presence of a non-stochastic mechanism influencing tumor LINE-1 methylation level. Thus, it is of particular interest to examine whether its wide variation can be attributed to clinical, pathologic or molecular features. Design Utilizing a database of 869 colorectal cancers in two prospective cohort studies, we constructed multivariate linear and logistic regression models for LINE-1 methylation (quantified by Pyrosequencing. Variables included age, sex, body mass index, family history of colorectal cancer, smoking status, tumor location, stage, grade, mucinous component, signet ring cells, tumor infiltrating lymphocytes, CpG island methylator phenotype (CIMP, microsatellite instability, expression of TP53 (p53, CDKN1A (p21, CTNNB1 (β-catenin, PTGS2 (cyclooxygenase-2, and FASN, and mutations in KRAS, BRAF, and PIK3CA. Results Tumoral LINE-1 methylation ranged from 23.1 to 90.3 of 0-100 scale (mean 61.4; median 62.3; standard deviation 9.6, and distributed approximately normally except for extreme hypomethylators [LINE-1 methylation Conclusions LINE-1 extreme hypomethylators appear to constitute a previously-unrecognized, distinct subtype of colorectal cancers, which needs to be confirmed by additional studies. Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers.

  3. Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C

    Xi-yu Liu

    2017-01-01

    Full Text Available Aims. Latent autoimmune diabetes in adults (LADA is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods. Blood CD4+ T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results. Reduced global H3 lysine 9 methylation was observed in LADA patients’ CD4+ T lymphocytes, compared to healthy controls (P < 0.05. H3 lysine 4 methylation was not statistically different. The reduced H3 lysine 9 methylation was associated with GADA titer but not correlated with glycosylated hemoglobin (HbA1c. When the LADA patient group was divided into those with complication and those without, relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication (P < 0.05. The expression of histone methyltransferase SUV39H2 for H3 lysine 9 methylation was downregulated in LADA patients, and the expression of histone demethylase KDM4C which made H3 lysine 9 demethylation was upregulated. Conclusion. The reduction of histone H3 lysine 9 methylation which may due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in CD4+ T lymphocytes of LADA patients.

  4. Cytosine methylation alteration in natural populations of Leymus chinensis induced by multiple abiotic stresses.

    Yingjie Yu

    Full Text Available BACKGROUND: Human activity has a profound effect on the global environment and caused frequent occurrence of climatic fluctuations. To survive, plants need to adapt to the changing environmental conditions through altering their morphological and physiological traits. One known mechanism for phenotypic innovation to be achieved is environment-induced rapid yet inheritable epigenetic changes. Therefore, the use of molecular techniques to address the epigenetic mechanisms underpinning stress adaptation in plants is an important and challenging topic in biological research. In this study, we investigated the impact of warming, nitrogen (N addition, and warming+nitrogen (N addition stresses on the cytosine methylation status of Leymus chinensis Tzvel. at the population level by using the amplified fragment length polymorphism (AFLP, methylation-sensitive amplified polymorphism (MSAP and retrotransposon based sequence-specific amplification polymorphism (SSAP techniques. METHODOLOGY/PRINCIPAL FINDINGS: Our results showed that, although the percentages of cytosine methylation changes in SSAP are significantly higher than those in MSAP, all the treatment groups showed similar alteration patterns of hypermethylation and hypomethylation. It meant that the abiotic stresses have induced the alterations in cytosine methylation patterns, and the levels of cytosine methylation changes around the transposable element are higher than the other genomic regions. In addition, the identification and analysis of differentially methylated loci (DML indicated that the abiotic stresses have also caused targeted methylation changes at specific loci and these DML might have contributed to the capability of plants in adaptation to the abiotic stresses. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that abiotic stresses related to global warming and nitrogen deposition readily evoke alterations of cytosine methylation, and which may provide a molecular basis for rapid

  5. Cytosine Methylation Alteration in Natural Populations of Leymus chinensis Induced by Multiple Abiotic Stresses

    Yu, Yingjie; Yang, Xuejiao; Wang, Huaying; Shi, Fengxue; Liu, Ying; Liu, Jushan; Li, Linfeng; Wang, Deli; Liu, Bao

    2013-01-01

    Background Human activity has a profound effect on the global environment and caused frequent occurrence of climatic fluctuations. To survive, plants need to adapt to the changing environmental conditions through altering their morphological and physiological traits. One known mechanism for phenotypic innovation to be achieved is environment-induced rapid yet inheritable epigenetic changes. Therefore, the use of molecular techniques to address the epigenetic mechanisms underpinning stress adaptation in plants is an important and challenging topic in biological research. In this study, we investigated the impact of warming, nitrogen (N) addition, and warming+nitrogen (N) addition stresses on the cytosine methylation status of Leymus chinensis Tzvel. at the population level by using the amplified fragment length polymorphism (AFLP), methylation-sensitive amplified polymorphism (MSAP) and retrotransposon based sequence-specific amplification polymorphism (SSAP) techniques. Methodology/Principal Findings Our results showed that, although the percentages of cytosine methylation changes in SSAP are significantly higher than those in MSAP, all the treatment groups showed similar alteration patterns of hypermethylation and hypomethylation. It meant that the abiotic stresses have induced the alterations in cytosine methylation patterns, and the levels of cytosine methylation changes around the transposable element are higher than the other genomic regions. In addition, the identification and analysis of differentially methylated loci (DML) indicated that the abiotic stresses have also caused targeted methylation changes at specific loci and these DML might have contributed to the capability of plants in adaptation to the abiotic stresses. Conclusions/Significance Our results demonstrated that abiotic stresses related to global warming and nitrogen deposition readily evoke alterations of cytosine methylation, and which may provide a molecular basis for rapid adaptation by

  6. Status of pesticide management in the practice of vector control: a global survey in countries at risk of malaria or other major vector-borne diseases

    Berg, van den H.; Hii, J.; Soares, A.; Mnzava, A.; Ameneshewa, B.; Dash, A.P.; Ejov, M.; Tan, S.H.; Matthews, G.; Yadav, R.S.; Zaim, M.

    2011-01-01

    Background: It is critical that vector control pesticides are used for their acceptable purpose without causing adverse effects on health and the environment. This paper provides a global overview of the current status of pesticides management in the practice of vector control. Methods: A

  7. Cancer Incidence in Five Continents: Inclusion criteria, highlights from Volume X and the global status of cancer registration.

    Bray, F; Ferlay, J; Laversanne, M; Brewster, D H; Gombe Mbalawa, C; Kohler, B; Piñeros, M; Steliarova-Foucher, E; Swaminathan, R; Antoni, S; Soerjomataram, I; Forman, D

    2015-11-01

    Cancer Incidence in Five Continents (CI5), a longstanding collaboration between the International Agency for Research on Cancer and the International Association of Cancer Registries, serves as a unique source of cancer incidence data from high-quality population-based cancer registries around the world. The recent publication of Volume X comprises cancer incidence data from 290 registries covering 424 populations in 68 countries for the registration period 2003-2007. In this article, we assess the status of population-based cancer registries worldwide, describe the techniques used in CI5 to evaluate their quality and highlight the notable variation in the incidence rates of selected cancers contained within Volume X of CI5. We also discuss the Global Initiative for Cancer Registry Development as an international partnership that aims to reduce the disparities in availability of cancer incidence data for cancer control action, particularly in economically transitioning countries, already experiencing a rapid rise in the number of cancer patients annually. © 2015 UICC.

  8. Clinical Utility of promoter methylation of the tumor suppressor ...

    Aim: Aim is to examine the potential usefulness of blood based methylation specific polymerase chain reaction (MSP) of methylated DKK3 and RASSF1A genes in early detection of breast cancer. Method: Methylation status of DKK3 and RASSF1 was investigated in forty breast cancer patients, twenty fibroadenoma patients ...

  9. A lower degree of PBMC L1 methylation in women with lower folate status may explain the MTHFR C677T polymorphism associated higher risk of CIN in the US post folic acid fortification era.

    Suguna Badiga

    Full Text Available Studies in populations unexposed to folic acid (FA fortification have demonstrated that MTHFR C677T polymorphism is associated with increased risk of higher grades of cervical intraepithelial neoplasia (CIN 2+. However, it is unknown whether exposure to higher folate as a result of the FA fortification program has altered the association between MTHFR C677T and risk of CIN, or the mechanisms involved with such alterations. The current study investigated the following in a FA fortified population: 1 The association between MTHFR C677T polymorphism and risk of CIN 2+; 2 The modifying effects of plasma folate concentrations on this association; and 3 The modifying effects of plasma folate on the association between the polymorphism and degree of methylation of long interspersed nucleotide elements (L1s, in peripheral blood mononuclear cell (PBMC DNA, a documented biomarker of CIN risk.The study included 457 US women diagnosed with either CIN 2+ (cases or ≤ CIN 1 (non-cases. Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN.The 677CT/TT MTHFR genotypes were not associated with the risk of CIN 2+. Women with CT/TT genotype with lower folate, however, were more likely to be diagnosed with CIN 2+ compared to women with CT/TT genotype with higher folate (OR = 2.41, P = 0.030. Women with CT/TT genotype with lower folate were less likely to have a higher degree of PBMC L1 methylation compared to women with CT/TT genotype with higher folate (OR = 0.28, P = 0.017.This study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC L1 methylation increases the risk of CIN 2+ in women in the US post-FA fortification era. Thus, even in the post-FA fortification era, not all women have adequate folate status to overcome MTHFR 677CT/TT genotype-associated lower degree of L1 methylation.

  10. Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype

    Robinson Claire M

    2012-08-01

    Full Text Available Abstract Background Pulmonary fibrosis is a debilitating and lethal disease with no effective treatment options. Understanding the pathological processes at play will direct the application of novel therapeutic avenues. Hypoxia has been implicated in the pathogenesis of pulmonary fibrosis yet the precise mechanism by which it contributes to disease progression remains to be fully elucidated. It has been shown that chronic hypoxia can alter DNA methylation patterns in tumour-derived cell lines. This epigenetic alteration can induce changes in cellular phenotype with promoter methylation being associated with gene silencing. Of particular relevance to idiopathic pulmonary fibrosis (IPF is the observation that Thy-1 promoter methylation is associated with a myofibroblast phenotype where loss of Thy-1 occurs alongside increased alpha smooth muscle actin (α-SMA expression. The initial aim of this study was to determine whether hypoxia regulates DNA methylation in normal human lung fibroblasts (CCD19Lu. As it has been reported that hypoxia suppresses Thy-1 expression during lung development we also studied the effect of hypoxia on Thy-1 promoter methylation and gene expression. Methods CCD19Lu were grown for up to 8 days in hypoxia and assessed for global changes in DNA methylation using flow cytometry. Real-time PCR was used to quantify expression of Thy-1, α-SMA, collagen I and III. Genomic DNA was bisulphite treated and methylation specific PCR (MSPCR was used to examine the methylation status of the Thy-1 promoter. Results Significant global hypermethylation was detected in hypoxic fibroblasts relative to normoxic controls and was accompanied by increased expression of myofibroblast markers. Thy-1 mRNA expression was suppressed in hypoxic cells, which was restored with the demethylating agent 5-aza-2′-deoxycytidine. MSPCR revealed that Thy-1 became methylated following fibroblast exposure to 1% O2. Conclusion These data suggest that global and

  11. A novel method for identification and quantification of consistently differentially methylated regions.

    Ching-Lin Hsiao

    Full Text Available Advances in biotechnology have resulted in large-scale studies of DNA methylation. A differentially methylated region (DMR is a genomic region with multiple adjacent CpG sites that exhibit different methylation statuses among multiple samples. Many so-called "supervised" methods have been established to identify DMRs between two or more comparison groups. Methods for the identification of DMRs without reference to phenotypic information are, however, less well studied. An alternative "unsupervised" approach was proposed, in which DMRs in studied samples were identified with consideration of nature dependence structure of methylation measurements between neighboring probes from tiling arrays. Through simulation study, we investigated effects of dependencies between neighboring probes on determining DMRs where a lot of spurious signals would be produced if the methylation data were analyzed independently of the probe. In contrast, our newly proposed method could successfully correct for this effect with a well-controlled false positive rate and a comparable sensitivity. By applying to two real datasets, we demonstrated that our method could provide a global picture of methylation variation in studied samples. R source codes to implement the proposed method were freely available at http://www.csjfann.ibms.sinica.edu.tw/eag/programlist/ICDMR/ICDMR.html.

  12. Kajian metode Subjective Global Assessment (SGA dan Nutrition Services Screening Assesment (NSSA sebagai status gizi awal pasien dewasa sebagai prediktor lama rawat inap dan status pulang

    Agustinus I Wayan Harimawan

    2011-03-01

    Full Text Available Background: Assessment of nutrition status of newly hospitalized patients is an initial stage of nutrition intervention which will bring effects to the duration of stay and the history of patients' diseases during hospitalization. Appropriate nutrition intervention as part of  patients' care can be used as an indicator of the quality of hospital service. Objective: The study aimed to identify preliminary nutrition status of newly hospitalized adult patients using SGA method, its effects to length of stay and status of discharge and compare the capacity of SGA and NSSA indicators in predicting length of stay and status of discharge of adult patients. Method: This observational study used prospective cohort study design. It was carried out at Anuntaloko Hospital of Parigi, District of Parigi Moutong, Sulawesi Tengah from July to September 2008. Subject consisted of 162 people comprising 82 undernourished people and 80 people with good nutrition status based on assessment using SGA method. Data analysis used bivariable and multivariable, receiver operating characteristics (ROC curve and diagnostic methods using computer program. Result: The majority of newly hospitalized patients were undernourished (50.6%; preliminary status of patients assessed using SGA method could affect length of stay, relative risk (RR=3.67 but not status of discharge (RR=0.97. The capacity of SGA indicator, area under the curve (AUC=0.81 and maximum sum of sensitivity and specifcity (MSS =1.57 was better than NSSA indicator (AUC=0.76 and MSS 1.43 in predicting length of stay. The capacity of SGA indicator (AUC=0.50 and MSS=1.01 was better than NSSA indicator (AUC=0.49 and MSS=0.98 in predicting discharge status of the patient. Conclusion: SGA and NSSA indicators could be implemented in assessing preliminary nutrition status of newly hospitalized adult patients; SGA indicator had better capacity than NSSA indicator.

  13. Evaluation of conducting a screening assessment of nutritional status of hospitalized patients. Presentation of main goals and objectives of the global health project "NutritionDay".

    Jeznach-Steinhagen, Anna; Ostrowska, Joanna; Czerwonogrodzka-Senczyna, Aneta

    2016-01-01

    European Society for Clinical Nutrition and Metabolism (ESPEN) commenced in 2004 a global health project named "NutritionDay" aiming to promote awareness of proper nutritional status of hospitalized patients and to draw attention to the need for early detection of malnutrition among patients. Under the Polish law--pursunat to the regulation of the Minister of Health dated September 15, 2011 (amendment as of 27.12.2013)--a nutritional status of each patient should be assessed at the time of a hospital admission. of this study was to analyze the fulfilment of the mandatory questionnaire assessment of nutritional status at selected wards of one of Warsaw's clinical hospitals. The study included an analysis of medical records of patients hospitalized within 6 months (n = 26375). The correct fulfilment of screening questionnaire assessing nutritional status (NRS 2002 survey) and the information about patients' body weight as well as the results assessment of nutritional status were subject to the analysis. NRS 2002 questionnaire was present in only 67,14% medical records of patients, however 49.24% of them were unfilled. The obtained results confirming low degree of NRS 2002 questionnaires' fulfilment in one of the Warsaw clinical hospitals draws attention to the need for education of hospital personnel in the field of significance of screening of nutritional assessment and its regulations. The "NutritionDay" project is an interesting form to attract attention of the aforementioned problem and its global extent additionally encourage medical units to participate in the project.

  14. Validation and global uncertainty of a liquid chromatographic with diode array detection method for the screening of azoxystrobin, kresoxim-methyl, trifloxystrobin, famoxadone, pyraclostrobin and fenamidone in grapes and wine.

    de Melo Abreu, Susana; Caboni, Pierluigi; Cabras, Paolo; Garau, Vincenzo Luigi; Alves, Arminda

    2006-07-28

    Azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, famoxadone and fenamidone are permitted Q(o) Inhibitor (Q(o)I) fungicides applied to vine in some European countries for the treatment of downy and powdery mildews. In this work, a method is validated for the analysis of these fungicides in grapes and wine. This screening method consists in a simple one step liquid-liquid extraction followed by liquid chromatography (LC) fitted with a diode array detector (DAD). Limits of detection for grapes and wine were below 0.2 mg kg(-1) or mg l(-1), precision was not above 13%, and recoveries were, on average, 95+/-5% for grapes and 104+/-6% for wine. Global uncertainties evaluated in the concentration range from 0.25 to 2.50 mg l(-1) were below 20%. A confirmatory method by gas chromatography (GC) with mass spectrometry (MS) detection was used.

