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Sample records for adaptive epigenetic reorganization

  1. Epigenetics and the Adaptive Immune Response

    Kondilis-Mangum, Hrisavgi D.; Wade, Paul A.

    2012-01-01

    Cells of the adaptive immune response undergo dynamic epigenetic changes as they develop and respond to immune challenge. Plasticity is a necessary prerequisite for the chromosomal dynamics of lineage specification, development, and the immune effector function of the mature cell types. The alterations in DNA methylation and histone modification that characterize activation may be integral to the generation of immunologic memory, thereby providing an advantage on secondary exposure to pathoge...

  2. Multigenerational Epigenetic Adaptation of the Hepatic Wound-Healing Response

    Zeybel, Müjdat; Hardy, Timothy; Wong, Yi K.; Mathers, John C; Fox, Christopher R.; Gackowska, Agata; Oakley, Fiona; Burt, Alastair D; Wilson, Caroline L.; Anstee, Quentin M.; Barter, Matt J; Masson, Steven; Elsharkawy, Ahmed M.; Mann, Derek A.; Mann, Jelena

    2012-01-01

    We asked if ancestral liver damage leads to heritable reprogramming of hepatic wound-healing. We discovered that male rats with a history of liver damage transmit epigenetic suppressive adaptation of the fibrogenic component of wound-healing through male F1 and F2 generations. Underlying this adaptation was reduced generation of liver myofibroblasts, increased hepatic expression of antifibrogenic PPAR-γ and decreased expression of profibrogenic TGF-β1. Remodelling of DNA methylation and histo...

  3. Multigenerational epigenetic adaptation of the hepatic wound-healing response.

    Zeybel, Müjdat; Hardy, Timothy; Wong, Yi K; Mathers, John C; Fox, Christopher R; Gackowska, Agata; Oakley, Fiona; Burt, Alastair D; Wilson, Caroline L; Anstee, Quentin M; Barter, Matt J; Masson, Steven; Elsharkawy, Ahmed M; Mann, Derek A; Mann, Jelena

    2012-09-01

    We investigated whether ancestral liver damage leads to heritable reprogramming of hepatic wound healing in male rats. We found that a history of liver damage corresponds with transmission of an epigenetic suppressive adaptation of the fibrogenic component of wound healing to the male F1 and F2 generations. Underlying this adaptation was less generation of liver myofibroblasts, higher hepatic expression of the antifibrogenic factor peroxisome proliferator-activated receptor γ (PPAR-γ) and lower expression of the profibrogenic factor transforming growth factor β1 (TGF-β1) compared to rats without this adaptation. Remodeling of DNA methylation and histone acetylation underpinned these alterations in gene expression. Sperm from rats with liver fibrosis were enriched for the histone variant H2A.Z and trimethylation of histone H3 at Lys27 (H3K27me3) at PPAR-γ chromatin. These modifications to the sperm chromatin were transmittable by adaptive serum transfer from fibrotic rats to naive rats and similar modifications were induced in mesenchymal stem cells exposed to conditioned media from cultured rat or human myofibroblasts. Thus, it is probable that a myofibroblast-secreted soluble factor stimulates heritable epigenetic signatures in sperm so that the resulting offspring better adapt to future fibrogenic hepatic insults. Adding possible relevance to humans, we found that people with mild liver fibrosis have hypomethylation of the PPARG promoter compared to others with severe fibrosis. PMID:22941276

  4. Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism

    Buescher, Joerg Martin; Liebermeister, Wolfram; Jules, Matthieu;

    2012-01-01

    known transcription regulation network. Interactions across multiple levels of regulation were involved in adaptive changes that could also be achieved by controlling single genes. Our analysis suggests that global trade-offs and evolutionary constraints provide incentives to favor complex control......Adaptation of cells to environmental changes requires dynamic interactions between metabolic and regulatory networks, but studies typically address only one or a few layers of regulation. For nutritional shifts between two preferred carbon sources of Bacillus subtilis, we combined statistical and...... model-based data analyses of dynamic transcript, protein, and metabolite abundances and promoter activities. Adaptation to malate was rapid and primarily controlled posttranscriptionally compared with the slow, mainly transcriptionally controlled adaptation to glucose that entailed nearly half of the...

  5. How stable 'should' epigenetic modifications be? Insights from adaptive plasticity and bet hedging.

    Herman, Jacob J; Spencer, Hamish G; Donohue, Kathleen; Sultan, Sonia E

    2014-03-01

    Although there is keen interest in the potential adaptive value of epigenetic variation, it is unclear what conditions favor the stability of these variants either within or across generations. Because epigenetic modifications can be environmentally sensitive, existing theory on adaptive phenotypic plasticity provides relevant insights. Our consideration of this theory suggests that stable maintenance of environmentally induced epigenetic states over an organism's lifetime is most likely to be favored when the organism accurately responds to a single environmental change that subsequently remains constant, or when the environmental change cues an irreversible developmental transition. Stable transmission of adaptive epigenetic states from parents to offspring may be selectively favored when environments vary across generations and the parental environment predicts the offspring environment. The adaptive value of stability beyond a single generation of parent-offspring transmission likely depends on the costs of epigenetic resetting. Epigenetic stability both within and across generations will also depend on the degree and predictability of environmental variation, dispersal patterns, and the (epi)genetic architecture underlying phenotypic responses to environment. We also discuss conditions that favor stability of random epigenetic variants within the context of bet hedging. We conclude by proposing research directions to clarify the adaptive significance of epigenetic stability. PMID:24274594

  6. Factors Influencing Adaptive Capacity in the Reorganization of Forest Management in Alaska

    Colin Beier

    2011-03-01

    Full Text Available Several studies of U.S. National Forests suggest that declines of their associated forest products industries were driven by synergistic changes in federal governance and market conditions during the late 20th century. In Alaska, dramatic shifts in the economic and political settings of the Tongass National Forest (Tongass drove changes in governance leading to collapse of an industrial forest management system in the early 1990s. However, 15 years since collapse, the reorganization of Tongass governance to reflect 'new' economic and political realities has not progressed. To understand both the factors that hinder institutional change (inertia and the factors that enable progress toward reorganization (adaptation, I analyzed how Tongass forest management, specifically timber sale planning, has responded to changes in market conditions, local industry structure, and larger-scale political governance. Inertia was evidenced by continued emphasis on even-aged management and large-scale harvesting, i.e., the retention of an industrial forestry philosophy that, in the current political situation, yields mostly litigation and appeals, and relatively few forest products. Adaptation was evidenced by flexibility in harvest methods, a willingness to meet local demand instead of political targets, and a growing degree of cooperation with environmental advocacy groups. New partnerships, markets, and political leaders at state and national levels can frame a new blueprint for reorganization of Tongass management toward a more sustainable future.

  7. Adaptation or malignant transformation: the two faces of epigenetically mediated response to stress.

    Vojta, Aleksandar; Zoldoš, Vlatka

    2013-01-01

    Adaptive response to stress is a fundamental property of living systems. At the cellular level, many different types of stress elicit an essentially limited repertoire of adaptive responses. Epigenetic changes are the main mechanism for medium- to long-term adaptation to accumulated (intense, long-term, or repeated) stress. We propose the adaptive deregulation of the epigenome in response to stress (ADERS) hypothesis which assumes that the unspecific adaptive stress response grows stronger with the increasing stress level, epigenetically activating response gene clusters while progressively deregulating other cellular processes. The balance between the unspecific adaptive response and the general epigenetic deregulation is critical because a strong response can lead to pathology, particularly to malignant transformation. The main idea of our hypothesis is the continuum traversed by a cell subjected to accumulated stress, which lies between an unspecific adaptive response and pathological deregulation--the two extremes sharing the same underlying cause, which is a manifestation of a unified epigenetically mediated adaptive response to stress. The evolutionary potential of epigenetic regulation in multigenerational adaptation is speculatively discussed in the light of neo-Lamarckism. Finally, an approach to testing the proposed hypothesis is presented, relying on either the publicly available datasets or on conducting new experiments. PMID:24187667

  8. Adaptive radiation-induced epigenetic alterations mitigated by antioxidants

    Bernal, Autumn J.; Dolinoy, Dana C; Huang, Dale; Skaar, David A.; Weinhouse, Caren; Jirtle, Randy L

    2013-01-01

    Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (Avy) locus in a sex-specific man...

  9. Adaptive Epigenetic Differentiation between Upland and Lowland Rice Ecotypes Revealed by Methylation-Sensitive Amplified Polymorphism

    Xiong, Jie; Tao, Tao; Zheng, Xiaoguo; Wei, Haibin; Yue, Yunxia; Chen, Liang; Luo, Lijun

    2016-01-01

    The stress-induced epimutations could be inherited over generations and play important roles in plant adaption to stressful environments. Upland rice has been domesticated in water-limited environments for thousands of years and accumulated drought-induced epimutations of DNA methylation, making it epigenetically differentiated from lowland rice. To study the epigenetic differentiation between upland and lowland rice ecotypes on their drought-resistances, the epigenetic variation was investigated in 180 rice landraces under both normal and osmotic conditions via methylation-sensitive amplified polymorphism (MSAP) technique. Great alterations (52.9~54.3% of total individual-locus combinations) of DNA methylation are recorded when rice encountering the osmotic stress. Although the general level of epigenetic differentiation was very low, considerable level of ΦST (0.134~0.187) was detected on the highly divergent epiloci (HDE). The HDE detected in normal condition tended to stay at low levels in upland rice, particularly the ones de-methylated in responses to osmotic stress. Three out of four selected HDE genes differentially expressed between upland and lowland rice under normal or stressed conditions. Moreover, once a gene at HDE was up-/down-regulated in responses to the osmotic stress, its expression under the normal condition was higher/lower in upland rice. This result suggested expressions of genes at the HDE in upland rice might be more adaptive to the osmotic stress. The epigenetic divergence and its influence on the gene expression should contribute to the higher drought-resistance in upland rice as it is domesticated in the water-limited environment. PMID:27380174

  10. A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae.

    Atack, John M; Srikhanta, Yogitha N; Fox, Kate L; Jurcisek, Joseph A; Brockman, Kenneth L; Clark, Tyson A; Boitano, Matthew; Power, Peter M; Jen, Freda E-C; McEwan, Alastair G; Grimmond, Sean M; Smith, Arnold L; Barenkamp, Stephen J; Korlach, Jonas; Bakaletz, Lauren O; Jennings, Michael P

    2015-01-01

    Non-typeable Haemophilus influenzae contains an N(6)-adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10, account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis to identify the DNA-recognition motifs for all five of these modA alleles. Phase variation of these alleles regulates multiple proteins including vaccine candidates, and key virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10), biofilm formation (modA2) and immunoevasion (modA4). Analyses of a modA2 strain in the chinchilla model of otitis media show a clear selection for ON switching of modA2 in the middle ear. Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system. PMID:26215614

  11. ISSUES IN ROMANIAN BANKING SYSTEM IN THE CONTEXT OF REORGANIZING ITS ADAPTATION TO THE REQUIREMENTS OF THE MARKET ECONOMY

    IOAN DUMITRU MOTONIU

    2011-01-01

    Full Text Available Based on the concept that the banking system is the engine of economic development, the paper is intended as a blueprint for the banking system in Romania since 1989, stages and parts of its reorganizing process. In the article is also carried out an analysis of the Romanian banking system in terms of numerical development banks and through the two indicators considered fundamental in the banking system: market share, expressed in terms of net balance sheet asset, that social / endowment capital and are presented the conclusions that have been drawn from this analysis.

  12. Variation in genes involved in epigenetic processes offers insights into tropically adapted cattle diversity.

    Porto-Neto, Laercio R; Fortes, Marina R S; McWilliam, Sean M; Lehnert, Sigrid A; Reverter, Antonio

    2014-01-01

    We evaluated the relevance of the BovineHD Illumina SNP chip with respect to genes involved in epigenetic processes. Genotypes for 729,068 SNP on two tropical cattle breeds of Australia were used: Brahman (n = 2112) and Tropical Composite (n = 2550). We used data mining approaches to compile a list of bovine protein-coding genes involved in epigenetic processes. These genes represent 9 functional categories that contain between one (histone demethylases) and 99 (chromatin remodeling factors) genes. A total of 3091 SNP mapped to positions within 3000 bp of the 193 coding regions of those genes, including 113 SNP in transcribed regions, 2738 in intronic regions and 240 in up- or down-stream regions. For all these SNP categories, we observed differences in the allelic frequencies between Brahman and Tropical Composite cattle. These differences were larger than those observed for the entire set of 729,068 SNP (P = 1.79 x 10(-5)). A multidimensional scaling analysis using only the 113 SNP in transcribed regions allowed for the separation of the two populations and this separation was comparable to the one obtained with a random set of 113 SNP (Principal Component 1 r (2) > 0.84). To further characterize the differences between the breeds we defined a gene-differentiation metric based on the average genotypic frequencies of SNP connected to each gene and compared both cattle populations. The 10% most differentiated genes were distributed across 10 chromosomes, with significant (P < 0.05) enrichment on BTA 3 and 10. The 10% most conserved genes were located in 12 chromosomes. We conclude that there is variation between cattle populations in genes connected to epigenetic processes, and this variation can be used to differentiate cattle breeds. More research is needed to fully characterize the use of these SNP and its potential as means to further our understanding of biological variation and epigenetic processes. PMID:24795751

  13. Variation in genes involved in epigenetic processes offers insights into tropically adapted cattle diversity

    Laercio R Porto-Neto

    2014-04-01

    Full Text Available We evaluated the relevance of the BovineHD Illumina SNP chip with respect to genes involved in epigenetic processes. Genotypes for 729,068 SNP on two tropical cattle breeds of Australia were used: Brahman (n = 2,112 and Tropical Composite (n = 2,550. We used data mining approaches to compile a list of bovine protein-coding genes involved in epigenetic processes. These genes represent 9 functional categories that contain between one (histone demethylases and 99 (chromatin remodelling factors genes. A total of 3,091 SNP mapped to positions within 3,000 bp of the 193 coding regions of those genes, including 113 SNP in transcribed regions, 2,738 in intronic regions and 240 in up- or down-stream regions. For all these SNP categories, we observed differences in the allelic frequencies between Brahman and Tropical Composite cattle. These differences were larger than those observed for the entire set of 729,068 SNP (P = 1.79 x 10-5. A multidimensional scaling analysis using only the 113 SNP in transcribed regions allowed for the separation of the two populations and this separation was comparable to the one obtained with a random set of 113 SNP (Principal Component 1 r2 > 0.84. To further characterise the differences between the breeds we defined a gene-differentiation metric based on the average genotypic frequencies of SNP connected to each gene and compared both cattle populations. The 10% most differentiated genes were distributed across 10 chromosomes, with significant (P < 0.05 enrichment on BTA 3 and 10. The 10% most conserved genes were located in 12 chromosomes. We conclude that there is variation between cattle populations in genes connected to epigenetic processes, and this variation can be used to differentiate cattle breeds. More research is needed to fully characterise the use of these SNP and its potential as means to further our understanding of biological variation and epigenetic processes.

  14. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells.

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  15. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N8-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  16. Drilling reorganizes

    Richman, Barbara T.

    As the first in a proposed series of steps that would move scientific ocean drilling from its own niche within the National Science Foundation's (NSF) Directorate for Astronomical, Atmospheric, Earth, and Ocean Sciences (AAEO) into the agency's Division of Ocean Sciences, Grant Gross, division director, has been appointed acting director of the Office of Scientific Ocean Drilling (OSOD). Gross will retain the directorship of the division, which also is part of AAEO. Allen M. Shinn, Jr., OSOD director for nearly 2 years, has been reassigned effective July 10 to a position in NSF's Office of Planning and Resource Management.The move aims to tie drilling operations more closely to the science with which it is associated, Gross said. This first step is an organizational response to the current leaning toward using a commercial drilling vessel as the drilling platform, he said. Before the market for such commercial drill ships opened (Eos, February 22, 1983, p . 73), other ship options for scientific ocean drilling included refurbishing the aging Glomar Challenger or renovating, at great expense, the Glomar Explorer. A possible next step in the reorganization is to make OSOD the third section within the Ocean Sciences Division. Currently, the division is divided into the Oceanographic Facilities and Support Section and the Ocean Sciences Research Section.

  17. Control of cognition and adaptive behavior by the GLP/G9a epigenetic suppressor complex

    Schaefer, Anne; Sampath, Srihari C.; Intrator, Adam; Min, Alice; Gertler, Tracy S.; Surmeier, D. James; Tarakhovsky, Alexander; Greengard, Paul

    2009-01-01

    The genetic basis of cognition and behavioral adaptation to the environment remains poorly understood. Here we demonstrate that the histone methyltransferase complex GLP/G9a controls cognition and adaptive responses in a region-specific fashion in the adult brain. Using conditional mutagenesis in mice, we show that postnatal, neuron-specific deficiency of GLP/G9a leads to de-repression of numerous non-neuronal and neuron progenitor genes in adult neurons. This transcriptional alteration is as...

  18. Molecular Mechanisms of Processing Proteome Reorganization of Interphase Chromatin During Stress and Adaptation to Winter in Wheat

    Ivanov R.S.

    2015-06-01

    Full Text Available Research of fundamental molecular and genetic processes of plant interaction with the environment, is a progressive field of understanding the fundamental problems of stress supramolecular biochemistry of developmental biology. The purpose of the work was the analysis of localization shielded to protease processing proteins of suprastructures of interphase chromatin matrix in the conditions of adaptation during vegetative phase of wheat to stressful environment factors. It is shown that in the conditions of perennial adaptation to cold shock of wheat at the level of chromatin suprastructures tightly bound to the nuclear matrix there is a total shielding of arginine-X sites to protease-processing. Perhaps these are zones that affect to the architecture organization of the cell nucleus that can help to survive in complex environmental conditions. According to the priorities in the study of agricultural plants, put forward by EPIC (The Epigenomics of Plants International Consortium in 2011 for the next decade, was included the point of necessity to understand the molecular basis of the interactions of genotype and environment that change the characteristics of plants in different conditions of the environment. These data will be useful for those who involved in the development of mathematical logic schemes of the theory and practice of biological specificity, and it could be included in the ontology of the stages plant growth and development.

  19. Adaptive plasticity and epigenetic variation in response to warming in an Alpine plant

    Adrienne B. Nicotra; Segal, Deborah L.; Hoyle, Gemma L; Schrey, Aaron W.; Verhoeven, Koen J. F.; Richards, Christina L.

    2015-01-01

    Environmentally induced phenotypic plasticity may be a critical component of response to changing environments. We examined local differentiation and adaptive phenotypic plasticity in response to elevated temperature in half-sib lines collected across an elevation gradient for the alpine herb, Wahlenbergia ceracea. Using Amplified Fragment Length Polymorphism (AFLP), we found low but significant genetic differentiation between low- and high-elevation seedlings, and seedlings originating from ...

  20. Epigenetic marks in an adaptive water stress-responsive gene in tomato roots under normal and drought conditions

    González, Rodrigo M; Martiniano M Ricardi; Iusem, Norberto D

    2013-01-01

    Tolerance to water deficits was evolutionarily relevant to the conquest of land by primitive plants. In this context, epigenetic events may have played important roles in the establishment of drought stress responses. We decided to inspect epigenetic marks in the plant organ that is crucial in the sensing of drought stress: the root. Using tomato as a crop model plant, we detected the methylated epialleles of Asr2, a protein-coding gene widespread in the plant kingdom and thought to alleviate...

  1. Epigenetics in an ecotoxicological context.

    Vandegehuchte, Michiel B; Janssen, Colin R

    2014-04-01

    Epigenetics can play a role in interactions between chemicals and exposed species, between species and abiotic ecosystem components or between species of the same or another population in a community. Technological progress and advanced insights into epigenetic processes have led to the description of epigenetic features (mainly DNA methylation) in many ecologically relevant species: algae, plants, several invertebrates and fish. Epigenetic changes in plants, insects and cladocerans have been reported to be induced by various environmental stress factors including nutrition or water deficiency, grazing, light or temperature alterations, social environment, and dissolved organic matter concentrations. As regards chemicals, studies in rats and mice exposed to specific pesticides, hydrocarbons, dioxins, and endocrine disrupting chemicals demonstrated the induction of epigenetic changes, suggesting the need for further research with these substances in an ecotoxicological context. In fish and plants, exposure to polyaromatic hydrocarbons, metals, and soluble fractions of solid waste affected the epigenetic status. A novel concept in ecotoxicological epigenetics is the induction of transgenerational stress resistance upon chemical exposure, as demonstrated in rice exposed to metals. Evaluating epigenetics in ecotoxicological field studies is a second relatively new approach. A cryptic lineage of earthworms had developed arsenic tolerance in the field, concurrent with specific DNA methylation patterns. Flatfish caught in the framework of environmental monitoring had developed tumours, exhibiting specific DNA methylation patterns. Two main potential implications of epigenetics in an ecotoxicological context are (1) the possibility of transgenerationally inherited, chemical stress-induced epigenetic changes with associated phenotypes and (2) epigenetically induced adaptation to stress upon long-term chemical exposure. Key knowledge gaps are concerned with the causality of

  2. Nutritional epigenetics

    This chapter is intended to provide a timely overview of the current state of research at the intersection of nutrition and epigenetics. I begin by describing epigenetics and molecular mechanisms of eigenetic regulation, then highlight four classes of nutritional exposures currently being investiga...

  3. Bacterial Stationary-State Mutagenesis and Mammalian Tumorigenesis as Stress-Induced Cellular Adaptations and the Role of Epigenetics

    Karpinets, TV; Greenwood, DJ; Pogribny, IP; Samatova, NF

    2006-01-01

    Mechanisms of cellular adaptation may have some commonalities across different organisms. Revealing these common mechanisms may provide insight in the organismal level of adaptation and suggest solutions to important problems related to the adaptation. An increased rate of mutations, referred as the mutator phenotype, and beneficial nature of these mutations are common features of the bacterial stationary-state mutagenesis and of the tumorigenic transformations in mammalian cells. We argue th...

  4. Skeletal muscle cells possess a 'memory' of acute early life TNF-α exposure: role of epigenetic adaptation.

    Sharples, Adam P; Polydorou, Ioanna; Hughes, David C; Owens, Daniel J; Hughes, Thomas M; Stewart, Claire E

    2016-06-01

    Sufficient quantity and quality of skeletal muscle is required to maintain lifespan and healthspan into older age. The concept of skeletal muscle programming/memory has been suggested to contribute to accelerated muscle decline in the elderly in association with early life stress such as fetal malnutrition. Further, muscle cells in vitro appear to remember the in vivo environments from which they are derived (e.g. cancer, obesity, type II diabetes, physical inactivity and nutrient restriction). Tumour-necrosis factor alpha (TNF-α) is a pleiotropic cytokine that is chronically elevated in sarcopenia and cancer cachexia. Higher TNF-α levels are strongly correlated with muscle loss, reduced strength and therefore morbidity and earlier mortality. We have extensively shown that TNF-α impairs regenerative capacity in mouse and human muscle derived stem cells [Meadows et al. (J Cell Physiol 183(3):330-337, 2000); Foulstone et al. (J Cell Physiol 189(2):207-215, 2001); Foulstone et al. (Exp Cell Res 294(1):223-235, 2004); Stewart et al. (J Cell Physiol 198(2):237-247, 2004); Al-Shanti et al. (Growth factors (Chur, Switzerland) 26(2):61-73, 2008); Saini et al. (Growth factors (Chur, Switzerland) 26(5):239-253, 2008); Sharples et al. (J Cell Physiol 225(1):240-250, 2010)]. We have also recently established an epigenetically mediated mechanism (SIRT1-histone deacetylase) regulating survival of myoblasts in the presence of TNF-α [Saini et al. (Exp Physiol 97(3):400-418, 2012)]. We therefore wished to extend this work in relation to muscle memory of catabolic stimuli and the potential underlying epigenetic modulation of muscle loss. To enable this aim; C2C12 myoblasts were cultured in the absence or presence of early TNF-α (early proliferative lifespan) followed by 30 population doublings in the absence of TNF-α, prior to the induction of differentiation in low serum media (LSM) in the absence or presence of late TNF-α (late proliferative lifespan). The cells that

  5. Epigenetics and child abuse: Modern-day Darwinism--The miraculous ability of the human genome to adapt, and then adapt again.

