'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Thu, 30 Oct 2014 21:57:55 PDT Thu, 30 Oct 2014 21:57:55 PDT jirtle@radonc.duke.edu james001@jirtle.com Parent-of-origin growth effects and the evolution of hybrid inviability in dwarf hamsters. Brekke TD, Good JM
Evolution (Nov 2014)

Mammalian hybrids often show abnormal growth, indicating that developmental inviability may play an important role in mammalian speciation. Yet, it is unclear if this recurrent phenotype reflects a common genetic basis. Here, we describe extreme parent-of-origin-dependent growth in hybrids from crosses between two species of dwarf hamsters, Phodopus campbelli and Phodopus sungorus. One cross type resulted in massive placental and embryonic overgrowth, severe developmental defects, and maternal death. Embryos from the reciprocal cross were viable and normal sized, but adult hybrid males were relatively small. These effects are strikingly similar to patterns from several other mammalian hybrids. Using comparative sequence data from dwarf hamsters and several other hybridizing mammals, we argue that extreme hybrid growth can contribute to reproductive isolation during the early stages of species divergence. Next, we tested if abnormal growth in hybrid hamsters was associated with disrupted genomic imprinting. We found no association between imprinting status at several candidate genes and hybrid growth, though two interacting genes involved in embryonic growth did show reduced expression in overgrown hybrids. Collectively, our study indicates that growth-related hybrid inviability may play an important role in mammalian speciation but that the genetic underpinnings of these phenotypes remain unresolved.]]>
Wed, 29 Oct 2014 00:00:00 PDT
Analytical tools and current challenges in the modern era of neuroepigenomics. Maze I, Shen L, Zhang B, Garcia BA, Shao N, Mitchell A, Sun H, Akbarian S, Allis CD, Nestler EJ
Nat Neurosci (Nov 2014)

Over the past decade, rapid advances in epigenomics research have extensively characterized critical roles for chromatin regulatory events during normal periods of eukaryotic cell development and plasticity, as well as part of aberrant processes implicated in human disease. Application of such approaches to studies of the CNS, however, is more recent. Here we provide a comprehensive overview of available tools for analyzing neuroepigenomics data, as well as a discussion of pending challenges specific to the field of neuroscience. Integration of numerous unbiased genome-wide and proteomic approaches will be necessary to fully understand the neuroepigenome and the extraordinarily complex nature of the human brain. This will be critical to the development of future diagnostic and therapeutic strategies aimed at alleviating the vast array of heterogeneous and genetically distinct disorders of the CNS.]]>
Tue, 28 Oct 2014 00:00:00 PDT
DLK1/PREF1 regulates nutrient metabolism and protects from steatosis. Charalambous M, Da Rocha ST, Radford EJ, Medina-Gomez G, Curran S, Pinnock SB, Ferrón SR, Vidal-Puig A, Ferguson-Smith AC
Proc Natl Acad Sci U S A (Oct 2014)

Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and obesity, as well as progressive liver dysfunction. Recent animal studies have underscored the importance of hepatic growth hormone (GH) signaling in the development of NAFLD. The imprinted Delta-like homolog 1 (Dlk1)/preadipocyte factor 1 (Pref1) gene encodes a complex protein producing both circulating and membrane-tethered isoforms whose expression dosage is functionally important because even modest elevation during embryogenesis causes lethality. DLK1 is up-regulated during embryogenesis, during suckling, and in the mother during pregnancy. We investigated the normal role for elevated DLK1 dosage by overexpressing Dlk1 from endogenous control elements. This increased DLK1 dosage caused improved glucose tolerance with no primary defect in adipose tissue expansion even under extreme metabolic stress. Rather, Dlk1 overexpression caused reduced fat stores, pituitary insulin-like growth factor 1 (IGF1) resistance, and a defect in feedback regulation of GH. Increased circulatory GH culminated in a switch in whole body fuel metabolism and a reduction in hepatic steatosis. We propose that the function of DLK1 is to shift the metabolic mode of the organism toward peripheral lipid oxidation and away from lipid storage, thus mediating important physiological adaptations associated with early life and with implications for metabolic disease resistance.]]>
Tue, 28 Oct 2014 00:00:00 PDT
Genomics and epigenomics in novel schizophrenia drug discovery: translating animal models to clinical research and back. Bosia M, Pigoni A, Cavallaro R
Expert Opin Drug Discov (Oct 2014)