  15. High food prices and the global financial crisis have reduced access to nutritious food and worsened nutritional status and health.

    Brinkman, Henk-Jan; de Pee, Saskia; Sanogo, Issa; Subran, Ludovic; Bloem, Martin W

    2010-01-01

    A global economic and financial crisis is engulfing the developing world, coming on top of high food and fuel prices. This paper assesses the impact of the crises on food consumption, nutrition, and health. Several methods were applied, including risk analysis using the cost of the food basket, assessment surveys, simulations, regression analysis using a food consumption score (FCS), reflecting diet frequency and diversity, and a review of the impact of such dietary changes on nutritional status and health. The cost of the food basket increased in several countries, forcing households to reduce quality and quantity of food consumed. The FCS, which is a measure of diet diversity, is negatively correlated with food prices. Simulations show that energy consumption declined during 2006-2010 in nearly all developing regions, resulting potentially in an additional 457 million people (of 4.5 billion) at risk of being hungry and many more unable to afford the dietary quality required to perform, develop, and grow well. As a result of the crises, large numbers of vulnerable households have reduced the quality and quantity of foods they consume and are at risk of increased malnutrition. Population groups most affected are those with the highest requirements, including young children, pregnant and lactating women, and the chronically ill (particularly people with HIV/AIDS and tuberculosis). Because undernutrition during the first 2 y of life has life-long consequences, even short-term price rises will have long-term effects. Thus, measures to mitigate the impact of the crises are urgently required.

  16. Modification of oxidative status in Plasmodium berghei-infected erythrocytes by E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl-2'-methyliden]-quinoline compared to chloroquine

    Juan Rodrigues

    2009-09-01

    Full Text Available E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl-2'-methyliden]-quinoline (IQ is a new quinoline derivative which has been reported as a haemoglobin degradation and ß-haematin formation inhibitor. The haemoglobin proteolysis induced by Plasmodium parasites represents a source of amino acids and haeme, leading to oxidative stress in infected cells. In this paper, we evaluated oxidative status in Plasmodium berghei-infected erythrocytes in the presence of IQ using chloroquine (CQ as a control. After haemolysis, superoxide dismutase (SOD, catalase, glutathione cycle and NADPH + H+-dependent dehydrogenase enzyme activities were investigated. Lipid peroxidation was also assayed to evaluate lipid damage. The results showed that the overall activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were significantly diminished by IQ (by 53.5% and 100%, respectively. Glutathione peroxidase activity was also lowered (31% in conjunction with a higher GSSG/GSH ratio. As a compensatory response, overall SOD activity increased and lipid peroxidation decreased, protecting the cells from the haemolysis caused by the infection. CQ shared most of the effects showed by IQ; however it was able to inhibit the activity of isocitrate dehydrogenase and glutathione-S-transferase. In conclusion, IQ could be a candidate for further studies in malaria research interfering with the oxidative status in Plasmodium berghei infection.

  17. SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells.

    Toghill, Bradley J; Saratzis, Athanasios; Freeman, Peter J; Sylvius, Nicolas; Bown, Matthew J

    2018-01-01

    Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter ( P  AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R , 2 CpGs were hyper-methylated ( P  = 0.0145); in ERG , 13 CpGs were hyper-methylated ( P  = 0.0005); in SERPINB9 , 6 CpGs were hypo-methylated ( P  = 0.0037) and 1 CpG was hyper-methylated ( P  = 0.0098); and in SMYD2 , 4 CpGs were hypo-methylated ( P  = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression ( P  = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that methylation status of the SMYD2 promoter may be linked with decreased SMYD2 expression in disease pathobiology. In

  18. DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients

    Crujeiras, A. B.; Diaz-Lagares, A.; Sandoval, J.; Milagro, F. I.; Navas-Carretero, S.; Carreira, M. C.; Gomez, A.; Hervas, D.; Monteiro, M. P.; Casanueva, F. F.; Esteller, M.; Martinez, J. A.

    2017-01-01

    The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip. Data were compared between samples from obese (n = 45) and non-obese (n = 8–10) patients by Wilcoxon-rank test, unadjusted for cell type distributions. A global hypomethylation of the differentially methylated CpG sites (DMCpGs) was observed in the obese subcutaneous adipose tissue and leukocytes. The overlap analysis yielded a number of genes mapped by the common DMCpGs that were identified to reflect the obesity state in the leukocytes. Specifically, the methylation levels of FGFRL1, NCAPH2, PNKD and SMAD3 exhibited excellent and statistically significant efficiencies in the discrimination of obesity from non-obesity status (AUC > 0.80; p obesity-related adipose tissue pathogenesis through peripheral blood analysis, an easily accessible and minimally invasive biological material instead of adipose tissue. PMID:28211912

  19. Effects of nickel, chromate, and arsenite on histone 3 lysine methylation

    Zhou Xue; Li Qin; Arita, Adriana; Sun Hong; Costa, Max

    2009-01-01

    Occupational exposure to nickel (Ni), chromium (Cr), and arsenic (As) containing compounds has been associated with lung cancer and other adverse health effects. Their carcinogenic properties may be attributable in part, to activation and/or repression of gene expression induced by changes in the DNA methylation status and histone tail post-translational modifications. Here we show that individual treatment with nickel, chromate, and arsenite all affect the gene activating mark H3K4 methylation. We found that nickel (1 mM), chromate (10 μM), and arsenite (1 μM) significantly increase tri-methyl H3K4 after 24 h exposure in human lung carcinoma A549 cells. Seven days of exposure to lower levels of nickel (50 and 100 μM), chromate (0.5 and 1 μM) or arsenite (0.1, 0.5 and 1 μM) also increased tri-methylated H3K4 in A549 cells. This mark still remained elevated and inherited through cell division 7 days following removal of 1 μM arsenite. We also demonstrate by dual staining immunofluorescence microscopy that both H3K4 tri-methyl and H3K9 di-methyl marks increase globally after 24 h exposure to each metal treatment in A549 cells. However, the tri-methyl H3K4 and di-methyl H3K9 marks localize in different regions in the nucleus of the cell. Thus, our study provides further evidence that a mechanism(s) of carcinogenicity of nickel, chromate, and arsenite metal compounds may involve alterations of various histone tail modifications that may in turn affect the expression of genes that may cause transformation

  20. Association between human papillomavirus and Epstein - Barr virus DNA and gene promoter methylation of RB1 and CDH1 in the cervical lesions: a transversal study.

    McCormick, Thaís M; Canedo, Nathalie H S; Furtado, Yara L; Silveira, Filomena A; de Lima, Roberto J; Rosman, Andréa D F; Almeida Filho, Gutemberg L; Carvalho, Maria da Glória da C

    2015-06-02

    Human papillomavirus (HPV) inactivates the retinoblastoma 1 (RB1) gene by promoter methylation and reduces cellular E-cadherin expression by overexpression of DNA methyltransferase 1 (DNMT1). The Epstein-Barr virus (EBV) is an oncogenic virus that may be related to cervical carcinogenesis. In gastric cancer, it has been demonstrated that E-cadherin gene (CDH1) hypermethylation is associated with DNMT1 overexpression by EBV infection. Our aim was to analyze the gene promoter methylation frequency of RB1 and CDH1 and verify the association between that methylation frequency and HPV and EBV infection in cervical lesions. Sixty-five samples were obtained from cervical specimens: 15 normal cervices, 17 low-grade squamous intraepithelial lesions (LSIL), 15 high-grade squamous intraepithelial lesions (HSIL), and 18 cervical cancers. HPV and EBV DNA testing was performed by PCR, and the methylation status was verified by MSP. HPV frequency was associated with cervical cancer cases (p = 0.005) but not EBV frequency (p = 0.732). Viral co-infection showed a statistically significant correlation with cancer (p = 0.027). No viral infection was detected in 33.3% (5/15) of controls. RB1 methylated status was associated with cancer (p = 0.009) and HPV infection (p = 0.042). CDH1 methylation was not associated with cancer (p = 0.181). Controls and LSIL samples did not show simultaneous methylation, while both genes were methylated in 27.8% (5/18) of cancer samples. In the presence of EBV, CDH1 methylation was present in 27.8% (5/18) of cancer samples. Only cancer cases presented RB1 promoter methylation in the presence of HPV and EBV (33.3%). The methylation status of both genes increased with disease progression. With EBV, RB1 methylation was a tumor-associated event because only the cancer group presented methylated RB1 with HPV infection. HPV infection was shown to be significantly correlated with cancer conditions. The global methylation frequency was

  1. Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth.

    Angela M Devlin

    2010-08-01

    Full Text Available Prenatal and early postnatal exposure to maternal depression may "program" childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR is an important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour.Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS and the Hamilton Rating Scale for Depression (HAM-D in women (n = 82, all taking folate during the 2(nd and 3(rd trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2(nd trimester depressed mood (p<0.05. Increased 2(nd trimester maternal depressed mood (EPDS scores was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05, but had no effect on BDNF promoter methylation.These findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.

  2. Sun exposure and vitamin D supplementation in relation to vitamin D status of breastfeeding mothers and infants in the global exploration of human milk study.

    Dawodu, Adekunle; Davidson, Barbara; Woo, Jessica G; Peng, Yong-Mei; Ruiz-Palacios, Guillermo M; de Lourdes Guerrero, Maria; Morrow, Ardythe L

    2015-02-05

    Although vitamin D (vD) deficiency is common in breastfed infants and their mothers during pregnancy and lactation, a standardized global comparison is lacking. We studied the prevalence and risk factors for vD deficiency using a standardized protocol in a cohort of breastfeeding mother-infant pairs, enrolled in the Global Exploration of Human Milk Study, designed to examine longitudinally the effect of environment, diet and culture. Mothers planned to provide breast milk for at least three months post-partum and were enrolled at four weeks postpartum in Shanghai, China (n=112), Cincinnati, Ohio (n=119), and Mexico City, Mexico (n=113). Maternal serum 25(OH)D was measured by radioimmunoassay (obesity (p=0.03), season (p=0.001) and sites (p<0.001) predicted maternal vD status. vD deficiency in order of magnitude was found in 62%, 28%, and 6% of Mexican, Cincinnati and Shanghai infants, respectively (p<0.001). Season (p=0.022), adding formula feeding (p<0.001) and a higher sun index (p=0.085) predicted higher infant vD status. vD deficiency appears to be a global problem in mothers and infants, though the prevalence in diverse populations may depend upon sun exposure behaviors and vD supplementation. Greater attention to maternal and infant vD status starting during pregnancy is warranted worldwide.

  3. Homogalacturonan methyl-esterification and plant development.

    Wolf, Sebastian; Mouille, Grégory; Pelloux, Jérome

    2009-09-01

    The ability of a plant cell to expand is largely defined by the physical constraints imposed by its cell wall. Accordingly, cell wall properties have to be regulated during development. The pectic polysaccharide homogalacturonan is a major component of the plant primary walls. Biosynthesis and in muro modification of homogalacturonan have recently emerged as key determinants of plant development, controlling cell adhesion, organ development, and phyllotactic patterning. This review will focus on recent findings regarding impact of homogalacturonan content and methyl-esterification status of this polymer on plant life. De-methyl-esterification of homogalacturonan occurs through the action of the ubiquitous enzyme 'pectin methyl-esterase'. We here describe various strategies developed by the plant to finely tune the methyl-esterification status of homogalacturonan along key events of the plant lifecycle.

  4. Modeling spatiotemporal dynamics of DNA methylation

    Lövkvist, Cecilia Elisabet

    into how epigenetic marks are distributed in the human genome. In the first part of the thesis, we investigate DNA methylation and maintenance of methylation patterns throughout cell division. We argue that collaborative models, those where the methylation of CpG sites depends on the methylation status...... into the game more explicitly in another type of model that speaks out the duality of the two aspects. Using statistical analysis of experimental data, this thesis further explores a link between DNA methylation and nucleosome occupancy. By comparing the patterns on promoters to regions with similar Cp...... division. The patterns of epigentic marks depend on enzymes that ensure their maintenance and introduction. Using theoretical models, this thesis proposes new mechanisms for how enzymes operate to maintain patterns of epigenetic marks. Through analysis of experimental data this work gives new insight...

  5. Methyl chloride in the UT/LS observed by CARIBIC: global distribution, Asian summer monsoon outflow, and use as a tracer for tropical air

    Baker, A. K.; Umezawa, T.; Oram, D.; Sauvage, C.; Rauthe-Schoech, A.; Montzka, S. A.; Zahn, A.; Brenninkmeijer, C. A. M.

    2014-12-01

    We present spatiotemporal variations of methyl chloride (CH3Cl) in the UT/LS observed mainly by the CARIBIC passenger aircraft for the years 2005-2011. The CH3Cl mixing ratio in the UT over Europe was higher than that observed at a European surface baseline station year-round, indicative of a persistent positive vertical gradient at NH mid latitudes. A series of flights over Africa and South Asia show that CH3Cl mixing ratios increase toward tropical latitudes, and the observed UT CH3Cl level over these two regions and the Atlantic was higher than that measured at remote surface sites. Strong emissions of CH3Cl in the tropics combined with meridional transport through the UT may explain such vertical and latitudinal gradients. Comparisons with CO data indicate that non-combustion sources in the tropics dominantly contribute to forming the latitudinal gradient of CH3Cl in the UT. We also observed elevated CH3Cl and CO in air influenced by biomass burning in South America and Africa, and the enhancement ratios derived for CH3Cl to CO in those regions agree with previous observations. In contrast, correlations indicate a high CH3Cl to CO ratio of 2.9±0.5 ppt ppb-1 in the Asian summer monsoon anticyclone and domestic biofuel emissions in South Asia are inferred to be responsible. We estimated CH3Cl emissions from South Asia to be 134±23 Gg Cl yr-1, which is higher than a previous estimate due to the higher CH3Cl to CO ratio observed in this study. We also examine the use of CH3Cl as a tracer of tropical tropospheric air in the LMS, where we identified air masses with elevated CH3Cl that were however stratospheric in terms of N2O. Back trajectories suggest recent low-latitude origins of such air masses in early summer. In this season, high CH3Cl LMS air shows a clear branch connecting stratospheric and tropical tropospheric air on N2O-CH3Cl scatterplots. This distinct feature vanishes in late summer when the LMS is ventilated by tropospheric air.

  6. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    Yamada, Akifumi; Momosaki, Sotaro; Hosoi, Rie; Abe, Kohji; Yamaguchi, Masatoshi; Inoue, Osamu

    2009-01-01

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [ 14 C]2-deoxyglucose ([ 14 C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [ 14 C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [ 14 C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [ 14 C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  7. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    Yamada, Akifumi [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Momosaki, Sotaro; Hosoi, Rie [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Abe, Kohji [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Developmental Research Laboratories, Shionogi and Co., Ltd., Toyonaka, Osaka, 561-0825 (Japan); Yamaguchi, Masatoshi [Faculty of Pharmaceutical Sciences, Fukuoka University, Johnan, Fukuoka 814-0180 (Japan); Inoue, Osamu [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)

    2009-11-15

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [{sup 14}C]2-deoxyglucose ([{sup 14}C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [{sup 14}C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [{sup 14}C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [{sup 14}C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  8. A cohort study evaluating the implications of biology, weight status and socioeconomic level on global self-esteem competence among female African-American adolescents.

    Powell-Young, Yolanda M; Zabaleta, Jovanny; Velasco-Gonzalez, Cruz; Sothern, Melinda S

    2013-07-01

    The link between obesity and self-esteem among minority youth has received minimal empirical evaluation. This study aims to describe the magnitude of risk that body mass index, household income, and transitional age have on global self-esteem levels among African-American adolescents. These analyses were conducted on cross-sectional data obtained from 264 urban-dwelling African-American females between 14 and 18 years of age. Survey data on global self-esteem levels, transitory age, and socioeconomic levels were collected using self-administered questionnaires. Measured height and weight values were used to calculate and categorize weight status according to body mass index. Logistic regression models examined the probability of reporting less than average levels of global self-esteem. Adolescent African-American females residing in low-income households were 10 times more likely to report lower global self-esteem scores than those individuals from more affluent households (95% CI: 1.94, 60.19, p self-esteem among participants in this study. Household income appears to be the greatest predictor of global self-esteem levels. Further research in this area is needed to fully elucidate precursors for psychological health vulnerability and facilitate intervention development.