    Gershon, Naomi B; High, Pamela C

    2015-12-01

    It has long been recognized that early adversity can have life-long consequences, and the extent to which this is true is gaining increasing attention. A growing body of literature implicates Adverse Childhood Experiences, including physical, sexual, and emotional abuse, in a broad range of negative health consequences including adult psychopathology, cardiovascular, and immune disease. Increasing evidence from animal, clinical, and epidemiological studies highlight the critical role of epigenetic programing, such as DNA methylation and histone modification, in altering gene expression, brain structure and function, and ultimately life-course trajectories. This review outlines our developing insight into the interplay between our human biology and our changing environment, and explores the growing evidence base for how interventions may prevent and ameliorate damage inflicted by toxic stress in early life. PMID:26502111

  6. Epigenetics and nutritional environmental signals.

    Mazzio, Elizabeth A; Soliman, Karam F A

    2014-07-01

    All terrestrial life is influenced by multi-directional flows of information about its environment, enabling malleable phenotypic change through signals, chemical processes, or various forms of energy that facilitate acclimatization. Billions of biological co-inhabitants of the earth, including all plants and animals, collectively make up a genetic/epigenetic ecosystem by which adaptation/survival (inputs and outputs) are highly interdependent on one another. As an ecosystem, the solar system, rotation of the planets, changes in sunlight, and gravitational pull influence cyclic epigenetic transitions and chromatin remodeling that constitute biological circadian rhythms controlling senescence. In humans, adverse environmental conditions such as poverty, stress, alcohol, malnutrition, exposure to pollutants generated from industrialization, man-made chemicals, and use of synthetic drugs can lead to maladaptive epigenetic-related illnesses with disease-specific genes being atypically activated or silenced. Nutrition and dietary practices are one of the largest facets in epigenetic-related metabolism, where specific "epi-nutrients" can stabilize the genome, given established roles in DNA methylation, histone modification, and chromatin remodeling. Moreover, food-based "epi-bioactive" constituents may reverse maladaptive epigenetic patterns, not only prior to conception and during fetal/early postnatal development but also through adulthood. In summary, in contrast to a static genomic DNA structure, epigenetic changes are potentially reversible, raising the hope for therapeutic and/or dietary interventions that can reverse deleterious epigenetic programing as a means to prevent or treat major illnesses. PMID:24861811

  7. LOS ALAMOS: Reorganization

    Full text: A few months ago Los Alamos National Laboratory embarked on a major reorganization. All upper management was invited to submit their resignations and reapply for new positions, of which there are only about one third as many. This action was coordinated with an attractive early retirement incentive so that displaced managers, as well as any other employee, could choose to retire if they were unhappy with the reorganization, or for any other reason. About 850 of the Lab's 7,700 employees have chosen retirement. MP (Meson or Medium Energy Physics) and AT (Accelerator Technology) Divisions have been combined into the AOT (Accelerator Operations and Technology) Division. Stanley O. Schriber is its new Director. AOT Division is responsible for operations and improvements at the Los Alamos Meson Physics Facility (LAMPF) and supports traditional users, LANSCE (the Los Alamos Neutron Scattering Center), and the emerging neutron applications community. Advanced accelerator development, including beam transport theory, instrumentation, free electron laser technology, and engineering for research, defence, industrial, and medical applications will be a major focus

  8. Evolution, epigenetics and cooperation

    Patrick Bateson

    2014-04-01

    Explanations for biological evolution in terms of changes in gene frequencies refer to outcomes rather than process. Integrating epigenetic studies with older evolutionary theories has drawn attention to the ways in which evolution occurs. Adaptation at the level of the gene is givingway to adaptation at the level of the organism and higher-order assemblages of organisms. These ideas impact on the theories of how cooperation might have evolved. Two of the theories, i.e. that cooperating individuals are genetically related or that they cooperate for self-interested reasons, have been accepted for a long time. The idea that adaptation takes place at the level of groups is much more controversial. However, bringing together studies of development with those of evolution is taking away much of the heat in the debate about the evolution of group behaviour.

  9. Epigenetics protocols

    Manuela Monti

    2012-06-01

    Full Text Available Thanks to the creative effort of Prof. Trygve O. Tollefsbol (Dept. of Biology, University of Alabama at Birmingham, USA we can handle the second edition in just seven years of this must needed volume devoted to the study of the epigenome. In the very same window-time the field of epigenetics is dramatically changed as for the technical tools employed by the pupils of this pervasive discipline: actually there is no one hot topics in biology (e.g., development, differentiation, genomic toxicity and medicine .....

  10. Epistemological Pluralism: Reorganizing Interdisciplinary Research

    F. Stuart Chapin III

    2008-12-01

    Full Text Available Despite progress in interdisciplinary research, difficulties remain. In this paper, we argue that scholars, educators, and practitioners need to critically rethink the ways in which interdisciplinary research and training are conducted. We present epistemological pluralism as an approach for conducting innovative, collaborative research and study. Epistemological pluralism recognizes that, in any given research context, there may be several valuable ways of knowing, and that accommodating this plurality can lead to more successful integrated study. This approach is particularly useful in the study and management of social–ecological systems. Through resilience theory's adaptive cycle, we demonstrate how a focus on epistemological pluralism can facilitate the reorganization of interdisciplinary research and avoid the build-up of significant, but insufficiently integrative, disciplinary-dominated research. Finally, using two case studies—urban ecology and social–ecological research in Alaska—we highlight how interdisciplinary work is impeded when divergent epistemologies are not recognized and valued, and that by incorporating a pluralistic framework, these issues can be better explored, resulting in more integrated understanding.

  11. Epigenetic Memory in Mammals

    Migicovsky, Zoë; Kovalchuk, Igor

    2011-01-01

    Epigenetic information can be passed on from one generation to another via DNA methylation, histone modifications, and changes in small RNAs, a process called epigenetic memory. During a mammal’s lifecycle epigenetic reprogramming, or the resetting of most epigenetic marks, occurs twice. The first instance of reprogramming occurs in primordial germ cells and the second occurs following fertilization. These processes may be both passive and active. In order for epigenetic inheritance to occur ...

  12. A Guide to School District Reorganization.

    Warner, Allan K.

    School district reorganization is a process that requires considerable planning. This guide provides information on school district reorganization in the state of Nebraska, to interested boards of education and county and citizen reorganization committees. Topics discussed include planning for reorganization, establishing citizen committees, using…

  13. Natural epigenetic variation in bats and its role in evolution.

    Liu, Sen; Sun, Keping; Jiang, Tinglei; Feng, Jiang

    2015-01-01

    When facing the challenges of environmental change, such as habitat fragmentation, organisms have to adjust their phenotype to adapt to various environmental stresses. Recent studies show that epigenetic modifications could mediate environmentally induced phenotypic variation, and this epigenetic variance could be inherited by future generations, indicating that epigenetic processes have potential evolutionary effects. Bats living in diverse environments show geographic variations in phenotype, and the females usually have natal philopatry, presenting an opportunity to explore how environments shape epigenetic marks on the genome and the evolutionary potential of epigenetic variance in bat populations for adaptation. We have explored the natural epigenetic diversity and structure of female populations of the great roundleaf bat (Hipposideros armiger), the least horseshoe bat (Rhinolophus pusillus) and the eastern bent-winged bat (Miniopterus fuliginosus) using a methylation-sensitive amplified polymorphism technique. We have also estimated the effects of genetic variance and ecological variables on epigenetic diversification. All three bat species have a low level of genomic DNA methylation and extensive epigenetic diversity that exceeds the corresponding genetic variance. DNA sequence divergence, epigenetic drift and environmental variables contribute to the epigenetic diversities of each species. Environment-induced epigenetic variation may be inherited as a result of both mitosis and meiosis, and their potential roles in evolution for bat populations are also discussed in this review. PMID:25568456

  14. Nutritional Epigenetics

    L. Preston Mercer

    2013-12-01

    Full Text Available Questions concerning the fundamental effects of nutrition on gene function are now being elucidated as the human genome project has been completed. Nutritional genomics seeks to expand the use of foods to achieve human genetic potential, while reducing the risk of diseases. As issues such as nutrigenomics (dietary influence on gene function and nutrigenetics (genomic reaction to diet are unraveled, thepotential for personalized nutrition becomes attainable. It has been stated that “genomics is to the 21st century what infectious disease was to the 20th century”. The nucleotide sequence of DNA was once seen as the only mechanism by which genetic information could be transmitted between generations. Phenotypic variation resulted from recombination and, occasionally, genetic mutation. This widely accepted concept is now undergoing modification as evidence builds to support the idea that reversible, heritable changes in gene function - termed “epigenetics”- can occur without a change in the sequence of nuclear DNA (i.e., non-Mendelian inheritance. The word epigenetics is of Greek origin and literallymeans over and above (epi the genome. The terminology“same genome, different epigenome” has been demonstrated in several experiments. As research and understanding advances, dietary advice based on the human genome will become more prevalent and new pharmacological interventions may be developed.

  15. Dynamic epigenetic responses to muscle contraction

    Rasmussen, Morten; Zierath, Juleen R; Barrès, Romain

    2014-01-01

    Skeletal muscle is a malleable organ that responds to a single acute exercise bout by inducing the expression of genes involved in structural, metabolic and functional adaptations. Several epigenetic mechanisms including histone H4 deacetylation and loss of promoter methylation have been implicated...... in modifying exercise-responsive gene expression. These transient changes suggest that epigenetic mechanisms are not restricted to early stages of human development but are broad dynamic controllers of genomic plasticity in response to environmental factors....

  16. Epigenetics and Nutritional Environmental Signals

    Mazzio, Elizabeth A.; Soliman, Karam F. A.

    2014-01-01

    All terrestrial life is influenced by multi-directional flows of information about its environment, enabling malleable phenotypic change through signals, chemical processes, or various forms of energy that facilitate acclimatization. Billions of biological co-inhabitants of the earth, including all plants and animals, collectively make up a genetic/epigenetic ecosystem by which adaptation/survival (inputs and outputs) are highly interdependent on one another. As an ecosystem, the solar system...

  17. Epigenetics in the Placenta

    Maccani, Matthew A; Marsit, Carmen J.

    2009-01-01

    Epigenetics is focused on understanding the control of gene expression beyond what is encoded in the sequence of DNA. Central to growing interest in the field is the hope that more can be learned about the epigenetic regulatory mechanisms underlying processes of human development and disease. Researchers have begun to examine epigenetic alterations – such as changes in promoter DNA methylation, genomic imprinting, and expression of miRNA – to learn more about epigenetic regulation in the plac...

  18. Chromatin resetting mechanisms preventing transgenerational inheritance of epigenetic states

    Iwasaki, Mayumi

    2015-01-01

    Epigenetic regulation can be altered by environmental cues including abiotic and biotic stresses. In most cases, environmentally-induced epigenetic changes are transient, but in some cases they are maintained for extensive periods of time and may even be transmitted to the next generation. However, the underlying mechanisms of transgenerational transmission of environmentally-induced epigenetic states remain largely unknown. Such traits can be adaptive, but also can have negative consequences...

  19. Prospects for Epigenetic Epidemiology

    Debra L Foley; Craig, Jeffrey M; Morley, Ruth; Olsson, Craig J.; Dwyer, Terence; Smith, Katherine; Saffery, Richard

    2009-01-01

    Epigenetic modification can mediate environmental influences on gene expression and can modulate the disease risk associated with genetic variation. Epigenetic analysis therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. The spatial and temporal variance in epigenetic profile is of particular relevance for developmental epidemiology and the study of aging, including the variable age at onset for man...

  20. Epigenetics and cancer

    Lund, Anders H; van Lohuizen, Maarten

    2004-01-01

    Epigenetic mechanisms act to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modification or rearrangement of nucleosomes. Epigenetic gene regulation collaborates with genetic alterations in cancer development....... This is evident from every aspect of tumor biology including cell growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and evasion of host immunosurveillance. In contrast to genetic cancer causes, the possibility of reversing epigenetic codes may provide new targets for therapeutic...

  1. Epigenetics in liver disease

    Mann, Derek A.

    2014-01-01

    Epigenetics is a term that encompasses a variety of regulatory processes that are able to crosstalk in order to influence gene expression and cell phenotype in response to environmental cues. A deep understanding of epigenetics offers the potential for fresh insights into the basis for complex chronic diseases and improved diagnostic and prognostic tools. Moreover, as epigenetic modifications are highly plastic and responsive to the environment, there is much excitement around the theme of ep...

  2. Comparative epigenomics: an emerging field with breakthrough potential to understand evolution of epigenetic regulation

    Deakin, Janine E; Renae Domaschenz; Pek Siew Lim; Tariq Ezaz; Sudha Rao

    2014-01-01

    Epigenetic mechanisms regulate gene expression, thereby mediating the interaction between environment, genotype and phenotype. Changes to epigenetic regulation of genes may be heritable, permitting rapid adaptation of a species to environmental cues. However, most of the current understanding of epigenetic gene regulation has been gained from studies of mice and humans, with only a limited understanding of the conservation of epigenetic mechanisms across divergent taxa. The relative ease at w...

  3. Reorganization: premises, processes, and pitfalls.

    Jacobson, S.

    1994-01-01

    As the technological environment changes and libraries assume new and more active roles in their institutions, the traditional library hierarchy ceases to be an effective organizational structure. Guided by theories that emphasize teamwork, quality, and employee empowerment and participation, libraries are developing flatter, more networked organizations. The Health Sciences Library at Columbia University in New York, New York, recently underwent a reorganization in an effort to become a more...

  4. Epigenetics and aging

    Pal, Sangita; Tyler, Jessica K.

    2016-01-01

    Over the past decade, a growing number of studies have revealed that progressive changes to epigenetic information accompany aging in both dividing and nondividing cells. Functional studies in model organisms and humans indicate that epigenetic changes have a huge influence on the aging process. These epigenetic changes occur at various levels, including reduced bulk levels of the core histones, altered patterns of histone posttranslational modifications and DNA methylation, replacement of canonical histones with histone variants, and altered noncoding RNA expression, during both organismal aging and replicative senescence. The end result of epigenetic changes during aging is altered local accessibility to the genetic material, leading to aberrant gene expression, reactivation of transposable elements, and genomic instability. Strikingly, certain types of epigenetic information can function in a transgenerational manner to influence the life span of the offspring. Several important conclusions emerge from these studies: rather than being genetically predetermined, our life span is largely epigenetically determined; diet and other environmental influences can influence our life span by changing the epigenetic information; and inhibitors of epigenetic enzymes can influence life span of model organisms. These new findings provide better understanding of the mechanisms involved in aging. Given the reversible nature of epigenetic information, these studies highlight exciting avenues for therapeutic intervention in aging and age-associated diseases, including cancer. PMID:27482540

  5. Maintenance of Epigenetic Information.

    Almouzni, Geneviève; Cedar, Howard

    2016-01-01

    SUMMARYThe genome is subject to a diverse array of epigenetic modifications from DNA methylation to histone posttranslational changes. Many of these marks are somatically stable through cell division. This article focuses on our knowledge of the mechanisms governing the inheritance of epigenetic marks, particularly, repressive ones, when the DNA and chromatin template are duplicated in S phase. This involves the action of histone chaperones, nucleosome-remodeling enzymes, histone and DNA methylation binding proteins, and chromatin-modifying enzymes. Last, the timing of DNA replication is discussed, including the question of whether this constitutes an epigenetic mark that facilitates the propagation of epigenetic marks. PMID:27141050

  6. [Epigenetics and cancer].

    Deltour, Sophie; Chopin, Valérie; Leprince, Dominique

    2005-04-01

    Epigenetics is defined as "the study of mitotically and/or meiotically heritable changes in gene expression that cannot be explained by changes in the DNA sequence". Setting up the epigenetic program is crucial for correct development and its stable inheritance throughout its lifespan is essential for the maintenance of the tissue- and cell-specific functions of the organism. For many years, the genetic causes of cancer have hold centre stage. However, the recent wealth of information about the molecular mechanisms which, by modulating the chromatin structure, can regulate gene expression has high-lighted the predominant role of epigenetic modifications in the initiation and progression of numerous pathologies, including cancer. The nucleosome is the major target of these epigenetic regulation mechanisms. They include a series of tightly interconnected steps which starting with the setting ("writing") of the epigenetic mark till its "reading" and interpretation will result in long-term gene regulation. The major epigenetic changes associated with tumorigenesis are aberrant DNA methylation of CpG islands located in the promoter region of tumor suppressor gene, global genomic hypomethylation and covalent modifications of histone N-terminal tails which are protruding out from the nucleosome core. In sharp contrast with genetic modifications, epigenetic modifications are highly dynamic and reversible. The characterization of specific inhibitors directed against some key epigenetic players has opened a new and promising therapeutic avenue, the epigenetic therapy, since some inhibitors are already used in clinical trials. PMID:15811306

  7. Epigenetics, Nervous System Tumors, and Cancer Stem Cells

    Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors

  8. Epigenetics, Nervous System Tumors, and Cancer Stem Cells

    Qureshi, Irfan A. [Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Mehler, Mark F., E-mail: mark.mehler@einstein.yu.edu [Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States)

    2011-09-13

    Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors.

  9. Epigenetic mechanisms and gastrointestinal development

    This review considers the hypothesis that nutrition during infancy affects developmental epigenetics in the gut, causing metabolic imprinting of gastrointestinal (GI) structure and function. Fundamentals of epigenetic gene regulation are reviewed, with an emphasis on the epigenetic mechanism of DNA ...

  10. [Early attachement relationships and epigenetic customization].

    Rocchi, Giordana; Serio, Valentina; Carluccio, Giuseppe Mattia; Marini, Isabella; Meuti, Valentina; Zaccagni, Michela; Giacchetti, Nicoletta; Aceti, Franca

    2015-01-01

    Recently, new findings in epigenetic science switched the focus from the observation of physiological intragenomic dynamics to the idea of an environmental co-construction of phenotypic expression. In psichodynamic field, objectual relations and attachement theoreticians emphasized the interpersonal dimension of individual development, focusing the attention on the relational matrix of self organization. The construction of stable affective-behavioral traits throughout different parenting styles has actually found a coincidence in ethological studies, which have explored the epigenetic processes underlying the relationship between caregiving and HPA stress responsiveness. An adequate parenting style seems to support affective regulation throughout psychobiological hidden moderators, which would tend to rebalance the physiological systems homeostasis; an unconfident attachment style would promote, on the other hand, the allostatic load rise. Sites of longlife epigenetic susceptibility have also been identified in humans; although associated with risk of maladaptive developing in adverse environmental conditions, they seem to confer protection under favorable conditions. This persisting possibility of reorganization of stable traits throughout lifetime, which seems to be activated by a relevant environmental input, grant to significant relationships, and to therapeutical one as well, an implicit reconditioning potential which could result into the configuration of new stable affective-behavioral styles. PMID:26418595

  11. Epigenetics Research on the International Space Station

    Love, John; Cooley, Vic

    2016-01-01

    The International Space Station (ISS) is a state-of-the orbiting laboratory focused on advancing science and technology research. Experiments being conducted on the ISS include investigations in the emerging field of Epigenetics. Epigenetics refers to stably heritable changes in gene expression or cellular phenotype (the transcriptional potential of a cell) resulting from changes in a chromosome without alterations to the underlying DNA nucleotide sequence (the genetic code), which are caused by external or environmental factors, such as spaceflight microgravity. Molecular mechanisms associated with epigenetic alterations regulating gene expression patterns include covalent chemical modifications of DNA (e.g., methylation) or histone proteins (e.g., acetylation, phorphorylation, or ubiquitination). For example, Epigenetics ("Epigenetics in Spaceflown C. elegans") is a recent JAXA investigation examining whether adaptations to microgravity transmit from one cell generation to another without changing the basic DNA of the organism. Mouse Epigenetics ("Transcriptome Analysis and Germ-Cell Development Analysis of Mice in Space") investigates molecular alterations in organ-specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight, as well as assessing changes in offspring DNA. NASA's first foray into human Omics research, the Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), includes investigations evaluating differential epigenetic effects via comprehensive whole genome analysis, the landscape of DNA and RNA methylation, and biomolecular changes by means of longitudinal integrated multi-omics research. And the inaugural Genes in Space student challenge experiment (Genes in Space-1) is aimed at understanding how epigenetics plays a role in immune system dysregulation by assaying DNA methylation in immune cells

  12. Reorganization of Human Cerebral Cortex : the Range of Changes following Use and Injury

    Elbert, Thomas; Rockstroh, Brigitte

    2004-01-01

    Animal and human research over the past decades have increasingly detailed the brain s capacity for reorganization of neural network architecture to adapt to environmental needs. In this article, the authors outline the range of reorganization of human representational cortex, encompassing reconstruction in concurrence with enhanced behaviorally relevant afferent activity (examples include skilled musicians and blind Braille readers); injury-related response dynamics as, for instance, driven ...

  13. Epigenetic memory in mammals

    Zoe eMigicovsky

    2011-06-01

    Full Text Available Epigenetic information can be passed on from one generation to another via DNA methylation, histone modifications and changes in small RNAs, a process called epigenetic memory. During a mammal’s lifecycle epigenetic reprogramming, or the resetting of most epigenetic marks, occurs twice. The first instance of reprogramming occurs in primordial germ cells and the second occurs following fertilization. These processes may be both passive and active. In order for epigenetic inheritance to occur the epigenetic modifications must be able to escape reprogramming. There are several examples supporting this non-Mendelian mechanism of inheritance including the prepacking of early developmental genes in histones instead of protamines in sperm, genomic imprinting via methylation marks, the retention of CenH3 in mammalian sperm and the inheritance of piwi-associated interfering RNAs. The ability of mammals to pass on epigenetic information to their progeny provides clear evidence that inheritance is not restricted to DNA sequence and epigenetics plays a key role in producing viable offspring.

  14. Epigenetic learning in non-neural organisms

    Simona Ginsburg; Eva Jablonka

    2009-10-01

    Learning involves a usually adaptive response to an input (an external stimulus or the organism’s own behaviour) in which the input-response relation is memorized; some physical traces of the relation persist and can later be the basis of a more effective response. Using toy models we show that this characterization applies not only to the paradigmatic case of neural learning, but also to cellular responses that are based on epigenetic mechanisms of cell memory. The models suggest that the research agenda of epigenetics needs to be expanded.

  15. Scrutinizing the epigenetics revolution.

    Meloni, Maurizio; Testa, Giuseppe

    2014-11-01

    Epigenetics is one of the most rapidly expanding fields in the life sciences. Its rise is frequently framed as a revolutionary turn that heralds a new epoch both for gene-based epistemology and for the wider discourse on life that pervades knowledge-intensive societies of the molecular age. The fundamentals of this revolution remain however to be scrutinized, and indeed the very contours of what counts as 'epigenetic' are often blurred. This is reflected also in the mounting discourse on the societal implications of epigenetics, in which vast expectations coexist with significant uncertainty about what aspects of this science are most relevant for politics or policy alike. This is therefore a suitable time to reflect on the directions that social theory could most productively take in the scrutiny of this revolution. Here we take this opportunity in both its scholarly and normative dimension, that is, proposing a roadmap for social theorizing on epigenetics that does not shy away from, and indeed hopefully guides, the framing of its most socially relevant outputs. To this end, we start with an epistemological reappraisal of epigenetic discourse that valorizes the blurring of meanings as a critical asset for the field and privileged analytical entry point. We then propose three paths of investigation. The first looks at the structuring elements of controversies and visions around epigenetics. The second probes the mutual constitution between the epigenetic reordering of living phenomena and the normative settlements that orient individual and collective responsibilities. The third highlights the material import of epigenetics and the molecularization of culture that it mediates. We suggest that these complementary strands provide both an epistemically and socially self-reflective framework to advance the study of epigenetics as a molecular juncture between nature and nurture and thus as the new critical frontier in the social studies of the life sciences. PMID

  16. Models of epigenetics

    Alsing, Anne

    genomic material can show quiet diverse phenotypes characterized by organ speci c gene expression patterns. The mechanisms responsible for this phenotypic plasticity are characterized as epigenetic, as they in ict their e ect \\epi-" (Greek for \\above" or \\on top") of the genetic code. For a gene...... regulatory mechanism to be classi ed as epigenetic, it is required that it is self-sustainable in the sense that the governed gene expression or repression should prevail for the lifetime of the cell and must be inherited by possible daughter cells. An example of epigenetic di erentiation is the bistable...

