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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. 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.

  14. 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

  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. 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...

  3. 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...

  4. [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

  5. 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

  6. 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

  7. 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.

  8. 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

  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. [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

  19. [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

  20. 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

  1. 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.

  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. 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.

  12. 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.

  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. 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

  6. 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

  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. 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.

  13. 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...

  14. 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...

  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. 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

  2. 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

  3. 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.

  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. 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.

  7. 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.

  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. 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

  2. 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

  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 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

  6. 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 ...

  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. 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.

  10. 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

  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. 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.

  13. 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

  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. 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....

  16. 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...

  17. 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...

  18. 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...

  19. 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....

  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 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.

  3. 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

  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. 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...

  7. 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 ...

  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. 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...

  13. 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…

  14. 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....

  15. 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...

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  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. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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 ...

  19. 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.

  20. 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

  1. 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...

  2. 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,...

  3. 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...

  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. 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 ...

  9. 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...

  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. 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

  5. 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...

  6. 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.

  7. 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

  8. 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.

  9. 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...

  10. 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

  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

    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.

  14. 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

  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. 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.

  4. 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...

  5. 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.

  6. 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)

  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. 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...

  11. 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....

  12. 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

  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. 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

  18. 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.

  19. 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...

  20. 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...

  1. 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 ...

  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 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.

  4. 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.

  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

  11. 75 FR 29451 - Agency Reorganization and Delegations of Authority

    2010-05-26

    ...; Reorganization Plan No. 7 of 1961, 26 FR 7315, August 12, 1961; Pub. L. 89-56, 70 Stat. 195; 5 CFR Part 2638; Pub..., 41301-41309, 44101-44106; E.O. 11222 of May 8, 1965, 30 FR 6469, 3 CFR 1964-1965 Comp. P. 306; 21 U.S.C... 205B, JFK International Airport, Jamaica, NY 11430-1827. Seattle Area Representative, The...

  12. Reorganization of a granular medium around a localized transformation

    Merceron, Aymeric; Sauret, Alban; Jop, Pierre

    2016-01-01

    Physical and chemical transformation processes in reactive granular media involve the reorganization of the structure. In this paper, we study experimentally the rearrangements of a two-dimensional (2D) granular packing undergoing a localized transformation. We track the position and evolution of all the disks that constitute the granular packing when either a large intruder shrinks in size or is pulled out of the granular structure. In the two situations the displacements at long time are si...

  13. Bankruptcy Resolution in Japan: Civil Rehabilitation vs. Corporate Reorganization

    Peng Xu

    2004-01-01

    I present evidence on recent bankruptcy resolution and bankruptcy reform in Japan. Prior to bankruptcy, bank lenders are less likely to intervene than they did before. Most bankrupt firms experience abnormal president turnover around bankruptcy filings, regardless types of filings. Priority of claims is less violated in bankruptcy resolution in Japan than in the United States. A Civil Rehabilitation firm spends in bankruptcy substantially shorter than a Corporate Reorganization firm. Also, a ...

  14. Perinatal epigenetic determinants of cognitive and metabolic disorders.

    Lupu, Daniel S; Tint, Diana; Niculescu, Mihai D

    2012-12-01

    Multiple cues from the environment of our indirect and immediate ancestors, which often persist throughout the prenatal period and adulthood, are shaping our phenotypes through either direct, parent-to-child influences, or transgenerational inheritance. These effects are due to gene-environment interactions, which are intended to be a predictive tool and a mechanism of quick adaptation to the environment, as compared with genetic variations that are inherited over many generations. In certain circumstances the influences induced by the gene-environment interactions can have deleterious effects upon the health status, in the context of a radical change in the environment that does not fit with the predicted conditions, via epigenetic alterations. Conversely the best fit to the expected environment might have a delayed aging process and a longer life span. This review will touch upon the Developmental Origins of Health and Disease (DoHAD) concept, while discussing recent advances in the understanding of metabolic and cognitive disruptions, with a focus on epigenetic factors, their transgenerational effects, and the consequences they might have upon the onset of chronic disease and premature exitus. PMID:23251850

  15. A molecularly based theory for electron transfer reorganization energy

    Using field-theoretic techniques, we develop a molecularly based dipolar self-consistent-field theory (DSCFT) for charge solvation in pure solvents under equilibrium and nonequilibrium conditions and apply it to the reorganization energy of electron transfer reactions. The DSCFT uses a set of molecular parameters, such as the solvent molecule’s permanent dipole moment and polarizability, thus avoiding approximations that are inherent in treating the solvent as a linear dielectric medium. A simple, analytical expression for the free energy is obtained in terms of the equilibrium and nonequilibrium electrostatic potential profiles and electric susceptibilities, which are obtained by solving a set of self-consistent equations. With no adjustable parameters, the DSCFT predicts activation energies and reorganization energies in good agreement with previous experiments and calculations for the electron transfer between metallic ions. Because the DSCFT is able to describe the properties of the solvent in the immediate vicinity of the charges, it is unnecessary to distinguish between the inner-sphere and outer-sphere solvent molecules in the calculation of the reorganization energy as in previous work. Furthermore, examining the nonequilibrium free energy surfaces of electron transfer, we find that the nonequilibrium free energy is well approximated by a double parabola for self-exchange reactions, but the curvature of the nonequilibrium free energy surface depends on the charges of the electron-transferring species, contrary to the prediction by the linear dielectric theory

  16. Forelimb training drives transient map reorganization in ipsilateral motor cortex.

    Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A

    2016-10-15

    Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. PMID:27392641

  17. Epigenetic responses to heat stress at different time scales and the involvement of small RNAs

    Stief, Anna; Brzezinka, Krzysztof; Lämke, Jörn; Bäurle, Isabel

    2014-01-01

    The hypothesis that plants can benefit from a memory of past stress exposure has recently attracted a lot of attention. Here, we discuss two different examples of heat stress memory to elucidate the potential benefits that epigenetic responses may provide at both the level of acclimation of the individual plant and adaptation at a species-wide level. Specifically, we discuss how microRNAs regulate the heat stress memory and thereby increase survival upon a recurring heat stress. Secondly, we ...

  18. On-Chip Cellomics Assay Enabling Algebraic and Geometric Understanding of Epigenetic Information in Cellular Networks of Living Systems. 1. Temporal Aspects of Epigenetic Information in Bacteria

    Kenji Yasuda

    2012-05-01

    Full Text Available A series of studies aimed at developing methods and systems of analyzing epigenetic information in cells and in cell networks, as well as that of genetic information, was examined to expand our understanding of how living systems are determined. Because cells are minimum units reflecting epigenetic information, which is considered to map the history of a parallel-processing recurrent network of biochemical reactions, their behaviors cannot be explained by considering only conventional DNA information-processing events. The role of epigenetic information on cells, which complements their genetic information, was inferred by comparing predictions from genetic information with cell behaviour observed under conditions chosen to reveal adaptation processes, population effects and community effects. A system of analyzing epigenetic information was developed starting from the twin complementary viewpoints of cell regulation as an “algebraic” system (emphasis on temporal aspects and as a “geometric” system (emphasis on spatial aspects. Exploiting the combination of latest microfabrication technology and measurement technologies, which we call on-chip cellomics assay, we can control and re-construct the environments and interaction of cells from “algebraic” and “geometric” viewpoints. In this review, temporal viewpoint of epigenetic information, a part of the series of single-cell-based “algebraic” and “geometric” studies of celluler systems in our research groups, are summerized and reported. The knowlege acquired from this study may lead to the use of cells that fully control practical applications like cell-based drug screening and the regeneration of organs.

  19. Epigenetic biomarkers in esophageal cancer.

    Kaz, Andrew M; Grady, William M

    2014-01-28

    The aberrant DNA methylation of tumor suppressor genes is well documented in esophageal cancer, including adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) as well as in Barrett's esophagus (BE), a pre-malignant condition that is associated with chronic acid reflux. BE is a well-recognized risk factor for the development of EAC, and consequently the standard of care is for individuals with BE to be placed in endoscopic surveillance programs aimed at detecting early histologic changes that associate with an increased risk of developing EAC. Yet because the absolute risk of EAC in individuals with BE is minimal, a clinical need in the management of BE is the identification of additional risk markers that will indicate individuals who are at a significant absolute risk of EAC so that they may be subjected to more intensive surveillance. The best currently available risk marker is the degree of dysplasia in endoscopic biopsies from the esophagus; however, this marker is suboptimal for a variety of reasons. To date, there are no molecular biomarkers that have been translated to widespread clinical practice. The search for biomarkers, including hypermethylated genes, for either the diagnosis of BE, EAC, or ESCC or for risk stratification for the development of EAC in those with BE is currently an area of active research. In this review, we summarize the status of identified candidate epigenetic biomarkers for BE, EAC, and ESCC. Most of these aberrantly methylated genes have been described in the context of early detection or diagnostic markers; others might prove useful for estimating prognosis or predicting response to treatment. Finally, special attention will be paid to some of the challenges that must be overcome in order to develop clinically useful esophageal cancer biomarkers. PMID:22406828

  20. Epigenetic mechanism of radiation carcinogenesis

    Carcinogenic action of radiations has long been thought to be due to its mutagenic activity. Since DNA damage is induced and distributes in a stochastic fashion, radiation induction of cancers was also assumed to follow a stochastic kinetics. However, recent progress in radiation research has revealed that some features of radiation carcinogenesis are not explainable by the simple action of radiation as a DNA damaging and mutagenic agent. Firstly, frequencies of radiation-induced transformation in vitro and radiation-induced mammary cancers in rats are too high to be accounted for by the frequency of radiation-induced mutation. Secondly, trans-generation carcinogenesis among F1 mice born to irradiated parents occurs also much more frequently than to be predicted by the frequency of radiation induced germline mutation. Thirdly, multistage carcinogenesis theory predicts that carcinogens give hits to the target cells so as to shorten the latency of cancers. However, latencies of radiation induced solid cancers among atomic bomb survivors are similar to those of the control population. Fourthly, although radiation elevates the frequency of cancers, the induced cancers seem to share the same spectrum of cancer types as in the unirradiated control populations. This suggests that radiation induces cancer by enhancement of the spontaneous carcinogenesis process. These data suggest that the first step of radiation carcinogenesis may not be the direct induction of mutation. Radiation may induce genetic instability which increases the spontaneous mutation rate in the cells to produce carcinogenic mutations. Growth stimulatory effect of radiation may also contribute to the process. Thus, epigenetic, but not genetic effect of radiation might better contribute in the process of carcinogenesis. (author)

  1. Epigenetic mechanism of radiation carcinogenesis

    Niwa, Ohtsura [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

    1995-12-01

    Carcinogenic action of radiations has long been thought to be due to its mutagenic activity. Since DNA damage is induced and distributes in a stochastic fashion, radiation induction of cancers was also assumed to follow a stochastic kinetics. However, recent progress in radiation research has revealed that some features of radiation carcinogenesis are not explainable by the simple action of radiation as a DNA damaging and mutagenic agent. Firstly, frequencies of radiation-induced transformation in vitro and radiation-induced mammary cancers in rats are too high to be accounted for by the frequency of radiation-induced mutation. Secondly, trans-generation carcinogenesis among F1 mice born to irradiated parents occurs also much more frequently than to be predicted by the frequency of radiation induced germline mutation. Thirdly, multistage carcinogenesis theory predicts that carcinogens give hits to the target cells so as to shorten the latency of cancers. However, latencies of radiation induced solid cancers among atomic bomb survivors are similar to those of the control population. Fourthly, although radiation elevates the frequency of cancers, the induced cancers seem to share the same spectrum of cancer types as in the unirradiated control populations. This suggests that radiation induces cancer by enhancement of the spontaneous carcinogenesis process. These data suggest that the first step of radiation carcinogenesis may not be the direct induction of mutation. Radiation may induce genetic instability which increases the spontaneous mutation rate in the cells to produce carcinogenic mutations. Growth stimulatory effect of radiation may also contribute to the process. Thus, epigenetic, but not genetic effect of radiation might better contribute in the process of carcinogenesis. (author)

  2. Epigenetic mechanisms of Rubinstein-Taybi syndrome.

    Park, Elizabeth; Kim, Yunha; Ryu, Hyun; Kowall, Neil W; Lee, Junghee; Ryu, Hoon

    2014-03-01

    Rubinstein-Taybi syndrome (RTS) is an incurable genetic disorder with combination of mental retardation and physical features including broad thumbs and toes, craniofacial abnormalities, and growth deficiency. While the autosomal dominant mode of transmission is limitedly known, the majority of cases are attributable to de novo mutations in RTS. The first identified gene associated with RTS is CREB-binding protein (CREBBP/CBP). Alterations of the epigenetic 'histone code' due to dysfunction of the CBP histone acetyltransferase activity deregulate gene transcriptions that are prominently linked to RTS pathogenesis. In this review, we discuss how CBP mutation contributes to modifications of histone and how histone deacetylase inhibitors are therapeutically applicable to epigenetic conditioning in RTS. Since most genetic mutations are irreversible and therapeutic approaches are limited, therapeutic targeting of reversible epigenetic components altered in RTS may be an ideal strategy. Expeditious further study on the role of the epigenetic mechanisms in RTS is encouraged to identify novel epigenetic markers and therapeutic targets to treat RTS. PMID:24381114

  3. A special issue on ‘epigenetics'

    Wenlin Xu; Minghua Xu

    2012-01-01

    The term epigenetics was coined by Waddington CH in 1940s as a portmanteau of the words genetics and epigenesis to describe the differentiation of cells from their initial totipotent state in embryonic development.With the explosion of knowledge in this field in the recent 10 years,epigenetics is now typically defined as the study of heritable changes in gene expression that are not due to changes in the nucleotide sequence of DNA.The field of epigenetics is revolutionizing our understanding of biology and medicine.Recent studies have been focusing on the mechanisms of epigenetic regulation,including DNA methylation, histone modification,chromatin remodeling,etc.,and on their contributions to development and diseases.In this special issue,nine review articles written by prominent experts in this field are put together,trying to give our readers a broad picture of epigenetics and a summary of most recent research progress in this field.Here is a preview of what you will find in this issue.

  4. Diet and epigenetics in colon cancer

    Minna Nystr(o)m; Marja Mutanen

    2009-01-01

    Over the past few years, evidence has accumulated indicating that apart from genetic alterations, epigenetic alterations, through e.g. aberrant promoter methylation, play a major role in the initiation and progression of colorectal cancer (CRC). Even in the hereditary colon cancer syndromes, in which the susceptibility is inherited dominantly, cancer develops only as the result of the progressive accumulation of genetic and epigenetic alterations. Diet can both prevent and induce colon carcinogenesis, for instance, through epigenetic changes, which regulate the homeostasis of the intestinal mucosa. Food-derived compounds are constantly present in the intestine and may shift cellular balance toward harmful outcomes, such as increased susceptibility to mutations. There is strong evidence that a major component of cancer risk may involve epigenetic changes in normal cells that increase the probability of cancer after genetic mutation. The recognition of epigenetic changes as a driving force in colorectal neoplasia would open new areas of research in disease epidemiology, risk assessment, and treatment, especially in mutation carriers who already have an inherited predisposition to cancer.(c) 2009 The WJG Press and Baishideng. All rights reserved.

  5. Epigenetic Mechanisms of Rubinstein-Taybi Syndrome

    Park, Elizabeth; Kim, Yunha; Ryu, Hyun; Kowall, Neil W.; Lee, Junghee; Ryu, Hoon

    2014-01-01

    Rubinstein-Taybi Syndrome (RTS) is an incurable genetic disorder with combination of mental retardation and physical features including broad thumbs and toes, craniofacial abnormalities, and growth deficiency. While the autosomal dominant mode of transmission is limitedly known, the majority of cases are attributable to de novo mutations in RTS. The first identified gene associated with RTS is CREB-binding protein (CREBBP/CBP). Alterations of the epigenetic ‘histone code’ due to dysfunction of the CBP histone acetyltransferase (HAT) activity deregulates gene transcription that are prominently linked to RTS pathogenesis. In this review, we discuss how CBP mutation contributes to modifications of histone and how HDAC inhibitors are therapeutically applicable to epigenetic conditioning in RTS. Since most genetic mutations are irreversible and therapeutic approaches are limited, therapeutic targeting of reversible epigenetic components altered in RTS may be an ideal strategy. Expeditious further study on the role of the epigenetic mechanisms in RTS is encouraged to identify novel epigenetic biological markers and therapeutic targets to treat RTS. PMID:24381114

  6. Simultaneous DNA and RNA isolation from brain punches for epigenetics

    Spengler Dietmar

    2011-08-01

    Full Text Available Abstract Background Epigenetic modifications such as DNA methylation play an important role for gene expression and are regulated by developmental and environmental signals. DNA methylation typically occurs in a highly tissue- and cell-specific manner. This raises a severe challenge when studying discrete, small regions of the brain where cellular heterogeneity is high and tissue quantity limited. Because gene expression and methylation are often tightly linked it appears of interest to compare both parameters in the same sample. Findings We present a refined method for the simultaneous extraction of DNA for bisulfite sequencing and RNA for expression analysis from small mouse brain tissue punches. This method can also be easily adapted for other small tissues or cell populations. Conclusions The method described herein results in DNA and RNA of a quantity and quality permitting highly reliable bisulfite analysis and quantitative RT-PCR measurements, respectively.

  7. Epigenetics and Bruxism: Possible Role of Epigenetics in the Etiology of Bruxism.

    Čalić, Aleksandra; Peterlin, Borut

    2015-01-01

    Bruxism is defined as a repetitive jaw muscle activity characterized by clenching or grinding of the teeth and/or bracing or thrusting of the mandible. There are two distinct circadian phenotypes for bruxism: sleep bruxism (SB) and awake bruxism, which are considered separate entities due to the putative difference in their etiology and phenotypic variance. The detailed etiology of bruxism so far remains unknown. Recent theories suggest the central regulation of certain pathophysiological or psychological pathways. Current proposed causes of bruxism appear to be a combination of genetic and environmental (G×E) factors, with epigenetics providing a robust framework for investigating G×E interactions, and their involvement in bruxism makes it a suitable candidate for epigenetic research. Both types of bruxism are associated with certain epigenetically determined disorders, such as Rett syndrome (RTT), Prader-Willi syndrome (PWS), and Angelman syndrome (AS), and these associations suggest a mechanistic link between epigenetic deregulation and bruxism. The present article reviews the possible role of epigenetic mechanisms in the etiology of both types of bruxism based on the epigenetic pathways involved in the pathophysiology of RTT, PWS, and AS, and on other epigenetic disruptions associated with risk factors for bruxism, including sleep disorders, altered stress response, and psychopathology. PMID:26523718

  8. Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders.

    Kubota, Takeo; Mochizuki, Kazuki

    2016-01-01

    Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility. PMID:27187441

  9. Individual epigenetic variation: When, why, and so what?

    Epigenetics provides a potential explanation for how environmental factors modify the risk for common diseases among individuals. Interindividual variation in DNA methylation and epigenetic regulation has been reported at specific genomic regions including transposable elements, genomically imprinte...

  10. Epigenetic Mechanisms Facilitating Oligodendrocyte Development, Maturation, and Aging

    Copray, Sjef; Huynh, Jimmy Long; Sher, Falak; Casaccia-Bonnefil, Patrizia; Boddeke, Erik

    2009-01-01

    The process of oligodendrocyte differentiation is regulated by a dynamic interaction between a genetic and an epigenetic program. Recent studies, addressing nucleosomal histone modifications have considerably increased our knowledge regarding epigenetic regulation of gene expression during oligodend

  11. Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders

    Kubota, Takeo; Mochizuki, Kazuki

    2016-01-01

    Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility. PMID:27187441

  12. Epigenetics of Alzheimer’s Disease and Frontotemporal Dementia

    Veerappan, Chendhore S; Sleiman, Sama; Coppola, Giovanni

    2013-01-01

    This article will review the recent advances in the understanding of the role of epigenetic modifications and the promise of future epigenetic therapy in neurodegenerative dementias, including Alzheimer’s disease and frontotemporal dementia.

  13. Epigenetic perturbations in aging stem cells.

    Krauss, Sara Russo; de Haan, Gerald

    2016-08-01

    Stem cells maintain homeostasis in all regenerating tissues during the lifespan of an organism. Thus, age-related functional decline of such tissues is likely to be at least partially explained by molecular events occurring in the stem cell compartment. Some of these events involve epigenetic changes, which may dictate how an aging genome can lead to differential gene expression programs. Recent technological advances have made it now possible to assess the genome-wide distribution of an ever-increasing number of epigenetic marks. As a result, the hypothesis that there may be a causal role for an altered epigenome contributing to the functional decline of cells, tissues, and organs in aging organisms can now be explored. In this paper, we review recent developments in the field of epigenetic regulation of stem cells, and how this may contribute to aging. PMID:27229519

  14. Interactions between epigenetics and metabolism in cancers

    JihyeYun

    2012-11-01

    Full Text Available Cancer progression is accompanied by widespread transcriptional changes and metabolic alterations. Although it is widely accepted that the origin of cancer can be traced to the mutations that accumulate over time, relatively recent evidence favors a similarly fundamental role for alterations in the epigenome during tumorigenesis. Changes in epigenetics that arise from post-translational modifications of histones and DNA, are exploited by cancer cells to upregulate and/or downregulate the expression levels of oncogenes and tumor suppressors, respectively. Although the mechanisms behind these modifications, in particular how they lead to gene silencing and activation, are still being understood, many enzymes that carry out post-translational modifications that alter epigenetics require metabolites as substrates or cofactors. As a result, their activities can be influenced by the metabolic state of the cell. The purpose of this review is to give an overview of cancer epigenetics and metabolism and provide examples of where they converge.

  15. Epigenetics: A key paradigm in reproductive health

    Bunkar, Neha; Pathak, Neelam; Lohiya, Nirmal Kumar

    2016-01-01

    It is well established that there is a heritable element of susceptibility to chronic human ailments, yet there is compelling evidence that some components of such heritability are transmitted through non-genetic factors. Due to the complexity of reproductive processes, identifying the inheritance patterns of these factors is not easy. But little doubt exists that besides the genomic backbone, a range of epigenetic cues affect our genetic programme. The inter-generational transmission of epigenetic marks is believed to operate via four principal means that dramatically differ in their information content: DNA methylation, histone modifications, microRNAs and nucleosome positioning. These epigenetic signatures influence the cellular machinery through positive and negative feedback mechanisms either alone or interactively. Understanding how these mechanisms work to activate or deactivate parts of our genetic programme not only on a day-to-day basis but also over generations is an important area of reproductive health research. PMID:27358824

  16. Evidence of Epigenetic Mechanisms Affecting Carotenoids.

    Arango, Jacobo; Beltrán, Jesús; Nuñez, Jonathan; Chavarriaga, Paul

    2016-01-01

    Epigenetic mechanisms are able to regulate plant development by generating non-Mendelian allelic interactions. An example of these are the responses to environmenal stimuli that result in phenotypic variability and transgression amongst important crop traits. The need to predict phenotypes from genotypes to understand the molecular basis of the genotype-by-environment interaction is a research priority. Today, with the recent discoveries in the field of epigenetics, this challenge goes beyond analyzing how DNA sequences change. Here we review examples of epigenetic regulation of genes involved in carotenoid synthesis and degradation, cases in which histone- and/or DNA-methylation, and RNA silencing at the posttranscriptional level affect carotenoids in plants. PMID:27485227

  17. Epigenetics, cellular memory and gene regulation.

    Henikoff, Steven; Greally, John M

    2016-07-25

    The field described as 'epigenetics' has captured the imagination of scientists and the lay public. Advances in our understanding of chromatin and gene regulatory mechanisms have had impact on drug development, fueling excitement in the lay public about the prospects of applying this knowledge to address health issues. However, when describing these scientific advances as 'epigenetic', we encounter the problem that this term means different things to different people, starting within the scientific community and amplified in the popular press. To help researchers understand some of the misconceptions in the field and to communicate the science accurately to each other and the lay audience, here we review the basis for many of the assumptions made about what are currently referred to as epigenetic processes. PMID:27458904

  18. Epigenetic mechanisms in neurological and neurodegenerative diseases.

    Jorge eLandgrave-Gómez

    2015-02-01

    Full Text Available The role of epigenetic mechanisms in the function and homeostasis of the central nervous system (CNS and its regulation in diseases is one of the most interesting processes of contemporary neuroscience. In the last decade, a growing body of literature suggests that long-term changes in gene transcription associated with CNS´s regulation and neurological disorders are mediated via modulation of chromatin structure.Epigenetics, introduced for the first time by Waddington in the early 1940s, has been traditionally referred to a variety of mechanisms that allow heritable changes in gene expression even in the absence of DNA mutation. However, new definitions acknowledge that many of these mechanisms used to perpetuate epigenetic traits in dividing cells are used by neurons to control a variety of functions dependent on gene expression. Indeed, in the recent years these mechanisms have shown their importance in the maintenance of a healthy CNS. Moreover, environmental inputs that have shown effects in CNS diseases, such as nutrition, that can modulate the concentration of a variety of metabolites such as acetyl-coenzyme A (acetyl-coA, nicotinamide adenine dinucleotide (NAD+ and beta hydroxybutyrate (β-HB, regulates some of these epigenetic modifications, linking in a precise way environment with gene expression.This manuscript will portray what is currently understood about the role of epigenetic mechanisms in the function and homeostasis of the CNS and their participation in a variety of neurological disorders. We will discuss how the machinery that controls these modifications plays an important role in processes involved in neurological disorders such as neurogenesis and cell growth. Moreover, we will discuss how environmental inputs modulate these modifications producing metabolic and physiological alterations that could exert beneficial effects on neurological diseases. Finally, we will highlight possible future directions in the field of

  19. Epigenetics and Vasculitis: a Comprehensive Review.

    Renauer, Paul; Coit, Patrick; Sawalha, Amr H

    2016-06-01

    Vasculitides represent a group of relatively rare systemic inflammatory diseases of the blood vessels. Despite recent progress in understanding the genetic basis and the underlying pathogenic mechanisms in vasculitis, the etiology and pathogenesis of vasculitis remain incompletely understood. Epigenetic dysregulation plays an important role in immune-mediated diseases, and the contribution of epigenetic aberrancies in vasculitis is increasingly being recognized. Histone modifications in the PR3 and MPO gene loci might be mechanistically involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Similarly, other studies revealed important epigenetic contribution to other vasculitides, including Kawasaki disease and IgA vasculitis. More recently, genome-wide epigenomic studies have been performed in several vasculitides. A recent genome-wide DNA methylation study uncovered an important role for epigenetic remodeling of cytoskeleton-related genes in the pathogenesis of Behçet's disease and suggested that reversal of some of these DNA methylation changes associates with disease remission. Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling, prompting the suggestion that a specific calcineurin/NFAT inhibitor that is well tolerated and with the added beneficial anti-platelet activity, such as dipyridamole, might be of therapeutic potential in giant cell arteritis. While epigenetic studies in systemic vasculitis are still in their infancy, currently available data clearly indicate that investigating the epigenetic mechanisms underlying these diseases will help to better understand the pathogenesis of vasculitis and provide novel targets for the development of disease biomarkers and new therapies. PMID:26093659

  20. Structural and functional reorganization of propriospinal connections promotes functional recovery after spinal cord injury

    Linard Filli

    2015-01-01

    Full Text Available Axonal regeneration and fiber regrowth is limited in the adult central nervous system, but research over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorganize after smaller injuries or denervation. Short-distance fiber growth and synaptic rewiring was found in cortex, brain stem and spinal cord and could be associated with restoration of sensorimotor functions that were impaired by the injury. Such processes of structural plasticity were initially observed in the corticospinal system following spinal cord injury or stroke, but recent studies showed an equally high potential for structural and functional reorganization in reticulospinal, rubrospinal or propriospinal projections. Here we review the lesion-induced plastic changes in the propriospinal pathways, and we argue that they represent a key mechanism triggering sensorimotor recovery upon incomplete spinal cord injury. The formation or strengthening of spinal detour pathways bypassing supraspinal commands around the lesion site to the denervated spinal cord were identified as prominent neural substrate inducing substantial motor recovery in different species from mice to primates. Indications for the existence of propriospinal bypasses were also found in humans after cortical stroke. It is mandatory for current research to dissect the biological mechanisms underlying spinal circuit remodeling and to investigate how these processes can be stimulated in an optimal way by therapeutic interventions (e.g., fiber-growth enhancing interventions, rehabilitation. This knowledge will clear the way for the development of novel strategies targeting the remarkable plastic potential of propriospinal circuits to maximize functional recovery after spinal cord injury.