Introduction: Schizophrenia is a major psychiatric disorder that afflicts about 1% of the world's population, falling into the top 10 medical disorders causing disability. Existing therapeutic strategies have had limited success; they have poor effects on core cognitive impairment and long-term disability. They are also burdened by relevant side effects. Although new antipsychotic medications have been launched in the past decades, there has been a general lack of significant innovation over the past 60 years. This lack of significant progress in the pharmacotherapy of schizophrenia is a reflection of the complexity and heterogeneity of its etiopathogenetic mechanisms. Areas covered: In this article, the authors briefly review genetic models of schizophrenia, focusing on examples of how new therapeutic strategies have been developed from them. They report on the evidence of epigenetic alterations in schizophrenia and their relevance to pharmacological studies. Further, they describe the implications of epigenetic mechanisms in the etiopathogenesis of the disease and the effects of current antipsychotic drugs on epigenetic processes. Finally, they provide their perspective of using epigenetic drugs for treating schizophrenia. Expert opinion: Current genetic and epigenetic studies are finally shedding light on the biomolecular mechanisms linked to the core pathogenetic alterations in schizophrenia, rather than just their symptoms. These advancements in the understanding of the physiopathology of schizophrenia provide exciting new perspectives for treatments. Indeed, the possibility of looking directly at the biomolecular level allows us to bypass the age-old issues of animal studies pertaining to their questionable validity as behavioral models.]]>
Mon, 27 Oct 2014 00:00:00 PDT
Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line. de Araújo ES, Vasques LR, Stabellini R, Krepischi AC, Pereira LV
Braz J Med Biol Res (Oct 2014)

DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2'-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.]]>
Wed, 22 Oct 2014 00:00:00 PDT
Overview of the "Epigenetic End Points in Toxicologic Pathology and Relevance to Human Health" Session of the 2014 Society of Toxicologic Pathology Annual Symposium. Hoenerhoff MJ, Hartke J
Toxicol Pathol (Oct 2014)

The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies.]]>
Tue, 21 Oct 2014 00:00:00 PDT
Epigenomics and the Microbiota. Alenghat T
Toxicol Pathol (Oct 2014)

The mammalian gastrointestinal tract is home to trillions of commensal microorganisms that collectively make up the intestinal microbiota. These microbes are important environmental factors that regulate homeostasis, and alterations in the composition of the microbiota have been associated with several diseases, including inflammatory bowel disease, diabetes, and cancer. New research is beginning to uncover epigenomic pathways that may regulate this relationship with the microbiota. Epigenomic modifications alter the structure of the chromatin and therefore regulate the transcriptional program of a cell. These modifications are maintained by the dynamic activity of various modifying and demodifying enzymes, the activities of which can be influenced by metabolites and other environmental cues. Histone deacetylases (HDACs) are a class of epigenomic-modifying enzymes that are regulated by both endogenous and exogenous factors, and recent studies have suggested that host HDAC expression is important for regulating communication between the intestinal microbiota and mammalian host cells.]]>
Tue, 21 Oct 2014 00:00:00 PDT
Mating ecology explains patterns of genome elimination. Gardner A, Ross L
Ecol Lett (Oct 2014)