  17. Transposable element origins of epigenetic gene regulation.

    Lisch, Damon; Bennetzen, Jeffrey L

    2011-04-01

    Transposable elements (TEs) are massively abundant and unstable in all plant genomes, but are mostly silent because of epigenetic suppression. Because all known epigenetic pathways act on all TEs, it is likely that the specialized epigenetic regulation of regular host genes (RHGs) was co-opted from this ubiquitous need for the silencing of TEs and viruses. With their internally repetitive and rearranging structures, and the acquisition of fragments of RHGs, the expression of TEs commonly makes antisense RNAs for both TE genes and RHGs. These antisense RNAs, particularly from heterochromatic reservoirs of 'zombie' TEs that are rearranged to form variously internally repetitive structures, may be advantageous because their induction will help rapidly suppress active TEs of the same family. RHG fragments within rapidly rearranging TEs may also provide the raw material for the ongoing generation of miRNA genes. TE gene expression is regulated by both environmental and developmental signals, and insertions can place nearby RHGs under the regulation (both standard and epigenetic) of the TE. The ubiquity of TEs, their frequent preferential association with RHGs, and their ability to be programmed by epigenetic signals all indicate that RGHs have nearly unlimited access to novel regulatory cassettes to assist plant adaptation. PMID:21444239

  18. [Epigenetics in Parkinson's Disease].

    Wüllner, U

    2016-07-01

    The genetic information encoded in the DNA sequence provides a blueprint of the entire organism. The epigenetic modifications, in particular DNA methylation and histone modifications, determine how and when this information is made available and define the specific gene transcription pattern of a given cell. Epigenetic modifications determine the functional differences of genetically identical cells in multicellular organisms and are important factors in various processes from embryonic development to learning and memory consolidation. DNA methylation patterns are altered by environmental conditions and some alterations are preserved through mitosis and meiosis. Thus, DNA methylation can mediate environmental impact on health and disease, contributes to the severity of diseases and probably contributes to the effects and side effects of drugs. In addition to the classical monogenic epigenetic diseases such as Prader-Willi syndrome and Rett syndrome, recent data point to an epigenetic component also in sporadic neuro-psychiatric disorders. PMID:27299943

  19. Epigenetics: Biology's Quantum Mechanics.

    Jorgensen, Richard A

    2011-01-01

    The perspective presented here is that modern genetics is at a similar stage of development as were early formulations of quantum mechanics theory in the 1920s and that in 2010 we are at the dawn of a new revolution in genetics that promises to enrich and deepen our understanding of the gene and the genome. The interrelationships and interdependence of two views of the gene - the molecular biological view and the epigenetic view - are explored, and it is argued that the classical molecular biological view is incomplete without incorporation of the epigenetic perspective and that in a sense the molecular biological view has been evolving to include the epigenetic view. Intriguingly, this evolution of the molecular view toward the broader and more inclusive epigenetic view of the gene has an intriguing, if not precise, parallel in the evolution of concepts of atomic physics from Newtonian mechanics to quantum mechanics that are interesting to consider. PMID:22639577

  20. Epigenetics: Biology's Quantum Mechanics

    Richard A Jorgensen

    2011-04-01

    Full Text Available The perspective presented here is that modern genetics is at a similar stage of development as were early formulations of quantum mechanics theory in the 1920's and that in 2010 we are at the dawn of a new revolution in genetics that promises to enrich and deepen our understanding of the gene and the genome. The interrelationships and interdependence of two views of the gene - the molecular biological view and the epigenetic view - are explored, and it is argued that the classical molecular biological view is incomplete without incorporation of the epigenetic perspective and that in a sense the molecular biological view has been evolving to include the epigenetic view. Intriguingly, this evolution of the molecular view toward the broader and more inclusive epigenetic view of the gene has an intriguing, if not precise, parallel in the evolution of concepts of atomic physics from Newtonian mechanics to quantum mechanics that are interesting to consider.

  1. [The meaning of epigenetics].

    Hu, Kai

    2002-11-01

    Epigenetics, the term was introduced by Conrad H.Waddington, in 1942,he said that to compare genetics with epigenetics, the study of the processes by which genotype gives rise to phenotype. In 1987, Robin Holliday redefined epigenetic as "Nuclear inheritance which is not based on differences in DNA sequence". The author of this paper introduced that in Science,10 August 2001,there was a special collection of review articles focused on the topic of epigenetics. The new "histone code" hypothesis states that the highly modifiable amino termini could carry their own combinatorial codes to help control phenotype,and that part of this code is heritable. And in light of this hypothesis,researchers are approaching further possibilities in human biology and types of cancer and other diseases. PMID:15979980

  2. Epigenetics and addiction.

    Cadet, J L; McCoy, M T; Jayanthi, S

    2016-05-01

    Addictions are public health menaces. However, despite advances in addiction research, the cellular or molecular mechanisms that cause transition from recreational use to addiction remain to be elucidated. We have recently suggested that addiction may be secondary to long-term epigenetic modifications that determine the clinical course of substance use disorders. A better understanding of epigenetic mechanisms in animal models that mimic human conditions should help to usher in a new area of drug development against addiction. PMID:26841306

  3. Epigenetic Mechanisms of Depression

    Nestler, Eric J.

    2014-01-01

    Growing evidence supports the hypothesis that epigenetics is a key mechanism through which environmental exposures interact with an individual’s genetic constitution to determine risk for depression throughout life.1 Epigenetics, in its broadest meaning, refers to stable changes in gene expression that are mediated via altered chromatin structure without modification of DNA sequence. According to this hypothesis, severe stress triggers changes—in vulnerable individuals—in chromatin structure ...

  4. Fatty acids and epigenetics

    Burdge, Graham C; Lillycrop, Karen A.

    2014-01-01

    Purpose of review The purpose of this review is to assess the findings of recent studies on the effects of fatty acids on epigenetic process and the role of epigenetics in regulating fatty acid metabolism. Recent findings The DNA methylation status of the Fads2 promoter was increased in the liver of the offspring of mice fed an ?-linolenic acid-enriched diet during pregnancy. In rats, increasing total maternal fat intake during pregnancy and lactation induced persistent hypermethyl...

  5. Epigenetics of Lung Cancer

    Langevin, Scott M; Kratzke, Robert A.; Kelsey, Karl T.

    2014-01-01

    Lung cancer is the leading cause of cancer-related mortality in the United States. Epigenetic alterations, including DNA methylation, histone modifications, and non-coding RNA expression, have widely been reported in the literature to play a major role in the genesis of lung cancer. The goal of this review is to summarize the common epigenetic changes associated with lung cancer to give some clarity to its etiology, and provide an overview of the potential translational applications of these ...

  6. Photovoltaic industry, towards a reorganization

    During the first semester 2011 the sales of photovoltaic equipment have dropped unexpectedly, certainly due to the harsh winter in Europe and the reduction of the policy of financial incentives in some countries. This drop in demand has triggered such a drop in prices that some manufacturers face financial difficulties, for instance the American Evergreen Solar was declared bankrupt in mid august 2011. Today the production of solar panels exceeds the demand. The third term of 2011 shows an improvement but the sector will not escape a reorganization: there are too many manufacturers, some will disappear, other will merge, the biggest will stay. Some economists see the future market divided into 2 sectors: one sector dedicated to the mass production of classical solar panels at very low cost, this sector will be occupied mainly by Chinese companies and another sector demanding a more specialized know-how will be driven by American, Japanese and European companies. (A.C.)

  7. Adapt

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  8. Genome reorganization in F1 hybrids uncovers the role of retrotransposons in reproductive isolation.

    Senerchia, Natacha; Felber, François; Parisod, Christian

    2015-04-01

    Interspecific hybridization leads to new interactions among divergent genomes, revealing the nature of genetic incompatibilities having accumulated during and after the origin of species. Conflicts associated with misregulation of transposable elements (TEs) in hybrids expectedly result in their activation and genome-wide changes that may be key to species boundaries. Repetitive genomes of wild wheats have diverged under differential dynamics of specific long terminal repeat retrotransposons (LTR-RTs), offering unparalleled opportunities to address the underpinnings of plant genome reorganization by selfish sequences. Using reciprocal F1 hybrids between three Aegilops species, restructuring and epigenetic repatterning was assessed at random and LTR-RT sequences with amplified fragment length polymorphism and sequence-specific amplified polymorphisms as well as their methylation-sensitive counterparts, respectively. Asymmetrical reorganization of LTR-RT families predicted to cause conflicting interactions matched differential survival of F1 hybrids. Consistent with the genome shock model, increasing divergence of merged LTR-RTs yielded higher levels of changes in corresponding genome fractions and lead to repeated reorganization of LTR-RT sequences in F1 hybrids. Such non-random reorganization of hybrid genomes is coherent with the necessary repression of incompatible TE loci in support of hybrid viability and indicates that TE-driven genomic conflicts may represent an overlooked factor supporting reproductive isolation. PMID:25716787

  9. Functional Reorganizations of Brain Network in Prelingually Deaf Adolescents.

    Li, Wenjing; Li, Jianhong; Wang, Jieqiong; Zhou, Peng; Wang, Zhenchang; Xian, Junfang; He, Huiguang

    2016-01-01

    Previous neuroimaging studies suggested structural or functional brain reorganizations occurred in prelingually deaf subjects. However, little is known about the reorganizations of brain network architectures in prelingually deaf adolescents. The present study aims to investigate alterations of whole-brain functional network using resting-state fMRI and graph theory analysis. We recruited 16 prelingually deaf adolescents (10~18 years) and 16 normal controls matched in age and gender. Brain networks were constructed from mean time courses of 90 regions. Widely distributed network was observed in deaf subjects, with increased connectivity between the limbic system and regions involved in visual and language processing, suggesting reinforcement of the processing for the visual and verbal information in deaf adolescents. Decreased connectivity was detected between the visual regions and language regions possibly due to inferior reading or speaking skills in deaf subjects. Using graph theory analysis, we demonstrated small-worldness property did not change in prelingually deaf adolescents relative to normal controls. However, compared with healthy adolescents, eight regions involved in visual, language, and auditory processing were identified as hubs only present in prelingually deaf adolescents. These findings revealed reorganization of brain functional networks occurred in prelingually deaf adolescents to adapt to deficient auditory input. PMID:26819781

  10. Functional Reorganizations of Brain Network in Prelingually Deaf Adolescents

    Li, Wenjing; Li, Jianhong; Wang, Jieqiong; Zhou, Peng; Wang, Zhenchang; Xian, Junfang; He, Huiguang

    2016-01-01

    Previous neuroimaging studies suggested structural or functional brain reorganizations occurred in prelingually deaf subjects. However, little is known about the reorganizations of brain network architectures in prelingually deaf adolescents. The present study aims to investigate alterations of whole-brain functional network using resting-state fMRI and graph theory analysis. We recruited 16 prelingually deaf adolescents (10~18 years) and 16 normal controls matched in age and gender. Brain networks were constructed from mean time courses of 90 regions. Widely distributed network was observed in deaf subjects, with increased connectivity between the limbic system and regions involved in visual and language processing, suggesting reinforcement of the processing for the visual and verbal information in deaf adolescents. Decreased connectivity was detected between the visual regions and language regions possibly due to inferior reading or speaking skills in deaf subjects. Using graph theory analysis, we demonstrated small-worldness property did not change in prelingually deaf adolescents relative to normal controls. However, compared with healthy adolescents, eight regions involved in visual, language, and auditory processing were identified as hubs only present in prelingually deaf adolescents. These findings revealed reorganization of brain functional networks occurred in prelingually deaf adolescents to adapt to deficient auditory input. PMID:26819781

  11. The physics of epigenetics

    Cortini, Ruggero; Barbi, Maria; Caré, Bertrand R.; Lavelle, Christophe; Lesne, Annick; Mozziconacci, Julien; Victor, Jean-Marc

    2016-04-01

    In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the daughter cells. This intriguing phenomenon is achieved by a variety of processes that have been collectively termed epigenetics: the stable and inheritable changes in gene expression patterns. This article reviews the extremely rich and exquisitely multiscale physical mechanisms that govern the biological processes behind the initiation, spreading, and inheritance of epigenetic states. These include not only the changes in the molecular properties associated with the chemical modifications of DNA and histone proteins, such as methylation and acetylation, but also less conventional changes, typically in the physics that governs the three-dimensional organization of the genome in cell nuclei. Strikingly, to achieve stability and heritability of epigenetic states, cells take advantage of many different physical principles, such as the universal behavior of polymers and copolymers, the general features of dynamical systems, and the electrostatic and mechanical properties related to chemical modifications of DNA and histones. By putting the complex biological literature in this new light, the emerging picture is that a limited set of general physical rules play a key role in initiating, shaping, and transmitting this crucial "epigenetic landscape." This new perspective not only allows one to rationalize the normal cellular functions, but also helps to understand the emergence of pathological states, in which the epigenetic landscape becomes dysfunctional.

  12. Epigenetics in neonatal diseases

    XU Xue-feng; DU Li-zhong

    2010-01-01

    Objective To review the role of epigenetic regulation in neonatal diseases and better understand Barker's "fetal origins of adult disease hypothesis".Data sources The data cited in this review were mainly obtained from the articles published in Medline/PubMed between January 1953 and December 2009.Study selection Articles associated with epigenetics and neonatal diseases were selected.Results There is a wealth of epidemiological evidence that lower birth weight is strongly correlated with an increased risk of adult diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. This phenomenon of fetal origins of adult disease is strongly associated with fetal insults to epigenetic modifications of genes. A potential role of epigenetic modifications in congenital disorders, transient neonatal diabetes mellitus (TNDM), intrauterine growth retardation (IUGR), and persistent pulmonary hypertension of the newborn (PPHN) have been studied.Conclusions Acknowledgment of the role of these epigenetic modifications in neonatal diseases would be conducive to better understanding the pathogenesis of these diseases, and provide new insight for improved treatment and prevention of later adult diseases.

  13. Farthest First Clustering in Links Reorganization

    Deepshree A. Vadeyar

    2014-07-01

    Full Text Available Website can be easily design but to efficient user navigation is not a easy task since user behavior is keep changing and developer view is quite different from what user wants, so to improve navigation one way is reorganization of website structure. For reorganization here proposed strategy is farthest first traversal clustering algorithm perform clustering on two numeric parameters and for finding frequent traversal path of user Apriori algorithm is used. Our aim is to perform reorganization with fewer changes in website structure.

  14. Epigenetics: heterochromatin meets RNAi

    Ingela Djupedal; Karl Ekwall

    2009-01-01

    The term epigenetics refers to heritable changes not encoded by DNA. The organization of DNA into chromatin fibers affects gene expression in a heritable manner and is therefore one mechanism of epigenetic inheritance. Large parts of eukaryotic genomes consist of constitutively highly condensed heterochromatin, important for maintaining genome integrity but also for silencing of genes within. Small RNA, together with factors typically associated with RNA interference (RNAi) targets homologous DNA sequences and recruits factors that modify the chromatin, com-monly resulting in formation of heterochromatin and silencing of target genes. The scope of this review is to provide an overview of the roles of small RNA and the RNAi components, Dicer, Argonaute and RNA dependent polymeras-es in epigenetic inheritance via heterochromatin formation, exemplified with pathways from unicellular eukaryotes, plants and animals.

  15. Epigenetics in Prostate Cancer

    Costantine Albany

    2011-01-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a “normal” epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

  16. The physics of epigenetics

    Cortini, Ruggero; Caré, Bertrand R; Lavelle, Christophe; Lesne, Annick; Mozziconacci, Julien; Victor, Jean-Marc

    2015-01-01

    In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the daughter cells. This intriguing phenomenon is achieved by a variety of processes that have been collectively termed epigenetics: the stable and inheritable changes in gene expression patterns. This article reviews the extremely rich and exquisitely multi-scale physical mechanisms that govern the biological processes behind the initiation, spreading and inheritance of epigenetic states. These include not only the change in the molecular properties associated with the chemical modifications of DNA and histone proteins - such as methylation and acetylation - but also less conventional ones, such as the physics that governs the three-dimensional organization of the genome in cell nuclei. Strikingly, to achieve stability and heritability of epigenetic states, cells take advantage of m...

  17. Epigenetic Therapy for Breast Cancer

    Xiao-Yan Zhong; Feng-Feng Cai; Corina Kohler; Wei-Jie Chen; Bei Zhang; Ming-Hong Wang

    2011-01-01

    Both genetic and epigenetic alterations can control the progression of cancer. Genetic alterations are impossible to reverse, while epigenetic alterations are reversible. This advantage suggests that epigenetic modifications should be preferred in therapy applications. DNA methyltransferases and histone deacetylases have become the primary targets for studies in epigenetic therapy. Some DNA methylation inhibitors and histone deacetylation inhibitors are approved by the US Food and Drug Admini...

  18. Epigenetic Risk Factors in PTSD and Depression

    Florian Joachim Raabe

    2013-08-01

    Full Text Available Epidemiological and clinical studies have shown that children exposed to adverse experiences are at increased risk for the development of depression, anxiety disorders and PTSD. A history of child abuse and maltreatment increases the likelihood of being subsequently exposed to traumatic events or of developing PTSD as an adult. The brain is highly plastic during early life and encodes acquired information into lasting memories that normally subserve adaptation. Translational studies in rodents showed that enduring sensitization of neuronal and neuroendocrine circuits in response to early life adversity are likely risk factors of life time vulnerability to stress. Hereby, the hypothalamic-pituitary-adrenal (HPA axis integrates cognitive, behavioural and emotional responses to early-life stress and can be epigenetically programmed during sensitive windows of development. Epigenetic mechanisms, comprising reciprocal regulation of chromatin structure and DNA methylation, are important to establish and maintain sustained, yet potentially reversible, changes in gene transcription. The relevance of these findings for the development of PTSD requires further studies in humans where experience-dependent epigenetic programming can additionally depend on genetic variation in the underlying substrates which may protect from or advance disease development. Overall, identification of early-life stress associated epigenetic risk markers informing on previous stress history can help to advance early diagnosis, personalized prevention and timely therapeutic interventions, thus reducing long-term social and health costs.

  19. Epigenetic Therapy in Lung Cancer

    Liu, Stephen V.; Fabbri, Muller; Gitlitz, Barbara J.; Laird-Offringa, Ite A.

    2013-01-01

    Epigenetic deregulation of gene function has been strongly implicated in carcinogenesis and is one of the mechanisms contributing to the development of lung cancer. The inherent reversibility of epigenetic alterations makes them viable therapeutic targets. Here, we review the therapeutic implications of epigenetic changes in lung cancer, and recent advances in therapeutic strategies targeting DNA methylation and histone acetylation.

  20. Environmentally induced epigenetic toxicity: potential public health concerns.

    Marczylo, Emma L; Jacobs, Miriam N; Gant, Timothy W

    2016-09-01

    Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection. PMID:27278298

  1. Epigenetics and Future Generations.

    Del Savio, Lorenzo; Loi, Michele; Stupka, Elia

    2015-10-01

    Recent evidence of intergenerational epigenetic programming of disease risk broadens the scope of public health preventive interventions to future generations, i.e. non existing people. Due to the transmission of epigenetic predispositions, lifestyles such as smoking or unhealthy diet might affect the health of populations across several generations. While public policy for the health of future generations can be justified through impersonal considerations, such as maximizing aggregate well-being, in this article we explore whether there are rights-based obligations supervening on intergenerational epigenetic programming despite the non-identity argument, which challenges this rationale in case of policies that affect the number and identity of future people. We propose that rights based obligations grounded in the interests of non-existing people might fall upon existing people when generations overlap. In particular, if environmental exposure in F0 (i.e. existing people) will affect the health of F2 (i.e. non-existing people) through epigenetic programming, then F1 (i.e. existing and overlapping with both F0 and F2) might face increased costs to address F2's condition in the future: this might generate obligations upon F0 from various distributive principles, such as the principle of equal opportunity for well being. PMID:25644664

  2. Epigenetic Regulation of Virulence Gene Expression in Parasitic Protozoa.

    Duraisingh, Manoj T; Horn, David

    2016-05-11

    Protozoan parasites colonize numerous metazoan hosts and insect vectors through their life cycles, with the need to respond quickly and reversibly while encountering diverse and often hostile ecological niches. To succeed, parasites must also persist within individuals until transmission between hosts is achieved. Several parasitic protozoa cause a huge burden of disease in humans and livestock, and here we focus on the parasites that cause malaria and African trypanosomiasis. Efforts to understand how these pathogens adapt to survive in varied host environments, cause disease, and transmit between hosts have revealed a wealth of epigenetic phenomena. Epigenetic switching mechanisms appear to be ideally suited for the regulation of clonal antigenic variation underlying successful parasitism. We review the molecular players and complex mechanistic layers that mediate the epigenetic regulation of virulence gene expression. Understanding epigenetic processes will aid the development of antiparasitic therapeutics. PMID:27173931

  3. Epigenetic methylations and their connections with metabolism.

    Chiacchiera, Fulvio; Piunti, Andrea; Pasini, Diego

    2013-05-01

    Metabolic pathways play fundamental roles in several processes that regulate cell physiology and adaptation to environmental changes. Altered metabolic pathways predispose to several different pathologies ranging from diabetes to cancer. Specific transcriptional programs tightly regulate the enzymes involved in cell metabolism and dictate cell fate regulating the differentiation into specialized cell types that contribute to metabolic adaptation in higher organisms. For these reasons, it is of extreme importance to identify signaling pathways and transcription factors that positively and negatively regulate metabolism. Genomic organization allows a plethora of different strategies to regulate transcription. Importantly, large evidence suggests that the quality of diet and the caloric regimen can influence the epigenetic state of our genome and that certain metabolic pathways are also epigenetically controlled reveling a tight crosstalk between metabolism and epigenomes. Here we focus our attention on methylation-based epigenetic reactions, on how different metabolic pathways control these activities, and how these can influence metabolism. Altogether, the recent discoveries linking these apparent distant areas reveal that an exciting field of research is emerging. PMID:23456257

  4. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation

    Flor, Herta; Elbert, Thomas; Knecht, Stefan; Wienbruch, Christian; Pantev, Christo; Birbaumer, Niels; Larbig, Wolfgang; Taub, Edward

    1995-01-01

    Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin1-4. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation5 or somatosensory deafferentation in adult monkeys6, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function2,5,7,8. ...

  5. Principles of epigenetic inheritance

    Vyskot, Boris

    České Budějovice, 2008. s. 11-13. ISBN 80-85645-59-9. [XXIII Genetic Days. 10.09.2008-12.09.2008, České Budějovice] R&D Projects: GA MŠk(CZ) LC06004; GA ČR(CZ) GA521/06/0056 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : epigenetics * inheritance * gene Subject RIV: BO - Biophysics

  6. Cortical reorganization in children with cochlear implants.

    Gilley, Phillip M; Sharma, Anu; Dorman, Michael F

    2008-11-01

    Congenital deafness leads to atypical organization of the auditory nervous system. However, the extent to which auditory pathways reorganize during deafness is not well understood. We recorded cortical auditory evoked potentials in normal hearing children and in congenitally deaf children fitted with cochlear implants. High-density EEG and source modeling revealed principal activity from auditory cortex in normal hearing and early implanted children. However, children implanted after a critical period of seven years revealed activity from parietotemporal cortex in response to auditory stimulation, demonstrating reorganized cortical pathways. Reorganization of central auditory pathways is limited by the age at which implantation occurs, and may help explain the benefits and limitations of implantation in congenitally deaf children. PMID:18775684

  7. Reorganizing the nursing home industry: a proposal.

    Shulman, D; Galanter, R

    1976-01-01

    This paper proposes a reorganization of the nursing home industry with capital facilities owned by government, but with management conducted through a system of competitive contracts with the private sector. The paper explicity demonstrates in real estate finance terms how the present system of private ownership of capital facilities inherently impedes providing a high quality of care. The authors believe that in the proposed industry reorganization, market forces, instead of working against quality care, would be supportive of quality care in a framework that would involve generally less regulation than exists today. PMID:1272543

  8. Shareholders, creditors approve utility reorganization plan

    Shareholders and all classes of secured creditors of Public Service Company of New Hampshire voted overwhelmingly last month to approve Northeast Utilities' Chapter 11 reorganization plan for PSNH, the utility announced. PSNH filed for bankruptcy protection in January 1988. Under the reorganization plan, Connecticut-based NU would acquire the utility for $2.3 billion. While PSNH's preferred and common stockholders voted to accept the proposal, holders of warrants to purchase PSNH common stock rejected the plan. Except for the votes of a group of independent power producers, PSNH's unsecured creditors also voted to accept the plan

  9. Epigenetic microRNA Regulation

    Wiklund, Erik Digman

    2011-01-01

    and confirming transcriptional start sites can be difficult. Epigenetics, gene regulatory and DNA modification mechanisms not involving a change to the primary sequence, have been implied in the regulation of a number of miRNA loci. Both epigenetic and miRNA signatures are broadly altered in cancer......, and are thought to play essential roles in cancer etiology and progression. Here, we aimed to identify epigenetic miRNA deregulation in bladder and oral carcinoma, and to develop a robust approach to epigenetic miRNA prediction and detection. In addition, non-canonical epigenetic functions directed by a nuclear...... miRNA were investigated. In summary, we report that the miR-200 family and miR-205 are coordinately epigenetically regulated in a variety of cell lines, tumors and normal tissues. MiR-200c expression is correlated with bladder cancer disease progression, and miR-375 levels in oral rinse can...