  1. Structural and functional reorganization of propriospinal connections promotes functional recovery after spinal cord injury

    Linard Filli; Martin E Schwab

    2015-01-01

    Axonal regeneration and ifber regrowth is limited in the adult central nervous system, but re-search over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorganize after smaller injuries or denervation. Short-distance ifber growth and synaptic rewiring was found in cortex, brain stem and spinal cord and could be associated with restoration of sensorimotor functions that were impaired by the injury. Such processes of struc-tural plasticity were initially observed in the corticospinal system following spinal cord injury or stroke, but recent studies showed an equally high potential for structural and functional reorganization in reticulospinal, rubrospinal or propriospinal projections. Here we review the lesion-induced plastic changes in the propriospinal pathways, and we argue that they represent a key mechanism triggering sensorimotor recovery upon incomplete spinal cord injury. The for-mation or strengthening of spinal detour pathways bypassing supraspinal commands around the lesion site to the denervated spinal cord were identiifed as prominent neural substrate inducing substantial motor recovery in different species from mice to primates. Indications for the exis-tence of propriospinal bypasses were also found in humans after cortical stroke. It is mandatory for current research to dissect the biological mechanisms underlying spinal circuit remodeling and to investigate how these processes can be stimulated in an optimal way by therapeutic inter-ventions (e.g., ifber-growth enhancing interventions, rehabilitation). This knowledge will clear the way for the development of novel strategies targeting the remarkable plastic potential of pro-priospinal circuits to maximize functional recovery after spinal cord injury.

  2. KNOX1 is expressed and epigenetically regulated during in vitro conditions in Agave spp

    De-la-Peña Clelia

    2012-11-01

    Full Text Available Abstract Background The micropropagation is a powerful tool to scale up plants of economical and agronomical importance, enhancing crop productivity. However, a small but growing body of evidence suggests that epigenetic mechanisms, such as DNA methylation and histone modifications, can be affected under the in vitro conditions characteristic of micropropagation. Here, we tested whether the adaptation to different in vitro systems (Magenta boxes and Bioreactors modified epigenetically different clones of Agave fourcroydes and A. angustifolia. Furthermore, we assessed whether these epigenetic changes affect the regulatory expression of KNOTTED1-like HOMEOBOX (KNOX transcription factors. Results To gain a better understanding of epigenetic changes during in vitro and ex vitro conditions in Agave fourcroydes and A. angustifolia, we analyzed global DNA methylation, as well as different histone modification marks, in two different systems: semisolid in Magenta boxes (M and temporary immersion in modular Bioreactors (B. No significant difference was found in DNA methylation in A. fourcroydes grown in either M or B. However, when A. fourcroydes was compared with A. angustifolia, there was a two-fold difference in DNA methylation between the species, independent of the in vitro system used. Furthermore, we detected an absence or a low amount of the repressive mark H3K9me2 in ex vitro conditions in plants that were cultured earlier either in M or B. Moreover, the expression of AtqKNOX1 and AtqKNOX2, on A. fourcroydes and A. angustifolia clones, is affected during in vitro conditions. Therefore, we used Chromatin ImmunoPrecipitation (ChIP to know whether these genes were epigenetically regulated. In the case of AtqKNOX1, the H3K4me3 and H3K9me2 were affected during in vitro conditions in comparison with AtqKNOX2. Conclusions Agave clones plants with higher DNA methylation during in vitro conditions were better adapted to ex vitro conditions. In addition

  3. Epigenetic cell response to an influence of ionizing radiation

    Importance of radiation modification of epigenetic activity in the general mechanism of radiobiological reactions is proved. Inheritable epigenetic changes induced by irradiation are one of the basic reasons of formation of the remote radiation pathology. It is noted that epigenetic inheritable changes of cells have the determined character distinguishing them mutation changes, being individual and not directed. It is underlined the ability of ionizing radiation to modify level of spontaneous genetic instability inherited in a number of cell generations on epigenetic mechanism

  4. [The alchemy--epigenetic regulation of pluripotency].

    Bem, Joanna; Grabowska, Iwona

    2013-01-01

    Embryonic stem cells (ESCs) self renew their population, also they are pluripotent which means they can differentiate into any given cell type. In specific culture conditions they remain undifferentiated. On the cellular level pluripotency is determined by many transcription factors, e.g. Sox2, Nanog, Klf4, Oct4. Epigenetic regulation is also crucial for both self renewal and pluripotency. This review focuses on epigenetic mechanisms, among them DNA methylation, posttranslational histone modifications, ATP dependent chromatin remodeling and miRNAs interactions. These mechanisms affect embryonic stem cells functions keeping them poised for differentiation. PMID:24044279

  5. Epigenetic Aspects of Posttraumatic Stress Disorder

    Ulrike Schmidt

    2011-01-01

    Full Text Available Development of psychiatric diseases such as posttraumatic stress disorder (PTSD invokes, as with most complex diseases, both genetic and environmental factors. The era of genome-wide high throughput technologies has sparked the initiation of genotype screenings in large cohorts of diseased and control individuals, but had limited success in identification of disease causing genetic variants. It has become evident that these efforts at the genomic level need to be complemented with endeavours in elucidating the proteome, transcriptome and epigenetic profiles. Epigenetics is attractive in particular because there is accumulating evidence that the lasting impact of adverse life events is reflected in certain covalent modifications of the chromatin.

  6. Epigenetics of dominance for enzyme activity

    Kuldip S Trehan; Kulbir S Gill

    2002-03-01

    We have isolated and purified two parental homodimers and a unique heterodimer of acid phosphatase [coded by Acph-11.05() and Acph-10.95()] from isogenic homozygotes and heterozygotes of Drosophila malerkotliana. and produce qualitatively different allozymes and the two alleles are expressed equally within and across all three genotypes and and play an equal role in the epigenetics of dominance. Subunit interaction in the heterodimer over a wide range of H+ concentrations accounts for the epigenetics of dominance for enzyme activity.

  7. Epigenetic dominance of prion conformers.

    Eri Saijo

    2013-10-01

    the otherwise unfavorable U conformer. This epigenetic mechanism thus expands the range of selectable conformations that can be adopted by PrP, and therefore the variety of options for strain propagation.

  8. 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…

  9. Epigenetic alteration of sedimentary rocks at hydrogenic uranium deposit

    The author introduces the concept, the recognition criteria, the genesis and classification of the epigenetic alteration of sedimentary rocks in brief, and expounds the mineral-geochemical indications and characteristics of oxidation and reduction alterations in different geochemical zones in detail, and proposes the two models of ore-controlling zonation of epigenetic alteration. The authors finally introduce research methods of epigenetic alteration

  10. Epigenetic Regulation of Cancer-Associated Genes in Ovarian Cancer

    Mi Jeong Kwon

    2011-01-01

    Full Text Available The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except for the DNA hypomethylation of some genes. Recently, we reported that the overexpression of cancer-promoting genes in ovarian cancer is associated with the loss of repressive histone modifications. This discovery suggested that epigenetic derepression may contribute to ovarian tumorigenesis by constituting a possible mechanism for the overexpression of oncogenes or cancer-promoting genes in tumors. The emerging importance of epigenetic aberrations in tumor initiation and in the regulation of cancer-initiating cells, suggests that epigenetically regulated genes may be promising therapeutic targets and biomarkers. Given that the current challenges in ovarian cancer include the identification of biomarkers for early cancer detection and the discovery of novel therapeutic targets for patients with recurrent malignancies undergoing chemotherapy, understanding the epigenetic changes that occur in ovarian cancer is crucial. This review looks at epigenetic mechanisms involved in the regulation of cancer-associated genes, including the contribution of epigenetic derepression to the activation of cancer-associated genes in ovarian cancer. In addition, possible epigenetic therapies targeting epigenetically dysregulated genes are discussed. A better understanding of the epigenetic changes in ovarian cancer will contribute to the improvement of patient outcomes.

  11. The Ambivalence of Creative Activism as a Reorganization of Critique

    Harrebye, Silas

    2015-01-01

    This article identifies an emerging type of critique and defines it as creative activism. It is argued why this is distinguishable from earlier similar forms of protests and shown why traditional theories of political art, social movements and citizenship are in themselves insufficient to accurat......This article identifies an emerging type of critique and defines it as creative activism. It is argued why this is distinguishable from earlier similar forms of protests and shown why traditional theories of political art, social movements and citizenship are in themselves insufficient...... the reorganization of critique regardless of whether one views creative activism suspiciously as a societal symptom or more optimistically as a democratic potential...

  12. Spectrum Reorganization and Bundling for Power Efficient Mobile Networks

    Micallef, Gilbert; Mogensen, Preben; Scheck, Hans-Otto

    2012-01-01

    still required for supporting legacy devices and providing wider network coverage. In order to facilitate and reduce the cost of rolling out a new network, mobile operators often reuse existing sites. Radio frequency modules in base station sites house power amplifiers, which are designed to operate...... can be reorganized within a single band, and have multiple carriers bundled together to fully exploit the capabilities of modern equipment. These modifications are applied on all network layers, maintaining the same number of carriers and baseband capacity. For the presented case, this results in the...

  13. The reorganization of the nuclear sector in France

    In November 2000, the French ministry of economy, finances and industry presented a project of reorganization of the overall French nuclear sector which aims at grouping together the activities of CEA-Industrie, Cogema and Framatome in a single huge industrial group. This group will comprise two main poles, a purely nuclear one around Cogema and Framatome, and a pole devoted to new technologies with the connector activities of Framatome and the shares of CEA-Industrie in STMicroelectronics. This new group should make a funded turnover of 10 billions of euros with a net result (share of the group) of 500 millions of euros. It will employ 45000 people. (J.S.)

  14. Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

    Kristensen, Dina Graae; Skakkebæk, Niels E; Rajpert-De Meyts, Ewa;

    2013-01-01

    Foetal development of germ cells is a unique biological process orchestrated by cellular specification, migration and niche development in concert with extensive epigenetic and transcriptional programs. Many of these processes take place early in foetal life and are hence very difficult to study....... In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3......K9me2, H3K27me3 and H3K9ac. We also show that CIS cells contain high levels of H3K27ac, which is known to mark active enhancers. Proper epigenetic reprogramming seems to be a pre-requisite of normal foetal germ cell development and we propose that alterations in these programs may be a pathogenic...

  15. The epigenetics of estrogen: Epigenetic regulation of hormone-induced memory enhancement

    Frick, Karyn M.; Zhao, Zaorui; Fan, Lu

    2011-01-01

    Epigenetic processes have been implicated in everything from cell proliferation to maternal behavior. Epigenetic alterations, including histone alterations and DNA methylation, have also been shown to play critical roles in the formation of some types of memory, and in the modulatory effects that factors, such as stress, drugs of abuse and environmental stimulation, have on the brain and memory function. Recently, we demonstrated that the ability of the sex-steroid hormone 17β-estradiol (E2) ...

  16. Formation of sanitation potential as an instrument of light industry enterprises reorganization management

    Larionova, Katerina Leonidivna; Donchenko, Tetyana Vitaliyivna

    2012-01-01

    Some existing approaches to defining the essence of reorganization potential aredescribed and the author's vision of this category is offered in the article. This definition takes intoaccount not only the resource approach, but a systematic and an effective ones as well. Theinterrelation between the concepts of reorganization potential and sanitation ability is substantiatedas well as the reorganization potential structure taking into account the industry sector theenterprises belong to is de...

  17. Magnetic resonance imaging research progress on brain functional reorganization after peripheral nerve injury

    In the recent years, with the development of functional magnetic resonance imaging technology the brain plasticity and functional reorganization are hot topics in the central nervous system imaging studies. Brain functional reorganization and rehabilitation after peripheral nerve injury may have certain regularity. In this paper, the progress of brain functional magnetic resonance imaging technology and its applications in the world wide clinical and experimental researches of the brain functional reorganization after peripheral nerve injury is are reviewed. (authors)

  18. Reorganization and Preservation of Motor Control of the Brain in Spinal Cord Injury: A Systematic Review

    Kokotilo, K J; Eng, J; Curt, A.

    2009-01-01

    Reorganization of brain function in people with CNS damage has been identified as one of the fundamental mechanisms involved in the recovery of sensori-motor function. Spinal cord injury (SCI) brain mapping studies during motor tasks aim for assessing the reorganization and preservation of brain networks involved in motor control. Revealing the activation of cortical and sub-cortical brain areas in people with SCI can indicate principal patterns of brain reorganization when the neurotrauma is...

  19. Epigenetic control of cell identity and plasticity

    Orlando, Valerio

    2014-04-02

    The DNA centered dogma for genetic information and cell identity is now evolving into a much more complex and flexible dimension provided by the discovery of the Epigenome. This comprises those chromosome structural and topological components that complement DNA information and contribute to genome functional organization. Current concept is that the Epigenome constitutes the dynamic molecular interface allowing the Genome to interact with the Environment. Exploring how the genome interacts with the environment is a key to fully understand cellular and complex organism mechanisms of adaptation and plasticity. Our work focuses on the role of an essential, specialized group or chromatin associated proteins named Polycomb (PcG) that control maintenance of transcription programs during development and in adult life. In particular PcG proteins exert epigenetic “memory” function by modifying chromosome structures at various levels to maintain gene silencing in particular through cell division. While in the past decade substantial progress was made in understanding PcG mechanisms acting in development and partially during cell cycle, very little is known about their role in adult post-mitotic tissues and more in general the role of the epigenome in adaptation. To this, we studied the role of PcG in the context of mammalian skeletal muscle cell differentiation. We previously reported specific dynamics of PRC2 proteins in myoblasts and myotubes, in particular the dynamics of PcG Histone H3 K27 Methyl Transferases (HMT), EZH2 and EZH1, the latter apparently replacing for EZH2 in differentiated myotubes. Ezh1 protein, although almost identical to Ezh2, shows a weak H3K27 HMT activity and its primary function remains elusive. Recent ChIPseq studies performed in differentiating muscle cells revealed that Ezh1 associates with active and not repressed regulatory regions to control RNA pol II elongation. Since H3K27 tri-methylation levels are virtually steady in non

  20. The Mendelian disorders of the epigenetic machinery.

    Bjornsson, Hans Tomas

    2015-10-01

    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 common phenotype; however, this is often seen in association with other more specific features in respective disorders. The specificity of some of the clinical features raises the question whether specific cell types are particularly sensitive to the loss of these factors. Most of these disorders demonstrate dosage sensitivity as loss of a single allele appears to be sufficient to cause the observed phenotypes. Although the pathogenic sequence is unknown for most of these disorders, there are several examples where disrupted expression of downstream target genes accounts for a substantial portion of the phenotype; hence, it may be useful to systematically map such disease-relevant target genes. Finally, two of these disorders (Rubinstein-Taybi and Kabuki syndromes) have shown post-natal rescue of markers of the neurological dysfunction with drugs that lead to histone deacetylase inhibition, indicating that some of these disorders may be treatable causes of intellectual disability. PMID:26430157

  1. Phenotype as Agent for Epigenetic Inheritance.

    Torday, John S; Miller, William B

    2016-01-01

    The conventional understanding of phenotype is as a derivative of descent with modification through Darwinian random mutation and natural selection. Recent research has revealed Lamarckian inheritance as a major transgenerational mechanism for environmental action on genomes whose extent is determined, in significant part, by germ line cells during meiosis and subsequent stages of embryological development. In consequence, the role of phenotype can productively be reconsidered. The possibility that phenotype is directed towards the effective acquisition of epigenetic marks in consistent reciprocation with the environment during the life cycle of an organism is explored. It is proposed that phenotype is an active agent in niche construction for the active acquisition of epigenetic marks as a dominant evolutionary mechanism rather than a consequence of Darwinian selection towards reproductive success. The reproductive phase of the life cycle can then be appraised as a robust framework in which epigenetic inheritance is entrained to affect growth and development in continued reciprocal responsiveness to environmental stresses. Furthermore, as first principles of physiology determine the limits of epigenetic inheritance, a coherent justification can thereby be provided for the obligate return of all multicellular eukaryotes to the unicellular state. PMID:27399791

  2. Epigenetics and Systemic Lupus Erythematosus: Unmet Needs.

    Meroni, Pier Luigi; Penatti, Alessandra Emiliana

    2016-06-01

    Systemic lupus erythematosus (SLE) is a chronic relapsing-remitting autoimmune disease affecting several organs. Although the management of lupus patients has improved in the last years, several aspects still remain challenging. More sensitive and specific biomarkers for an early diagnosis as well as for monitoring disease activity and tissue damage are needed. Genome-wide association and gene mapping studies have supported the genetic background for SLE susceptibility. However, the relatively modest risk association and the studies in twins have suggested a role for environmental and epigenetic factors, as well as genetic-epigenetic interaction. Accordingly, there is evidence that differences in DNA methylation, histone modifications, and miRNA profiling can be found in lupus patients versus normal subjects. Moreover, impaired DNA methylation on the inactive X-chromosome was suggested to explain, at least in part, the female prevalence of the disease. Epigenetic markers may be help in fulfilling the unmet needs for SLE by offering new diagnostic tools, new biomarkers for monitoring disease activity, or to better characterize patients with a silent clinical disease but with an active serology. Anti-DNA, anti-phospholipid, and anti-Ro/SSA autoantibodies are thought to be pathogenic for glomerulonephritis, recurrent thrombosis and miscarriages, and neonatal lupus, respectively. However, tissue damage occurs occasionally or, in some patients, only in spite of the persistent presence of the antibodies. Preliminary studies suggest that epigenetic mechanisms may explain why the damage takes place in some patients only or at a given time. PMID:26206675

  3. Epigenetic Systems View of Human Development.

    Gottlieb, Gilbert

    1991-01-01

    Discusses the history of the hierarchical epigenetic systems view as applied to human development and offers examples of its implementation. Notes the agreement by many authors that the multilevel systems view is the right model for developmental psychology in both human and animal studies. (BC)

  4. Design and Synthesis of Epigenetic Drugs

    Leurs, Ulrike

    2014-01-01

    Epigenetics have within the last decade evolved into an exciting new strategy to target diseases linked to changes in the transcriptome of a cell. Both DNA methylation and posttranslational modifications of histone proteins are important regulators of gene expression, and aberrant regulation...

  5. Epigenetics of inflammation, maternal infection and nutrition

    Studies have demonstrated that epigenetic changes such as DNA methylation, histone modification, and chromatin remodeling are linked to an increased inflammatory response as well as increased risk for chronic disease development. A few studies have begun to investigate whether dietary nutrients play...

  6. Dietary effects on adipocyte metabolism and epigenetics

    Obesity risk appears to be perpetuated across generations by way of programmed DNA alterations that occur in utero and that affect gene expression throughout the life span. Studies have demonstrated associations of maternal obesity and epigenetic changes, such as DNA methylation, histone modifica...

  7. Epigenetic control of embryonic stem cell fate

    Christophersen, Nicolaj Strøyer; Helin, Kristian

    2010-01-01

    be induced rapidly to differentiate. Maintaining this balance of stability versus plasticity is a challenge, and extensive studies in recent years have focused on understanding the contributions of transcription factors and epigenetic enzymes to the "stemness" properties of these cells. Identifying...

  8. Epigenetics and the Social Work Imperative

    Combs-Orme, Terri

    2013-01-01

    "Epigenesis" is the biochemical process through which some genes are expressed and others remain silent, and it reinforces and explains the powerful impact that the environment has on human development. Epigenetic effects occur not only through diet, chemical exposure, and high levels of environmental stress, but also through chronic poverty and…

  9. Chromatin and epigenetics in all their states

    Bey, Till; Jamge, Suraj; Klemme, Sonja; Komar, Dorota Natalia; Gall, Le Sabine; Mikulski, Pawel; Schmidt, Martin; Zicola, Johan; Berr, Alexandre

    2016-01-01

    In January 2016, the first Epigenetic and Chromatin Regulation of Plant Traits conference was held in Strasbourg, France. An all-star lineup of speakers, a packed audience of 130 participants from over 20 countries, and a friendly scientific atmosphere contributed to make this conference a meetin

  10. Nonlinear Epigenetic Variance: Review and Simulations

    Kan, Kees-Jan; Ploeger, Annemie; Raijmakers, Maartje E. J.; Dolan, Conor V.; van Der Maas, Han L. J.

    2010-01-01

    We present a review of empirical evidence that suggests that a substantial portion of phenotypic variance is due to nonlinear (epigenetic) processes during ontogenesis. The role of such processes as a source of phenotypic variance in human behaviour genetic studies is not fully appreciated. In addition to our review, we present simulation studies…

  11. Epigenetic regulation of caloric restriction in aging

    Daniel Michael

    2011-08-01

    Full Text Available Abstract The molecular mechanisms of aging are the subject of much research and have facilitated potential interventions to delay aging and aging-related degenerative diseases in humans. The aging process is frequently affected by environmental factors, and caloric restriction is by far the most effective and established environmental manipulation for extending lifespan in various animal models. However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. Epigenetic mechanisms have recently been recognized as major contributors to nutrition-related longevity and aging control. Two primary epigenetic codes, DNA methylation and histone modification, are believed to dynamically influence chromatin structure, resulting in expression changes of relevant genes. In this review, we assess the current advances in epigenetic regulation in response to caloric restriction and how this affects cellular senescence, aging and potential extension of a healthy lifespan in humans. Enhanced understanding of the important role of epigenetics in the control of the aging process through caloric restriction may lead to clinical advances in the prevention and therapy of human aging-associated diseases.

  12. Epigenetics as a First Exit Problem

    Aurell, E.; Sneppen, K.

    2002-01-01

    We develop a framework to discuss the stability of epigenetic states as first exit problems in dynamical systems with noise. We consider in particular the stability of the lysogenic state of the λ prophage. The formalism defines a quantitative measure of robustness of inherited states.

  13. Nonlinear epigenetic variance: review and simulations

    K.J. Kan; A. Ploeger; M.E.J. Raijmakers; C.V. Dolan; H.L.J. van der Maas

    2010-01-01

    We present a review of empirical evidence that suggests that a substantial portion of phenotypic variance is due to nonlinear (epigenetic) processes during ontogenesis. The role of such processes as a source of phenotypic variance in human behaviour genetic studies is not fully appreciated. In addit

  14. An Architectural Genetic and Epigenetic Perspective

    Stein, Gary S.; Stein, Janet L.; van Wijnen, Andre; Lian, Jane B.; Zaidi, Sayyed K.; Nickerson, Jeffrey; Montecino, Martin; Young, Daniel

    2010-01-01

    The organization and intranuclear localization of nucleic acids and regulatory proteins contribute to both genetic and epigenetic parameters of biological control. Regulatory machinery in the cell nucleus is functionally compartmentalized in microenvironments (focally organized sites where regulatory factors reside) that provide threshold levels of factors required for transcription, replication, repair and cell survival. The common denominator for nuclear organization of regulatory machinery...

  15. Epigenetics: an emerging player in gastric cancer.

    Kang, Changwon; Song, Ji-Joon; Lee, Jaeok; Kim, Mi Young

    2014-06-01

    Cancers, like other diseases, arise from gene mutations and/or altered gene expression, which eventually cause dysregulation of numerous proteins and noncoding RNAs. Changes in gene expression, i.e., upregulation of oncogenes and/or downregulation of tumor suppressor genes, can be generated not only by genetic and environmental factors but also by epigenetic factors, which are inheritable but nongenetic modifications of cellular chromosome components. Identification of the factors that contribute to individual cancers is a prerequisite to a full understanding of cancer mechanisms and the development of customized cancer therapies. The search for genetic and environmental factors has a long history in cancer research, but epigenetic factors only recently began to be associated with cancer formation, progression, and metastasis. Epigenetic alterations of chromatin include DNA methylation and histone modifications, which can affect gene-expression profiles. Recent studies have revealed diverse mechanisms by which chromatin modifiers, including writers, erasers and readers of the aforementioned modifications, contribute to the formation and progression of cancer. Furthermore, functional RNAs, such as microRNAs and long noncoding RNAs, have also been identified as key players in these processes. This review highlights recent findings concerning the epigenetic alterations associated with cancers, especially gastric cancer. PMID:24914365

  16. Epigenetic Effects of Human Breast Milk

    Elvira Verduci

    2014-04-01

    Full Text Available A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant’s health and his later life.