  9. A Cohort Study Evaluating the Implications of Biology, Weight Status and Socioeconomic Level on Global Self-Esteem Competence Among Female African-American Adolescents

    Powell-Young, Yolanda M.; Zabaleta, Jovanny; Velasco-Gonzalez, Cruz; Sothern, Melinda S.

    2014-01-01

    The link between obesity and self-esteem among minority youth has received minimal empirical evaluation. This study aims to describe the magnitude of risk that body mass index, household income, and transitional age have on global self-esteem levels among African-American adolescents. These analyses were conducted on cross-sectional data obtained from 264 urban-dwelling African-American females between 14 and 18 years of age. Survey data on global self-esteem levels, transitory age, and socioeconomic levels were collected using self-administered questionnaires. Measured height and weight values were used to calculate and categorize weight status according to body mass index. Logistic regression models examined the probability of reporting less than average levels of global self-esteem. Adolescent African-American females residing in low-income households were 10 times more likely to report lower global self-esteem scores than those individuals from more affluent households (95% CI: 1.94, 60.19, p self-esteem among participants in this study. Household income appears to be the greatest predictor of global self-esteem levels. Further research in this area is needed to fully elucidate precursors for psychological health vulnerability and facilitate intervention development. PMID:24218867

  10. CpG Island Methylator Phenotype in Primary Gastric Carcinoma

    TOJO Masayuki:筆頭著者; KONISHI Kazuo; YANO Yuichiro; KATAGIRI Atsushi; NOZAWA Hisako; KUBOTA Yutaro; MURAMOTO Takashi; KONDA Kenichi; SHINMURA Kensuke; TAKIMOTO Masafumi; IMAWARI Michio; YOSHIDA Hitoshi

    2013-01-01

    Gastric cancers (GC) with methylation of multiple CpG islands have a CpG island methylator phenotype (CIMP) and they can have different biological features. The aim of this study was to investigate the DNA methylation status of GCs and its association with their clinicopathological features. We evaluated the methylation status of four genes (MINT1, MINT2, MINT25 and MINT31) in 105 primary GCs using bisulfite-pyrosequencing analysis. We classified tumors as CIMP-high (CIMP-H), CIMP-low (CIMP-L...

  11. Phosphatase Rtr1 Regulates Global Levels of Serine 5 RNA Polymerase II C-Terminal Domain Phosphorylation and Cotranscriptional Histone Methylation.

    Hunter, Gerald O; Fox, Melanie J; Smith-Kinnaman, Whitney R; Gogol, Madelaine; Fleharty, Brian; Mosley, Amber L

    2016-09-01

    In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3). Using chromatin immunoprecipitation and high-resolution microarrays, we show that RTR1 deletion results in global changes in RNAPII Ser5-P levels on genes with different lengths and transcription rates consistent with its role as a CTD phosphatase. Although Ser5-P levels increase, the overall occupancy of RNAPII either decreases or stays the same in the absence of RTR1 Additionally, the loss of Rtr1 in vivo leads to increases in H3K36me3 levels genome-wide, while total histone H3 levels remain relatively constant within coding regions. Overall, these findings suggest that Rtr1 regulates H3K36me3 levels through changes in the number of binding sites for the histone methyltransferase Set2, thereby influencing both the CTD and histone codes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast adenocarcinoma cells to radiation-induced apoptosis

    Luzhna, Lidia [Department of Biological Sciences, University of Lethbridge, AB, Canada T1K 3M4 (Canada); Kovalchuk, Olga, E-mail: olga.kovalchuk@uleth.ca [Department of Biological Sciences, University of Lethbridge, AB, Canada T1K 3M4 (Canada)

    2010-02-05

    Chemoresistant tumors often fail to respond to other cytotoxic treatments such as radiation therapy. The mechanisms of chemo- and radiotherapy cross resistance are not fully understood and are believed to be epigenetic in nature. We hypothesize that MCF-7 cells and their doxorubicin-resistant variant MCF-7/DOX cells may exhibit different responses to ionizing radiation due to their dissimilar epigenetic status. Similar to previous studies, we found that MCF-7/DOX cells harbor much lower levels of global DNA methylation than MCF-7 cells. Furthermore, we found that MCF-7/DOX cells had lower background apoptosis levels and were less responsive to radiation than MCF-7 cells. Decreased radiation responsiveness correlated to significant global DNA hypomethylation in MCF-7/DOX cells. Here, for the first time, we show that the radiation resistance of MCF-7/DOX cells can be reversed by an epigenetic treatment - the application of methyl-donor SAM. SAM-mediated reversal of DNA methylation led to elevated radiation sensitivity in MCF-7/DOX cells. Contrarily, application of SAM on the radiation sensitive and higher methylated MCF-7 cells resulted in a decrease in their radiation responsiveness. This data suggests that a fine balance of DNA methylation is needed to insure proper radiation and drug responsiveness.

  13. Integrated analysis of gene expression, CpG island methylation, and gene copy number in breast cancer cells by deep sequencing.

    Zhifu Sun

    Full Text Available We used deep sequencing technology to profile the transcriptome, gene copy number, and CpG island methylation status simultaneously in eight commonly used breast cell lines to develop a model for how these genomic features are integrated in estrogen receptor positive (ER+ and negative breast cancer. Total mRNA sequence, gene copy number, and genomic CpG island methylation were carried out using the Illumina Genome Analyzer. Sequences were mapped to the human genome to obtain digitized gene expression data, DNA copy number in reference to the non-tumor cell line (MCF10A, and methylation status of 21,570 CpG islands to identify differentially expressed genes that were correlated with methylation or copy number changes. These were evaluated in a dataset from 129 primary breast tumors. Gene expression in cell lines was dominated by ER-associated genes. ER+ and ER- cell lines formed two distinct, stable clusters, and 1,873 genes were differentially expressed in the two groups. Part of chromosome 8 was deleted in all ER- cells and part of chromosome 17 amplified in all ER+ cells. These loci encoded 30 genes that were overexpressed in ER+ cells; 9 of these genes were overexpressed in ER+ tumors. We identified 149 differentially expressed genes that exhibited differential methylation of one or more CpG islands within 5 kb of the 5' end of the gene and for which mRNA abundance was inversely correlated with CpG island methylation status. In primary tumors we identified 84 genes that appear to be robust components of the methylation signature that we identified in ER+ cell lines. Our analyses reveal a global pattern of differential CpG island methylation that contributes to the transcriptome landscape of ER+ and ER- breast cancer cells and tumors. The role of gene amplification/deletion appears to more modest, although several potentially significant genes appear to be regulated by copy number aberrations.

  14. Evaluation of Nutritional Status of Cancer Patients during Treatment by Patient-Generated Subjective Global Assessment: a Hospital-Based Study.

    Sharma, Dibyendu; Kannan, Ravi; Tapkire, Ritesh; Nath, Soumitra

    2015-01-01

    Cancer patients frequently experience malnutrition. Cancer and cancer therapy effects nutritional status through alterations in the metabolic system and reduction in food intake. In the present study, fifty seven cancer patients were selected as subjects from the oncology ward of Cachar Cancer Hospital and Research Centre, Silchar, India. Evaluation of nutritional status of cancer patients during treatment was carried out by scored Patient-Generated Subjective Global Assessment (PG-SGA). The findings of PG-SGA showed that 15.8% (9) were well nourished, 31.6% (18) were moderately or suspected of being malnourished and 52.6% (30) were severely malnourished. The prevalence of malnutrition was highest in lip/oral (33.33%) cancer patients. The study showed that the prevalence of malnutrition (84.2%) was high in cancer patients during treatment.

  15. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

    Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

    2004-01-01

    The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16 INKa and DNA repair gene O 6 -methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16 INKa promoter methylation upon LDR exposure. In male liver tissue, p16 INKa promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16 INKa promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16 INKa and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure

  16. Evidence for non-CpG methylation in mammals

    Yan, Jie; Zierath, Juleen R; Barres, Romain

    2011-01-01

    In mammals, the existence of cytosine methylation on non-CpG sequences is controversial. Here, we adapted a LuminoMetric-based Assay (LUMA) to determine global non-CpG methylation levels in rodent and human tissues. We observed that......In mammals, the existence of cytosine methylation on non-CpG sequences is controversial. Here, we adapted a LuminoMetric-based Assay (LUMA) to determine global non-CpG methylation levels in rodent and human tissues. We observed that...

  17. DNA Methylation Modulates Nociceptive Sensitization after Incision.

    Yuan Sun

    Full Text Available DNA methylation is a key epigenetic mechanism controlling DNA accessibility and gene expression. Blockade of DNA methylation can significantly affect pain behaviors implicated in neuropathic and inflammatory pain. However, the role of DNA methylation with regard to postoperative pain has not yet been explored. In this study we sought to investigate the role of DNA methylation in modulating incisional pain and identify possible targets under DNA methylation and contributing to incisional pain. DNA methyltranferase (DNMT inhibitor 5-Aza-2'-deoxycytidine significantly reduced incision-induced mechanical allodynia and thermal sensitivity. Aza-2'-deoxycytidine also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. Global DNA methylation and DNMT3b expression were increased in skin after incision, but none of DNMT1, DNMT3a or DNMT3b was altered in spinal cord or DRG. The expression of proopiomelanocortin Pomc encoding β-endorphin and Oprm1 encoding the mu-opioid receptor were upregulated peripherally after incision; moreover, Oprm1 expression was further increased under DNMT inhibitor treatment. Finally, local peripheral injection of the opioid receptor antagonist naloxone significantly exacerbated incision-induced mechanical hypersensitivity. These results suggest that DNA methylation is functionally relevant to incisional nociceptive sensitization, and that mu-opioid receptor signaling might be one methylation regulated pathway controlling sensitization after incision.

  18. Renewable energy from wind and sun. Status quo and development perspectives at the global level; Erneuerbare Energie aus Sonne und Wind. Status quo und Entwicklungsperspektiven weltweit

    Graichen, Patrick; Grotewold, Lars [Agora Energiewende, Berlin (Germany); Kordowski, Klaus; Wesemann, Philipp [Stiftung Mercator, Essen (Germany)

    2015-01-15

    The global market for renewable energy technologies has experienced strong growth since the year 2000. In 2013 newly installed electricity production plants based on renewable energy for the first time outnumbered the aggregate of newly installed plants based on coal, gas or nuclear energy. In more and more parts of the world, wind and solar energy plants are becoming the most cost-effective means of electricity production. As renewable energy resources begin to claim significant shares in the energy mix they also become more system-relevant, resulting in a need for more investment as well as regulatory changes. Due to their specific features (high capital intensity, low incremental costs, fluctuating electricity production), and in spite of the marked decline in costs, wind and solar energy are still dependent on proactive policies in support of renewable energy.

  19. DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors

    Amatruda, James F; Frazier, A Lindsay; Poynter, Jenny N; Ross, Julie A; Christensen, Brock; Fustino, Nicholas J; Chen, Kenneth S; Hooten, Anthony J; Nelson, Heather; Kuriger, Jacquelyn K; Rakheja, Dinesh

    2013-01-01

    Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy

  20. Methyl-perfluoroheptene-ethers (CH3OC7F13): measured OH radical reaction rate coefficients for several isomers and enantiomers and their atmospheric lifetimes and global warming potentials.

    Jubb, Aaron M; Gierczak, Tomasz; Baasandorj, Munkhbayar; Waterland, Robert L; Burkholder, James B

    2014-05-06

    Mixtures of methyl-perfluoroheptene-ethers (CH3OC7F13, MPHEs) are currently in use as replacements for perfluorinated alkanes (PFCs) and poly-ether heat transfer fluids, which are persistent greenhouse gases with lifetimes >1000 years. At present, the atmospheric processing and environmental impact from the use of MPHEs is unknown. In this work, rate coefficients at 296 K for the gas-phase reaction of the OH radical with six key isomers (including stereoisomers and enantiomers) of MPHEs used commercially were measured using a relative rate method. Rate coefficients for the six MPHE isomers ranged from ∼ 0.1 to 2.9 × 10(-12) cm(3) molecule(-1) s(-1) with a strong stereoisomer and -OCH3 group position dependence; the (E)-stereoisomers with the -OCH3 group in an α- position relative to the double bond had the greatest reactivity. Rate coefficients measured for the d3-MPHE isomer analogues showed decreased reactivity consistent with a minor contribution of H atom abstraction from the -OCH3 group to the overall reactivity. Estimated atmospheric lifetimes for the MPHE isomers range from days to months. Atmospheric lifetimes, radiative efficiencies, and global warming potentials for these short-lived MPHE isomers were estimated based on the measured OH rate coefficients along with measured and theoretically calculated MPHE infrared absorption spectra. Our results highlight the importance of quantifying the atmospheric impact of individual components in an isomeric mixture.

  1. Global Diversity and Local Consensus in Status Beliefs : The Role of Network Clustering and Resistance to Belief Change

    Grow, André; Flache, Andreas; Wittek, Rafael

    2017-01-01

    Formal models of status construction theory suggest that beliefs about the relative social worth and competence of members of different social groups can emerge from face-to-face interactions in task-focused groups and eventually become consensual in large populations. We propose two extensions of

  2. Implementation status of the global and local beam position feedback systems for the Advanced Photon Source storage ring

    Chung, Y.; Barr, D.; Decker, G.; Galayda, J.; Kirchman, J.; Lenkszus, F.; Lumpkin, A.; Votaw, A.J.

    1995-01-01

    The Advanced Photon Source (APS) is implementing an extensive beam position feedback system for both global and local stabilization of particle and photon beams based on digital signal processing. The description and operational experience of the system will be given in this paper. In particular, we will discuss the underlying fundamental principles, hardware layout, controls interface, and automatic software generation for multiple digital signal processors (DSPS) distributed in 20 VME crates around the ring. The feedback system runs at 4-kHz sampling frequency in order to achieve the correction bandwidth of approximately 100 Hz. For the maximum correction efficiency and resolution of conflicts among multiple local feedback systems due to the local bump closure error, the global and local feedback systems are combined into a single unified system. This novel approach is made possible through data sharing among the global and local systems via the fiber-optically networked reflective memories

  3. What’s Next: The Status of ISO Global KM Standards and the Importance of Managing Knowledge Assets

    Young, R.

    2016-01-01

    Full text: Ron Young, CEO of Knowledge Associates International, based in Cambridge UK, is Chair of the BSI KM Standards Committee KMS/1, member of the BSI Asset Management Committee AMS/1 working with ISO 55000, and member of the ISO 30401 workgroup developing a global KM Standard. He will present the benefits, challenges and implications of a global KM standard, from his perspective, and give an update on the ISO/BSI standard development. He will also provide insights into the latest developments with knowledge asset management. (author

  4. Dissociation dynamics of methylal

    Beaud, P; Frey, H -M; Gerber, T; Mischler, B; Radi, P P; Tzannis, A -P [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    The dissociation of methylal is investigated using mass spectrometry, combined with a pyrolytic radical source and femtosecond pump probe experiments. Based on preliminary results two reaction paths of methylal dissociation are proposed and discussed. (author) 4 fig., 3 refs.

  5. Experimental vapor pressures (from 1 Pa to 100 kPa) of six saturated Fatty Acid Methyl Esters (FAMEs): Methyl hexanoate, methyl octanoate, methyl decanoate, methyl dodecanoate, methyl tetradecanoate and methyl hexadecanoate

    Sahraoui, Lakhdar; Khimeche, Kamel; Dahmani, Abdallah; Mokbel, Ilham; Jose, Jacques

    2016-01-01

    Highlight: • Vapor-liquid equilibria, Enthalpy of Vaporization, saturated Fatty Acid Methyl Ester. - Abstract: Vapor pressures of six saturated Fatty Acid Methyl Esters (FAMEs), methyl hexanoate (or methyl caproate), methyl octanoate (or methyl caprylate), Methyl decanoate (or methyl caprate), methyl dodecanoate (or methyl laurate), methyl tetradecanoate (or methyl myristate), and methyl hexadecanoate (or methyl palmitate) were measured from 1 Pa to 100 kPa and at temperature range between 262 and 453 K using a static apparatus. The experimental data (P-T) were compared with the available literature data.