  10. Epigenetics in the hematologic malignancies

    Fong, Chun Yew; Morison, Jessica; Dawson, Mark A.

    2014-01-01

    A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies...

  11. Epigenetic advances in clinical neuroscience

    Abel, Ted; Poplawski, Shane

    2014-01-01

    Epigenetics, broadly defined as the regulation of gene expression without alteration of the genome, has become a field of tremendous interest in neuroscience, neurology, and psychiatry. This research has rapidly changed the way researchers think about brain function. Exciting epigenetic discoveries have been found in addiction, early life stress, neurodegeneration, post-traumatic stress disorder, and depression. As researchers more precisely define the epigenetic landscape that regulates dise...

  12. An operational definition of epigenetics

    Berger, Shelley L.; Kouzarides, Tony; Shiekhattar, Ramin; Shilatifard, Ali

    2009-01-01

    A recent meeting (December 2008) regarding chromatin-based epigenetics was hosted by the Banbury Conference Center and Cold Spring Harbor Laboratory. The intent was to discuss aspects of epigenetic control of genomic function, and to arrive at a consensus definition of “epigenetics” to be considered by the broader community. It was evident that multiple mechanistic steps lead to the stable heritance of the epigenetic phenotype. Below we provide our view and interpretation of the proceedings a...

  13. EPIGENETIC MODIFICATIONS OF SWINE GENOME

    Kristina Budimir; Gordana Kralik; Vladimir Margeta

    2013-01-01

    Epigenetics is represents a new way of genome analysis, respectively gene expression that occurs without DNA sequence change. Changes that occur are epigenetic modifications and they include post-translational histone modification and DNA methylation. Chemical groups that are added on DNA molecule cause changes in DNA and create epigenome. The consequence of that is appearance of imprinted genes in genome. Genetic imprinting is epigenetic modification in which one of inherited alleles inactiv...

  14. Epigenetics: What it is about?

    Saade E.

    2014-01-01

    Full Text Available Epigenetics has captured the attention of scientists in the past decades, yet its scope has been continuously changing. In this paper, we give an overview on how and why its definition has evolved and suggest several clarification on the concepts used in this field. Waddington coined the term in 1942 to describe genes interaction with each other and with their environment and insisted on dissociating these events from development. Then, Holliday and others argued that epigenetic phenomena are characterized by their heritability. However, differentiated cells can maintain their phenotypes for decades without undergoing division, which points out the limitation of the «heritability» criterion for a particular phenomenon to qualify as epigenetic. «Epigenetic stability» encompasses traits preservation in both dividing and non dividing cells. Likewise, the use of the term «epigenetic regulation» has been misleading as it overlaps with «regulation of gene expression», whereas «epigenetic information» clearly distinguishes epigenetic from genetic phenomena. Consequently, how could epigenetic information be transmitted and perpetuated? The term «epigenetic templating» has been proposed to refer to a general mechanism of perpetuation of epigenetic information that is based on the preferential activity of enzymes that deposit a particular epigenetic mark on macromolecular complexes already containing the same mark. Another issue that we address is the role of epigenetic information. Not only it is important in allowing alternative interpretations of genetic information, but it appears to be important in protecting the genome, as can be illustrated by bacterial endonucleases that targets non methylated DNA – i. e. foreign DNA – and not the endogenous methylated DNA.

  15. Reorganizing Complex Network to Improve Large-Scale Multiagent Teamwork

    Yang Xu

    2014-01-01

    Full Text Available Large-scale multiagent teamwork has been popular in various domains. Similar to human society infrastructure, agents only coordinate with some of the others, with a peer-to-peer complex network structure. Their organization has been proven as a key factor to influence their performance. To expedite team performance, we have analyzed that there are three key factors. First, complex network effects may be able to promote team performance. Second, coordination interactions coming from their sources are always trying to be routed to capable agents. Although they could be transferred across the network via different paths, their sources and sinks depend on the intrinsic nature of the team which is irrelevant to the network connections. In addition, the agents involved in the same plan often form a subteam and communicate with each other more frequently. Therefore, if the interactions between agents can be statistically recorded, we are able to set up an integrated network adjustment algorithm by combining the three key factors. Based on our abstracted teamwork simulations and the coordination statistics, we implemented the adaptive reorganization algorithm. The experimental results briefly support our design that the reorganized network is more capable of coordinating heterogeneous agents.

  16. Exploiting tumor epigenetics to improve oncolytic virotherapy

    Nicole E. Forbes

    2013-09-01

    Full Text Available Oncolytic viruses (OVs comprise a versatile and multi-mechanistic therapeutic platform in the growing arsenal of anticancer biologics. These replicating therapeutics find favorable conditions in the tumor niche, characterized among others by increased metabolism, reduced anti-tumor/antiviral immunity, and disorganized vasculature. Through a self-amplification that is dependent on multiple cancer-specific defects, these agents exhibit remarkable tumor selectivity. With several OVs completing or entering Phase III clinical evaluation, their therapeutic potential as well as the challenges ahead are increasingly clear. One key hurdle is tumor heterogeneity, which results in variations in the ability of tumors to support productive infection by OVs and to induce adaptive anti-tumor immunity. To this end, mounting evidence suggests tumor epigenetics may play a key role. This review will focus on the epigenetic landscape of tumors and how it relates to OV infection. Therapeutic strategies aiming to exploit the epigenetic identity of tumors in order to improve OV therapy are also discussed.

  17. Reorganizing the Biological Sciences at Berkeley.

    Trow, Martin A.

    1983-01-01

    The University of California at Berkeley's substantial reorganization of the biological sciences due to internal and external needs is chronicled, focusing on the coordinated efforts of the institution and the strong, supportive leadership of the chancellor. The story is presented as an unusual case of institutional leadership within a highly…

  18. The Factors and Transversal Reorganizations Principles of Romanian Textile Industry Enterprises using Activity-Based Costing Method

    Sorinel Capusneanu

    2007-04-01

    Full Text Available This article describes the factors and the principles of transversal reorganization of the enterprises from the Romanian textile industry by adapting the Activity-Based Costing method (ABC to its specific. There are presented and analyzed the real possibilities of reorganization of the enterprises in Romania by elaboration of methodological phases that will be covered until the implementation of their transversal organization. Are we ready to adapt the Activity-Based Costing method to the specific of the Romanian textile industry and not only? Here is the question whose response we will find in this article.

  19. Epigenetics, Behaviour, and Health

    Szyf Moshe

    2008-03-01

    Full Text Available The long-term effects of behaviour and environmental exposures, particularly during childhood, on health outcomes are well documented. Particularly thought provoking is the notion that exposures to different social environments have a long-lasting impact on human physical health. However, the mechanisms mediating the effects of the environment are still unclear. In the last decade, the main focus of attention was the genome, and interindividual genetic polymorphisms were sought after as the principal basis for susceptibility to disease. However, it is becoming clear that recent dramatic increases in the incidence of certain human pathologies, such as asthma and type 2 diabetes, cannot be explained just on the basis of a genetic drift. It is therefore extremely important to unravel the molecular links between the "environmental" exposure, which is believed to be behind this emerging incidence in certain human pathologies, and the disease's molecular mechanisms. Although it is clear that most human pathologies involve long-term changes in gene function, these might be caused by mechanisms other than changes in the deoxyribonucleic acid (DNA sequence. The genome is programmed by the epigenome, which is composed of chromatin and a covalent modification of DNA by methylation. It is postulated here that "epigenetic" mechanisms mediate the effects of behavioural and environmental exposures early in life, as well as lifelong environmental exposures and the susceptibility to disease later in life. In contrast to genetic sequence differences, epigenetic aberrations are potentially reversible, raising the hope for interventions that will be able to reverse deleterious epigenetic programming.

  20. Nucleosome Positioning and Epigenetics

    Schwab, David; Bruinsma, Robijn

    2008-03-01

    The role of chromatin structure in gene regulation has recently taken center stage in the field of epigenetics, phenomena that change the phenotype without changing the DNA sequence. Recent work has also shown that nucleosomes, a complex of DNA wrapped around a histone octamer, experience a sequence dependent energy landscape due to the variation in DNA bend stiffness with sequence composition. In this talk, we consider the role nucleosome positioning might play in the formation of heterochromatin, a compact form of DNA generically responsible for gene silencing. In particular, we discuss how different patterns of nucleosome positions, periodic or random, could either facilitate or suppress heterochromatin stability and formation.

  1. Is Glioblastoma an Epigenetic Malignancy?

    Epigenetic modifications control gene expression by regulating the access of nuclear proteins to their target DNA and have been implicated in both normal cell differentiation and oncogenic transformation. Epigenetic abnormalities can occur both as a cause and as a consequence of cancer. Oncogenic transformation can deeply alter the epigenetic information enclosed in the pattern of DNA methylation or histone modifications. In addition, in some cancers epigenetic dysfunctions can drive oncogenic transformation. Growing evidence emphasizes the interplay between metabolic disturbances, epigenomic changes and cancer, i.e., mutations in the metabolic enzymes SDH, FH, and IDH may contribute to cancer development. Epigenetic-based mechanisms are reversible and the possibility of “resetting” the abnormal cancer epigenome by applying pharmacological or genetic strategies is an attractive, novel approach. Gliomas are incurable with all current therapeutic approaches and new strategies are urgently needed. Increasing evidence suggests the role of epigenetic events in development and/or progression of gliomas. In this review, we summarize current data on the occurrence and significance of mutations in the epigenetic and metabolic enzymes in pathobiology of gliomas. We discuss emerging therapies targeting specific epigenetic modifications or chromatin modifying enzymes either alone or in combination with other treatment regimens

  2. Is Glioblastoma an Epigenetic Malignancy?

    Maleszewska, Marta; Kaminska, Bozena, E-mail: B.Kaminska@nencki.gov.pl [Laboratory of Molecular Neurobiology, Neurobiology Center, The Nencki Institute of Experimental Biology, 3 Pasteur Str., Warsaw 02-093 (Poland)

    2013-09-03

    Epigenetic modifications control gene expression by regulating the access of nuclear proteins to their target DNA and have been implicated in both normal cell differentiation and oncogenic transformation. Epigenetic abnormalities can occur both as a cause and as a consequence of cancer. Oncogenic transformation can deeply alter the epigenetic information enclosed in the pattern of DNA methylation or histone modifications. In addition, in some cancers epigenetic dysfunctions can drive oncogenic transformation. Growing evidence emphasizes the interplay between metabolic disturbances, epigenomic changes and cancer, i.e., mutations in the metabolic enzymes SDH, FH, and IDH may contribute to cancer development. Epigenetic-based mechanisms are reversible and the possibility of “resetting” the abnormal cancer epigenome by applying pharmacological or genetic strategies is an attractive, novel approach. Gliomas are incurable with all current therapeutic approaches and new strategies are urgently needed. Increasing evidence suggests the role of epigenetic events in development and/or progression of gliomas. In this review, we summarize current data on the occurrence and significance of mutations in the epigenetic and metabolic enzymes in pathobiology of gliomas. We discuss emerging therapies targeting specific epigenetic modifications or chromatin modifying enzymes either alone or in combination with other treatment regimens.

  3. Epigenetics & chromatin: Interactions and processes

    S. Henikoff (Steven); F.G. Grosveld (Frank)

    2013-01-01

    textabstractOn 11 to 13 March 2013, BioMed Central will be hosting its inaugural conference, Epigenetics & Chromatin: Interactions and Processes, at Harvard Medical School, Cambridge, MA, USA. Epigenetics & Chromatin has now launched a special article series based on the general themes of the confer

  4. The changing concept of epigenetics.

    Jablonka, Eva; Lamb, Marion J

    2002-12-01

    We discuss the changing use of epigenetics, a term coined by Conrad Waddington in the 1940s, and how the epigenetic approach to development differs from the genetic approach. Originally, epigenetics referred to the study of the way genes and their products bring the phenotype into being. Today, it is primarily concerned with the mechanisms through which cells become committed to a particular form or function and through which that functional or structural state is then transmitted in cell lineages. We argue that modern epigenetics is important not only because it has practical significance for medicine, agriculture, and species conservation, but also because it has implications for the way in which we should view heredity and evolution. In particular, recognizing that there are epigenetic inheritance systems through which non-DNA variations can be transmitted in cell and organismal lineages broadens the concept of heredity and challenges the widely accepted gene-centered neo-Darwinian version of Darwinism. PMID:12547675

  5. Active Polymers Confer Fast Reorganization Kinetics

    Swanson, Douglas

    2011-01-01

    Many cytoskeletal biopolymers are "active," consuming energy in large quantities. In this Letter, we identify a fundamental difference between active polymers and passive, equilibrium polymers: for equal mean lengths, active polymers can reorganize faster than equilibrium polymers. We show that equilibrium polymers are intrinsically limited to linear scaling between mean lifetime and mean length, MFPT ~ , by analogy to 1-d Potts models. By contrast, we present a simple active-polymer model that improves upon this scaling, such that MFPT ~ ^{1/2}. Since to be biologically useful, structural biopolymers must typically be many monomers long, yet respond dynamically to the needs of the cell, the difference in reorganization kinetics may help to justify active polymers' greater energy cost. PACS numbers: 87.10.Ed, 87.16.ad, 87.16.Ln

  6. Low Dose Radiation-Induced Genome and Epigenome Instability Symposium and Epigenetic Mechanisms, DNA Repair, and Chromatin Symposium at the EMS 2008 Annual Meeting - October 2008

    Morgan, William F; Kovalchuk, Olga; Dolinoy, Dana C; Dubrova, Yuri E; Coleman, Matthew A; Schär, Primo; Pogribny, Igor; Hendzel, Michael

    2010-02-19

    The Low Dose Radiation Symposium thoughtfully addressed ionizing radiation non-mutational but transmissable alterations in surviving cells. Deregulation of epigenetic processes has been strongly implicated in carcinogenesis, and there is increasing realization that a significant fraction of non-targeted and adaptive mechanisms in response to ionizing radiation are likely to be epigenetic in nature. Much remains to be learned about how chromatin and epigenetic regulators affect responses to low doses of radiation, and how low dose radiation impacts other epigenetic processes. The Epigenetic Mechanisms Symposium focused on on epigenetic mechanisms and their interplay with DNA repair and chromatin changes. Addressing the fact that the most well understood mediators of epigenetic regulation are histone modifications and DNA methylation. Low levels of radiation can lead to changes in the methylation status of certain gene promoters and the expression of DNA methyltransferases, However, epigenetic regulation can also involve changes in higher order chromosome structure.

  7. Reorganizing and restructuring the human resources function

    Alexandrina Mirela, Stan

    2010-01-01

    To determine what kind of skills (internal or external) of human resources are adequate organization can use human resources audit. Audit is an action guide that provides step by step consistency of human resources activities within the organization with legal regulations and informal practices. This paper aims to highlight the importance of human resources audit which is an essential activity and is basis for the reorganization and restructuring of human resources function.

  8. Complex disease, gender and epigenetics.

    Kaminsky, Zachary; Wang, Sun-Chong; Petronis, Arturas

    2006-01-01

    Gender differences in susceptibility to complex disease such as asthma, diabetes, lupus, autism and major depression, among numerous other disorders, represent one of the hallmarks of non-Mendelian biology. It has been generally accepted that endocrinological differences are involved in the sexual dimorphism of complex disease; however, specific molecular mechanisms of such hormonal effects have not been elucidated yet. This paper will review evidence that sex hormone action may be mediated via gene-specific epigenetic modifications of DNA and histones. The epigenetic modifications can explain sex effects at DNA sequence polymorphisms and haplotypes identified in gender-stratified genetic linkage and association studies. Hormone-induced DNA methylation and histone modification changes at specific gene regulatory regions may increase or reduce the risk of a disease. The epigenetic interpretation of sexual dimorphism fits well into the epigenetic theory of complex disease, which argues for the primary pathogenic role of inherited and/or acquired epigenetic misregulation rather than DNA sequence variation. The new experimental strategies, especially the high throughput microarray-based epigenetic profiling, can be used for testing the epigenetic hypothesis of gender effects in complex diseases. PMID:17438668

  9. Epigenetics in preimplantation mammalian development.

    Canovas, Sebastian; Ross, Pablo Juan

    2016-07-01

    Fertilization is a very dynamic period of comprehensive chromatin remodeling, from which two specialized cells result in a totipotent zygote. The formation of a totipotent cell requires extensive epigenetic remodeling that, although independent of modifications in the DNA sequence, still entails a profound cell-fate change, supported by transcriptional profile modifications. As a result of finely tuned interactions between numerous mechanisms, the goal of fertilization is to form a full healthy new individual. To avoid the persistence of alterations in epigenetic marks, the epigenetic information contained in each gamete is reset during early embryogenesis. Covalent modification of DNA by methylation, as well as posttranslational modifications of histone proteins and noncoding RNAs, appears to be the main epigenetic mechanisms that control gene expression. These allow different cells in an organism to express different transcription profiles, despite each cell containing the same DNA sequence. In the context of replacement of spermatic protamine with histones from the oocyte, active cell division, and specification of different lineages, active and passive mechanisms of epigenetic remodeling have been revealed as critical for editing the epigenetic profile of the early embryo. Importantly, redundant factors and mechanisms are likely in place, and only a few have been reported as critical for fertilization or embryo survival by the use of knockout models. The aim of this review is to highlight the main mechanisms of epigenetic remodeling that ensue after fertilization in mammals. PMID:27165992

  10. Chromatin, epigenetics and stem cells.

    Roloff, Tim C; Nuber, Ulrike A

    2005-03-01

    Epigenetics is a term that has changed its meaning with the increasing biological knowledge on developmental processes. However, its current application to stem cell biology is often imprecise and is conceptually problematic. This article addresses two different subjects, the definition of epigenetics and chromatin states of stem and differentiated cells. We describe mechanisms that regulate chromatin changes and provide an overview of chromatin states of stem and differentiated cells. Moreover, a modification of the current epigenetics definition is proposed that is not restricted by the heritability of gene expression throughout cell divisions and excludes translational gene expression control. PMID:15819395

  11. EPIGENETIC MODIFICATIONS OF SWINE GENOME

    Kristina Budimir

    2013-06-01

    Full Text Available Epigenetics is represents a new way of genome analysis, respectively gene expression that occurs without DNA sequence change. Changes that occur are epigenetic modifications and they include post-translational histone modification and DNA methylation. Chemical groups that are added on DNA molecule cause changes in DNA and create epigenome. The consequence of that is appearance of imprinted genes in genome. Genetic imprinting is epigenetic modification in which one of inherited alleles inactivates. Its influence can be seen on productive and reproductive traits. Discovering new imprinted genes is important because of their conservation and understanding their function.

  12. Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment.

    Ramo-Fernández, Laura; Schneider, Anna; Wilker, Sarah; Kolassa, Iris-Tatjana

    2015-10-01

    Survivors of war trauma or childhood maltreatment are at increased risk for trauma-spectrum disorders such as post-traumatic stress disorder (PTSD). In addition, traumatic stress has been associated with alterations in the neuroendocrine and the immune system, enhancing the risk for physical diseases. Traumatic experiences might even affect psychological as well as biological parameters in the next generation, i.e. traumatic stress might have transgenerational effects. This article outlines how epigenetic processes, which represent a pivotal biological mechanism for dynamic adaptation to environmental challenges, might contribute to the explanation of the long-lasting and transgenerational effects of trauma. In particular, epigenetic alterations in genes regulating the hypothalamus-pituitary-adrenal axis as well as the immune system have been observed in survivors of childhood and adult trauma. These changes could result in enduring alterations of the stress response as well as the physical health risk. Furthermore, the effects of parental trauma could be transmitted to the next generation by parental distress and the pre- and postnatal environment, as well as by epigenetic marks transmitted via the germline. While epigenetic research has a high potential of advancing our understanding of the consequences of trauma, the findings have to be interpreted with caution, as epigenetics only represent one piece of a complex puzzle of interacting biological and environmental factors. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26358541

  13. Reassessing cortical reorganization in the primary sensorimotor cortex following arm amputation.

    Makin, Tamar R; Scholz, Jan; Henderson Slater, David; Johansen-Berg, Heidi; Tracey, Irene

    2015-08-01

    The role of cortical activity in generating and abolishing chronic pain is increasingly emphasized in the clinical community. Perhaps the most striking example of this is the maladaptive plasticity theory, according to which phantom pain arises from remapping of cortically neighbouring representations (lower face) into the territory of the missing hand following amputation. This theory has been extended to a wide range of chronic pain conditions, such as complex regional pain syndrome. Yet, despite its growing popularity, the evidence to support the maladaptive plasticity theory is largely based on correlations between pain ratings and oftentimes crude measurements of cortical reorganization, with little consideration of potential contributions of other clinical factors, such as adaptive behaviour, in driving the identified brain plasticity. Here, we used a physiologically meaningful measurement of cortical reorganization to reassess its relationship to phantom pain in upper limb amputees. We identified small yet consistent shifts in lip representation contralateral to the missing hand towards, but not invading, the hand area. However, we were unable to identify any statistical relationship between cortical reorganization and phantom sensations or pain either with this measurement or with the traditional Euclidian distance measurement. Instead, we demonstrate that other factors may contribute to the observed remapping. Further research that reassesses more broadly the relationship between cortical reorganization and chronic pain is warranted. PMID:26072517

  14. Epigenetics and assisted reproductive technologies

    Pinborg, Anja; Loft, Anne; Romundstad, Liv Bente;

    2016-01-01

    Epigenetic modification controls gene activity without changes in the DNA sequence. The genome undergoes several phases of epigenetic programming during gametogenesis and early embryo development coinciding with assisted reproductive technologies (ART) treatments. Imprinting disorders have been...... with cryopreserved/thawed embryos results in a higher risk of large-for-gestational age babies, which may be due to epigenetic modification. Further animal studies have shown altered gene expression profiles in offspring conceived by ART related to altered glucose metabolism. It is controversial whether human...... adolescents conceived by ART have altered lipid and glucose profiles and thereby a higher long-term risk of cardiovascular disease and diabetes. This commentary describes the basic concepts of epigenetics and gives a short overview of the existing literature on the association between imprinting disorders...

  15. Twin methodology in epigenetic studies

    Tan, Qihua; Christiansen, Lene; von Bornemann Hjelmborg, Jacob;

    2015-01-01

    of diseases to molecular phenotypes in functional genomics especially in epigenetics, a thriving field of research that concerns the environmental regulation of gene expression through DNA methylation, histone modification, microRNA and long non-coding RNA expression, etc. The application of the twin method...... to molecular phenotypes offers new opportunities to study the genetic (nature) and environmental (nurture) contributions to epigenetic regulation of gene activity during developmental, ageing and disease processes. Besides the classical twin model, the case co-twin design using identical twins discordant...... for a trait or disease is becoming a popular and powerful design for epigenome-wide association study in linking environmental exposure to differential epigenetic regulation and to disease status while controlling for individual genetic make-up. It can be expected that novel uses of twin methods in epigenetic...

  16. Epigenetic Regulation of Telomere Maintenance

    Fojtová, M.; Fajkus, Jiří

    2014-01-01

    Roč. 143, 1-3 (2014), s. 125-135. ISSN 1424-8581 Institutional support: RVO:68081707 Keywords : Chromatin * DNA methylation * Epigenetics Subject RIV: BO - Biophysics Impact factor: 1.561, year: 2014

  17. Epigenetic Treatments for Cognitive Impairments

    Day, Jeremy J.; Sweatt, J. David

    2011-01-01

    Epigenetic mechanisms integrate signals from diverse intracellular transduction cascades and in turn regulate genetic readout. Accumulating evidence has revealed that these mechanisms are critical components of ongoing physiology and function in the adult nervous system, and are essential for many cognitive processes, including learning and memory. Moreover, a number of psychiatric disorders and syndromes that involve cognitive impairments are associated with altered epigenetic function. In t...