  17. Epigenetic Modulation in the treatment Atherosclerotic disease

    Mikaela M Byrne

    2014-10-01

    Full Text Available Cardiovascular disease is the single largest cause of death in the western world and its incidence is on the rise globally. Atherosclerosis, characterised by the development of atheromatus plaque, can trigger luminal narrowing and upon rupture result in myocardial infarction or ischemic stroke. Epigenetic mechanisms are a source of considerable research interest due to the role they play in gene regulation. Epigenetic mechanisms such as DNA methylation and histone acetylation have been identified as potential drug targets in the treatment of cardiovascular disease. miRNAs are known to play a role in gene silencing, which has been widely investigated in cancer. In comparison, the role they play in cardiovascular disease and plaque rupture is not well understood. Nutritional epigenetic modifiers from dietary components, for instance sulforaphane found in broccoli, have been shown to suppress the pro-inflammatory response through transcription factor activation. This review will discuss current and potential epigenetic therapeutics for the treatment of cardiovascular disease, focusing on the use of miRNAs and dietary supplements such as sulforaphane and protocatechuic aldehyde.

  18. Epigenetic architecture and miRNA: reciprocal regulators

    Wiklund, Erik Digman; Kjems, Jørgen; Clark, Susan

    2010-01-01

    Deregulation of epigenetic and microRNA (miRNA) pathways are emerging as key events in carcinogenesis. miRNA genes can be epigenetically regulated and miRNAs can themselves repress key enzymes that drive epigenetic remodeling. Epigenetic and miRNA functions are thus tightly interconnected......RNAs) are considered especially promising in clinical applications, and their biogenesis and function is a subject of active research. In this review, the current status of epigenetic miRNA regulation is summarized and future therapeutic prospects in the field are discussed with a focus on cancer....

  19. Epigenetic disruption of cell signaling in nasopharyngeal carcinoma

    Li-Li Li; Xing-Sheng Shu; Zhao-Hui Wang; Ya Cao; Qian Tao

    2011-01-01

    Nasopharyngeal carcinoma (NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia. Alternative to genetic changes, aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/ or histone modifications. These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC. In this review, we summariye the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research. Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.

  20. Epigenetics and etiology of neurodegenerative diseases

    Beata M. Gruber

    2011-08-01

    Full Text Available Determination of specific gene profile expression is essential for morphological and functional differentiation of cells in the human organism. The human genome consists of 25–30 thousands genes but only some of them are expressed in each cell. Epigenetic modifications such as DNA methylation, histone and chromatin modifications or non-coding RNA functions are also responsible for the unique gene expression patterns. It is suggested that transcriptional gene activation is related to hypomethylation and the transcriptionally non-active sequences are hypermethylated. Covalent histone modifications and DNA methylation are correlated and interacting. Chromatin modeling is regulated not only by specific enzymes but also by protein kinases or phosphatases and coactivators, such as CBP. Such interaction makes the “histone code” which with the chromatin proteins determines gene expression patterns as the response to external agents. Evidence of a major role for epigenetic modifications in neurological disease has come from three converging lines of enquiry: high conservation throughout evolution of the histone residues that are the target for epigenetic modifications; association between mutations in epigenetic components and multisystem disease syndrome in the nervous system; and broad efficacy of small-molecule epigenetic modulators, e.g. histone deacetylase inhibitors, in models of neurological diseases incurable up to now, such as Huntington’s disease, (HD, Parkinson’s disease (PD and Alzheimer’s disease (AD. This article is a survey of the literature concerning the characterization of gene expression patterns correlated with some neurodegenerative diseases. The processes of DNA hypomethylation and histone acetylation are emphasized. The histone deacetylases are indicated as the basis for design of potential drugs.

  1. Lipid reorganization induced by Shiga toxin clustering on planar membranes.

    Barbara Windschiegl

    Full Text Available The homopentameric B-subunit of bacterial protein Shiga toxin (STxB binds to the glycolipid Gb(3 in plasma membranes, which is the initial step for entering cells by a clathrin-independent mechanism. It has been suggested that protein clustering and lipid reorganization determine toxin uptake into cells. Here, we elucidated the molecular requirements for STxB induced Gb(3 clustering and for the proposed lipid reorganization in planar membranes. The influence of binding site III of the B-subunit as well as the Gb(3 lipid structure was investigated by means of high resolution methods such as fluorescence and scanning force microscopy. STxB was found to form protein clusters on homogenous 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC/cholesterol/Gb(3 (65:30:5 bilayers. In contrast, membranes composed of DOPC/cholesterol/sphingomyelin/Gb(3 (40:35:20:5 phase separate into a liquid ordered and liquid disordered phase. Dependent on the fatty acid composition of Gb(3, STxB-Gb(3 complexes organize within the liquid ordered phase upon protein binding. Our findings suggest that STxB is capable of forming a new membrane phase that is characterized by lipid compaction. The significance of this finding is discussed in the context of Shiga toxin-induced formation of endocytic membrane invaginations.

  2. Dynamic reorganization of photosynthetic supercomplexes during environmental acclimation

    Jun eMinagawa

    2013-12-01

    Full Text Available Plants and algae have acquired the ability to acclimate to ever-changing environments in order to survive. During photosynthesis, light energy is converted by several membrane protein supercomplexes into electrochemical energy, which is eventually used to assimilate CO2. The efficiency of photosynthesis is modulated by many environmental factors such as quality and quantity of light, temperature, drought, and CO2 concentration, among others. Accumulating evidence indicates that photosynthetic supercomplexes undergo supramolecular reorganization within a short timeframe during acclimation to an environmental change. This reorganization includes state transitions that balance the excitation of photosystem I and II by shuttling peripheral antenna proteins between the two, thermal energy dissipation that occurs at energy-quenching sites within the light-harvesting antenna generated for negative feedback when excess light is absorbed, and cyclic electron flow that is facilitated between photosystem I and the cytochrome bf complex when cells demand more ATP and/or need to activate energy dissipation. This review will highlight the recent findings regarding these environmental acclimation events in model organisms with particular attention to the unicellular green alga C. reinhardtii and with reference to the vascular plant A. thaliana, which offers a glimpse into the dynamic behavior of photosynthetic machineries in nature.

  3. From network structure to network reorganization: implications for adult neurogenesis

    Schneider-Mizell, Casey M.; Parent, Jack M.; Ben-Jacob, Eshel; Zochowski, Michal R.; Sander, Leonard M.

    2010-12-01

    Networks can be dynamical systems that undergo functional and structural reorganization. One example of such a process is adult hippocampal neurogenesis, in which new cells are continuously born and incorporate into the existing network of the dentate gyrus region of the hippocampus. Many of these introduced cells mature and become indistinguishable from established neurons, joining the existing network. Activity in the network environment is known to promote birth, survival and incorporation of new cells. However, after epileptogenic injury, changes to the connectivity structure around the neurogenic niche are known to correlate with aberrant neurogenesis. The possible role of network-level changes in the development of epilepsy is not well understood. In this paper, we use a computational model to investigate how the structural and functional outcomes of network reorganization, driven by addition of new cells during neurogenesis, depend on the original network structure. We find that there is a stable network topology that allows the network to incorporate new neurons in a manner that enhances activity of the persistently active region, but maintains global network properties. In networks having other connectivity structures, new cells can greatly alter the distribution of firing activity and destroy the initial activity patterns. We thus find that new cells are able to provide focused enhancement of network only for small-world networks with sufficient inhibition. Network-level deviations from this topology, such as those caused by epileptogenic injury, can set the network down a path that develops toward pathological dynamics and aberrant structural integration of new cells.

  4. Reorganization of the power distribution sector in India

    This paper presents the central issues for electricity-sector reform in India, as they grew out of the reform process that began in 1991, and within the context of the sector's organization, regulatory structure, and other institutional characteristics. The paper argues that India's current reform policies will not be sufficient to achieve reliable, efficient power because distribution reform has not been done. Undertaking distribution reform is a difficult path to tread because of the absence of global consensus on best practices and conflicting forces, both economic and political. The paper analyzes alternative institutional structures for reform in the distribution sector. The findings include that the objectives of coverage and efficiency may conflict, that economically efficient reorganization may be politically unachievable and that the small, municipally owned firm may be the best compromise. Since many Indian states are economically and politically diverse from each other, and include both large served and unserved areas, there is scope to vary the organizational structure depending on the state's situation. This paper provides a means to do so. The agenda for policymakers is to identify the situation in their respective states and choose a reorganization path that is the best compromise

  5. From network structure to network reorganization: implications for adult neurogenesis

    Networks can be dynamical systems that undergo functional and structural reorganization. One example of such a process is adult hippocampal neurogenesis, in which new cells are continuously born and incorporate into the existing network of the dentate gyrus region of the hippocampus. Many of these introduced cells mature and become indistinguishable from established neurons, joining the existing network. Activity in the network environment is known to promote birth, survival and incorporation of new cells. However, after epileptogenic injury, changes to the connectivity structure around the neurogenic niche are known to correlate with aberrant neurogenesis. The possible role of network-level changes in the development of epilepsy is not well understood. In this paper, we use a computational model to investigate how the structural and functional outcomes of network reorganization, driven by addition of new cells during neurogenesis, depend on the original network structure. We find that there is a stable network topology that allows the network to incorporate new neurons in a manner that enhances activity of the persistently active region, but maintains global network properties. In networks having other connectivity structures, new cells can greatly alter the distribution of firing activity and destroy the initial activity patterns. We thus find that new cells are able to provide focused enhancement of network only for small-world networks with sufficient inhibition. Network-level deviations from this topology, such as those caused by epileptogenic injury, can set the network down a path that develops toward pathological dynamics and aberrant structural integration of new cells

  6. Congruency of body-related information induces somatosensory reorganization.

    Cardini, Flavia; Longo, Matthew R

    2016-04-01

    Chronic pain and impaired tactile sensitivity are frequently associated with "blurred" representations in the somatosensory cortex. The factors that produce such somatosensory blurring, however, remain poorly understood. We manipulated visuo-tactile congruence to investigate its role in promoting somatosensory reorganization. To this aim we used the mirror box illusion that produced in participants the subjective feeling of looking directly at their left hand, though they were seeing the reflection of their right hand. Simultaneous touches were applied to the middle or ring finger of each hand. In one session, the same fingers were touched (for example both middle fingers), producing a congruent percept; in the other session different fingers were touched, producing an incongruent percept. In the somatosensory system, suppressive interactions between adjacent stimuli are an index of intracortical inhibitory function. After each congruent and incongruent session, we recorded somatosensory evoked potential (SEPs) elicited by electrocutaneous stimulation of the left ring and middle fingers, either individually or simultaneously. A somatosensory suppression index (SSI) was calculated as the difference in amplitude between the sum of potentials evoked by the two individually stimulated fingers and the potentials evoked by simultaneous stimulation of both fingers. This SSI can be taken as an index of the strength of inhibitory interactions and consequently can provide a measure of how distinct the representations of the two fingers are. Results showed stronger SSI in the P100 component after congruent than incongruent stimulation, suggesting the key role of congruent sensory information about the body in inducing somatosensory reorganization. PMID:26902158

  7. Using reinforcement learning to provide stable brain-machine interface control despite neural input reorganization.

    Pohlmeyer, Eric A; Mahmoudi, Babak; Geng, Shijia; Prins, Noeline W; Sanchez, Justin C

    2014-01-01

    Brain-machine interface (BMI) systems give users direct neural control of robotic, communication, or functional electrical stimulation systems. As BMI systems begin transitioning from laboratory settings into activities of daily living, an important goal is to develop neural decoding algorithms that can be calibrated with a minimal burden on the user, provide stable control for long periods of time, and can be responsive to fluctuations in the decoder's neural input space (e.g. neurons appearing or being lost amongst electrode recordings). These are significant challenges for static neural decoding algorithms that assume stationary input/output relationships. Here we use an actor-critic reinforcement learning architecture to provide an adaptive BMI controller that can successfully adapt to dramatic neural reorganizations, can maintain its performance over long time periods, and which does not require the user to produce specific kinetic or kinematic activities to calibrate the BMI. Two marmoset monkeys used the Reinforcement Learning BMI (RLBMI) to successfully control a robotic arm during a two-target reaching task. The RLBMI was initialized using random initial conditions, and it quickly learned to control the robot from brain states using only a binary evaluative feedback regarding whether previously chosen robot actions were good or bad. The RLBMI was able to maintain control over the system throughout sessions spanning multiple weeks. Furthermore, the RLBMI was able to quickly adapt and maintain control of the robot despite dramatic perturbations to the neural inputs, including a series of tests in which the neuron input space was deliberately halved or doubled. PMID:24498055

  8. Using reinforcement learning to provide stable brain-machine interface control despite neural input reorganization.

    Eric A Pohlmeyer

    Full Text Available Brain-machine interface (BMI systems give users direct neural control of robotic, communication, or functional electrical stimulation systems. As BMI systems begin transitioning from laboratory settings into activities of daily living, an important goal is to develop neural decoding algorithms that can be calibrated with a minimal burden on the user, provide stable control for long periods of time, and can be responsive to fluctuations in the decoder's neural input space (e.g. neurons appearing or being lost amongst electrode recordings. These are significant challenges for static neural decoding algorithms that assume stationary input/output relationships. Here we use an actor-critic reinforcement learning architecture to provide an adaptive BMI controller that can successfully adapt to dramatic neural reorganizations, can maintain its performance over long time periods, and which does not require the user to produce specific kinetic or kinematic activities to calibrate the BMI. Two marmoset monkeys used the Reinforcement Learning BMI (RLBMI to successfully control a robotic arm during a two-target reaching task. The RLBMI was initialized using random initial conditions, and it quickly learned to control the robot from brain states using only a binary evaluative feedback regarding whether previously chosen robot actions were good or bad. The RLBMI was able to maintain control over the system throughout sessions spanning multiple weeks. Furthermore, the RLBMI was able to quickly adapt and maintain control of the robot despite dramatic perturbations to the neural inputs, including a series of tests in which the neuron input space was deliberately halved or doubled.

  9. Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors.

    Andrea Sottoriva

    2011-05-01

    Full Text Available The cancer stem cell (CSC concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult to interpret. An important reason for this is that most experimental data that support this model rely on transplantation studies. In this study we use a novel cellular Potts model to elucidate the dynamics of established malignancies that are driven by a small subset of CSCs. Our results demonstrate that epigenetic mutations that occur during mitosis display highly altered dynamics in CSC-driven malignancies compared to a classical, non-hierarchical model of growth. In particular, the heterogeneity observed in CSC-driven tumors is considerably higher. We speculate that this feature could be used in combination with epigenetic (methylation sequencing studies of human malignancies to prove or refute the CSC hypothesis in established tumors without the need for transplantation. Moreover our tumor growth simulations indicate that CSC-driven tumors display evolutionary features that can be considered beneficial during tumor progression. Besides an increased heterogeneity they also exhibit properties that allow the escape of clones from local fitness peaks. This leads to more aggressive phenotypes in the long run and makes the neoplasm more adaptable to stringent selective forces such as cancer treatment. Indeed when therapy is applied the clone landscape of the regrown tumor is more aggressive with respect to the primary tumor, whereas the classical model demonstrated similar patterns before and after therapy. Understanding these often counter-intuitive fundamental properties of (non-hierarchically organized malignancies is a crucial step in validating the CSC concept as well as providing insight into the therapeutical consequences of this model.

  10. Transgenerational epigenetic inheritance in mammals: how good is the evidence?

    van Otterdijk, Sanne D; Michels, Karin B

    2016-07-01

    Epigenetics plays an important role in orchestrating key biologic processes. Epigenetic marks, including DNA methylation, histones, chromatin structure, and noncoding RNAs, are modified throughout life in response to environmental and behavioral influences. With each new generation, DNA methylation patterns are erased in gametes and reset after fertilization, probably to prevent these epigenetic marks from being transferred from parents to their offspring. However, some recent animal studies suggest an apparent resistance to complete erasure of epigenetic marks during early development, enabling transgenerational epigenetic inheritance. Whether there are similar mechanisms in humans remains unclear, with the exception of epigenetic imprinting. Nevertheless, a distinctly different mechanism-namely, intrauterine exposure to environmental stressors that may affect establishment of the newly composing epigenetic patterns after fertilization-is often confused with transgenerational epigenetic inheritance. In this review, we delineate the definition of and requirement for transgenerational epigenetic inheritance, differentiate it from the consequences of intrauterine exposure, and discuss the available evidence in both animal models and humans.-Van Otterdijk, S. D., Michels, K. B. Transgenerational epigenetic inheritance in mammals: how good is the evidence? PMID:27037350

  11. Relationship between chronic pain and brain reorganization after deafferentation: A systematic review of functional MRI findings

    C.R. Jutzeler

    2015-01-01

    Conclusion: Based solely on advanced functional neuroimaging results, there is only limited evidence for a relationship between chronic pain intensity and reorganization after deafferentation. The review demonstrates the need for additional neuroimaging studies to clarify the relationship between chronic pain and reorganization.

  12. 13 CFR 108.470 - SBA approval of merger, consolidation, or reorganization of NMVC Company.

    2010-01-01

    ... Control Change in Structure of Nmvc Company § 108.470 SBA approval of merger, consolidation, or reorganization of NMVC Company. You may not merge, consolidate, change form of organization (corporation or..., consolidation, or reorganization of NMVC Company. 108.470 Section 108.470 Business Credit and Assistance...

  13. 44 CFR 64.4 - Effect on community eligibility resulting from boundary changes, governmental reorganization, etc.

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Effect on community eligibility resulting from boundary changes, governmental reorganization, etc. 64.4 Section 64.4 Emergency... Effect on community eligibility resulting from boundary changes, governmental reorganization, etc....

  14. A theoretical description of charge reorganization energies in molecular organic P-type semiconductors.

    Brückner, Charlotte; Engels, Bernd

    2016-06-01

    Charge transport properties of materials composed of small organic molecules are important for numerous optoelectronic applications. A material's ability to transport charges is considerably influenced by the charge reorganization energies of the composing molecules. Hence, predictions about charge-transport properties of organic materials deserve reliable statements about these charge reorganization energies. However, using density functional theory which is mostly used for the predictions, the computed reorganization energies depend strongly on the chosen functional. To gain insight, a benchmark of various density functionals for the accurate calculation of charge reorganization energies is presented. A correlation between the charge reorganization energies and the ionization potentials is found which suggests applying IP-tuning to obtain reliable values for charge reorganization energies. According to benchmark investigations with IP-EOM-CCSD single-point calculations, the tuned functionals provide indeed more reliable charge reorganization energies. Among the standard functionals, ωB97X-D and SOGGA11X yield accurate charge reorganization energies in comparison with IP-EOM-CCSD values. © 2016 Wiley Periodicals, Inc. PMID:27059122

  15. Epigenetics of the yeast galactose genetic switch

    Paike Jayadeva Bhat; Revathi S Iyer

    2009-10-01

    The transcriptional activation of enzymes involved in galactose utilization (GAL genes) in Saccharomyces cerevisiae is regulated by a complex interplay between three regulatory proteins encoded by GAL4 (transcriptional activator), GAL3 (signal transducer) and GAL80 (repressor). The relative concentrations of the signal transducer and the repressor are maintained by autoregulation. Cells disabled for autoregulation exhibit phenotypes distinctly different from that of the wild type cells, enabling us to explore the biological significance of autoregulation. The redundancy in signal transduction due to the presence of GAL1 (alternate signal transducer) also makes it a suitable model to understand the phenomenon of epigenetics. In this article we review some of the recent attempts made to understand the importance of epigenetics in the establishment of cellular and transcriptional memory.

  16. [Transcriptome analysis and epigenetic analysis during osteoclastogenesis].

    Nakamura, Shinya; Tanaka, Sakae

    2016-04-01

    The importance of receptor activator of nuclear factor-κB ligand(RANKL)during osteoclastogenesis was discovered in 1998. After that Nfatc1, downstream gene of RANKL-RANK signaling, was identified as a master regulator of osteoclastogenesis by transcriptome analysis. In recent years, with the advancement of epigenetic analysis method and big data analysis technology, epigenetic analysis about osteoclastogenesis gradually progresses. Some papers using H3K4me3 and H3K27me3 histone modification change data, DNase-seq data and formaldehyde-assisted isolation of regulatory elements(FAIRE)-seq data during osteoclastogenesis were published recently. It will probably contribute to elucidate the crosstalk between osteoclasts and osteoblasts, osteocytes or chondrocytes in the future. PMID:27013627

  17. Epigenetic Modifications of Major Depressive Disorder

    Kathleen Saavedra

    2016-08-01

    Full Text Available Major depressive disorder (MDD is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders.

  18. Epigenetic alterations associated with cholangiocarcinoma (review).

    Isomoto, Hajime

    2009-08-01

    Cholangiocarcinoma (CCA) is a highly lethal malignant tumor arising from the biliary tract epithelium. Chronic inflammatory conditions, including primary sclerosing cholangitis, liver fluke infestation, and hepatolithiasis, are considered risk factors, but the cause is still unknown in most cases. Recent advances in molecular pathogenesis have highlighted the importance of epigenetic alterations, including promoter hypermethylation and histone deacetylation, in the process of cholangiocarcinogenesis. More recently, research interest has been focusing on microRNA (mir), a major subtype of non-coding RNA. Mir is highly conserved among species and regulates the expression of specific target genes by binding to the 3'-untranslated regions of messenger RNA. The number of studies on a possible link between mir and various cancers is growing. This review provides a comprehensive overview of the genes currently known to be hypermethylated in CCA and their putative roles in cholangiocarcinogenesis. The epigenetic role of mir in the pathogenesis of CCA is also discussed. PMID:19578760

  19. Atherogenic Factors and Their Epigenetic Relationships

    Ana Z. Fernandez

    2010-01-01

    Full Text Available Hypercholesterolemia, homocysteine, oxidative stress, and hyperglycemia have been recognized as the major risk factors for atherogenesis. Their impact on the physiology and biochemistry of vascular cells has been widely demonstrated for the last century. However, the recent discovery of the role of epigenetics in human disease has opened up a new field in the study of atherogenic factors. Thus, epigenetic tags in endothelial, smooth muscle, and immune cells seem to be differentially affected by similar atherogenic stimuli. This paper summarizes some recent works on expression of histone-modifying enzymes and DNA methylation directly linked to the presence of risk factors that could lead to the development or prevention of the atherosclerotic process.

  20. Reorganization of a granular medium around a localized transformation

    Merceron, Aymeric; Sauret, Alban; Jop, Pierre

    2016-06-01

    Physical and chemical transformation processes in reactive granular media involve the reorganization of the structure. In this paper, we study experimentally the rearrangements of a two-dimensional (2D) granular packing undergoing a localized transformation. We track the position and evolution of all the disks that constitute the granular packing when either a large intruder shrinks in size or is pulled out of the granular structure. In the two situations the displacements at long time are similar to 2D quasistatic silo flows whereas the short-time dynamic is heterogeneous in both space and time. We observe an avalanchelike behavior with power-law distributed events uncorrelated in time. In addition, the instantaneous evolutions of the local solid fraction exhibit self-similar distributions. The averages and the standard deviations of the solid fraction variations can be rescaled, suggesting a single mechanism of rearrangement.

  1. Glassy protein dynamics and gigantic solvent reorganization energy of plastocyanin

    LeBard, David N

    2007-01-01

    We report the results of Molecular Dynamics simulations of electron transfer activation parameters of plastocyanin metalloprotein involved as electron carrier in natural photosynthesis. We have discovered that slow, non-ergodic conformational fluctuations of the protein, coupled to hydrating water, result in a very broad distribution of donor-acceptor energy gaps far exceeding that observed for commonly studied inorganic and organic donor-acceptor complexes. The Stokes shift is not affected by these fluctuations and can be calculated from solvation models in terms of the response of the solvent dipolar polarization. The non-ergodic character of large-amplitude protein/water mobility breaks the strong link between the Stokes shift and reorganization energy characteristic of equilibrium (ergodic) theories of electron transfer. This mechanism might be responsible for low activation barriers in natural electron transfer proteins characterized by low reaction free energy.

  2. A gauge-invariant reorganization of thermal gauge theory

    This dissertation is devoted to the study of thermodynamics for quantum gauge theories. The poor convergence of quantum field theory at finite temperature has been the main obstacle in the practical applications of thermal QCD for decades. In this dissertation I apply hard-thermal-loop perturbation theory, which is a gauge-invariant reorganization of the conventional perturbative expansion for quantum gauge theories to the thermodynamics of QED and Yang-Mills theory to three-loop order. For the Abelian case, I present a calculation of the free energy of a hot gas of electrons and photons by expanding in a power series in mD/T, mf/T and e2, where mD and mf are the photon and electron thermal masses, respectively, and e is the coupling constant. I demonstrate that the hard-thermal-loop perturbation reorganization improves the convergence of the successive approximations to the QED free energy at large coupling, e ∝ 2. For the non-Abelian case, I present a calculation of the free energy of a hot gas of gluons by expanding in a power series in mD/T and g2, where mD is the gluon thermal mass and g is the coupling constant. I show that at three-loop order hard-thermal-loop perturbation theory is compatible with lattice results for the pressure, energy density, and entropy down to temperatures T ∝ 2 - 3 Tc. The results suggest that HTLpt provides a systematic framework that can be used to calculate static and dynamic quantities for temperatures relevant at LHC. (orig.)