Genome elimination - whereby an individual discards chromosomes inherited from one parent, and transmits only those inherited from the other parent - is found across thousands of animal species. It is more common in association with inbreeding, under male heterogamety, in males, and in the form of paternal genome elimination. However, the reasons for this broad pattern remain unclear. We develop a mathematical model to determine how degree of inbreeding, sex determination, genomic location, pattern of gene expression and parental origin of the eliminated genome interact to determine the fate of genome-elimination alleles. We find that: inbreeding promotes paternal genome elimination in the heterogametic sex; this may incur population extinction under female heterogamety, owing to eradication of males; and extinction is averted under male heterogamety, owing to countervailing sex-ratio selection. Thus, we explain the observed pattern of genome elimination. Our results highlight the interaction between mating system, sex-ratio selection and intragenomic conflict.]]>
Mon, 20 Oct 2014 00:00:00 PDT
Single-nucleotide polymorphisms and DNA methylation markers associated with central obesity and regulation of body weight. Goni L, Milagro FI, Cuervo M, Martínez JA
Nutr Rev (Oct 2014)

Visceral fat is strongly associated with the development of specific obesity-related metabolic alterations. Genetic and epigenetic mechanisms seem to be involved in the development of obesity and visceral adiposity. The aims of this review are to identify the single-nucleotide polymorphisms related to central obesity and to summarize the main findings on DNA methylation and obesity. A search of the MEDLINE database was conducted to identify genome-wide association studies, meta-analyses of genome-wide association studies, and gene-diet interaction studies related to central obesity, and, in addition, studies that analyzed DNA methylation in relation to body weight regulation. A total of 8 genome-wide association studies and 9 meta-analyses of genome-wide association studies reported numerous single-nucleotide polymorphisms to be associated with central obesity. Ten studies analyzed gene-diet interactions and central obesity, while 2 epigenome-wide association studies analyzed DNA methylation patterns and obesity. Nine studies investigated the relationship between DNA methylation and weight loss, excess body weight, or adiposity outcomes. Given the development of new sequencing and omics technologies, significantly more knowledge on genomics and epigenomics of obesity and body fat distribution will emerge in the near future.]]>
Fri, 17 Oct 2014 00:00:00 PDT
Highly sensitive targeted methylome sequencing by post-bisulfite adaptor tagging. Miura F, Ito T
DNA Res (Oct 2014)

The current gold standard method for methylome analysis is whole-genome bisulfite sequencing (WGBS), but its cost is substantial, especially for the purpose of multi-sample comparison of large methylomes. Shotgun bisulfite sequencing of target-enriched DNA, or targeted methylome sequencing (TMS), can be a flexible, cost-effective alternative to WGBS. However, the current TMS protocol requires a considerable amount of input DNA and hence is hardly applicable to samples of limited quantity. Here we report a method to overcome this limitation by using post-bisulfite adaptor tagging (PBAT), in which adaptor tagging is conducted after bisulfite treatment to circumvent bisulfite-induced loss of intact sequencing templates, thereby enabling TMS of a 100-fold smaller amount of input DNA with far fewer cycles of polymerase chain reaction than in the current protocol. We thus expect that the PBAT-mediated TMS will serve as an invaluable method in epigenomics.]]>
Fri, 17 Oct 2014 00:00:00 PDT
Epigenomics of macrophages. Gosselin D, Glass CK
Immunol Rev (Nov 2014)

Macrophages play essential roles in tissue homeostasis, pathogen elimination, and tissue repair. A defining characteristic of these cells is their ability to efficiently adapt to a variety of abruptly changing and complex environments. This ability is intrinsically linked to a capacity to quickly alter their transcriptome, and this is tightly associated with the epigenomic organization of these cells and, in particular, their enhancer repertoire. Indeed, enhancers are genomic sites that serve as platforms for the integration of signaling pathways with the mechanisms that regulate mRNA transcription. Notably, transcription is pervasive at active enhancers and enhancer RNAs (eRNAs) are tightly coupled to regulated transcription of protein-coding genes. Furthermore, given that each cell type possesses a defining enhancer repertoire, studies on enhancers provide a powerful method to study how specialization of functions among the diverse macrophage subtypes may arise. Here, we review recent studies providing insights into the distinct mechanisms that contribute to the establishment of enhancers and their role in the regulation of transcription in macrophages.]]>
Thu, 16 Oct 2014 00:00:00 PDT
Altered gene expression in human placentas after IVF/ICSI. Nelissen EC, Dumoulin JC, Busato F, Ponger L, Eijssen LM, Evers JL, Tost J, van Montfoort AP
Hum Reprod (Oct 2014)