  6. A Comparison of the Nutritional Risk Screening 2002 Tool With the Subjective Global Assessment Tool to Detect Nutritional Status in Chinese Patients Undergoing Surgery With Gastrointestinal Cancer.

    Chi, Juntao; Yin, Shaohua; Zhu, Yongjian; Gao, Fengli; Song, Xinna; Song, Zhenlan; Lv, Junying; Li, Miaomiao

    The objectives of this study were to describe the nutritional status of Chinese patients with gastrointestinal cancer undergoing surgery and to compare the ease of use, diversity, and concordance of the Nutritional Risk Screening 2002 with the Subjective Global Assessment in the same patients. A total of 280 gastrointestinal cancer patients admitted for elective surgery were evaluated by the Nutritional Risk Screening 2002 (NRS 2002) and Subjective Global Assessment (SGA) tools within 48 hours of admission from April to October 2012. Related opinions about ease of using the tools were obtained from 10 nurses. The prevalence of patients at nutritional risk with the SGA and NRS 2002 was 33.9% and 53.2% on admission. In the total group, ≤70 age group, and >70 age group, respectively, consistency was observed in 214 (76.4%), 175 (91.1%), and 39 (44.3%); and kappa values were 0.54 (p 70 age group (p nutritional status of patients with gastrointestinal cancer undergoing surgery, but it appeared to detect more patients at nutritional risk in the >70 age group.

  7. Use of Subjective Global Assessment, Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 to evaluate the nutritional status of non-critically ill patients on parenteral nutrition.

    Badia-Tahull, M B; Cobo-Sacristán, S; Leiva-Badosa, E; Miquel-Zurita, M E; Méndez-Cabalerio, N; Jódar-Masanés, R; Llop-Talaverón, J

    2014-02-01

    To evaluate the nutritional status of non-critically ill digestive surgery patients at the moment of parenteral nutrition initiation using three different nutritional test tools and to study their correlation. To study the association between the tests and the clinical and laboratory parameters used in the follow-up of PN treatment. Prospective study over 4 months. Anthropometric and clinical variables were recorded. Results of Subjective Global Assessment; Patient-Generated Subjective Global Assessment; and Nutritional Risk Screening 2002 were compared applying kappa test. Relationship between the clinical and laboratory parameters with Subjective Global Assessment was studied by multinominal regression and with the other two tests by multiple linear regression models. Age and sex were included as adjustment variables. Malnutrition in 45 studied patients varied from 51% to 57%. Subjective Global Assessment correlated well with Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 (κ = 0531 p = 0.000). The test with the greatest correlation with the clinical and analytical variables was the Nutritional Risk Screening 2002. Worse nutritional state in this test was associated with worse results in albumin (B = -0.087; CI = -0.169/-0.005], prealbumin (B = -0.005; CI = [-0.011/-0.001]), C-reactive protein (B = 0.006;CI = [0.001/ 0.011]) and leukocytes (B = 0.134; CI = [0.031/0.237]) at the en of parenteral nutrition treatment. Half of the digestive surgery patients were at malnutritional risk at the moment of initiating parenteral nutrition. Nutritional Risk Screening 2002 was the test with best association with the parameters used in the clinical follow-up of parenteral nutrition treated patients. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  8. Global Inequalities in Cervical Cancer Incidence and Mortality are Linked to Deprivation, Low Socioeconomic Status, and Human Development

    Gopal K. Singh, PhD; Romuladus E. Azuine, DrPH, RN; Mohammad Siahpush, PhD

    2012-01-01

    Objectives This study examined global inequalities in cervical cancer incidence and mortality rates as a function of cross-national variations in the Human Development Index (HDI), socioeconomic factors, Gender Inequality Index (GII), and healthcare expenditure. Methods Age-adjusted incidence and mortality rates were calculated for women in 184 countries using the 2008 GLOBOCAN database, and incidence and mortality trends were analyzed using the WHO cancer mortality database. Log-linear regre...

  9. Self-reported health status of older adults in Malaysia and Singapore: evidence from the 2007 Global Ageing Survey

    Khan, Hafiz T. A.; Flynn, Matthew

    2015-01-01

    The aim of this study is to investigate the correlates of self-reported health (SRH) among older adults in Malaysia and Singapore. The study uses data collected in the Global Ageing Study (GLAS) 2007, one of the largest surveys of its kind, specially designed to investigate attitudes towards later life, ageing and retirement. Data were collected from 1002 and 1004 respondents from Malaysia and Singapore respectively. The study found that Singaporeans report a healthier life than Malaysians. T...

  10. Status, progress and plans for the U.S. Department of Energy, National Nuclear Security Administration, Global Threat Reduction Initiative

    Bieniawski, Andrew

    2005-01-01

    This presentation discusses the efforts under the US Department of Energy/National Nuclear Security Administration's Global Threat Reduction Initiative, also known as GTRI. On May 26, 2004, then Secretary of Energy Abraham established GTRI. GTRI is a cooperative program to provide international support for countries' national programs to identify, secure, recover or facilitate the disposition of vulnerable nuclear and radiological materials around the world that pose a potential threat to the international community. The formation of GTRI consolidated a number of nonproliferation programs you may be familiar with that work together to minimize and, to the extent possible, eliminate the use of highly enriched uranium (HEU) in civil nuclear applications worldwide. In particular, the Office of Global Threat Reduction, which was set up to implement GTRI, has oversight of the Reduced Enrichment for Research and Test Reactors program, the Foreign Research Reactor Spent Nuclear Fuel Acceptance program, and the Russian Research Reactor Fuel Return program. This consolidation allows these three programs to work in concert to bring about the elimination of research reactor materials as a source of proliferation concern. This speech is highlighting the work that these programs have undertaken in cooperation with the global research reactor community and the importance placed on fuel development under the RERTR program It contains an update on the work done to support the US - Russian Presidential Bratislava Summit Statement

  11. CORRELATION BETWEEN ANTHROPOMETRY, BIOCHEMICAL MARKERS AND SUBJECTIVE GLOBAL ASSESSMENT – DIALYSIS MALNUTRITION SCORE AS PREDICTORS OF NUTRITIONAL STATUS OF THE MAINTENANCE HEMODIALYSIS PATIENTS

    Vanitha Rani N, S. Kavimani, Soundararajan P, Chamundeeswari D, Kannan Gopal

    2015-10-01

    Full Text Available Background: Protein energy malnutrition is the major cause of poor prognostic outcome in patients on maintenance hemodialysis (MHD. The assessment of nutritional status in patients on maintenance hemodialysis should be done both subjectively and objectively by integrating clinical, biochemical and anthropometric measurements. A study was conducted to assess the possible correlations between the subjective global assessment-dialysis malnutrition score (SGA-DMS, anthropometric measurements, and biochemical parameters in hemodialysis patients. Methods: The study included 90 patients (55 males and 35 females; age range of 25 to 73 years; mean age 52.62 ± 11.7 years undergoing twice/thrice weekly maintenance hemodialysis for six months and above in the dialysis unit of a tertiary care teaching hospital. The MHD patients were assessed by SGA -DMS, anthropometry and biochemical indicators (serum albumin, iron, ferritin and transferrin of nutritional status. Results: According to the SGA-DMS 54.4 % were moderate to severely malnourished, 31% were mild to moderately nourished and 14.4% were well nourished. There was a highly significant negative correlation between SGA –DMS and serum albumin, iron, transferrin; positive correlation between SGA-DMS and ferritin (P<0.0001. Body mass index, upper arm circumferences, and skin fold thickness had a highly significant negative correlation with SGA-DMS (P<0.001, where as the lean body mass, total body water and the fat free mass had a significant negative correlation (P<0.05. Conclusion: SGA-DMS correlated with anthropometric and biochemical parameters that are indicative of nutritional status. SGA –DMS used in conjunction with other objective nutritional assessment methods may be of greater impact in determining nutritional status of hemodialysis patients.

  12. Global Birth Prevalence of Spina Bifida by Folic Acid Fortification Status: A Systematic Review and Meta-Analysis.

    Atta, Callie A M; Fiest, Kirsten M; Frolkis, Alexandra D; Jette, Nathalie; Pringsheim, Tamara; St Germaine-Smith, Christine; Rajapakse, Thilinie; Kaplan, Gilaad G; Metcalfe, Amy

    2016-01-01

    Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply leads to a decrease in spina bifida (a birth defect of the spine). Still, many countries around the world have yet to approve mandatory fortification through government legislation. We sought to perform a systematic review and meta-analysis of period prevalence of spina bifida by folic acid fortification status, geographic region, and study population. An expert research librarian used terms related to neural tube defects and epidemiology from primary research from 1985 to 2010 to search in EMBASE and MEDLINE. We searched the reference lists of included articles and key review articles identified by experts. Inclusion criteria included studies in English or French reporting on prevalence published between January 1985 and December 2010 that (1) were primary research, (2) were population-based, and (3) reported a point or period prevalence estimate of spina bifida (i.e., prevalence estimate with confidence intervals or case numerator and population denominator). Two independent reviewers screened titles and abstracts for eligible articles, then 2 authors screened full texts in duplicate for final inclusion. Disagreements were resolved through consensus or a third party. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, abstracting data related to case ascertainment, study population, folic acid fortification status, geographic region, and prevalence estimate independently and in duplicate. We extracted overall data and any subgroups reported by age, gender, time period, or type of spina bifida. We classified each period prevalence estimate as "mandatory" or "voluntary" folic acid fortification according to each country's folic acid fortification status at the time data were collected (as determined by a well-recognized fortification monitoring body, Food

  13. Assessment of the terrestrial water balance using the global water availability and use model WaterGAP - status and challenges

    Müller Schmied, Hannes; Döll, Petra

    2017-04-01

    The estimation of the World's water resources has a long tradition and numerous methods for quantification exists. The resulting numbers vary significantly, leaving room for improvement. Since some decades, global hydrological models (GHMs) are being used for large scale water budget assessments. GHMs are designed to represent the macro-scale hydrological processes and many of those models include human water management, e.g. irrigation or reservoir operation, making them currently the first choice for global scale assessments of the terrestrial water balance within the Anthropocene. The Water - Global Assessment and Prognosis (WaterGAP) is a model framework that comprises both the natural and human water dimension and is in development and application since the 1990s. In recent years, efforts were made to assess the sensitivity of water balance components to alternative climate forcing input data and, e.g., how this sensitivity is affected by WaterGAP's calibration scheme. This presentation shows the current best estimate of terrestrial water balance components as simulated with WaterGAP by 1) assessing global and continental water balance components for the climate period 1971-2000 and the IPCC reference period 1986-2005 for the most current WaterGAP version using a homogenized climate forcing data, 2) investigating variations of water balance components for a number of state-of-the-art climate forcing data and 3) discussing the benefit of the calibration approach for a better observation-data constrained global water budget. For the most current WaterGAP version 2.2b and a homogenized combination of the two WATCH Forcing Datasets, global scale (excluding Antarctica and Greenland) river discharge into oceans and inland sinks (Q) is assessed to be 40 000 km3 yr-1 for 1971-2000 and 39 200 km3 yr-1 for 1986-2005. Actual evapotranspiration (AET) is close to each other with around 70 600 (70 700) km3 yr-1 as well as water consumption with 1000 (1100) km3 yr-1. The

  14. Regulation and function of DNA methylation in plants and animals

    He, Xinjian

    2011-02-15

    DNA methylation is an important epigenetic mark involved in diverse biological processes. In plants, DNA methylation can be established through the RNA-directed DNA methylation pathway, an RNA interference pathway for transcriptional gene silencing (TGS), which requires 24-nt small interfering RNAs. In mammals, de novo DNA methylation occurs primarily at two developmental stages: during early embryogenesis and during gametogenesis. While it is not clear whether establishment of DNA methylation patterns in mammals involves RNA interference in general, de novo DNA methylation and suppression of transposons in germ cells require 24-32-nt piwi-interacting small RNAs. DNA methylation status is dynamically regulated by DNA methylation and demethylation reactions. In plants, active DNA demethylation relies on the repressor of silencing 1 family of bifunctional DNA glycosylases, which remove the 5-methylcytosine base and then cleave the DNA backbone at the abasic site, initiating a base excision repair (BER) pathway. In animals, multiple mechanisms of active DNA demethylation have been proposed, including a deaminase- and DNA glycosylase-initiated BER pathway. New information concerning the effects of various histone modifications on the establishment and maintenance of DNA methylation has broadened our understanding of the regulation of DNA methylation. The function of DNA methylation in plants and animals is also discussed in this review. © 2011 IBCB, SIBS, CAS All rights reserved.

  15. Status Report of the DPHEP Collaboration: A Global Effort for Sustainable Data Preservation in High Energy Physics

    Amerio, Silvia; Berghaus, Frank; Blomer, Jakob; Branson, Andrew; Cancio, Germán; Cartaro, Concetta; Chen, Gang; Dallmeier-Tiessen, Sünje; Diaconu, Cristinel; Ganis, Gerardo; Gheata, Mihaela; Hara, Takanori; Herner, Ken; Hildreth, Mike; Jones, Roger; Kluth, Stefan; Krücker, Dirk; Lassila-Perini, Kati; Maggi, Marcello; Marco de Lucas, Jesus; Mele, Salvatore; Pace, Alberto; Schröder, Matthias; Shamdasani, Jetendr; Shiers, Jamie; Smith, Tim; Sobie, Randall; South, David Michael; Verbytskyi, Andrii; Viljoen, Matthew; Wang, Lu; Zimmermann, Markus

    2015-01-01

    Data from High Energy Physics (HEP) experiments are collected with significant financial and human effort and are mostly unique. An inter-experimental study group on HEP data preservation and long-term analysis was convened as a panel of the International Committee for Future Accelerators (ICFA). The group was formed by large collider-based experiments and investigated the technical and organizational aspects of HEP data preservation. An intermediate report was released in November 2009 addressing the general issues of data preservation in HEP and an extended blueprint paper was published in 2012. In July 2014 the DPHEP collaboration was formed as a result of the signature of the Collaboration Agreement by seven large funding agencies (others have since joined or are in the process of acquisition) and in June 2015 the first DPHEP Collaboration Workshop and Collaboration Board meeting took place. This status report of the DPHEP collaboration details the progress during the period from 2013 to 2015 inclusive.

  16. Search for methylation-sensitive amplification polymorphisms associated with the mantled variant phenotype in oil palm (Elaeis guineensis Jacq).

    Jaligot, E; Beulé, T; Baurens, F-C; Billotte, N; Rival, A

    2004-02-01

    The methylation-sensitive amplification polymorphism (MSAP) technique has been employed on somatic embryo-derived oil palms (Elaeis guineensis Jacq.) to identify methylation polymorphisms correlated with the "mantled" somaclonal variation. The variant phenotype displays an unstable feminization of male organs in both male and female flowers. Using MSAP, the methylation status of CCGG sites was compared in three normal versus three mantled regenerants sampled in clonal populations obtained through somatic embryogenesis from four genotypically distinct mother palms. Overall, 64 selective primer combinations were used and they have amplified 23 markers exhibiting a differential methylation pattern between the two phenotypes. Our results indicate that CCGG sites are poorly affected by the considerable decrease in global DNA methylation that has been previously associated with the mantled phenotype. Each of the 23 markers isolated in the present study could discriminate between the two phenotypes only when they were from the same genetic origin. This result hampers at the moment the direct use of MSAP markers for the early detection of variants, even though valuable information on putative target sequences will be obtained from a further characterization of these polymorphic markers.

  17. MicroRNA-137 promoter methylation in oral lichen planus and oral squamous cell carcinoma

    Dang, Jun; Bian, Yong-qian; Sun, Jian-yong

    2013-01-01

    and patients with oral squamous cell carcinoma (OSCC). A total of 20 OLP and 12 patients with OSCC as well as 10 healthy subjects were subjected to miR-137 promoter methylation analysis using methylation-specific PCR (MSP). To address the malignancy prediction potential from miR-137 promoter methylation status...

  18. Indices of methylation in sperm DNA from fertile men differ between distinct geographical regions

    Consales, C; Leter, G; Bonde, Jens Peter

    2014-01-01

    STUDY QUESTION: Which are the main determinants, if any, of sperm DNA methylation levels? SUMMARY ANSWER: Geographical region resulted associated with the sperm methylation status assessed on genome-wide repetitive sequences. WHAT IS KNOWN ALREADY: DNA methylation level, assessed on repetitive se...