  18. Epigenetic Modifications and Diabetic Retinopathy

    Renu A. Kowluru

    2013-01-01

    Full Text Available Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2 and matrix metalloproteinase-9 (MMP-9 are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1, and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.

  19. Transgenerational inheritance or resetting of stress-induced epigenetic modifications: two sides of the same coin.

    Penny J Tricker

    2015-09-01

    Full Text Available The transgenerational inheritance of stress-induced epigenetic modifications is still controversial. Despite several examples of defence ‘priming’ and induced genetic rearrangements, the involvement and persistence of transgenerational epigenetic modifications is not known to be general. Here I argue that non-transmission of epigenetic marks through meiosis may be regarded as an epigenetic modification in itself, and that we should understand the implications for plant evolution in the context of both selection for and selection against transgenerational epigenetic memory. Recent data suggest that both epigenetic inheritance and resetting are mechanistically directed and targeted. Stress-induced epigenetic modifications may buffer against DNA sequence-based evolution to maintain plasticity, or may form part of plasticity’s adaptive potential. To date we have tended to concentrate on the question of whether and for how long epigenetic memory persists. I argue that we should now re-direct our question to investigate the differences between where it persists and where it does not, to understand the higher order evolutionary methods in play and their contribution.

  20. The epigenetic footprint of poleward range-expanding plants in apomictic dandelions.

    Preite, V; Snoek, L B; Oplaat, C; Biere, A; van der Putten, W H; Verhoeven, K J F

    2015-09-01

    Epigenetic modifications, such as DNA methylation variation, can generate heritable phenotypic variation independent of the underlying genetic code. However, epigenetic variation in natural plant populations is poorly documented and little understood. Here, we test whether northward range expansion of obligate apomicts of the common dandelion (Taraxacum officinale) is associated with DNA methylation variation. We characterized and compared patterns of genetic and DNA methylation variation in greenhouse-reared offspring of T. officinale that were collected along a latitudinal transect of northward range expansion in Europe. Genetic AFLP and epigenetic MS-AFLP markers revealed high levels of local diversity and modest but significant heritable differentiation between sampling locations and between the southern, central and northern regions of the transect. Patterns of genetic and epigenetic variation were significantly correlated, reflecting the genetic control over epigenetic variation and/or the accumulation of lineage-specific spontaneous epimutations, which may be selectively neutral. In addition, we identified a small component of DNA methylation differentiation along the transect that is independent of genetic variation. This epigenetic differentiation might reflect environment-specific induction or, in case the DNA methylation variation affects relevant traits and fitness, selection of heritable DNA methylation variants. Such generated epigenetic variants might contribute to the adaptive capacity of individual asexual lineages under changing environments. Our results highlight the potential of heritable DNA methylation variation to contribute to population differentiation along ecological gradients. Further studies are needed using higher resolution methods to understand the functional significance of such natural occurring epigenetic differentiation. PMID:26206253

  1. Stress Response and Perinatal Reprogramming: Unraveling (Mal)adaptive Strategies.

    Musazzi, Laura; Marrocco, Jordan

    2016-01-01

    Environmental stressors induce coping strategies in the majority of individuals. The stress response, involving the activation of the hypothalamic-pituitary-adrenocortical axis and the consequent release of corticosteroid hormones, is indeed aimed at promoting metabolic, functional, and behavioral adaptations. However, behavioral stress is also associated with fast and long-lasting neurochemical, structural, and behavioral changes, leading to long-term remodeling of glutamate transmission, and increased susceptibility to neuropsychiatric disorders. Of note, early-life events, both in utero and during the early postnatal life, trigger reprogramming of the stress response, which is often associated with loss of stress resilience and ensuing neurobehavioral (mal)adaptations. Indeed, adverse experiences in early life are known to induce long-term stress-related neuropsychiatric disorders in vulnerable individuals. Here, we discuss recent findings about stress remodeling of excitatory neurotransmission and brain morphology in animal models of behavioral stress. These changes are likely driven by epigenetic factors that lie at the core of the stress-response reprogramming in individuals with a history of perinatal stress. We propose that reprogramming mechanisms may underlie the reorganization of excitatory neurotransmission in the short- and long-term response to stressful stimuli. PMID:27057367

  2. The IDC-thesaurus and its reorganization

    Final report on the IDC-Thesaurus and its reorganization. The Thesaurus set up for documentation of chemistry and its borderline areas is built up of concept sets. These concept sets unite all synonyms and are linked by concept relations reflecting the hierarchical structure of the Thesaurus. Analysis of the polyhierarchy of the Thesaurus. Composite concepts are subdivided into their broader terms of the abstraction system. These concepts as well as words with different spelling are transferred from the retrieval Thesaurus to a Thesaurus dictionary from which a file is set up for correcting the complete documentation file. (orig.) 891 WB 892 MB

  3. Introduction to the Special Section on Epigenetics.

    Lester, Barry M; Conradt, Elisabeth; Marsit, Carmen

    2016-01-01

    Epigenetics provides the opportunity to revolutionize our understanding of the role of genetics and the environment in explaining human behavior, although the use of epigenetics to study human behavior is just beginning. In this introduction, the authors present the basics of epigenetics in a way that is designed to make this exciting field accessible to a wide readership. The authors describe the history of human behavioral epigenetic research in the context of other disciplines and graphically illustrate the burgeoning of research in the application of epigenetic methods and principles to the study of human behavior. The role of epigenetics in normal embryonic development and the influence of biological and environmental factors altering behavior through epigenetic mechanisms and developmental programming are discussed. Some basic approaches to the study of epigenetics are reviewed. The authors conclude with a discussion of challenges and opportunities, including intervention, as the field of human behavioral epigenetics continue to grow. PMID:26822440

  4. Evolution or adaptation? What do heritable adaptive changes imply?

    M. Kemal Irmak

    2014-01-01

    Interactions between environmental factors and epigenetic inheritance system produce a great deal of variation from one geographic region to another in human craniofacial morphology, skin color, hair form, stature and body proportions. In this system, while environmental factors produce modifications in the body, they simultaneously induce long-term epigenetic modifications in the germ cells that are inherited to offspring. This kind of heritable changes is called biological adaptation. It wa...

  5. Epigenetics of drought-induced trans-generational plasticity: consequences for range limit development

    Alsdurf, Jacob; Anderson, Cynthia; Siemens, David H

    2015-01-01

    Genetic variation gives plants the potential to adapt to stressful environments that often exist beyond their geographic range limits. However, various genetic, physiological or developmental constraints might prevent the process of adaptation. Alternatively, environmentally induced epigenetic changes might sustain populations for several generations in stressful areas across range boundaries, but previous work on Boechera stricta, an upland mustard closely related to Arabidopsis, documented ...

  6. Epigenetics and the regulation of stress vulnerability and resilience.

    Zannas, A S; West, A E

    2014-04-01

    The human brain has a remarkable capacity to adapt to and learn from a wide range of variations in the environment. However, environmental challenges can also precipitate psychiatric disorders in susceptible individuals. Why any given experience should induce one brain to adapt while another is edged toward psychopathology remains poorly understood. Like all aspects of psychological function, both nature (genetics) and nurture (life experience) sculpt the brain's response to stressful stimuli. Here we review how these two influences intersect at the epigenetic regulation of neuronal gene transcription, and we discuss how the regulation of genomic DNA methylation near key stress-response genes may influence psychological susceptibility or resilience to environmental stressors. Our goal is to offer a perspective on the epigenetics of stress responses that works to bridge the gap between the study of this molecular process in animal models and its potential usefulness for understanding stress vulnerabilities in humans. PMID:24333971

  7. Epigenetics and Colorectal Cancer Pathogenesis

    Bardhan, Kankana; Liu, Kebin, E-mail: Kliu@gru.edu [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)

    2013-06-05

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  8. Epigenetic mechanisms in penile carcinoma

    Kuasne, Hellen; Marchi, Fabio Albuquerque; Rogatto, Silvia Regina;

    2013-01-01

    Penile carcinoma (PeCa) represents an important public health problem in poor and developing countries. Despite its unpredictable behavior and aggressive treatment, there have only been a few reports regarding its molecular data, especially epigenetic mechanisms. The functional diversity in diffe......Penile carcinoma (PeCa) represents an important public health problem in poor and developing countries. Despite its unpredictable behavior and aggressive treatment, there have only been a few reports regarding its molecular data, especially epigenetic mechanisms. The functional diversity...... in different cell types is acquired by chromatin modifications, which are established by epigenetic regulatory mechanisms involving DNA methylation, histone acetylation, and miRNAs. Recent evidence indicates that the dysregulation in these processes can result in the development of several diseases, including...... cancer. Epigenetic alterations, such as the methylation of CpGs islands, may reveal candidates for the development of specific markers for cancer detection, diagnosis and prognosis. There are a few reports on the epigenetic alterations in PeCa, and most of these studies have only focused on alterations...

  9. Epigenetics and assisted reproductive technologies.

    Pinborg, Anja; Loft, Anne; Romundstad, Liv B; Wennerholm, Ulla-Britt; Söderström-Anttila, Viveca; Bergh, Christina; Aittomäki, Kristiina

    2016-01-01

    Epigenetic modification controls gene activity without changes in the DNA sequence. The genome undergoes several phases of epigenetic programming during gametogenesis and early embryo development, coinciding with assisted reproductive technologies (ART) treatments. Imprinting disorders have been associated with ART techniques, but disentangling the influence of the ART procedures per se from the effect of the reproductive disease of the parents is a challenge. Epidemiological human studies have shown altered birthweight profiles in ART compared with spontaneously conceived singletons. Conception with cryopreserved/thawed embryos results in a higher risk of large-for-gestational-age babies, which may be due to epigenetic modification. Further animal studies have shown altered gene expression profiles in offspring conceived by ART related to altered glucose metabolism. It is controversial whether human adolescents conceived by ART have altered lipid and glucose profiles and thereby a higher long-term risk of cardiovascular disease and diabetes. This commentary describes the basic concepts of epigenetics and gives a short overview of the existing literature on the association between imprinting disorders, epigenetic modification and ART. PMID:26458360

  10. Epigenetic Disregulation in Oral Cancer

    Stefania Staibano

    2012-02-01

    Full Text Available Squamous cell carcinoma of the oral region (OSCC is one of the most common and highly aggressive malignancies worldwide, despite the fact that significant results have been achieved during the last decades in its detection, prevention and treatment. Although many efforts have been made to define the molecular signatures that identify the clinical outcome of oral cancers, OSCC still lacks reliable prognostic molecular markers. Scientific evidence indicates that transition from normal epithelium to pre-malignancy, and finally to oral carcinoma, depends on the accumulation of genetic and epigenetic alterations in a multistep process. Unlike genetic alterations, epigenetic changes are heritable and potentially reversible. The most common examples of such changes are DNA methylation, histone modification, and small non-coding RNAs. Although several epigenetic changes have been currently linked to OSCC initiation and progression, they have been only partially characterized. Over the last decade, it has been demonstrated that especially aberrant DNA methylation plays a critical role in oral cancer. The major goal of the present paper is to review the recent literature about the epigenetic modifications contribution in early and later phases of OSCC malignant transformation; in particular we point out the current evidence of epigenetic marks as novel markers for early diagnosis and prognosis as well as potential therapeutic targets in oral cancer.

  11. [Advances in epigenetic researches of Toxoplasma gondii].

    Yang, Pei-Liang; Chen, Xiao-Guang

    2012-06-30

    Toxoplasma gondii undergoes a complex life cycle that involves multiple development stages, hosts and environments. The ability to transform from one stage to another and adapt to changing environments demands precise regulation of gene expression. Bioinformatic surveys of the sequenced genomes of T. gondii revealed a peculiar absence of DNA-binding transcription factors that are well-conserved from yeast through humans, but a wealth of epigenetic machinery present in T. gondii. Evidence from reports demonstrates that remodeling of the chromatin structure particularly through post-translational modifications of histones, such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, is potentially a major process that coordinates regulation of its gene expression. In addition, no-coding RNAs may play an important role in modulating gene expression of T. gondii. These results provide reliable foundations for prevention of toxoplasmosis by revealing its pathogenic mechanism. PMID:23072142

  12. Epigenetics in heart failure phenotypes.

    Berezin, Alexander

    2016-12-01

    Chronic heart failure (HF) is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF) and HF with preserved left ventricular ejection fraction (HFpEF). Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF. PMID:27335803

  13. Epigenetic changes in colorectal cancer

    Yan Jia; Mingzhou Guo

    2013-01-01

    Epigenetic changes frequently occur in human colorectal cancer.Genomic global hypomethylation,gene promoter region hypermethylation,histone modifications,and alteration of miRNA patterns are major epigenetic changes in colorectal cancer.Loss of imprinting (LOI) is associated with colorectal neoplasia.Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation.HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment.Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer.This review is mainly focused on DNA methylation,histone modification,and microRNA changes in colorectal cancer.

  14. Epigenetic alterations underlying autoimmune diseases.

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-03-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases. PMID:26761426

  15. Epigenetic Epidemiology: Promises for Public Health Research

    Bakulski, Kelly M.; Fallin, M. Daniele

    2014-01-01

    Epigenetic changes underlie developmental and age related biology. Promising epidemiologic research implicates epigenetics in disease risk and progression, and suggests epigenetic status depends on environmental risks as well as genetic predisposition. Epigenetics may represent a mechanistic link between environmental exposures, or genetics, and many common diseases, or may simply provide a quantitative biomarker for exposure or disease for areas of epidemiology currently lacking such measure...

  16. The Mendelian disorders of the epigenetic machinery

    Bjornsson, Hans Tomas

    2015-01-01

    The Mendelian disorders of the epigenetic machinery are genetic disorders that involve disruption of the various components of the epigenetic machinery (writers, erasers, readers, and remodelers) and are thus expected to have widespread downstream epigenetic consequences. Studying this group may offer a unique opportunity to learn about the role of epigenetics in health and disease. Among these patients, neurological dysfunction and, in particular, intellectual disability appears to be a comm...

  17. Epigenetic dynamics across the cell cycle

    Kheir, Tony Bou; Lund, Anders H.

    2010-01-01

    Progression of the mammalian cell cycle depends on correct timing and co-ordination of a series of events, which are managed by the cellular transcriptional machinery and epigenetic mechanisms governing genome accessibility. Epigenetic chromatin modifications are dynamic across the cell cycle...... a correct inheritance of epigenetic chromatin modifications to daughter cells. In this chapter, we summarize the current knowledge on the dynamics of epigenetic chromatin modifications during progression of the cell cycle....

  18. Workplace Re-organization and Changes in Physiological Stress Markers

    Carlsson, Rikke Hinge; Hansen, Åse Marie; Kristiansen, Jesper;

    2014-01-01

    The aim of this study was to investigate changes in physiological stress markers as a consequence of workplace reorganization. Moreover, we aimed to investigate changes in the psychosocial work environment (job strain, effortreward imbalance (ERI), in psychological distress (stress symptoms...... reorganization and changes in several physiological stress markers. However, these changes could not be explained by a significant change in psychological distress....

  19. 26 CFR 1.585-4 - Reorganizations and asset acquisitions.

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Reorganizations and asset acquisitions. 1.585-4... TAX (CONTINUED) INCOME TAXES (CONTINUED) Banking Institutions § 1.585-4 Reorganizations and asset... accounting for bad debts prior to July 11, 1969. For the taxable year 1970 through 1973, X and Y...

  20. Epigenetic alterations in gastric carcinogenesis

    In-Seon CHOI; Tsung-Teh WU

    2005-01-01

    Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play important roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpG island methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesis and its relevance of clinical implications.

  1. Epigenetic regulation in cardiac fibrosis

    Li-Ming; Yu; Yong; Xu

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  2. Epigenetic inheritance and evolution: A paternal perspective on dietary influences.

    Soubry, Adelheid

    2015-07-01

    The earliest indications for paternally induced transgenerational effects from the environment to future generations were based on a small number of long-term epidemiological studies and some empirical observations. Only recently have experimental animal models and a few analyses on human data explored the transgenerational nature of phenotypic changes observed in offspring. Changes include multiple metabolic disorders, cancer and other chronic diseases. These phenotypes cannot always be explained by Mendelian inheritance, DNA mutations or genetic damage. Hence, a new compelling theory on epigenetic inheritance is gaining interest, providing new concepts that extend Darwin's evolutionary theory. Epigenetic alterations or "epimutations" are being considered to explain transgenerational inheritance of parentally acquired traits. The responsible mechanisms for these epimutations include DNA methylation, histone modification, and RNA-mediated effects. This review explores the literature on a number of time-dependent environmentally induced epigenetic alterations, specifically those from dietary exposures. We suggest a role for the male germ line as one of nature's tools to capture messages from our continuously changing environment and to transfer this information to subsequent generations. Further, we open the discussion that the paternally inherited epigenetic information may contribute to evolutionary adaptation. PMID:25769497

  3. Epigenetic phenomena and the evolution of plant allopolyploids

    BaoLiu; JonathanF.Wendel

    2005-01-01

    Allopolyploid speciation is widespread in plants, yet the molecular requirements for successful orchestration of coordinated gene expression for two divergent and reunited genomes are poorly understood. Recent studies in several plant systems have revealed that allopolyploid genesis under both synthetic and natural conditions often is accompanied by rapid and sometimes evolutionarily conserved epigeuetic changes, including alteration in cytosine methylation patterns, rapid silencing in ribosomal RNA and proteincoding genes, and de-repression of dormant transposable elements. These changes are inter-related and likely arise from chromatin remodeling and its effects on epigenetic codes during and subsequent to allopolyploid formation. Epigenetic modifications could produce adaptive epimutations and novel phenotypes, some of which may be evolutionarily stable for millions of years, thereby representing a vast reservoir of latent variation that may be episodically released and made visible to selection. This epigenetic variation may contribute to several important attributes of allopolyploidy, including functional diversification or subfunctionalization of duplicated genes, genetic and cytological diploidization, and quenching of incompatible inter-genomic interactions that are characteristic of allopolyploids. It is likely that the evolutionary success of allopolyploidy is in part attributatble to epigenetic phenomena that we are only just beginning to understand.

  4. Genome reorganization during aging of dividing cells

    The study of the effect of low dose rate ionizing radiation on the long-term proliferation of fibroblasts led to the observation that radiation accentuated the growth potential of the cells, favoring events which normally take place during division. These events could be related to the genome reorganization taking place during division. Hence, it has been hypothesized that the long-term proliferation of fibroblasts depends upon the potential for reorganization of the genome, the latter being a self-limiting process. At each division residual quantitative and qualitative changes would accumulate in chromatin, limiting the long-term potential for further rearrangements. The hypothesis was checked looking for quantitative and qualitative changes in DNA through the in vitro lifespan of human fibroblast populations. It was found that at each population doubling in 20% of the cells there is unequal distribution of DNA between sister cells. Results show that this could be due to errors in chromosome assembly and segregation, to loss of DNA, to errors during semiconservative DNA synthesis and to multiple rounds of DNA replication at a single origin. An increased alkali- and thermo-lability of chromatin was found during in vitro aging. At the ultrastructural level after mild decondensation, chromatin fibers were spaced and shorter. After Miller's spreading, most of the chromatin of old cells had lost the nucleosome organization and was fragmented. These chromatin changes became apparent only towards the end of the life span of human embryonic fibroblasts but were already present in a significant fraction of low population doubling level (PDL) fibroblasts from human adults. Almost all cells of low-PDL fibroblasts from the Werner syndrome presented these chromatin changes

  5. Epigenetic Epidemiology of Complex Diseases Using Twins

    Tan, Qihua

    2013-01-01

    through multiple epigenetic mechanisms. This paper reviews the new developments in using twins to study disease-related epigenetic alterations, links them to lifetime environmental exposure with a focus on the discordant twin design and proposes novel data-analytical approaches with the aim of promoting...... a more efficient use of twins in epigenetic studies of complex human diseases....

  6. Epigenetic drift in the aging genome

    Tan, Qihua; Heijmans, Bastiaan T; Hjelmborg, Jacob V B;

    2016-01-01

    BACKGROUND: Current epigenetic studies on aging are dominated by the cross-sectional design that correlates subjects' ages or age groups with their measured epigenetic profiles. Such studies have been more aimed at age prediction or building up the epigenetic clock of age rather than focusing on ...

  7. Review: Epigenetic mechanisms in ocular disease

    He, Shikun; Li, Xiaohua; Chan, Nymph; Hinton, David R.

    2013-01-01

    Epigenetics has become an increasingly important area of biomedical research. Increasing evidence shows that epigenetic alterations influence common pathologic responses including inflammation, ischemia, neoplasia, aging, and neurodegeneration. Importantly, epigenetic mechanisms may have a pathogenic role in many complex eye diseases such as corneal dystrophy, cataract, glaucoma, diabetic retinopathy, ocular neoplasia, uveitis, and age-related macular degeneration. The emerging emphasis on ep...

  8. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

    Mimi L. Phan

    2016-01-01

    Full Text Available Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded.

  9. Epigenetic Editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes.

    Groote, De, T.; Verschure, P.J.; Rots, M G

    2012-01-01

    Despite significant advances made in epigenetic research in recent decades, many questions remain unresolved, especially concerning cause and consequence of epigenetic marks with respect to gene expression modulation (GEM). Technologies allowing the targeting of epigenetic enzymes to predetermined DNA sequences are uniquely suited to answer such questions and could provide potent (bio)medical tools. Toward the goal of gene-specific GEM by overwriting epigenetic marks (Epigenetic Editing, EGE)...

  10. Epigenetic Editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes

    Groote, de, Robert; Verschure, P.J.; Rots, M.G.

    2012-01-01

    Despite significant advances made in epigenetic research in recent decades, many questions remain unresolved, especially concerning cause and consequence of epigenetic marks with respect to gene expression modulation (GEM). Technologies allowing the targeting of epigenetic enzymes to predetermined DNA sequences are uniquely suited to answer such questions and could provide potent (bio)medical tools. Toward the goal of gene-specific GEM by overwriting epigenetic marks (Epigenetic Editing, EGE)...

  11. 26 CFR 54.4980B-9 - Business reorganizations and employer withdrawals from multiemployer plans.

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Business reorganizations and employer...-9 Business reorganizations and employer withdrawals from multiemployer plans. The following... affected qualified beneficiaries in the context of business reorganizations and employer withdrawals...

  12. Comparative epigenomics: an emerging field with breakthrough potential to understand evolution of epigenetic regulation

    Janine E. Deakin

    2014-12-01

    Full Text Available Epigenetic mechanisms regulate gene expression, thereby mediating the interaction between environment, genotype and phenotype. Changes to epigenetic regulation of genes may be heritable, permitting rapid adaptation of a species to environmental cues. However, most of the current understanding of epigenetic gene regulation has been gained from studies of mice and humans, with only a limited understanding of the conservation of epigenetic mechanisms across divergent taxa. The relative ease at which genome sequence data is now obtained and the advancements made in epigenomics techniques for non-model species provides a basis for carrying out comparative epigenomic studies across a wider range of species, making it possible to start unraveling the evolution of epigenetic mechanisms. We review the current knowledge of epigenetic mechanisms obtained from studying model organisms, give an example of how comparative epigenomics using non-model species is helping to trace the evolutionary history of X chromosome inactivation in mammals and explore the opportunities to study comparative epigenomics in biological systems displaying adaptation between species, such as the immune system and sex determination.

  13. Epigenetic Placental Programming of Preeclampsia

    Preeclampsia (PE) affects 8-10% of women in the US and long-term consequences include subsequent development of maternal hypertension and hypertension in offspring. As methylation patterns are established during fetal life, we focused on epigenetic alterations in DNA methylation as a plausible expla...