Is gene expression in placental tissue of IVF/ICSI patients altered when compared with a spontaneously conceived group, and are these alterations due to loss of imprinting (LOI) in the case of imprinted genes?]]>
Wed, 15 Oct 2014 00:00:00 PDT
Cooperativity, specificity, and evolutionary stability of polycomb targeting in Drosophila. Schuettengruber B, Oded Elkayam N, Sexton T, Entrevan M, Stern S, Thomas A, Yaffe E, Parrinello H, Tanay A, Cavalli G
Cell Rep (Oct 2014)

Metazoan genomes are partitioned into modular chromosomal domains containing active or repressive chromatin. In flies, Polycomb group (PcG) response elements (PREs) recruit PHO and other DNA-binding factors and act as nucleation sites for the formation of Polycomb repressive domains. The sequence specificity of PREs is not well understood. Here, we use comparative epigenomics and transgenic assays to show that Drosophila domain organization and PRE specification are evolutionarily conserved despite significant cis-element divergence within Polycomb domains, whereas cis-element evolution is strongly correlated with transcription factor binding divergence outside of Polycomb domains. Cooperative interactions of PcG complexes and their recruiting factor PHO stabilize PHO recruitment to low-specificity sequences. Consistently, PHO recruitment to sites within Polycomb domains is stabilized by PRC1. These data suggest that cooperative rather than hierarchical interactions among low-affinity sequences, DNA-binding factors, and the Polycomb machinery are giving rise to specific and strongly conserved 3D structures in Drosophila.]]>
Sat, 11 Oct 2014 00:00:00 PDT
Phytoestrogens and prevention of breast cancer: The contentious debate. Bilal I, Chowdhury A, Davidson J, Whitehead S
World J Clin Oncol (Oct 2014)

Phytoestrogens have multiple actions within target cells, including the epigenome, which could be beneficial to the development and progression of breast cancer. In this brief review the action of phytoestrogens on oestrogen receptors, cell signalling pathways, regulation of the cell cycle, apoptosis, steroid synthesis and epigenetic events in relation to breast cancer are discussed. Phytoestrogens can bind weakly to oestrogen receptors (ERs) and some have a preferential affinity for ERβ which can inhibit the transcriptional growth-promoting activity of ERα. However only saturating doses of phytoestrogens, stimulating both ERα and β, exert growth inhibitory effects. Such effects on growth may be through phytoestrogens inhibiting cell signalling pathways. Phytoestrogens have also been shown to inhibit cyclin D1 expression but increase the expression of cyclin-dependent kinase inhibitors (p21 and p27) and the tumour suppressor gene p53. Again these effects are only observed at high (> 10) µmol/L doses of phytoestrogens. Finally the effects of phytoestrogens on breast cancer may be mediated by their ability to inhibit local oestrogen synthesis and induce epigenetic changes. There are, though, difficulties in reconciling epidemiological and experimental data due to the fact experimental doses, both in vivo and in vitro, far exceed the circulating concentrations of "free" unbound phytoestrogens measured in women on a high phytoestrogen diet or those taking phytoestrogen supplements.]]>
Fri, 10 Oct 2014 00:00:00 PDT
Twists and turns: a scientific journey. Tilghman SM
Annu Rev Cell Dev Biol (Oct 2014)