  3. A gauge-invariant reorganization of thermal gauge theory

    Su, Nan

    2010-07-01

    This dissertation is devoted to the study of thermodynamics for quantum gauge theories. The poor convergence of quantum field theory at finite temperature has been the main obstacle in the practical applications of thermal QCD for decades. In this dissertation I apply hard-thermal-loop perturbation theory, which is a gauge-invariant reorganization of the conventional perturbative expansion for quantum gauge theories to the thermodynamics of QED and Yang-Mills theory to three-loop order. For the Abelian case, I present a calculation of the free energy of a hot gas of electrons and photons by expanding in a power series in m{sub D}/T, m{sub f}/T and e{sup 2}, where m{sub D} and m{sub f} are the photon and electron thermal masses, respectively, and e is the coupling constant. I demonstrate that the hard-thermal-loop perturbation reorganization improves the convergence of the successive approximations to the QED free energy at large coupling, e {proportional_to} 2. For the non-Abelian case, I present a calculation of the free energy of a hot gas of gluons by expanding in a power series in m{sub D}/T and g{sup 2}, where m{sub D} is the gluon thermal mass and g is the coupling constant. I show that at three-loop order hard-thermal-loop perturbation theory is compatible with lattice results for the pressure, energy density, and entropy down to temperatures T {proportional_to} 2 - 3 T{sub c}. The results suggest that HTLpt provides a systematic framework that can be used to calculate static and dynamic quantities for temperatures relevant at LHC. (orig.)

  4. Epigenetic Mechanisms of Rubinstein-Taybi Syndrome

    Park, Elizabeth; Kim, Yunha; Ryu, Hyun; Kowall, Neil W.; Lee, Junghee; Ryu, Hoon

    2014-01-01

    Rubinstein-Taybi Syndrome (RTS) is an incurable genetic disorder with combination of mental retardation and physical features including broad thumbs and toes, craniofacial abnormalities, and growth deficiency. While the autosomal dominant mode of transmission is limitedly known, the majority of cases are attributable to de novo mutations in RTS. The first identified gene associated with RTS is CREB-binding protein (CREBBP/CBP). Alterations of the epigenetic ‘histone code’ due to dysfunction o...

  5. Epigenetics and etiology of neurodegenerative diseases

    Beata M. Gruber

    2011-01-01

    Determination of specific gene profile expression is essential for morphological and functional differentiation of cells in the human organism. The human genome consists of 25–30 thousands genes but only some of them are expressed in each cell. Epigenetic modifications such as DNA methylation, histone and chromatin modifications or non-coding RNA functions are also responsible for the unique gene expression patterns. It is suggested that transcriptional gene activation is related to hypomethy...

  6. On the road to epigenetic therapy.

    Walton, Emma L

    2016-06-01

    In this issue of the Biomedical Journal, we examine how far the explosion of epigenetic studies in recent years has translated to benefits for patients in the clinic, and we highlight an original study suggesting that increased vegetable intake protects against osteoporotic fractures. We also hear several opinions on the use, or perhaps misuse, of Impact Factor and what the future should hold for this publication metric. PMID:27621116

  7. Epigenetic Influences on Brain Development and Plasticity

    Fagiolini, Michela; Jensen, Catherine L.; Champagne, Frances A.

    2009-01-01

    A fine interplay exists between sensory experience and innate genetic programs leading to the sculpting of neuronal circuits during early brain development. Recent evidence suggests that the dynamic regulation of gene expression through epigenetic mechanisms is at the interface between environmental stimuli and long-lasting molecular, cellular and complex behavioral phenotypes acquired during periods of developmental plasticity. Understanding these mechanisms may give insight into the formati...

  8. Epigenetic Regulation of EBV Persistence and Oncogenesis

    Tempera, Italo; Lieberman, Paul M

    2014-01-01

    Epigenetic mechanisms play a fundamental role in generating diverse and heritable patterns of viral and cellular gene expression. Epstein-Barr Virus (EBV) can adopt a variety of gene expression programs that are necessary for long-term viral persistence and latency in multiple host-cell types and conditions. The latent viral genomes assemble into chromatin structures with different histone and DNA modifications patterns that control viral gene expression. Variations in nucleosome organization...

  9. Noncoding Elements: Evolution and Epigenetic Regulation

    Seridi, Loqmane

    2016-03-09

    When the human genome project was completed, it revealed a surprising result. 98% of the genome did not code for protein of which more than 50% are repeats— later known as ”Junk DNA”. However, comparative genomics unveiled that many noncoding elements are evolutionarily constrained; thus luckily to have a role in genome stability and regulation. Though, their exact functions remained largely unknown. Several large international consortia such as the Functional Annotation of Mammalian Genomes (FANTOM) and the Encyclopedia of DNA Elements (ENCODE) were set to understand the structure and the regulation of the genome. Specifically, these endeavors aim to measure and reveal the transcribed components and functional elements of the genome. One of the most the striking findings of these efforts is that most of the genome is transcribed, including non-conserved noncoding elements and repeat elements. Specifically, we investigated the evolution and epigenetic properties of noncoding elements. 1. We compared genomes of evolutionarily distant species and showed the ubiquity of constrained noncoding elements in metazoa. 2. By integrating multi-omic data (such as transcriptome, nucleosome profiling, histone modifications), I conducted a comprehensive analysis of epigenetic properties (chromatin states) of conserved noncoding elements in insects. We showed that those elements have distinct and protective sequence features, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. 3. I focused on the relationship between enhancers and repetitive elements. Using Cap Analysis of Gene Expression (CAGE) and RNASeq, I compiled a full catalog of active enhancers (a class of noncoding elements) during myogenesis of human primary cells of healthy donors and donors affected by Duchenne muscular dystrophy (DMD). Comparing the two time-courses, a significant change in the epigenetic

  10. Adaptive Insecure Attachment and Resource Control Strategies during Middle Childhood

    Chen, Bin-Bin; Chang, Lei

    2012-01-01

    By integrating the life history theory of attachment with resource control theory, the current study examines the hypothesis that insecure attachment styles reorganized in middle childhood are alternative adaptive strategies used to prepare for upcoming competition with the peer group. A sample of 654 children in the second through seventh grades…

  11. Formation of sanitation potential as an instrument of light industry enterprises reorganization management

    Larionova, Katerina Leonidivna

    2012-11-01

    Full Text Available Some existing approaches to defining the essence of reorganization potential aredescribed and the author's vision of this category is offered in the article. This definition takes intoaccount not only the resource approach, but a systematic and an effective ones as well. Theinterrelation between the concepts of reorganization potential and sanitation ability is substantiatedas well as the reorganization potential structure taking into account the industry sector theenterprises belong to is determined . On the basis of the certain peculiarities of light industryenterprises activity it's quite reasonable to identifiy the main components of reorganizationpotential of such enterprises, namely: financial, labor, marketing, production and innovation andinvestment potential. A system of light industry enterprises reorganization potential interrelationswas developed for being used while constructing the organizational and economic mechanism ofenterprise’s rehabilitation. The place of reorganization potential’s assessment in the economictheoreticalresearch of this phenomenon by integral expression considering the influence ofexogenous and endogenous factors is defined in the article

  12. Epigenetic targeting of ovarian cancer stem cells.

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  13. Titration and hysteresis in epigenetic chromatin silencing

    Epigenetic mechanisms of silencing via heritable chromatin modifications play a major role in gene regulation and cell fate specification. We consider a model of epigenetic chromatin silencing in budding yeast and study the bifurcation diagram and characterize the bistable and the monostable regimes. The main focus of this paper is to examine how the perturbations altering the activity of histone modifying enzymes affect the epigenetic states. We analyze the implications of having the total number of silencing proteins, given by the sum of proteins bound to the nucleosomes and the ones available in the ambient, to be constant. This constraint couples different regions of chromatin through the shared reservoir of ambient silencing proteins. We show that the response of the system to perturbations depends dramatically on the titration effect caused by the above constraint. In particular, for a certain range of overall abundance of silencing proteins, the hysteresis loop changes qualitatively with certain jump replaced by continuous merger of different states. In addition, we find a nonmonotonic dependence of gene expression on the rate of histone deacetylation activity of Sir2. We discuss how these qualitative predictions of our model could be compared with experimental studies of the yeast system under anti-silencing drugs. (paper)

  14. Epigenetics and cardiovascular risk in childhood.

    Martino, Francesco; Magenta, Alessandra; Pannarale, Giuseppe; Martino, Eliana; Zanoni, Cristina; Perla, Francesco M; Puddu, Paolo E; Barillà, Francesco

    2016-08-01

    Cardiovascular disease (CVD) can arise at the early stages of development and growth. Genetic and environmental factors may interact resulting in epigenetic modifications with abnormal phenotypic expression of genetic information without any change in the nucleotide sequence of DNA. Maternal dietary imbalance, inadequate to meet the nutritional needs of the fetus can lead to intrauterine growth retardation, decreased gestational age, low birth weight, excessive post-natal growth and metabolic alterations, with subsequent appearance of CVD risk factors. Fetal exposure to high cholesterol, diabetes and maternal obesity is associated with increased risk and progression of atherosclerosis. Maternal smoking during pregnancy and exposure to various environmental pollutants induce epigenetic alterations of gene expression relevant to the onset or progression of CVD. In children with hypercholesterolemia and/or obesity, oxidative stress activates platelets and monocytes, which release proinflammatory and proatherogenic substances, inducing endothelial dysfunction, decreased Doppler flow-mediated dilation and increased carotid intima-media thickness. Primary prevention of atherosclerosis should be implemented early. It is necessary to identify, through screening, high-risk apparently healthy children and take care of them enforcing healthy lifestyle (mainly consisting of Mediterranean diet and physical activity), prescribing nutraceuticals and eventual medications, if required by a high-risk profile. The key issue is the restoration of endothelial function in the reversible stage of atherosclerosis. Epigenetics may provide new markers for an early identification of children at risk and thereby develop innovative therapies and specific nutritional interventions in critical times. PMID:27367935

  15. Epigenetic Changes in Diabetes and Cardiovascular Risk.

    Keating, Samuel T; Plutzky, Jorge; El-Osta, Assam

    2016-05-27

    Cardiovascular complications remain the leading causes of morbidity and premature mortality in patients with diabetes mellitus. Studies in humans and preclinical models demonstrate lasting gene expression changes in the vasculopathies initiated by previous exposure to high glucose concentrations and the associated overproduction of reactive oxygen species. The molecular signatures of chromatin architectures that sensitize the genome to these and other cardiometabolic risk factors of the diabetic milieu are increasingly implicated in the biological memory underlying cardiovascular complications and now widely considered as promising therapeutic targets. Atherosclerosis is a complex heterocellular disease where the contributing cell types possess distinct epigenomes shaping diverse gene expression. Although the extent that pathological chromatin changes can be manipulated in human cardiovascular disease remains to be established, the clinical applicability of epigenetic interventions will be greatly advanced by a deeper understanding of the cell type-specific roles played by writers, erasers, and readers of chromatin modifications in the diabetic vasculature. This review details a current perspective of epigenetic mechanisms of macrovascular disease in diabetes mellitus and highlights recent key descriptions of chromatinized changes associated with persistent gene expression in endothelial, smooth muscle, and circulating immune cells relevant to atherosclerosis. Furthermore, we discuss the challenges associated with pharmacological targeting of epigenetic networks to correct abnormal or deregulated gene expression as a strategy to alleviate the clinical burden of diabetic cardiovascular disease. PMID:27230637

  16. Dynamic and task-dependent encoding of speech and voice by phase reorganization of cortical oscillations.

    Bonte, Milene; Valente, Giancarlo; Formisano, Elia

    2009-02-11

    Speech and vocal sounds are at the core of human communication. Cortical processing of these sounds critically depends on behavioral demands. However, the neurocomputational mechanisms enabling this adaptive processing remain elusive. Here we examine the task-dependent reorganization of electroencephalographic responses to natural speech sounds (vowels /a/, /i/, /u/) spoken by three speakers (two female, one male) while listeners perform a one-back task on either vowel or speaker identity. We show that dynamic changes of sound-evoked responses and phase patterns of cortical oscillations in the alpha band (8-12 Hz) closely reflect the abstraction and analysis of the sounds along the task-relevant dimension. Vowel categorization leads to a significant temporal realignment of responses to the same vowel, e.g., /a/, independent of who pronounced this vowel, whereas speaker categorization leads to a significant temporal realignment of responses to the same speaker, e.g., speaker 1, independent of which vowel she/he pronounced. This transient and goal-dependent realignment of neuronal responses to physically different external events provides a robust cortical coding mechanism for forming and processing abstract representations of auditory (speech) input. PMID:19211877

  17. Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies

    Silvia Consalvi

    2016-01-01

    Full Text Available In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD.

  18. Epigenetics and complex disease: from etiology to new therapeutics.

    Ptak, Carolyn; Petronis, Arturas

    2008-01-01

    Epigenetics is a new development in complex non-Mendelian disease, which may not only uncover etiologic and pathogenic mechanisms but may also provide the basis for the development of medications that would target the primary epigenetic causes of such diseases. Such epigenetic drugs would be novel, potentially possessing substantially higher therapeutic potential and a much lower rate of adverse effects in comparison to current symptomatic treatments. A collection of epigenetic drugs already exist at various stages of development and, although their effectiveness has yet to be maximized, they show great promise in the treatment of cancer, psychiatric disorders, and other complex diseases. Here we present a review of the epigenetic theory of complex disease and an evaluation of current epigenetic therapies, as well as predictions of the future directions in this expanding field. PMID:17883328

  19. Valproic acid modulates brain plasticity through epigenetic chromatin remodeling in the blind rat: implications for human sight recovery.

    Fetter-Pruneda, I; Martínez-Méndez, R; Olivos-Cisneros, L; Diaz, D; Padilla-Cortés, P; Báez-Saldaña, A; Gutiérrez-Ospina, G

    2011-01-01

    Blindness is a pervasive sensory condition that imposes diverse difficulties to carry on with activities of daily living. In blind individuals, the brain is subjected to a large scale reorganization characterized by expanded cortical territories associated with somatosensory and auditory functions and the recruitment of the former visual areas to perform bimodal somatosensory and auditory integration. This poses obstacles to efforts aimed at reassigning visual functions to the recruited visual cortex in the blind, especially after the end of the ontogentic sensitive period. Devising pharmacological measures to modulate the magnitude of brain plasticity could improve our chances of recovering visual functions in the blind. Here, by using the primary somatosensory cortex (S1) in the rat as a working model, we showed that valproic acid administered through the mother's milk prevents cortical reorganization in blinded rats by delaying neuronal histone de-acetylation. These results suggest that in the future, we might be able to devise epigenetic pharmacological measures that could improve our chances of reassigning visual functions to the once deprived former visual cortex in the blind, by modulating the magnitude of brain plasticity during critical times of development. PMID:22423589

  20. Epileptogenesis: Can the Science of Epigenetics Give Us Answers?

    Lubin, Farah D.

    2012-01-01

    Epigenetic mechanisms are regulatory processes that control gene expression changes involved in multiple aspects of neuronal function, including central nervous system development, synaptic plasticity, and memory. Recent evidence indicates that dysregulation of epigenetic mechanisms occurs in several human epilepsy syndromes. Despite this discovery of a potential role for epigenetic mechanisms in epilepsy, few studies have fully explored their contribution to the process of epilepsy developme...

  1. Potential of epigenetic therapies in the management of solid tumors

    Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails

  2. Past, present, and future of epigenetics applied to livestock breeding

    González-Recio, Oscar; Toro, Miguel A; Bach, Alex

    2015-01-01

    This article reviews the concept of Lamarckian inheritance and the use of the term epigenetics in the field of animal genetics. Epigenetics was first coined by Conrad Hal Waddington (1905–1975), who derived the term from the Aristotelian word epigenesis. There exists some controversy around the word epigenetics and its broad definition. It includes any modification of the expression of genes due to factors other than mutation in the DNA sequence. This involves DNA methylation, post-translatio...

  3. The Structural Determinants behind the Epigenetic Role of Histone Variants

    Manjinder S. Cheema; Juan Ausió

    2015-01-01

    Histone variants are an important part of the histone contribution to chromatin epigenetics. In this review, we describe how the known structural differences of these variants from their canonical histone counterparts impart a chromatin signature ultimately responsible for their epigenetic contribution. In terms of the core histones, H2A histone variants are major players while H3 variant CenH3, with a controversial role in the nucleosome conformation, remains the genuine epigenetic histone v...

  4. Epigenetic therapy in gastrointestinal cancer: the right combination.

    Abdelfatah, Eihab; Kerner, Zachary; Nanda, Nainika; Ahuja, Nita

    2016-07-01

    Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer. PMID:27366224

  5. The Role of Redox Signaling in Epigenetics and Cardiovascular Disease

    Kim, Gene H.; Ryan, John J.; Archer, Stephen L.

    2013-01-01

    Significance: The term epigenetics refers to the changes in the phenotype and gene expression that occur without alterations in the DNA sequence. There is a rapidly growing body of evidence that epigenetic modifications are involved in the pathological mechanisms of many cardiovascular diseases (CVDs), which intersect with many of the pathways involved in oxidative stress. Recent Advances: Most studies relating epigenetics and human pathologies have focused on cancer. There has been a limited...

  6. Epigenetic differences after prenatal adversity: the Dutch hunger winter

    Tobi, Elmar Wouter

    2013-01-01

    This thesis is a study on the link between early development and adult health. Studies in animal models indicate that so-called epigenetic marks may be influenced by nutrition during development, changing the expression of genes implicated in disease. Epigenetics may therefore link development and disease. To investigate this hypothesis in humans we studied DNA methylation, a key epigenetic mark, in individuals exposed during early gestation to the Dutch Famine and individuals born growth res...

  7. 2009 Epigenetics Gordon Research Conference (August 9 - 14, 2009)

    Jeanie Lee

    2009-08-14

    Epigenetics refers to the study of heritable changes in genome function that occur without a change in primary DNA sequence. The 2009 Gordon Conference in Epigenetics will feature discussion of various epigenetic phenomena, emerging understanding of their underlying mechanisms, and the growing appreciation that human, animal, and plant health all depend on proper epigenetic control. Special emphasis will be placed on genome-environment interactions particularly as they relate to human disease. Towards improving knowledge of molecular mechanisms, the conference will feature international leaders studying the roles of higher order chromatin structure, noncoding RNA, repeat elements, nuclear organization, and morphogenic evolution. Traditional and new model organisms are selected from plants, fungi, and metazoans.

  8. Epigenetic mechanisms in the initiation of hematological malignancies

    Ali Maleki

    2011-10-01

    Full Text Available Background: Cancer development is not restricted to the genetic changes, but also to epigenetic changes. Epigenetic processes are very important in the development of hematological malignancies. The main epigenetic alterations are aberrations in DNA methylation, post-translational modifications of histones, chromatin remodeling and microRNAs patterns, and these are associated with tumor genesis. All the various cellular pathways contributing to the neoplastic phenotype are affected by epigenetic genes in cancer. These pathways can be explored as biomarkers in clinical use for early detection of disease, malignancy classification and response to treatment with classical chemotherapy agents and epigenetic drugs. Materials and Method: A literature review was performed using PUBMED from 1985 to 2008. Cross referencing of discovered articles was also reviewed.Results: In chronic lymphocytic leukemia, regional hypermethylation of gene promoters leads to gene silencing. Many of these genes have tumor suppressor phenotypes. In myelodysplastic syndrome (MDS, CDKN2B (alias, P15, a cyclin-dependent kinase inhibitor that negatively regulates the cell cycle, has been shown to be hypermethylated in marrow stem (CD34+ cells in patients with MDS. At present both Vidaza and Decitabine (DNA methyltransferase inhibitors are approved for the treatment of MDS.Conclusion: Unlike mutations or deletions, DNA hypermethylation and histone deacetylation are potentially reversible by pharmacological inhibition, therefore those epigenetic changes have been recognized as promising novel therapeutic targets in hematopoietic malignances. In this review, we discussed molecular mechanisms of epigenetics, epigenetic changes in hematological malignancies and epigenetic based treatments

  9. Study on epigenetic alterations of ore-enclosing sedimentary rocks

    Epigenetic alterations of sedimentary rocks under effect of exogenous undeground waters of various types: near-surface, ground, stratum, and deep circulation waters, are considered. Association to postsedimentary tectonic structures, confinement of neogenesis to areas of high permeability (porous or crack one), geochemical contradictions between mineral neogenis and facial outlook of deposits, noncoincidence of variability gradient of authigenous mineral associations with variability of primary facial signs of deposits, regular position of mineral formations and ore concentrations in epigenetic mineralogo-geochemical zonation are referred to epigenetic criteria. The complex of epigenetic alterations accompanying mineralization is frequently used as a search sign of uranium deposit of a certain type

  10. Niche adaptation by expansion and reprogramming of general transcription factors

    Turkarslan, Serdar; Reiss, David J; Gibbins, Goodwin; Su, Wan Lin; Pan, Min; Bare, J Christopher; Plaisier, Christopher L.; Baliga, Nitin S

    2011-01-01

    The evolutionary success of an organism depends on its ability to continually adapt to changes in the patterns of constant, periodic, and transient challenges within its environment. This process of ‘niche adaptation' requires reprogramming of the organism's environmental response networks by reorganizing interactions among diverse parts including environmental sensors, signal transducers, and transcriptional and post-transcriptional regulators. Gene duplications have been discovered to be on...

  11. Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum

    Lu, Ake T.; Hannon, Eilis; Levine, Morgan E.; Hao, Ke; Crimmins, Eileen M.; Lunnon, Katie; Kozlenkov, Alexey; Mill, Jonathan; Dracheva, Stella; Horvath, Steve

    2016-02-01

    DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the `epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (Pepigenetic tissue age as endophenotype in GWAS.

  12. Is epigenetics an important link between early life events and adult disease?

    Epigenetic mechanisms provide one potential explanation for how environmental influences in early life cause long-term changes in chronic disease susceptibility. Whereas epigenetic dysregulation is increasingly implicated in various rare developmental syndromes and cancer, the role of epigenetics in...

  13. Methylome analysis reveals an important role for epigenetic changes in the regulation of the Arabidopsis response to phosphate starvation

    Yong-Villalobos, Lenin; González-Morales, Sandra Isabel; Wrobel, Kazimierz; Gutiérrez-Alanis, Dolores; Cervantes-Peréz, Sergio Alan; Hayano-Kanashiro, Corina; Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Martínez, Octavio; Herrera-Estrella, Luis

    2015-01-01

    Significant progress has been achieved in our understanding of plant adaptive responses to ensure growth and reproduction in soils with low phosphate (Pi) availability. However, the potential role of epigenetic mechanisms in the modulation of these responses remains largely unknown. In this article, we describe dynamic changes in global DNA methylation patterns that occur in Arabidopsis plants exposed to low Pi availability; these changes are associated with the onset of Pi starvation respons...

  14. The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development.

    Lendvai, Ágnes; Deutsch, Manuel J; Plösch, Torsten; Ensenauer, Regina

    2016-05-15

    The placental metabolism can adapt to the environment throughout pregnancy to both the demands of the fetus and the signals from the mother. Such adaption processes include epigenetic mechanisms, which alter gene expression and may influence the offspring's health. These mechanisms are linked to the diversity of prenatal environmental exposures, including maternal under- or overnutrition or gestational diabetes. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that contribute to the developmental plasticity of the placenta by regulating lipid and glucose metabolism pathways, including lipogenesis, steroidogenesis, glucose transporters, and placental signaling pathways, thus representing a link between energy metabolism and reproduction. Among the PPAR isoforms, PPARγ appears to be the main modulator of mammalian placentation. Certain fatty acids and lipid-derived moieties are the natural activating PPAR ligands. By controlling the amounts of maternal nutrients that go across to the fetus, the PPARs play an important regulatory role in placenta metabolism, thereby adapting to the maternal nutritional status. As demonstrated in animal studies, maternal nutrition during gestation can exert long-term influences on the PPAR methylation pattern in offspring organs. This review underlines the current state of knowledge on the relationship between environmental factors and the epigenetic regulation of the PPARs in placenta metabolism and offspring development. PMID:26860983

  15. Cortical reorganization after macroreplantation at the upper extremity: a magnetoencephalographic study.

    Blume, Kathrin R; Dietrich, Caroline; Huonker, Ralph; Götz, Theresa; Sens, Elisabeth; Friedel, Reinhard; Hofmann, Gunther O; Miltner, Wolfgang H R; Weiss, Thomas

    2014-03-01

    With the development of microsurgical techniques, replantation has become a feasible alternative to stump treatment after the amputation of an extremity. It is known that amputation often induces phantom limb pain and cortical reorganization within the corresponding somatosensory areas. However, whether replantation reduces the risk of comparable persisting pain phenomena as well as reorganization of the primary somatosensory cortex is still widely unknown. Therefore, the present study aimed to investigate the potential development of persistent pain and cortical reorganization of the hand and lip areas within the sensory cortex by means of magnetoencephalographic dipole analyses after replantation of a traumatically amputated upper limb proximal to the radiocarpal joint. Cortical reorganization was investigated in 13 patients with limb replantation using air puff stimulation of the phalanges of both thumbs and both corners of the lower lip. Displacement of the centre of gravity of lip and thumb representations and increased cortical activity were found in the limb and face areas of the primary somatosensory cortex contralateral to the replanted arm when compared to the ipsilateral hemisphere. Thus, cortical reorganization in the primary somatosensory cortex also occurs after replantation of the upper extremity. Patients' reports of pain in the replanted body part were negatively correlated with the amount of cortical reorganization, i.e. the more pain the patients reported, the less reorganization of the subjects' hand representation within the primary somatosensory cortex was observed. Longitudinal studies in patients after macroreplantation are necessary to assess whether the observed reorganization in the primary somatosensory cortex is a result of changes within the representation of the replanted arm and/or neighbouring representations and to assess the relationship between the development of persistent pain and reorganization. PMID:24480484

  16. Radiation-induced myosin IIA expression stimulates collagen type I matrix reorganization

    Background and purpose: Extracellular matrix (ECM) reorganization critically contributes to breast cancer (BC) progression and radiotherapy response. We investigated the molecular background and functional consequences of collagen type I (col-I) reorganization by irradiated breast cancer cells (BCC). Materials and methods: Radiation-induced (RI) col-I reorganization was evaluated for MCF-7/6, MCF-7/AZ, T47D and SK-BR-3 BCC. Phase-contrast microscopy and a stressed matrix contraction assay were used for visualization and quantification of col-I reorganization. Cell–matrix interactions were assessed by the inhibition of β1 integrin (neutralizing antibody ‘P5D2’) or focal adhesion kinase (FAK; GSK22560098 small molecule kinase inhibitor). The role of the actomyosin cytoskeleton was explored by western blotting analysis of myosin II expression and activity; and by gene silencing of myosin IIA and pharmacological inhibition of the actomyosin system (blebbistatin, cytochalasin D). BCC death was evaluated by propidium iodide staining. Results: We observed a radiation dose-dependent increase of col-I reorganization by BCC. β1 Integrin/FAK-mediated cell–matrix interactions are essential for RI col-I reorganization. Irradiated BCC are characterized by increased myosin IIA expression and myosin IIA-dependent col-I reorganization. Moreover, RI col-I reorganization by BCC is associated with decreased BCC death, as suggested by pharmacological targeting of the β1 integrin/FAK/myosin IIA pathway. Conclusions: Our data indicate the role of myosin IIA in col-I reorganization by irradiated BCC and reciprocal BCC death

  17. Defining the Functional Network of Epigenetic Regulators in Arabidopsis thaliana

    Chongyuan Luo; Brittany G.Durgin; Naohide Watanabe; Eric Lam

    2009-01-01

    Development of ChiP-chip and ChlP-seq technologies has allowed genome-wide high-resolution profiling of chromatin-associated marks and binding sites for epigenetic regulators.However,signals for directing epigenetic modi fiers to their target sites are not understood.In this paper,we tested the hypothesis that genome location can affect the involvement of epigenetic regulators using Chromatin Charting (CC) Lines,which have an identical transgene construct inserted at different locations in the Arabidopsis genome.Four CC lines that showed evidence for epigenetic silencing of the luciferase reporter gene were transformed with RNAi vectors individually targeting epigenetic regulators LHP1,MOM1,CMT3,DRD1,DRM2,SUVH2,CLF,and HD1.Involvement of a particular epigenetic regulator in silencing the transgene locus in a CC line was determined by significant alterations in luciferase expression after suppression of the regulator's expression.Our results suggest that the targeting of epigenetic regulators can be influenced by genome location as well as sequence context.In addition,the relative importance of an epigenetic regulator can be influenced by tissue identity.We also report a novel approach to predict interactions between epigenetic regulators through clustering analysis of the regulators using alterations in gene expression of putative downstream targets,including endogenous loci and transgenes,in epigenetic mutants or RNAi lines.Our data support the existence of a complex and dynamic network of epigenetic regulators that serves to coordinate and control global gene expression in higher plants.