  14. Mitochondrial Epigenetics and Environmental Exposure.

    Lambertini, Luca; Byun, Hyang-Min

    2016-09-01

    The rising toll of chronic and debilitating diseases brought about by the exposure to an ever expanding number of environmental pollutants and socio-economic factors is calling for action. The understanding of the molecular mechanisms behind the effects of environmental exposures can lead to the development of biomarkers that can support the public health fields of both early diagnosis and intervention to limit the burden of environmental diseases. The study of mitochondrial epigenetics carries high hopes to provide important biomarkers of exposure and disease. Mitochondria are in fact on the frontline of the cellular response to the environment. Modifications of the epigenetic factors regulating the mitochondrial activity are emerging as informative tools that can effectively report on the effects of the environment on the phenotype. Here, we will discuss the emerging field of mitochondrial epigenetics. This review describes the main epigenetic phenomena that modify the activity of the mitochondrial DNA including DNA methylation, long and short non-coding RNAs. We will discuss the unique pattern of mitochondrial DNA methylation, describe the challenges of correctly measuring it, and report on the existing studies that have analysed the correlation between environmental exposures and mitochondrial DNA methylation. Finally, we provide a brief account of the therapeutic approaches targeting mitochondria currently under consideration. PMID:27344144

  15. Epigenetics of Early Child Development

    ChrisMurgatroyd

    2011-04-01

    To date, the study of gene-environment interactions in the human population has been dominated by epidemiology. However, recent research in the neuroscience field is now advancing clinical studies by addressing specifically the mechanisms by which gene-environment interactions can predispose individuals towards psychopathology. To this end, appropriate animal models are being developed in which early environmental factors can be manipulated in a controlled manner. Here we will review recent studies performed with the common aim of understanding the effects of the early environment in shaping brain development and discuss the newly developing role of epigenetic mechanisms in translating early life conditions into long-lasting changes in gene expression underpinning brain functions. Particularly, we argue that epigenetic mechanisms can mediate the gene-environment dialogue in early life and give rise to persistent epigenetic programming of adult physiology and dysfunction eventually resulting in disease. Understanding how early life experiences can give raise to lasting epigenetic memories conferring increased risk for mental disorders, how they are maintained and how they could be reversed, is increasingly becoming a focus of modern psychiatry and should pave new guidelines for timely therapeutic interventions.

  16. Epigenetics mechanisms in renal development.

    Hilliard, Sylvia A; El-Dahr, Samir S

    2016-07-01

    Appreciation for the role of epigenetic modifications in the diagnosis and treatment of diseases is fast gaining attention. Treatment of chronic kidney disease stemming from diabetes or hypertension as well as Wilms tumor will all profit from knowledge of the changes in the epigenomic landscapes. To do so, it is essential to characterize the epigenomic modifiers and their modifications under normal physiological conditions. The transcription factor Pax2 was identified as a major epigenetic player in the early specification of the kidney. Notably, the progenitors of all nephrons that reside in the cap mesenchyme display a unique bivalent histone signature (expressing repressive epigenetic marks alongside activation marks) on lineage-specific genes. These cells are deemed poised for differentiation and commitment to the nephrogenic lineage. In response to the appropriate inducing signal, these genes lose their repressive histone marks, which allow for their expression in nascent nephron precursors. Such knowledge of the epigenetic landscape and the resultant cell fate or behavior in the developing kidney will greatly improve the overall success in designing regenerative strategies and tissue reprogramming methodologies from pluripotent cells. PMID:26493068

  17. Circadian clocks, epigenetics, and cancer

    Masri, Selma

    2015-01-01

    The interplay between circadian rhythm and cancer has been suggested for more than a decade based on the observations that shift work and cancer incidence are linked. Accumulating evidence implicates the circadian clock in cancer survival and proliferation pathways. At the molecular level, multiple control mechanisms have been proposed to link circadian transcription and cell-cycle control to tumorigenesis.The circadian gating of the cell cycle and subsequent control of cell proliferation is an area of active investigation. Moreover, the circadian clock is a transcriptional system that is intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape at the level of histone modifications, DNA methylation, and small regulatory RNAs are differentially controlled in cancer cells. This concept raises the possibility that epigenetic control is a common thread linking the clock with cancer, though little scientific evidence is known to date.This review focuses on the link between circadian clock and cancer, and speculates on the possible connections at the epigenetic level that could further link the circadian clock to tumor initiation or progression.

  18. Mass spectrometry in epigenetic research

    Beck, Hans Christian

    2010-01-01

    -based proteomics techniques to histone biology has gained new insight into the function of the nucleosome: Novel posttranslational modifications have been discovered at the lateral surface of the nucleosome. These modifications regulate histone-DNA interactions, adding a new dimension to the epigenetic regulation...

  19. Autism Spectrum Disorders and Epigenetics

    Grafodatskaya, Daria; Chung, Brian; Szatmari, Peter; Weksberg, Rosanna

    2010-01-01

    Objective: Current research suggests that the causes of autism spectrum disorders (ASD) are multifactorial and include both genetic and environmental factors. Several lines of evidence suggest that epigenetics also plays an important role in ASD etiology and that it might, in fact, integrate genetic and environmental influences to dysregulate…

  20. Predicting response to epigenetic therapy

    Treppendahl, Marianne B; Sommer Kristensen, Lasse; Grønbæk, Kirsten

    2014-01-01

    Drugs targeting the epigenome are new promising cancer treatment modalities; however, not all patients receive the same benefit from these drugs. In contrast to conventional chemotherapy, responses may take several months after the initiation of treatment to occur. Accordingly, identification of ......-approved epigenetic drugs....

  1. Epigenetics of hepatocellular carcinoma: a new horizon

    LIU Wei-ren; SHI Ying-hong; PENG Yuan-fei; FAN Jia

    2012-01-01

    Epigenetic changes refer to stable alterations in gene expression with no underlying modifications in the genetic sequence itself.It has become clear that not only gene variations but also epigenetic modifications may contribute to varied diseases,including cancer.This review will provide an overview of how epigenetic factors,including genomic DNA methylation,histone modifications,and miRNA regulation,contribute to hepatocellular carcinoma (HCC) dissemination,invasion,and metastasis.Additionally,the reversal of dysregulated epigenetic changes has emerged as a potential strategy for the treatment of HCC,and we will summarize the latest epigenetic therapies for HCC.

  2. Epigenetic mechanisms of drug addiction.

    Nestler, Eric J

    2014-01-01

    Drug addiction involves potentially life-long behavioral abnormalities that are caused in vulnerable individuals by repeated exposure to a drug of abuse. The persistence of these behavioral changes suggests that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype. Work over the past decade has demonstrated a crucial role for epigenetic mechanisms in driving lasting changes in gene expression in diverse tissues, including brain. This has prompted recent research aimed at characterizing the influence of epigenetic regulatory events in mediating the lasting effects of drugs of abuse on the brain in animal models of drug addiction. This review provides a progress report of this still early work in the field. As will be seen, there is robust evidence that repeated exposure to drugs of abuse induces changes within the brain's reward regions in three major modes of epigenetic regulation-histone modifications such as acetylation and methylation, DNA methylation, and non-coding RNAs. In several instances, it has been possible to demonstrate directly the contribution of such epigenetic changes to addiction-related behavioral abnormalities. Studies of epigenetic mechanisms of addiction are also providing an unprecedented view of the range of genes and non-genic regions that are affected by repeated drug exposure and the precise molecular basis of that regulation. Work is now needed to validate key aspects of this work in human addiction and evaluate the possibility of mining this information to develop new diagnostic tests and more effective treatments for addiction syndromes. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. PMID:23643695

  3. The ambiguous nature of epigenetic responsibility.

    Dupras, Charles; Ravitsky, Vardit

    2016-08-01

    Over the past decade, epigenetic studies have been providing further evidence of the molecular interplay between gene expression and its health outcomes on one hand, and the physical and social environments in which individuals are conceived, born and live on the other. As knowledge of epigenetic programming expands, a growing body of literature in social sciences and humanities is exploring the implications of this new field of study for contemporary societies. Epigenetics has been mobilised to support political claims, for instance, with regard to collective obligations to address socio-environmental determinants of health. The idea of a moral 'epigenetic responsibility' has been proposed, meaning that individuals and/or governments should be accountable for the epigenetic programming of children and/or citizens. However, these discussions have largely overlooked important biological nuances and ambiguities inherent in the field of epigenetics. In this paper, we argue that the identification and assignment of moral epigenetic responsibilities should reflect the rich diversity and complexity of epigenetic mechanisms, and not rely solely on a gross comparison between epigenetics and genetics. More specifically, we explore how further investigation of the ambiguous notions of epigenetic normality and epigenetic plasticity should play a role in shaping this emerging debate. PMID:27015741

  4. Epigenetic Pathways of Oncogenic Viruses: Therapeutic Promises.

    El-Araby, Amr M; Fouad, Abdelrahman A; Hanbal, Amr M; Abdelwahab, Sara M; Qassem, Omar M; El-Araby, Moustafa E

    2016-02-01

    Cancerous transformation comprises different events that are both genetic and epigenetic. The ultimate goal for such events is to maintain cell survival and proliferation. This transformation occurs as a consequence of different features such as environmental and genetic factors, as well as some types of infection. Many viral infections are considered to be causative agents of a number of different malignancies. To convert normal cells into cancerous cells, oncogenic viruses must function at the epigenetic level to communicate with their host cells. Oncogenic viruses encode certain epigenetic factors that lead to the immortality and proliferation of infected cells. The epigenetic effectors produced by oncogenic viruses constitute appealing targets to prevent and treat malignant diseases caused by these viruses. In this review, we highlight the importance of epigenetic reprogramming for virus-induced oncogenesis, with special emphasis on viral epigenetic oncoproteins as therapeutic targets. The discovery of molecular components that target epigenetic pathways, especially viral factors, is also discussed. PMID:26754591

  5. Epigenetic modifications as new targets for liver disease therapies.

    Zeybel, Müjdat; Mann, Derek A; Mann, Jelena

    2013-12-01

    An important discovery from the human genome mapping project was that it is comprised of a surprisingly low number of genes,with recent estimates suggesting they are as few as 25,000 [1].This supported an alternative hypothesis that our complexity in comparison with lower order species is likely to be determined by regulatory mechanisms operating at levels above the fundamental DNA sequences of the genome [2]. One set of mechanisms that dictate tissue and cellular complexity can be described by the overarching term "epigenetics". In the 1940s, Conrad Waddington described epigenetics as "the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being". Today we understand epigenetics as a gene regulatory system comprised of 3 major mechanisms including DNA modifications (e.g., methylation), use of histone variants and post-translational modifications of the amino acid tails of histones and non-coding RNAs of which microRNAs are the best characterized [3,4]. Together, these mechanisms orchestrate numerous sets of chemical reactions that switch parts of the genome on and off at specific times and locations.Epigenetic marks, or the epigenome, exhibit a high degree of cellular-specificity and developmental or environmentally driven dynamic plasticity. Due to being at the interface between genome and the environment, the epigenome evolves at a very high rate compared to genetic mutations. Indeed, the differences in the epigenome account for most of the phenotypic uniqueness between closely related species, especially primates. More interestingly,the epigenetic changes, or epimutations, within an individual are not only maintained over cellular generations, but may also be transmitted between generations, such that adaptive epimutations generated in response to a particular environmental cue can influence phenotypes in our children and grandchildren [5]. PMID:23747756

  6. A Topology Reorganization Scheme for Reliable Communication in Underwater Wireless Sensor Networks Affected by Shadow Zones

    Mari Carmen Domingo

    2009-10-01

    Full Text Available Effective solutions should be devised to handle the effects of shadow zones in Underwater Wireless Sensor Networks (UWSNs. An adaptive topology reorganization scheme that maintains connectivity in multi-hop UWSNs affected by shadow zones has been developed in the context of two Spanish-funded research projects. A mathematical model has been proposed to find the optimal location for sensors with two objectives: the minimization of the transmission loss and the maintenance of network connectivity. The theoretical analysis and the numerical evaluations reveal that our scheme reduces the transmission loss under all propagation phenomena scenarios for all water depths in UWSNs and improves the signal-to-noise ratio.

  7. An Epigenetic Pathway Regulates Sensitivity of Breast Cancer Cells to HER2 Inhibition via FOXO/c-Myc Axis

    Matkar, Smita; Sharma, Paras; Gao, Shubin; Gurung, Buddha; Katona, Bryson W; Liao, Jennifer; Muhammad, Abdul Bari; Kong, Xiang-Cheng; Wang, Lei; Jin, Guanghui; Dang, Chi; Hua, Xianxin

    2016-01-01

    SUMMARY Human epidermal growth factor receptor 2 (HER2) is upregulated in a subset of human breast cancers. However, the cancer cells often quickly develop an adaptive response to HER2 kinase inhibitors. We found that an epigenetic pathway involving MLL2 is crucial for growth of HER2+ cells and MLL2 reduces sensitivity of the cancer cells to a HER2 inhibitor, Lapatinib. Lapatinib-induced FOXO transcription factors, normally tumor-suppressing, paradoxically upregulate c-Myc epigenetically, in concert with a cascade of MLL2-associating epigenetic regulators, to dampen sensitivity of the cancer cells to Lapatinib. An epigenetic inhibitor suppressing c-Myc synergizes with Lapatinib to suppress cancer growth in vivo, partly by repressing the FOXO/c-Myc axis, unraveling an epigenetically regulated FOXO/c-Myc axis as a potential target to improve therapy. PMID:26461093

  8. Natural epigenetic variation contributes to heritable flowering divergence in a widespread asexual dandelion lineage.

    Wilschut, Rutger A; Oplaat, Carla; Snoek, L Basten; Kirschner, Jan; Verhoeven, Koen J F

    2016-04-01

    Epigenetic variation has been proposed to contribute to the success of asexual plants, either as a contributor to phenotypic plasticity or by enabling transient adaptation via selection on transgenerationally stable, but reversible, epialleles. While recent studies in experimental plant populations have shown the potential for epigenetic mechanisms to contribute to adaptive phenotypes, it remains unknown whether heritable variation in ecologically relevant traits is at least partially epigenetically determined in natural populations. Here, we tested the hypothesis that DNA methylation variation contributes to heritable differences in flowering time within a single widespread apomictic clonal lineage of the common dandelion (Taraxacum officinale s. lat.). Apomictic clone members of the same apomictic lineage collected from different field sites showed heritable differences in flowering time, which was correlated with inherited differences in methylation-sensitive AFLP marker profiles. Differences in flowering between apomictic clone members were significantly reduced after in vivo demethylation using the DNA methyltransferase inhibitor zebularine. This synchronization of flowering times suggests that flowering time divergence within an apomictic lineage was mediated by differences in DNA methylation. While the underlying basis of the methylation polymorphism at functional flowering time-affecting loci remains to be demonstrated, our study shows that epigenetic variation contributes to heritable phenotypic divergence in ecologically relevant traits in natural plant populations. This result also suggests that epigenetic mechanisms can facilitate adaptive divergence within genetically uniform asexual lineages. PMID:26615058

  9. Case managers reorganize to challenge claims denials.

    1999-08-01

    A combination of diminished reimbursement, decreased funding for residency programs, an epidemic of claims denials, and the skilled nursing crisis has imperiled teaching hospitals across the country. Increasingly, these hospitals are looking to case management departments as potential saviors. In the short term, that could mean more staff and a beefier budget, but if your department can't produce, cuts later on could be drastic. The University of Pennsylvania Health System in Philadelphia lost $90 million in FY1998 and responded by cutting 1,100 positions--9% of its work force. The case management department lost eight positions and is trying to take up the slack with a massive reorganization of its care delivery system and a rigorous education program designed to reduce claims denials. At Georgetown University Medical Center in Washington, DC, however, case management staff and resources have been increased for now. The department is using its new-found prosperity to thoroughly screen all incoming patients for appropriateness of admission, upgrade its discharge planning capabilities, and hire a full-time employee to appeal denied claims. PMID:10557727

  10. The danger of epigenetics misconceptions (epigenetics and stuff…).

    Georgel, Philippe T

    2015-12-01

    Within the past two decades, the fields of chromatin structure and function and transcription regulation research started to fuse and overlap, as evidence mounted to support a very strong regulatory role in gene expression that was associated with histone post-translational modifications, DNA methylation, as well as various chromatin-associated proteins (the pillars of the "Epigenetics" building). The fusion and convergence of these complementary fields is now often simply referred to as "Epigenetics". During these same 20 years, numerous new research groups have started to recognize the importance of chromatin composition, conformation, and its plasticity. However, as the field started to grow exponentially, its growth came with the spreading of several important misconceptions, which have unfortunately led to improper or hasty conclusions. The goal of this short "opinion" piece is to attempt to minimize future misinterpretations of experimental results and ensure that the right sets of experiment are used to reach the proper conclusion, at least as far as epigenetic mechanisms are concerned. PMID:26492160

  11. Epigenetic Effects of Cannabis Exposure.

    Szutorisz, Henrietta; Hurd, Yasmin L

    2016-04-01

    The past decade has witnessed a number of societal and political changes that have raised critical questions about the long-term impact of marijuana (Cannabis sativa) that are especially important given the prevalence of its abuse and that potential long-term effects still largely lack scientific data. Disturbances of the epigenome have generally been hypothesized as the molecular machinery underlying the persistent, often tissue-specific transcriptional and behavioral effects of cannabinoids that have been observed within one's lifetime and even into the subsequent generation. Here, we provide an overview of the current published scientific literature that has examined epigenetic effects of cannabinoids. Though mechanistic insights about the epigenome remain sparse, accumulating data in humans and animal models have begun to reveal aberrant epigenetic modifications in brain and the periphery linked to cannabis exposure. Expansion of such knowledge and causal molecular relationships could help provide novel targets for future therapeutic interventions. PMID:26546076

  12. Computational micromodel for epigenetic mechanisms.

    Raghavan, Karthika

    2010-11-01

    Characterization of the epigenetic profile of humans since the initial breakthrough on the human genome project has strongly established the key role of histone modifications and DNA methylation. These dynamic elements interact to determine the normal level of expression or methylation status of the constituent genes in the genome. Recently, considerable evidence has been put forward to demonstrate that environmental stress implicitly alters epigenetic patterns causing imbalance that can lead to cancer initiation. This chain of consequences has motivated attempts to computationally model the influence of histone modification and DNA methylation in gene expression and investigate their intrinsic interdependency. In this paper, we explore the relation between DNA methylation and transcription and characterize in detail the histone modifications for specific DNA methylation levels using a stochastic approach.

  13. Longevity: epigenetic and biomolecular aspects.

    Taormina, Giusi; Mirisola, Mario G

    2015-04-01

    Many aging theories and their related molecular mechanisms have been proposed. Simple model organisms such as yeasts, worms, fruit flies and others have massively contributed to their clarification, and many genes and pathways have been associated with longevity regulation. Among them, insulin/IGF-1 plays a key and evolutionary conserved role. Interestingly, dietary interventions can modulate this pathway. Calorie restriction (CR), intermittent fasting, and protein and amino acid restriction prolong the lifespan of mammals by IGF-1 regulation. However, some recent findings support the hypothesis that the long-term effects of diet also involve epigenetic mechanisms. In this review, we describe the best characterized aging pathways and highlight the role of epigenetics in diet-mediated longevity. PMID:25883209

  14. Diabetes Mellitus and Epigenetic Mechanisms

    Bekir Engin Eser

    2016-06-01

    Full Text Available Diabetes Mellitus (DM is an important disease caused by insulin deficiency or insulin receptor resistance and characterized by hyperglycemia. The prevalence rate of DM is increasing rapidly worldwide and its associated complications affect the quality of life of patients adverse­ly. In addition, high medical costs for its treatment bring significant economic load on countries. Epigenetics is the reversible modifications on the genome, which lead to changes in gene expression without any alteration in the DNA sequence. Epigenetic modifications can easily be affected by environmental factors and abnormalities in these modifications have been linked to many diseases including cancer and neurodegenerative disorders. In this review, we will summarize the relationship of DM and its complications with DNA and RNA methylation, which are among the most important modifications.

  15. Lifestyle, pregnancy and epigenetic effects.

    Barua, Subit; Junaid, Mohammed A

    2015-01-01

    Rapidly growing evidences link maternal lifestyle and prenatal factors with serious health consequences and diseases later in life. Extensive epidemiological studies have identified a number of factors such as diet, stress, gestational diabetes, exposure to tobacco and alcohol during gestation as influencing normal fetal development. In light of recent discoveries, epigenetic mechanisms such as alteration of DNA methylation, chromatin modifications and modulation of gene expression during gestation are believed to possibly account for various types of plasticity such as neural tube defects, autism spectrum disorder, congenital heart defects, oral clefts, allergies and cancer. The purpose of this article is to review a number of published studies to fill the gap in our understanding of how maternal lifestyle and intrauterine environment influence molecular modifications in the offspring, with an emphasis on epigenetic alterations. To support these associations, we highlighted laboratory studies of rodents and epidemiological studies of human based on sampling population cohorts. PMID:25687469

  16. Treatment of recurrent nightmares by the dream reorganization approach.

    Palace, E M; Johnston, C

    1989-09-01

    Dream reorganization is introduced as a new theoretical and treatment approach to the alleviation of recurrent nightmares, derived from the principles of the Seligman and Yellen (1987) theory of dream construction. The cognitive-behavioral dream reorganization treatment package consists of two treatment components. Systematic desensitization with coping self-statements is employed to alter the emotional episode by counterconditioning a relaxation response to anxiety-evoking nightmare content. Guided rehearsal of mastery endings to dream content hierarchy items is added to modify the secondary visual stimuli associated with recurrent nightmares. The dream reorganization approach is presented in the case of a 10-year-old male with a fear of sleeping alone due to recurrent nightmares. Following treatment, the client reported 100% reduction in nightmares and demonstrated 100% reduction in night time arrival in the parents' room. The present report provides a theoretical rationale for dream reorganization, and future directions for research in the treatment of recurrent nightmares. PMID:2576657

  17. Prolonged reorganization of thiol-capped Au nanoparticles layered structures

    Sarathi Kundu

    2013-09-01

    Full Text Available Prolonged reorganization behaviour of mono-, di-, tri- and multi-layer films of Au nanoparticles prepared by Langmuir-Blodgett method on hydrophobic Si(001 substrates have been studied by using X-ray scattering techniques. Out-of-plane study shows that although at the initial stage the reorganization occurs through the compaction of the films keeping the layered structure unchanged but finally all layered structures modify to monolayer structure. Due to this reorganization the Au density increases within the nanometer thick films. In-plane study shows that inside the reorganized films Au nanoparticles are distributed randomly and the particle size modifies as the metallic core of Au nanoparticles coalesces.

  18. Epigenetic mechanisms in drug addiction

    Renthal, William; Nestler, Eric J.

    2008-01-01

    Changes in gene expression in brain reward regions are thought to contribute to the pathogenesis and persistence of drug addiction. Recent studies have begun to focus on the molecular mechanisms by which drugs of abuse and related environmental stimuli, such as drug-associated cues or stress, converge on the genome to alter specific gene programs. Increasing evidence suggests that these stable gene expression changes in neurons are mediated in part by epigenetic mechanisms that alter chromati...

  19. Epigenetic Mechanisms of Drug Addiction

    Nestler, Eric J.

    2013-01-01

    Drug addiction involves potentially life-long behavioral abnormalities that are caused in vulnerable individuals by repeated exposure to a drug of abuse. The persistence of these behavioral changes suggests that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype. Work over the past decade has demonstrated a crucial role for epigenetic mechanisms in driving lasting changes in gene expression in diverse tissues,...

  20. Epigenetics of the antibody response

    Li, Guideng; Zan, Hong; Xu, Zhenming; Casali, Paolo

    2013-01-01

    Epigenetic marks, such as DNA methylation, histone posttranslational modifications and microRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR) and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and microRNAs modulate t...

  1. Chromocentre integrity and epigenetic marks

    Harničarová, Andrea; Galiová-Šustáčková, Gabriela; Legartová, Soňa; Kozubek, Stanislav; Matula, P.; Bártová, Eva

    2010-01-01

    Roč. 169, č. 1 (2010), s. 124-133. ISSN 1047-8477 R&D Projects: GA MŠk ME 919; GA MŠk(CZ) LC06027; GA MŠk(CZ) LC535 Grant ostatní: GA MŠk(CZ) ME919 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : SUV39h * histone methylation * epigenetics Subject RIV: BO - Biophysics Impact factor: 3.497, year: 2010

  2. Stemming Epigenetics in Marine Stramenopiles

    Maumus, Florian; Rabinowicz, Pablo; Bowler, Chris; Rivarola, Maximo

    2011-01-01

    Epigenetics include DNA methylation, the modification of histone tails that affect chromatin states, and small RNAs that are involved in the setting and maintenance of chromatin modifications. Marine stramenopiles (MAS), which are a diverse assemblage of algae that acquired photosynthesis from secondary endosymbiosis, include single-celled organisms such as diatoms as well as multicellular forms such as brown algae. The recent publication of two diatom genomes that diverged ~90 million years ...

  3. Epigenetic changes in tumor microenvironment

    P Dey

    2011-01-01

    Full Text Available The drama of cancer is not the solo performance of the malignant cells. Microenvironment of the tumor has significant contribution in carcinogenesis. Recent evidences show distinct gene promoter methylation in stromal cells of various malignant and pre-malignant tumors. These changes probably create unique tumor microenvironment, which is responsible for initiation, proliferation, invasion, and metastasis of tumor cells. In this mini review the role of epigenetic changes of tumor microenvironment in carcinogenesis has been discussed.

  4. An Analysis of the Bankruptcy Reorganization Procedure in China

    Fei Leng

    2013-01-01

    This paper analyzes the reorganization procedure introduced into the Chinese bankruptcy system in 2007. It shows that managers devote more effort during the reorganization than before the bankruptcy when the emergence value of the bankrupt firm is substantial. In addition, in the pre-bankruptcy period, managers were shown to input less effort under the new law than under the old law. Finally, the paper demonstrates that the market interest rate under the new bankruptcy law is not necessarily ...

  5. Functional reorganization of sensorimotor cortex in early Parkinson disease.

    Kojovic, M.; Bologna, M; Kassavetis, P.; Murase, N.; Palomar, F. J.; Berardelli, A; Rothwell, J C; Edwards, M. J.; Bhatia, K P

    2012-01-01

    OBJECTIVE: Compensatory reorganization of the nigrostriatal system is thought to delay the onset of symptoms in early Parkinson disease (PD). Here we sought evidence that compensation may be a part of a more widespread functional reorganization in sensorimotor networks, including primary motor cortex. METHODS: Several neurophysiologic measures known to be abnormal in the motor cortex (M1) of patients with advanced PD were tested on the more and less affected side of 16 newly diagnosed and dru...

  6. Targeting DNA Methylation for Epigenetic Therapy

    Yang, Xiaojing; Lay, Fides; Han, Han; Jones, Peter A.

    2010-01-01

    DNA methylation patterns are established during embryonic development and faithfully copied through somatic cell divisions. Based on our understanding of DNA methylation and other interrelated epigenetic modifications, a comprehensive view of the epigenetic landscape and cancer epigenome is evolving. The cancer methylome is highly disrupted, making DNA methylation an excellent target for anti-cancer therapies. During the last few decades, an increasing number of drugs targeting DNA methylation have been developed in an effort to increase efficacy, stability and to decrease toxicity. The earliest and the most successful epigenetic drug to date, 5-Azacytidine, is currently recommended as the first-line treatment for high risk myelodysplastic syndromes (MDS) patients. Encouraging results from clinical trials have prompted further efforts to elucidate epigenetic alterations in cancer and subsequently develop new epigenetic therapies. This review delineates the latest cancer epigenetic models, recent discovery of hypomethylation agents and their application in the clinic. PMID:20846732

  7. Epigenetic alterations of sedimentary rocks at deposits

    Notions are explained, and technique for studying epigenetic alterations of sedimentary rocks at uranium deposits is described. Main types of epigenetic transformations and their mineralogic-geochemical characteristics are considered. Rock alterations, accompanying uranium mineralization, can be related to 2 types: oxidation and reduction. The main mineralogic-geochemical property of oxidation transformations is epigenetic limonitization. Stratal limonitization in primary grey-coloured terrigenic rocks and in epigenetically reduced (pyritized) rocks, as well as in rock, subjected to epigenetic gleying, are characterized. Reduction type of epigenetic transformations is subdivided into sulphidic and non-sulphidic (gley) subtypes. Sulphidic transformations in grey-coloured terrigenic rocks with organic substance of carbonic row, in rocks, containing organic substance of oil row, sulphide transformations of sedimentary rocks, as well as gley transformations, are considered

  8. Environmental epigenetics and allergic diseases: Recent advances

    Kuriakose, Julie S; Miller, Rachel L.

    2010-01-01

    Significant strides in the understanding of the role of epigenetic regulation in asthma and allergy using both epidemiological approaches as well as experimental ones have been made. This review focuses on new research within the last two years. These include advances in determining how environmental agents implicated in airway disease can induce epigenetic changes, how epigenetic regulation can influence T helper cell (Th) differentiation and T regulatory (Treg) cell production, and new disc...

  9. Epigenetic impact of curcumin on stroke prevention

    Kalani, Anuradha; Kamat, Pradip K.; Kalani, Komal; Tyagi, Neetu

    2014-01-01

    The epigenetic impact of curcumin in stroke and neurodegenerative disorders is curiosity-arousing. It is derived from Curcuma longa (spice), possesses anti-oxidative, anti-inflammatory, anti-lipidemic, neuro-protective and recently shown to exhibit epigenetic modulatory properties. Epigenetic studies include DNA methylation, histone modifications and RNA-based mechanisms which regulate gene expression without altering nucleotide sequences. Curcumin has been shown to affect cancer by altering ...

  10. Epigenetics and the power of art

    Karlic, Heidrun; Baurek, Pia

    2011-01-01

    This review presents an epigenetic view on complex factors leading to development and perception of “genius.” There is increasing evidence which indicates that artistic creativity is influenced by epigenetic processes that act both as targets and mediators of neurotransmitters as well as steroid hormones. Thus, perception and production of art appear to be closely associated with epigenetic contributions to physical and mental health.

  11. Interindividual variability in stress susceptibility: A role for epigenetic mechanisms in PTSD

    J.DavidSweatt

    2013-06-01

    Full Text Available Post-traumatic stress disorder (PTSD is a psychiatric condition characterized by intrusive and persistent memories of a psychologically traumatic event that leads to significant functional and social impairment in affected individuals. The molecular bases underlying persistent outcomes of a transient traumatic event have remained elusive for many years, but recent studies in rodents have implicated epigenetic modifications of chromatin structure and DNA methylation as fundamental mechanisms for the induction and stabilization of fear memory. In addition to mediating adaptations to traumatic events that ultimately cause PTSD, epigenetic mechanisms are also involved in establishing individual differences in PTSD risk and resilience by mediating long-lasting effects of genes and early environment on adult function and behavior. In this review, we discuss the current evidence for epigenetic regulation of PTSD in human studies and in animal models and comment on ways in which these models can be expanded. In addition, we identify key outstanding questions in the study of epigenetic mechanisms of PTSD in the context of rapidly evolving technologies that are constantly updating and adjusting our understanding of epigenetic modifications and their functional roles. Finally, we discuss the potential application of epigenetic approaches in identifying markers of risk and resilience that can be utilized to promote early intervention and develop therapeutic strategies to combat PTSD after symptom onset.

  12. Epigenetic regulatory mechanisms associated with infertility

    Minocherhomji, Sheroy; Madon, Prochi F; Parikh, Firuza R

    2010-01-01

    Infertility is a complex human condition and is known to be caused by numerous factors including genetic alterations and abnormalities. Increasing evidence from studies has associated perturbed epigenetic mechanisms with spermatogenesis and infertility. However, there has been no consensus...... on whether one or a collective of these altered states is responsible for the onset of infertility. Epigenetic alterations involve changes in factors that regulate gene expression without altering the physical sequence of DNA. Understanding these altered epigenetic states at the genomic level along...... with the phenotype could further determine what possible mechanisms are involved. This paper reviews certain mechanisms of epigenetic regulation with particular emphasis on their possible role in infertility....

  13. Transcriptome analysis of human primary endothelial cells (HUVEC) from umbilical cords of gestational diabetic mothers reveals candidate sites for an epigenetic modulation of specific gene expression.

    Ambra, R; Manca, S; Palumbo, M C; Leoni, G; Natarelli, L; De Marco, A; Consoli, A; Pandolfi, A; Virgili, F

    2014-01-01

    Within the complex pathological picture associated to diabetes, high glucose (HG) has "per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG. PMID:24667242

  14. Cocaine triggers epigenetic alterations in the corticostriatal circuit.

    Sadri-Vakili, Ghazaleh

    2015-12-01

    Acute and repeated exposure to cocaine induces long-lasting alterations in neural networks that underlie compulsive drug seeking and taking. Cocaine exposure triggers complex adaptations in the brain that are mediated by dynamic patterns of gene expression that are translated into enduring changes. Recently, epigenetic modifications have been unveiled as critical mechanisms underlying addiction that contribute to drug-induced plasticity by regulating gene expression. These alterations are also now linked to the heritability of cocaine-induced phenotypes. This review focuses on how changes in the epigenome, such as altered DNA methylation, histone modifications, and microRNAs, regulate transcription of specific genes that contribute to cocaine addiction. PMID:25301690

  15. Heritable epigenetic variation among maize inbreds.

    Steve R Eichten

    2011-11-01

    Full Text Available Epigenetic variation describes heritable differences that are not attributable to changes in DNA sequence. There is the potential for pure epigenetic variation that occurs in the absence of any genetic change or for more complex situations that involve both genetic and epigenetic differences. Methylation of cytosine residues provides one mechanism for the inheritance of epigenetic information. A genome-wide profiling of DNA methylation in two different genotypes of Zea mays (ssp. mays, an organism with a complex genome of interspersed genes and repetitive elements, allowed the identification and characterization of examples of natural epigenetic variation. The distribution of DNA methylation was profiled using immunoprecipitation of methylated DNA followed by hybridization to a high-density tiling microarray. The comparison of the DNA methylation levels in the two genotypes, B73 and Mo17, allowed for the identification of approximately 700 differentially methylated regions (DMRs. Several of these DMRs occur in genomic regions that are apparently identical by descent in B73 and Mo17 suggesting that they may be examples of pure epigenetic variation. The methylation levels of the DMRs were further studied in a panel of near-isogenic lines to evaluate the stable inheritance of the methylation levels and to assess the contribution of cis- and trans- acting information to natural epigenetic variation. The majority of DMRs that occur in genomic regions without genetic variation are controlled by cis-acting differences and exhibit relatively stable inheritance. This study provides evidence for naturally occurring epigenetic variation in maize, including examples of pure epigenetic variation that is not conditioned by genetic differences. The epigenetic differences are variable within maize populations and exhibit relatively stable trans-generational inheritance. The detected examples of epigenetic variation, including some without tightly linked genetic

  16. Epigenetic Therapy in Human Choriocarcinoma

    Takai, Noriyuki, E-mail: takai@oita-u.ac.jp [Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita (Japan); Narahara, Hisashi [Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593 (Japan)

    2010-09-10

    Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in choriocarcinomas, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. HDAC inhibitors (HDACIs) were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in choriocarcinoma cell lines. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating choriocarcinoma, with a special focus on preclinical studies.

  17. Epigenetic Therapy in Human Choriocarcinoma

    Hisashi Narahara

    2010-09-01

    Full Text Available Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in choriocarcinomas, novel compounds endowed with a histone deacetylase (HDAC inhibitory activity are an attractive therapeutic approach. HDAC inhibitors (HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in choriocarcinoma cell lines. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating choriocarcinoma, with a special focus on preclinical studies.

  18. Epigenetic Therapy in Human Choriocarcinoma

    Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in choriocarcinomas, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. HDAC inhibitors (HDACIs) were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in choriocarcinoma cell lines. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating choriocarcinoma, with a special focus on preclinical studies

  19. [Epigenetics of childhood obesity and diabetes].

    Valladares-Salgado, Adán; Suárez-Sánchez, Fernando; Burguete-García, Ana I; Cruz, Miguel

    2014-01-01

    Obesity and type 2 diabetes mellitus (T2DM) result from sedentary lifestyle, high-carbohydrate diets and genetic predisposition. Epigenetics is a form of genetic regulation in specialized cells that does not involve changes in the deoxyribonucleic acid (DNA) sequence, but it can be inherited to one or more generations through mitosis or meiosis. Children whose mothers develop gestational diabetes are more likely to become obese and diabetic in adult life. DNA methylation is a major mechanism in the regulation of transcription and gene expression of several genes. High levels of glucose and insulin during pregnancy modify the risk of developing T2DM, suggesting that the expression pattern is modified due to cell memory in a specific tissue. If T2DM is linked to adaptation in utero, the obvious primary prevention is to protect the fetal development. Future epidemiological studies need to employ more accurate indicators or markers of development to show the relationship between a specific disease and the exposure to environmental factors. The mechanisms by which malnutrition, and intrauterine growth retardation produce changes in the metabolism of glucose and insuline are worth to explore in order to control obesity and T2DM. PMID:24866314

  20. Reorganization of neuronal circuits in growing visual cortex

    Keil, Wolfgang; Loewel, Siegrid; Wolf, Fred; Kaschube, Matthias

    2009-03-01

    The dynamics of reorganization of large cortical circuits is rooted in plasticity of individual synapses, but rules governing the collective behavior of large networks of neurons are only poorly understood. The postnatal brain growth partly evoked by extensive formation of new synaptic connections may expose cortical areas to a 'natural perturbation' sufficiently strong to observe signatures of large scale reorganization. Quantifying large sets of imaging data from juvenile cat visual cortex, we observe a novel mode of reorganization of domains that prefer inputs from one eye or the other. Our theoretical analysis shows that this mode can be explained quantitatively by the so called Zigzag instability, a dynamical reorganization, well-known in the field of pattern formation in physics, by which 2D isotropic Turing patterns respond to an increase in their typical spatial scale with a zigzag-like bending of domains. We point out that this instability has in fact been predicted, albeit implicitly, by most models of visual cortical development that have been proposed so far. We conclude that cortical networks can undergo large scale reorganizations during normal postnatal development.

  1. On the origin of sperm epigenetic heterogeneity.

    Laurentino, Sandra; Borgmann, Jennifer; Gromoll, Jörg

    2016-05-01

    The influence of epigenetic modifications on reproduction and on the function of male germ cells has been thoroughly demonstrated. In particular, aberrant DNA methylation levels in sperm have been associated with abnormal sperm parameters, lower fertilization rates and impaired embryo development. Recent reports have indicated that human sperm might be epigenetically heterogeneous and that abnormal DNA methylation levels found in the sperm of infertile men could be due to the presence of sperm populations with different epigenetic quality. However, the origin and the contribution of different germ cell types to this suspected heterogeneity remain unclear. In this review, we focus on sperm epigenetics at the DNA methylation level and its importance in reproduction. We take into account the latest developments and hypotheses concerning the functional significance of epigenetic heterogeneity coming from the field of stem cell and cancer biology and discuss the potential importance and consequences of sperm epigenetic heterogeneity for reproduction, male (in)fertility and assisted reproductive technologies (ART). Based on the current information, we propose a model in which spermatogonial stem cell variability, either intrinsic or due to external factors (such as endocrine action and environmental stimuli), can lead to epigenetic sperm heterogeneity, sperm epimutations and male infertility. The elucidation of the precise causes for epimutations, the conception of adequate therapeutic options and the development of sperm selection technologies based on epigenetic quality should be regarded as crucial to the improvement of ART outcome in the near future. PMID:26884419

  2. Epigenetics in mammary gland biology and cancer

    In the post genome era, the focus has shifted to understanding the mechanisms that regulate the interpretation of the genetic code. "Epigenetics" as a research field is taking center stage. Epigenetics is a term which is now being used throughout the scientific community in different contexts from p...

  3. Epigenetics and environmental impacts in cattle

    This chapter reviews the major advances in the field of epigenetics as well as the environmental impacts of cattle. Many findings from our own research endeavors related to the topic of this chapter are also introduced. The phenotypic characterization of an animal can be changed through epigenetic ...

  4. Epigenetics, estradiol, and hippocampal memory consolidation

    Frick, Karyn M.

    2013-01-01

    Epigenetic alterations of histone proteins and DNA are essential for hippocampal synaptic plasticity and cognitive function, and contribute to the etiology of psychiatric disorders and neurodegenerative diseases. Hippocampal memory formation depends on histone alterations and DNA methylation, and increasing evidence suggests that regulation of these epigenetic processes by modulatory factors such as environmental enrichment, stress, and hormones substantially influences memory function. Recen...

  5. Orchestrating epigenetic roles targeting ocular tumors

    Wen X

    2016-02-01

    Full Text Available Xuyang Wen*, Linna Lu*, He Zhang, Xianqun Fan Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Epigenetics is currently one of the most promising areas of study in the field of biomedical research. Scientists have dedicated their efforts to studying epigenetic mechanisms in cancer for centuries. Additionally, the field has expanded from simply studying DNA methylation to other areas, such as histone modification, non-coding RNA, histone variation, nucleosome location, and chromosome remodeling. In ocular tumors, a large amount of epigenetic exploration has expanded from single genes to the genome-wide level. Most importantly, because epigenetic changes are reversible, several epigenetic drugs have been developed for the treatment of cancer. Herein, we review the current understanding of epigenetic mechanisms in ocular tumors, including but not limited to retinoblastoma and uveal melanoma. Furthermore, the development of new pharmacological strategies is summarized. Keywords: ocular tumors, epigenetics, retinoblastoma, uveal melanoma, epigenetic drugs

  6. Epigenetic regulation of skeletal muscle metabolism.

    Howlett, Kirsten F; McGee, Sean L

    2016-07-01

    Normal skeletal muscle metabolism is essential for whole body metabolic homoeostasis and disruptions in muscle metabolism are associated with a number of chronic diseases. Transcriptional control of metabolic enzyme expression is a major regulatory mechanism for muscle metabolic processes. Substantial evidence is emerging that highlights the importance of epigenetic mechanisms in this process. This review will examine the importance of epigenetics in the regulation of muscle metabolism, with a particular emphasis on DNA methylation and histone acetylation as epigenetic control points. The emerging cross-talk between metabolism and epigenetics in the context of health and disease will also be examined. The concept of inheritance of skeletal muscle metabolic phenotypes will be discussed, in addition to emerging epigenetic therapies that could be used to alter muscle metabolism in chronic disease states. PMID:27215678

  7. Peromyscus as a Mammalian Epigenetic Model

    Kimberly R. Shorter

    2012-01-01

    Full Text Available Deer mice (Peromyscus offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential.

  8. Epigenetic field cancerization in gastrointestinal cancers.

    Baba, Yoshifumi; Ishimoto, Takatsugu; Kurashige, Junji; Iwatsuki, Masaaki; Sakamoto, Yasuo; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

    2016-06-01

    Epigenetic alterations, including aberrant DNA methylation, play an important role in human cancer development. Importantly, epigenetic alterations are reversible and can be targets for therapy or chemoprevention for various types of human cancers. A field for cancerization, or a field defect, is formed by the accumulation of genetic and/or epigenetic alterations in normal-appearing tissues and can correlate with risk of cancer development. Thus, a better understanding of epigenetic field cancerization may represent a useful translational opportunity for cancer risk assessment, including previous history and exposure to carcinogenic factors, and for cancer prevention. In this article, we summarize current knowledge regarding epigenetic field cancerization and its clinical implications in gastrointestinal cancers, including colorectal cancer, gastric cancer and esophageal cancer. PMID:26971491

  9. Daphnia as an Emerging Epigenetic Model Organism

    Kami D. M. Harris

    2012-01-01

    Full Text Available Daphnia offer a variety of benefits for the study of epigenetics. Daphnia’s parthenogenetic life cycle allows the study of epigenetic effects in the absence of confounding genetic differences. Sex determination and sexual reproduction are epigenetically determined as are several other well-studied alternate phenotypes that arise in response to environmental stressors. Additionally, there is a large body of ecological literature available, recently complemented by the genome sequence of one species and transgenic technology. DNA methylation has been shown to be altered in response to toxicants and heavy metals, although investigation of other epigenetic mechanisms is only beginning. More thorough studies on DNA methylation as well as investigation of histone modifications and RNAi in sex determination and predator-induced defenses using this ecologically and evolutionarily important organism will contribute to our understanding of epigenetics.

  10. Epigenetic reprogramming in the porcine germ line

    Matzen, Sara Maj Hyldig; Croxall, Nicola; Contreras, David A.;

    2011-01-01

    BACKGROUND: Epigenetic reprogramming is critical for genome regulation during germ line development. Genome-wide demethylation in mouse primordial germ cells (PGC) is a unique reprogramming event essential for erasing epigenetic memory and preventing the transmission of epimutations to the next...... an increased proportion of cells in G2. CONCLUSIONS: Our study demonstrates that epigenetic reprogramming occurs in pig migratory and gonadal PGC, and establishes the window of time for the occurrence of these events. Reprogramming of histone H3K9me2 and H3K27me3 detected between E15-E21 precedes the dynamic...... DNA demethylation at imprinted loci and DNA repeats between E22-E42. Our findings demonstrate that major epigenetic reprogramming in the pig germ line follows the overall dynamics shown in mice, suggesting that epigenetic reprogramming of germ cells is conserved in mammals. A better understanding...

  11. Deprivation-induced cortical reorganization in children with cochlear implants.

    Sharma, Anu; Gilley, Phillip M; Dorman, Michael F; Baldwin, Robert

    2007-09-01

    A basic finding in developmental neurophysiology is that some areas of the cortex cortical areas will reorganize following a period of stimulus deprivation. In this review, we discuss mainly electroencephalography (EEG) studies of normal and deprivation-induced abnormal development of the central auditory pathways in children and in animal models. We describe age cut-off for sensitive periods for central auditory development in congenitally deaf children who are fitted with a cochlear implant. We speculate on mechanisms of decoupling and reorganization which may underlie the end of the sensitive period. Finally, we describe new magentoencephalography (MEG) evidence of somatosensory cross-modal plasticity following long-term auditory deprivation. PMID:17828665

  12. Biotechnology approach to determination of genetic and epigenetic control in cells

    Yasuda Kenji

    2004-11-01

    Full Text Available Abstract A series of studies aimed at developing methods and systems for analyzing epigenetic information in cells are presented. The role of the epigenetic information of cells, which is complementary to their genetic information, was inferred by comparing the predictions of genetic information with the cell behaviour observed under conditions chosen to reveal adaptation processes and community effects. Analysis of epigenetic information was developed starting from the twin complementary viewpoints of cells regulation as an 'algebraic' system (emphasis on the temporal aspect and as a 'geometric' system (emphasis on the spatial aspect. The knowlege acquired from this study will lead to the use of cells for fully controlled practical applications like cell-based drug screening and the regeneration of organs.

  13. Prostate cancer epigenetics and its clinical implications.

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

  14. Prostate cancer epigenetics and its clinical implications

    Srinivasan Yegnasubramanian

    2016-01-01

    Full Text Available Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  15. Cancer Control and Prevention by Nutrition and Epigenetic Approaches

    Verma, Mukesh

    2012-01-01

    Significance: Epigenetics involves alterations in gene expression without changing the nucleotide sequence. Because some epigenetic changes can be reversed chemically, epigenetics has tremendous implications for disease intervention and treatment. Recent Advances: After epigenetic components in cancer were characterized, genes and pathways are being characterized in other diseases such as diabetes, obesity, and neurological disorders. Observational, experimental, and clinical studies in diffe...

  16. Evolution or adaptation? What do heritable adaptive changes imply?

    M. Kemal Irmak

    2014-02-01

    Full Text Available Interactions between environmental factors and epigenetic inheritance system produce a great deal of variation from one geographic region to another in human craniofacial morphology, skin color, hair form, stature and body proportions. In this system, while environmental factors produce modifications in the body, they simultaneously induce long-term epigenetic modifications in the germ cells that are inherited to offspring. This kind of heritable changes is called biological adaptation. It was previously reported that biological adaptation is limited to neural crest derivatives such as craniofacial tissues, melanocytes, and structures related to hair form, stature and body proportions. Thus, inheritance of adaptive changes is limited to a number of traits and species-to-species evolution seems unlikely. [J Exp Integr Med 2014; 4(1.000: 13-16

  17. Epigenetic Regulation of Cholesterol Homeostasis

    Steve eMeaney

    2014-09-01

    Full Text Available Although best known as a risk factor for cardiovascular disease, cholesterol is a vital component of all mammalian cells. In addition to key structural roles, cholesterol is a vital biochemical precursor for numerous biologically important compounds including oxysterols and bile acids, as well as acting as an activator of critical morphogenic systems (e.g. the Hedgehog system. A variety of sophisticated regulatory mechanisms interact to coordinate the overall level of cholesterol in cells, tissues and the entire organism. Accumulating evidence indicates that in additional to the more ‘traditional’ regulatory schemes, cholesterol homeostasis is also under the control of epigenetic mechanisms such as histone acetylation and DNA methylation. The available evidence supporting a role for these mechanisms in the control of cholesterol synthesis, elimination, transport and storage are the focus of this review.