In this perspective I look back on the twists and turns that influenced the direction of my scientific career over the past 40 years. From my early ambition to be a chemist to my training in Philadelphia and Bethesda as a molecular biologist, I benefited enormously from generous and valuable mentoring. In my independent career in Philadelphia and Princeton, I was motivated by a keen interest in the changes in gene expression that direct the development of the mammalian embryo and inspired by the creativity and energy of my students, fellows, and research staff. After twelve years as President of Princeton University, I have happily returned to the faculty of the Department of Molecular Biology.]]>
Tue, 07 Oct 2014 00:00:00 PDT
Haploid mouse embryonic stem cells: rapid genetic screening and germline transmission. Wutz A
Annu Rev Cell Dev Biol (Oct 2014)

Most animal genomes are diploid, and mammalian development depends on specific adaptations that have evolved secondary to diploidy. Genomic imprinting and dosage compensation restrict haploid development to early embryos. Recently, haploid mammalian development has been reinvestigated since the establishment of haploid embryonic stem cells (ESCs) from mouse embryos. Haploid cells possess one copy of each gene, facilitating the generation of loss-of-function mutations in a single step. Recessive mutations can then be assessed in forward genetic screens. Applications of haploid mammalian cell systems in screens have been illustrated in several recent publications. Haploid ESCs are characterized by a wide developmental potential and can contribute to chimeric embryos and mice. Different strategies for introducing genetic modifications from haploid ESCs into the mouse germline have been further developed. Haploid ESCs therefore introduce new possibilities in mammalian genetics and could offer an unprecedented tool for genome exploration in the future.]]>
Tue, 07 Oct 2014 00:00:00 PDT
Long non-coding RNAs in glioma: Functional roles and clinical perspectives. Zhang XQ, Leung GK
Neurochem Int (Nov 2014)

Long non-coding RNAs (lncRNAs) are a new class of non-coding gene regulators. But unlike their smaller counterparts, microRNAs, relatively less is known about the roles and functions of lncRNAs. Current evidence suggests that lncRNAs may play important roles in a wide range of biological processes in human cancers, including glioma. By acting as oncogenes or tumor suppressors, lncRNAs may contribute to glioma initiation, progression and other malignant phenotypes. Their expression profiles may also have important clinical implications in glioma subclassification and patients' prognostication. Here, we review current evidence related to the functional roles of lncRNAs in glioma. We will discuss the aberrant lncRNA expression signatures associated with glioma initiation and progression, as well as the potential mechanisms underlying lncRNA dysregulation. We also discuss the functional roles of lncRNAs in glioma biological behavior. Finally, the potentials and prospects of employing lncRNAs as novel biomarkers and therapeutic targets for glioma clinical practice will also be addressed.]]>
Fri, 26 Sep 2014 00:00:00 PDT
Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects. Byars SG, Stearns SC, Boomsma JJ
Proc Biol Sci (Nov 2014)

Opposite phenotypic and behavioural traits associated with copy number variation and disruptions to imprinted genes with parent-of-origin effects have led to the hypothesis that autism and schizophrenia share molecular risk factors and pathogenic mechanisms, but a direct phenotypic comparison of how their risks covary has not been attempted. Here, we use health registry data collected on Denmark's roughly 5 million residents between 1978 and 2009 to detect opposing risks of autism and schizophrenia depending on normal variation (mean ± 1 s.d.) in adjusted birth size, which we use as a proxy for diametric gene-dosage variation in utero. Above-average-sized babies (weight, 3691-4090 g; length, 52.8-54.3 cm) had significantly higher risk for autism spectrum (AS) and significantly lower risk for schizophrenia spectrum (SS) disorders. By contrast, below-average-sized babies (2891-3290 g; 49.7-51.2 cm) had significantly lower risk for AS and significantly higher risk for SS disorders. This is the first study directly comparing autism and schizophrenia risks in the same population, and provides the first large-scale empirical support for the hypothesis that diametric gene-dosage effects contribute to these disorders. Only the kinship theory of genomic imprinting predicts the opposing risk patterns that we discovered, suggesting that molecular research on mental disease risk would benefit from considering evolutionary theory.]]>
Thu, 18 Sep 2014 00:00:00 PDT
Exploring breast carcinogenesis through integrative genomics and epigenomics analyses. Minning C, Mokhtar NM, Abdullah N, Muhammad R, Emran NA, Ali SA, Harun R, Jamal R
Int J Oncol (Nov 2014)