  19. Global analysis of threat status reveals higher extinction risk in tropical than in temperate bird sister species

    Reif Jiří

    2016-06-01

    Full Text Available Given increasing pressures upon biodiversity, identification of species’ traits related to elevated extinction risk is useful for more efficient allocation of limited resources for nature conservation. Despite its need, such a global analysis was lacking in the case of birds. Therefore, we performed this exercise for avian sister species using information about their global extinction risk from IUCN Red List. We focused on 113 pairs of sister species, each containing a threatened and an unthreatened species to factor out the effects of common evolutionary history on the revealed relationship. We collected data on five traits with expected relationships to species’ extinction risk based on previous studies performed at regional or national levels: breeding habitat (recognizing forest, grassland, wetland and oceanic species, latitudinal range position (temperate and tropics species, migration strategy (migratory and resident species, diet (carnivorous, insectivorous, herbivorous and omnivorous species and body mass. We related the extinction risk using IUCN threat level categories to species’ traits using generalised linear mixed effects models expecting lower risk for forest, temperate, omnivorous and smaller-bodied species. Our expectation was confirmed only in the case of latitudinal range position, as we revealed higher threat level for tropical than for temperate species. This relationship was robust to different methods of threat level expression and cannot be explained by a simple association of high bird species richness with the tropical zone. Instead, it seems that tropical species are more threatened because of their intrinsic characteristics such as slow life histories, adaptations to stable environments and small geographic ranges. These characteristics are obviously disadvantageous in conditions of current human-induced environmental perturbations. Moreover, given the absence of habitat effects, our study indicates that such

  20. Evaluating the Global Precipitation Measurement mission with NOAA/NSSL Multi-Radar Multisensor: current status and future directions.

    Kirstetter, P. E.; Petersen, W. A.; Gourley, J. J.; Kummerow, C.; Huffman, G. J.; Turk, J.; Tanelli, S.; Maggioni, V.; Anagnostou, E. N.; Hong, Y.; Schwaller, M.

    2017-12-01

    Accurate characterization of uncertainties in space-borne precipitation estimates is critical for many applications including water budget studies or prediction of natural hazards at the global scale. The GPM precipitation Level II (active and passive) and Level III (IMERG) estimates are compared to the high quality and high resolution NEXRAD-based precipitation estimates derived from the NOAA/NSSL's Multi-Radar, Multi-Sensor (MRMS) platform. A surface reference is derived from the MRMS suite of products to be accurate with known uncertainty bounds and measured at a resolution below the pixel sizes of any GPM estimate, providing great flexibility in matching to grid scales or footprints. It provides an independent and consistent reference research framework for directly evaluating GPM precipitation products across a large number of meteorological regimes as a function of resolution, accuracy and sample size. The consistency of the ground and space-based sensors in term of precipitation detection, typology and quantification are systematically evaluated. Satellite precipitation retrievals are further investigated in terms of precipitation distributions, systematic biases and random errors, influence of precipitation sub-pixel variability and comparison between satellite products. Prognostic analysis directly provides feedback to algorithm developers on how to improve the satellite estimates. Specific factors for passive (e.g. surface conditions for GMI) and active (e.g. non uniform beam filling for DPR) sensors are investigated. This cross products characterization acts as a bridge to intercalibrate microwave measurements from the GPM constellation satellites and propagate to the combined and global precipitation estimates. Precipitation features previously used to analyze Level II satellite estimates under various precipitation processes are now intoduced for Level III to test several assumptions in the IMERG algorithm. Specifically, the contribution of Level II is

  1. Renewables 2016 Global Status Report. Key findings. A Record Breaking Year for Renewable Energy: New Installations, Policy Targets, Investment and Jobs. Mainstreaming renewables: guidance for policy makers

    Sawin, Janet L.; Sverrisson, Freyr; Seyboth, Kristin; Adib, Rana; Murdock, Hannah E.; Lins, Christine; Brown, Adam; Di Domenico, Stefanie E.; Kielmanowicz, Daniele; Williamson, Laura E.; Jawahar, Rashmi; Appavou, Fabiani; Musolino, Evan; Petrichenko, Ksenia; Farrell, Timothy C.; Thorsch Krader, Thomas; Skeen, Jonathan; Epp, Baerbel; Anna Leidreiter; Tsakiris, Aristeidis; Sovacool, Benjamin; Saraph, Aarth; Mastny, Lisa; Martinot, Eric

    2016-01-01

    2015 was an extraordinary year for renewable energy. Renewables are now cost competitive with fossil fuels in many markets and are established around the world as mainstream sources of energy. Cities, communities and companies are leading the rapidly expanding '100% renewable' movement. Distributed renewable energy is advancing rapidly to close the energy access gap. The REN21 Renewables Global Status Report (GSR) provides an annual look at the tremendous advances in renewable energy markets, policy frameworks and industries globally. Each report uses formal and informal data to provide the most up-to-date information available. Reliable, timely and regularly updated data on renewables energy are essential as they are used for establishing baselines for decision makers; for demonstrating the increasing role that renewables play in the energy sector; and illustrating that the renewable energy transition is a reality. This year's GSR marks 11 years of REN21 reporting. Over the past decade the GSR has expanded in scope and depth with its thematic and regional coverage and the refinement of data collection. The GSR is the product of systematic data collection resulting in thousands of data points, the use of hundreds of documents, and personal communication with experts from around the world. It benefits from a multi-stakeholder community of over 700 experts. Country information for 148 countries were received and used as basis for GSR2016 preparation. The country data received is featured in the REN21 Renewables Interactive Map (www.ren21.net/map)

  2. Mega-events, Local Economies, and Global Status: What Happened before the 2008 Olympics in Beijing and the 2010 World Expo in Shanghai

    Jian Sun

    2010-01-01

    Full Text Available Mega-events such as the World Cup and the Olympics have been used for economic development, urban transformation and global status enhancement. Beijing and Shanghai embraced these purposes when they won the bids for the 2008 Olympics and the 2010 World Expo respectively. This article examines the pre-event economic changes in Beijing and Shanghai that are associated with their pursuit of mega-events. Changes in a group of economic indicators are tracked from 1997 to 2006. It was found that after winning the bids for the Olympics and the World Expo, Beijing and Shanghai experienced greater growth in construction and tourism, a speeding-up in economic development and restructuring, and an improvement in physical infrastructure. However, the enhancement of global exposure was not accompanied by growth in foreign trade and in the finance, insurance and real estate (FIRE industries. The empirical analyses place the mega-events in large economic contexts and provide a base for future post-event studies.

  3. Status of pesticide management in the practice of vector control: a global survey in countries at risk of malaria or other major vector-borne diseases

    Tan Soo

    2011-05-01

    Full Text Available Abstract Background It is critical that vector control pesticides are used for their acceptable purpose without causing adverse effects on health and the environment. This paper provides a global overview of the current status of pesticides management in the practice of vector control. Methods A questionnaire was distributed to WHO member states and completed either by the director of the vector-borne disease control programme or by the national manager for vector control. In all, 113 countries responded to the questionnaire (80% response rate, representing 94% of the total population of the countries targeted. Results Major gaps were evident in countries in pesticide procurement practices, training on vector control decision making, certification and quality control of pesticide application, monitoring of worker safety, public awareness programmes, and safe disposal of pesticide-related waste. Nevertheless, basic conditions of policy and coordination have been established in many countries through which the management of vector control pesticides could potentially be improved. Most countries responded that they have adopted relevant recommendations by the WHO. Conclusions Given the deficiencies identified in this first global survey on public health pesticide management and the recent rise in pesticide use for malaria control, the effectiveness and safety of pesticide use are being compromised. This highlights the urgent need for countries to strengthen their capacity on pesticide management and evidence-based decision making within the context of an integrated vector management approach.

  4. Status of pesticide management in the practice of vector control: a global survey in countries at risk of malaria or other major vector-borne diseases.

    van den Berg, Henk; Hii, Jeffrey; Soares, Agnes; Mnzava, Abraham; Ameneshewa, Birkinesh; Dash, Aditya P; Ejov, Mikhail; Tan, Soo Hian; Matthews, Graham; Yadav, Rajpal S; Zaim, Morteza

    2011-05-14

    It is critical that vector control pesticides are used for their acceptable purpose without causing adverse effects on health and the environment. This paper provides a global overview of the current status of pesticides management in the practice of vector control. A questionnaire was distributed to WHO member states and completed either by the director of the vector-borne disease control programme or by the national manager for vector control. In all, 113 countries responded to the questionnaire (80% response rate), representing 94% of the total population of the countries targeted. Major gaps were evident in countries in pesticide procurement practices, training on vector control decision making, certification and quality control of pesticide application, monitoring of worker safety, public awareness programmes, and safe disposal of pesticide-related waste. Nevertheless, basic conditions of policy and coordination have been established in many countries through which the management of vector control pesticides could potentially be improved. Most countries responded that they have adopted relevant recommendations by the WHO. Given the deficiencies identified in this first global survey on public health pesticide management and the recent rise in pesticide use for malaria control, the effectiveness and safety of pesticide use are being compromised. This highlights the urgent need for countries to strengthen their capacity on pesticide management and evidence-based decision making within the context of an integrated vector management approach.

  5. Early Childhood Developmental Status in Low- and Middle-Income Countries: National, Regional, and Global Prevalence Estimates Using Predictive Modeling.

    McCoy, Dana Charles; Peet, Evan D; Ezzati, Majid; Danaei, Goodarz; Black, Maureen M; Sudfeld, Christopher R; Fawzi, Wafaie; Fink, Günther

    2016-06-01

    The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs) are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development. The present paper uses Early Childhood Development Index (ECDI) data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS) and Demographic and Health Surveys (DHS) programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI) and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million) in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y), followed by

  6. Early Childhood Developmental Status in Low- and Middle-Income Countries: National, Regional, and Global Prevalence Estimates Using Predictive Modeling.

    Dana Charles McCoy

    2016-06-01

    Full Text Available The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development.The present paper uses Early Childhood Development Index (ECDI data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS and Demographic and Health Surveys (DHS programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y

  7. Whole-genome methylation caller designed for methyl- DNA ...

    etchie

    2013-02-20

    Feb 20, 2013 ... Our method uses a single-CpG-resolution, whole-genome methylation ... Key words: Methyl-DNA immunoprecipitation, next-generation sequencing, ...... methylation is prevalent in embryonic stem cells andmaybe mediated.

  8. DNA methylation abnormalities in congenital heart disease.

    Serra-Juhé, Clara; Cuscó, Ivon; Homs, Aïda; Flores, Raquel; Torán, Núria; Pérez-Jurado, Luis A

    2015-01-01

    Congenital heart defects represent the most common malformation at birth, occurring also in ∼50% of individuals with Down syndrome. Congenital heart defects are thought to have multifactorial etiology, but the main causes are largely unknown. We have explored the global methylation profile of fetal heart DNA in comparison to blood DNA from control subjects: an absolute correlation with the type of tissue was detected. Pathway analysis revealed a significant enrichment of differential methylation at genes related to muscle contraction and cardiomyopathies in the developing heart DNA. We have also searched for abnormal methylation profiles on developing heart-tissue DNA of syndromic and non-syndromic congenital heart defects. On average, 3 regions with aberrant methylation were detected per sample and 18 regions were found differentially methylated between groups. Several epimutations were detected in candidate genes involved in growth regulation, apoptosis and folate pathway. A likely pathogenic hypermethylation of several intragenic sites at the MSX1 gene, involved in outflow tract morphogenesis, was found in a fetus with isolated heart malformation. In addition, hypermethylation of the GATA4 gene was present in fetuses with Down syndrome with or without congenital heart defects, as well as in fetuses with isolated heart malformations. Expression deregulation of the abnormally methylated genes was detected. Our data indicate that epigenetic alterations of relevant genes are present in developing heart DNA in fetuses with both isolated and syndromic heart malformations. These epimutations likely contribute to the pathogenesis of the malformation by cis-acting effects on gene expression.

  9. Methylation pathways in schizophrenia

    Sargent, T.W. III.

    1982-01-01

    Research on the biochemical causes of human psychosis concentrates on investigating whether schizophremia is linked to abnormalities in the metabolism of methyl carbon groups in the body. The metabolism of C-14 labeled methyl groups in methionine is studied in animals, normal subjects and patient volunteers

  10. Analysis of DNA Cytosine Methylation Patterns Using Methylation-Sensitive Amplification Polymorphism (MSAP).

    Guevara, María Ángeles; de María, Nuria; Sáez-Laguna, Enrique; Vélez, María Dolores; Cervera, María Teresa; Cabezas, José Antonio

    2017-01-01

    Different molecular techniques have been developed to study either the global level of methylated cytosines or methylation at specific gene sequences. One of them is the methylation-sensitive amplified polymorphism technique (MSAP) which is a modification of amplified fragment length polymorphism (AFLP). It has been used to study methylation of anonymous CCGG sequences in different fungi, plants, and animal species. The main variation of this technique resides on the use of isoschizomers with different methylation sensitivity (such as HpaII and MspI) as a frequent-cutter restriction enzyme. For each sample, MSAP analysis is performed using both EcoRI/HpaII- and EcoRI/MspI-digested samples. A comparative analysis between EcoRI/HpaII and EcoRI/MspI fragment patterns allows the identification of two types of polymorphisms: (1) methylation-insensitive polymorphisms that show common EcoRI/HpaII and EcoRI/MspI patterns but are detected as polymorphic amplified fragments among samples and (2) methylation-sensitive polymorphisms which are associated with the amplified fragments that differ in their presence or absence or in their intensity between EcoRI/HpaII and EcoRI/MspI patterns. This chapter describes a detailed protocol of this technique and discusses the modifications that can be applied to adjust the technology to different species of interest.

  11. Epigenetic status of H19/IGF2 and SNRPN imprinted genes in aborted and successfully derived embryonic stem cell lines in non-human primates

    Florence Wianny

    2016-05-01

    Full Text Available The imprinted genes of primate embryonic stem cells (ESCs often show altered DNA methylation. It is unknown whether these alterations emerge while deriving the ESCs. Here we studied the methylation patterns of two differentially methylated regions (DMRs, SNRPN and H19/IGF2 DMRs, during the derivation of monkey ESCs. We show that the SNRPN DMR is characteristically methylated at maternal alleles, whereas the H19/IGF2 DMR is globally highly methylated, with unusual methylation on the maternal alleles. These methylation patterns remain stable from the early stages of ESC derivation to late passages of monkey ESCs and following differentiation. Importantly, the methylation status of H19/IGF2 DMR and the expression levels of IGF2, H19, and DNMT3B mRNAs in early embryo-derived cells were correlated with their capacity to generate genuine ESC lines. Thus, we propose that these markers could be useful to predict the outcomes of establishing an ESC line in primates.

  12. Methyl-Analyzer--whole genome DNA methylation profiling.

    Xin, Yurong; Ge, Yongchao; Haghighi, Fatemeh G

    2011-08-15

    Methyl-Analyzer is a python package that analyzes genome-wide DNA methylation data produced by the Methyl-MAPS (methylation mapping analysis by paired-end sequencing) method. Methyl-MAPS is an enzymatic-based method that uses both methylation-sensitive and -dependent enzymes covering >80% of CpG dinucleotides within mammalian genomes. It combines enzymatic-based approaches with high-throughput next-generation sequencing technology to provide whole genome DNA methylation profiles. Methyl-Analyzer processes and integrates sequencing reads from methylated and unmethylated compartments and estimates CpG methylation probabilities at single base resolution. Methyl-Analyzer is available at http://github.com/epigenomics/methylmaps. Sample dataset is available for download at http://epigenomicspub.columbia.edu/methylanalyzer_data.html. fgh3@columbia.edu Supplementary data are available at Bioinformatics online.

  13. Heterogeneity of DNA methylation in multifocal prostate cancer.

    Serenaite, Inga; Daniunaite, Kristina; Jankevicius, Feliksas; Laurinavicius, Arvydas; Petroska, Donatas; Lazutka, Juozas R; Jarmalaite, Sonata

    2015-01-01

    Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (≥75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p epigenetic profile of recurrent tumors can be inferred from our data.