  18. Epigenetic Effects of Diet on Fruit Fly Lifespan: An Investigation to Teach Epigenetics to Biology Students

    Billingsley, James; Carlson, Kimberly A.

    2010-01-01

    Do our genes exclusively control us, or are other factors at play? Epigenetics can provide a means for students to use inquiry-based methods to understand a complex biological concept. Students research and design an experiment testing whether dietary supplements affect the lifespan of Drosophila melanogaster over multiple generations.

  19. Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees

    Flor, Herta; Elbert, Thomas; Mühlnickel, Werner; Pantev, Christo; Wienbruch, Christian; Taub, Edward

    1998-01-01

    The relationship between phantom limb phenomena and cortical reorganization was examined in five subjects with congenital absence of an upper limb and nine traumatic amputees. Neuromagnetic source imaging revealed minimal reorganization of primary somatosensory cortex in the congenital amputees (M=0.69 cm, SD 0.24) and the traumatic amputees without phantom limb pain (M=0.27 cm, SD 0.25); the amputees with phantom limb pain showed massive cortical reorganization (M=2.22 cm, SD 0.78). Phantom ...

  20. Does skeletal muscle have an 'epi'-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise.

    Sharples, Adam P; Stewart, Claire E; Seaborne, Robert A

    2016-08-01

    Skeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can 'remember' early-life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an 'epi'-memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re-encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early-life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise-induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the 'epi'-memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging. PMID:27102569

  1. Epigenetic estimation of age in humpback whales.

    Polanowski, Andrea M; Robbins, Jooke; Chandler, David; Jarman, Simon N

    2014-09-01

    Age is a fundamental aspect of animal ecology, but is difficult to determine in many species. Humpback whales exemplify this as they have a lifespan comparable to humans, mature sexually as early as 4 years and have no reliable visual age indicators after their first year. Current methods for estimating humpback age cannot be applied to all individuals and populations. Assays for human age have recently been developed based on age-induced changes in DNA methylation of specific genes. We used information on age-associated DNA methylation in human and mouse genes to identify homologous gene regions in humpbacks. Humpback skin samples were obtained from individuals with a known year of birth and employed to calibrate relationships between cytosine methylation and age. Seven of 37 cytosines assayed for methylation level in humpback skin had significant age-related profiles. The three most age-informative cytosine markers were selected for a humpback epigenetic age assay. The assay has an R(2) of 0.787 (P = 3.04e-16) and predicts age from skin samples with a standard deviation of 2.991 years. The epigenetic method correctly determined which of parent-offspring pairs is the parent in more than 93% of cases. To demonstrate the potential of this technique, we constructed the first modern age profile of humpback whales off eastern Australia and compared the results to population structure 5 decades earlier. This is the first epigenetic age estimation method for a wild animal species and the approach we took for developing it can be applied to many other nonmodel organisms. PMID:24606053

  2. Derangement of a factor upstream of RARalpha triggers the repression of a pleiotropic epigenetic network.

    Francesca Corlazzoli

    Full Text Available BACKGROUND: Chromatin adapts and responds to extrinsic and intrinsic cues. We hypothesize that inheritable aberrant chromatin states in cancer and aging are caused by genetic/environmental factors. In previous studies we demonstrated that either genetic mutations, or loss, of retinoic acid receptor alpha (RARalpha, can impair the integration of the retinoic acid (RA signal at the chromatin of RA-responsive genes downstream of RARalpha, and can lead to aberrant repressive chromatin states marked by epigenetic modifications. In this study we tested whether the mere interference with the availability of RA signal at RARalpha, in cells with an otherwise functional RARalpha, can also induce epigenetic repression at RA-responsive genes downstream of RARalpha. METHODOLOGY/PRINCIPAL FINDINGS: To hamper the availability of RA at RARalpha in untransformed human mammary epithelial cells, we targeted the cellular RA-binding protein 2 (CRABP2, which transports RA from the cytoplasm onto the nuclear RARs. Stable ectopic expression of a CRABP2 mutant unable to enter the nucleus, as well as stable knock down of endogenous CRABP2, led to the coordinated transcriptional repression of a few RA-responsive genes downstream of RARalpha. The chromatin at these genes acquired an exacerbated repressed state, or state "of no return". This aberrant state is unresponsive to RA, and therefore differs from the physiologically repressed, yet "poised" state, which is responsive to RA. Consistent with development of homozygosis for epigenetically repressed loci, a significant proportion of cells with a defective CRABP2-mediated RA transport developed heritable phenotypes indicative of loss of function. CONCLUSION/SIGNIFICANCE: Derangement/lack of a critical factor necessary for RARalpha function induces epigenetic repression of a RA-regulated gene network downstream of RARalpha, with major pleiotropic biological outcomes.

  3. Integrated molecular mechanism directing nucleosome reorganization by human FACT.

    Tsunaka, Yasuo; Fujiwara, Yoshie; Oyama, Takuji; Hirose, Susumu; Morikawa, Kosuke

    2016-03-15

    Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT-histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3-H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid-H2A steric collision on the H2A-docking surface of the H3-H4 tetramer within the nucleosome induces H2A-H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone. PMID:26966247

  4. Enhancing Physical Activity and Brain Reorganization after Stroke

    Janet H. Carr

    2011-01-01

    Full Text Available It is becoming increasingly clear that, if reorganization of brain function is to be optimal after stroke, there needs to be a reorganisation of the methods used in physical rehabilitation and the time spent in specific task practice, strength and endurance training, and aerobic exercise. Frequency and intensity of rehabilitation need to be increased so that patients can gain the energy levels and vigour necessary for participation in physical activity both during rehabilitation and after discharge. It is evident that many patients are discharged from inpatient rehabilitation severely deconditioned, meaning that their energy levels are too low for active participation in daily life. Physicians, therapists, and nursing staff responsible for rehabilitation practice should address this issue not only during inpatient rehabilitation but also after discharge by promoting and supporting community-based exercise opportunities. During inpatient rehabilitation, group sessions should be frequent and need to include specific aerobic training. Physiotherapy must take advantage of the training aids available, including exercise equipment such as treadmills, and of new developments in computerised feedback systems, robotics, and electromechanical trainers. For illustrative purposes, this paper focuses on the role of physiotherapists, but the necessary changes in practice and in attitude will require cooperation from many others.

  5. Global Reorganization of the Nuclear Landscape in Senescent Cells

    Tamir Chandra

    2015-02-01

    Full Text Available Cellular senescence has been implicated in tumor suppression, development, and aging and is accompanied by large-scale chromatin rearrangements, forming senescence-associated heterochromatic foci (SAHF. However, how the chromatin is reorganized during SAHF formation is poorly understood. Furthermore, heterochromatin formation in senescence appears to contrast with loss of heterochromatin in Hutchinson-Gilford progeria. We mapped architectural changes in genome organization in cellular senescence using Hi-C. Unexpectedly, we find a dramatic sequence- and lamin-dependent loss of local interactions in heterochromatin. This change in local connectivity resolves the paradox of opposing chromatin changes in senescence and progeria. In addition, we observe a senescence-specific spatial clustering of heterochromatic regions, suggesting a unique second step required for SAHF formation. Comparison of embryonic stem cells (ESCs, somatic cells, and senescent cells shows a unidirectional loss in local chromatin connectivity, suggesting that senescence is an endpoint of the continuous nuclear remodelling process during differentiation.

  6. Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling.

    Poulomi Ray

    Full Text Available Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF, Bone Morphogenetic Protein (BMP and Transforming Growth Factor beta (TGF-β signaling pathways. Rho Kinase (ROCK-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis.

  7. Reorganization of the North Atlantic Oscillation during early Holocene deglaciation

    Wassenburg, Jasper A.; Dietrich, Stephan; Fietzke, Jan; Fohlmeister, Jens; Jochum, Klaus Peter; Scholz, Denis; Richter, Detlev K.; Sabaoui, Abdellah; Spötl, Christoph; Lohmann, Gerrit; Andreae, Meinrat O.; Immenhauser, Adrian

    2016-08-01

    The North Atlantic Oscillation is the dominant atmospheric pressure mode in the North Atlantic region and affects winter temperature and precipitation in the Mediterranean, northwest Europe, Greenland, and Asia. The index that describes the sea-level pressure difference between Iceland and the Azores is correlated with a dipole precipitation pattern over northwest Europe and northwest Africa. How the North Atlantic Oscillation will develop as the Greenland ice sheet melts is unclear. A potential past analogue is the early Holocene, during which melting ice sheets around the North Atlantic freshened surface waters, affecting the strength of the meridional overturning circulation. Here we present a Holocene rainfall record from northwest Africa based on speleothem δ18O and compare it against a speleothem-based rainfall record from Europe. The two records are positively correlated during the early Holocene, followed by a shift to an anti-correlation, similar to the modern record, during the mid-Holocene. On the basis of our simulations with an Earth system model, we suggest the shift to the anti-correlation reflects a large-scale atmospheric and oceanic reorganization in response to the demise of the Laurentide ice sheet and a strong reduction of meltwater flux to the North Atlantic, pointing to a potential sensitivity of the North Atlantic Oscillation to the melting of ice sheets.

  8. Epigenetic memory of PTGS-induced epialelles of tobacco transgenes

    Lunerová Bedřichová, Jana; Bleys, A.; Fojtová, Miloslava; Crhák Khaitová, Lucie; Depicker, A.; Kovařík, Aleš

    Heidelberg, 2007. s. 155-155. [EMBO Conference on Chromatin and Epigenetics. 03.05.2007-06.05.2007, Heidelberg] R&D Projects: GA MŠk(CZ) LC06004; GA AV ČR(CZ) IAA600040611 Institutional research plan: CEZ:AV0Z50040507 Keywords : DNA methylation * epigenetic inheritance * silencing Subject RIV: BO - Biophysics

  9. Analysis of epigenetic modifications of DNA in human cells

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

    2013-01-01

    Epigenetics, the study of somatically heritable changes in gene expression not related to changes in the DNA sequence, is a rapidly expanding research field that plays important roles in healthy as well as in diseased cells. DNA methylation and hydroxymethylation are epigenetic modifications found...

  10. Epigenetic Contributions to Cognitive Aging: Disentangling Mindspan and Lifespan

    Spiegel, Amy M.; Sewal, Angila S.; Rapp, Peter R.

    2014-01-01

    Epigenetic modifications of chromatin structure provide a mechanistic interface for gene-environment interactions that impact the individualization of health trajectories across the lifespan. A growing body of research indicates that dysfunctional epigenetic regulation contributes to poor cognitive outcomes among aged populations. Here we review…

  11. Cancer Development, Progression, and Therapy: An Epigenetic Overview

    McKenna Longacre

    2013-10-01

    Full Text Available Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

  12. Epigenetics in adipose tissue, obesity, weight loss and diabetes

    Given the role that the diet and other environmental factors play in the development of obesity and type 2 diabetes, the implication of different epigenetic processes is being investigated. Although it is well known that the environmental factors can cause cell type-dependent epigenetic changes, inc...

  13. Nutritional influences on epigenetics and age-related disease

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  14. Environmental Epigenetics: Potential Application in Human Health Risk Assessment

    Although previous studies have shown a significant involvement of epigenetic dysregulation in human diseases, the applicability of epigenetic data in the current human health risk assessment paradigm is unclear. The goals of this study are to compare the relative sensitivities of...

  15. Ontogeny and Phylogeny from an Epigenetic Point of View.

    Lovtrup, Soren

    1984-01-01

    The correlation between ontogeny and phylogeny is analyzed through the discussion of four theories on the reality, history, epigenetic, and ecological aspects of the mechanism of evolution. Also discussed are historical and creative aspects of evolution and three epigenetic mechanisms instantiated in the case of the amphibian embryo. (Author/RH)

  16. The epigenetic landscape of mammary gland development and functional differentiation

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

  17. Epigenetic maturation in colonic mucosa continues beyond infancy in mice.

    Monozygotic twin and other epidemiologic studies indicate that epigenetic processes may play an important role in the pathogenesis of inflammatory bowel diseases that commonly affect the colonic mucosa. The peak onset of these disorders in young adulthood, suggests that epigenetic changes normally o...

  18. Epigenetic biomarkers in laboratory diagnostics: emerging approaches and opportunities.

    Sandoval, Juan; Peiró-Chova, Lorena; Pallardó, Federico V; García-Giménez, José Luis

    2013-06-01

    Epigenetics has emerged as a new and promising field in recent years. Lifestyle, stress, drugs, physiopathological situations and pharmacological interventions have a great impact on the epigenetic code of the cells by altering the methylome, miRNA expression and the covalent histone modifications. Since there exists a need to find new biomarkers and improve diagnosis for several diseases, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice. In this context, deciphering intricate epigenetic modifications involved in several molecular processes is a challenge that will be solved in the near future. In this review, the authors present an overview of the high-throughput technologies and laboratory techniques available for epigenetic studies, and also discuss which of them are more reliable to be used in a clinical diagnostic laboratory. In addition, the authors describe the most promising epigenetic biomarkers in lung, colorectal and prostate cancer, in which most advances have been achieved. Finally, the authors describe epigenetic biomarkers in some rare diseases; these rare syndromes are paradigms for a specific impaired molecular pathway, thus providing valuable information on the discovery of new epigenetic biomarkers. PMID:23782253

  19. Epigenetic differences after prenatal adversity : the Dutch hunger winter

    Tobi, Elmar Wouter

    2013-01-01

    This thesis is a study on the link between early development and adult health. Studies in animal models indicate that so-called epigenetic marks may be influenced by nutrition during development, changing the expression of genes implicated in disease. Epigenetics may therefore link development and d

  20. The role of epigenetic mechanisms and processes in autoimmune disorders

    Greer JM

    2012-09-01

    Full Text Available Judith M Greer, Pamela A McCombeThe University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, AustraliaAbstract: The lack of complete concordance of autoimmune disease in identical twins suggests that nongenetic factors play a major role in determining disease susceptibility. In this review, we consider how epigenetic mechanisms could affect the immune system and effector mechanisms in autoimmunity and/or the target organ of autoimmunity and thus affect the development of autoimmune diseases. We also consider the types of stimuli that lead to epigenetic modifications and how these relate to the epidemiology of autoimmune diseases and the biological pathways operative in different autoimmune diseases. Increasing our knowledge of these epigenetic mechanisms and processes will increase the prospects for controlling or preventing autoimmune diseases in the future through the use of drugs that target the epigenetic pathways.Keywords: twins, concordance, autoimmune disease, nongenetic factors, immune system, epigenetic modifications

  1. Epigenetic changes in virus-associated human cancers

    Hsin Pai LI; Yu Wei LEU; Yu Sun CHANG

    2005-01-01

    Epigenetics of human cancer becomes an area of emerging research direction due to a growing understanding of specific epigenetic pathways and rapid development of detection technologies. Aberrant promoter hypermethylation is a prevalent phenonmena in human cancers. Tumor suppressor genes are often hypermethylated due to the increased activity or deregulation of DNMTs. Increasing evidence also reveals that viral genes are one of the key players in regulating DNA methylation. In this review, we will focus on hypermethylation and tumor suppressor gene silencing and the signal pathways that are involved, particularly in cancers closely associated with the hepatitis B virus, simian virus 40 (SV40), and Epstein-Barr virus. In addition, we will discuss current technologies for genome-wide detection of epigenetically regulated targets, which allow for systematic DNA hypermethylation analysis. The study of epigenetic changes should provide a global view of gene profile in cancer, and epigenetic markers could be used for early detection,prognosis, and therapy of cancer.

  2. Implication of epigenetics in pancreas development and disease.

    Quilichini, Evans; Haumaitre, Cécile

    2015-12-01

    Pancreas development is controlled by a complex interaction of signaling pathways and transcription factor networks that determine pancreatic specification and differentiation of exocrine and endocrine cells. Epigenetics adds a new layer of gene regulation. DNA methylation, histone modifications and non-coding RNAs recently appeared as important epigenetic factors regulating pancreas development. In this review, we report recent findings obtained by analyses in model organisms as well as genome-wide approaches that demonstrate the role of these epigenetic regulators in the control of exocrine and endocrine cell differentiation, identity, function, proliferation and regeneration. We also highlight how altered epigenetic processes contribute to pancreatic disorders: diabetes and pancreatic cancer. Uncovering these epigenetic events can help to better understand these diseases, provide novel therapeutical targets for their treatment, and improve cell-based therapies for diabetes. PMID:26696517

  3. Designed azurins show lower reorganization free energies for intraprotein electron transfer

    Farver, Ole; Marshall, Nicholas M; Wherland, Scot;

    2013-01-01

    Low reorganization free energies are necessary for fast electron transfer (ET) reactions. Hence, rational design of redox proteins with lower reorganization free energies has been a long-standing challenge, promising to yield a deeper understanding of the underlying principles of ET reactivity and...... span a wide range of reduction potentials while leaving the metal binding site effectively undisrupted. We find that the reorganization free energies of ET within the mutants are indeed lower than that of WT azurin, increasing the intramolecular ET rate constants almost 10-fold: changes that are...... correlated with increased flexibility of their copper sites. Moreover, the lower reorganization free energy results in the ET rate constants reaching a maximum value at higher driving forces, as predicted by the Marcus theory....

  4. University To Reorganize Business Functions; Raymond Smoot To Head Virginia Tech Foundation

    Hincker, Lawrence

    2003-01-01

    Raymond Smoot, vice president for administration and treasurer, will assume a new role as executive vice president and chief operating officer for the Virginia Tech Foundation. Concurrent with this move, the university business and administrative functions will be reorganized.

  5. 78 FR 24154 - Notice of Availability of a National Animal Health Laboratory Network Reorganization Concept Paper

    2013-04-24

    ... Network Reorganization Concept Paper AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION... for the National Animal Health Laboratory Network (NAHLN) for public review and comment. The NAHLN is a nationally coordinated network and partnership of Federal, State, and university-...

  6. Developmental Origins, Epigenetics, and Equity: Moving Upstream.

    Wallack, Lawrence; Thornburg, Kent

    2016-05-01

    The Developmental Origins of Health and Disease and the related science of epigenetics redefines the meaning of what constitutes upstream approaches to significant social and public health problems. An increasingly frequent concept being expressed is "When it comes to your health, your zip code may be more important than your genetic code". Epigenetics explains how the environment-our zip code-literally gets under our skin, creates biological changes that increase our vulnerability for disease, and even children's prospects for social success, over their life course and into future generations. This science requires us to rethink where disease comes from and the best way to promote health. It identifies the most fundamental social equity issue in our society: that initial social and biological disadvantage, established even prior to birth, and linked to the social experience of prior generations, is made worse by adverse environments throughout the life course. But at the same time, it provides hope because it tells us that a concerted focus on using public policy to improve our social, physical, and economic environments can ultimately change our biology and the trajectory of health and social success into future generations. PMID:27029539

  7. Epigenetic modification of OXT and human sociability.

    Haas, Brian W; Filkowski, Megan M; Cochran, R Nick; Denison, Lydia; Ishak, Alexandra; Nishitani, Shota; Smith, Alicia K

    2016-07-01

    Across many mammalian species there exist genetic and biological systems that facilitate the tendency to be social. Oxytocin is a neuropeptide involved in social-approach behaviors in humans and others mammals. Although there exists a large, mounting body of evidence showing that oxytocin signaling genes are associated with human sociability, very little is currently known regarding the way the structural gene for oxytocin (OXT) confers individual differences in human sociability. In this study, we undertook a comprehensive approach to investigate the association between epigenetic modification of OXT via DNA methylation, and overt measures of social processing, including self-report, behavior, and brain function and structure. Genetic data were collected via saliva samples and analyzed to target and quantify DNA methylation across the promoter region of OXT We observed a consistent pattern of results across sociability measures. People that exhibit lower OXT DNA methylation (presumably linked to higher OXT expression) display more secure attachment styles, improved ability to recognize emotional facial expressions, greater superior temporal sulcus activity during two social-cognitive functional MRI tasks, and larger fusiform gyrus gray matter volume than people that exhibit higher OXT DNA methylation. These findings provide empirical evidence that epigenetic modification of OXT is linked to several overt measures of sociability in humans and serve to advance progress in translational social neuroscience research toward a better understanding of the evolutionary and genetic basis of normal and abnormal human sociability. PMID:27325757

  8. Molecular genetics and epigenetics of CACTA elements

    Fedoroff, Nina V.

    2013-08-21

    The CACTA transposons, so named for a highly conserved motif at element ends, comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) plant transposons. CACTA transposons characteristically include subterminal sequences of several hundred nucleotides containing closely spaced direct and inverted repeats of a short, conserved sequence of 14-15 bp. The Supressor-mutator (Spm) transposon, identified and subjected to detailed genetic analysis by Barbara McClintock, remains the paradigmatic element of the CACTA family. The Spm transposon encodes two proteins required for transposition, the transposase (TnpD) and a regulatory protein (TnpA) that binds to the subterminal repeats. Spm expression is subject to both genetic and epigenetic regulation. The Spm-encoded TnpA serves as an activator of the epigenetically inactivated, methylated Spm, stimulating both transient and heritable activation of the transposon. TnpA also serves as a negative regulator of the demethylated active element promoter and is required, in addition to the TnpD, for transposition. © Springer Science+Business Media, New York 2013.

  9. Inflammatory and Epigenetic Pathways for Perinatal Depression.

    Garfield, Lindsey; Mathews, Herbert L; Janusek, Linda Witek

    2016-05-01

    Depression during the perinatal period is common and can have adverse consequences for women and their children. Yet, the biobehavioral mechanisms underlying perinatal depression are not known. Adverse early life experiences increase the risk for adult depression. One potential mechanism by which this increased risk occurs is epigenetic embedding of inflammatory pathways. The purpose of this article is to propose a conceptual model that explicates the linkage between early life adversity and the risk for maternal depression. The model posits that early life adversity embeds a proinflammatory epigenetic signature (altered DNA methylation) that predisposes vulnerable women to depression during pregnancy and the postpartum period. As proposed, women with a history of early life adversity are more likely to exhibit higher levels of proinflammatory cytokines and lower levels of oxytocin in response to the demands of pregnancy and new motherhood, both of which are associated with the risk for perinatal depression. The model is designed to guide investigations into the biobehavioral basis for perinatal depression, with emphasis upon the impact of early life adversity. Testing this model will provide a better understanding of maternal depressive risk and improve identification of vulnerable women who would benefit from targeted interventions that can reduce the impact of perinatal depression on maternal-infant health. PMID:26574573

  10. Epigenetic Silencing of DKK3 in Medulloblastoma

    André Oberthuer

    2013-04-01

    Full Text Available Medulloblastoma (MB is a malignant pediatric brain tumor arising in the cerebellum consisting of four distinct subgroups: WNT, SHH, Group 3 and Group 4, which exhibit different molecular phenotypes. We studied the expression of Dickkopf (DKK 1–4 family genes, inhibitors of the Wnt signaling cascade, in MB by screening 355 expression profiles derived from four independent datasets. Upregulation of DKK1, DKK2 and DKK4 mRNA was observed in the WNT subgroup, whereas DKK3 was downregulated in 80% MBs across subgroups with respect to the normal cerebellum (p < 0.001. Since copy number aberrations targeting the DKK3 locus (11p15.3 are rare events, we hypothesized that epigenetic factors could play a role in DKK3 regulation. Accordingly, we studied 77 miRNAs predicting to repress DKK3; however, no significant inverse correlation between miRNA/mRNA expression was observed. Moreover, the low methylation levels in the DKK3 promoters (median: 3%, 5% and 5% for promoter 1, 2 and 3, respectively excluded the downregulation of gene expression by methylation. On the other hand, the treatment of MB cells with Trichostatin A (TSA, a potent inhibitor of histone deacetylases (HDAC, was able to restore both DKK3 mRNA and protein. In conclusion, DKK3 downregulation across all MB subgroups may be due to epigenetic mechanisms, in particular, through chromatin condensation.