  18. Ancient evolutionary origins of epigenetic regulation associated with posttraumatic stress disorder

    Monica Uddin

    2014-05-01

    Full Text Available Epigenetic marks, including DNA methylation, are modifiable molecular factors that may underlie mental disorders, especially responses to trauma, including the development of and resilience to posttraumatic stress disorder (PTSD. Previous work has identified differential DNA methylation at CpG dinucleotide sites genomewide between trauma exposed individuals with and without PTSD, suggesting a role for epigenetic potential – the capacity to epigenetically regulate behavior and physiology in response to lived experiences. The human species is characterized by an increased period of adaptive plasticity during brain development. The evolutionary history of epigenetic potential in relation to adaptive plasticity is currently unknown. Using phylogenetic methods and functional annotation analyses, we trace the evolution of over 7,000 CpG dinucleotides, including 203 associated with PTSD, during the descent of humans in during mammalian evolution and characterize the biological significance of this evolution. We demonstrate that few (7% PTSD-associated CpG sites are unique to humans, while the vast majority of sites have deep evolutionary origins: 73% and 93% were unambiguously present in the last common ancestor of humans/orangutans and humans/chimpanzees, respectively. Genes proximal to evolved PTSD-associated CpG sites revealed significant enrichment for immune function during recent human evolution and regulation of gene expression during more ancient periods of human evolution. Additionally, 765 putative transcription factor binding sites (TFBS were identified that overlap with PTSD-associated CpG sites. Elucidation of the evolutionary history of PTSD-associated CpG sites may provide insights into the function and origin of epigenetic potential in trauma responses, generally, and PTSD, specifically. The human capacity to respond to trauma with stable physiologic and behavioral changes may be due to epigenetic potentials that are shared among many

  19. Epigenetic reprogramming in plant sexual reproduction.

    Kawashima, Tomokazu; Berger, Frédéric

    2014-09-01

    Epigenetic reprogramming consists of global changes in DNA methylation and histone modifications. In mammals, epigenetic reprogramming is primarily associated with sexual reproduction and occurs during both gametogenesis and early embryonic development. Such reprogramming is crucial not only to maintain genomic integrity through silencing transposable elements but also to reset the silenced status of imprinted genes. In plants, observations of stable transgenerational inheritance of epialleles have argued against reprogramming. However, emerging evidence supports that epigenetic reprogramming indeed occurs during sexual reproduction in plants and that it has a major role in maintaining genome integrity and a potential contribution to epiallelic variation. PMID:25048170

  20. Epigenetic variation during the adult lifespan

    Talens, Rudolf P; Christensen, Kaare; Putter, Hein;

    2012-01-01

    The accumulation of epigenetic changes was proposed to contribute to the age-related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged 18-89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass......-related increase in methylation variation was generally attributable to unique environmental factors, except for CRH, for which familial factors may play a more important role. In conclusion, sustained epigenetic differences arise from early adulthood to old age and contribute to an increasing discordance of MZ...

  1. Erwin Schroedinger, Francis Crick and epigenetic stability

    Ogryzko, Vasily

    2007-01-01

    Schroedinger's book 'What is Life?' is widely credited for having played a crucial role in development of molecular and cellular biology. My essay revisits the issues raised by this book from the modern perspective of epigenetics and systems biology. I contrast two classes of potential mechanisms of epigenetic stability: 'epigenetic templating' and 'systems biology' approaches, and consider them from the point of view expressed by Schroedinger. I also discuss how quantum entanglement, a nonclassical feature of quantum mechanics, can help to address the 'problem of small numbers' that lead Schroedinger to promote the idea of molecular code-script for explanation of stability of biological order.

  2. Epigenetic reprogramming in mammalian nuclear transfer

    LI Shijie; DU Weihua; LI Ning

    2004-01-01

    Somatic cloning has been succeeded in some species, but the cloning efficiency is very low, which limits the application of the technique in many areas of research and biotechnology. The cloning of mammals by somatic cell nuclear transfer (NT) requires epigenetic reprogramming of the differentiated state of donor cell to a totipotent, embryonic ground state. Accumulating evidence indicates that incomplete or inappropriate epigenetic reprogramming of donor nuclei is likely to be the primary cause of failures in nuclear transfer. This review summarizes the roles of various epigenetic mechanisms, including DNA methylation, histone acetylation, imprinting, X-chromosome inactivation, telomere maintenance and expressions of development-related genes on somatic nuclear transfer.

  3. 12 CFR 5.32 - Expedited procedures for certain reorganizations.

    2010-01-01

    ... at 12 CFR part 11. (2) Any applicant not subject to the registration provisions of the Securities..., POLICIES, AND PROCEDURES FOR CORPORATE ACTIVITIES Expansion of Activities § 5.32 Expedited procedures for... changes to the bank's business plan resulting from the reorganization. (3) Financial and...

  4. Expediting Scientific Data Analysis with Reorganization of Data

    Byna, Surendra; Wu, Kesheng

    2013-08-19

    Data producers typically optimize the layout of data files to minimize the write time. In most cases, data analysis tasks read these files in access patterns different from the write patterns causing poor read performance. In this paper, we introduce Scientific Data Services (SDS), a framework for bridging the performance gap between writing and reading scientific data. SDS reorganizes data to match the read patterns of analysis tasks and enables transparent data reads from the reorganized data. We implemented a HDF5 Virtual Object Layer (VOL) plugin to redirect the HDF5 dataset read calls to the reorganized data. To demonstrate the effectiveness of SDS, we applied two parallel data organization techniques: a sort-based organization on a plasma physics data and a transpose-based organization on mass spectrometry imaging data. We also extended the HDF5 data access API to allow selection of data based on their values through a query interface, called SDS Query. We evaluated the execution time in accessing various subsets of data through existing HDF5 Read API and SDS Query. We showed that reading the reorganized data using SDS is up to 55X faster than reading the original data.

  5. Reorganization of AECL and the future marketing program

    Atomic Energy of Canada Ltd. Engineering Co. has been reorganized to support the new emphasis on foreign sales of CANDU reactors. Much has been learned from reactor sales to Argentina, Korea, and Romania, but Canada needs to sell one 600 MWe reactor a year in order to avoid a decline in its nuclear industry. (LL)

  6. SUPPLY REORGANIZATION IN THE SOUTHERN POLAND POWER CONCERN

    Janusz Grabara

    2008-01-01

    The paper presents problems of procurement and supply materials to power plants in case of merger of a few plant in one power concern. The author present the analysis of present situation and proposals of supply reorganization considering technical and organizational problems.

  7. 16 CFR 802.10 - Stock dividends and splits; reorganizations.

    2010-01-01

    ... INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 EXEMPTION RULES § 802.10 Stock dividends and splits; reorganizations. (a) The acquisition of voting securities pursuant to a stock split or... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Stock dividends and splits;...

  8. Simulating Dynamics: Using Role-Playing to Teach the Process of Bankruptcy Reorganization.

    Fry, Patricia Brumfield

    1987-01-01

    A course focusing on bankruptcy reorganization uses simulation and role-playing to increase the depth and speed of students' comprehension of the substantive concepts inherent in reorganization proceedings and their place in the process. (MSE)

  9. Final Report - Epigenetics of low dose radiation effects in an animal model

    Kovalchuk, Olga

    2014-10-22

    This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis of induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low

  10. Dubbing SAGA unveils new epigenetic crosstalk.

    Pijnappel, W W M Pim; Timmers, H Th Marc

    2008-02-01

    In a recent issue of Molecular Cell, two independent studies (Zhang et al., 2008; Zhao et al., 2008) provide compelling evidence that targeted deubiquitylation of histones is intimately linked to transcription activation, epigenetic regulation, and cancer progression. PMID:18243109

  11. MicroRNAs, epigenetics and disease

    Silahtaroglu, Asli; Stenvang, Jan

    2010-01-01

    Epigenetics is defined as the heritable chances that affect gene expression without changing the DNA sequence. Epigenetic regulation of gene expression can be through different mechanisms such as DNA methylation, histone modifications and nucleosome positioning. MicroRNAs are short RNA molecules...... which do not code for a protein but have a role in post-transcriptional silencing of multiple target genes by binding to their 3' UTRs (untranslated regions). Both epigenetic mechanisms, such as DNA methylation and histone modifications, and the microRNAs are crucial for normal differentiation......, development and maintenance of tissue-specific gene expression. These mechanisms also explain how cells with the same DNA content can differentiate into cells with different functions. Changes in epigenetic processes can lead to changes in gene function, cancer formation and progression, as well as other...

  12. Epigenetic variation, phenotypic heritability, and evolution

    Furrow, Robert E.; Christiansen, Freddy Bugge; Feldman, Marcus W.

    2014-01-01

    families. The potential importance of this interaction, recognized in classical studies of the genetic epidemiology of complex diseases and other quantitative characters, has reemerged in studies of the effects of epigenetic modifications, their variation, and their transmission between generations....

  13. Glucocorticoids, epigenetic control and stress resilience

    Reul, Johannes M.H.M.; Collins, Andrew; Saliba, Richard S.; Mifsud, Karen R.; Carter, Sylvia D.; Gutierrez-Mecinas, Maria; Qian, Xiaoxiao; Linthorst, Astrid C.E.

    2014-01-01

    Glucocorticoid hormones play a pivotal role in the response to stressful challenges. The surge in glucocorticoid hormone secretion after stress needs to be tightly controlled with characteristics like peak height, curvature and duration depending on the nature and severity of the challenge. This is important as chronic hyper- or hypo-responses are detrimental to health due to increasing the risk for developing a stress-related mental disorder. Proper glucocorticoid responses to stress are critical for adaptation. Therefore, the tight control of baseline and stress-evoked glucocorticoid secretion are important constituents of an organism's resilience. Here, we address a number of mechanisms that illustrate the multitude and complexity of measures safeguarding the control of glucocorticoid function. These mechanisms include the control of mineralocorticoid (MR) and glucocorticoid receptor (GR) occupancy and concentration, the dynamic control of free glucocorticoid hormone availability by corticosteroid-binding globulin (CBG), and the control exerted by glucocorticoids at the signaling, epigenetic and genomic level on gene transcriptional responses to stress. We review the beneficial effects of regular exercise on HPA axis and sleep physiology, and cognitive and anxiety-related behavior. Furthermore, we describe that, possibly through changes in the GABAergic system, exercise reduces the impact of stress on a signaling pathway specifically in the dentate gyrus that is strongly implicated in the behavioral response to that stressor. These observations underline the impact of life style on stress resilience. Finally, we address how single nucleotide polymorphisms (SNPs) affecting glucocorticoid action can compromise stress resilience, which becomes most apparent under conditions of childhood abuse.

  14. The C. elegans CSR-1 Argonaute pathway counteracts epigenetic silencing to promote germline gene expression

    Seth, Meetu; Shirayama, Masaki; Gu, Weifeng; Ishidate, Takao; Conte, Darryl; Mello, Craig C

    2013-01-01

    Organisms can develop adaptive sequence-specific immunity by re-expressing pathogen-specific small RNAs that guide gene silencing. For example, the C. elegans PIWI-Argonaute/piRNA pathway recruits RNA-dependent RNA polymerase RdRP to foreign sequences to amplify a trans-generational small RNA-induced epigenetic silencing signal (termed RNAe). Here we provide evidence that in addition to an adaptive memory of silenced sequences, C. elegans can also develop an opposing adaptive memory of expres...

  15. From Neo-Darwinism to Epigenetic Inheritance

    Axholm, Ida; Ranum, Kasper; Al-Makdisi Razeeghi, Redaa

    2014-01-01

    Transgenerational epigenetic inheritance is at variance with the neo-Darwinian theory of inheritance, and this possibly has important implications for how we view evolution, since it could allow for a kind of inheritance of acquired characteristics. We have applied Imre Lakatos and Thomas Kuhn’s models of scientific change and investigated if they can accurately describe the change in the view on inheritance from neo-Darwinism to a view that includes transgenerational epigenetic inheritance, ...

  16. Epigenetic Mechanisms of Facioscapulohumeral Muscular Dystrophy

    de Greef, Jessica C; Frants, Rune R; van der Maarel, Silvère M.

    2008-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) seems to be caused by a complex epigenetic disease mechanism as a result of contraction of the polymorphic macrosatellite repeat D4Z4 on chromosome 4qter. Currently, the exact mechanism causing the FSHD phenotype is still not elucidated. In this review, we discuss the genetic and epigenetic changes observed in patients with FSHD and the possible disease mechanisms that may be associated with FSHD pathogenesis.

  17. Environmental stress and epigenetic transgenerational inheritance

    Skinner, Michael K.

    2014-01-01

    Previous studies have shown a wide variety of environmental toxicants and abnormal nutrition can promote the epigenetic transgenerational inheritance of disease. More recently a number of studies have indicated environmental stress can also promote epigenetic alterations that are transmitted to subsequent generations to induce pathologies. A recent study by Yao and colleagues demonstrated gestational exposure to restraint stress and forced swimming promoted preterm birth risk and adverse newb...

  18. Epigenetics, society, and bio-objects

    Svalastog, Anna Lydia; Damjanovicova, Maria

    2015-01-01

    The molecular account of the environmental that epigenetics offers bestow it with paramount importance for biomedical perspective of health and disease and for social sciences perspective on human interactions and well-being. It offers new prospects for interventions to shape the health of both individuals and populations, and invokes its own ethical, legal, and social implications. We here propose treatment of the relation between epigenetics and society through the framework of bio-objectif...

  19. Host epigenetic modifications by oncogenic viruses

    Flanagan, J. M.

    2006-01-01

    Epigenetic alterations represent an important step in the initiation and progression of most human cancers, but it is difficult to differentiate the early cancer causing alterations from later consequences. Oncogenic viruses can induce transformation via expression of only a small number of viral genes. Therefore, the mechanisms by which oncogenic viruses cause cancer may provide clues as to which epigenetic alterations are critical in early carcinogenesis.

  20. Orchestrating epigenetic roles targeting ocular tumors

    Wen X; Lu L; Zhang H.; Fan X

    2016-01-01

    Xuyang Wen*, Linna Lu*, He Zhang, Xianqun Fan Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Epigenetics is currently one of the most promising areas of study in the field of biomedical research. Scientists have dedicated their efforts to studying epigenetic mechanisms in cancer for centuries. Additionally, the ...

  1. Epigenetics of multiple sclerosis: an updated review.

    Küçükali, Cem İsmail; Kürtüncü, Murat; Çoban, Arzu; Çebi, Merve; Tüzün, Erdem

    2015-06-01

    Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease characterized with autoimmune response against myelin proteins and progressive axonal loss. The heterogeneity of the clinical course and low concordance rates in monozygotic twins have indicated the involvement of complex heritable and environmental factors in MS pathogenesis. MS is more often transmitted to the next generation by mothers than fathers suggesting an epigenetic influence. One of the possible reasons of this parent-of-origin effect might be the human leukocyte antigen-DRB1*15 allele, which is the major risk factor for MS and regulated by epigenetic mechanisms such as DNA methylation and histone deacetylation. Moreover, major environmental risk factors for MS, vitamin D deficiency, smoking and Ebstein-Barr virus are all known to exert epigenetic changes. In the last few decades, compelling evidence implicating the role of epigenetics in MS has accumulated. Increased or decreased acetylation, methylation and citrullination of genes regulating the expression of inflammation and myelination factors appear to be particularly involved in the epigenetics of MS. Although much less is known about epigenetic factors causing neurodegeneration, epigenetic mechanisms regulating axonal loss, apoptosis and mitochondrial dysfunction in MS are in the process of identification. Additionally, expression levels of several microRNAs (miRNAs) (e.g., miR-155 and miR-326) are increased in MS brains and potential mechanisms by which these factors might influence MS pathogenesis have been described. Certain miRNAs may also be potentially used as diagnostic biomarkers in MS. Several reagents, especially histone deacetylase inhibitors have been shown to ameliorate the symptoms of experimental allergic encephalomyelitis. Ongoing efforts in this field are expected to result in characterization of epigenetic factors that can be used in prediction of treatment responsive MS patients, diagnostic screening panels

  2. Emerging Trends in Epigenetic Regulation of Nutrient Deficiency Response in Plants.

    Sirohi, Gunjan; Pandey, Bipin K; Deveshwar, Priyanka; Giri, Jitender

    2016-03-01

    Diverse environmental stimuli largely affect the ionic balance of soil, which have a direct effect on growth and crop yield. Details are fast emerging on the genetic/molecular regulators, at whole-genome levels, of plant responses to mineral deficiencies in model and crop plants. These genetic regulators determine the root architecture and physiological adaptations for better uptake and utilization of minerals from soil. Recent evidence also shows the potential roles of epigenetic mechanisms in gene regulation, driven by minerals imbalance. Mineral deficiency or sufficiency leads to developmental plasticity in plants for adaptation, which is preceded by a change in the pattern of gene expression. Notably, such changes at molecular levels are also influenced by altered chromatin structure and methylation patterns, or involvement of other epigenetic components. Interestingly, many of the changes induced by mineral deficiency are also inheritable in the form of epigenetic memory. Unravelling these mechanisms in response to mineral deficiency would further advance our understanding of this complex plant response. Further studies on such approaches may serve as an exciting interaction model of epigenetic and genetic regulations of mineral homeostasis in plants and designing strategies for crop improvement. PMID:26829932

  3. Epigenetic regulation of hematopoietic stem cell aging

    Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States); Rossi, Derrick J. [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States)

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  4. Epigenetic regulation in alcoholic liver disease

    Pranoti Mandrekar

    2011-01-01

    Alcoholic liver disease (ALD) is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and phosphorylation, hypomethylation of DNA, and alterations in miRNAs. These modifications can be induced by alcohol-induced oxidative stress that results in altered recruitment of transcriptional machinery and abnormal gene expression. Delineating these mechanisms in initiation and progression of ALD is becoming a major area of interest. This review summarizes key epigenetic mechanisms that are dysregulated by alcohol in the liver. Alterations by alcohol in histone and DNA modifications, enzymes related to histone acetylation such as histone acetyltransferases, histone deacetylases and sirtuins, and methylation enzymes such as DNA methyltransferases are discussed. Chromatin modifications and miRNA alterations that result in immune cell dysfunction contributing to inflammatory cytokine production in ALD is reviewed. Finally, the role of alcohol-mediated oxidative stress in epigenetic regulation in ALD is described. A better understanding of these mechanisms is crucial for designing novel epigenetic based therapies to ameliorate ALD.

  5. Epigenetic regulation of hematopoietic stem cell aging

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging

  6. Reorganization of auditory map and pitch discrimination in adult rats chronically exposed to low-level ambient noise

    Weimin Zheng

    2012-09-01

    Full Text Available Behavioral adaption to a changing environment is critical for an animal’s survival. How well the brain can modify its functional properties based on experience essentially defines the limits of behavioral adaptation. In adult animals the extent to which experience shapes brain function has not been fully explored. Moreover, the perceptual consequences of experience-induced changes in the brains of adults remain unknown. Here we show that the tonotopic map in the primary auditory cortex of adult rats living with low-level ambient noise underwent a dramatic reorganization. Behaviorally, chronic noise-exposure impaired fine, but not coarse pitch discrimination. When tested in a noisy environment, the noise-exposed rats performed as well as in a quiet environment whereas the control rats performed poorly. This suggests that noise-exposed animals had adapted to living in a noisy environment. Behavioral pattern analyses revealed that stress or distraction engendered by the noisy background could not account for the poor performance of the control rats in a noisy environment. A reorganized auditory map may therefore have served as the neural substrate for the consistent performance of the noise-exposed rats in a noisy environment.

  7. Epigenetic approaches towards radiation countermeasure

    In the recent years, histone deacetylase inhibitors (HDACi) have gained tremendous attention for their anticancer, tumor radiosensitising and chemosensitising properties. HDACi enhance the acetylation status of histone proteins of the chromatin besides other non-histone target proteins, an effect that is regulated by the HDACs (histone deacetylases) and HATs (histone acetyltransferases) in the cells. HDACi affect the cell cycle progression, differentiation, DNA damage and repair processes and cell death which contributes to their anticancer properties. One of the main reasons for HDACi gaining attention as potential anticancer therapeutics is their profound action on cancer cells with minimal or no effect on normal cells. However, in recent years, the possible non-oncological applications of HDACi are being explored extensively viz, in neurodegenerative diseases. Ionizing radiation exposure leads to significant alterations in signal transduction processes, changes gene expression patterns, affects DNA damage and repair processes, cell cycle progression and the underlying epigenetic changes (acetylation of histones and methylation of DNA and histones in particular) are now emerging. Some recent literatures suggest that HDACi can render cytoprotective properties in normal tissues. We at INMAS evaluated certain weak HDACi molecules of dietary origin for their ability to modulate cellular radiation in normal cells and animals. As per our expectations, post irradiation treatment with selected HDACi molecules rendered significant reduction in radiation induced damages. The possible mechanisms of action of HDACi in reducing radiation injuries with be discussed based on our won results and recent reports. (author)

  8. Gut indigenous microbiota and epigenetics

    Boris Arkadievich Shenderov

    2012-03-01

    Full Text Available This review introduces and discusses data regarding fundamental and applied investigations in mammalian epigenomics and gut microbiota received over the last 10 years. Analysis of these data enabled the author first to come to the conclusion that the multiple low molecular weight substances of indigenous gut microbiota origin should be considered one of the main endogenous factors actively participating in epigenomic mechanisms that responsible for the mammalian genome reprogramming and post-translated modifications. Gut microecological imbalance coursed by various biogenic and abiogenic agents and factors can produce the different epigenetic abnormalities and the onset and progression of metabolic diseases associated. The author substantiates the necessity to create an international project ‘Human Gut Microbiota and Epigenomics’ that facilitates interdisciplinary collaborations among scientists and clinicians engaged in host microbial ecology, nutrition, metagenomics, epigenomics and metabolomics investigations as well as in diseases prevention and treatment. Some priority scientific and applied directions in the current omic technologies coupled with gnotobiological approaches are suggested that can open a new era in characterizing the role of the symbiotic microbiota small metabolic and signal molecules in the host epigenomics. Although discussed subject is only at an early stage its validation can open novel approaches in drug discovery studies.

  9. Drying induced upright sliding and reorganization of carbon nanotube arrays

    Li Qingwen [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); De Paula, Raymond [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Zhang Xiefei [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Zheng Lianxi [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Arendt, Paul N [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Mueller, Fred M [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Zhu, Y T [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Tu Yi [CVD-First Nano, 1860 Smithtown Avenue, Ronkonkoma, NY 11779 (United States)

    2006-09-28

    Driven by capillary force, wet carbon nanotube (CNT) arrays have been found to reorganize into cellular structures upon drying. During the reorganization process, individual CNTs are firmly attached to the substrate and have to lie down on the substrate at cell bottoms, forming closed cells. Here we demonstrate that by modifying catalyst structures, the adhesion of CNTs to the substrate can be weakened. Upon drying such CNT arrays, CNTs may slide away from their original sites on the surface and self-assemble into cellular patterns with bottoms open. It is also found that the sliding distance of CNTs increases with array height, and drying millimetre tall arrays leads to the sliding of CNTs over a few hundred micrometres and the eventual self-assembly into discrete islands. By introducing regular vacancies in CNT arrays, CNTs may be manipulated into different patterns.

  10. Drying induced upright sliding and reorganization of carbon nanotube arrays

    Driven by capillary force, wet carbon nanotube (CNT) arrays have been found to reorganize into cellular structures upon drying. During the reorganization process, individual CNTs are firmly attached to the substrate and have to lie down on the substrate at cell bottoms, forming closed cells. Here we demonstrate that by modifying catalyst structures, the adhesion of CNTs to the substrate can be weakened. Upon drying such CNT arrays, CNTs may slide away from their original sites on the surface and self-assemble into cellular patterns with bottoms open. It is also found that the sliding distance of CNTs increases with array height, and drying millimetre tall arrays leads to the sliding of CNTs over a few hundred micrometres and the eventual self-assembly into discrete islands. By introducing regular vacancies in CNT arrays, CNTs may be manipulated into different patterns