There have been many DNA methylation studies on breast cancer which showed various methylation patterns involving tumour suppressor genes and oncogenes but only a few of those studies link the methylation data with gene expression. More data are required especially from the Asian region and to analyse how the epigenome data correlate with the transcriptome. DNA methylation profiling was carried out on 76 fresh frozen primary breast tumour tissues and 25 adjacent non-cancerous breast tissues using the Illumina Infinium(®) HumanMethylation27 BeadChip. Validation of methylation results was performed on 7 genes using either MS-MLPA or MS-qPCR. Gene expression profiling was done on 15 breast tumours and 5 adjacent non-cancerous breast tissues using the Affymetrix GeneChip(®) Human Gene 1.0 ST array. The overlapping genes between DNA methylation and gene expression datasets were further mapped to the KEGG database to identify the molecular pathways that linked these genes together. Supervised hierarchical cluster analysis revealed 1,389 hypermethylated CpG sites and 22 hypomethylated CpG sites in cancer compared to the normal samples. Gene expression microarray analysis using a fold-change of at least 1.5 and a false discovery rate (FDR) at p>0.05 identified 404 upregulated and 463 downregulated genes in cancer samples. Integration of both datasets identified 51 genes with hypermethylation with low expression (negative association) and 13 genes with hypermethylation with high expression (positive association). Most of the overlapping genes belong to the focal adhesion and extracellular matrix-receptor interaction that play important roles in breast carcinogenesis. The present study displayed the value of using multiple datasets in the same set of tissues and how the integrative analysis can create a list of well-focused genes as well as to show the correlation between epigenetic changes and gene expression. These gene signatures can help us understand the epigenetic regulation of gene expression and could be potential targets for therapeutic intervention in the future.]]>
Mon, 15 Sep 2014 00:00:00 PDT
Differential DNA methylation analysis of breast cancer reveals the impact of immune signaling in radiation therapy. Halvorsen AR, Helland A, Fleischer T, Haug KM, Grenaker Alnaes GI, Nebdal D, SyljuÃ¥sen RG, Touleimat N, Busato F, Tost J, Saetersdal AB, Børresen-Dale AL, Kristensen V, Edvardsen H
Int J Cancer (Nov 2014)

Radiotherapy (RT) is a central treatment modality for breast cancer patients. The purpose of our study was to investigate the DNA methylation changes in tumors following RT, and to identify epigenetic markers predicting treatment outcome. Paired biopsies from patients with inoperable breast cancer were collected both before irradiation (n = 20) and after receiving 10-24 Gray (Gy) (n = 19). DNA methylation analysis was performed by using Illumina Infinium 27K arrays. Fourteen genes were selected for technical validation by pyrosequencing. Eighty-two differentially methylated genes were identified in irradiated (n = 11) versus nonirradiated (n = 19) samples (false discovery rate, FDR = 1.1%). Methylation levels in pathways belonging to the immune system were most altered after RT. Based on methylation levels before irradiation, a panel of five genes (H2AFY, CTSA, LTC4S, IL5RA and RB1) were significantly associated with clinical response (p = 0.041). Furthermore, the degree of methylation changes for 2,516 probes correlated with the given radiation dose. Within the 2,516 probes, an enrichment for pathways involved in cellular immune response, proliferation and apoptosis was identified (FDR < 5%). Here, we observed clear differences in methylation levels induced by radiation, some associated with response to treatment. Our study adds knowledge on the molecular mechanisms behind radiation response.]]>
Fri, 15 Aug 2014 00:00:00 PDT