  11. The Epigenetic Landscape of Acute Myeloid Leukemia

    Emma Conway O’Brien

    2014-01-01

    Full Text Available Acute myeloid leukemia (AML is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated.

  12. Genetic and epigenetic mechanisms of NASH.

    Eslam, Mohammed; George, Jacob

    2016-05-01

    Along with the obesity epidemic, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased exponentially. The histological disease spectrum of NAFLD ranges from bland fatty liver (hepatic steatosis), to the concomitant presence of inflammation and ballooning which defines nonalcoholic steatohepatitis (NASH). The latter can progress in a subset to fibrosis, leading ultimately to cirrhosis and hepatocellular carcinoma. The past decade has seen tremendous advances in our understanding of the genetic and epigenetic bases of NAFLD, mainly through the application of high end technology platforms including genome-wide association studies (GWAS). These have helped to define common gene variants (minor allele frequency >5 %) that contribute to the NAFLD phenotype. Looking to the future, these discoveries are expected to lead to improved diagnostics, the personalization of medicine, and a better understanding of the pathophysiological underpinnings that drive the transition from NAFLD to steatohepatitis and fibrosis, leading to the identification of novel therapeutic targets. In this review, we summarize data on the current state of knowledge with regard to the genetic and epigenetic mechanisms for the development of NASH. PMID:26683320

  13. М. SCHUMPETER’S INNOVATION PARADIGM AND PRINCIPLES OF ECONOMIC SYSTEM REORGANIZATION

    Kravchenko, M; E. Shergelashvili

    2013-01-01

    The paper is devoted to the principles of the reorganization of the economic system of Ukraine. The principles of the economic system reorganization presented in the paper as a consequence Schumpeter’s theory of economic development. The main idea of the article is that institutions of modern society should systematically promote the establishment, operation and development of a new appropriation form that follows from both the role of innovation as a factor in Schumpeter’s theory of economic...

  14. A drastic reorganization of industry in the world.What is the driving force

    Shinji Naruo

    2010-01-01

    The purpose of this paper is to show the method and model to analyze the driving force to reorganize the industry. Due to the global economy, many large scale M&A and affiliations are happening in the world. The business alliance and integration are happening in the advanced countries, the transition countries, and the developing countries. There are some factors to impact the reorganization of industry. One is government policy. Another is the market economy. The government has the industria...

  15. Kinetics of structural reorganizations in multilamellarphotosynthetic membranes monitored by small-angle neutronscattering

    Nagy, Gergely; Kovacs, Laszlo; Unnep, Renata;

    2013-01-01

    We demonstrate the power of time-resolved small-angle neutron scattering experiments for the investigation of the structure and structural reorganizations of multilamellar photosynthetic membranes. In addition to briefly summarizing our results on thylakoid membranes isolated from higher plants...... and in unicellular organisms, we discuss the advantages and technical and methodological limitations of timeresolved SANS. We present a detailed and more systematical investigation of the kinetics of light-induced structural reorganizations in isolated spinach thylakoid membranes, which show how changes...

  16. Job control mediates change in a work reorganization: intervention for stress reduction

    Bond, Frank W.; Bunce, David

    2001-01-01

    This longitudinal, quasi-experiment tested whether a work reorganization intervention can improve stress-related outcomes by increasing people's job control. To this end, the authors used a participative action research (PAR) intervention that had the goal of reorganizing work to increase the extent to which people had discretion and choice in their work. Results indicated that the PAR intervention significantly improved people's mental health, sickness absence rates, and self-rated performan...

  17. Reorganization of the interchromosomal network during keratinocyte differentiation.

    Sehgal, Nitasha; Seifert, Brandon; Ding, Hu; Chen, Zihe; Stojkovic, Branislav; Bhattacharya, Sambit; Xu, Jinhui; Berezney, Ronald

    2016-06-01

    The well-established human epidermal keratinocyte (HEK) differentiation model was investigated to determine possible alterations in chromosome territory (CT) association during differentiation. The seven human chromosomes (1, 4, 11, 12, 16, 17, and 18) selected for this analysis are representative of the chromosome size and gene density range of the overall human genome as well as including a majority of genes involved in epidermal development and differentiation (CT1, 12, and 17). Induction with calcium chloride (Ca(2+)) resulted in morphological changes characteristic of keratinocyte differentiation. Combined multi-fluorescence in situ hybridization (FISH) and computational image analysis on the undifferentiated (0 h) and differentiated (24 h after Ca(2+) treatment) HEK revealed that (a) increases in CT volumes correspond to overall nuclear volume increases, (b) radial positioning is gene density-dependent at 0 h but neither gene density- nor size-dependent at 24 h, (c) the average number of interchromosomal associations for each CT is gene density-dependent and similar at both time points, and (d) there are striking differences in the single and multiple pairwise interchromosomal association profiles. Probabilistic network models of the overall interchromosomal associations demonstrate major reorganization of the network during differentiation. Only ~40 % of the CT pairwise connections in the networks are common to both 0 and 24 h HEK. We propose that there is a probabilistic chromosome positional code which can be significantly altered during cell differentiation in coordination with reprogramming of gene expression. PMID:26490167

  18. Functional Reorganization of the Primary Somatosensory Cortex of a Phantom Limb Pain Patient.

    Zhao, Jia; Guo, Xiaoli; Xia, Xiaolei; Peng, Weiwei; Wang, Wuchao; Li, Shulin; Zhang, Ya; Hu, Li

    2016-07-01

    Functional reorganization of the somatosensory system was widely observed in phantom limb pain patients. Whereas some studies demonstrated that the primary somatosensory cortex (S1) of the amputated limb was engaged with the regions around it, others showed that phantom limb pain was associated with preserved structure and functional organization in the former brain region. However, according to the law of use and disuse, the sensitivity of S1 of the amputated limb to pain-related context should be enhanced due to the adaptation to the long-lasting phantom limb pain experience. Here, we collected neurophysiological data from a patient with 21-year phantom limb pain using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) techniques. EEG data showed that both laser-evoked potentials (LEPs) and tactile-evoked potentials (TEPs) were clearly presented only when radiant-heat laser pulses and electrical pulses were delivered to the shoulder of the healthy limb, but not of the amputated limb. This observation suggested the functional deficit of somatosensory pathways at the amputated side. FMRI data showed that significant larger brain activations by painful rather than non-painful stimuli in video clips were observed not only at visual-related brain areas and anterior/mid-cingulate cortex, but also at S1 contralateral to the amputated limb. This observation suggested the increased sensitivity of S1 of the amputated limb to the pain-related context. In addition, such increase of sensitivity was significantly larger if the context was associated with the amputated limb of the patient. In summary, our findings provided novel evidence for a possible neuroplasticity of S1 of the amputated limb: in an amputee with long-lasting phantom limb pain, the sensitivity of S1 to pain-related and amputated-limb-related context was greatly enhanced. PMID:27389122

  19. Genetic alterations and epigenetic changes in hepatocarcinogenesis

    Luz Stella Hoyos Giraldo

    2007-02-01

    Full Text Available

    Hepatocarcinogenesis as hepatocellular carcinoma (HCC is associated with background of chronic liver disease usually in association with cirrhosis, marked hepatic fibrosis, hepatitis B virus (HBV and/or hepatitis virus (HCV infection, chronic inflammation, Aflatoxin B1(AFB1 exposure, chronic alcoholism, metabolic disorder of the liver and necroinflamatory liver disease. Hepatocarcinogenesis involve two mechanisms, genetic alterations (with changes in the cell's DNA sequence and epigenetic changes (without changes in the cell's DNA sequence, but changes in the pattern of gene expression that can persist through one or more generations (somatic sense. Hepatocarcinogenesis is associated with activation of oncogenes and decreased expression of tumor suppressor genes (TSG; include those involved in cell cycle control, apoptosis, DNA repair, immortalization and angiogenesis. AFB1 is metabolized in the liver into a potent carcinogen, aflatoxin 8, 9-epoxide, which is detoxified by epoxide hydrolase (EPHX and glutathione S-transferase M1 (GSTM1.

    A failure of detoxification processes can allow to mutagenic metabolite to bind to DNA and inducing P53 mutation. Genetic polymorphism of EPHX and GSTM1 can make individuals more susceptible to AFB1. Epigenetic inactivation of GSTP1 by promoter hypermethylation plays a role in the development of HCC because, it leads that electrophilic metabolite increase DNA damage and mutations. HBV DNA integration into the host chromosomal DNA of hepatocytes has been detected in HBV-related HCC.

    DNA tumor viruses cause cancer mainly by interfering with cell cycle controls, and activating the cell's replication machinery by blocking the action of key TSG. HBx protein is a

  20. Epigenetic upregulation of corticotrophin-releasing hormone mediates postnatal maternal separation-induced memory deficiency.

    Aiyun Wang

    Full Text Available Accumulating evidences demonstrated that early postnatal maternal separation induced remarkable social and memory defects in the adult rodents. Early-life stress induced long-lasting functional adaptation of neuroendocrine hypothalamic-pituitary-adrenal axis, including neuropeptide corticotrophin-releasing hormone (CRH in the brain. In the present study, a significantly increased hippocampal CRH was observed in the adult rats with postnatal maternal separation, and blockade of CRHR1 signaling significantly attenuated the hippocampal synaptic dysfunction and memory defects in the modeled rats. Postnatal maternal separation enduringly increased histone H3 acetylation and decreased cytosine methylation in Crh promoter region, resulting from the functional adaptation of several transcriptional factors, in the hippocampal CA1 of the modeled rats. Enriched environment reversed the epigenetic upregulation of CRH, and ameliorated the hippocampal synaptic dysfunction and memory defects in the adult rats with postnatal maternal separation. This study provided novel insights into the epigenetic mechanism underlying postnatal maternal separation-induced memory deficiency, and suggested environment enrichment as a potential approach for the treatment of this disorder.

  1. Genetic syndromes caused by mutations in epigenetic genes.

    Berdasco, María; Esteller, Manel

    2013-04-01

    The orchestrated organization of epigenetic factors that control chromatin dynamism, including DNA methylation, histone marks, non-coding RNAs (ncRNAs) and chromatin-remodeling proteins, is essential for the proper function of tissue homeostasis, cell identity and development. Indeed, deregulation of epigenetic profiles has been described in several human pathologies, including complex diseases (such as cancer, cardiovascular and neurological diseases), metabolic pathologies (type 2 diabetes and obesity) and imprinting disorders. Over the last decade it has become increasingly clear that mutations of genes involved in epigenetic mechanism, such as DNA methyltransferases, methyl-binding domain proteins, histone deacetylases, histone methylases and members of the SWI/SNF family of chromatin remodelers are linked to human disorders, including Immunodeficiency Centromeric instability Facial syndrome 1, Rett syndrome, Rubinstein-Taybi syndrome, Sotos syndrome or alpha-thalassemia/mental retardation X-linked syndrome, among others. As new members of the epigenetic machinery are described, the number of human syndromes associated with epigenetic alterations increases. As recent examples, mutations of histone demethylases and members of the non-coding RNA machinery have recently been associated with Kabuki syndrome, Claes-Jensen X-linked mental retardation syndrome and Goiter syndrome. In this review, we describe the variety of germline mutations of epigenetic modifiers that are known to be associated with human disorders, and discuss the therapeutic potential of epigenetic drugs as palliative care strategies in the treatment of such disorders. PMID:23370504

  2. [Epigenetics: a novel tool for early diagnosis and tumor therapy].

    Filetici, Patrizia

    2015-01-01

    Epigenetics, first described by Conrad Waddington, defines how pathways setting a specific phenotype and heritable cellular functions are activated in a DNA independent way. Epigenetics concerns the study of genome structure and accessibility that regulates patterns of gene expression through the dynamic compaction and opening the chromatin structure. Vincent Allfrey profetically declared in 1964 that histone modifications could influence gene expression. In cancer very often cells show a profound modification of DNA methylation and mutations in chromatin regulators. These evidences provided therefore a clear link between epigenetics and neoplasia. Advanced molecular technology such as Deep-sequencing and ChIP-Seq revealed the frequent relocalization in cancer of many PTM readers such the Ac-Lys binding bromodomain. These results were important for the development of novel classes of epigenetic drugs some of which are inhibitors of histone modifyers or molecule interacting with reader domains. Since cancer imply profound changes in the epigenetic profile and in gene transcription a future challenge of molecular and chemical biology will be to develop novel epigenetic compounds able to correct the epigenetic disfunction and, possibly, coadiuvate canonical therapy in the cure of cancer. PMID:25621778

  3. The Epigenetic Switches for Neural Development and Psychiatric Disorders

    Jingwen Lv; Yongjuan Xin; Wenhao Zhou; Zilong Qiu

    2013-01-01

    The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences,in joint with genetic landscapes.The nature vs.nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain.The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade.Moreover,the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders,such as autism spectrum disorders.The epigenetic study has initiated in the neuroscience field for a relative short period of time.In this review,we will summarize recent discoveries about epigenetic regulation on neural development,synaptic plasticity,learning and memory,as well as neuropsychiatric disorders.Although the comprehensive view of how epigenetic regulation contributes to the function of the brain is still not completed,the notion that brain,the most complicated organ of organisms,is profoundly shaped by epigenetic switches is widely accepted.

  4. Sperm is epigenetically programmed to regulate gene transcription in embryos.

    Teperek, Marta; Simeone, Angela; Gaggioli, Vincent; Miyamoto, Kei; Allen, George E; Erkek, Serap; Kwon, Taejoon; Marcotte, Edward M; Zegerman, Philip; Bradshaw, Charles R; Peters, Antoine H F M; Gurdon, John B; Jullien, Jerome

    2016-08-01

    For a long time, it has been assumed that the only role of sperm at fertilization is to introduce the male genome into the egg. Recently, ideas have emerged that the epigenetic state of the sperm nucleus could influence transcription in the embryo. However, conflicting reports have challenged the existence of epigenetic marks on sperm genes, and there are no functional tests supporting the role of sperm epigenetic marking on embryonic gene expression. Here, we show that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos, we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks at fertilization de-regulates gene expression in the resulting embryos in a paternal chromatin-dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits. Understanding how parental experience can influence development of the progeny has broad potential for improving human health. PMID:27034506

  5. Epigenetic Therapy in Acute Myeloid Leukemia: Current and Future Directions.

    Kim, Tae Kon; Gore, Steven D; Zeidan, Amer M

    2015-07-01

    Epigenetic modifications affect gene expression without changes in the actual DNA sequence. Two of the most important mechanisms include DNA methylation and histone tail modifications (especially acetylation and methylation). Epigenetic modulation is a part of normal physiologic development; its dysregulation is an important mechanism of pathogenesis of some cancers, including acute myeloid leukemia (AML). Despite significant progress in understanding the pathogenesis of AML, therapeutic options remain quite limited. Technological advances have facilitated understanding of aberrant DNA methylation and histone methylation/acetylation as key elements in the development of AML and uncovered several recurrent mutations in genes important for epigenetic regulation. However, much remains to be learned about how to exploit this knowledge for epigenetic therapeutic targeting. Currently, no epigenetic therapy is approved for the treatment of AML, although two DNA methyltransferase inhibitors (azacitidine and decitabine) are commonly used in clinical practice. Among the other epigenetic modifiers undergoing research in AML, the histone deacetylase inhibitors are the most studied. Other promising drugs, such as inhibitors of histone methylation (eg, EZH2 and DOT1L inhibitors), inhibitors of histone demethylases (eg, LSD1 inhibitors), inhibitors of bromodomain-containing epigenetic "reader" BET proteins, and inhibitors of mutant isocitrate dehydrogenases, are at early stages of clinical evaluation. PMID:26111464

  6. Bifurcation in epigenetics: Implications in development, proliferation, and diseases

    Jost, Daniel

    2014-01-01

    Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of biochemical marks on chromatin. Here, we develop a stochastic model that describes the dynamics of epigenetic marks along a given DNA region. Through mathematical analysis, we show the emergence of bistable and persistent epigenetic states from the cooperative recruitment of modifying enzymes. We also find that the dynamical system exhibits a critical point and displays, in the presence of asymmetries in recruitment, a bifurcation diagram with hysteresis. These results have deep implications for our understanding of epigenetic regulation. In particular, our study allows one to reconcile within the same formalism the robust maintenance of epigenetic identity observed in differentiated cells, the epigenetic plasticity of pluripotent cells during differentiation, and the effects of epigenetic misregulation in diseases. Moreover, it suggests a possible mechanism for developmental transitions where the system is shifted close to the critical point to benefit from high susceptibility to developmental cues.

  7. Neurogenesis-based epigenetic therapeutics for Alzheimer's disease (Review).

    Li, Xueyuan; Bao, Xinjie; Wang, Renzhi

    2016-08-01

    Alzheimer's disease (AD) is a worldwide health problem with multiple pathogenic causes including aging, and genetic and environmental factors. As the interfaces between genes and the environment, epigenetic mechanisms, including DNA methylation, histone modification and microRNAs, are also involved in the pathogenesis of AD. Neurogenesis occurs throughout life in the normal adult brain of mammals. The neurogenic process, consisting of the proliferation, differentiation and maturation of neural stem cells (NSC), is regulated via epigenetic mechanisms by controlling the expression of specific sets of genes. In the pathology of AD, due to impairments in epigenetic mechanisms, the generation of neurons from NSCs is damaged, which exacerbates the loss of neurons and the deficits in learning and memory function associated with AD. Based on neurogenesis, a number of therapeutic strategies have shown capability in promoting neuronal generation to compensate for the neurons lost in AD, thereby improving cognitive function through epigenetic modifications. This provides potential for the treatment of AD by stimulating neurogenesis using epigenetic strategies. The present review discusses the epigenetics of AD and adult neurogenesis, and summarizes the neurogenesis-based epigenetic therapies targeted at AD. Such a review may offer information for the guidance of future developments of therapeutic strategies for AD. PMID:27314984

  8. Epigenetic programming and risk: the birthplace of cardiovascular disease?

    Vinci, Maria Cristina; Polvani, Gianluca; Pesce, Maurizio

    2013-06-01

    Epigenetics, through control of gene expression circuitries, plays important roles in various physiological processes such as stem cell differentiation and self renewal. This occurs during embryonic development, in different tissues, and in response to environmental stimuli. The language of epigenetic program is based on specific covalent modifications of DNA and chromatin. Thus, in addition to the individual identity, encoded by sequence of the four bases of the DNA, there is a cell type identity characterized by its positioning in the epigenetic "landscape". Aberrant changes in epigenetic marks induced by environmental cues may contribute to the development of abnormal phenotypes associated with different human diseases such as cancer, neurological disorders and inflammation. Most of the epigenetic studies have focused on embryonic development and cancer biology, while little has been done to explore the role of epigenetic mechanisms in the pathogenesis of cardiovascular disease. This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodeling and histone modifications play key roles in the pathogenesis of cardiovascular disease through (re)programming of cardiovascular (stem) cells commitment, identity and function. PMID:22773406

  9. Understanding type 2 diabetes: from genetics to epigenetics.

    Raciti, Gregory Alexander; Longo, Michele; Parrillo, Luca; Ciccarelli, Marco; Mirra, Paola; Ungaro, Paola; Formisano, Pietro; Miele, Claudia; Béguinot, Francesco

    2015-10-01

    The known genetic variability (common DNA polymorphisms) does not account either for the current epidemics of type 2 diabetes or for the family transmission of this disorder. However, clinical, epidemiological and, more recently, experimental evidence indicates that environmental factors have an extraordinary impact on the natural history of type 2 diabetes. Some of these environmental hits are often shared in family groups and proved to be capable to induce epigenetic changes which alter the function of genes affecting major diabetes traits. Thus, epigenetic mechanisms may explain the environmental origin as well as the familial aggregation of type 2 diabetes much easier than common polymorphisms. In the murine model, exposure of parents to environmental hits known to cause epigenetic changes reprograms insulin sensitivity as well as beta-cell function in the progeny, indicating that certain epigenetic changes can be transgenerationally transmitted. Studies from different laboratories revealed that, in humans, lifestyle intervention modulates the epigenome and reverts environmentally induced epigenetic modifications at specific target genes. Finally, specific human epigenotypes have been identified which predict adiposity and type 2 diabetes with much greater power than any polymorphism so far identified. These epigenotypes can be recognized in easily accessible white cells from peripheral blood, indicating that, in the future, epigenetic profiling may enable effective type 2 diabetes prediction. This review discusses recent evidence from the literature supporting the immediate need for further investigation to uncover the power of epigenetics in the prediction, prevention and treatment of type 2 diabetes. PMID:25841587

  10. The epigenetic switches for neural development and psychiatric disorders.

    Lv, Jingwen; Xin, Yongjuan; Zhou, Wenhao; Qiu, Zilong

    2013-07-20

    The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences, in joint with genetic landscapes. The nature vs. nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain. The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade. Moreover, the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders, such as autism spectrum disorders. The epigenetic study has initiated in the neuroscience field for a relative short period of time. In this review, we will summarize recent discoveries about epigenetic regulation on neural development, synaptic plasticity, learning and memory, as well as neuropsychiatric disorders. Although the comprehensive view of how epigenetic regulation contributes to the function of the brain is still not completed, the notion that brain, the most complicated organ of organisms, is profoundly shaped by epigenetic switches is widely accepted. PMID:23876774

  11. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression.

    Feinberg, Andrew P; Koldobskiy, Michael A; Göndör, Anita

    2016-05-01

    This year is the tenth anniversary of the publication in this journal of a model suggesting the existence of 'tumour progenitor genes'. These genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, and thus cause altered differentiation throughout tumour evolution. The past decade of discovery in cancer epigenetics has revealed a number of similarities between cancer genes and stem cell reprogramming genes, widespread mutations in epigenetic regulators, and the part played by chromatin structure in cellular plasticity in both development and cancer. In the light of these discoveries, we suggest here a framework for cancer epigenetics involving three types of genes: 'epigenetic mediators', corresponding to the tumour progenitor genes suggested earlier; 'epigenetic modifiers' of the mediators, which are frequently mutated in cancer; and 'epigenetic modulators' upstream of the modifiers, which are responsive to changes in the cellular environment and often linked to the nuclear architecture. We suggest that this classification is helpful in framing new diagnostic and therapeutic approaches to cancer. PMID:26972587

  12. Epi-genetics modifications induced by a depleted uranium exposure in the zebra fish

    Gombeau, K.; Pereira, S.; Adam-Guillermin, C. [IRSN/PRP-ENV/SERIS/LECO (France); Bourdineaud, J.P. [UMR CNRS 5805 EPOC (France); Ravanat, J.L. [INAC/Scib UMR E3 CEA-UJF (France)

    2014-07-01

    The work presented here integrates in the general framework of assessment of effects of chronic exposure to low doses of radionuclides. This evaluation necessarily involves the study of the mechanisms of toxic action at the cellular or subcellular level, in order to better understand the processes of propagation of effects to the level of the populations or ecosystems. As such, the question of the mechanisms underlying the trans-generational effects and the adaptive capacity of organisms is central, both in humans and in animal species. Epigenetic refer to changes in gene function that do not involve changes in DNA sequence, and which are transmitted in a hereditary manner by mitosis or meiosis. The latter plays a key role in these trans-generational effects. Among these changes, DNA-methylation is one of the most studied epigenetic parameters. This work is part of a PhD, included in the European COMET project (Euratom 7. Framework Program), and focuses on epigenetic modifications induced in zebra fish after a chronic exposure to radionuclides. Male and female fishes were exposed to 2 and 20 μg.L{sup -1} of depleted uranium for 24 days. After 7 and 24 days of exposure, brain, gonads, and eyes were collected in order to study changes in DNA methylation. In addition, genotoxicity was measured by the γH2AX assay. The overall changes in DNA methylation were studied by AFLP-MS and HPLC-MS, in order to know if the exposure to depleted uranium changes the global status of DNA methylation. We have found a decrease in the global level of methylation in the eyes of males after 24 days of exposure, the diminution being much more important and significant at the higher concentration of exposure (11.79 ± 3.62 against 52.43 ± 3.01 for controls) This study will be refined by analyzing the methylation of specific regions of the genome, because it represent the sequences of genes involved in major physiological functions and that may be subject to variations in the methylation

  13. Epi-genetics modifications induced by a depleted uranium exposure in the zebra fish

    The work presented here integrates in the general framework of assessment of effects of chronic exposure to low doses of radionuclides. This evaluation necessarily involves the study of the mechanisms of toxic action at the cellular or subcellular level, in order to better understand the processes of propagation of effects to the level of the populations or ecosystems. As such, the question of the mechanisms underlying the trans-generational effects and the adaptive capacity of organisms is central, both in humans and in animal species. Epigenetic refer to changes in gene function that do not involve changes in DNA sequence, and which are transmitted in a hereditary manner by mitosis or meiosis. The latter plays a key role in these trans-generational effects. Among these changes, DNA-methylation is one of the most studied epigenetic parameters. This work is part of a PhD, included in the European COMET project (Euratom 7. Framework Program), and focuses on epigenetic modifications induced in zebra fish after a chronic exposure to radionuclides. Male and female fishes were exposed to 2 and 20 μg.L-1 of depleted uranium for 24 days. After 7 and 24 days of exposure, brain, gonads, and eyes were collected in order to study changes in DNA methylation. In addition, genotoxicity was measured by the γH2AX assay. The overall changes in DNA methylation were studied by AFLP-MS and HPLC-MS, in order to know if the exposure to depleted uranium changes the global status of DNA methylation. We have found a decrease in the global level of methylation in the eyes of males after 24 days of exposure, the diminution being much more important and significant at the higher concentration of exposure (11.79 ± 3.62 against 52.43 ± 3.01 for controls) This study will be refined by analyzing the methylation of specific regions of the genome, because it represent the sequences of genes involved in major physiological functions and that may be subject to variations in the methylation of the

  14. Genetic and epigenetic variants influencing the development of nonalcoholic fatty liver disease

    Yu-Yuan Li

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is common worldwide.The importance of genetic and epigenetic changes in etiology and pathogenesis of NAFLD has been increasingly recognized.However,the exact mechanism is largely unknown.A large number of single nucleotide polymorphisms (SNPs) related to NAFLD has been documented by candidate gene studies (CGSs).Among these genes,peroxisome proliferatoractivated receptor-y,adiponectin,leptin and tumor necrosis factor-α were frequently reported.Since the introduction of genome-wide association studies (GWASs),there have been significant advances in our understanding of genomic variations of NAFLD.Patatinlike phospholipase domain containing family member A3 (PNPLA3,SNP rs738409,encoding I148M),also termed adiponutrin,has caught most attention.The evidence that PNPLA3 is associated with increased hepatic fat levels and hepatic inflammation has been validated by a series of studies.Epigenetic modification refers to phenotypic changes caused by an adaptive mechanism unrelated to alteration of primary DNA sequences.Epigenetic regulation mainly includes microRNAs (miRs),DNA methylation,histone modifications and ubiquitination,among which miRs are studied most extensively.miRs are small natural single stranded RNA molecules regulating mRNA degradation or translation inhibition,subsequently altering protein expression of target genes.The miR-122,a highly abundant miR accounting for nearly 70% of all miRs in the liver,is significantly under-expressed in NAFLD subjects.Inhibition of miR-122 with an antisense oligonucleotide results in decreased mRNA expression of lipogenic genes and improvement of liver steatosis.The investigation into epigenetic involvement in NAFLD pathogenesis is just at the beginning and needs to be refined.This review summarizes the roles of genetics and epigenetics in the development of NAFLD.The progress made in this field may provide novel diagnostic biomarkers and therapeutic targets for NAFLD management.