  14. DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.

    Isagawa, Takayuki; Nagae, Genta; Shiraki, Nobuaki; Fujita, Takanori; Sato, Noriko; Ishikawa, Shumpei; Kume, Shoen; Aburatani, Hiroyuki

    2011-01-01

    Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes.

  15. Methylated genes as new cancer biomarkers

    Brunner, Nils; Duffy, M.J; Napieralski, R.

    2009-01-01

    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that meas......Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested...... that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2...... for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene...

  16. A review on environmental factors regulating arsenic methylation in humans

    Tseng, C.-H.

    2009-01-01

    Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers

  17. Global Positioning System – A new tool to measure the distribution of anaemia and nutritional status of children (5-10years in a rural area, South India

    Sathish Chandra MR

    2014-11-01

    Full Text Available Introduction: The Global Positioning System (GPS is a satellite based navigation system which is of late being used in the health field. Objectives: 1.To describe the geographical distribution of anaemia and malnutrition with GPS; 2.To assess the prevalence of anaemia and malnutrition in children aged 5-10 years. Subjects and methods: This exploratory study was conducted over a period of 2 months in the rural field practice area of a medical college situated in Bangalore during the months of June - July, 2012. Children in the age group of 5-10 years of age were the study subjects. Results: GPS was used for the describing the geographical distribution of anaemia and nutrition status on the Google earth map. The prevalence of anaemia in the study subjects was 8.7%.The prevalence of underweight, stunting, thinness and severe thinness among the study subjects was 52.8%, 28.5%, 23.5 % and 29.1% respectively, however  overweight  and obesity was observed only in 0.9 % and 1.2% of the study subjects respectively. Conclusion: GPS was easy to use and was able to demonstrate the actual distribution of morbidity at the household level in the rural area.

  18. Iodine nutrition in elementary state schools of Queretaro, Mexico: correlations between urinary iodine concentration with global nutrition status and social gap index.

    García-Solís, Pablo; Solís-S, Juan Carlos; García-Gaytán, Ana Cristina; Reyes-Mendoza, Vanessa A; Robles-Osorio, Ludivina; Villarreal-Ríos, Enrique; Leal-García, Luisa; Hernández-Montiel, Hebert Luis

    2013-08-01

    To estimate median urinary iodine concentration (UIC), and to correlate it with global nutrition indicators and social gap index (SGI) in 50 elementary state schools from 10 municipalities in the State of Queretaro, Mexico. 1,544 students were enrolled and an above of requirements of iodine intake was found (median UIC of 297 µg/L). Iodine status was found as deficient, adequate, more than adequate and excessive in 2, 4, 19 and 25 schools, respectively. Seventy seven percent of table salt samples showed adequate iodine content (20-40 ppm), while 9.6% of the samples had low iodine content (school were positively correlated with medians of body mass index (BMI) by using the standard deviation score (SDS) (r = 0.47; p school were negatively correlated with stunting prevalence (r = -0.39; p = 005) and social gap index (r = -0.36; p coexistence between the two extremes of iodine intake (insufficient and excessive). To our knowledge, the observed positive correlation between UIC and overweight and obesity has not been described before, and could be explained by the availability and consumption of snack food rich in energy and iodized salt.

  19. A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer.

    Schwartzman, Jacob; Mongoue-Tchokote, Solange; Gibbs, Angela; Gao, Lina; Corless, Christopher L; Jin, Jennifer; Zarour, Luai; Higano, Celestia; True, Lawrence D; Vessella, Robert L; Wilmot, Beth; Bottomly, Daniel; McWeeney, Shannon K; Bova, G Steven; Partin, Alan W; Mori, Motomi; Alumkal, Joshi

    2011-10-01

    DNA methylation of promoter regions is a common event in prostate cancer, one of the most common cancers in men worldwide. Because prior reports demonstrating that DNA methylation is important in prostate cancer studied a limited number of genes, we systematically quantified the DNA methylation status of 1505 CpG dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and three normal prostate samples. The ERG gene, commonly repressed in prostate cells in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most commonly methylated genes, occurring in 74% of prostate cancer specimens. In an independent group of patient samples, we confirmed that ERG DNA methylation was common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is marked by repressive chromatin marks mediated by polycomb proteins in both normal prostate cells and prostate cancer cells, which may explain ERG's predisposition to DNA methylation and the fact that tumors with ERG DNA methylation were more methylated, in general. These results demonstrate that bead arrays offer a high-throughput method to discover novel genes with promoter DNA methylation such as ERG, whose measurement may improve our ability to more accurately detect prostate cancer.

  20. DNA methylation-based variation between human populations.

    Kader, Farzeen; Ghai, Meenu

    2017-02-01

    Several studies have proved that DNA methylation affects regulation of gene expression and development. Epigenome-wide studies have reported variation in methylation patterns between populations, including Caucasians, non-Caucasians (Blacks), Hispanics, Arabs, and numerous populations of the African continent. Not only has DNA methylation differences shown to impact externally visible characteristics, but is also a potential biomarker for underlying racial health disparities between human populations. Ethnicity-related methylation differences set their mark during early embryonic development. Genetic variations, such as single-nucleotide polymorphisms and environmental factors, such as age, dietary folate, socioeconomic status, and smoking, impacts DNA methylation levels, which reciprocally impacts expression of phenotypes. Studies show that it is necessary to address these external influences when attempting to differentiate between populations since the relative impacts of these factors on the human methylome remain uncertain. The present review summarises several reported attempts to establish the contribution of differential DNA methylation to natural human variation, and shows that DNA methylation could represent new opportunities for risk stratification and prevention of several diseases amongst populations world-wide. Variation of methylation patterns between human populations is an exciting prospect which inspires further valuable research to apply the concept in routine medical and forensic casework. However, trans-generational inheritance needs to be quantified to decipher the proportion of variation contributed by DNA methylation. The future holds thorough evaluation of the epigenome to understand quantification, heritability, and the effect of DNA methylation on phenotypes. In addition, methylation profiling of the same ethnic groups across geographical locations will shed light on conserved methylation differences in populations.

  1. DNA damage, homology-directed repair, and DNA methylation.

    Concetta Cuozzo

    2007-07-01

    Full Text Available To explore the link between DNA damage and gene silencing, we induced a DNA double-strand break in the genome of Hela or mouse embryonic stem (ES cells using I-SceI restriction endonuclease. The I-SceI site lies within one copy of two inactivated tandem repeated green fluorescent protein (GFP genes (DR-GFP. A total of 2%-4% of the cells generated a functional GFP by homology-directed repair (HR and gene conversion. However, approximately 50% of these recombinants expressed GFP poorly. Silencing was rapid and associated with HR and DNA methylation of the recombinant gene, since it was prevented in Hela cells by 5-aza-2'-deoxycytidine. ES cells deficient in DNA methyl transferase 1 yielded as many recombinants as wild-type cells, but most of these recombinants expressed GFP robustly. Half of the HR DNA molecules were de novo methylated, principally downstream to the double-strand break, and half were undermethylated relative to the uncut DNA. Methylation of the repaired gene was independent of the methylation status of the converting template. The methylation pattern of recombinant molecules derived from pools of cells carrying DR-GFP at different loci, or from an individual clone carrying DR-GFP at a single locus, was comparable. ClustalW analysis of the sequenced GFP molecules in Hela and ES cells distinguished recombinant and nonrecombinant DNA solely on the basis of their methylation profile and indicated that HR superimposed novel methylation profiles on top of the old patterns. Chromatin immunoprecipitation and RNA analysis revealed that DNA methyl transferase 1 was bound specifically to HR GFP DNA and that methylation of the repaired segment contributed to the silencing of GFP expression. Taken together, our data support a mechanistic link between HR and DNA methylation and suggest that DNA methylation in eukaryotes marks homologous recombined segments.

  2. Double-labelling immunohistochemistry for MGMT and a “cocktail” of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours

    Burke, Elinor; Grobler, Mariana; Elderfield, Kay; Bond, Frances; Crocker, Matthew; Taylor, Rohan; Bridges, Leslie R

    2013-01-01

    Background Our aim was to develop a new protocol for MGMT immunohistochemistry with good agreement between observers and good correlation with molecular genetic tests of tumour methylation. We examined 40 primary brain tumours (30 glioblastomas and 10 oligodendroglial tumours) with our new technique, namely double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumour antigens (CD34, CD45 and CD68). We compared the results with single-labelling immunohistochemistry for MGMT an...

  3. Methylation screening of the TGFBI promoter in human lung and prostate cancer by methylation-specific PCR

    Shah, Jinesh N; Shao, Genze; Hei, Tom K; Zhao, Yongliang

    2008-01-01

    Hypermethylation of the TGFBI promoter has been shown to correlate with decreased expression of this gene in human tumor cell lines. In this study, we optimized a methylation-specific polymerase chain reaction (MSP) method and investigated the methylation status of the TGFBI promoter in human lung and prostate cancer specimens. Methylation-specific primers were designed based on the methylation profiles of the TGFBI promoter in human tumor cell lines, and MSP conditions were optimized for accurate and efficient amplification. Genomic DNA was isolated from lung tumors and prostatectomy tissues of prostate cancer patients, bisulfite-converted, and analyzed by MSP. Among 50 lung cancer samples, 44.0% (22/50) harbored methylated CpG sites in the TGFBI promoter. An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the TGFBI promoter was associated with a metastatic phenotype, with 42.9% (6/14) of metastatic lung cancer samples demonstrating dense methylation vs. only 5.6% (2/36) of primary lung cancer samples (p < 0.05). Similar to these lung cancer results, 82.0% (41/50) of prostate cancer samples harbored methylated CpG sites in the TGFBI promoter, and dense methylation of the promoter was present in 38.9% (7/18) of prostate cancer samples with the feature of locoregional invasiveness vs. only 19.4% (6/31) of prostate cancer samples without locoregional invasiveness (p < 0.05). Furthermore, promoter hypermethylation correlated with highly reduced expression of the TGFBI gene in human lung and prostate tumor cell lines. We successfully optimized a MSP method for the precise and efficient screening of TGFBI promoter methylation status. Dense methylation of the TGFBI promoter correlated with the extent of TGFBI gene silencing in tumor cell lines and was related to invasiveness of prostate tumors and metastatic status of lung cancer tumors. Thus, TGFBI promoter methylation can be used as a potential

  4. Global Status of Neutrino Oscillation

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    ν2. Hence, as flavour states propagate, they mix because of overlapping of the mass states. After a time t, a νe is no longer a pure flavour state but contains other flavours. Can define the probability of finding a different flavour β starting from a flavour α after a time t: Pαβ. Contains information on both mixing angle θ as well as ...

  5. Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer

    Shigeyasu, Kunitoshi; Nagasaka, Takeshi; Mori, Yoshiko; Yokomichi, Naosuke; Kawai, Takashi; Fuji, Tomokazu; Kimura, Keisuke; Umeda, Yuzo; Kagawa, Shunsuke; Goel, Ajay; Fujiwara, Toshiyoshi

    2015-01-01

    Background To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown. Methods This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox’s proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS). Results By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3' methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis. Conclusions CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer. PMID:26121593

  6. Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer.

    Kunitoshi Shigeyasu

    Full Text Available To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP and microsatellite instability (MSI have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown.This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox's proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS.By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088, better tumor differentiation (P = 0.0267 and CIMP-high and MLH1 3' methylated status (P = 0.0312. Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis.CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer.

  7. Trichloroethylene-Induced DNA Methylation Changes in Male F344 Rat Liver.

    Jiang, Yan; Chen, Jiahong; Yue, Cong; Zhang, Hang; Chen, Tao

    2016-10-17

    Trichloroethylene (TCE), a common environmental contaminant, causes hepatocellular carcinoma in mice but not in rats. To understand the mechanisms of the species-specific hepatocarcinogenecity of TCE, we examined the methylation status of DNA in the liver of rats exposed to TCE at 0 or 1000 mg/kg b.w. for 5 days using MeDIP-chip, bisulfite sequencing, COBRA, and LC-MS/MS. The related mRNA expression levels were measured by qPCR. Although no global DNA methylation change was detected, 806 genes were hypermethylated and 186 genes were hypomethylated. The genes with hypermethylated DNA were enriched in endocytosis, MAPK, and cAMP signaling pathways. We further confirmed the hypermethylation of Uhrf2 DNA and the hypomethylation of Hadhb DNA, which were negatively correlated with their mRNA expression levels. The transcriptional levels of Jun, Ihh, and Tet2 were significantly downregulated, whereas Cdkn1a was overexpressed. No mRNA expression change was found for Mki67, Myc, Uhrf1, and Dnmt1. In conclusion, TCE-induced DNA methylation changes in rats appear to suppress instead of promote hepatocarcinogenesis, which might play a role in the species-specific hepatocarcinogenecity of TCE.

  8. Usability of human Infinium MethylationEPIC BeadChip for mouse DNA methylation studies.

    Needhamsen, Maria; Ewing, Ewoud; Lund, Harald; Gomez-Cabrero, David; Harris, Robert Adam; Kular, Lara; Jagodic, Maja

    2017-11-15

    The advent of array-based genome-wide DNA methylation methods has enabled quantitative measurement of single CpG methylation status at relatively low cost and sample input. Whereas the use of Infinium Human Methylation BeadChips has shown great utility in clinical studies, no equivalent tool is available for rodent animal samples. We examined the feasibility of using the new Infinium MethylationEPIC BeadChip for studying DNA methylation in mouse. In silico, we identified 19,420 EPIC probes (referred as mEPIC probes), which align with a unique best alignment score to the bisulfite converted reference mouse genome mm10. Further annotation revealed that 85% of mEPIC probes overlapped with mm10.refSeq genes at different genomic features including promoters (TSS1500 and TSS200), 1st exons, 5'UTRs, 3'UTRs, CpG islands, shores, shelves, open seas and FANTOM5 enhancers. Hybridization of mouse samples to Infinium Human MethylationEPIC BeadChips showed successful measurement of mEPIC probes and reproducibility between inter-array biological replicates. Finally, we demonstrated the utility of mEPIC probes for data exploration such as hierarchical clustering. Given the absence of cost and labor convenient genome-wide technologies in the murine system, our findings show that the Infinium MethylationEPIC BeadChip platform is suitable for investigation of the mouse methylome. Furthermore, we provide the "mEPICmanifest" with genomic features, available to users of Infinium Human MethylationEPIC arrays for mouse samples.

  9. What do unicellular organisms teach us about DNA methylation?

    Harony, Hala; Ankri, Serge

    2008-05-01

    DNA methylation is an epigenetic hallmark that has been studied intensively in mammals and plants. However, knowledge of this phenomenon in unicellular organisms is scanty. Examining epigenetic regulation, and more specifically DNA methylation, in these organisms represents a unique opportunity to better understand their biology. The determination of their methylation status is often complicated by the presence of several differentiation stages in their life cycle. This article focuses on some recent advances that have revealed the unexpected nature of the epigenetic determinants present in protozoa. The role of the enigmatic DNA methyltransferase Dnmt2 in unicellular organisms is discussed.

  10. [Neuroepigenetics: Desoxyribonucleic acid methylation in Alzheimer's disease and other dementias].

    Mendioroz Iriarte, Maite; Pulido Fontes, Laura; Méndez-López, Iván

    2015-05-21

    DNA methylation is an epigenetic mechanism that controls gene expression. In Alzheimer's disease (AD), global DNA hypomethylation of neurons has been described in the human cerebral cortex. Moreover, several variants in the methylation pattern of candidate genes have been identified in brain tissue when comparing AD patients and controls. Specifically, DNA methylation changes have been observed in PSEN1 and APOE, both genes previously being involved in the pathophysiology of AD. In other degenerative dementias, methylation variants have also been described in key genes, such as hypomethylation of the SNCA gene in Parkinson's disease and dementia with Lewy bodies or hypermethylation of the GRN gene promoter in frontotemporal dementia. The finding of aberrant DNA methylation patterns shared by brain tissue and peripheral blood opens the door to use those variants as epigenetic biomarkers in the diagnosis of neurodegenerative diseases. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  11. Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

    Mossman, David; Kim, Kyu-Tae; Scott, Rodney J

    2010-01-01

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC). Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS). In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically silenced gene is associated with the long term reversion of

  12. International global climate change negotiations. Hearings before the Subcommittee on Energy and Power of the Committee on Commerce, House of Representatives, One Hundred Fifth Congress, First Session, July 15, 1997--The economic and environmental impact of the proposed agreement -- November 11, 1997--Status of International Global Climate Change Negotiations

    1997-01-01

    In these hearings attention was focused on the following: the economic and environmental impact of the proposed agreement; and the status of international global climate change negotiations. US policy must be based on both the best scientific information available and on a clear understanding of the economic impacts of any actions that may be taken to reduce greenhouse gas emissions

  13. Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation.

    Pauwels, Sara; Ghosh, Manosij; Duca, Radu Corneliu; Bekaert, Bram; Freson, Kathleen; Huybrechts, Inge; A S Langie, Sabine; Koppen, Gudrun; Devlieger, Roland; Godderis, Lode

    2017-01-02

    Maternal nutrition is critically involved in the development and health of the fetus. We evaluated maternal methyl-group donor intake through diet (methionine, betaine, choline, folate) and supplementation (folic acid) before and during pregnancy in relation to global DNA methylation and hydroxymethylation and gene specific (IGF2 DMR, DNMT1, LEP, RXRA) cord blood methylation. A total of 115 mother-infant pairs were enrolled in the MAternal Nutrition and Offspring's Epigenome (MANOE) study. The intake of methyl-group donors was assessed using a food-frequency questionnaire. LC-MS/MS and pyrosequencing were used to measure global and gene specific methylation, respectively. Dietary intake of methyl-groups before and during pregnancy was associated with changes in LEP, DNMT1, and RXRA cord blood methylation. Statistically significant higher cord blood LEP methylation was observed when mothers started folic acid supplementation more than 6 months before conception compared with 3-6 months before conception (34.6 ± 6.3% vs. 30.1 ± 3.6%, P = 0.011, LEP CpG1) or no folic acid used before conception (16.2 ± 4.4% vs. 13.9 ± 3%, P = 0.036 for LEP CpG3 and 24.5 ± 3.5% vs. 22.2 ± 3.5%, P = 0.045 for LEP mean CpG). Taking folic acid supplements during the entire pregnancy resulted in statistically significantly higher cord blood RXRA methylation as compared with stopping supplementation in the second trimester (12.3 ± 1.9% vs. 11.1 ± 2%, P = 0.008 for RXRA mean CpG). To conclude, long-term folic acid use before and during pregnancy was associated with higher LEP and RXRA cord blood methylation, respectively. To date, pregnant women are advised to take a folic acid supplement of 400 µg/day from 4 weeks before until 12 weeks of pregnancy. Our results suggest significant epigenetic modifications when taking a folic acid supplement beyond the current advice.

  14. Folate, colorectal cancer and the involvement of DNA methylation.

    Williams, Elizabeth A

    2012-11-01

    Diet is a major factor in the aetiology of colorectal cancer (CRC). Epidemiological evidence suggests that folate confers a modest protection against CRC risk. However, the relationship is complex, and evidence from human intervention trials and animal studies suggests that a high-dose of folic acid supplementation may enhance the risk of colorectal carcinogenesis in certain circumstances. The molecular mechanisms underlying the apparent dual modulatory effect of folate on colorectal carcinogenesis are not fully understood. Folate is central to C1 metabolism and is needed for both DNA synthesis and DNA methylation, providing plausible biological mechanisms through which folate could modulate cancer risk. Aberrant DNA methylation is an early event in colorectal carcinogenesis and is typically associated with the transcriptional silencing of tumour suppressor genes. Folate is required for the production of S-adenosyl methionine, which serves as a methyl donor for DNA methylation events; thereby folate availability is proposed to modulate DNA methylation status. The evidence for an effect of folate on DNA methylation in the human colon is limited, but a modulation of DNA methylation in response to folate has been demonstrated. More research is required to clarify the optimum intake of folate for CRC prevention and to elucidate the effect of folate availability on DNA methylation and the associated impact on CRC biology.

  15. Abiotic Formation of Methyl Halides in the Terrestrial Environment

    Keppler, F.

    2011-12-01

    include a consideration on how stable isotope studies assisted advancements in this subject area. For example, it has been shown that the methoxyl groups of lignin and pectin which together constitute the bulk of the C1 plant pool have a carbon isotope signature significantly depleted in 13C. Plant-derived C1 volatile organic compounds (VOCs) are also highly depleted in 13C compared with Cn+1 VOCs. These observations suggest that the plant methoxyl pool is the predominant source of methyl halides released from senescent and dead plant litter. The distinct 13C depletion of plant methoxyl groups and naturally produced methyl halides may provide a helpful tool in constraining complex environmental processes and therefore improve our understanding of the global cycles of atmospheric methyl halides.

  16. Genome-wide DNA methylation sequencing reveals miR-663a is a novel epimutation candidate in CIMP-high endometrial cancer

    Yanokura, Megumi; Banno, Kouji; Adachi, Masataka; Aoki, Daisuke; Abe, Kuniya

    2017-01-01

    Aberrant DNA methylation is widely observed in many cancers. Concurrent DNA methylation of multiple genes occurs in endometrial cancer and is referred to as the CpG island methylator phenotype (CIMP). However, the features and causes of CIMP-positive endometrial cancer are not well understood. To investigate DNA methylation features characteristic to CIMP-positive endometrial cancer, we first classified samples from 25 patients with endometrial cancer based on the methylation status of three ...

  17. DNA methylation in obesity

    Małgorzata Pokrywka

    2014-11-01

    Full Text Available The number of overweight and obese people is increasing at an alarming rate, especially in the developed and developing countries. Obesity is a major risk factor for diabetes, cardiovascular disease, and cancer, and in consequence for premature death. The development of obesity results from the interplay of both genetic and environmental factors, which include sedentary life style and abnormal eating habits. In the past few years a number of events accompanying obesity, affecting expression of genes which are not directly connected with the DNA base sequence (e.g. epigenetic changes, have been described. Epigenetic processes include DNA methylation, histone modifications such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, as well as non-coding micro-RNA (miRNA synthesis. In this review, the known changes in the profile of DNA methylation as a factor affecting obesity and its complications are described.

  18. DNA methylation and healthy human aging.

    Jones, Meaghan J; Goodman, Sarah J; Kobor, Michael S

    2015-12-01

    The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  19. Disclosing bias in bisulfite assay: MethPrimers underestimate high DNA methylation.

    Andrea Fuso

    Full Text Available Discordant results obtained in bisulfite assays using MethPrimers (PCR primers designed using MethPrimer software or assuming that non-CpGs cytosines are non methylated versus primers insensitive to cytosine methylation lead us to hypothesize a technical bias. We therefore used the two kinds of primers to study different experimental models and methylation statuses. We demonstrated that MethPrimers negatively select hypermethylated DNA sequences in the PCR step of the bisulfite assay, resulting in CpG methylation underestimation and non-CpG methylation masking, failing to evidence differential methylation statuses. We also describe the characteristics of "Methylation-Insensitive Primers" (MIPs, having degenerated bases (G/A to cope with the uncertain C/U conversion. As CpG and non-CpG DNA methylation patterns are largely variable depending on the species, developmental stage, tissue and cell type, a variable extent of the bias is expected. The more the methylome is methylated, the greater is the extent of the bias, with a prevalent effect of non-CpG methylation. These findings suggest a revision of several DNA methylation patterns so far documented and also point out the necessity of applying unbiased analyses to the increasing number of epigenomic studies.

  20. Kismeth: Analyzer of plant methylation states through bisulfite sequencing

    Martienssen Robert A

    2008-09-01

    Full Text Available Abstract Background There is great interest in probing the temporal and spatial patterns of cytosine methylation states in genomes of a variety of organisms. It is hoped that this will shed light on the biological roles of DNA methylation in the epigenetic control of gene expression. Bisulfite sequencing refers to the treatment of isolated DNA with sodium bisulfite to convert unmethylated cytosine to uracil, with PCR converting the uracil to thymidine followed by sequencing of the resultant DNA to detect DNA methylation. For the study of DNA methylation, plants provide an excellent model system, since they can tolerate major changes in their DNA methylation patterns and have long been studied for the effects of DNA methylation on transposons and epimutations. However, in contrast to the situation in animals, there aren't many tools that analyze bisulfite data in plants, which can exhibit methylation of cytosines in a variety of sequence contexts (CG, CHG, and CHH. Results Kismeth http://katahdin.mssm.edu/kismeth is a web-based tool for bisulfite sequencing analysis. Kismeth was designed to be used with plants, since it considers potential cytosine methylation in any sequence context (CG, CHG, and CHH. It provides a tool for the design of bisulfite primers as well as several tools for the analysis of the bisulfite sequencing results. Kismeth is not limited to data from plants, as it can be used with data from any species. Conclusion Kismeth simplifies bisulfite sequencing analysis. It is the only publicly available tool for the design of bisulfite primers for plants, and one of the few tools for the analysis of methylation patterns in plants. It facilitates analysis at both global and local scales, demonstrated in the examples cited in the text, allowing dissection of the genetic pathways involved in DNA methylation. Kismeth can also be used to study methylation states in different tissues and disease cells compared to a reference sequence.

  1. The Clinical Implications of Methylated p15 and p73 Genes in Adult Acute Lymphoblastic Leukemia

    ABD EL-HAMID, Th.M.; SHERISHER, M.A.; MOSSALLAM, Gh.I.

    2010-01-01

    Aberrant methylation of promoter associated CpG islands is an epigenetic modification of DNA which is associated with gene silencing. It plays an important role in the leukemia pathogenesis. This phenomenon is frequently observed in acute lymphoblastic leukemia (ALL) and results in the functional inactivation of its associated genes. The aim of this study is to investigate the frequency and the prognostic impact of p15 and p73 genes methylation in adult acute lymphoblastic leukemia patients. Patients and Methods: Methylation-specific polymerase chain reaction (PCR) was used to analyze methylation of the p15 and p73 genes in 51 newly diagnosed adult ALL patients. Results: The methylation frequencies of p15 and p73 genes at diagnosis were 41.2% and 27.5% respectively, while concomitant methylation was detected in 14% of the patients. Concomitant methylation of p15 and p73 genes was associated with significant lower rate of CR compared to patients without methylation (57% versus 90%), p=0.008. Overall survival (OS) was not affected by p15 methylation, but was poorer with p73 methylation and the difference was near significant (p=0.059). For patients without meyhylation, the survival benefit was significant when compared to patients with p15, p73 or both genes methylation (p=0.047). The leukemia free survival was not affected by the methylation status of single gene p15 or p73, but tended to be worse in patients with methylated p15, p73 or both genes when compared to patients without methylation (p= 0.08). Conclusion: Aberrant p73 promoter methylation is a potential prognostic factor in adult ALL patients. P15 methylation is frequent in Egyptian adult ALL patients, its concomitant methylation with p73 is of poor prognostic significance. Identification of these molecular targets improve risk assessment and selection of appropriate therapy.

  2. A genome-wide methylation study on obesity: differential variability and differential methylation.

    Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Hidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling

    2013-05-01

    Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14-20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances.

  3. Evolutionary Transition of Promoter and Gene Body DNA Methylation across Invertebrate-Vertebrate Boundary.

    Keller, Thomas E; Han, Priscilla; Yi, Soojin V

    2016-04-01

    Genomes of invertebrates and vertebrates exhibit highly divergent patterns of DNA methylation. Invertebrate genomes tend to be sparsely methylated, and DNA methylation is mostly targeted to a subset of transcription units (gene bodies). In a drastic contrast, vertebrate genomes are generally globally and heavily methylated, punctuated by the limited local hypo-methylation of putative regulatory regions such as promoters. These genomic differences also translate into functional differences in DNA methylation and gene regulation. Although promoter DNA methylation is an important regulatory component of vertebrate gene expression, its role in invertebrate gene regulation has been little explored. Instead, gene body DNA methylation is associated with expression of invertebrate genes. However, the evolutionary steps leading to the differentiation of invertebrate and vertebrate genomic DNA methylation remain unresolved. Here we analyzed experimentally determined DNA methylation maps of several species across the invertebrate-vertebrate boundary, to elucidate how vertebrate gene methylation has evolved. We show that, in contrast to the prevailing idea, a substantial number of promoters in an invertebrate basal chordate Ciona intestinalis are methylated. Moreover, gene expression data indicate significant, epigenomic context-dependent associations between promoter methylation and expression in C. intestinalis. However, there is no evidence that promoter methylation in invertebrate chordate has been evolutionarily maintained across the invertebrate-vertebrate boundary. Rather, body-methylated invertebrate genes preferentially obtain hypo-methylated promoters among vertebrates. Conversely, promoter methylation is preferentially found in lineage- and tissue-specific vertebrate genes. These results provide important insights into the evolutionary origin of epigenetic regulation of vertebrate gene expression. © The Author(s) 2015. Published by Oxford University Press on behalf

  4. Methylated β-Cyclodextrins

    Schönbeck, Jens Christian Sidney; Westh, Peter; Madsen, Jens Christian

    2011-01-01

    The complexation of 6 bile salts with various methylated β-cyclodextrins was studied to elucidate how the degree and pattern of substitution affects the binding. The structures of the CDs were determined by mass spectrometry and NMR techniques, and the structures of the inclusion complexes were...

  5. A relative quantitative Methylation-Sensitive Amplified Polymorphism (MSAP) method for the analysis of abiotic stress

    Bednarek, Piotr T.; Or?owska, Renata; Niedziela, Agnieszka

    2017-01-01

    Background We present a new methylation-sensitive amplified polymorphism (MSAP) approach for the evaluation of relative quantitative characteristics such as demethylation, de novo methylation, and preservation of methylation status of CCGG sequences, which are recognized by the isoschizomers HpaII and MspI. We applied the technique to analyze aluminum (Al)-tolerant and non-tolerant control and Al-stressed inbred triticale lines. The approach is based on detailed analysis of events affecting H...

  6. Epigenetic regulation during fetal femur development: DNA methylation matters.

    María C de Andrés

    Full Text Available Epigenetic modifications are heritable changes in gene expression without changes in DNA sequence. DNA methylation has been implicated in the control of several cellular processes including differentiation, gene regulation, development, genomic imprinting and X-chromosome inactivation. Methylated cytosine residues at CpG dinucleotides are commonly associated with gene repression; conversely, strategic loss of methylation during development could lead to activation of lineage-specific genes. Evidence is emerging that bone development and growth are programmed; although, interestingly, bone is constantly remodelled throughout life. Using human embryonic stem cells, human fetal bone cells (HFBCs, adult chondrocytes and STRO-1(+ marrow stromal cells from human bone marrow, we have examined a spectrum of developmental stages of femur development and the role of DNA methylation therein. Using pyrosequencing methodology we analysed the status of methylation of genes implicated in bone biology; furthermore, we correlated these methylation levels with gene expression levels using qRT-PCR and protein distribution during fetal development evaluated using immunohistochemistry. We found that during fetal femur development DNA methylation inversely correlates with expression of genes including iNOS (NOS2 and COL9A1, but not catabolic genes including MMP13 and IL1B. Furthermore, significant demethylation was evident in the osteocalcin promoter between the fetal and adult developmental stages. Increased TET1 expression and decreased expression of DNA (cytosine-5--methyltransferase 1 (DNMT1 in adult chondrocytes compared to HFBCs could contribute to the loss of methylation observed during fetal development. HFBC multipotency confirms these cells to be an ideal developmental system for investigation of DNA methylation regulation. In conclusion, these findings demonstrate the role of epigenetic regulation, specifically DNA methylation, in bone development

  7. The altered promoter methylation of oxytocin receptor gene in autism.

    Elagoz Yuksel, Mine; Yuceturk, Betul; Karatas, Omer Faruk; Ozen, Mustafa; Dogangun, Burak

    Autism spectrum disorder (ASD) is one of the lifelong existing disorders. Abnormal methylation status of gene promoters of oxytonergic system has been implicated as among the etiologic factors of ASDs. We, therefore, investigated the methylation frequency of oxytocin receptor gene (OXTR) promoter from peripheral blood samples of children with autistic features. Our sample includes 66 children in total (22-94 months); 27 children with ASDs according to the DSM-IV-TR and the Childhood Autism Rating Scale (CARS) and 39 children who do not have any autistic like symptoms as the healthy control group. We investigated the DNA methylation status of OXTR promoter by methylation specific enzymatic digestion of genomic DNA and polymerase chain reaction. A significant relationship has been found between ASDs and healthy controls for the reduction of methylation frequency of the regions MT1 and MT3 of OXTR. We could not find any association in the methylation frequency of MT2 and MT4 regions of OXTR. Although our findings indicate high frequency of OXTR promoter hypomethylation in ASDs, there is need for independent replication of the results for a bigger sample set. We expect that future studies with the inclusion of larger, more homogeneous samples will attempt to disentangle the causes of ASDs.

  8. Quantitative analysis of DNA methylation in chronic lymphocytic leukemia patients.

    Lyko, Frank; Stach, Dirk; Brenner, Axel; Stilgenbauer, Stephan; Döhner, Hartmut; Wirtz, Michaela; Wiessler, Manfred; Schmitz, Oliver J

    2004-06-01

    Changes in the genomic DNA methylation level have been found to be closely associated with tumorigenesis. In order to analyze the relation of aberrant DNA methylation to clinical and biological risk factors, we have determined the cytosine methylation level of 81 patients diagnosed with chronic lymphocytic leukemia (CLL). The analysis was based on DNA hydrolysis followed by derivatization of the 2'-desoxyribonucleoside-3'-monophosphates with BODIPY FL EDA. Derivatives were separated by micellar electrokinetic chromatography, and laser-induced fluorescence was used for detection. We analyzed potential correlations between DNA methylation levels and numerous patient parameters, including clinical observations and biological data. As a result, we observed a significant correlation with the immunoglobulin variable heavy chain gene (VH) mutation status. This factor has been repeatedly proposed as a reliable prognostic marker for CLL, which suggests that the methylation level might be a valuable factor in determining the prognostic outcome of CLL. We are now in the process of refining our method to broaden its application potential. In this context, we show here that the oxidation of the fluorescence marker in the samples and the evaporation of methanol in the electrolytes can be prevented by a film of paraffin oil. In summary, our results thus establish capillary electrophoresis as a valuable tool for analyzing the DNA methylation status of clinical samples.

  9. [Methylation of selected tumor-supressor genes in benign and malignant ovarian tumors].

    Cul'bová, M; Lasabová, Z; Stanclová, A; Tilandyová, P; Zúbor, P; Fiolka, R; Danko, J; Visnovský, J

    2011-09-01

    To evaluate the usefullness of examination of methylation status of selected tumor-supressor genes in early diagnosis of ovarian cancer. Prospective clinical study. Department of Gynecology and Obstetrics, Department of Molecular Biology, Jessenius Medical Faculty, Commenius University, Martin, Slovak Republic. In this study we analyzed hypermethylation of 5 genes RASSF1A, GSTP, E-cadherin, p16 and APC in ovarian tumor samples from 34 patients - 13 patients with epithelial ovarian cancer, 2 patients with border-line ovarian tumors, 12 patients with benign lesions of ovaries and 7 patients with healthy ovarian tissue. The methylation status of promoter region of tumor-supressor genes was determined by Methylation Specific Polymerase Chain Reaction (MSP) using a nested two-step approach with bisulfite modified DNA template and specific primers. Gene methylation analysis revealed hypermethylation of gene RASSF1A (46%) and GSTP (8%) only in malignant ovarian tissue samples. Ecad, p16 and APC genes were methylated both in maignant and benign tissue samples. Methylation positivity in observed genes was present independently to all clinical stages of ovarian cancer and to tumor grades. However, there was observed a trend of increased number and selective involvement of methylated genes with increasing disease stages. Furthermore, there was no association between positive methylation status and histological subtypes of ovarian carcinomas. RASSF1A and GSTP promoter methylation positivity is associated with ovarian cancer. The revealed gene-selective methylation positivity and the increased number of methylated genes with advancing disease stages could be considered as a useful molecular marker for early detection of ovarian cancer. However, there is need to find diagnostic approach of specifically and frequently methylated genes to determining a methylation phenotype for early detection of ovarian malignancies.

  10. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

    Nordlund, Jessica; Bäcklin, Christofer L; Wahlberg, Per

    2013-01-01

    BACKGROUND: Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic...... background, drug resistance and relapse in ALL is poorly understood. RESULTS: We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. This survey uncovered four characteristic methylation signatures. First, compared...... cells at relapse, compared with matched samples at diagnosis. Analysis of relapse-free survival identified CpG sites with subtype-specific differential methylation that divided the patients into different risk groups, depending on their methylation status. CONCLUSIONS: Our results suggest an important...

  11. Reference Materials for Calibration of Analytical Biases in Quantification of DNA Methylation.

    Yu, Hannah; Hahn, Yoonsoo; Yang, Inchul

    2015-01-01

    Most contemporary methods for the quantification of DNA methylation employ bisulfite conversion and PCR amplification. However, many reports have indicated that bisulfite-mediated PCR methodologies can result in inaccurate measurements of DNA methylation owing to amplification biases. To calibrate analytical biases in quantification of gene methylation, especially those that arise during PCR, we utilized reference materials that represent exact bisulfite-converted sequences with 0% and 100% methylation status of specific genes. After determining relative quantities using qPCR, pairs of plasmids were gravimetrically mixed to generate working standards with predefined DNA methylation levels at 10% intervals in terms of mole fractions. The working standards were used as controls to optimize the experimental conditions and also as calibration standards in melting-based and sequencing-based analyses of DNA methylation. Use of the reference materials enabled precise characterization and proper calibration of various biases during PCR and subsequent methylation measurement processes, resulting in accurate measurements.

  12. Protein methylation in pea chloroplasts

    Niemi, K.J.; Adler, J.; Selman, B.R.

    1990-01-01

    The methylation of chloroplast proteins has been investigated by incubating intact pea (Pisum sativum) chloroplasts with [ 3 H-methyl]-S-adenosylmethionine. Incubation in the light increases the amount of methylation in both the thylakoid and stromal fractions. Numerous thylakoid proteins serve as substrates for the methyltransfer reactions. Three of these thylakoid proteins are methylated to a significantly greater extent in the light than in the dark. The primary stromal polypeptide methylated is the large subunit of ribulose bisphosphate carboxylase/oxygenase. One other stromal polypeptide is also methylated much more in the light than in the dark. Two distinct types of protein methylation occur. One methylinkage is stable to basic conditions whereas a second type is base labile. The base-stable linkage is indicative of N-methylation of amino acid residues while base-lability is suggestive of carboxymethylation of amino acid residues. Labeling in the light increases the percentage of methylation that is base labile in the thylakoid fraction while no difference is observed in the amount of base-labile methylations in light-labeled and dark-labeled stromal proteins. Also suggestive of carboxymethylation is the detection of volatile [ 3 H]methyl radioactivity which increases during the labeling period and is greater in chloroplasts labeled in the light as opposed to being labeled in the dark; this implies in vivo turnover of the [ 3 H]methyl group

  13. Methylation of food commodities during fumigation with methyl bromide

    Starratt, A.N.; Bond, E.J.

    1990-01-01

    Sites of methylation in several commodities (wheat, oatmeal, peanuts, almonds, apples, oranges, maize, alfalfa and potatoes) during fumigation with 14 C-methyl bromide were studied. Differences were observed in levels of the major volatiles: methanol, dimethyl sulphide and methyl mercaptan, products of O- and S-methylation, resulting from treatment of the fumigated materials with 1N sodium hydroxide. In studies of maize and wheat, histidine was the amino acid which underwent the highest level of N-methylation. (author). 24 refs, 3 tabs

  14. Patterns of DNA methylation in the normal colon vary by anatomical location, gender, and age

    Kaz, Andrew M; Wong, Chao-Jen; Dzieciatkowski, Slavomir; Luo, Yanxin; Schoen, Robert E; Grady, William M

    2014-01-01

    Alterations in DNA methylation have been proposed to create a field cancerization state in the colon, where molecular alterations that predispose cells to transformation occur in histologically normal tissue. However, our understanding of the role of DNA methylation in field cancerization is limited by an incomplete characterization of the methylation state of the normal colon. In order to determine the colon’s normal methylation state, we extracted DNA from normal colon biopsies from the rectum, sigmoid, transverse, and ascending colon and assessed the methylation status of the DNA by pyrosequencing candidate loci as well as with HumanMethylation450 arrays. We found that methylation levels of repetitive elements LINE-1 and SAT-α showed minimal variability throughout the colon in contrast to other loci. Promoter methylation of EVL was highest in the rectum and progressively lower in the proximal segments, whereas ESR1 methylation was higher in older individuals. Genome-wide methylation analysis of normal DNA revealed 8388, 82, and 93 differentially methylated loci that distinguished right from left colon, males from females, and older vs. younger individuals, respectively. Although variability in methylation between biopsies and among different colon segments was minimal for repetitive elements, analyses of specific cancer-related genes as well as a genome-wide methylation analysis demonstrated differential methylation based on colon location, individual age, and gender. These studies advance our knowledge regarding the variation of DNA methylation in the normal colon, a prerequisite for future studies aimed at understanding methylation differences indicative of a colon field effect. PMID:24413027

  15. Effect of DNA methylation on identification of aggressive prostate cancer.

    Alumkal, Joshi J; Zhang, Zhe; Humphreys, Elizabeth B; Bennett, Christina; Mangold, Leslie A; Carducci, Michael A; Partin, Alan W; Garrett-Mayer, Elizabeth; DeMarzo, Angelo M; Herman, James G

    2008-12-01

    Biochemical (prostate-specific antigen) recurrence of prostate cancer after radical prostatectomy remains a major problem. Better biomarkers are needed to identify high-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the effect of DNA methylation on the identification of recurrent prostate cancer. We studied the methylation status of 15 pre-specified genes using methylation-specific polymerase chain reaction on tissue samples from 151 patients with localized prostate cancer and at least 5 years of follow-up after prostatectomy. On multivariate logistic regression analysis, a high Gleason score and involvement of the capsule, lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of biochemical recurrence. Methylation of CDH13 by itself (odds ratio 5.50, 95% confidence interval [CI] 1.34 to 22.67; P = 0.02) or combined with methylation of ASC (odds ratio 5.64, 95% CI 1.47 to 21.7; P = 0.01) was also associated with an increased risk of biochemical recurrence. The presence of methylation of ASC and/or CDH13 yielded a sensitivity of 72.3% (95% CI 57% to 84.4%) and negative predictive value of 79% (95% CI 66.8% to 88.3%), similar to the weighted risk of recurrence (determined from the lymph node status, seminal vesicle status, surgical margin status, and postoperative Gleason score), a powerful clinicopathologic prognostic score. However, 34% (95% CI 21% to 49%) of the patients with recurrence were identified by the methylation profile of ASC and CDH13 rather than the weighted risk of recurrence. The results of our study have shown that methylation of CDH13 alone or combined with methylation of ASC is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even considering the weighted risk of recurrence score. These findings should be validated in an independent, larger cohort of patients with prostate cancer who have

  16. Altered placental DNA methylation patterns associated with maternal smoking: current perspectives

    Maccani JZ

    2015-05-01

    Full Text Available Jennifer ZJ Maccani, Matthew A Maccani Penn State Tobacco Center of Regulatory Science, College of Medicine, Department of Public Health Sciences, Hershey, PA, USA Abstract: The developmental origins of health and disease hypothesis states that adverse early life exposures can have lasting, detrimental effects on lifelong health. Exposure to maternal cigarette smoking during pregnancy is associated with morbidity and mortality in offspring, including increased risks for miscarriage, stillbirth, low birth weight, preterm birth, asthma, obesity, altered neurobehavior, and other conditions. Maternal cigarette smoking during pregnancy interferes with placental growth and functioning, and it has been proposed that this may occur through the disruption of normal and necessary placental epigenetic patterns. Epigenome-wide association studies have identified a number of differentially methylated placental genes that are associated with maternal smoking during pregnancy, including RUNX3, PURA, GTF2H2, GCA, GPR135, and HKR1. The placental methylation status of RUNX3 and NR3C1 has also been linked to adverse infant outcomes, including preterm birth and low birth weight, respectively. Candidate gene analyses have also found maternal smoking-associated placental methylation differences in the NR3C1, CYP1A1, HTR2A, and HSD11B2 genes, as well as in the repetitive elements LINE-1 and AluYb8. The differential methylation patterns of several genes have been confirmed to also exhibit altered gene expression patterns, including CYP1A1, CYP19A1, NR3C1, and HTR2A. Placental methylation patterns associated with maternal smoking during pregnancy may be largely gene-specific and tissue-specific and, to a lesser degree, involve global changes. It is important for future research to investigate the mechanistic roles that these differentially methylated genes may play in mediating the association between maternal smoking during pregnancy and disease in later life, as well

  17. Evaluation of methylation pattern in promoter region of E-cadherin ...

    user

    2011-03-07

    Mar 7, 2011 ... promoter methylation in CDH1 gene inactivation in breast cancer, the CpG methylation status of E- ..... 5'CpG island of CDH1 in prostate, lung, liver, bladder, .... and estrogen receptor alpha from Sp1 sites to induce cell cycle.

  18. Bisulfite sequencing reveals that Aspergillus flavus holds a hollow in DNA methylation.

    Si-Yang Liu

    Full Text Available Aspergillus flavus first gained scientific attention for its production of aflatoxin. The underlying regulation of aflatoxin biosynthesis has been serving as a theoretical model for biosynthesis of other microbial secondary metabolites. Nevertheless, for several decades, the DNA methylation status, one of the important epigenomic modifications involved in gene regulation, in A. flavus remains to be controversial. Here, we applied bisulfite sequencing in conjunction with a biological replicate strategy to investigate the DNA methylation profiling of A. flavus genome. Both the bisulfite sequencing data and the methylome comparisons with other fungi confirm that the DNA methylation level of this fungus is negligible. Further investigation into the DNA methyltransferase of Aspergillus uncovers its close relationship with RID-like enzymes as well as its divergence with the methyltransferase of species with validated DNA methylation. The lack of repeat contents of the A. flavus' genome and the high RIP-index of the small amount of remanent repeat potentially support our speculation that DNA methylation may be absent in A. flavus or that it may possess de novo DNA methylation which occurs very transiently during the obscure sexual stage of this fungal species. This work contributes to our understanding on the DNA methylation status of A. flavus, as well as reinforces our views on the DNA methylation in fungal species. In addition, our strategy of applying bisulfite sequencing to DNA methylation detection in species with low DNA methylation may serve as a reference for later scientific investigations in other hypomethylated species.

  19. Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors

    Durr, Megan L.; Mydlarz, Wojciech K.; Shao, Chunbo; Zahurak, Marianna L.; Chuang, Alice Y.; Hoque, Mohammad O.; Westra, William H.; Liegeois, Nanette J.; Califano, Joseph A.; Sidransky, David; Ha, Patrick K.

    2010-01-01

    Background Methylation profiling of tumor suppressor gene (TSGs) promoters is quickly becoming a powerful diagnostic tool for the early detection, prognosis, and even prediction of clinical response to treatment. Few studies address this in salivary gland tumors (SGTs); hence the promoter methylation profile of various TSGs was quantitatively assessed in primary SGT tissue to determine if tumor-specific alterations could be detected. Methodology DNA isolated from 78 tumor and 17 normal parotid gland specimens was assayed for promoter methylation status of 19 TSGs by fluorescence-based, quantitative methylation-specific PCR (qMSP). The data were utilized in a binary fashion as well as quantitatively (using a methylation quotient) allowing for better profiling and interpretation of results. Principal Findings The average number of methylation events across the studied genes was highest in salivary duct carcinoma (SDC), with a methylation value of 9.6, compared to the normal 4.5 (ptrend for increasing methylation in APC, Mint 1, PGP9.5, RAR-β, and Timp3. Conclusions/Significance Screening promoter methylation profiles in SGTs showed considerable heterogeneity. The methylation status of certain markers was surprisingly high in even normal salivary tissue, confirming the need for such controls. Several TSGs were found to be associated with malignant SGTs, especially SDC. Further study is needed to evaluate the potential use of these associations in the detection, prognosis, and therapeutic outcome of these rare tumors. PMID:20520817

  20. DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells

    Roost, Matthias S; Slieker, Roderick C; Bialecka, Monika; van Iperen, Liesbeth; Gomes Fernandes, Maria M; He, Nannan; Suchiman, H Eka D; Szuhai, Karoly; Carlotti, Françoise; de Koning, Eelco J P; Mummery, Christine L; Heijmans, Bastiaan T; Chuva de Sousa Lopes, Susana M

    2017-01-01

    Determining cell identity and maturation status of differentiated pluripotent stem cells (PSCs) requires knowledge of the transcriptional and epigenetic trajectory of organs during development. Here, we generate a transcriptional and DNA methylation atlas covering 21 organs during human fetal