  15. Epigenetic processes and cancer risk assessment

    The U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment encourages the use of mechanistic data in the assessment of human cancer risk at low (environmental) exposure levels. The key events that define a particular mode of action for tumor formation have been concentrated to date more on mutational responses that are broadly the result of induced DNA damage and enhanced cell proliferation. While it is clear that these processes are important in terms of tumor induction, other modes that fall under the umbrella of epigenetic responses are increasingly being considered to play an important role in susceptibility to tumor induction by environmental chemicals and as significant modifiers of tumor responses. Alterations in gene expression, DNA repair, cell cycle control, genome stability and genome reprogramming could be the result of modification of DNA methylation and chromatin remodeling patterns as a consequence of exposure to environmental chemicals. These concepts are described and discussed

  16. Chemical Inhibitors of Epigenetic Methyllysine Reader Proteins.

    Milosevich, Natalia; Hof, Fraser

    2016-03-22

    Protein methylation is a common post-translational modification with diverse biological functions. Methyllysine reader proteins are increasingly a focus of epigenetics research and play important roles in regulating many cellular processes. These reader proteins are vital players in development, cell cycle regulation, stress responses, oncogenesis, and other disease pathways. The recent emergence of a small number of chemical inhibitors for methyllysine reader proteins supports the viability of these proteins as targets for drug development. This article introduces the biochemistry and biology of methyllysine reader proteins, provides an overview of functions for those families of readers that have been targeted to date (MBT, PHD, tudor, and chromodomains), and reviews the development of synthetic agents that directly block their methyllysine reading functions. PMID:26650180

  17. Evolution of Epigenetic Regulation in Vertebrate Genomes.

    Lowdon, Rebecca F; Jang, Hyo Sik; Wang, Ting

    2016-05-01

    Empirical models of sequence evolution have spurred progress in the field of evolutionary genetics for decades. We are now realizing the importance and complexity of the eukaryotic epigenome. While epigenome analysis has been applied to genomes from single-cell eukaryotes to human, comparative analyses are still relatively few and computational algorithms to quantify epigenome evolution remain scarce. Accordingly, a quantitative model of epigenome evolution remains to be established. We review here the comparative epigenomics literature and synthesize its overarching themes. We also suggest one mechanism, transcription factor binding site (TFBS) turnover, which relates sequence evolution to epigenetic conservation or divergence. Lastly, we propose a framework for how the field can move forward to build a coherent quantitative model of epigenome evolution. PMID:27080453

  18. Epigenetic effects of ethanol on liver and gastrointestinal injury

    Shivendra D Shukla; Annayya R Aroor

    2006-01-01

    Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.

  19. Cancer-germline antigen vaccines and epigenetic enhancers

    Gjerstorff, Morten Frier; Burns, Jorge; Ditzel, Henrik Jorn

    2010-01-01

    can be achieved using epigenetic modifiers. AREAS COVERED IN THIS REVIEW: We provide an overview of the potential of CG antigens as targets for cancer immunotherapy, including advantages and disadvantages. We also discuss the current state of development of CG antigen vaccines, and the potential...... synergistic effect of combining CG antigen immunotherapeutic strategies with epigenetic modifiers. WHAT THE READER WILL GAIN: The reader will gain an overview of the past, present and future role of CG antigens in cancer immunotherapy. TAKE HOME MESSAGE: Chemoimmunotherapy using epigenetic drugs and CG...

  20. Epigenetic biomarkers in prostate cancer: Current and future uses.

    Chiam, Karen; Ricciardelli, Carmela; Bianco-Miotto, Tina

    2014-01-28

    Epigenome alterations are characteristic of nearly all human malignancies and include changes in DNA methylation, histone modifications and microRNAs (miRNAs). However, what induces these epigenetic alterations in cancer is largely unknown and their mechanistic role in prostate tumorigenesis is just beginning to be evaluated. Identification of the epigenetic modifications involved in the development and progression of prostate cancer will not only identify novel therapeutic targets but also prognostic and diagnostic markers. This review will focus on the use of epigenetic modifications as biomarkers for prostate cancer. PMID:22391123

  1. Measuring topology of low-intensity DNA methylation sites for high-throughput assessment of epigenetic drug-induced effects in cancer cells

    Epigenetic anti-cancer drugs with demethylating effects have shown to alter genome organization in mammalian cell nuclei. The interest in the development of novel epigenetic drugs has increased the demand for cell-based assays to evaluate drug performance in pre-clinical studies. An imaging-based cytometrical approach that can measure demethylation effects as changes in the spatial nuclear distributions of methylated cytosine and global DNA in cancer cells is introduced in this paper. The cells were studied by immunofluorescence with a specific antibody against 5-methylcytosine (MeC), and 4,6-diamidino-2-phenylindole (DAPI) for delineation of methylated sites and global DNA in nuclei. In the preprocessing step the segmentation of nuclei in three-dimensional images (3-D) is followed by an automated assessment of nuclear DAPI/MeC patterns to exclude dissimilar entities. Next, low-intensity MeC (LIM) and low-intensity DNA (LID) sites of similar nuclei are localized and processed to obtain specific nuclear density profiles. These profiles sampled at half of the total nuclear volume yielded two parameters: LIM0.5 and LID0.5. The analysis shows that zebularine and 5-azacytidine-the two tested epigenetic drugs introduce changes in the spatial distribution of low-intensity DNA and MeC signals. LIM0.5 and LID0.5 were significantly different (p < 0.001) in 5-azacytidine treated (n = 660) and zebularine treated (n = 496) vs. untreated (n = 649) DU145 human prostate cancer cells. In the latter case the LIM sites were predominantly found at the nuclear border, whereas treated populations showed different degrees of increase in LIMs towards the interior nuclear space, in which a large portion of heterochromatin is located. The cell-by-cell evaluation of changes in the spatial reorganization of MeC/DAPI signals revealed that zebularine is a more gentle demethylating agent than 5-azacytidine. Measuring changes in the topology of low-intensity sites can potentially be a valuable

  2. Adaptive Lighting

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive LightingAdaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled i...

  3. MeCP2 dependent heterochromatin reorganization during neural differentiation of a novel Mecp2-deficient embryonic stem cell reporter line.

    Bianca Bertulat

    Full Text Available The X-linked Mecp2 is a known interpreter of epigenetic information and mutated in Rett syndrome, a complex neurological disease. MeCP2 recruits HDAC complexes to chromatin thereby modulating gene expression and, importantly regulates higher order heterochromatin structure. To address the effects of MeCP2 deficiency on heterochromatin organization during neural differentiation, we developed a versatile model for stem cell in vitro differentiation. Therefore, we modified murine Mecp2 deficient (Mecp2(-/y embryonic stem cells to generate cells exhibiting green fluorescent protein expression upon neural differentiation. Subsequently, we quantitatively analyzed heterochromatin organization during neural differentiation in wild type and in Mecp2 deficient cells. We found that MeCP2 protein levels increase significantly during neural differentiation and accumulate at constitutive heterochromatin. Statistical analysis of Mecp2 wild type neurons revealed a significant clustering of heterochromatin per nuclei with progressing differentiation. In contrast we found Mecp2 deficient neurons and astroglia cells to be significantly impaired in heterochromatin reorganization. Our results (i introduce a new and manageable cellular model to study the molecular effects of Mecp2 deficiency, and (ii support the view of MeCP2 as a central protein in heterochromatin architecture in maturating cells, possibly involved in stabilizing their differentiated state.

  4. Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis.

    Harris, N G; Verley, D R; Gutman, B A; Thompson, P M; Yeh, H J; Brown, J A

    2016-03-01

    While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity

  5. The use of high-density EEG to map out cortical motor activity and reorganization following lower-limb amputation

    Valur Guðnason 1991

    2016-01-01

    Introduction: Studies have shown that after amputation, changes occur in the sensory and motor cortex. These changes are called cortical reorganization, where adjacent cortical areas occupy the cortical area of the amputated limb. High-density electroencephalography (EEG) has been used to observe cortical reorganization in the motor cortex following upper limb amputation. The aim of this study was to use high-density EEG to map out motor cortical activity and cortical reorganization following...

  6. How can IT Raise Productivity Linked with Workplace Re-organization and Human Capital in Japan ?" (in Japanese)

    Futoshi Kurokawa; Kazunori Minetaki

    2006-01-01

    This paper examines the impact of Information and Communication Technology (ICT) on the productivity linked with workplace re-organization and human capital using large-scale cross-sectional data of Japanese firms Our results suggest that the progress of ICT has positive effect on productivity and this effect become more effective by combining with firm's re-organization and human capital accumulation. However, our results also suggest that re-organizations have not made enough especially wit...

  7. Between the streets and the shelter: everyday reorganization

    Flávia Barbosa de Oliveira; Samira Lima da Costa

    2015-01-01

    The street situation population has been shown as a growing urban phenomenon, becoming an object of interest to public managers and academics. This paper presents the results of a research aimed at understanding the context of street situation residents, under current provisory institutional shelter care, analyzing why the streets have become the home for some people; how the process of development and adaptation of daily activities in this new reality occurred; when and why they decided to l...

  8. Epigenetic transmission of Holocaust trauma: can nightmares be inherited?

    Kellermann, Natan Pf

    2013-01-01

    The Holocaust left its visible and invisible marks not only on the survivors, but also on their children. Instead of numbers tattooed on their forearms, however, they may have been marked epigenetically with a chemical coating upon their chromosomes, which would represent a kind of biological memory of what the parents experienced. as a result, some suffer from a general vulnerability to stress while others are more resilient. Previous research assumed that such transmission was caused by environmental factors, such as the parents' childrearing behavior. New research, however, indicates that these transgenerational effects may have been also (epi) genetically transmitted to their children. Integrating both hereditary and environmental factors, epigenetics adds a new and more comprehensive psychobiological dimension to the explanation of transgenerational transmission of trauma. Specifically, epigenetics may explain why latent transmission becomes manifest under stress. a general theoretical overview of epigenetics and its relevance to research on trauma transmission is presented. PMID:24029109

  9. Prenatal and early life influences on epigenetic age in children

    Simpkin, Andrew J; Hemani, Gibran; Suderman, Matthew;

    2016-01-01

    DNA methylation based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration in adults. Very little is known about genetic or environmental determinants...... of these epigenetic measures of aging. We obtained DNA methylation profiles using Infinium HumanMethylation450 BeadChips across five time points in 1018 mother-child pairs from the Avon Longitudinal Study of Parents and Children. Using the Horvath age estimation method, we calculated epigenetic age for these samples....... Age acceleration (AA) was defined as the residuals from regressing epigenetic age on actual age. AA was tested for associations with cross-sectional clinical variables in children. We identified associations between AA and sex, birth weight, birth by caesarean section and several maternal...

  10. Mitochondrial regulation of epigenetics and its role in human diseases

    Minocherhomji, Sheroy; Tollefsbol, Trygve O; Singh, Keshav K

    2012-01-01

    as the sole pathogenic factor suggesting that additional mechanisms contribute to lack of genotype and clinical phenotype correlationship. An increasing number of studies have identified a possible effect on the epigenetic landscape of the nuclear genome as a consequence of mitochondrial dysfunction....... In particular, these studies demonstrate reversible or irreversible changes in genomic DNA methylation profiles of the nuclear genome. Here we review how mitochondria damage checkpoint (mitocheckpoint) induces epigenetic changes in the nucleus. Persistent pathogenic mutations in mtDNA may also lead...... to epigenetic changes causing genomic instability in the nuclear genome. We propose that "mitocheckpoint" mediated epigenetic and genetic changes may play key roles in phenotypic variation related to mitochondrial diseases or host of human diseases in which mitochondrial defect plays a primary role....

  11. Twins for epigenetic studies of human aging and development

    Tan, Qihua; Christiansen, Lene; Thomassen, Mads;

    2013-01-01

    Most of the complex traits including aging phenotypes are caused by the interaction between genome and environmental conditions and the interface of epigenetics may be a central mechanism. Although modern technologies allow us high-throughput profiling of epigenetic patterns already at genome level......, our understanding of genetic and environmental influences on the epigenetic processes remains limited. Twins are of special interest for genetic studies due to their genetic similarity and rearing-environment sharing. The classical twin design has made a great contribution in dissecting the genetic...... and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable sample of twins is helping to bridge the gap between gene activity and the environments through epigenetic mechanisms unlimited by DNA sequence variations. We propose to extend the classical twin...

  12. Epigenetics and the Developmental Origins of Health and Disease#

    Epigenetic programming is likely to be an important mechanism underlying the lasting influence of the reproductive and developmental environment on lifelong health, a concept known as the Developmental Origins of Health and Disease (DOHaD). Environmental exposures including paren...

  13. Epigenetics: a new bridge between nutrition and health

    Nutrients can reverse or change epigenetic phenomena such as DNA methylation and histone modifications, thereby modifying the expression of critical genes associated with physiologic and pathologic processes, including embryonic development, aging, and carcinogenesis. It appears that nutrients and b...

  14. Molecular targets of epigenetic regulation and effectors of environmental influences

    The true understanding of what we currently define as epigenetics evolved over time as our knowledge on DNA methylation and chromatin modifications and their effects on gene expression increased. The current explosion of research on epigenetics and the increasing documentation of the effects of various environmental factors on DNA methylation, chromatin modification, as well as on the expression of small non-coding RNAs (ncRNAs) have expanded the scope of research on the etiology of various diseases including cancer. The current review briefly discusses the molecular mechanisms of epigenetic regulation and expands the discussion with examples on the role of environment, such as the immediate environment during development, in inducing epigenetic changes and modulating gene expression.

  15. Epigenetic Stability of Cryopreserved and Cold-Stored Hops

    Three hop accessions representative of commercially cultivated hops were selected for the analysis of epigenetic stability; females of different origins, including a cultivar developed in New Zealand (Calicross) from American cultivars, a landrace derived European cultivar (Tardif de Bourgogne), and...

  16. Epigenetics changes associated to environmental triggers in autoimmunity.

    Cañas, Carlos A; Cañas, Felipe; Bonilla-Abadía, Fabio; Ospina, Fabio E; Tobón, Gabriel J

    2016-02-01

    Autoimmune diseases (AIDs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens and represent a heterogeneous group of disorders that affect specific target organs or multiple organs in different systems. While the pathogenesis of AID remains unclear, its aetiology is multifunctional and includes a combination of genetic, epigenetic, immunological and environmental factors. In AIDs, several epigenetic mechanisms are defective including DNA demethylation, abnormal chromatin positioning associated with autoantibody production and abnormalities in the expression of RNA interference (RNAi). It is known that environmental factors may interfere with DNA methylation and histone modifications, however, little is known about epigenetic changes derived of regulation of RNAi. An approach to the known environmental factors and the mechanisms that alter the epigenetic regulation in AIDs (with emphasis in systemic lupus erythematosus, the prototype of systemic AID) are showed in this review. PMID:26369426

  17. Burnout in health-care professionals during reorganizations and downsizing. A cohort study in nurses

    Hall-Lord Marie-Louise

    2010-06-01

    Full Text Available Abstract Background Burnout is a psychological reaction triggered by interaction between personal characteristics and stress factors. Reorganizations and downsizing with increased workload imply stress for health-care professionals. This is a study of burnout in nurses during a period with two comprehensive reorganizations. Methods In this quasi-experimental retrospective cohort study, burnout was assessed in nurses with long work experience in three surveys during a 30 months' period with two comprehensive reorganizations and downsizing of a hospital unit with mostly seriously ill patients with cancer. Burnout was measured with Bergen Burnout Indicator (BBI at each survey, and "Sense of Coherence" (SOC with Antonovsky's questionnaire at the last survey. Results One man and 45 women aged 30 to 65 years were invited to the surveys. There was a significant increase in burnout during the study period, the mean increase in BBI-score was 12.5 pr year (p Conclusions There was a significant development of burnout in a group of nurses during a period with two reorganizations and downsizing. Burnout was associated with low SOC. Working with seriously ill patients with cancer has probably made the nurses exceptionally vulnerable to the stress and workload related to the reorganizations.

  18. Phasevarion mediated epigenetic gene regulation in Helicobacter pylori.

    Yogitha N Srikhanta

    Full Text Available Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression. In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M system, controls expression of a phase-variable regulon of genes (a "phasevarion", via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16% of isolates. Microarray analysis comparing the wild-type P12modH5 ON strain to a P12ΔmodH5 mutant revealed that six genes were either up- or down-regulated, and some were virulence-associated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis.

  19. Phasevarion mediated epigenetic gene regulation in Helicobacter pylori.

    Srikhanta, Yogitha N; Gorrell, Rebecca J; Steen, Jason A; Gawthorne, Jayde A; Kwok, Terry; Grimmond, Sean M; Robins-Browne, Roy M; Jennings, Michael P

    2011-01-01

    Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M) system, controls expression of a phase-variable regulon of genes (a "phasevarion"), via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16% of isolates). Microarray analysis comparing the wild-type P12modH5 ON strain to a P12ΔmodH5 mutant revealed that six genes were either up- or down-regulated, and some were virulence-associated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis. PMID:22162751

  20. Molecular and Epigenetic Mechanisms of MLL in Human Leukemogenesis

    Ballabio, Erica; Milne, Thomas A., E-mail: thomas.milne@imm.ox.ac.uk [MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital Headington, Oxford OX3 9DS (United Kingdom)

    2012-09-10

    Epigenetics is often defined as the study of heritable changes in gene expression or chromosome stability that don’t alter the underlying DNA sequence. Epigenetic changes are established through multiple mechanisms that include DNA methylation, non-coding RNAs and the covalent modification of specific residues on histone proteins. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukemia, but that these changes by their very nature are malleable, and thus are amenable to treatment. Epigenetic based therapies have so far focused on the use of histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors, which tend to have more general and widespread effects on gene regulation in the cell. However, if a unique molecular pathway can be identified, diseases caused by epigenetic mechanisms are excellent candidates for the development of more targeted therapies that focus on specific gene targets, individual binding domains, or specific enzymatic activities. Designing effective targeted therapies depends on a clear understanding of the role of epigenetic mutations during disease progression. The Mixed Lineage Leukemia (MLL) protein is an example of a developmentally important protein that controls the epigenetic activation of gene targets in part by methylating histone 3 on lysine 4. MLL is required for normal development, but is also mutated in a subset of aggressive human leukemias and thus provides a useful model for studying the link between epigenetic cell memory and human disease. The most common MLL mutations are chromosome translocations that fuse the MLL gene in frame with partner genes creating novel fusion proteins. In this review, we summarize recent work that argues MLL fusion proteins could function through a single molecular pathway, but we also highlight important data that suggests instead that multiple independent mechanisms underlie MLL mediated leukemogenesis.

  1. Epigenetic signature of birth weight discordance in adult twins

    Tan, Qihua; Nielsen, Morten Frost Munk; Heijmans, Bastiaan T;

    2014-01-01

    between birth weight and adult life health while controlling for not only genetics but also postnatal rearing environment. We performed an epigenome-wide profiling on blood samples from 150 pairs of adult monozygotic twins discordant for birth weight to look for molecular evidence of epigenetic signatures...... profiling did not reveal epigenetic signatures of birth weight discordance although some sites displayed age-dependent intra-pair differential methylation in the extremely discordant twin pairs....

  2. Molecular and Epigenetic Mechanisms of MLL in Human Leukemogenesis

    Thomas A. Milne

    2012-09-01

    Full Text Available Epigenetics is often defined as the study of heritable changes in gene expression or chromosome stability that don’t alter the underlying DNA sequence. Epigenetic changes are established through multiple mechanisms that include DNA methylation, non-coding RNAs and the covalent modification of specific residues on histone proteins. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukemia, but that these changes by their very nature are malleable, and thus are amenable to treatment. Epigenetic based therapies have so far focused on the use of histone deacetylase (HDAC inhibitors and DNA methyltransferase inhibitors, which tend to have more general and widespread effects on gene regulation in the cell. However, if a unique molecular pathway can be identified, diseases caused by epigenetic mechanisms are excellent candidates for the development of more targeted therapies that focus on specific gene targets, individual binding domains, or specific enzymatic activities. Designing effective targeted therapies depends on a clear understanding of the role of epigenetic mutations during disease progression. The Mixed Lineage Leukemia (MLL protein is an example of a developmentally important protein that controls the epigenetic activation of gene targets in part by methylating histone 3 on lysine 4. MLL is required for normal development, but is also mutated in a subset of aggressive human leukemias and thus provides a useful model for studying the link between epigenetic cell memory and human disease. The most common MLL mutations are chromosome translocations that fuse the MLL gene in frame with partner genes creating novel fusion proteins. In this review, we summarize recent work that argues MLL fusion proteins could function through a single molecular pathway, but we also highlight important data that suggests instead that multiple independent mechanisms underlie MLL mediated leukemogenesis.

  3. Epigenetic coordination of acute systemic inflammation: potential therapeutic targets

    Vachharajani, Vidula; Liu, Tiefu; McCall, Charles E.

    2014-01-01

    Epigenetic reprogramming of thousands of genes directs the course of acute systemic inflammation, which is highly lethal when dysregulated during sepsis. No molecular-based treatments for sepsis are available. A new concept supports that sepsis is an immunometabolic disease and that loss of control of nuclear epigenetic regulator Sirtuin 1 (SIRT-1), a NAD+ sensor directs immune and metabolic pathways during sepsis. SIRT-1, acting as homeostasis checkpoint, controls hyper and hypo inflammatory...

  4. Quantitative population epigenetics - a catalyst for sustainable agriculture

    Stauß, Reinhold

    2014-01-01

    Ecological intensification of agricultural practices can be a minimum input agriculture with a maximum utilization of the epigenetic potential for a maximum output. The application of Quantitative Population Epigenetics as a catalyst for sustainable agriculture offers earning opportunities (market segments or business cases) for the existing players in the high-input agriculture in terms of win-win. For example, agriculture is a major factor in eutrophication of surface waters. By using...

  5. Epigenetic Effect of Chronic Stress on Dopamine Signaling and Depression

    Sofia Moriam; Mahbub E. Sobhani

    2013-01-01

    Because of the complex causal factors leading to depression, epigenetics is of considerable interest for the understanding effect of stress in depression. Dopamine is a key neurotransmitter important in many physiological functions, including motor control, mood, and the reward pathway. These factors lead many drugs to target Dopamine receptors in treating depressive disorders. In this review, we try to portray how chronic stress as an epigenetic factor changes the gene regulation pattern by ...

  6. RNA-directed epigenetic regulations of DNA rearrangements

    Mochizuki, Kazufumi

    2010-01-01

    Ciliated protozoa undergo extensive DNA rearrangements, including DNA elimination, chromosome breakage and DNA descrambling, when the germline micronucleus produces the new macronucleus during sexual reproduction. It has long been known that many of these events are epigenetically controlled by DNA sequences of the parental macronuclear genome. Recent studies in some model ciliates have revealed that these epigenetic regulations are mediated by non-coding RNAs. DNA elimination in Paramecium a...

  7. Combinatorial epigenetic patterns as quantitative predictors of chromatin biology

    Cieślik, Marcin; Bekiranov, Stefan

    2014-01-01

    Background Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) is the most widely used method for characterizing the epigenetic states of chromatin on a genomic scale. With the recent availability of large genome-wide data sets, often comprising several epigenetic marks, novel approaches are required to explore functionally relevant interactions between histone modifications. Computational discovery of "chromatin states" defined by such combinatorial interactions enabled desc...

  8. Molecular and Epigenetic Mechanisms of MLL in Human Leukemogenesis

    Epigenetics is often defined as the study of heritable changes in gene expression or chromosome stability that don’t alter the underlying DNA sequence. Epigenetic changes are established through multiple mechanisms that include DNA methylation, non-coding RNAs and the covalent modification of specific residues on histone proteins. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukemia, but that these changes by their very nature are malleable, and thus are amenable to treatment. Epigenetic based therapies have so far focused on the use of histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors, which tend to have more general and widespread effects on gene regulation in the cell. However, if a unique molecular pathway can be identified, diseases caused by epigenetic mechanisms are excellent candidates for the development of more targeted therapies that focus on specific gene targets, individual binding domains, or specific enzymatic activities. Designing effective targeted therapies depends on a clear understanding of the role of epigenetic mutations during disease progression. The Mixed Lineage Leukemia (MLL) protein is an example of a developmentally important protein that controls the epigenetic activation of gene targets in part by methylating histone 3 on lysine 4. MLL is required for normal development, but is also mutated in a subset of aggressive human leukemias and thus provides a useful model for studying the link between epigenetic cell memory and human disease. The most common MLL mutations are chromosome translocations that fuse the MLL gene in frame with partner genes creating novel fusion proteins. In this review, we summarize recent work that argues MLL fusion proteins could function through a single molecular pathway, but we also highlight important data that suggests instead that multiple independent mechanisms underlie MLL mediated leukemogenesis

  9. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders

    Abel, Ted; Zukin, R. Suzanne

    2008-01-01

    Epigenetic chromatin remodeling and modifications of DNA represent central mechanisms for regulation of gene expression during brain development and in memory formation. Emerging evidence implicates epigenetic modifications in disorders of synaptic plasticity and cognition. This review focuses on recent findings that HDAC inhibitors can ameliorate deficits in synaptic plasticity, cognition and stress-related behaviors in a wide range of neurologic and psychiatric disorders including Huntingto...

  10. Epigenetic reprogramming of breast cancer cells with oocyte extracts

    Kumari Rajendra

    2011-01-01

    Full Text Available Abstract Background Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis. Results We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts. Conclusions This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.

  11. Environment, epigenetics and neurodegeneration: Focus on nutrition in Alzheimer's disease.

    Nicolia, Vincenzina; Lucarelli, Marco; Fuso, Andrea

    2015-08-01

    Many different environmental factors (nutrients, pollutants, chemicals, physical activity, lifestyle, physical and mental stress) can modulate epigenetic markers in the developing and adult organism. Epigenetics, in turn, can cause and is associated with several neurodegenerative and aging-dependent human diseases. Alzheimer's disease certainly represents one of the most relevant neurodegenerative disorders due to its incidence and its huge socio-economic impact. Therefore, it is easy to understand why recent literature focuses on the epigenetic modifications associated with Alzheimer's disease and other neurodegenerative disorders. One of the most intriguing and, at the same time, worrying evidence is that even "mild" environmental factors (such as behavioral or physical stress) as well as the under-threshold exposure to pollutants and chemicals, can be effective. Finally, even mild nutrients disequilibria can result in long-lasting and functional alterations of many epigenetic markers, although they don't have an immediate acute effect. Therefore, we will probably have to re-define the current risk threshold for many factors, molecules and stresses. Among the many different environmental factors affecting the epigenome, nutrition represents one of the most investigated fields; the reasons are probably that each person interacts with nutrients and that, in turn, nutrients can modulate at molecular level the epigenetic biochemical pathways. The role that nutrition can exert in modulating epigenetic modifications in Alzheimer's disease will be discussed with particular emphasis on the role of B vitamins and DNA methylation. PMID:25456841

  12. Epigenetics, the holy grail in the pathogenesis of systemic sclerosis.

    Altorok, Nezam; Almeshal, Nawaf; Wang, Yongqing; Kahaleh, Bashar

    2015-10-01

    The objective of this review is to present evidence that supports the central role of epigenetic regulation in the pathogenesis of SSc. SSc is a complex autoimmune disease characterized by immune activation, fibrosis of the skin and internal organs and obliterative vasculopathy affecting predominantly the microvessels. Remarkable progress has been made in the past few years emphasizing the importance of epigenetic modifications in the pathogenesis of many disorders, including SSc. Current evidence demonstrates alterations in DNA methylation, histone code modifications and changes in microRNA (miRNA) expression levels in SSc cells. Recent reports have described the differential expression of numerous regulatory miRNAs in SSc, mainly in SSc fibroblasts, a number of which are important in TGF-β pathways and downstream signalling cascades. While studies to date have revealed the significant role of epigenetic modifications in the pathogenesis of SSc, the causal nature of epigenetic alterations in SSc pathogenesis remains elusive. Additional longitudinal and comprehensive epigenetic studies designed to evaluate the effect of environmental epigenetic factors on disease pathogenesis are needed. PMID:24740406

  13. From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research.

    Pagliaroli, Luca; Vető, Borbála; Arányi, Tamás; Barta, Csaba

    2016-01-01

    Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome. This review provides a summary of the recent findings in genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS. PMID:27462201

  14. [How to localize epigenetics in the landscape of biological research?].

    Morange, Michel

    2005-04-01

    Today, epigenetics is a very fashionable field of research. Modification of DNA by methylation, and of chromatin by histone modification or substitution represents a major fraction of the studies; but this special issue shows that epigenetic studies are very diverse, and not limited to the study of chromatin. What is common behind these different uses of the word epigenetics? A brief historical survey shows that epigenetics was invented twice, with different meanings: in the 1940s, by Conrad Waddington, as the study of the relations between the genotype and the phenotype; in the 1960s, as the global mechanisms of gene regulation involved in differentiation and development; what is common is that an approach distinct from genetics was in both cases considered as necessary because genetic models were incapable to address these problems. A good way to appreciate the relations between genetics and epigenetics is to realize that the main aim of organisms is to reproduce, and to consider the way organisms perform this task. Genetics is the precise means organisms have invented to reproduce the structure of their macromolecular components; the genome is also used to control the level and place of this reproduction. All the other means organisms have used to reproduce were more or less the result of tinkering, and constitute the field of epigenetics, with its diversity and richness. PMID:15811300

  15. Genetic and epigenetic control of plant heat responses

    Junzhong eLiu

    2015-04-01

    Full Text Available Plants have evolved sophisticated genetic and epigenetic regulatory systems to respond quickly to unfavorable environmental conditions such as heat, cold, drought, and pathogen infections. In particular, heat greatly affects plant growth and development, immunity and circadian rhythm, and poses a serious threat to the global food supply. According to temperatures exposing, heat can be usually classified as warm ambient temperature (about 22-27℃, high temperature (27-30℃ and extremely high temperature (37-42℃, also known as heat stress for the model plant Arabidopsis thaliana. The genetic mechanisms of plant responses to heat have been well studied, mainly focusing on elevated ambient temperature-mediated morphological acclimation and acceleration of flowering, modulation of plant immunity and circadian clock by high temperatures, and thermotolerance to heat stress. Recently, great progress has been achieved on epigenetic regulation of heat responses, including DNA methylation, histone modifications, histone variants, ATP-dependent chromatin remodeling, histone chaperones, small RNAs, long non-coding RNAs and other undefined epigenetic mechanisms. These epigenetic modifications regulate the expression of heat-responsive genes and function to prevent heat-related damage. This review focuses on recent progresses regarding the genetic and epigenetic control of heat responses in plants, and pays more attention to the role of the major epigenetic mechanisms in plant heat responses. Further research perspectives are also discussed.

  16. DNA Methylation and Chromatin Remodeling: The Blueprint of Cancer Epigenetics

    Dipanjan Bhattacharjee

    2016-01-01

    Full Text Available Epigenetics deals with the interactions between genes and the immediate cellular environment. These interactions go a long way in shaping up each and every person’s individuality. Further, reversibility of epigenetic interactions may offer a dynamic control over the expression of various critical genes. Thus, tweaking the epigenetic machinery may help cause or cure diseases, especially cancer. Therefore, cancer epigenetics, especially at a molecular level, needs to be scrutinised closely, as it could potentially serve as the future pharmaceutical goldmine against neoplastic diseases. However, in view of its rapidly enlarging scope of application, it has become difficult to keep abreast of scientific information coming out of various epigenetic studies directed against cancer. Using this review, we have attempted to shed light on two of the most important mechanisms implicated in cancer, that is, DNA (deoxyribonucleic acid methylation and histone modifications, and their place in cancer pathogenesis. Further, we have attempted to take stock of the new epigenetic drugs that have emerged onto the market as well as those in the pipeline that offer hope in mankind’s fight against cancer.

  17. The Impact of Epigenetics on Mesenchymal Stem Cell Biology.

    Ozkul, Yusuf; Galderisi, Umberto

    2016-11-01

    Changes in epigenetic marks are known to be important regulatory factors in stem cell fate determination and differentiation. In the past years, the investigation of the epigenetic regulation of stem cell biology has largely focused on embryonic stem cells (ESCs). Contrarily, less is known about the epigenetic control of gene expression during differentiation of adult stem cells (AdSCs). Among AdSCs, mesenchymal stem cells (MSCs) are the most investigated stem cell population because of their enormous potential for therapeutic applications in regenerative medicine and tissue engineering. In this review, we analyze the main studies addressing the epigenetic changes in MSC landscape during in vitro cultivation and replicative senescence, as well as follow osteocyte, chondrocyte, and adipocyte differentiation. In these studies, histone acetylation, DNA methylation, and miRNA expression are among the most investigated phenomena. We describe also epigenetic changes that are associated with in vitro MSC trans-differentiation. Although at the at initial stage, the epigenetics of MSCs promise to have profound implications for stem cell basic and applied research. J. Cell. Physiol. 231: 2393-2401, 2016. © 2016 Wiley Periodicals, Inc. PMID:26960183

  18. Epigenetics of complex diseases: from general theory to laboratory experiments.

    Schumacher, A; Petronis, A

    2006-01-01

    Despite significant effort, understanding the causes and mechanisms of complex non-Mendelian diseases remains a key challenge. Although numerous molecular genetic linkage and association studies have been conducted in order to explain the heritable predisposition to complex diseases, the resulting data are quite often inconsistent and even controversial. In a similar way, identification of environmental factors causal to a disease is difficult. In this article, a new interpretation of the paradigm of "genes plus environment" is presented in which the emphasis is shifted to epigenetic misregulation as a major etiopathogenic factor. Epigenetic mechanisms are consistent with various non-Mendelian irregularities of complex diseases, such as the existence of clinically indistinguishable sporadic and familial cases, sexual dimorphism, relatively late age of onset and peaks of susceptibility to some diseases, discordance of monozygotic twins and major fluctuations on the course of disease severity. It is also suggested that a substantial portion of phenotypic variance that traditionally has been attributed to environmental effects may result from stochastic epigenetic events in the cell. It is argued that epigenetic strategies, when applied in parallel with the traditional genetic ones, may significantly advance the discovery of etiopathogenic mechanisms of complex diseases. The second part of this chapter is dedicated to a review of laboratory methods for DNA methylation analysis, which may be useful in the study of complex diseases. In this context, epigenetic microarray technologies are emphasized, as it is evident that such technologies will significantly advance epigenetic analyses in complex diseases. PMID:16909908

  19. The paternal hidden agenda: Epigenetic inheritance through sperm chromatin.

    Puri, Deepika; Dhawan, Jyotsna; Mishra, Rakesh K

    2010-07-01

    Epigenetic modifications play a crucial role in developmental gene regulation. These modifications, being reversible, provide a layer of information over and above the DNA sequence, that has plasticity and leads to the generation of cell type-specific epigenomes during cellular differentiation. In almost all higher eukaryotes, the oocyte provides not only its cytoplasm, mitochondria, maternally deposited RNA and proteins but also an epigenetic component in the form of DNA and histone-modifications. During spermeiogenesis however, most of the histones are replaced by protamines, leading to a loss of the epigenetic component. The sperm is, therefore, viewed as a passive carrier of the paternal genome with a disproportionate, lower epigenetic contribution except for DNA methylation, to the next generation. A recent study overturns this view by demonstrating a locus-specific retention of histones, with specific modifications in the sperm chromatin at the promoters of developmentally important genes. This programmed retention of epigenetic marks with a role in embryonic development is suggested to offset, in some measure, the dominant maternal effect. This new finding helps in addressing the question of epigenetic transmission of environmental and 'lifestyle' experiences across generations and raises the question of 'parental conflict' at the loci that may be differentially marked. PMID:20448473

  20. From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research

    Pagliaroli, Luca; Vető, Borbála; Arányi, Tamás; Barta, Csaba

    2016-01-01

    Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome. This review provides a summary of the recent findings in genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS. PMID:27462201

  1. Epigenetics: new concepts of old phenomena in vascular physiology.

    Krause, Bernardo; Sobrevia, Luis; Casanello, Paola

    2009-10-01

    The hypothesis of 'Developmental Origins of Health and Disease' (DOHaD) relies on the presence of mechanisms sensing and signalling a diversity of stimuli during fetal development. The mechanisms that have been broadly suggested to be involved in these processes are the epigenetic modifications that could 'record' perinatal stimuli. Since the definition of epigenetic and the associated mechanisms are conflictive, in this review epigenetic was defined as 'chromosome-based mechanisms that can change the phenotypic plasticity in a cell or organism'. The most understood epigenetic mechanisms (i.e. DNA methylation, histone post-translational modifications (PTM), ATP-dependent chromatin modifications and non-coding RNAs) and reported evidence for their role in fetal programming were briefly reviewed. The development of the vascular system is strongly influenced by epigenetic mechanisms. For that reason vascular cells are good candidates to be explored regarding epigenetic programming since its proved susceptibility to be imprinted. This has been described in pregnancy diseases such as intra-uterine growth restriction, gestational diabetes and pre-eclampsia, where changes in vascular function are preserved in vitro. PMID:19485890

  2. DNA Methylation and Chromatin Remodeling: The Blueprint of Cancer Epigenetics.

    Bhattacharjee, Dipanjan; Shenoy, Smita; Bairy, Kurady Laxminarayana

    2016-01-01

    Epigenetics deals with the interactions between genes and the immediate cellular environment. These interactions go a long way in shaping up each and every person's individuality. Further, reversibility of epigenetic interactions may offer a dynamic control over the expression of various critical genes. Thus, tweaking the epigenetic machinery may help cause or cure diseases, especially cancer. Therefore, cancer epigenetics, especially at a molecular level, needs to be scrutinised closely, as it could potentially serve as the future pharmaceutical goldmine against neoplastic diseases. However, in view of its rapidly enlarging scope of application, it has become difficult to keep abreast of scientific information coming out of various epigenetic studies directed against cancer. Using this review, we have attempted to shed light on two of the most important mechanisms implicated in cancer, that is, DNA (deoxyribonucleic acid) methylation and histone modifications, and their place in cancer pathogenesis. Further, we have attempted to take stock of the new epigenetic drugs that have emerged onto the market as well as those in the pipeline that offer hope in mankind's fight against cancer. PMID:27119045

  3. An epigenetic hypothesis of aging-related cognitive dysfunction

    Tania L Roth

    2010-03-01

    Full Text Available This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction. Here we focus on this theme, reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging. Finally, several open questions will be discussed that we believe will fuel experimental discovery.

  4. A major reorganization of Asian climate by the early Miocene

    Z. T. Guo

    2008-08-01

    circulations, one from the ocean carrying moisture and another from the inland deserts transporting dust. The formation of the early Miocene paleosols resulted from interactive soil forming and dust deposition processes in these two seasonally alternating monsoonal circulations. The much stronger development of the early Miocene soils compared to those in the Quaternary loess indicates that summer monsoons were either significantly stronger, more persistent through the year, or both.

    These lines of evidence indicate a joint change in circulation and inland aridity by the early Miocene and suggest a dynamic linkage of them. Our recent sensitivity tests with a general circulation model, along with relevant geological data, suggest that the onset of these contrasting wet/dry responses, as well as the change from the "planetary" subtropical aridity pattern to the "inland" aridity pattern, resulted from the combined effects of Tibetan uplift and withdrawal of the Paratethys seaway in central Asia, as suggested by earlier experiments. The spreading of South China Sea also helped to enhance the south-north contrast of humidity. The Miocene loess record provides a vital insight that these tectonic factors had evolved by the early Miocene to a threshold sufficient to cause this major climate reorganization in Asia.

  5. Epigenetic mechanisms and the evolution of virulence

    The interaction between pathogenic organisms and their hosts presents numerous opportunities to observe and test basic biological concepts such as adaptation, fitness, selection, and coevolution. The host-pathogen interaction is an inherently unstable relationship that makes hard evolutionary demand...

  6. Heterochromatin Reorganization during Early Mouse Development Requires a Single-Stranded Noncoding Transcript

    Miguel Casanova

    2013-09-01

    Full Text Available The equalization of pericentric heterochromatin from distinct parental origins following fertilization is essential for genome function and development. The recent implication of noncoding transcripts in this process raises questions regarding the connection between RNA and the nuclear organization of distinct chromatin environments. Our study addresses the interrelationship between replication and transcription of the two parental pericentric heterochromatin (PHC domains and their reorganization during early embryonic development. We demonstrate that the replication of PHC is dispensable for its clustering at the late two-cell stage. In contrast, using parthenogenetic embryos, we show that pericentric transcripts are essential for this reorganization independent of the chromatin marks associated with the PHC domains. Finally, our discovery that only reverse pericentric transcripts are required for both the nuclear reorganization of PHC and development beyond the two-cell stage challenges current views on heterochromatin organization.

  7. Effect of a reorganized after-hours family practice service on frequent attenders

    Vedsted, Peter; Olesen, Frede

    1999-01-01

    BACKGROUND AND OBJECTIVES: A governmental reorganization of the after-hours general practice service in Denmark was launched in January 1992. The biggest change was the introduction of mandatory county-wide telephone triage systems staffed by general practitioners. This study assesses the effect of...... County, Denmark (600,000 inhabitants). The study only included attenders ages 18 and over. FAs were defined as the group that, within each calendar year (12 months), had 4 or more contacts with the after-hours family practice service. RESULTS: FAs made up 9.5% of the attenders and accounted for more than...... 40% of the contacts and the aggregate costs. The effect of the reorganization was a 12% decrease in the number of attenders, a 16% decrease in the number of contacts, and a 29% decrease in the costs. Reorganization had a significantly bigger effect on FA attendance than on non-FA attendance, and more...

  8. Reorganization of Nuclear Pore Complexes and the Lamina in Late-Stage Parvovirus Infection.

    Mäntylä, Elina; Niskanen, Einari A; Ihalainen, Teemu O; Vihinen-Ranta, Maija

    2015-11-01

    Canine parvovirus (CPV) infection induces reorganization of nuclear structures. Our studies indicated that late-stage infection induces accumulation of nuclear pore complexes (NPCs) and lamin B1 concomitantly with a decrease of lamin A/C levels on the apical side of the nucleus. Newly formed CPV capsids are located in close proximity to NPCs on the apical side. These results suggest that parvoviruses cause apical enrichment of NPCs and reorganization of nuclear lamina, presumably to facilitate the late-stage infection. PMID:26311881

  9. Reorganization and plastic changes of the human brain associated with skill learning and expertise

    Yongmin eChang

    2014-02-01

    Full Text Available Novel experience and learning new skills are known as modulators of brain function. Advances in non-invasive brain imaging have provided new insight into structural and functional reorganization associated with skill learning and expertise. Especially, significant imaging evidences come from the domains of sports and music. Data from in vivo imaging studies in sports and music have provided vital information on plausible neural substrates contributing to brain reorganization underlying skill acquisition in humans. This mini review will attempt to take a narrow snapshot of imaging findings demonstrating functional and structural plasticity that mediate skill learning and expertise while identifying converging areas of interest and possible avenues for future research.

  10. Genetics and Epigenetics of Eating Disorders

    Yilmaz, Zeynep; Hardaway, J. Andrew; Bulik, Cynthia M.

    2015-01-01

    Eating disorders (EDs) are serious psychiatric conditions influenced by biological, psychological, and sociocultural factors. A better understanding of the genetics of these complex traits and the development of more sophisticated molecular biology tools have advanced our understanding of the etiology of EDs. The aim of this review is to critically evaluate the literature on the genetic research conducted on three major EDs: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). We will first review the diagnostic criteria, clinical features, prevalence, and prognosis of AN, BN, and BED, followed by a review of family, twin, and adoption studies. We then review the history of genetic studies of EDs covering linkage analysis, candidate gene association studies, genome-wide association studies, and the study of rare variants in EDs. Our review also incorporates a translational perspective by covering animal models of ED-related phenotypes. Finally, we review the nascent field of epigenetics of EDs and a look forward to future directions for ED genetic research. PMID:27013903

  11. Epigenetic regulation of iron homeostasis in Arabidopsis.

    Xing, Jiewen; Wang, Tianya; Ni, Zhongfu

    2015-01-01

    Iron (Fe) is one of the most important microelement required for plant growth and development because of its unique property of catalyzing oxidation/reduction reactions. Iron deficiency impairs fundamental processes which could lead to a decrease in chlorophyll production and pollen fertility, thus influencing crop productivity and quality. However, iron in excess is toxic to the cell and is harmful to the plant. To exactly control the iron content in all tissues, plants have evolved many strategies to regulate iron homeostasis, which refers to 2 successive steps: iron uptake at the root surface, and iron distribution in vivo. In the last decades, a number of transporters and regulatory factors involved in this process have been isolated and identified. To cope with the complicated flexible environmental conditions, plants apply diverse mechanisms to regulate the expression and activity of these components. One of the most important mechanisms is epigenetic regulation of iron homeostasis. This review has been presented to provide an update on the information supporting the involvement of histone modifications in iron homeostasis and possible future course of the field. PMID:26313698

  12. Epigenetic Alterations in a Gastric Leiomyoma

    M. T. Branham

    2014-01-01

    Full Text Available Leiomyomas constitute 2.5% of all resected neoplasms of the stomach. They are usually asymptomatic, but may present mucosal ulceration. Aberrant DNA methylation is a well-defined epigenetic change in human neoplasms; however, gene-acquired methylation may not necessarily be related with a malignant phenotype. In this report we analyzed in a gastric leiomyoma, the methylation status of 84 CpGI in tumor suppressor and DNA repair genes. We analyzed the tumor center (TC and tumor periphery (TP separately. We found aberrant methylation in 2/84 CpGI in the TC portion, that is, MLH1 and MSH3, and 5/84 CpGI in the TP, that is, MLH1, MSH3, APC, MSH6, and MGMT. The gene with the highest methylation percentage in the TC and TP was MLH1. Given that MLH1 methylation has been associated with microsatellite instability, we analyzed the status of the microsatellite Bat-26. We found that neither the TC nor the TP presented instability. The methylation of MLH1, MGMT, and APC has been described in GISTs, but to the best of our knowledge this is the first time that the methylation of these genes has been associated with gastric leiomyoma. Further research should be conducted to identify reliable molecular markers that could differentiate between GISTs and gastric leiomyomas.

  13. Epigenetics in Intestinal Epithelial Cell Renewal.

    Roostaee, Alireza; Benoit, Yannick D; Boudjadi, Salah; Beaulieu, Jean-François

    2016-11-01

    A controlled balance between cell proliferation and differentiation is essential to maintain normal intestinal tissue renewal and physiology. Such regulation is powered by several intracellular pathways that are translated into the establishment of specific transcription programs, which influence intestinal cell fate along the crypt-villus axis. One important check-point in this process occurs in the transit amplifying zone of the intestinal crypts where different signaling pathways and transcription factors cooperate to manage cellular proliferation and differentiation, before secretory or absorptive cell lineage terminal differentiation. However, the importance of epigenetic modifications such as histone methylation and acetylation in the regulation of these processes is still incompletely understood. There have been recent advances in identifying the impact of histone modifications and chromatin remodelers on the proliferation and differentiation of normal intestinal crypt cells. In this review we discuss recent discoveries on the role of the cellular epigenome in intestinal cell fate, development, and tissue renewal. J. Cell. Physiol. 231: 2361-2367, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27061836

  14. Epigenetic regulation of iron homeostasis in Arabidopsis

    Xing, Jiewen; Wang, Tianya; Ni, Zhongfu

    2015-01-01

    Iron (Fe) is one of the most important microelement required for plant growth and development because of its unique property of catalyzing oxidation/reduction reactions. Iron deficiency impairs fundamental processes which could lead to a decrease in chlorophyll production and pollen fertility, thus influencing crop productivity and quality. However, iron in excess is toxic to the cell and is harmful to the plant. To exactly control the iron content in all tissues, plants have evolved many strategies to regulate iron homeostasis, which refers to 2 successive steps: iron uptake at the root surface, and iron distribution in vivo. In the last decades, a number of transporters and regulatory factors involved in this process have been isolated and identified. To cope with the complicated flexible environmental conditions, plants apply diverse mechanisms to regulate the expression and activity of these components. One of the most important mechanisms is epigenetic regulation of iron homeostasis. This review has been presented to provide an update on the information supporting the involvement of histone modifications in iron homeostasis and possible future course of the field. PMID:26313698

  15. Adaptive skills

    Staša Stropnik; Jana Kodrič

    2013-01-01

    Adaptive skills are defined as a collection of conceptual, social and practical skills that are learned by people in order to function in their everyday lives. They include an individual's ability to adapt to and manage her or his surroundings to effectively function and meet social or community expectations. Good adaptive skills promote individual's independence in different environments, whereas poorly developed adaptive skills are connected to individual's dependency and with g...

  16. Urban Resilience in Climate Change Adaptation: A Conceptual Framework

    Donghyun Kim; Up Lim

    2016-01-01

    This study presents a conceptual framework for analyzing urban resilience in the context of climate change. The key conceptual elements of resilience are first identified and then reorganized with a focus on cities and climate change adaptation. This study covers not only ecological and engineering resilience but also resilience as a sociopolitical process from an evolutionary perspective. The study’s conceptual framework centers on resilience as it relates to cities and climate change. Its f...

  17. Climate Change in the High Andes:implications and adaptation strategies for small-scale farmers

    Perez, C.; Nicklin, C.; Dangles, O.; Vanek, S.; Sherwood, S.G.; Halloy, S.; Garrett, K.A.; Forbes, G.A.

    2010-01-01

    Abstract: Global climate change represents a major threat to sustainable farming in the Andes. Farmers have used local ecological knowledge and intricate production systems to cope, adapt and reorganize to meet climate uncertainty and risk, which have always been a fact of life. Those traditional sy

  18. The Epigenetic Reprogramming Roadmap in Generation of iPSCs from Somatic Cells

    Brix, Jacob; Zhou, Yan; Luo, Yonglun

    2015-01-01

    Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, which subsequently affects iPSC reprograming, pluripotency, and differentiation...... capacity. Here we review the epigenetic changes with a focus on histone modification (methylation and acetylation) and DNA modification (methylation) during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules...... influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations....

  19. 75 FR 24570 - Foreign-Trade Zone 177-Mount Vernon/Evansville, IN; Application for Reorganization Under...

    2010-05-05

    ... reorganize the zone under the alternative site framework (ASF) adopted by the Board (74 FR 1170, 1/ 12/09; correction 74 FR 3987, 1/22/09). The ASF is an option for grantees for the establishment or reorganization of... Foreign-Trade Zones Board Foreign-Trade Zone 177--Mount Vernon/Evansville, IN; Application...

  20. Adaptive Lighting

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... distributed differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial...