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Sample records for genome damage sravnenie

  1. Transliterating transmission of genome damage in rats

    International Nuclear Information System (INIS)

    Slovinska, L.; Sanova, S.; Misurova, E.

    2004-01-01

    We studied the influence of gamma radiation (3 Gy) on slowly proliferating liver tissue of male rats and their progeny considering to induction and duration of latent damage. The irradiation caused latent cytogenetic damage in the liver in irradiated males of the F 0 generation manifesting itself during induced proliferation of hepatocytes (after partial hepatectomy) by reduced proliferating activity, a higher frequency of chromosomal aberrations and higher proportion of cells with apoptotic DNA fragments. In the progeny of irradiated males (F 1 and F 2 generation), the latent genome damage manifested itself during liver regeneration after partial hepatectomy by similar, but less pronounced changes compared with irradiated males of the parental generation. This finding indicates the transfer of the part of radiation-induced genome damage from parents to their progeny. Irradiation of F 1 and F 2 progeny of irradiated males (their total radiation load was 3+3 Gy, 3+0+3 Gy respectively) caused less changes as irradiation of progeny of non-irradiated control males (their total radiation load was 0+3 Gy, 0+0+3 Gy respectively). (authors)

  2. Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients.

    Science.gov (United States)

    Schupp, Nicole; Dette, Eva Maria; Schmid, Ursula; Bahner, Udo; Winkler, Michaela; Heidland, August; Stopper, Helga

    2008-09-01

    Hemodialysis patients have an elevated genomic damage in peripheral blood lymphocytes (PBLs) and an increased cancer incidence, possibly due to accumulation of uremic toxins like advanced glycation end products (AGEs). Because the vitamin B1 prodrug benfotiamine reduces AGE levels in experimental diabetes, and dialysis patients often suffer from vitamin B1 deficiency, we conducted two consecutive studies supplementing hemodialysis patients with benfotiamine. In both studies, genomic damage was measured as micronucleus frequency of PBLs before and at three time-points after initiation of benfotiamine supplementation. AGE-associated fluorescence in plasma, and in the second study additionally, the antioxidative capacity of plasma was analyzed. Benfotiamine significantly lowered the genomic damage of PBLs in hemodialysis patients of both studies independent of changes in plasma AGE levels. The second study gave a hint to the mechanism, as the antioxidative capacity of the plasma of the treated patients clearly increased, which might ameliorate the DNA damage.

  3. ATM signaling and genomic stability in response to DNA damage

    International Nuclear Information System (INIS)

    Lavin, Martin F.; Birrell, Geoff; Chen, Philip; Kozlov, Sergei; Scott, Shaun; Gueven, Nuri

    2005-01-01

    DNA double strand breaks represent the most threatening lesion to the integrity of the genome in cells exposed to ionizing radiation and radiomimetic chemicals. Those breaks are recognized, signaled to cell cycle checkpoints and repaired by protein complexes. The product of the gene (ATM) mutated in the human genetic disorder ataxia-telangiectasia (A-T) plays a central role in the recognition and signaling of DNA damage. ATM is one of an ever growing number of proteins which when mutated compromise the stability of the genome and predispose to tumour development. Mechanisms for recognising double strand breaks in DNA, maintaining genome stability and minimizing risk of cancer are discussed

  4. Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae.

    Science.gov (United States)

    Doudican, Nicole A; Song, Binwei; Shadel, Gerald S; Doetsch, Paul W

    2005-06-01

    Mitochondria contain their own genome, the integrity of which is required for normal cellular energy metabolism. Reactive oxygen species (ROS) produced by normal mitochondrial respiration can damage cellular macromolecules, including mitochondrial DNA (mtDNA), and have been implicated in degenerative diseases, cancer, and aging. We developed strategies to elevate mitochondrial oxidative stress by exposure to antimycin and H(2)O(2) or utilizing mutants lacking mitochondrial superoxide dismutase (sod2Delta). Experiments were conducted with strains compromised in mitochondrial base excision repair (ntg1Delta) and oxidative damage resistance (pif1Delta) in order to delineate the relationship between these pathways. We observed enhanced ROS production, resulting in a direct increase in oxidative mtDNA damage and mutagenesis. Repair-deficient mutants exposed to oxidative stress conditions exhibited profound genomic instability. Elimination of Ntg1p and Pif1p resulted in a synergistic corruption of respiratory competency upon exposure to antimycin and H(2)O(2). Mitochondrial genomic integrity was substantially compromised in ntg1Delta pif1Delta sod2Delta strains, since these cells exhibit a total loss of mtDNA. A stable respiration-defective strain, possessing a normal complement of mtDNA damage resistance pathways, exhibited a complete loss of mtDNA upon exposure to antimycin and H(2)O(2). This loss was preventable by Sod2p overexpression. These results provide direct evidence that oxidative mtDNA damage can be a major contributor to mitochondrial genomic instability and demonstrate cooperation of Ntg1p and Pif1p to resist the introduction of lesions into the mitochondrial genome.

  5. Genomic damage in children accidentally exposed to ionizing radiation

    DEFF Research Database (Denmark)

    Fucic, A; Brunborg, G; Lasan, R

    2007-01-01

    During the last decade, our knowledge of the mechanisms by which children respond to exposures to physical and chemical agents present in the environment, has significantly increased. Results of recent projects and programmes focused on children's health underline a specific vulnerability of chil...... and efficient preventive measures, by means of a better knowledge of the early and delayed health effects in children resulting from radiation exposure....... of children to environmental genotoxicants. Environmental research on children predominantly investigates the health effects of air pollution while effects from radiation exposure deserve more attention. The main sources of knowledge on genome damage of children exposed to radiation are studies performed...... after the Chernobyl nuclear plant accident in 1986. The present review presents and discusses data collected from papers analyzing genome damage in children environmentally exposed to ionizing radiation. Overall, the evidence from the studies conducted following the Chernobyl accident, nuclear tests...

  6. Role of oxidative DNA damage in genome instability and cancer

    International Nuclear Information System (INIS)

    Bignami, M.; Kunkel, T.

    2009-01-01

    Inactivation of mismatch repair (MMR) is associated with a dramatic genomic instability that is observed experimentally as a mutator phenotype and micro satellite instability (MSI). It has been implicit that the massive genetic instability in MMR defective cells simply reflects the accumulation of spontaneous DNA polymerase errors during DNA replication. We recently identified oxidation damage, a common threat to DNA integrity to which purines are very susceptible, as an important cofactor in this genetic instability

  7. Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

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    Theo A. Knijnenburg

    2018-04-01

    Full Text Available Summary: DNA damage repair (DDR pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy. : Knijnenburg et al. present The Cancer Genome Atlas (TCGA Pan-Cancer analysis of DNA damage repair (DDR deficiency in cancer. They use integrative genomic and molecular analyses to identify frequent DDR alterations across 33 cancer types, correlate gene- and pathway-level alterations with genome-wide measures of genome instability and impaired function, and demonstrate the prognostic utility of DDR deficiency scores. Keywords: The Cancer Genome Atlas PanCanAtlas project, DNA damage repair, somatic mutations, somatic copy-number alterations, epigenetic silencing, DNA damage footprints, mutational signatures, integrative statistical analysis, protein structure analysis

  8. Telomeres and genomic damage repair. Their implication in human pathology

    International Nuclear Information System (INIS)

    Perez, Maria del R.; Dubner, Diana; Michelin, Severino; Gisone, Pablo; Carosella, Edgardo D.

    2002-01-01

    Telomeres, functional complexed that protect eukaryotic chromosome ends, participate in the regulation of cell proliferation and could play a role in the stabilization of genomic regions in response to genotoxic stress. Their significance in human pathology becomes evident in several diseases sharing genomic instability as a common trait, in which alterations of the telomere metabolism have been demonstrated. Many of them are also associated with hypersensitivity to ionizing radiation and cancer susceptibility. Besides the specific proteins belonging to the telomeric complex, other proteins involved in the DNA repair machinery, such as ATM, BRCA1, BRCA2, PARP/tankyrase system, DNA-PK and RAD50-MRE11-NBS1 complexes, are closely related with the telomere. This suggests that the telomere sequesters DNA repair proteins for its own structure maintenance, with could also be released toward damaged sites in the genomic DNA. This communication describes essential aspects of telomere structure and function and their links with homologous recombination, non-homologous end-joining (NHEJ), V(D)J system and mismatch-repair (MMR). Several pathological conditions exhibiting alterations in some of these mechanisms are also considered. The cell response to ionizing radiation and its relationship with the telomeric metabolism is particularly taken into account as a model for studying genotoxicity. (author)

  9. Dynamic maps of UV damage formation and repair for the human genome.

    Science.gov (United States)

    Hu, Jinchuan; Adebali, Ogun; Adar, Sheera; Sancar, Aziz

    2017-06-27

    Formation and repair of UV-induced DNA damage in human cells are affected by cellular context. To study factors influencing damage formation and repair genome-wide, we developed a highly sensitive single-nucleotide resolution damage mapping method [high-sensitivity damage sequencing (HS-Damage-seq)]. Damage maps of both cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] from UV-irradiated cellular and naked DNA revealed that the effect of transcription factor binding on bulky adducts formation varies, depending on the specific transcription factor, damage type, and strand. We also generated time-resolved UV damage maps of both CPDs and (6-4)PPs by HS-Damage-seq and compared them to the complementary repair maps of the human genome obtained by excision repair sequencing to gain insight into factors that affect UV-induced DNA damage and repair and ultimately UV carcinogenesis. The combination of the two methods revealed that, whereas UV-induced damage is virtually uniform throughout the genome, repair is affected by chromatin states, transcription, and transcription factor binding, in a manner that depends on the type of DNA damage.

  10. Impact of genomic damage and ageing on stem cell function

    Science.gov (United States)

    Behrens, Axel; van Deursen, Jan M.; Rudolph, K. Lenhard; Schumacher, Björn

    2014-01-01

    Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. PMID:24576896

  11. Genome health nutrigenomics and nutrigenetics--diagnosis and nutritional treatment of genome damage on an individual basis.

    Science.gov (United States)

    Fenech, Michael

    2008-04-01

    The term nutrigenomics refers to the effect of diet on gene expression. The term nutrigenetics refers to the impact of inherited traits on the response to a specific dietary pattern, functional food or supplement on a specific health outcome. The specific fields of genome health nutrigenomics and genome health nutrigenetics are emerging as important new research areas because it is becoming increasingly evident that (a) risk for developmental and degenerative disease increases with DNA damage which in turn is dependent on nutritional status and (b) optimal concentration of micronutrients for prevention of genome damage is also dependent on genetic polymorphisms that alter function of genes involved directly or indirectly in uptake and metabolism of micronutrients required for DNA repair and DNA replication. Development of dietary patterns, functional foods and supplements that are designed to improve genome health maintenance in humans with specific genetic backgrounds may provide an important contribution to a new optimum health strategy based on the diagnosis and individualised nutritional treatment of genome instability i.e. Genome Health Clinics.

  12. DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Mankgopo Magdeline Kgatle

    2017-01-01

    Full Text Available Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV, hepatitis B virus (HBV, and Epstein-Barr virus (EBV. Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

  13. Genomic Damage in Endstage Renal Disease—Contribution of Uremic Toxins

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    Helga Stopper

    2010-10-01

    Full Text Available Patients with end-stage renal disease (ESRD, whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-a. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation.

  14. Maintaining Genome Stability in Defiance of Mitotic DNA Damage

    Science.gov (United States)

    Ferrari, Stefano; Gentili, Christian

    2016-01-01

    The implementation of decisions affecting cell viability and proliferation is based on prompt detection of the issue to be addressed, formulation and transmission of a correct set of instructions and fidelity in the execution of orders. While the first and the last are purely mechanical processes relying on the faithful functioning of single proteins or macromolecular complexes (sensors and effectors), information is the real cue, with signal amplitude, duration, and frequency ultimately determining the type of response. The cellular response to DNA damage is no exception to the rule. In this review article we focus on DNA damage responses in G2 and Mitosis. First, we set the stage describing mitosis and the machineries in charge of assembling the apparatus responsible for chromosome alignment and segregation as well as the inputs that control its function (checkpoints). Next, we examine the type of issues that a cell approaching mitosis might face, presenting the impact of post-translational modifications (PTMs) on the correct and timely functioning of pathways correcting errors or damage before chromosome segregation. We conclude this essay with a perspective on the current status of mitotic signaling pathway inhibitors and their potential use in cancer therapy. PMID:27493659

  15. Links between persistent DNA damage, genome instability, and aging

    Energy Technology Data Exchange (ETDEWEB)

    Dynan, William S. [Emory Univ., Atlanta, GA (United States). Dept. of Radiation Oncology

    2016-11-14

    The goal of this study was to examine long-term effects of low-dose radiation exposure. One of the hypotheses was that radiation exposure would accelerate the normal aging process. The study was jointly funded by NASA and examined both low-LET radiation (γ-rays) and high-LET radiation (1000 MeV/nucleon 56Fe ions) at doses of 0.1 Gy and up. The work used the Japanese medaka fish (Oryzias latipes), as a vertebrate model organism that can be maintained in large numbers at low cost for lifetime studies. Like other small laboratory fish, Japanese medaka share many anatomical and histological characteristics with other vertebrates, and a variety of genetic and genomic resources are available. Some work also used the zebrafish (Danio rerio), another widely used laboratory model organism.

  16. Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

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    Scott Cukras

    Full Text Available Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

  17. Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

    Science.gov (United States)

    Cukras, Scott; Morffy, Nicholas; Ohn, Takbum; Kee, Younghoon

    2014-01-01

    Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

  18. Higher-Density Culture in Human Embryonic Stem Cells Results in DNA Damage and Genome Instability

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    Kurt Jacobs

    2016-03-01

    Full Text Available Human embryonic stem cells (hESC show great promise for clinical and research applications, but their well-known proneness to genomic instability hampers the development to their full potential. Here, we demonstrate that medium acidification linked to culture density is the main cause of DNA damage and genomic alterations in hESC grown on feeder layers, and this even in the short time span of a single passage. In line with this, we show that increasing the frequency of the medium refreshments minimizes the levels of DNA damage and genetic instability. Also, we show that cells cultured on laminin-521 do not present this increase in DNA damage when grown at high density, although the (long-term impact on their genomic stability remains to be elucidated. Our results explain the high levels of genome instability observed over the years by many laboratories worldwide, and show that the development of optimal culture conditions is key to solving this problem.

  19. Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis

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    Ifigeneia V. Mavragani

    2017-07-01

    Full Text Available Cellular effects of ionizing radiation (IR are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs, single strand breaks (SSBs and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1 repair resistant, increasing genomic instability (GI and malignant transformation and (2 can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity. Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair.

  20. Genome-Wide Requirements for Resistance to Functionally Distinct DNA-Damaging Agents.

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    2005-08-01

    Full Text Available The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of ~4,700 barcoded homozygous deletion strains of Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNA-damage-response pathways as well as genes whose role in the DNA-damage response had not been previously established. High-throughput individual growth analysis was used to independently confirm microarray results. Each compound produced a unique genome-wide profile. Analysis of these data allowed us to determine the relative importance of DNA-repair modules for resistance to each of the 12 profiled compounds. Clustering the data for 12 distinct compounds uncovered both known and novel functional interactions that comprise the DNA-damage response and allowed us to define the genetic determinants required for repair of interstrand cross-links. Further genetic analysis allowed determination of epistasis for one of these functional groups.

  1. New elements of molecular orchestra at radiation-induced damaged genomic sites

    International Nuclear Information System (INIS)

    Wani, Altaf A.; Battu, Aruna; Ray, Alo

    2012-01-01

    DNA damage promptly activates cell cycle checkpoints enabling cells to repair their genome. ATR and ATM kinases are central to the checkpoint activation in response to DNA damage and replication stress. Activated ATR and ATM phosphorylate several downstream proteins involved in DNA repair and cell cycle arrest. However, the nature of the signal, which initially activates these kinases in response to UV damage and how they interact with nucleotide excision repair (NER) pathway, is unclear. Our research has shown that DDB2 and XPC, two early damage recognition factors, promoted ATR and ATM recruitment and phosphorylation. ATR and ATM localized to the damage site and physically interact with XPC. ATR and ATM recruitment and their phosphorylation is negatively affected in cells defective in DDB2 and XPC functions while conversely ATR- and ATM-deficiency fail to influence the damage recruitment of DDB2 and XPC proteins. Consequently, the phosphorylation of ATR and ATM substrates, Chk1, Chk2, H2AX, and BRCA1 is significantly reduced or abrogated in mutant cells, indicating that defective DDB2 and XPC function impaired the checkpoint signal transduction cascade in response to UV damage. DDB2 and XPC also regulated the BRCA1 and Rad51 recruitment to the damage site, implicating their role in homologous recombination-mediated DNA repair pathway. Supporting data reveal that the depletion of ATR and ATM influenced the NER efficiency. Moreover, upon completion of NER, ordered restoration of chromatin structure and key epigenetic marks are necessary for resumption of the cell's normal function. We have demonstrated such a restoration role of H3K56 acetylation (H3K56Ac) mark in response to UV irradiation, In human cells a fast initial deacetylation of H3K56 is followed by full renewal of an acetylated state at ∼ 24-48 hr post-irradiation. Histone chaperone, anti-silencing function-1A (ASF1A), is crucial for post-repair H3K56Ac restoration, which in turn, is needed for the

  2. DNA damage response and spindle assembly checkpoint function throughout the cell cycle to ensure genomic integrity.

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    Katherine S Lawrence

    2015-04-01

    Full Text Available Errors in replication or segregation lead to DNA damage, mutations, and aneuploidies. Consequently, cells monitor these events and delay progression through the cell cycle so repair precedes division. The DNA damage response (DDR, which monitors DNA integrity, and the spindle assembly checkpoint (SAC, which responds to defects in spindle attachment/tension during metaphase of mitosis and meiosis, are critical for preventing genome instability. Here we show that the DDR and SAC function together throughout the cell cycle to ensure genome integrity in C. elegans germ cells. Metaphase defects result in enrichment of SAC and DDR components to chromatin, and both SAC and DDR are required for metaphase delays. During persistent metaphase arrest following establishment of bi-oriented chromosomes, stability of the metaphase plate is compromised in the absence of DDR kinases ATR or CHK1 or SAC components, MAD1/MAD2, suggesting SAC functions in metaphase beyond its interactions with APC activator CDC20. In response to DNA damage, MAD2 and the histone variant CENPA become enriched at the nuclear periphery in a DDR-dependent manner. Further, depletion of either MAD1 or CENPA results in loss of peripherally associated damaged DNA. In contrast to a SAC-insensitive CDC20 mutant, germ cells deficient for SAC or CENPA cannot efficiently repair DNA damage, suggesting that SAC mediates DNA repair through CENPA interactions with the nuclear periphery. We also show that replication perturbations result in relocalization of MAD1/MAD2 in human cells, suggesting that the role of SAC in DNA repair is conserved.

  3. Archaeal Genome Guardians Give Insights into Eukaryotic DNA Replication and Damage Response Proteins

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    David S. Shin

    2014-01-01

    Full Text Available As the third domain of life, archaea, like the eukarya and bacteria, must have robust DNA replication and repair complexes to ensure genome fidelity. Archaea moreover display a breadth of unique habitats and characteristics, and structural biologists increasingly appreciate these features. As archaea include extremophiles that can withstand diverse environmental stresses, they provide fundamental systems for understanding enzymes and pathways critical to genome integrity and stress responses. Such archaeal extremophiles provide critical data on the periodic table for life as well as on the biochemical, geochemical, and physical limitations to adaptive strategies allowing organisms to thrive under environmental stress relevant to determining the boundaries for life as we know it. Specifically, archaeal enzyme structures have informed the architecture and mechanisms of key DNA repair proteins and complexes. With added abilities to temperature-trap flexible complexes and reveal core domains of transient and dynamic complexes, these structures provide insights into mechanisms of maintaining genome integrity despite extreme environmental stress. The DNA damage response protein structures noted in this review therefore inform the basis for genome integrity in the face of environmental stress, with implications for all domains of life as well as for biomanufacturing, astrobiology, and medicine.

  4. DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds.

    Science.gov (United States)

    Waterworth, Wanda M; Footitt, Steven; Bray, Clifford M; Finch-Savage, William E; West, Christopher E

    2016-08-23

    Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.

  5. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

    Science.gov (United States)

    Harley, Margaret E; Murina, Olga; Leitch, Andrea; Higgs, Martin R; Bicknell, Louise S; Yigit, Gökhan; Blackford, Andrew N; Zlatanou, Anastasia; Mackenzie, Karen J; Reddy, Kaalak; Halachev, Mihail; McGlasson, Sarah; Reijns, Martin A M; Fluteau, Adeline; Martin, Carol-Anne; Sabbioneda, Simone; Elcioglu, Nursel H; Altmüller, Janine; Thiele, Holger; Greenhalgh, Lynn; Chessa, Luciana; Maghnie, Mohamad; Salim, Mahmoud; Bober, Michael B; Nürnberg, Peter; Jackson, Stephen P; Hurles, Matthew E; Wollnik, Bernd; Stewart, Grant S; Jackson, Andrew P

    2016-01-01

    DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.

  6. A multistep damage recognition mechanism for global genomic nucleotide excision repair.

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    Sugasawa, K; Okamoto, T; Shimizu, Y; Masutani, C; Iwai, S; Hanaoka, F

    2001-03-01

    A mammalian nucleotide excision repair (NER) factor, the XPC-HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed analysis of its binding specificity using various DNA substrates, each containing a single defined lesion. A highly sensitive gel mobility shift assay revealed that XPC-HR23B specifically binds a small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in the bubble. This is evidence that damage recognition for NER is accomplished through at least two steps; XPC-HR23B first binds to a site that has a DNA helix distortion, and then the presence of injured bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs) were hardly recognized by XPC-HR23B, suggesting that additional factors may be required for CPD recognition. Although the presence of mismatched bases opposite a CPD potentiated XPC-HR23B binding, probably due to enhancement of the helix distortion, cell-free excision of such compound lesions was much more efficient than expected from the observed affinity for XPC-HR23B. This also suggests that additional factors and steps are required for the recognition of some types of lesions. A multistep mechanism of this sort may provide a molecular basis for ensuring the high level of damage discrimination that is required for global genomic NER.

  7. Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs

    Directory of Open Access Journals (Sweden)

    D. Markovic

    2013-12-01

    Full Text Available Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5-nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

  8. ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage.

    Science.gov (United States)

    Perkhofer, Lukas; Schmitt, Anna; Romero Carrasco, Maria Carolina; Ihle, Michaela; Hampp, Stephanie; Ruess, Dietrich Alexander; Hessmann, Elisabeth; Russell, Ronan; Lechel, André; Azoitei, Ninel; Lin, Qiong; Liebau, Stefan; Hohwieler, Meike; Bohnenberger, Hanibal; Lesina, Marina; Algül, Hana; Gieldon, Laura; Schröck, Evelin; Gaedcke, Jochen; Wagner, Martin; Wiesmüller, Lisa; Sipos, Bence; Seufferlein, Thomas; Reinhardt, Hans Christian; Frappart, Pierre-Olivier; Kleger, Alexander

    2017-10-15

    Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements, and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC. Cancer Res; 77(20); 5576-90. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Wyrobek, Andrew J.

    2009-01-18

    Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.

  10. Genome-wide maps of alkylation damage, repair, and mutagenesis in yeast reveal mechanisms of mutational heterogeneity.

    Science.gov (United States)

    Mao, Peng; Brown, Alexander J; Malc, Ewa P; Mieczkowski, Piotr A; Smerdon, Michael J; Roberts, Steven A; Wyrick, John J

    2017-10-01

    DNA base damage is an important contributor to genome instability, but how the formation and repair of these lesions is affected by the genomic landscape and contributes to mutagenesis is unknown. Here, we describe genome-wide maps of DNA base damage, repair, and mutagenesis at single nucleotide resolution in yeast treated with the alkylating agent methyl methanesulfonate (MMS). Analysis of these maps revealed that base excision repair (BER) of alkylation damage is significantly modulated by chromatin, with faster repair in nucleosome-depleted regions, and slower repair and higher mutation density within strongly positioned nucleosomes. Both the translational and rotational settings of lesions within nucleosomes significantly influence BER efficiency; moreover, this effect is asymmetric relative to the nucleosome dyad axis and is regulated by histone modifications. Our data also indicate that MMS-induced mutations at adenine nucleotides are significantly enriched on the nontranscribed strand (NTS) of yeast genes, particularly in BER-deficient strains, due to higher damage formation on the NTS and transcription-coupled repair of the transcribed strand (TS). These findings reveal the influence of chromatin on repair and mutagenesis of base lesions on a genome-wide scale and suggest a novel mechanism for transcription-associated mutation asymmetry, which is frequently observed in human cancers. © 2017 Mao et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Genomics and radical mediated DNA damage: major differences between ionizing radiation and DNA-cleaving enediynes

    International Nuclear Information System (INIS)

    Cosgrove, J.P.; Begley, T.J.; Samson, L.D.; Dedon, P.C.

    2003-01-01

    While the evidence is strong for radical-mediated oxidative processes in the pathophysiology of cancer and aging, the mechanisms by which cells respond to oxidative stress have eluded definition. To this end, we have undertaken genomic studies comparing the response of S. cerevisiae to DNA-specific oxidizing agents, the enediynes calicheamicin (CAL), esperamicin (ESP), and neocarzinostatin (NCS), and the non-specific gamma-radiation (RAD). While RAD results in relatively indiscriminate oxidation of cellular molecules, the enediynes are highly specific to DNA and produce damage by a common mechanism involving radical-mediated oxidation of deoxyribose. Transcriptional profiling in response to these agents (80% survival; 15 min exposure; Affymetrix) revealed unexpected differences between RAD and the enediynes and among the three enediynes. Only 2 genes responded in common to all agents, while 9 genes were regulated in common for the 3 enediynes (no DNA repair genes altered in common). The limited common gene expression changes for the 3 enediynes may result from differences in deoxyribose oxidation chemistry, DNA and chromatin targets or the proportions of single- and double-strand DNA lesions. RAD produced a more robust response than the enediynes, altering expression of 195 and 52 genes by more than 2- and 5-fold, respectively, compared to 16-44 and *2 genes, respectively, for the enediynes. This suggests that the transcriptional response varies in intensity according to the number of cellular features affected by the toxin. Genes showing the strongest up-regulation with RAD: ribonucleotide reductase, multidrug resistance, DS break repair/RAD51, GSH transferase; strongly reduced gene expression: TEL1 (damage signaling), NAT2 (acetyltransferase). Genomic phenotyping studies, using a subset of the Research Genetics deletion library, revealed that loss of apn1, the major AP endonuclease, caused resistance to NCS, possibly due to reduced formation of protein-DNA cross

  12. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

    Energy Technology Data Exchange (ETDEWEB)

    Kiran, Shashi; Oddi, Vineesha [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Laboratory of Cancer Cell Biology, Department of Research, Institute of Liver and Biliary Sciences, Delhi 110070 (India)

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

  13. SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements.

    Directory of Open Access Journals (Sweden)

    Jason Liang

    2018-03-01

    Full Text Available Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO. Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs.

  14. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). Copyright © 2013 by the Research Society on Alcoholism.

  15. FANCG knockout CHO cells display sensitivity to diverse DNA damaging agents and possible genomic instability

    International Nuclear Information System (INIS)

    Hinz, J.M.; Tebbs, R.S.; Yamada, N.A.; Salazar, E.P.; Kopf, V.L.; Thompson, L.H.

    2003-01-01

    Full text: The function of the proteins encoded by the genes responsible for the disease Fanconi anemia (FA) have not been elucidated. Several of these proteins (FancA, C, E, F, and G) form a complex in the nucleus, and cells deficient in any one of these proteins are sensitive to crosslinking agents, suggesting a possible role for these proteins in some aspect of DNA repair, chromosomal maintenance, or replication. We constructed a FancG knockout mutant (FGKO40) in CHO AA8 cells, as well as FancG-corrected FGKO40 cells (KO40BP6, which is a pool of six BAC-clone transformants). FGKO40 cells are sensitive to a wide variety of DNA damaging agents. Sensitivity to the cross-linking agents MMC (3x) and chloroethyl-nitrosourea (3x) does not exceed that of methyl methanesulfonate (MMS) (4x), methyl-nitrosourea (4x), or ethyl-nitrosourea (3x), or the purine analog 6-thioguanine (5x). Other agents show mild sensitivity in FGKO40 cells: ionizing radiation (1.2x), UV-C (1.5x), hydroxyurea (1.2x), camptothecin (1.2x), and excess thymidine (normal). The length of S phase was carefully measured by monitoring the progression of highly synchronous G1 cells obtained by centrifugal elutriation. FGKO40 cells traversed S phase normally but had a slightly longer G2 phase than parental cells. Treatment of synchronized G1 cells with MMS did not increase S phase in parental or mutant cells, but again G2 was slightly longer for FGKO40. Mutation rates were measured at the hrpt and aprt loci, where gene inactivation confers resistance to 6-thioguanine or 8-azaadenine, respectively. FGKO40 had a slightly reduced mutation rate for hprt mutants, suggesting reduced recovery of large deletions at this locus. Moreover, the rate of methotrexate resistance was elevated 2.5-fold in mutant cells compared to controls. Resistance to this drug is generally associated with amplification of the dhfr locus, suggesting FancG plays a role in this aspect of genome stability. We suggest that the defect in FGKO

  16. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    OpenAIRE

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2012-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial fo...

  17. Choline and/or folic acid deficiency is associated with genomic damage and cell death in human lymphocytes in vitro.

    Science.gov (United States)

    Lu, Lin; Ni, Juan; Zhou, Tao; Xu, Weijiang; Fenech, Michael; Wang, Xu

    2012-04-01

    Choline and folate are interrelated methyl donors. Previous studies showed that folate prevents genomic damage in human lymphocytes in vitro; however, the association between choline and human genomic stability is uncertain. To explore the genotoxicity, cytotoxicity, and cytostatic effects and possible interactions of choline and/or folate deficiency on the human genome, lymphocytes from 6 volunteers were cultured in 18 combinations of choline (CC) and folic acid (FA) media for 9 days. The genotoxicity was evaluated by micronuclei, nucleoplasmic bridges, and nuclear buds in the binucleated cell; the cytotoxicity indices included apoptosis and necrosis, and the cytostatic effects were indicated by nuclear division index (NDI). Across all choline concentrations, the frequencies of all biomarkers except NDI were diminished when FA concentration was more than or equal to 120 nmol/L. The frequencies of micronuclei, buds, and necrosis were significantly higher at lower levels of CC (0-6 μmol/L) compared with higher concentrations of CC (12-21.5 μmol/L) while maintaining the same FA concentration. We concluded that both choline and folate significantly impact genomic stability and cell death, although effects of folate were 2.5- to 6.2-fold greater, depending on the biomarker and dose. A combination of 12 μmol/L CC and 120 nmol/L FA appears to be optimal for genomic integrity in vitro.

  18. Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes

    Directory of Open Access Journals (Sweden)

    Jolene Michelle Helena

    2018-04-01

    Full Text Available Deoxyribonucleic acid (DNA is the self-replicating hereditary material that provides a blueprint which, in collaboration with environmental influences, produces a structural and functional phenotype. As DNA coordinates and directs differentiation, growth, survival, and reproduction, it is responsible for life and the continuation of our species. Genome integrity requires the maintenance of DNA stability for the correct preservation of genetic information. This is facilitated by accurate DNA replication and precise DNA repair. DNA damage may arise from a wide range of both endogenous and exogenous sources but may be repaired through highly specific mechanisms. The most common mechanisms include mismatch, base excision, nucleotide excision, and double-strand DNA (dsDNA break repair. Concurrent with regulation of the cell cycle, these mechanisms are precisely executed to ensure full restoration of damaged DNA. Failure or inaccuracy in DNA repair contributes to genome instability and loss of genetic information which may lead to mutations resulting in disease or loss of life. A detailed understanding of the mechanisms of DNA damage and its repair provides insight into disease pathogeneses and may facilitate diagnosis and the development of targeted therapies.

  19. Evaluation of genome damage and transcription profile of DNA damage/repair response genes in peripheral blood mononuclear cells exposed to low dose radiation

    International Nuclear Information System (INIS)

    Soren, D.C.; Saini, Divyalakshmi; Das, Birajalaxmi

    2016-01-01

    Humans are exposed to various physical and chemical mutagens in their life time. Physical mutagens, like ionizing radiation (IR), may induce adverse effect at high acute dose exposures in human cells. However, there are inconsistent results on the effect of low dose radiation exposure in human cells. There are a variety of DNA damage endpoints to evaluate the effect of low dose radiation in human cells. DNA damage response (DDR) may lead to changes in expression profile of many genes. In the present study, an attempt has been made to evaluate genome damage at low dose IR exposure in human blood lymphocytes. Cytochalasin blocked micronuclei (CBMN) assay has been used to determine the frequency of micronuclei in binucleated cells in PBMCs exposed to IR. Transcription profile of ATM, P53, GADD45A, CDKN1A, TRF1 and TRF2 genes was studied using real time quantitative PCR. Venous blood samples collected from 10 random healthy donors were irradiated with different doses of γ-radiation ( 137 Cs) along with sham irradiated control. Whole blood culture was set up using microculture technique. Blood samples were stimulated with phytohemagglutinin, and CBMN assay was performed. An average of 2,500 binucleated cells was scored for each dose point. For gene expression analysis, total RNA was isolated, cDNA was prepared, and gene expression analysis for ATM, P53, CDKN1A, GADD45A, TRF1 and TRF2 was done using real time PCR. Our results revealed no significant increase in the frequency of MN up to 100 mGy as compared to control. However, no significant alteration in gene expression profile was observed. In conclusion, no significant dose response was observed at the frequency of MN as well as the expression profile of DDR/repair genes, suggesting low dose radiation did not induce significant DNA damage at these acute dose exposures. (author)

  20. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    Science.gov (United States)

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2013-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

  1. Multifunctional Role of ATM/Tel1 Kinase in Genome Stability: From the DNA Damage Response to Telomere Maintenance

    Science.gov (United States)

    2014-01-01

    The mammalian protein kinase ataxia telangiectasia mutated (ATM) is a key regulator of the DNA double-strand-break response and belongs to the evolutionary conserved phosphatidylinositol-3-kinase-related protein kinases. ATM deficiency causes ataxia telangiectasia (AT), a genetic disorder that is characterized by premature aging, cerebellar neuropathy, immunodeficiency, and predisposition to cancer. AT cells show defects in the DNA damage-response pathway, cell-cycle control, and telomere maintenance and length regulation. Likewise, in Saccharomyces cerevisiae, haploid strains defective in the TEL1 gene, the ATM ortholog, show chromosomal aberrations and short telomeres. In this review, we outline the complex role of ATM/Tel1 in maintaining genomic stability through its control of numerous aspects of cellular survival. In particular, we describe how ATM/Tel1 participates in the signal transduction pathways elicited by DNA damage and in telomere homeostasis and its importance as a barrier to cancer development. PMID:25247188

  2. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    N.B.R. Colombo

    2015-01-01

    Full Text Available The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

  3. Gross genomic damage measured by DNA image cytometry independently predicts gastric cancer patient survival

    NARCIS (Netherlands)

    Belien, J.A.M.; Buffart, T.E.; Gill, A.; Broeckaert, M.A.M.; Quirke, P.; Meijer, G.A.; Grabsch, H.

    2009-01-01

    BACKGROUND: DNA aneuploidy reflects gross genomic changes. It can be measured by flow cytometry (FCM-DNA) or image cytometry (ICM-DNA). In gastric cancer, the prevalence of DNA aneuploidy has been reported to range from 27 to 100%, with conflicting associations with clinicopathological variables.

  4. Collateral DNA damage produced by genome-editing drones: exception or rule?

    Science.gov (United States)

    Canela, Andres; Stanlie, Andre; Nussenzweig, André

    2015-05-21

    In the recent issue of Nature Biotechnology, Frock et al. (2015) developed an elegant technique to capture translocation partners that can be utilized to determine off-target regions of genome-editing endonucleases as well as endogenous mutators at nucleotide resolution. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.

    Directory of Open Access Journals (Sweden)

    Geoffrey R Bennett

    Full Text Available Host base excision repair (BER proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1 and mutY homolog (MYH as well as DNA polymerase beta (Polβ. While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggested Polβ DNA synthesis activity is not necessary while 5'dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level.

  6. Nitrogen gas plasma treatment of bacterial spores induces oxidative stress that damages the genomic DNA.

    Science.gov (United States)

    Sakudo, Akikazu; Toyokawa, Yoichi; Nakamura, Tetsuji; Yagyu, Yoshihito; Imanishi, Yuichiro

    2017-01-01

    Gas plasma, produced by a short high‑voltage pulse generated from a static induction thyristor power supply [1.5 kilo pulse/sec (kpps)], was demonstrated to inactivate Geobacillus stearothermophilus spores (decimal reduction time at 15 min, 2.48 min). Quantitative polymerase chain reaction and enzyme‑linked immunosorbent assays further indicated that nitrogen gas plasma treatment for 15 min decreased the level of intact genomic DNA and increased the level of 8-hydroxy-2'-deoxyguanosine, a major product of DNA oxidation. Three potential inactivation factors were generated during operation of the gas plasma instrument: Heat, longwave ultraviolet-A and oxidative stress (production of hydrogen peroxide, nitrite and nitrate). Treatment of the spores with hydrogen peroxide (3x2‑4%) effectively inactivated the bacteria, whereas heat treatment (100˚C), exposure to UV-A (75‑142 mJ/cm2) and 4.92 mM peroxynitrite (•ONOO‑), which is decomposed into nitrite and nitrate, did not. The results of the present study suggest the gas plasma treatment inactivates bacterial spores primarily by generating hydrogen peroxide, which contributes to the oxidation of the host genomic DNA.

  7. Genomes

    National Research Council Canada - National Science Library

    Brown, T. A. (Terence A.)

    2002-01-01

    ... of genome expression and replication processes, and transcriptomics and proteomics. This text is richly illustrated with clear, easy-to-follow, full color diagrams, which are downloadable from the book's website...

  8. Loss of yeast peroxiredoxin Tsa1p induces genome instability through activation of the DNA damage checkpoint and elevation of dNTP levels.

    Directory of Open Access Journals (Sweden)

    Hei-Man Vincent Tang

    2009-10-01

    Full Text Available Peroxiredoxins are a family of antioxidant enzymes critically involved in cellular defense and signaling. Particularly, yeast peroxiredoxin Tsa1p is thought to play a role in the maintenance of genome integrity, but the underlying mechanism is not understood. In this study, we took a genetic approach to investigate the cause of genome instability in tsa1Delta cells. Strong genetic interactions of TSA1 with DNA damage checkpoint components DUN1, SML1, and CRT1 were found when mutant cells were analyzed for either sensitivity to DNA damage or rate of spontaneous base substitutions. An elevation in intracellular dNTP production was observed in tsa1Delta cells. This was associated with constitutive activation of the DNA damage checkpoint as indicated by phosphorylation of Rad9/Rad53p, reduced steady-state amount of Sml1p, and induction of RNR and HUG1 genes. In addition, defects in the DNA damage checkpoint did not modulate intracellular level of reactive oxygen species, but suppressed the mutator phenotype of tsa1Delta cells. On the contrary, overexpression of RNR1 exacerbated this phenotype by increasing dNTP levels. Taken together, our findings uncover a new role of TSA1 in preventing the overproduction of dNTPs, which is a root cause of genome instability.

  9. LORD-Q: a long-run real-time PCR-based DNA-damage quantification method for nuclear and mitochondrial genome analysis

    Science.gov (United States)

    Lehle, Simon; Hildebrand, Dominic G.; Merz, Britta; Malak, Peter N.; Becker, Michael S.; Schmezer, Peter; Essmann, Frank; Schulze-Osthoff, Klaus; Rothfuss, Oliver

    2014-01-01

    DNA damage is tightly associated with various biological and pathological processes, such as aging and tumorigenesis. Although detection of DNA damage is attracting increasing attention, only a limited number of methods are available to quantify DNA lesions, and these techniques are tedious or only detect global DNA damage. In this study, we present a high-sensitivity long-run real-time PCR technique for DNA-damage quantification (LORD-Q) in both the mitochondrial and nuclear genome. While most conventional methods are of low-sensitivity or restricted to abundant mitochondrial DNA samples, we established a protocol that enables the accurate sequence-specific quantification of DNA damage in >3-kb probes for any mitochondrial or nuclear DNA sequence. In order to validate the sensitivity of this method, we compared LORD-Q with a previously published qPCR-based method and the standard single-cell gel electrophoresis assay, demonstrating a superior performance of LORD-Q. Exemplarily, we monitored induction of DNA damage and repair processes in human induced pluripotent stem cells and isogenic fibroblasts. Our results suggest that LORD-Q provides a sequence-specific and precise method to quantify DNA damage, thereby allowing the high-throughput assessment of DNA repair, genotoxicity screening and various other processes for a wide range of life science applications. PMID:24371283

  10. Common genomic signaling among initial DNA damage and radiation-induced apoptosis in peripheral blood lymphocytes from locally advanced breast cancer patients

    DEFF Research Database (Denmark)

    Henríquez-Hernández, Luis Alberto; Pinar, Beatriz; Carmona-Vigo, Ruth

    2013-01-01

    PURPOSE: To investigate the genomic signaling that defines sensitive lymphocytes to radiation and if such molecular profiles are consistent with clinical toxicity; trying to disclose the radiobiology mechanisms behind these cellular processes. PATIENTS AND METHODS: Twelve consecutive patients...... suffering from locally advanced breast cancer and treated with high-dose hyperfractionated radiotherapy were recruited. Initial DNA damage was measured by pulsed-field gel electrophoresis and radiation-induced apoptosis was measured by flow cytometry. Gene expression was assessed by DNA microarray. RESULTS...

  11. p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response.

    Science.gov (United States)

    Hattori, Hiroyoshi; Janky, Rekin's; Nietfeld, Wilfried; Aerts, Stein; Madan Babu, M; Venkitaraman, Ashok R

    2014-01-01

    The human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been implicated in the DDR, there is as yet no comprehensive description of genome-wide changes in the expression of miRNAs triggered by DNA breakage in human cells. We have used next-generation sequencing (NGS), combined with rigorous integrative computational analyses, to describe genome-wide changes in the expression of miRNAs during the human DDR. The changes affect 150 of 1523 miRNAs known in miRBase v18 from 4-24 h after the induction of DNA breakage, in cell-type dependent patterns. The regulatory regions of the most-highly regulated miRNA species are enriched in conserved binding sites for p53. Indeed, genome-wide changes in miRNA expression during the DDR are markedly altered in TP53-/- cells compared to otherwise isogenic controls. The expression levels of certain damage-induced, p53-regulated miRNAs in cancer samples correlate with patient survival. Our work reveals genome-wide and cell type-specific alterations in miRNA expression during the human DDR, which are regulated by the tumor suppressor protein p53. These findings provide a genomic resource to identify new molecules and mechanisms involved in the DDR, and to examine their role in tumor suppression and the clinical outcome of cancer patients.

  12. PprA contributes to Deinococcus radiodurans resistance to nalidixic acid, genome maintenance after DNA damage and interacts with deinococcal topoisomerases.

    Directory of Open Access Journals (Sweden)

    Swathi Kota

    Full Text Available PprA is known to contribute to Deinococcus radiodurans' remarkable capacity to survive a variety of genotoxic assaults. The molecular bases for PprA's role(s in the maintenance of the damaged D. radiodurans genome are incompletely understood, but PprA is thought to promote D. radiodurans's capacity for DSB repair. PprA is found in a multiprotein DNA processing complex along with an ATP type DNA ligase, and the D. radiodurans toposiomerase IB (DraTopoIB as well as other proteins. Here, we show that PprA is a key contributor to D. radiodurans resistance to nalidixic acid (Nal, an inhibitor of topoisomerase II. Growth of wild type D. radiodurans and a pprA mutant were similar in the absence of exogenous genotoxic insults; however, the pprA mutant exhibited marked growth delay and a higher frequency of anucleate cells following treatment with DNA-damaging agents. We show that PprA interacts with both DraTopoIB and the Gyrase A subunit (DraGyrA in vivo and that purified PprA enhances DraTopoIB catalysed relaxation of supercoiled DNA. Thus, besides promoting DNA repair, our findings suggest that PprA also contributes to preserving the integrity of the D. radiodurans genome following DNA damage by interacting with DNA topoisomerases and by facilitating the actions of DraTopoIB.

  13. E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells.

    Science.gov (United States)

    Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

    2015-01-01

    E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

  14. Spectroscopic approaches to study DNA damage induced in genome exposed to ionizing radiation and its enzymatic repair

    International Nuclear Information System (INIS)

    Yokoya, Akinari; Fujii, Kentaro; Oka, Toshitaka; Watanabe, Ritsuko

    2012-01-01

    Recent progress on spectroscopic study on physicochemical process of DNA damage induction will be reported. It has been predicted by computer track simulation studies that complex DNA damage, so called clustered DNA damage sites, is produced along the tack particularly of high Linear Energy Transfer (LET) ions. The clustered DNA damage, consisting of two or more isolated lesions such as single strand breaks or nucleobase lesions, is thought to compromise DNA repair enzymes. We have revealed that the nucleobase lesions produced by He 2+ ion impact to simple model DNA (plasmid) are hardly processed by base excision repair enzymes (E. coli DNA glycosylases). Using the third generation synchrotron radiation facility (SPring-8), we have studied unpaired electron species or desorbed ions as intermediates of DNA damage using an EPR apparatus or mass spectrometer installed in the soft X-ray beamline in SPring-8. These aspects are compared with the yields of final products of single- and double-strand breaks and base lesions revealed biochemical techniques. Models of complex DNA damage induction will be proposed considering various modification factors of the damage induction, ionization of valence and inner-shell electrons, OH radicals, hydration layer and the impact of secondary electrons. (author)

  15. The JAK-STAT transcriptional regulator, STAT-5, activates the ATM DNA damage pathway to induce HPV 31 genome amplification upon epithelial differentiation.

    Directory of Open Access Journals (Sweden)

    Shiyuan Hong

    Full Text Available High-risk human papillomavirus (HPV must evade innate immune surveillance to establish persistent infections and to amplify viral genomes upon differentiation. Members of the JAK-STAT family are important regulators of the innate immune response and HPV proteins downregulate expression of STAT-1 to allow for stable maintenance of viral episomes. STAT-5 is another member of this pathway that modulates the inflammatory response and plays an important role in controlling cell cycle progression in response to cytokines and growth factors. Our studies show that HPV E7 activates STAT-5 phosphorylation without altering total protein levels. Inhibition of STAT-5 phosphorylation by the drug pimozide abolishes viral genome amplification and late gene expression in differentiating keratinocytes. In contrast, treatment of undifferentiated cells that stably maintain episomes has no effect on viral replication. Knockdown studies show that the STAT-5β isoform is mainly responsible for this activity and that this is mediated through the ATM DNA damage response. A downstream target of STAT-5, the peroxisome proliferator-activated receptor γ (PPARγ contributes to the effects on members of the ATM pathway. Overall, these findings identify an important new regulatory mechanism by which the innate immune regulator, STAT-5, promotes HPV viral replication through activation of the ATM DNA damage response.

  16. New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.

    Science.gov (United States)

    Dutta, Arijit; Yang, Chunying; Sengupta, Shiladitya; Mitra, Sankar; Hegde, Muralidhar L

    2015-05-01

    Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mispairing property, are continuously induced by endogenous reactive oxygen species and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil, produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1's role in replicating template strand repair. The key requirement for this event, which we named as the 'cow-catcher' mechanism of pre-replicative BER, is NEIL1's non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in reannealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box-binding protein 1 as well as high mobility group box 1 protein, whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP-ribose) polymerase 1 and other accessory

  17. Activation of protein kinase A and clustering of cell surface receptors by N-methyl-N'-nitro-N-nitrosoguanidine are independent of genomic DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Wang Zheng; Wang Guliang; Yang Jun; Guo Lei; Yu Yingnian

    2003-07-25

    Alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces cellular stress leading to chromosomal aberrations, mutations and cell death. Previous reports from our laboratory have shown that low concentration of MNNG induces untargeted mutation (UTM), which occurs on intact DNA in mammalian cells through changes in gene expression profile. It also causes the activation of cAMP-protein kinase A (PKA) and up-regulation of POL-{beta}, which is demonstrated to play a role in DNA repair system. In order to find out the possible initial signal involved in UTM, we try to investigate whether the activation of PKA-CREB signal pathway is closely related to DNA damage. Our data shows that the treatment of low concentration MNNG (0.2 {mu}M) activates PKA-CREB pathway in a comparable level both in a nuclear and enucleated cell system. And similar to the cell response caused by UV, the clustering of cell surface receptors of epidermal growth factor (EGF) and tumor necrosis factor {alpha} (TNF{alpha}) was also observed in cells exposed to MNNG. It was further demonstrated that the clustering of the surface receptors is independent of the genomic DNA damage, as this phenomenon was also observed in enucleated cells. These observations indicate that the initiation of signal cascades induced by low concentration of MNNG might be associated with its interaction with cell surface receptors and/or direct activation of related signal proteins but not its DNA damaging property.

  18. Protection of vanillin derivative VND3207 on genome damage and apoptosis of human lymphoblastoid cells induced by γ-ray irradiation

    International Nuclear Information System (INIS)

    Huang Rui; Huang Bo; He Xingpeng; Xu Qinzhi; Wang Yu; Zhou Pingkun

    2009-01-01

    To determine the protective effect of vanillin derivative VND3207 on the genome damage and apoptosis of human lymphoblastoid AHH-1 cells induced by γ-ray irradiation, the techniques of single-cell gel electrophoresis, micronucleus test, Annexin V-FACS assay, and the double-fluorescein staining and fluorescent microscope observation were used. Neutral single-cell gel electrophoresis showed that the initial DNA double-strand breaks caused by 2 Gy 60 Co γ-ray was significantly decreased by VND3207 in the range of 540 μmol/L. This significant phenomenonwas demonstrated by the fact that the comet tail-moment was significantly shortened and the DNA content in the comet tail was reduced when the cells were protected with VND3207, and the radio-protective effect increases along with the increasing of drug concentration. Similarly, the yield of micronucleus was reduced by 540 μmol/L of VND3207 in a concentration-dependency in AHH-1 cells irradiated with 0.5 Gy, 1.0 Gy and 2.0 Gy 60 Co γ-rays. 40 μmol/L VND3207 resulted in 40% reduction in the yield of micronucleus induced by 2.0 Gy. The occurrence of apoptosis enhanced along with the time from 8 h to 48 h post 4 Gy irradiation, and 40 μmol/L of VND3207 significantly decreased the induction of apoptosis. This work has further demonstrated a good protection of VND3207 on γ-ray-induced cell genome damage and apoptosis. (authors)

  19. n-TiO{sub 2} and CdCl{sub 2} co-exposure to titanium dioxide nanoparticles and cadmium: Genomic, DNA and chromosomal damage evaluation in the marine fish European sea bass (Dicentrarchus labrax)

    Energy Technology Data Exchange (ETDEWEB)

    Nigro, M.; Bernardeschi, M. [Department of Clinical and Experimental Medicine, Pisa University, Pisa (Italy); Costagliola, D. [Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Caserta (Italy); Della Torre, C. [Department of Physical, Earth and Environmental Sciences, University of Siena, Siena (Italy); Frenzilli, G., E-mail: giada@biomed.unipi.it [Department of Clinical and Experimental Medicine, Pisa University, Pisa (Italy); Guidi, P.; Lucchesi, P. [Department of Clinical and Experimental Medicine, Pisa University, Pisa (Italy); Mottola, F.; Santonastaso, M. [Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Caserta (Italy); Scarcelli, V. [Department of Clinical and Experimental Medicine, Pisa University, Pisa (Italy); Monaci, F.; Corsi, I. [Department of Physical, Earth and Environmental Sciences, University of Siena, Siena (Italy); Stingo, V.; Rocco, L. [Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Caserta (Italy)

    2015-11-15

    Highlights: • European sea bass was exposed to CdCl{sub 2} and n-TiO{sub 2} alone and in combination. • Genotoxicity was evaluated by RAPD-assay, comet assay and cytome assay. • CdCl{sub 2} induced DNA primary damage but not chromosomal damage. • n-TiO{sub 2} induced chromosomal damage but not DNA primary damage. • Co-exposure effects depend on the biomarker used. - Abstract: Due to the large production and growing use of titanium dioxide nanoparticles (n-TiO{sub 2}), their release in the marine environment and their potential interaction with existing toxic contaminants represent a growing concern for biota. Different end-points of genotoxicity were investigated in the European sea bass Dicentrarchus labrax exposed to n-TiO{sub 2} (1 mg L{sup −1}) either alone and combined with CdCl{sub 2} (0.1 mg L{sup −1}) for 7 days. DNA primary damage (comet assay), apoptotic cells (diffusion assay), occurrence of micronuclei and nuclear abnormalities (cytome assay) were assessed in peripheral erythrocytes and genomic stability (random amplified polymorphism DNA-PCR, RAPD assay) in muscle tissue. Results showed that genome template stability was reduced after CdCl{sub 2} and n-TiO{sub 2} exposure. Exposure to n-TiO{sub 2} alone was responsible for chromosomal alteration but ineffective in terms of DNA damage; while the opposite was observed in CdCl{sub 2} exposed specimens. Co-exposure apparently prevents the chromosomal damage and leads to a partial recovery of the genome template stability.

  20. Mitosis, double strand break repair, and telomeres: a view from the end: how telomeres and the DNA damage response cooperate during mitosis to maintain genome stability.

    Science.gov (United States)

    Cesare, Anthony J

    2014-11-01

    Double strand break (DSB) repair is suppressed during mitosis because RNF8 and downstream DNA damage response (DDR) factors, including 53BP1, do not localize to mitotic chromatin. Discovery of the mitotic kinase-dependent mechanism that inhibits DSB repair during cell division was recently reported. It was shown that restoring mitotic DSB repair was detrimental, resulting in repair dependent genome instability and covalent telomere fusions. The telomere DDR that occurs naturally during cellular aging and in cancer is known to be refractory to G2/M checkpoint activation. Such DDR-positive telomeres, and those that occur as part of the telomere-dependent prolonged mitotic arrest checkpoint, normally pass through mitosis without covalent ligation, but result in cell growth arrest in G1 phase. The discovery that suppressing DSB repair during mitosis may function primarily to protect DDR-positive telomeres from fusing during cell division reinforces the unique cooperation between telomeres and the DDR to mediate tumor suppression. © 2014 The Author. Bioessays published by WILEY Periodicals, Inc.

  1. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  2. Selection of assessment methods for evaluating banana weevil Cosmopolites sordidus (Coleoptera: Curculionidae) damage on highland cooking banana (Musa spp., genome group AAA-EA).

    Science.gov (United States)

    Gold, C S; Ragama, P E; Coe, R; Rukazambuga, N D T M

    2005-04-01

    Cosmopolites sordidus (Germar) is an important pest on bananas and plantains. Population build-up is slow and damage becomes increasingly important in successive crop cycles (ratoons). Yield loss results from plant loss, mat disappearance and reduced bunch size. Damage assessment requires destructive sampling and is most often done on corms of recently harvested plants. A wide range of damage assessment methods exist and there are no agreed protocols. It is critical to know what types of damage best reflect C. sordidus pest status through their relationships with yield loss. Multiple damage assessment parameters (i.e. for the corm periphery, cortex and central cylinder) were employed in two yield loss trials and a cultivar-screening trial in Uganda. Damage to the central cylinder had a greater effect on plant size and yield loss than damage to the cortex or corm periphery. In some cases, a combined assessment of damage to the central cylinder and cortex showed a better relationship with yield loss than an assessment of the central cylinder alone. Correlation, logistic and linear regression analyses showed weak to modest correlations between damage to the corm periphery and damage to the central cylinder. Thus, damage to the corm periphery is not a strong predictor of the more important damage to the central cylinder. Therefore, C. sordidus damage assessment should target the central cylinder and cortex.

  3. Baseline frequency of chromosomal aberrations and sister chromatid exchanges in peripheral blood lymphocytes of healthy individuals living in Turin (North-Western Italy): assessment of the effects of age, sex and GSTs gene polymorphisms on the levels of genomic damage.

    Science.gov (United States)

    Santovito, Alfredo; Cervella, Piero; Delpero, Massimiliano

    2016-05-01

    The increased exposure to environmental pollutants has led to the awareness of the necessity for constant monitoring of human populations, especially those living in urban areas. This study evaluated the background levels of genomic damage in a sample of healthy subjects living in the urban area of Turin (Italy). The association between DNA damage with age, sex and GSTs polymorphisms was assessed. One hundred and one individuals were randomly sampled. Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays, as well as genotyping of GSTT1 and GSTM1 genes, were performed. Mean values of SCEs and CAs were 5.137 ± 0.166 and 0.018 ± 0.002, respectively. Results showed age and gender associated with higher frequencies of these two cytogenetic markers. The eldest subjects (51-65 years) showed significantly higher levels of genomic damage than younger individuals. GSTs polymorphisms did not appear to significantly influence the frequencies of either markers. The CAs background frequency observed in this study is one of the highest reported among European populations. Turin is one of the most polluted cities in Europe in terms of air fine PM10 and ozone and the clastogenic potential of these pollutants may explain the high frequencies of chromosomal rearrangements reported here.

  4. Genome-wide identification, sequence characterization, and protein-protein interaction properties of DDB1 (damaged DNA binding protein-1)-binding WD40-repeat family members in Solanum lycopersicum.

    Science.gov (United States)

    Zhu, Yunye; Huang, Shengxiong; Miao, Min; Tang, Xiaofeng; Yue, Junyang; Wang, Wenjie; Liu, Yongsheng

    2015-06-01

    One hundred DDB1 (damaged DNA binding protein-1)-binding WD40-repeat domain (DWD) family genes were identified in the S. lycopersicum genome. The DWD genes encode proteins presumably functioning as the substrate recognition subunits of the cullin4-ring ubiquitin E3 ligase complex. These findings provide candidate genes and a research platform for further gene functionality and molecular breeding study. A subclass of DDB1 (damaged DNA binding protein-1)-binding WD40-repeat domain (DWD) family proteins has been demonstrated to function as the substrate recognition subunits of the cullin4-ring ubiquitin E3 ligase complex. However, little information is available about the cognate subfamily genes in tomato (S. lycopersicum). In this study, based on the recently released tomato genome sequences, 100 tomato genes encoding DWD proteins that potentially interact with DDB1 were identified and characterized, including analyses of the detailed annotations, chromosome locations and compositions of conserved amino acid domains. In addition, a phylogenetic tree, which comprises of three main groups, of the subfamily genes was constructed. The physical interaction between tomato DDB1 and 14 representative DWD proteins was determined by yeast two-hybrid and co-immunoprecipitation assays. The subcellular localization of these 14 representative DWD proteins was determined. Six of them were localized in both nucleus and cytoplasm, seven proteins exclusively in cytoplasm, and one protein either in nucleus and cytoplasm, or exclusively in cytoplasm. Comparative genomic analysis demonstrated that the expansion of these subfamily members in tomato predominantly resulted from two whole-genome triplication events in the evolution history.

  5. Staining Against Phospho-H2AX (gamma-H2AX) as a Marker for DNA Damage and Genomic Instability in Cancer Tissues and Cells

    NARCIS (Netherlands)

    Nagelkerke, A.P.; Span, P.N.

    2016-01-01

    Phospho-H2AX or gamma-H2AX- is a marker of DNA double-stranded breaks and can therefore be used to monitor DNA repair after, for example, irradiation. In addition, positive staining for phospho-H2AX may indicate genomic instability and telomere dysfunction in tumour cells and tissues. Here, we

  6. Gene interactions in the DNA damage-response pathway identified by genome-wide RNA-interference analysis of synthetic lethality

    NARCIS (Netherlands)

    van Haaften, Gijs; Vastenhouw, Nadine L; Nollen, Ellen A A; Plasterk, Ronald H A; Tijsterman, Marcel

    2004-01-01

    Here, we describe a systematic search for synthetic gene interactions in a multicellular organism, the nematode Caenorhabditis elegans. We established a high-throughput method to determine synthetic gene interactions by genome-wide RNA interference and identified genes that are required to protect

  7. Chromatin dynamics in genome stability

    DEFF Research Database (Denmark)

    Nair, Nidhi; Shoaib, Muhammad; Sørensen, Claus Storgaard

    2017-01-01

    Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote...... access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance...... of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage....

  8. Ddx19 links mRNA nuclear export with progression of transcription and replication and suppresses genomic instability upon DNA damage in proliferating cells.

    Science.gov (United States)

    Hodroj, Dana; Serhal, Kamar; Maiorano, Domenico

    2017-09-03

    The DEAD-box Helicase 19 (Ddx19) gene codes for an RNA helicase involved in both mRNA (mRNA) export from the nucleus into the cytoplasm and in mRNA translation. In unperturbed cells, Ddx19 localizes in the cytoplasm and at the cytoplasmic face of the nuclear pore. Here we review recent findings related to an additional Ddx19 function in the nucleus in resolving RNA:DNA hybrids (R-loops) generated during collision between transcription and replication, and upon DNA damage. Activation of a DNA damage response pathway dependent upon the ATR kinase, a major regulator of replication fork progression, stimulates translocation of the Ddx19 protein from the cytoplasm into the nucleus. Only nuclear Ddx19 is competent to resolve R-loops, and down regulation of Ddx19 expression induces DNA double strand breaks only in proliferating cells. Overall these observations put forward Ddx19 as an important novel mediator of the crosstalk between transcription and replication.

  9. Identification of ‘safe harbor’ loci in indica rice genome by harnessing the property of zinc-finger nucleases to induce DNA damage and repair.

    Directory of Open Access Journals (Sweden)

    Christian eCantos

    2014-06-01

    Full Text Available Zinc-finger nucleases (ZFNs have proved to be successful tools for targeted genome manipulation in several organisms. Their main property is the induction of double-strand breaks (DSBs at specific sites, which are further repaired through homologous recombination (HR or non-homologous end joining (NHEJ. However, for the appropriate integration of genes at specific chromosomal locations, proper sites for gene integration need to be identified. These regions, hereby named safe harbor loci, must be localized in non-coding regions and possess high gene expression. In the present study, three different ZFN constructs (pZFN1, pZFN2, pZFN3, harboring β-glucuronidase (GUS as a reporter gene, were used to identify safe harbor loci regions on rice chromosomes. The constructs were delivered into IR64 rice by using an improved Agrobacterium-mediated transformation protocol, based on the use of immature embryos. Gene expression was measured by histochemical GUS activity and the flanking regions were determined through thermal-asymmetric interlaced polymerase chain reaction (TAIL PCR. Following sequencing, 28 regions were identified as putative sites for safe integration, but only one was localized in a non-coding region and it also possessed high GUS expression. These findings have significant applicability to create crops with new and valuable traits, since the site can be subsequently used to stably introduce one or more genes in a targeted manner.

  10. The Intertwined Roles of DNA Damage and Transcription

    OpenAIRE

    Di Palo, Giacomo

    2016-01-01

    DNA damage and transcription are two interconnected events. Transcription can induce damage and scheduled DNA damage can be required for transcription. Here, we analyzed genome-wide distribution of 8oxodG-marked oxidative DNA damage obtained by OxiDIP-Seq, and we found a correlation with transcription of protein coding genes.

  11. Pre-genomic, genomic and post-genomic study of microbial communities involved in bioenergy.

    Science.gov (United States)

    Rittmann, Bruce E; Krajmalnik-Brown, Rosa; Halden, Rolf U

    2008-08-01

    Microorganisms can produce renewable energy in large quantities and without damaging the environment or disrupting food supply. The microbial communities must be robust and self-stabilizing, and their essential syntrophies must be managed. Pre-genomic, genomic and post-genomic tools can provide crucial information about the structure and function of these microbial communities. Applying these tools will help accelerate the rate at which microbial bioenergy processes move from intriguing science to real-world practice.

  12. Telomeros y reparación de daño genómico: Su implicancia en patología humana Telomeres and genomic damage repair: Their implication in human pathology

    Directory of Open Access Journals (Sweden)

    M. del R. Perez

    2002-12-01

    which alterations of the telomere metabolism have been demonstrated. Many of them are also associated with hypersensitivity to ionizing radiation and cancer susceptibility. Besides the specific proteins belonging to the telomeric complex, other proteins involved in the DNA repair machinery, such as ATM, BRCA1, BRCA2, PARP/ tankyrase system, DNA-PK and RAD50-MRE11-NBS1 complexes, are closely related with the telomere. This suggests that the telomere sequesters DNA repair proteins for its own structure maintenance, which could also be released toward damaged sites in the genomic DNA. This communication describes essential aspects of telomere structure and function and their links with homologous recombination, non-homologous end-joining (NHEJ, V(DJ system and mismatch-repair (MMR. Several pathological conditions exhibiting alterations in some of these mechanisms are also considered. The cell response to ionizing radiation and its relationship with the telomeric metabolism is particularly taken into account as a model for studying genotoxicity.

  13. Genomic instability following irradiation

    International Nuclear Information System (INIS)

    Hacker-Klom, U.B.; Goehde, W.

    2001-01-01

    Ionising irradiation may induce genomic instability. The broad spectrum of stress reactions in eukaryontic cells to irradiation complicates the discovery of cellular targets and pathways inducing genomic instability. Irradiation may initiate genomic instability by deletion of genes controlling stability, by induction of genes stimulating instability and/or by activating endogeneous cellular viruses. Alternatively or additionally it is discussed that the initiation of genomic instability may be a consequence of radiation or other agents independently of DNA damage implying non nuclear targets, e.g. signal cascades. As a further mechanism possibly involved our own results may suggest radiation-induced changes in chromatin structure. Once initiated the process of genomic instability probably is perpetuated by endogeneous processes necessary for proliferation. Genomic instability may be a cause or a consequence of the neoplastic phenotype. As a conclusion from the data available up to now a new interpretation of low level radiation effects for radiation protection and in radiotherapy appears useful. The detection of the molecular mechanisms of genomic instability will be important in this context and may contribute to a better understanding of phenomenons occurring at low doses <10 cSv which are not well understood up to now. (orig.)

  14. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  15. Tort Damages

    NARCIS (Netherlands)

    L.T. Visscher (Louis)

    2008-01-01

    textabstractAbstract: In this Chapter, I provide an overview of Law and Economics literature regarding tort damages. Where necessary, attention is also spent to rules of tort liability. Both types of rules provide behavioral incentives to both injurers and victims, with respect to their level of

  16. Comparison Of The Worth Of Critical And Exponential Measurements For Heavy-Water-Moderated Reactors; Valeur Relative des Mesures Critiques et Exponentielles pour l'Etude des Reacteurs Ralentis a l'Eau Lourde; Sravnenie tsennosti kriticheskikh i ehksponentsial'nykh izmerenij dlya reaktorov s tyazhelovodnym zamedlitelem; Valor Relativo de las Mediciones Criticas y Exponenciales para los Reactores Moderados por Agua Pesada

    Energy Technology Data Exchange (ETDEWEB)

    Graves, W. E.; Hennelly, E. J. [Savannah River Laboratory, E.I. Du Pont De Nemours and Co., Aiken, SC (United States)

    1964-02-15

    para determinar el coeficiente termico del laplaciano para un calentamiento uniforme del reticulado. En el SRL hay una instalacion especial, el PSE, que permite establecer dicho coeficiente hasta temperaturas de 215 Degree-Sign C. En cambio, para un calentamiento no uniforme, se prefiere generalmente los conjuntos criticos. 5. Reticulados mixtos En los reactores en funcionamiento raramente se usan los reticulados uniformes simples a los cuales se aplican basicamente los experimentos exponenciales. En el SRL se recurre a los experimentos criticos con cargas mezcladas, tanto para medir los efectos directos en maquetas, como para verificar la correccion de los calculos de difusion en medios heterogeneos y bidimensionales. 6. Estudios de la criticidad en agua ligera de un combustible destinado a reticulados de agua pesada Se ha comprobado que los experimentos exponenciales del laboratorio del SRL son particularmente valiosos para los estudios de criticidad encaminados a encontrar metodos seguros de manipulacion en agua ligera del combustible enriquecido. Estos trabajos no exigen una exactitud muy grande, y cabe senalar que los estudios de tipo general del laplaciano efectuados en conjuntos exponenciales son decididamente preferibles a los estudios especializados con conjuntos criticos. (author) [Russian] Kriticheskie i jeksponencial'nye jeksperimenty dajut, kak pravilo, chastichno perekryvajushhiesja dannye po reaktornym reshetkam. V techenie poslednih desjati let v Laboratorii Savanna-River rabotali parallel'no tjazhelovodnaja kriticheskaja ustanovka PDP i jeksponencial'naja ustanovka SE. Obobshhaetsja opyt s cel'ju dat' rekomendacii v otnoshenii primenenija jetih dvuh ustanovok dlja razlichnyh jeksperimentov. Rassmatrivajutsja shest' vidov jeksperimentov: 1) . Izmerenija laplasiana v odnorodnyh izotopnyh reshetkah Osushhestvleno shirokoe sravnenie rezul'tatov, poluchennyh pri odnorodnyh kriticheskih, jeksponencial'nyh i podstanovochno-kriticheskih izmerenijah, a takzhe

  17. Reconstructing ancient genomes and epigenomes

    DEFF Research Database (Denmark)

    Orlando, Ludovic Antoine Alexandre; Gilbert, M. Thomas P.; Willerslev, Eske

    2015-01-01

    DNA studies have now progressed to whole-genome sequencing for an increasing number of ancient individuals and extinct species, as well as to epigenomic characterization. Such advances have enabled the sequencing of specimens of up to 1 million years old, which, owing to their extensive DNA damage...... and contamination, were previously not amenable to genetic analyses. In this Review, we discuss these varied technical challenges and solutions for sequencing ancient genomes and epigenomes....

  18. Extreme genomes

    OpenAIRE

    DeLong, Edward F

    2000-01-01

    The complete genome sequence of Thermoplasma acidophilum, an acid- and heat-loving archaeon, has recently been reported. Comparative genomic analysis of this 'extremophile' is providing new insights into the metabolic machinery, ecology and evolution of thermophilic archaea.

  19. Grass genomes

    OpenAIRE

    Bennetzen, Jeffrey L.; SanMiguel, Phillip; Chen, Mingsheng; Tikhonov, Alexander; Francki, Michael; Avramova, Zoya

    1998-01-01

    For the most part, studies of grass genome structure have been limited to the generation of whole-genome genetic maps or the fine structure and sequence analysis of single genes or gene clusters. We have investigated large contiguous segments of the genomes of maize, sorghum, and rice, primarily focusing on intergenic spaces. Our data indicate that much (>50%) of the maize genome is composed of interspersed repetitive DNAs, primarily nested retrotransposons that in...

  20. Comparison of Knolls Atomic Power Laboratory Clean Critical and Subcritical Experiments with Calculations; Etude Comparative des Calculs et des Experiences Critiques Non Empoisonnees et Souscritiques, Faits au Knolls Atomic Power Laboratory; Sravnenie chistykh kriticheskikh i podkriticheskikh opytov v nolle s raschetnymi dannymi; Comparacion de los Resultados Experimentales del Knolls Atomic Power Lamra Tory con los Valores Calculados Teoricamente en Conjuntos Criticos Limpios y Subcriticos

    Energy Technology Data Exchange (ETDEWEB)

    Bach, D. R.; Bistline, J. A.; Bunch, S. I.; Cerbone, R. J.; Feiner, F.; Skolnik, W.; Slovacek, R. E.; Weinstein, S. [Knolls Atomic Tower Laboratory, Schenectady, NY (United States)

    1964-02-15

    - dajushhimi harakteristikami. Mehanicheskie kachestva kriticheskoj sborki takovy, chto kriti- cheskie konfiguracii predstavljajut soboj prostye prjamougol'nye parallelepipedy bez ka- nalov dlja avarijnyh i regulirujushhih sterzhnej. Issledovalsja kriticheskij razmer v sistemah v uslovijah utechki bystyh nejtronov (bez otrazhatelja i {sup s} otrazhatelem) i sravnenija so standartnymi dvuh- i trehrazmernymi gruppo- vymi schetno-reshajushhimi programmami. V celom raschetnye postojannye kritichnosti, vychislen- nye na osnovanii samyh poslednih jadernyh dannyh, priblizitel'no na 3% vyshe. Opisyvaemye opyty s plastinkami ohvatyvali shkalu temperatur, nachinaja ot komnatnoj do 293 Degree-Sign S pri davlenii 84,4 kg/sm{sup 2}. V celjah ustranenija oslozhnenija, svjazannogo s dejstviem regulirujushhih sterzhnej, opredelenie temperatury, pri kotoroj aktivnaja zona dostigala kri- tichnosti, provodilos' pri pochti polnom izvlechenii regulirujushhih sterzhnej. Pri nalichii tekushhej informacii otnositel'no poprechnyh sechenij raschetnaja kritichnost' postojanno vyshe priblizitel'no na 2% na vsem diapazone jeksperimentov. Raschety postojannyh raspada, provedennye metodom ustranenija otravlenija po zakonu l /v s ispol'zovaniem standartnoj gruppovoj diffuzii s uchetom uslovij zavisimosti grupp ot .granicy ukazyvajut na sovpadenie v predelah neskol'kih procentov s izmerennymi postojan- nymi raspada v diapazone ot 100 do 45 000 sek{sup -1}. Sravnenie dannyh izmerenij spektra selektora medlennyh nejtronov s raschetnymi spektrami s pomoshh'ju nedavno poluchennyh funkcij vlijanija svjazannogo vodoroda kak dlja vody, tak i dlja polijetilena svidetel'stvujut o horoshem soglasii, za iskljucheniem vodnyh sistem s vysokimi poglotitel'nymi svojstvami. V poslednem sluchae izmerennye spektry, po- vidimomu, dazhe mjagche, chem raschetnye spektry svobodnyh atomov. (author)

  1. Cancer genomics

    DEFF Research Database (Denmark)

    Norrild, Bodil; Guldberg, Per; Ralfkiær, Elisabeth Methner

    2007-01-01

    Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines whe...

  2. Irradiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Howe, L.M

    2000-07-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization.

  3. Irradiation damage

    International Nuclear Information System (INIS)

    Howe, L.M.

    2000-01-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization

  4. Damaged Skylab

    Science.gov (United States)

    1973-01-01

    The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows a crippled Skylab in orbit. The crew found their home in space to be in serious shape; the heat shield gone, one solar wing gone, and the other jammed. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

  5. Structural damage

    International Nuclear Information System (INIS)

    Gray, R.E.; Bruhn, R.W.

    1992-01-01

    Virtually all structures show some signs of distress due to deterioration of the building components, to changed loads, or to changed support conditions. Changed support conditions result from ground movements. In mining regions many cases of structural distress are attributed to mining without considering alternative causes. This is particularly true of coal mining since it occurs under extensive areas. Coal mining is estimated to have already undermined more than eight million acres and may eventually undermine 40 million acres in the United States. Other nonmetal and metal underground mines impact much smaller areas. Although it is sometimes difficult, even with careful study, to identify the actual cause of damage, persons responsible for underground coal mining should at least be aware of possible causes of building stress other than mine subsidence. This paper presents information on distress to structures and briefly reviews a number of causes of ground movements other than subsidence: Mass movements, dissolution, erosion, frost action, shrinking and swelling, yield into excavations and compressibility

  6. Radiation damage prediction system using damage function

    International Nuclear Information System (INIS)

    Tanaka, Yoshihisa; Mori, Seiji

    1979-01-01

    The irradiation damage analysis system using a damage function was investigated. This irradiation damage analysis system consists of the following three processes, the unfolding of a damage function, the calculation of the neutron flux spectrum of the object of damage analysis and the estimation of irradiation effect of the object of damage analysis. The damage function is calculated by applying the SAND-2 code. The ANISN and DOT3, 5 codes are used to calculate neutron flux. The neutron radiation and the allowable time of reactor operation can be estimated based on these calculations of the damage function and neutron flux. The flow diagram of the process of analyzing irradiation damage by a damage function and the flow diagram of SAND-2 code are presented, and the analytical code for estimating damage, which is determined with a damage function and a neutron spectrum, is explained. The application of the irradiation damage analysis system using a damage function was carried out to the core support structure of a fast breeder reactor for the damage estimation and the uncertainty evaluation. The fundamental analytical conditions and the analytical model for this work are presented, then the irradiation data for SUS304, the initial estimated values of a damage function, the error analysis for a damage function and the analytical results are explained concerning the computation of a damage function for 10% total elongation. Concerning the damage estimation of FBR core support structure, the standard and lower limiting values of damage, the permissible neutron flux and the allowable years of reactor operation are presented and were evaluated. (Nakai, Y.)

  7. Single Molecule Scanning of DNA Radiation Oxidative Damage, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposal will develop an assay to map genomic DNA, at the single molecule level and in a nanodevice, for oxidative DNA damage arising from radiation exposure;...

  8. Mechanisms of dealing with DNA damage in terminally differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Fortini, P. [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, E., E-mail: eugenia.dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy)

    2010-03-01

    To protect genomic integrity living cells that are continuously exposed to DNA-damaging insults are equipped with an efficient defence mechanism termed the DNA damage response. Its function is to eliminate DNA damage through DNA repair and to remove damaged cells by apoptosis. The DNA damage response has been investigated mainly in proliferating cells, in which the cell cycle machinery is integrated with the DNA damage signalling. The current knowledge of the mechanisms of DNA repair, DNA damage signalling and cell death of post-mitotic cells that have undergone irreversible cell cycle withdrawal will be reviewed. Evidence will be provided that the protection of the genome integrity in terminally differentiated cells is achieved by different strategies than in proliferating cells.

  9. Mechanisms of dealing with DNA damage in terminally differentiated cells

    International Nuclear Information System (INIS)

    Fortini, P.; Dogliotti, E.

    2010-01-01

    To protect genomic integrity living cells that are continuously exposed to DNA-damaging insults are equipped with an efficient defence mechanism termed the DNA damage response. Its function is to eliminate DNA damage through DNA repair and to remove damaged cells by apoptosis. The DNA damage response has been investigated mainly in proliferating cells, in which the cell cycle machinery is integrated with the DNA damage signalling. The current knowledge of the mechanisms of DNA repair, DNA damage signalling and cell death of post-mitotic cells that have undergone irreversible cell cycle withdrawal will be reviewed. Evidence will be provided that the protection of the genome integrity in terminally differentiated cells is achieved by different strategies than in proliferating cells.

  10. Genome Imprinting

    Indian Academy of Sciences (India)

    the cell nucleus (mitochondrial and chloroplast genomes), and. (3) traits governed ... tively good embryonic development but very poor development of membranes and ... Human homologies for the type of situation described above are naturally ..... imprint; (b) New modifications of the paternal genome in germ cells of each ...

  11. Baculovirus Genomics

    NARCIS (Netherlands)

    Oers, van M.M.; Vlak, J.M.

    2007-01-01

    Baculovirus genomes are covalently closed circles of double stranded-DNA varying in size between 80 and 180 kilobase-pair. The genomes of more than fourty-one baculoviruses have been sequenced to date. The majority of these (37) are pathogenic to lepidopteran hosts; three infect sawflies

  12. Genomic Testing

    Science.gov (United States)

    ... this database. Top of Page Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) In 2004, the Centers for Disease Control and Prevention launched the EGAPP initiative to establish and test a ... and other applications of genomic technology that are in transition from ...

  13. Ancient genomes

    OpenAIRE

    Hoelzel, A Rus

    2005-01-01

    Ever since its invention, the polymerase chain reaction has been the method of choice for work with ancient DNA. In an application of modern genomic methods to material from the Pleistocene, a recent study has instead undertaken to clone and sequence a portion of the ancient genome of the cave bear.

  14. Delayed chromosomal instability induced by DNA damage

    International Nuclear Information System (INIS)

    Morgan, W.F.; Marder, B.A.; Day, J.P.

    1994-01-01

    Cellular exposure to DNA damaging agents rapidly results in a dose dependent increase in chromosomal breakage and gross structural chromosomal rearrangements. Over recent years, evidence has been accumulating indicating genomic instability can manifest multiple generations after cellular exposure to physical and chemical DNA damaging agents. Genomic instability manifests in the progeny of surviving cells, and has been implicated in mutation, gene application, cellular transformation, and cell killing. To investigate chromosome instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells surviving X-irradiation many generations after exposure. At higher radiation doses, chromosomal instability was observed in a relatively high frequency of surviving clones and, in general, those clones showed delayed chromosome instability also showed reduced survival as measured by colony forming ability

  15. Herbarium genomics

    DEFF Research Database (Denmark)

    Bakker, Freek T.; Lei, Di; Yu, Jiaying

    2016-01-01

    Herbarium genomics is proving promising as next-generation sequencing approaches are well suited to deal with the usually fragmented nature of archival DNA. We show that routine assembly of partial plastome sequences from herbarium specimens is feasible, from total DNA extracts and with specimens...... up to 146 years old. We use genome skimming and an automated assembly pipeline, Iterative Organelle Genome Assembly, that assembles paired-end reads into a series of candidate assemblies, the best one of which is selected based on likelihood estimation. We used 93 specimens from 12 different...... correlation between plastome coverage and nuclear genome size (C value) in our samples, but the range of C values included is limited. Finally, we conclude that routine plastome sequencing from herbarium specimens is feasible and cost-effective (compared with Sanger sequencing or plastome...

  16. Damage analysis: damage function development and application

    International Nuclear Information System (INIS)

    Simons, R.L.; Odette, G.R.

    1975-01-01

    The derivation and application of damage functions, including recent developments for the U.S. LMFBR and CTR programs, is reviewed. A primary application of damage functions is in predicting component life expectancies; i.e., the fluence required in a service spectrum to attain a specified design property change. An important part of the analysis is the estimation of the uncertainty in such fluence limit predictions. The status of standardizing the procedures for the derivation and application of damage functions is discussed. Improvements in several areas of damage function development are needed before standardization can be completed. These include increasing the quantity and quality of the data used in the analysis, determining the limitations of the analysis due to the presence of multiple damage mechanisms, and finally, testing of damage function predictions against data obtained from material surveillance programs in operating thermal and fast reactors. 23 references. (auth)

  17. Cephalopod genomics

    DEFF Research Database (Denmark)

    Albertin, Caroline B.; Bonnaud, Laure; Brown, C. Titus

    2012-01-01

    The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, ``Paths to Cephalopod Genomics-Strategies, Choices, Organization,'' held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austria......, Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers...... active in sequencing, assembling and annotating genomes, agreed on a set of cephalopod species of particular importance for initial sequencing and developed strategies and an organization (CephSeq Consortium) to promote this sequencing. The conclusions and recommendations of this meeting are described...

  18. Genome Sequencing

    DEFF Research Database (Denmark)

    Sato, Shusei; Andersen, Stig Uggerhøj

    2014-01-01

    The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based on transcr......The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based...

  19. DNA Damage and Pulmonary Hypertension

    Science.gov (United States)

    Ranchoux, Benoît; Meloche, Jolyane; Paulin, Roxane; Boucherat, Olivier; Provencher, Steeve; Bonnet, Sébastien

    2016-01-01

    Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and is diagnosed by right heart catheterization. Among the different groups of PH, pulmonary arterial hypertension (PAH) is characterized by a progressive obstruction of distal pulmonary arteries, related to endothelial cell dysfunction and vascular cell proliferation, which leads to an increased pulmonary vascular resistance, right ventricular hypertrophy, and right heart failure. Although the primary trigger of PAH remains unknown, oxidative stress and inflammation have been shown to play a key role in the development and progression of vascular remodeling. These factors are known to increase DNA damage that might favor the emergence of the proliferative and apoptosis-resistant phenotype observed in PAH vascular cells. High levels of DNA damage were reported to occur in PAH lungs and remodeled arteries as well as in animal models of PH. Moreover, recent studies have demonstrated that impaired DNA-response mechanisms may lead to an increased mutagen sensitivity in PAH patients. Finally, PAH was linked with decreased breast cancer 1 protein (BRCA1) and DNA topoisomerase 2-binding protein 1 (TopBP1) expression, both involved in maintaining genome integrity. This review aims to provide an overview of recent evidence of DNA damage and DNA repair deficiency and their implication in PAH pathogenesis. PMID:27338373

  20. Comparative Genomics

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 11; Issue 8. Comparative Genomics - A Powerful New Tool in Biology. Anand K Bachhawat. General Article Volume 11 Issue 8 August 2006 pp 22-40. Fulltext. Click here to view fulltext PDF. Permanent link:

  1. Parvovirus infection-induced DNA damage response

    Science.gov (United States)

    Luo, Yong; Qiu, Jianming

    2014-01-01

    Parvoviruses are a group of small DNA viruses with ssDNA genomes flanked by two inverted terminal structures. Due to a limited genetic resource they require host cellular factors and sometimes a helper virus for efficient viral replication. Recent studies have shown that parvoviruses interact with the DNA damage machinery, which has a significant impact on the life cycle of the virus as well as the fate of infected cells. In addition, due to special DNA structures of the viral genomes, parvoviruses are useful tools for the study of the molecular mechanisms underlying viral infection-induced DNA damage response (DDR). This review aims to summarize recent advances in parvovirus-induced DDR, with a focus on the diverse DDR pathways triggered by different parvoviruses and the consequences of DDR on the viral life cycle as well as the fate of infected cells. PMID:25429305

  2. Radiation damage of nonmetallic solids

    International Nuclear Information System (INIS)

    Goland, A.N.

    1975-01-01

    A review of data and information on radiation damage in nonmetallic solids is presented. Discussions are included on defects in nonmetals, radiation damage processes in nonmetals, electronic damage processes, physical damage processes, atomic displacement, photochemical damage processes, and ion implantation

  3. The DNA damage response in mammalian oocytes

    Directory of Open Access Journals (Sweden)

    John eCarroll

    2013-06-01

    Full Text Available DNA damage is one of the most common insults that challenge all cells. To cope, an elaborate molecular and cellular response has evolved to sense, respond to and correct the damage. This allows the maintenance of DNA fidelity essential for normal cell viability and the prevention of genomic instability that can lead to tumour formation. In the context of oocytes, the impact of DNA damage is not one of tumour formation but of the maintenance of fertility. Mammalian oocytes are particularly vulnerable to DNA damage because physiologically they may lie dormant in the ovary for many years (>40 in humans until they receive the stimulus to grow and acquire the competence to become fertilized. The implication of this is that in some organisms, such as humans, oocytes face the danger of cumulative genetic damage for decades. Thus, the ability to detect and repair DNA damage is essential to maintain the supply of oocytes necessary for reproduction. Therefore, failure to confront DNA damage in oocytes could cause serious anomalies in the embryo that may be propagated in the form of mutations to the next generation allowing the appearance of hereditary disease. Despite the potential impact of DNA damage on reproductive capacity and genetic fidelity of embryos, the mechanisms available to the oocyte for monitoring and repairing such insults have remained largely unexplored until recently. Here, we review the different aspects of the response to DNA damage in mammalian oocytes. Specifically, we address the oocyte DNA damage response from embryonic life to adulthood and throughout oocyte development.

  4. Genomic integrity and the ageing brain.

    Science.gov (United States)

    Chow, Hei-man; Herrup, Karl

    2015-11-01

    DNA damage is correlated with and may drive the ageing process. Neurons in the brain are postmitotic and are excluded from many forms of DNA repair; therefore, neurons are vulnerable to various neurodegenerative diseases. The challenges facing the field are to understand how and when neuronal DNA damage accumulates, how this loss of genomic integrity might serve as a 'time keeper' of nerve cell ageing and why this process manifests itself as different diseases in different individuals.

  5. Femoral nerve damage (image)

    Science.gov (United States)

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  6. Personal genomics services: whose genomes?

    Science.gov (United States)

    Gurwitz, David; Bregman-Eschet, Yael

    2009-07-01

    New companies offering personal whole-genome information services over the internet are dynamic and highly visible players in the personal genomics field. For fees currently ranging from US$399 to US$2500 and a vial of saliva, individuals can now purchase online access to their individual genetic information regarding susceptibility to a range of chronic diseases and phenotypic traits based on a genome-wide SNP scan. Most of the companies offering such services are based in the United States, but their clients may come from nearly anywhere in the world. Although the scientific validity, clinical utility and potential future implications of such services are being hotly debated, several ethical and regulatory questions related to direct-to-consumer (DTC) marketing strategies of genetic tests have not yet received sufficient attention. For example, how can we minimize the risk of unauthorized third parties from submitting other people's DNA for testing? Another pressing question concerns the ownership of (genotypic and phenotypic) information, as well as the unclear legal status of customers regarding their own personal information. Current legislation in the US and Europe falls short of providing clear answers to these questions. Until the regulation of personal genomics services catches up with the technology, we call upon commercial providers to self-regulate and coordinate their activities to minimize potential risks to individual privacy. We also point out some specific steps, along the trustee model, that providers of DTC personal genomics services as well as regulators and policy makers could consider for addressing some of the concerns raised below.

  7. Genomic instability and radiation effects

    International Nuclear Information System (INIS)

    Christian Streffer

    2007-01-01

    Complete text of publication follows. Cancer, genetic mutations and developmental abnormalities are apparently associated with an increased genomic instability. Such phenomena have been frequently shown in human cancer cells in vitro and in situ. It is also well-known that individuals with a genetic predisposition for cancer proneness, such as ataxia telangiectesia, Fanconi anaemia etc. demonstrate a general high genomic instability e.g. in peripheral lymphocytes before a cancer has developed. Analogous data have been found in mice which develop a specific congenital malformation which has a genetic background. Under these aspects it is of high interest that ionising radiation can increase the genomic instability of mammalian cells after exposures in vitro an in vivo. This phenomenon is expressed 20 to 40 cell cycles after the exposure e.g. by de novo chromosomal aberrations. Such effects have been observed with high and low LET radiation, high LET radiation is more efficient. With low LET radiation a good dose response is observed in the dose range 0.2 to 2.0 Gy, Recently it has been reported that senescence and genomic instability was induced in human fibroblasts after 1 mGy carbon ions (1 in 18 cells are hit), apparently bystander effects also occurred under these conditions. The instability has been shown with DNA damage, chromosomal aberrations, gene mutation and cell death. It is also transferred to the next generation of mice with respect to gene mutations, chromosomal aberrations and congenital malformations. Several mechanisms have been discussed. The involvement of telomeres has gained interest. Genomic instability seems to be induced by a general lesion to the whole genome. The transmission of one chromosome from an irradiated cell to an non-irradiated cell leads to genomic instability in the untreated cells. Genomic instability increases mutation rates in the affected cells in general. As radiation late effects (cancer, gene mutations and congenital

  8. Radiotaxons and reliability of a genome

    International Nuclear Information System (INIS)

    Korogodin, V.I.

    1982-01-01

    Radiosensitivity of cells (D 0 ) is considered with regard to the structural organization of the genome. The following terms are introduced: ''karyotaxon'', organisms with identical structural organization of the genome, and ''specific genome stability'' K=D 0 C, where C is the quantity of DNA in the cell nucleus; K is the amount of energy (eV) the sorption of which in DNA is necessary and sufficient for one elementary damage to occur. It was shown that Ksub(i)=const. within every karyotaxon ''i''. K 1 =100 eV for viruses, and K 4 =61000 eV for the highest level of genome organization (diploid eukaryotes including man). Potential mechanisms of increasing Ksub(i) with increasing level of genome organization and the role of this factor in evolution are discussed [ru

  9. Transcription as a Threat to Genome Integrity.

    Science.gov (United States)

    Gaillard, Hélène; Aguilera, Andrés

    2016-06-02

    Genomes undergo different types of sporadic alterations, including DNA damage, point mutations, and genome rearrangements, that constitute the basis for evolution. However, these changes may occur at high levels as a result of cell pathology and trigger genome instability, a hallmark of cancer and a number of genetic diseases. In the last two decades, evidence has accumulated that transcription constitutes an important natural source of DNA metabolic errors that can compromise the integrity of the genome. Transcription can create the conditions for high levels of mutations and recombination by its ability to open the DNA structure and remodel chromatin, making it more accessible to DNA insulting agents, and by its ability to become a barrier to DNA replication. Here we review the molecular basis of such events from a mechanistic perspective with particular emphasis on the role of transcription as a genome instability determinant.

  10. Visualization for genomics: the Microbial Genome Viewer.

    NARCIS (Netherlands)

    Kerkhoven, R.; Enckevort, F.H.J. van; Boekhorst, J.; Molenaar, D; Siezen, R.J.

    2004-01-01

    SUMMARY: A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a

  11. SIRT participates at DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Mi Yong; Joeng, Jae Min; Lee, Kee Ho [Korea Cancer Center Hospital, Seoul (Korea, Republic of); Park, Gil Hong [College of Medicine, Korea University, Seoul (Korea, Republic of)

    2009-05-15

    Sir2 maintains genomic stability in multiple ways in yeast. As a NAD{sup +}-dependent histone deacetylase, Sir2 has been reported to control chromatin silencing. In both budding yeast and Drosophila, overexpression of Sir2 extends life span. Previous reports have also demonstrated that Sir2 participate at DNA damage repair. A protein complex containing Sir2 has been reported to translocate to DNA double-strand breaks. Following DNA damage response, SIRT1 deacetylates p53 protein and attenuates its ability as a transcription factor. Consequently, SIRT1 over-expression increases cell survival under DNA damage inducing conditions. These previous observations mean a possibility that signals generated during the process of DNA repair are delivered through SIRT1 to acetylated p53. We present herein functional evidence for the involvement of SIRT1 in DNA repair response to radiation. In addition, this modulation of DNA repair activity may be connected to deacetylation of MRN proteins.

  12. Protein Dynamics in Mammalian Genome Maintenance

    NARCIS (Netherlands)

    A. Zotter (Angelika)

    2008-01-01

    textabstractThe integrity of the genome, carrier of the blueprint for each organism, is under constant attack from environmental as well as endogenous DNA damaging agents. An agent with substantial impact on our DNA is the UV-fraction of sunlight. It inflicts bulky DNA lesions, which can interfere

  13. Ancient genomics

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Allentoft, Morten Erik; Avila Arcos, Maria del Carmen

    2015-01-01

    throughput of next generation sequencing platforms and the ability to target short and degraded DNA molecules. Many ancient specimens previously unsuitable for DNA analyses because of extensive degradation can now successfully be used as source materials. Additionally, the analytical power obtained...... by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans...

  14. Marine genomics

    DEFF Research Database (Denmark)

    Oliveira Ribeiro, Ângela Maria; Foote, Andrew David; Kupczok, Anne

    2017-01-01

    Marine ecosystems occupy 71% of the surface of our planet, yet we know little about their diversity. Although the inventory of species is continually increasing, as registered by the Census of Marine Life program, only about 10% of the estimated two million marine species are known. This lag......-throughput sequencing approaches have been helping to improve our knowledge of marine biodiversity, from the rich microbial biota that forms the base of the tree of life to a wealth of plant and animal species. In this review, we present an overview of the applications of genomics to the study of marine life, from...

  15. Transcription and DNA Damage: Holding Hands or Crossing Swords?

    Science.gov (United States)

    D'Alessandro, Giuseppina; d'Adda di Fagagna, Fabrizio

    2017-10-27

    Transcription has classically been considered a potential threat to genome integrity. Collision between transcription and DNA replication machinery, and retention of DNA:RNA hybrids, may result in genome instability. On the other hand, it has been proposed that active genes repair faster and preferentially via homologous recombination. Moreover, while canonical transcription is inhibited in the proximity of DNA double-strand breaks, a growing body of evidence supports active non-canonical transcription at DNA damage sites. Small non-coding RNAs accumulate at DNA double-strand break sites in mammals and other organisms, and are involved in DNA damage signaling and repair. Furthermore, RNA binding proteins are recruited to DNA damage sites and participate in the DNA damage response. Here, we discuss the impact of transcription on genome stability, the role of RNA binding proteins at DNA damage sites, and the function of small non-coding RNAs generated upon damage in the signaling and repair of DNA lesions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. DETERIORO GENÓMICO Y MANIPULACIÓN GENÉTICA: DESEQUILIBRIO EN LA PRIORIDAD DE LAS AGENDAS PÚBLICAS DETERIORIZAÇÃO GENÔMICA E MANIPULAÇÃO GENÉTICA: DESEQUILÍBRIO NA PRIORIDADE DAS AGENDAS PÚBLICAS GENOME DAMAGE AND GENETIC MANIPULATION: UNBALANCE IN PUBLIC POLICIES PRIORITY

    Directory of Open Access Journals (Sweden)

    Elio A Prieto González

    2007-11-01

    Full Text Available Se analiza el desequilibrio en el tratamiento de dos temas que atañen a la conservación de la integridad del genoma humano: las tecnologías de manipulación genética y el deterioro genómico provocado por la contaminación ambiental. Las carencias educativas, la falta de información asentada en los hechos y un manejo sensacionalista en los medios, entre otros factores, desajustan las agendas mediáticas con las necesidades públicas, lo que desemboca en una falta de conciencia ciudadana acerca de las verdaderas amenazas a las que está expuesto el material genético y los riesgos de salud que ello implicaO presente texto analisa o desequilíbrio no tratamento de dois temas que dizem respeito à conservação da integridade do genoma humano: as tecnologias de manipulação genética e a deteriorização genômica provocada pela contaminação ambiental. As carências educativas, a falta de informação assentada nos fatos e um manejo sensacionalista dos meios, entre outros fatores, desajustam as agendas mediáticas com as necessidades públicas, o que desemboca numa falta de consciência cidadã em relação às verdadeiras ameaças à que se expôs o material genético e os riscos de saúde que isto implicaUnbalance in the treatment of two topics related to the conservation of the human genome integrity is analyzed here: the technologies for genetic manipulation and genome damage due to environmental pollution. Lack of education and of information based on real facts, and the media sensationalist treatment, among other factors, provoke an unbalance between the media agenda and public needs. This leads to a lack of citizenship consciousness over the true threats that genetic material faces and the health risks that it involves

  17. Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria.

    Science.gov (United States)

    Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

    2017-04-01

    A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compensate for the genome-destabilizing effect of environmental DNA damage and may be expected to result in a more conserved gene order in radiation-resistant species. However, here we show that rates of genome rearrangements, measured as loss of gene order conservation with time, are higher in radiation-resistant species in multiple, phylogenetically independent groups of bacteria. Comparison of indicators of selection for genome organization between radiation-resistant and phylogenetically matched, nonresistant species argues against tolerance to disruption of genome structure as a strategy for radiation resistance. Interestingly, an important mechanism affecting genome rearrangements in prokaryotes, the symmetrical inversions around the origin of DNA replication, shapes genome structure of both radiation-resistant and nonresistant species. In conclusion, the opposing effects of environmental DNA damage and DNA repair result in elevated rates of genome rearrangements in radiation-resistant bacteria. Copyright © 2017 Repar et al.

  18. Ensembl Genomes 2016: more genomes, more complexity.

    Science.gov (United States)

    Kersey, Paul Julian; Allen, James E; Armean, Irina; Boddu, Sanjay; Bolt, Bruce J; Carvalho-Silva, Denise; Christensen, Mikkel; Davis, Paul; Falin, Lee J; Grabmueller, Christoph; Humphrey, Jay; Kerhornou, Arnaud; Khobova, Julia; Aranganathan, Naveen K; Langridge, Nicholas; Lowy, Ernesto; McDowall, Mark D; Maheswari, Uma; Nuhn, Michael; Ong, Chuang Kee; Overduin, Bert; Paulini, Michael; Pedro, Helder; Perry, Emily; Spudich, Giulietta; Tapanari, Electra; Walts, Brandon; Williams, Gareth; Tello-Ruiz, Marcela; Stein, Joshua; Wei, Sharon; Ware, Doreen; Bolser, Daniel M; Howe, Kevin L; Kulesha, Eugene; Lawson, Daniel; Maslen, Gareth; Staines, Daniel M

    2016-01-04

    Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Rodent malaria parasites : genome organization & comparative genomics

    NARCIS (Netherlands)

    Kooij, Taco W.A.

    2006-01-01

    The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P.

  20. Radiation damage to mushrooms

    International Nuclear Information System (INIS)

    Sattler, P.W.

    1986-01-01

    This document contains newspaper cuttings and correspondence with various ministries in Hessen on the subject of radiation damage to mushrooms from the Odenwald area. The reader is given, amongst other things, detailed information on radiation damage to different types of mushroom in 1986. (MG) [de

  1. Animal damage to birch

    Science.gov (United States)

    James S. Jordan; Francis M. Rushmore

    1969-01-01

    A relatively few animal species are responsible for most of the reported damage to the birches. White-tailed deer, yellow-bellied sapsuckers, porcupines, moose, and hares are the major animals involved. We will review reports of damage, discuss the underlying causes, and describe possible methods of control. For example, heavy deer browsing that eliminates birch...

  2. Animal damage management handbook.

    Science.gov (United States)

    Hugh C. Black

    1994-01-01

    This handbook treats animal damage management (ADM) in the West in relation to forest, range, and recreation resources; predator management is not addressed. It provides a comprehensive reference of safe, effective, and practical methods for managing animal damage on National Forest System lands. Supporting information is included in references after each chapter and...

  3. Nuclear damage - civil liability

    International Nuclear Information System (INIS)

    Simoes, A.C.

    1980-01-01

    An analysis is made of the civil liability for nuclear damage since there is a need to adjust the existing rules to the new situations created. The conventions that set up the new disciplining rules not considered in the common law for the liability of nuclear damage are also mentioned. (A.L.) [pt

  4. DNA damage and autophagy

    International Nuclear Information System (INIS)

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Panayiotidis, Mihalis I.; Franco, Rodrigo

    2011-01-01

    Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.

  5. Metabolite damage and repair in metabolic engineering design.

    Science.gov (United States)

    Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

    2017-11-01

    The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

  6. Metabolite damage and repair in metabolic engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.; Bruner, Steven D.; Hanson, Andrew D.

    2017-11-01

    The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.

  7. MicroRNAs, the DNA damage response and cancer

    International Nuclear Information System (INIS)

    Wouters, Maikel D.; Gent, Dik C. van; Hoeijmakers, Jan H.J.; Pothof, Joris

    2011-01-01

    Many carcinogenic agents such as ultra-violet light from the sun and various natural and man-made chemicals act by damaging the DNA. To deal with these potentially detrimental effects of DNA damage, cells induce a complex DNA damage response (DDR) that includes DNA repair, cell cycle checkpoints, damage tolerance systems and apoptosis. This DDR is a potent barrier against carcinogenesis and defects within this response are observed in many, if not all, human tumors. DDR defects fuel the evolution of precancerous cells to malignant tumors, but can also induce sensitivity to DNA damaging agents in cancer cells, which can be therapeutically exploited by the use of DNA damaging treatment modalities. Regulation of and coordination between sub-pathways within the DDR is important for maintaining genome stability. Although regulation of the DDR has been extensively studied at the transcriptional and post-translational level, less is known about post-transcriptional gene regulation by microRNAs, the topic of this review. More specifically, we highlight current knowledge about DNA damage responsive microRNAs and microRNAs that regulate DNA damage response genes. We end by discussing the role of DNA damage response microRNAs in cancer etiology and sensitivity to ionizing radiation and other DNA damaging therapeutic agents.

  8. DNA damage in plant herbarium tissue.

    Science.gov (United States)

    Staats, Martijn; Cuenca, Argelia; Richardson, James E; Vrielink-van Ginkel, Ria; Petersen, Gitte; Seberg, Ole; Bakker, Freek T

    2011-01-01

    Dried plant herbarium specimens are potentially a valuable source of DNA. Efforts to obtain genetic information from this source are often hindered by an inability to obtain amplifiable DNA as herbarium DNA is typically highly degraded. DNA post-mortem damage may not only reduce the number of amplifiable template molecules, but may also lead to the generation of erroneous sequence information. A qualitative and quantitative assessment of DNA post-mortem damage is essential to determine the accuracy of molecular data from herbarium specimens. In this study we present an assessment of DNA damage as miscoding lesions in herbarium specimens using 454-sequencing of amplicons derived from plastid, mitochondrial, and nuclear DNA. In addition, we assess DNA degradation as a result of strand breaks and other types of polymerase non-bypassable damage by quantitative real-time PCR. Comparing four pairs of fresh and herbarium specimens of the same individuals we quantitatively assess post-mortem DNA damage, directly after specimen preparation, as well as after long-term herbarium storage. After specimen preparation we estimate the proportion of gene copy numbers of plastid, mitochondrial, and nuclear DNA to be 2.4-3.8% of fresh control DNA and 1.0-1.3% after long-term herbarium storage, indicating that nearly all DNA damage occurs on specimen preparation. In addition, there is no evidence of preferential degradation of organelle versus nuclear genomes. Increased levels of C→T/G→A transitions were observed in old herbarium plastid DNA, representing 21.8% of observed miscoding lesions. We interpret this type of post-mortem DNA damage-derived modification to have arisen from the hydrolytic deamination of cytosine during long-term herbarium storage. Our results suggest that reliable sequence data can be obtained from herbarium specimens.

  9. Funding Opportunity: Genomic Data Centers

    Science.gov (United States)

    Funding Opportunity CCG, Funding Opportunity Center for Cancer Genomics, CCG, Center for Cancer Genomics, CCG RFA, Center for cancer genomics rfa, genomic data analysis network, genomic data analysis network centers,

  10. Mechanisms of cadmium induced genomic instability

    Energy Technology Data Exchange (ETDEWEB)

    Filipic, Metka, E-mail: metka.filipic@nib.si [National Institute of Biology, Department for Genetic Toxicology and Cancer Biology, Ljubljana (Slovenia)

    2012-05-01

    Cadmium is an ubiquitous environmental contaminant that represents hazard to humans and wildlife. It is found in the air, soil and water and, due to its extremely long half-life, accumulates in plants and animals. The main source of cadmium exposure for non-smoking human population is food. Cadmium is primarily toxic to the kidney, but has been also classified as carcinogenic to humans by several regulatory agencies. Current evidence suggests that exposure to cadmium induces genomic instability through complex and multifactorial mechanisms. Cadmium dose not induce direct DNA damage, however it induces increase in reactive oxygen species (ROS) formation, which in turn induce DNA damage and can also interfere with cell signalling. More important seems to be cadmium interaction with DNA repair mechanisms, cell cycle checkpoints and apoptosis as well as with epigenetic mechanisms of gene expression control. Cadmium mediated inhibition of DNA repair mechanisms and apoptosis leads to accumulation of cells with unrepaired DNA damage, which in turn increases the mutation rate and thus genomic instability. This increases the probability of developing not only cancer but also other diseases associated with genomic instability. In the in vitro experiments cadmium induced effects leading to genomic instability have been observed at low concentrations that were comparable to those observed in target organs and tissues of humans that were non-occupationally exposed to cadmium. Therefore, further studies aiming to clarify the relevance of these observations for human health risks due to cadmium exposure are needed.

  11. Mechanisms of cadmium induced genomic instability

    International Nuclear Information System (INIS)

    Filipič, Metka

    2012-01-01

    Cadmium is an ubiquitous environmental contaminant that represents hazard to humans and wildlife. It is found in the air, soil and water and, due to its extremely long half-life, accumulates in plants and animals. The main source of cadmium exposure for non-smoking human population is food. Cadmium is primarily toxic to the kidney, but has been also classified as carcinogenic to humans by several regulatory agencies. Current evidence suggests that exposure to cadmium induces genomic instability through complex and multifactorial mechanisms. Cadmium dose not induce direct DNA damage, however it induces increase in reactive oxygen species (ROS) formation, which in turn induce DNA damage and can also interfere with cell signalling. More important seems to be cadmium interaction with DNA repair mechanisms, cell cycle checkpoints and apoptosis as well as with epigenetic mechanisms of gene expression control. Cadmium mediated inhibition of DNA repair mechanisms and apoptosis leads to accumulation of cells with unrepaired DNA damage, which in turn increases the mutation rate and thus genomic instability. This increases the probability of developing not only cancer but also other diseases associated with genomic instability. In the in vitro experiments cadmium induced effects leading to genomic instability have been observed at low concentrations that were comparable to those observed in target organs and tissues of humans that were non-occupationally exposed to cadmium. Therefore, further studies aiming to clarify the relevance of these observations for human health risks due to cadmium exposure are needed.

  12. DNA damage and polyploidization.

    Science.gov (United States)

    Chow, Jeremy; Poon, Randy Y C

    2010-01-01

    A growing body of evidence indicates that polyploidization triggers chromosomal instability and contributes to tumorigenesis. DNA damage is increasingly being recognized for its roles in promoting polyploidization. Although elegant mechanisms known as the DNA damage checkpoints are responsible for halting the cell cycle after DNA damage, agents that uncouple the checkpoints can induce unscheduled entry into mitosis. Likewise, defects of the checkpoints in several disorders permit mitotic entry even in the presence of DNA damage. Forcing cells with damaged DNA into mitosis causes severe chromosome segregation defects, including lagging chromosomes, chromosomal fragments and chromosomal bridges. The presence of these lesions in the cleavage plane is believed to abort cytokinesis. It is postulated that if cytokinesis failure is coupled with defects of the p53-dependent postmitotic checkpoint pathway, cells can enter S phase and become polyploids. Progress in the past several years has unraveled some of the underlying principles of these pathways and underscored the important role of DNA damage in polyploidization. Furthermore, polyploidization per se may also be an important determinant of sensitivity to DNA damage, thereby may offer an opportunity for novel therapies.

  13. Exploring Other Genomes: Bacteria.

    Science.gov (United States)

    Flannery, Maura C.

    2001-01-01

    Points out the importance of genomes other than the human genome project and provides information on the identified bacterial genomes Pseudomonas aeuroginosa, Leprosy, Cholera, Meningitis, Tuberculosis, Bubonic Plague, and plant pathogens. Considers the computer's use in genome studies. (Contains 14 references.) (YDS)

  14. Genomics With Cloud Computing

    OpenAIRE

    Sukhamrit Kaur; Sandeep Kaur

    2015-01-01

    Abstract Genomics is study of genome which provides large amount of data for which large storage and computation power is needed. These issues are solved by cloud computing that provides various cloud platforms for genomics. These platforms provides many services to user like easy access to data easy sharing and transfer providing storage in hundreds of terabytes more computational power. Some cloud platforms are Google genomics DNAnexus and Globus genomics. Various features of cloud computin...

  15. LSD and Genetic Damage

    Science.gov (United States)

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  16. Diabetes and nerve damage

    Science.gov (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  17. Genome Maps, a new generation genome browser.

    Science.gov (United States)

    Medina, Ignacio; Salavert, Francisco; Sanchez, Rubén; de Maria, Alejandro; Alonso, Roberto; Escobar, Pablo; Bleda, Marta; Dopazo, Joaquín

    2013-07-01

    Genome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org.

  18. Relationship between Deleterious Variation, Genomic Autozygosity, and Disease Risk: Insights from The 1000 Genomes Project.

    Science.gov (United States)

    Pemberton, Trevor J; Szpiech, Zachary A

    2018-04-05

    Genomic regions of autozygosity (ROAs) represent segments of individual genomes that are homozygous for haplotypes inherited identical-by-descent (IBD) from a common ancestor. ROAs are nonuniformly distributed across the genome, and increased ROA levels are a reported risk factor for numerous complex diseases. Previously, we hypothesized that long ROAs are enriched for deleterious homozygotes as a result of young haplotypes with recent deleterious mutations-relatively untouched by purifying selection-being paired IBD as a consequence of recent parental relatedness, a pattern supported by ROA and whole-exome sequence data on 27 individuals. Here, we significantly bolster support for our hypothesis and expand upon our original analyses using ROA and whole-genome sequence data on 2,436 individuals from The 1000 Genomes Project. Considering CADD deleteriousness scores, we reaffirm our previous observation that long ROAs are enriched for damaging homozygotes worldwide. We show that strongly damaging homozygotes experience greater enrichment than weaker damaging homozygotes, while overall enrichment varies appreciably among populations. Mendelian disease genes and those encoding FDA-approved drug targets have significantly increased rates of gain in damaging homozygotes with increasing ROA coverage relative to all other genes. In genes implicated in eight complex phenotypes for which ROA levels have been identified as a risk factor, rates of gain in damaging homozygotes vary across phenotypes and populations but frequently differ significantly from non-disease genes. These findings highlight the potential confounding effects of population background in the assessment of associations between ROA levels and complex disease risk, which might underlie reported inconsistencies in ROA-phenotype associations. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome Stability and Prevention of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Karras, Jenna R.; Paisie, Carolyn A.; Huebner, Kay, E-mail: kay.huebner@osumc.edu [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210 (United States)

    2014-06-04

    The fragile FHIT gene, encompassing the chromosomal fragile site FRA3B, is an early target of DNA damage in precancerous cells. While vulnerable to DNA damage itself, FHIT protein expression is essential to protect from DNA damage-induced cancer initiation and progression by modulating genome stability, oxidative stress and levels of accumulating DNA damage. Thus, FHIT, whose expression is lost or reduced in many human cancers, is a tumor suppressor and genome caretaker whose loss initiates genome instability in preneoplastic lesions. Ongoing studies are seeking more detailed understanding of the role of FHIT in the cellular response to oxidative damage. This review discusses the relationship between FHIT, reactive oxygen species production, and DNA damage in the context of cancer initiation and progression.

  20. JGI Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  1. Genomic Encyclopedia of Fungi

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-08-10

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 150 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.

  2. DNA alkylation damage as a sensor of nitrosative stress in Mycobacterium tuberculosis

    OpenAIRE

    Durbach, S I; Springer, B; Machowski, E E; North, R J; Papavinasasundaram, K G; Colston, M J; Böttger, E C; Mizrahi, V

    2003-01-01

    One of the cellular consequences of nitrosative stress is alkylation damage to DNA. To assess whether nitrosative stress is registered on the genome of Mycobacterium tuberculosis, mutants lacking an alkylation damage repair and reversal operon were constructed. Although hypersensitive to the genotoxic effects of N-methyl-N′-nitro-N-nitrosoguanidine in vitro, the mutants displayed no phenotype in vivo, suggesting that permeation of nitrosative stress to the level of cytotoxic DNA damage is res...

  3. Genomics With Cloud Computing

    Directory of Open Access Journals (Sweden)

    Sukhamrit Kaur

    2015-04-01

    Full Text Available Abstract Genomics is study of genome which provides large amount of data for which large storage and computation power is needed. These issues are solved by cloud computing that provides various cloud platforms for genomics. These platforms provides many services to user like easy access to data easy sharing and transfer providing storage in hundreds of terabytes more computational power. Some cloud platforms are Google genomics DNAnexus and Globus genomics. Various features of cloud computing to genomics are like easy access and sharing of data security of data less cost to pay for resources but still there are some demerits like large time needed to transfer data less network bandwidth.

  4. Coal transportation road damage

    International Nuclear Information System (INIS)

    Burtraw, D.; Harrison, K.; Pawlowski, J.A.

    1994-01-01

    Heavy trucks are primarily responsible for pavement damage to the nation's highways. In this paper we evaluate the pavement damage caused by coal trucks. We analyze the chief source of pavement damage (vehicle weight per axle, not total vehicle weight) and the chief cost involved (the periodic overlay that is required when a road's surface becomes worn). This analysis is presented in two stages. In the first section we present a synopsis of current economic theory including simple versions of the formulas that can be: used to calculate costs of pavement wear. In the second section we apply this theory to a specific example proximate to the reference environment for the Fuel Cycle Study in New Mexico in order to provide a numerical measure of the magnitude of the costs

  5. Natural resource damage assessment

    International Nuclear Information System (INIS)

    Seddelmeyer, J.

    1991-01-01

    The assessment and collection of natural resource damages from petroleum and chemical companies unfortunate enough to have injured publicly owned natural resources is perhaps the most rapidly expanding area of environmental liability. The idea of recovering for injury to publicly owned natural resources is an extension of traditional common law tort concepts under which a person who negligently injures another or his property is called upon to compensate the injured party. Normally, once liability has been established, it is a fairly straightforward matter to calculate the various elements of loss, such as the cost to repair or replace damaged property, or medical expenses, and lost income. More difficult questions, such as the amount to be awarded for pain and suffering or emotional distress, are left to the jury, although courts limit the circumstances in which the jury is permitted to award such damages

  6. Comparative Genome Analysis and Genome Evolution

    NARCIS (Netherlands)

    Snel, Berend

    2002-01-01

    This thesis described a collection of bioinformatic analyses on complete genome sequence data. We have studied the evolution of gene content and find that vertical inheritance dominates over horizontal gene trasnfer, even to the extent that we can use the gene content to make genome phylogenies.

  7. Genomic Data Commons launches

    Science.gov (United States)

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  8. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  9. Visualization for genomics: the Microbial Genome Viewer.

    Science.gov (United States)

    Kerkhoven, Robert; van Enckevort, Frank H J; Boekhorst, Jos; Molenaar, Douwe; Siezen, Roland J

    2004-07-22

    A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a MySQL database. The generated images are in scalable vector graphics (SVG) format, which is suitable for creating high-quality scalable images and dynamic Web representations. Gene-related data such as transcriptome and time-course microarray experiments can be superimposed on the maps for visual inspection. The Microbial Genome Viewer 1.0 is freely available at http://www.cmbi.kun.nl/MGV

  10. Genomic prediction using subsampling

    OpenAIRE

    Xavier, Alencar; Xu, Shizhong; Muir, William; Rainey, Katy Martin

    2017-01-01

    Background Genome-wide assisted selection is a critical tool for the?genetic improvement of plants and animals. Whole-genome regression models in Bayesian framework represent the main family of prediction methods. Fitting such models with a large number of observations involves a prohibitive computational burden. We propose the use of subsampling bootstrap Markov chain in genomic prediction. Such method consists of fitting whole-genome regression models by subsampling observations in each rou...

  11. Genomic footprinting in mammalian cells with ultraviolet light

    International Nuclear Information System (INIS)

    Becker, M.M.; Wang, Z.; Grossmann, G.; Becherer, K.A.

    1989-01-01

    A simple and accurate genomic primer extension method has been developed to detect ultraviolet footprinting patterns of regulatory protein-DNA interactions in mammalian genomic DNA. The technique can also detect footprinting or sequencing patterns introduced into genomic DNA by other methods. Purified genomic DNA, containing either damaged bases or strand breaks introduced by footprinting or sequencing reactions, is first cut with a convenient restriction enzyme to reduce its molecular weight. A highly radioactive single-stranded DNA primer that is complementary to a region of genomic DNA whose sequence or footprint one wishes to examine is then mixed with 50 micrograms of restriction enzyme-cut genomic DNA. The primer is approximately 100 bases long and contains 85 radioactive phosphates, each of specific activity 3000 Ci/mmol (1 Ci = 37 GBq). A simple and fast method for preparing such primers is described. Following brief heat denaturation at 100 degrees C, the solution of genomic DNA and primer is cooled to 74 degrees C and a second solution containing Taq polymerase (Thermus aquaticus DNA polymerase) and the four deoxynucleotide triphosphates is added to initiate primer extension of genomic DNA. Taq polymerase extends genomic hybridized primer until its polymerization reaction is terminated either by a damaged base or strand break in genomic DNA or by the addition of dideoxynucleotide triphosphates in the polymerization reaction. The concurrent primer hybridization-extension reaction is terminated after 5 hr and unhybridized primer is digested away by mung bean nuclease. Primer-extended genomic DNA is then denatured and electrophoresed on a polyacrylamide sequencing gel, and radioactive primer extension products are revealed by autoradiography

  12. Evaluating In Vitro DNA Damage Using Comet Assay.

    Science.gov (United States)

    Lu, Yanxin; Liu, Yang; Yang, Chunzhang

    2017-10-11

    DNA damage is a common phenomenon for each cell during its lifespan, and is defined as an alteration of the chemical structure of genomic DNA. Cancer therapies, such as radio- and chemotherapy, introduce enormous amount of additional DNA damage, leading to cell cycle arrest and apoptosis to limit cancer progression. Quantitative assessment of DNA damage during experimental cancer therapy is a key step to justify the effectiveness of a genotoxic agent. In this study, we focus on a single cell electrophoresis assay, also known as the comet assay, which can quantify single and double-strand DNA breaks in vitro. The comet assay is a DNA damage quantification method that is efficient and easy to perform, and has low time/budget demands and high reproducibility. Here, we highlight the utility of the comet assay for a preclinical study by evaluating the genotoxic effect of olaparib/temozolomide combination therapy to U251 glioma cells.

  13. Vitamin C for DNA damage prevention

    International Nuclear Information System (INIS)

    Sram, Radim J.; Binkova, Blanka; Rossner, Pavel

    2012-01-01

    The ability of vitamin C to affect genetic damage was reviewed in human studies that used molecular epidemiology methods, including analysis of DNA adducts, DNA strand breakage (using the Comet assay), oxidative damage measured as levels of 8-oxo-7,8-dihydroxy-2′-deoxyguanosine (8-oxodG), cytogenetic analysis of chromosomal aberrations and micronuclei, and the induction of DNA repair proteins. The protective effect of vitamin C was observed at plasma levels > 50 μmol/l. Vitamin C supplementation decreased the frequency of chromosomal aberrations in groups with insufficient dietary intake who were occupationally exposed to mutagens, and also decreased the sensitivity to mutagens as assessed using the bleomycin assay. High vitamin C levels in plasma decreased the frequency of genomic translocations in groups exposed to ionizing radiation or c-PAHs in polluted air. The frequency of micronuclei was decreased by vitamin C supplementation in smokers challenged with γ-irradiation, and higher vitamin C levels in plasma counteracted the damage induced by air pollution. The prevalence of DNA adducts inversely correlated with vitamin C levels in groups environmentally exposed to high concentrations of c-PAHs. Increased vitamin C levels decreased DNA strand breakage induced by air pollution. Oxidative damage (8-oxodG levels) was decreased by vitamin C supplementation in groups with plasma levels > 50 μmol/l exposed to PM2.5 and c-PAHs. Modulation of DNA repair by vitamin C supplementation was observed both in poorly nourished subjects and in groups with vitamin C plasma levels > 50 μmol/l exposed to higher concentrations of c-PAHs. It is possible that the impact of vitamin C on DNA damage depends both on background values of vitamin C in the individual as well as on the level of exposure to xenobiotics or oxidative stress.

  14. Vitamin C for DNA damage prevention

    Energy Technology Data Exchange (ETDEWEB)

    Sram, Radim J., E-mail: sram@biomed.cas.cz [Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague 4 (Czech Republic); Binkova, Blanka; Rossner, Pavel [Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague 4 (Czech Republic)

    2012-05-01

    The ability of vitamin C to affect genetic damage was reviewed in human studies that used molecular epidemiology methods, including analysis of DNA adducts, DNA strand breakage (using the Comet assay), oxidative damage measured as levels of 8-oxo-7,8-dihydroxy-2 Prime -deoxyguanosine (8-oxodG), cytogenetic analysis of chromosomal aberrations and micronuclei, and the induction of DNA repair proteins. The protective effect of vitamin C was observed at plasma levels > 50 {mu}mol/l. Vitamin C supplementation decreased the frequency of chromosomal aberrations in groups with insufficient dietary intake who were occupationally exposed to mutagens, and also decreased the sensitivity to mutagens as assessed using the bleomycin assay. High vitamin C levels in plasma decreased the frequency of genomic translocations in groups exposed to ionizing radiation or c-PAHs in polluted air. The frequency of micronuclei was decreased by vitamin C supplementation in smokers challenged with {gamma}-irradiation, and higher vitamin C levels in plasma counteracted the damage induced by air pollution. The prevalence of DNA adducts inversely correlated with vitamin C levels in groups environmentally exposed to high concentrations of c-PAHs. Increased vitamin C levels decreased DNA strand breakage induced by air pollution. Oxidative damage (8-oxodG levels) was decreased by vitamin C supplementation in groups with plasma levels > 50 {mu}mol/l exposed to PM2.5 and c-PAHs. Modulation of DNA repair by vitamin C supplementation was observed both in poorly nourished subjects and in groups with vitamin C plasma levels > 50 {mu}mol/l exposed to higher concentrations of c-PAHs. It is possible that the impact of vitamin C on DNA damage depends both on background values of vitamin C in the individual as well as on the level of exposure to xenobiotics or oxidative stress.

  15. Ebolavirus comparative genomics

    DEFF Research Database (Denmark)

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms...

  16. mapDamage

    DEFF Research Database (Denmark)

    Ginolhac, Aurélien; Rasmussen, Morten; Gilbert, Tom

    2011-01-01

    Ancient DNA extracts consist of a mixture of contaminant DNA molecules, most often originating from environmental microbes, and endogenous fragments exhibiting substantial levels of DNA damage. The latter introduce specific nucleotide misincorporations and DNA fragmentation signatures in sequenci...... of the SAMtools suite and R environment and has been validated on both GNU/Linux and MacOSX operating systems....

  17. Core damage risk indicators

    International Nuclear Information System (INIS)

    Szikszai, T.

    1994-01-01

    The purpose of this document is to show a method for the fast recalculation of the PSA. To avoid the information loose, it is necessary to simplify the PSA models, or at least reorganize them. The method, introduced in this document, require that preparation, so we try to show, how to do that. This document is an introduction. This is the starting point of the work related to the development of the risk indicators. In the future, with the application of this method, we are going to show an everyday use of the PSA results to produce the indicators of the core damage risk. There are two different indicators of the plant safety performance, related to the core damage risk. The first is the core damage frequency indicator (CDFI), and the second is the core damage probability indicator (CDPI). Of course, we cannot describe all of the possible ways to use these indicators, rather we will try to introduce the requirements to establish such an indicator system and the calculation process

  18. Risk of nuclear damage

    International Nuclear Information System (INIS)

    Kienzl, K.

    1997-01-01

    Following the opening and words of welcome by Mr. Fritz Unterpertinger (unit director at the Austrian Federal Ministry for the Environment, Youth and Family; BMUJF) Mrs Helga Kromp-Kolb (professor at the Institute for Meteorology and Physics of the University of Natural Resources Science Vienna) illustrated the risks of nuclear damage in Europe by means of a nuclear risk map. She explained that even from a scientific or technical point of view the assessment of risks arising from nuclear power stations was fraught with great uncertainties. Estimates about in how far MCAs (maximum credible accident) could still be controlled by safety systems vary widely and so do assessments of the probability of a core melt. But there is wide agreement in all risk assessments conducted so far that MCAs might occur within a - from a human point of view - conceivable number of years. In this connection one has to bear in mind that the occurrence of such a major accident - whatever its probability may be - could entail immense damage and the question arises whether or not it is at all justifiable to expose the general public to such a risk. Klaus Rennings (Centre for European Economic Research, Mannheim, Germany) dealt with the economic aspects of nuclear risk assessment. He explained that there are already a number of studies available aiming to assess the risk of damage resulting from a core melt accident in economic terms. As to the probability of occurrence estimates vary widely between one incident in 3,333 and 250,000 year of reactor operation. It is assumed, however, that a nuclear accident involving a core melt in Germany would probably exceed the damage caused by the Chernobyl accident. The following speakers addressed the legal aspects of risks associated with nuclear installations. Mrs Monika Gimpel-Hinteregger (professor at the Institute for Civil Law in Graz) gave an overview on the applicable Austrian law concerning third party liability in the field of nuclear energy

  19. The Sequenced Angiosperm Genomes and Genome Databases.

    Science.gov (United States)

    Chen, Fei; Dong, Wei; Zhang, Jiawei; Guo, Xinyue; Chen, Junhao; Wang, Zhengjia; Lin, Zhenguo; Tang, Haibao; Zhang, Liangsheng

    2018-01-01

    Angiosperms, the flowering plants, provide the essential resources for human life, such as food, energy, oxygen, and materials. They also promoted the evolution of human, animals, and the planet earth. Despite the numerous advances in genome reports or sequencing technologies, no review covers all the released angiosperm genomes and the genome databases for data sharing. Based on the rapid advances and innovations in the database reconstruction in the last few years, here we provide a comprehensive review for three major types of angiosperm genome databases, including databases for a single species, for a specific angiosperm clade, and for multiple angiosperm species. The scope, tools, and data of each type of databases and their features are concisely discussed. The genome databases for a single species or a clade of species are especially popular for specific group of researchers, while a timely-updated comprehensive database is more powerful for address of major scientific mysteries at the genome scale. Considering the low coverage of flowering plants in any available database, we propose construction of a comprehensive database to facilitate large-scale comparative studies of angiosperm genomes and to promote the collaborative studies of important questions in plant biology.

  20. Linking abnormal mitosis to the acquisition of DNA damage

    Science.gov (United States)

    Pellman, David

    2012-01-01

    Cellular defects that impair the fidelity of mitosis promote chromosome missegregation and aneuploidy. Increasing evidence reveals that errors in mitosis can also promote the direct and indirect acquisition of DNA damage and chromosome breaks. Consequently, deregulated cell division can devastate the integrity of the normal genome and unleash a variety of oncogenic stimuli that may promote transformation. Recent work has shed light on the mechanisms that link abnormal mitosis with the development of DNA damage, how cells respond to such affronts, and the potential impact on tumorigenesis. PMID:23229895

  1. Immunoassay of DNA damage

    International Nuclear Information System (INIS)

    Gasparro, F.P.; Santella, R.M.

    1988-01-01

    The direct photomodification of DNA by ultraviolet light or the photo-induced addition of exogenous compounds to DNA components results in alterations of DNA structure ranging from subtle to profound. There are two consequences of these conformational changes. First, cells in which the DNA has been damaged are capable of executing repair steps. Second, the DNA which is usually of very low immunogenicity now becomes highly antigenic. This latter property has allowed the production of a series of monoclonal antibodies that recognize photo-induced DNA damage. Monoclonal antibodies have been generated that recognize the 4',5'-monoadduct and the crosslink of 8-methoxypsoralen in DNA. In addition, another antibody has been prepared which recognizes the furan-side monoadduct of 6,4,4'-trimethylangelicin in DNA. These monoclonal antibodies have been characterized as to sensitivity and specificity using non-competitive and competitive enzyme-linked-immunosorbent assays (ELISA). (author)

  2. Neutron induced radiation damage

    International Nuclear Information System (INIS)

    Williams, M.M.R.

    1977-01-01

    We derive a general expression for the number of displaced atoms of type j caused by a primary knock-on of type i. The Kinchin-Pease model is used, but considerably generalised to allow for realistic atomic potentials. Two cases are considered in detail: the single particle problem causing a cascade and the neutron initiated problem which leads to multiple subcascades. Numerical results have been obtained for a variety of scattering laws. An important conclusion is that neutron initiated damage is much more severe than atom-initiated damage and leads to the number of displaced atoms being a factor of (A+1) 2 /4A larger than the single primary knock-on theory predicts. A is the ratio of the atomic mass to the neutron mass. The importance of this result to the theory of neutron sputtering is explained. (orig.) [de

  3. Immunoassay of DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Gasparro, F P; Santella, R M

    1988-09-01

    The direct photomodification of DNA by ultraviolet light or the photo-induced addition of exogenous compounds to DNA components results in alterations of DNA structure ranging from subtle to profound. There are two consequences of these conformational changes. First, cells in which the DNA has been damaged are capable of executing repair steps. Second, the DNA which is usually of very low immunogenicity now becomes highly antigenic. This latter property has allowed the production of a series of monoclonal antibodies that recognize photo-induced DNA damage. Monoclonal antibodies have been generated that recognize the 4',5'-monoadduct and the crosslink of 8-methoxypsoralen in DNA. In addition, another antibody has been prepared which recognizes the furan-side monoadduct of 6,4,4'-trimethylangelicin in DNA. These monoclonal antibodies have been characterized as to sensitivity and specificity using non-competitive and competitive enzyme-linked-immunosorbent assays (ELISA).

  4. Radiation damage in DNA

    International Nuclear Information System (INIS)

    Lafleur, V.

    1978-01-01

    A number of experiments are described with the purpose to obtain a better insight in the chemical nature and the biological significance of radiation-induced damage in DNA, with some emphasis on the significance of alkali-labile sites. It is shown that not only reactions of OH radicals but also of H radicals introduce breaks and other inactivating damage in single-standed phiX174 DNA. It is found that phosphate buffer is very suitable for the study of the reactions of H radicals with DNA, as the H 2 PO 4 - ions convert the hydrated electrons into H radicals. The hydrated electron, which does react with DNA, does not cause a detectable inactivation. (Auth.)

  5. Genome evolution during progression to breast cancer

    KAUST Repository

    Newburger, D. E.

    2013-04-08

    Cancer evolution involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Early neoplasias, which are often found concurrently with carcinomas and are histologically distinguishable from normal breast tissue, are less advanced in phenotype than carcinomas and are thought to represent precursor stages. To elucidate their role in cancer evolution we performed comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients, for a total of 31 samples. By using somatic mutations as lineage markers we built trees that relate the tissue samples within each patient. On the basis of these lineage trees we inferred the order, timing, and rates of genomic events. In four out of six cases, an early neoplasia and the carcinoma share a mutated common ancestor with recurring aneuploidies, and in all six cases evolution accelerated in the carcinoma lineage. Transition spectra of somatic mutations are stable and consistent across cases, suggesting that accumulation of somatic mutations is a result of increased ancestral cell division rather than specific mutational mechanisms. In contrast to highly advanced tumors that are the focus of much of the current cancer genome sequencing, neither the early neoplasia genomes nor the carcinomas are enriched with potentially functional somatic point mutations. Aneuploidies that occur in common ancestors of neoplastic and tumor cells are the earliest events that affect a large number of genes and may predispose breast tissue to eventual development of invasive carcinoma.

  6. Genome evolution during progression to breast cancer

    KAUST Repository

    Newburger, D. E.; Kashef-Haghighi, D.; Weng, Z.; Salari, R.; Sweeney, R. T.; Brunner, A. L.; Zhu, S. X.; Guo, X.; Varma, S.; Troxell, M. L.; West, R. B.; Batzoglou, S.; Sidow, A.

    2013-01-01

    Cancer evolution involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Early neoplasias, which are often found concurrently with carcinomas and are histologically distinguishable from normal breast tissue, are less advanced in phenotype than carcinomas and are thought to represent precursor stages. To elucidate their role in cancer evolution we performed comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients, for a total of 31 samples. By using somatic mutations as lineage markers we built trees that relate the tissue samples within each patient. On the basis of these lineage trees we inferred the order, timing, and rates of genomic events. In four out of six cases, an early neoplasia and the carcinoma share a mutated common ancestor with recurring aneuploidies, and in all six cases evolution accelerated in the carcinoma lineage. Transition spectra of somatic mutations are stable and consistent across cases, suggesting that accumulation of somatic mutations is a result of increased ancestral cell division rather than specific mutational mechanisms. In contrast to highly advanced tumors that are the focus of much of the current cancer genome sequencing, neither the early neoplasia genomes nor the carcinomas are enriched with potentially functional somatic point mutations. Aneuploidies that occur in common ancestors of neoplastic and tumor cells are the earliest events that affect a large number of genes and may predispose breast tissue to eventual development of invasive carcinoma.

  7. Radiation damage of uranium

    International Nuclear Information System (INIS)

    Lazarevic, Dj.

    1966-11-01

    Study of radiation damage covered the following: Kinetics of electric resistance of uranium and uranium alloy with 1% of molybdenum dependent on the second phase and burnup rate; Study of gas precipitation and diffusion of bubbles by transmission electron microscopy; Numerical analysis of the influence of defects distribution and concentration on the rare gas precipitation in uranium; study of thermal sedimentation of uranium alloy with molybdenum; diffusion of rare gas in metal by gas chromatography method

  8. Cavitation damage of ceramics

    International Nuclear Information System (INIS)

    Kovalenko, V.I.; Marinin, V.G.

    1988-01-01

    Consideration is given to results of investigation of ceramic material damage under the effect of cavitation field on their surface, formed in water under the face of exponential concentrator, connected with ultrasonic generator UZY-3-0.4. Amplitude of vibrations of concentrator face (30+-2)x10 -6 m, frequency-21 kHz. It was established that ceramics resistance to cavitation effect correlated with the product of critical of stress intensity factor and material hardness

  9. Nondestructive damage detection and evaluation technique for seismically damaged structures

    Science.gov (United States)

    Adachi, Yukio; Unjoh, Shigeki; Kondoh, Masuo; Ohsumi, Michio

    1999-02-01

    The development of quantitative damage detection and evaluation technique, and damage detection technique for invisible damages of structures are required according to the lessons from the 1995 Hyogo-ken Nanbu earthquake. In this study, two quantitative damage sensing techniques for highway bridge structures are proposed. One method is to measure the change of vibration characteristics of the bridge structure. According to the damage detection test for damaged bridge column by shaking table test, this method can successfully detect the vibration characteristic change caused by damage progress due to increment excitations. The other method is to use self-diagnosis intelligent materials. According to the reinforced concrete beam specimen test, the second method can detect the damage by rupture of intelligent sensors, such as optical fiber or carbon fiber reinforced plastic rod.

  10. Ion irradiation and biomolecular radiation damage II. Indirect effect

    OpenAIRE

    Wang, Wei; Yu, Zengliang; Su, Wenhui

    2010-01-01

    It has been reported that damage of genome in a living cell by ionizing radiation is about one-third direct and two-thirds indirect. The former which has been introduced in our last paper, concerns direct energy deposition and ionizing reactions in the biomolecules; the latter results from radiation induced reactive species (mainly radicals) in the medium (mainly water) surrounding the biomolecules. In this review, a short description of ion implantation induced radical formation in water is ...

  11. DNA damage caused by ionizing radiation

    International Nuclear Information System (INIS)

    Sachs, R.K.; Peili Chen; Hahnfeldt, P.J.; Klatky, L.R.

    1992-01-01

    A survey is given of continuous-time Markov chain models for ionizing radiation damage to the genome of mammalian cells. In such models, immediate damage induced by the radiation is regarded as a batch-Poisson arrival process of DNA double-strand breaks (DSBs). Enzymatic modification of the immediate damage is modeled as a Markov process similar to those described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete-exchange model. The model postulates that, after being induced by radiation, DSBs subsequently either undergo enzymatically mediated restitution (repair) or participate pairwise in chromosome exchanges. Some of the exchanges make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. Methods for analyzing the Markov chains include using an approximate model for expected values, the discrete-time Markov chain embedded at transitions, partial differential equations for generating functions, normal perturbation theory, singular perturbation theory with scaling, numerical computations, and certain matrix methods that combine Perron-Frobenius theory with variational estimates. Applications to experimental results on expected values, variances, and statistical distributions of DNA lesions are briefly outlined. Continuous-time Markov chains are the most systematic of those radiation damage models that treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g., ignore diffusion limitations). They contain virtually all other relevant homogeneous models and semiempirical summaries as special cases, limiting cases, or approximations. However, the Markov models do not seem to be well suited for studying spatial dependence of DSB interactions. 51 refs., 5 figs

  12. Military Robotics and Collateral Damage

    National Research Council Canada - National Science Library

    Kott, Robert Douglass ;Alexander

    2004-01-01

    .... Such concepts raise important questions in terms of their impact on collateral damage. In a broader context, western warfare in general places a continuously growing emphasis on issues of collateral damage...

  13. Bioinformatics decoding the genome

    CERN Multimedia

    CERN. Geneva; Deutsch, Sam; Michielin, Olivier; Thomas, Arthur; Descombes, Patrick

    2006-01-01

    Extracting the fundamental genomic sequence from the DNA From Genome to Sequence : Biology in the early 21st century has been radically transformed by the availability of the full genome sequences of an ever increasing number of life forms, from bacteria to major crop plants and to humans. The lecture will concentrate on the computational challenges associated with the production, storage and analysis of genome sequence data, with an emphasis on mammalian genomes. The quality and usability of genome sequences is increasingly conditioned by the careful integration of strategies for data collection and computational analysis, from the construction of maps and libraries to the assembly of raw data into sequence contigs and chromosome-sized scaffolds. Once the sequence is assembled, a major challenge is the mapping of biologically relevant information onto this sequence: promoters, introns and exons of protein-encoding genes, regulatory elements, functional RNAs, pseudogenes, transposons, etc. The methodological ...

  14. Genomic research in Eucalyptus.

    Science.gov (United States)

    Poke, Fiona S; Vaillancourt, René E; Potts, Brad M; Reid, James B

    2005-09-01

    Eucalyptus L'Hérit. is a genus comprised of more than 700 species that is of vital importance ecologically to Australia and to the forestry industry world-wide, being grown in plantations for the production of solid wood products as well as pulp for paper. With the sequencing of the genomes of Arabidopsis thaliana and Oryza sativa and the recent completion of the first tree genome sequence, Populus trichocarpa, attention has turned to the current status of genomic research in Eucalyptus. For several eucalypt species, large segregating families have been established, high-resolution genetic maps constructed and large EST databases generated. Collaborative efforts have been initiated for the integration of diverse genomic projects and will provide the framework for future research including exploiting the sequence of the entire eucalypt genome which is currently being sequenced. This review summarises the current position of genomic research in Eucalyptus and discusses the direction of future research.

  15. X-Ray induced DNA damage – why use plants?

    Directory of Open Access Journals (Sweden)

    John William Einset

    2015-06-01

    Full Text Available The comet assay was used to monitor DNA repair after X-ray exposures caused by 0.2-15 Gy. A clear distinction in the time course of DNA repair after 2 Gy was observed with an early ‘rapid phase’, lasting 20-40 minutes, being followed by a ‘slow phase’ which actually consists of a period of negligible repair and then rapid repair during 140-160 minutes. The fact that homozygous mutants for both ATM and BRCA1 fail to repair DNA completely during 3 hours after 2 Gy exposures indicates that repair processes occurring during the ‘slow phase’ involve ds breaks in DNA. Both BRCA1 and Rad51 expression are strongly upregulated by X-rays in Arabidopsis. Rye grass, Norway spruce and Sawara cypress also have ‘slow phase’ repair similar to Arabidopsis, suggesting that the requisite enzymes have to be induced in these plants as well. To look at the effect of genome size in relation to sensitivity to DNA damage, we exposed isolated nuclei from Norway spruce (19.2 Gbp genome, celery (14.1 Gbp, spinach (12.6 Gbp Sawara cypress (8.9 Gbp, lettuce (2.6 Gbp and Arabidopsis (0.135 Gbp to X-rays. After a 1 Gy exposure, a linear relationship was seen between % tails and genome size, confirming the idea that larger genomes are more sensitive to X-ray damage.

  16. Radiation damage in semiconductor detectors

    International Nuclear Information System (INIS)

    Kraner, H.W.

    1981-12-01

    A survey is presented of the important damage-producing interactions in semiconductor detectors and estimates of defect numbers are made for MeV protons, neutrons and electrons. Damage effects of fast neutrons in germanium gamma ray spectrometers are given in some detail. General effects in silicon detectors are discussed and damage constants and their relationship to leakage current is introduced

  17. Seeds as emerging hotspot for maintenance of genome stability

    Czech Academy of Sciences Publication Activity Database

    Diaz, Mariana; Pečinka, Aleš

    2017-01-01

    Roč. 82, č. 5 (2017), s. 467-470 ISSN 0011-4545 Institutional support: RVO:61389030 Keywords : Chromatin * Chromosome * DNA damage repair * Genome stability * Seed * Structural maintenance of chromosome Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 0.913, year: 2016

  18. Genome-wide mapping of DNA strand breaks.

    Directory of Open Access Journals (Sweden)

    Frédéric Leduc

    Full Text Available Determination of cellular DNA damage has so far been limited to global assessment of genome integrity whereas nucleotide-level mapping has been restricted to specific loci by the use of specific primers. Therefore, only limited DNA sequences can be studied and novel regions of genomic instability can hardly be discovered. Using a well-characterized yeast model, we describe a straightforward strategy to map genome-wide DNA strand breaks without compromising nucleotide-level resolution. This technique, termed "damaged DNA immunoprecipitation" (dDIP, uses immunoprecipitation and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labeling (TUNEL to capture DNA at break sites. When used in combination with microarray or next-generation sequencing technologies, dDIP will allow researchers to map genome-wide DNA strand breaks as well as other types of DNA damage and to establish a clear profiling of altered genes and/or intergenic sequences in various experimental conditions. This mapping technique could find several applications for instance in the study of aging, genotoxic drug screening, cancer, meiosis, radiation and oxidative DNA damage.

  19. Genome sequence of Stachybotrys chartarum Strain 51-11

    Science.gov (United States)

    Stachybotrys chartarum strain 51-11 genome was sequenced by shotgun sequencing utilizing Illumina Hiseq 2000 and PacBio long read technology. Since Stachybotrys chartarum has been implicated in health impacts within water-damaged buildings, any information extracted from the geno...

  20. Genome packaging in viruses

    OpenAIRE

    Sun, Siyang; Rao, Venigalla B.; Rossmann, Michael G.

    2010-01-01

    Genome packaging is a fundamental process in a viral life cycle. Many viruses assemble preformed capsids into which the genomic material is subsequently packaged. These viruses use a packaging motor protein that is driven by the hydrolysis of ATP to condense the nucleic acids into a confined space. How these motor proteins package viral genomes had been poorly understood until recently, when a few X-ray crystal structures and cryo-electron microscopy structures became available. Here we discu...

  1. Tokamak ARC damage

    International Nuclear Information System (INIS)

    Murray, J.G.; Gorker, G.E.

    1985-01-01

    Tokamak fusion reactors will have large plasma currents of approximately 10 MA with hundreds of megajoules stored in the magnetic fields. When a major plasma instability occurs, the disruption of the plasma current induces voltage in the adjacent conducting structures, giving rise to large transient currents. The induced voltages may be sufficiently high to cause arcing across sector gaps or from one protruding component to another. This report reviews a tokamak arcing scenario and provides guidelines for designing tokamaks to minimize the possibility of arc damage

  2. Fatigue Damage in Wood

    DEFF Research Database (Denmark)

    Clorius, Christian Odin; Pedersen, Martin Bo Uhre; Hoffmeyer, Preben

    1996-01-01

    An investigation of fatigue failure in wood subjected to load cycles in compression parallel to grain is presented. Fatigue failure is found to depend both on the total time under load and on the number of cycles.Recent accelerated fatigue research on wood is reviewed, and a discrepancy between...... to 10 Hz are used. The number of cycles to failure is found to be a poor measure of the fatigue performance of wood. Creep, maximum strain, stiffness and work are monitored throughout the fatigue tests. Accumulated creep is suggested identified with damage and a correlation between stiffness reduction...

  3. Contextualizing aquired brain damage

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2014-01-01

    Contextualizing aquired brain damage Traditional approaches study ’communicational problems’ often in a discourse of disabledness or deficitness. With an ontology of communcation as something unique and a presupposed uniqueness of each one of us, how could an integrational approach (Integrational...... for people with aquired brain injuries will be presented and comparatively discussed in a traditional versus an integrational perspective. Preliminary results and considerations on ”methods” and ”participation” from this study will be presented along with an overview of the project's empirical data....

  4. Severe fuel damage projects

    International Nuclear Information System (INIS)

    Sdouz, G.

    1987-10-01

    After the descriptions of the generation of a Severe Fuel Damage Accident in a LWR the hypothetical course of such an accident is explained. Then the most significant projects are described. At each project the experimental facility, the most important results and the concluding models and codes are discussed. The selection of the projects is concentrated on the German Projekt Nukleare Sicherheit (PNS), tests performed at the Idaho National Engineering Laboratory (INEL) and smaller projects in France and Great Britain. 25 refs., 26 figs. (Author)

  5. Tokamak ARC damage

    Energy Technology Data Exchange (ETDEWEB)

    Murray, J.G.; Gorker, G.E.

    1985-01-01

    Tokamak fusion reactors will have large plasma currents of approximately 10 MA with hundreds of megajoules stored in the magnetic fields. When a major plasma instability occurs, the disruption of the plasma current induces voltage in the adjacent conducting structures, giving rise to large transient currents. The induced voltages may be sufficiently high to cause arcing across sector gaps or from one protruding component to another. This report reviews a tokamak arcing scenario and provides guidelines for designing tokamaks to minimize the possibility of arc damage.

  6. gb4gv: a genome browser for geminivirus

    Directory of Open Access Journals (Sweden)

    Eric S. Ho

    2017-04-01

    Full Text Available Background Geminiviruses (family Geminiviridae are prevalent plant viruses that imperil agriculture globally, causing serious damage to the livelihood of farmers, particularly in developing countries. The virus evolves rapidly, attributing to its single-stranded genome propensity, resulting in worldwide circulation of diverse and viable genomes. Genomics is a prominent approach taken by researchers in elucidating the infectious mechanism of the virus. Currently, the NCBI Viral Genome website is a popular repository of viral genomes that conveniently provides researchers a centralized data source of genomic information. However, unlike the genome of living organisms, viral genomes most often maintain peculiar characteristics that fit into no single genome architecture. By imposing a unified annotation scheme on the myriad of viral genomes may downplay their hallmark features. For example, the viron of begomoviruses prevailing in America encapsulates two similar-sized circular DNA components and both are required for systemic infection of plants. However, the bipartite components are kept separately in NCBI as individual genomes with no explicit association in linking them. Thus, our goal is to build a comprehensive Geminivirus genomics database, namely gb4gv, that not only preserves genomic characteristics of the virus, but also supplements biologically relevant annotations that help to interrogate this virus, for example, the targeted host, putative iterons, siRNA targets, etc. Methods We have employed manual and automatic methods to curate 508 genomes from four major genera of Geminiviridae, and 161 associated satellites obtained from NCBI RefSeq and PubMed databases. Results These data are available for free access without registration from our website. Besides genomic content, our website provides visualization capability inherited from UCSC Genome Browser. Discussion With the genomic information readily accessible, we hope that our database

  7. SMC5/6: Shaping, protecting and preparing the genome for safe reproduction

    NARCIS (Netherlands)

    Verver, D.E.

    2015-01-01

    SMC5/6 is one of the three structural maintenance of chromosomes (SMC) protein complexes and is involved in numerous processes involving DNA damage repair and genomic integrity maintenance. Although such DNA damage control mechanisms, together with highly dynamic changes in chromatin composition and

  8. Between Two Fern Genomes

    Science.gov (United States)

    2014-01-01

    Ferns are the only major lineage of vascular plants not represented by a sequenced nuclear genome. This lack of genome sequence information significantly impedes our ability to understand and reconstruct genome evolution not only in ferns, but across all land plants. Azolla and Ceratopteris are ideal and complementary candidates to be the first ferns to have their nuclear genomes sequenced. They differ dramatically in genome size, life history, and habit, and thus represent the immense diversity of extant ferns. Together, this pair of genomes will facilitate myriad large-scale comparative analyses across ferns and all land plants. Here we review the unique biological characteristics of ferns and describe a number of outstanding questions in plant biology that will benefit from the addition of ferns to the set of taxa with sequenced nuclear genomes. We explain why the fern clade is pivotal for understanding genome evolution across land plants, and we provide a rationale for how knowledge of fern genomes will enable progress in research beyond the ferns themselves. PMID:25324969

  9. Causes of genome instability

    DEFF Research Database (Denmark)

    Langie, Sabine A S; Koppen, Gudrun; Desaulniers, Daniel

    2015-01-01

    function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make......Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus...

  10. Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  11. MIPS plant genome information resources.

    Science.gov (United States)

    Spannagl, Manuel; Haberer, Georg; Ernst, Rebecca; Schoof, Heiko; Mayer, Klaus F X

    2007-01-01

    The Munich Institute for Protein Sequences (MIPS) has been involved in maintaining plant genome databases since the Arabidopsis thaliana genome project. Genome databases and analysis resources have focused on individual genomes and aim to provide flexible and maintainable data sets for model plant genomes as a backbone against which experimental data, for example from high-throughput functional genomics, can be organized and evaluated. In addition, model genomes also form a scaffold for comparative genomics, and much can be learned from genome-wide evolutionary studies.

  12. Essential Function of Dicer in Resolving DNA Damage in the Rapidly Dividing Cells of the Developing and Malignant Cerebellum

    Directory of Open Access Journals (Sweden)

    Vijay Swahari

    2016-01-01

    Full Text Available Maintenance of genomic integrity is critical during neurodevelopment, particularly in rapidly dividing cerebellar granule neuronal precursors that experience constitutive replication-associated DNA damage. As Dicer was recently recognized to have an unexpected function in the DNA damage response, we examined whether Dicer was important for preserving genomic integrity in the developing brain. We report that deletion of Dicer in the developing mouse cerebellum resulted in the accumulation of DNA damage leading to cerebellar progenitor degeneration, which was rescued with p53 deficiency; deletion of DGCR8 also resulted in similar DNA damage and cerebellar degeneration. Dicer deficiency also resulted in DNA damage and death in other rapidly dividing cells including embryonic stem cells and the malignant cerebellar progenitors in a mouse model of medulloblastoma. Together, these results identify an essential function of Dicer in resolving the spontaneous DNA damage that occurs during the rapid proliferation of developmental progenitors and malignant cells.

  13. Thoracic damage control surgery.

    Science.gov (United States)

    Gonçalves, Roberto; Saad, Roberto

    2016-01-01

    The damage control surgery came up with the philosophy of applying essential maneuvers to control bleeding and abdominal contamination in trauma patients who are within the limits of their physiological reserves. This concept was extended to thoracic injuries, where relatively simple maneuvers can shorten operative time of in extremis patients. This article aims to revise the various damage control techniques in thoracic organs that must be known to the surgeon engaged in emergency care. RESUMO A cirurgia de controle de danos surgiu com a filosofia de se aplicar manobras essenciais para controle de sangramento e contaminação abdominal, em doentes traumatizados, nos limites de suas reservas fisiológicas. Este conceito se estendeu para as lesões torácicas, onde manobras relativamente simples, podem abreviar o tempo operatório de doentes in extremis. Este artigo tem como objetivo, revisar as diversas técnicas de controle de dano em órgãos torácicos, que devem ser de conhecimento do cirurgião que atua na emergência.

  14. Hydrogen damage in stainless steel

    International Nuclear Information System (INIS)

    Caskey, G.R. Jr.

    1981-01-01

    Hydrogen damage has been studied in a wide variety of stainless steels. Both internal and external hydrogen damage were evaluated by ductility or J-integral under rising tensile loads and by fractography. Analysis of the data has emphasized the potential effects of strain-induced martensite on hydrogen damage. Strain-induced martensite was neither necessary nor sufficient for hydrogen damage in the alloys studied. Neither ductility loss nor fracture-mode change correlated generally with martensite formation. Alloy composition, particularly nickel and nitrogen contents, was the primary factor in resistance to hydrogen damage. Thermomechanical processing, however, could alter the degree of hydrogen damage in an alloy and was critical for optimizing resistance to hydrogen damage. 10 figures, 10 tables

  15. The nucleosome: orchestrating DNA damage signaling and repair within chromatin.

    Science.gov (United States)

    Agarwal, Poonam; Miller, Kyle M

    2016-10-01

    DNA damage occurs within the chromatin environment, which ultimately participates in regulating DNA damage response (DDR) pathways and repair of the lesion. DNA damage activates a cascade of signaling events that extensively modulates chromatin structure and organization to coordinate DDR factor recruitment to the break and repair, whilst also promoting the maintenance of normal chromatin functions within the damaged region. For example, DDR pathways must avoid conflicts between other DNA-based processes that function within the context of chromatin, including transcription and replication. The molecular mechanisms governing the recognition, target specificity, and recruitment of DDR factors and enzymes to the fundamental repeating unit of chromatin, i.e., the nucleosome, are poorly understood. Here we present our current view of how chromatin recognition by DDR factors is achieved at the level of the nucleosome. Emerging evidence suggests that the nucleosome surface, including the nucleosome acidic patch, promotes the binding and activity of several DNA damage factors on chromatin. Thus, in addition to interactions with damaged DNA and histone modifications, nucleosome recognition by DDR factors plays a key role in orchestrating the requisite chromatin response to maintain both genome and epigenome integrity.

  16. Iron and genome stability: An update

    International Nuclear Information System (INIS)

    Prá, Daniel; Franke, Silvia Isabel Rech; Henriques, João Antonio Pêgas; Fenech, Michael

    2012-01-01

    Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7 mg/day to 18 mg/day depending on life stage and gender. Pregnant women need 27 mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40–45 mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20 mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

  17. Iron and genome stability: An update

    Energy Technology Data Exchange (ETDEWEB)

    Pra, Daniel, E-mail: daniel_pra@yahoo.com [PPG em Promocao da Saude, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS (Brazil); PPG em Saude e Comportamento, Universidade Catolica de Pelotas, Pelotas, RS (Brazil); Franke, Silvia Isabel Rech [PPG em Promocao da Saude, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS (Brazil); Henriques, Joao Antonio Pegas [Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS (Brazil); Fenech, Michael [CSIRO Food and Nutritional Sciences, Adelaide, SA (Australia)

    2012-05-01

    Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7 mg/day to 18 mg/day depending on life stage and gender. Pregnant women need 27 mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40-45 mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20 mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

  18. Computational genomics of hyperthermophiles

    NARCIS (Netherlands)

    Werken, van de H.J.G.

    2008-01-01

    With the ever increasing number of completely sequenced prokaryotic genomes and the subsequent use of functional genomics tools, e.g. DNA microarray and proteomics, computational data analysis and the integration of microbial and molecular data is inevitable. This thesis describes the computational

  19. Safeguarding genome integrity

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G

    2012-01-01

    Mechanisms that preserve genome integrity are highly important during the normal life cycle of human cells. Loss of genome protective mechanisms can lead to the development of diseases such as cancer. Checkpoint kinases function in the cellular surveillance pathways that help cells to cope with D...

  20. Human genome I

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    An international conference, Human Genome I, was held Oct. 2-4, 1989 in San Diego, Calif. Selected speakers discussed: Current Status of the Genome Project; Technique Innovations; Interesting regions; Applications; and Organization - Different Views of Current and Future Science and Procedures. Posters, consisting of 119 presentations, were displayed during the sessions. 119 were indexed for inclusion to the Energy Data Base

  1. Damage scenarios and an onboard support system for damaged ships

    Directory of Open Access Journals (Sweden)

    Choi Jin

    2014-06-01

    Full Text Available Although a safety assessment of damaged ships, which considers environmental conditions such as waves and wind, is important in both the design and operation phases of ships, in Korea, rules or guidelines to conduct such assessments are not yet developed. However, NATO and European maritime societies have developed guidelines for a safety assessment. Therefore, it is required to develop rules or guidelines for safety assessments such as the Naval Ship Code (NSC of NATO. Before the safety assessment of a damaged ship can be performed, the available damage scenarios must be developed and the safety assessment criteria must be established. In this paper, the parameters related to damage by accidents are identified and categorized when developing damage scenarios. The need for damage safety assessment criteria is discussed, and an example is presented. In addition, a concept and specifications for the DB-based supporting system, which is used in the operation phases, are proposed.

  2. Rumen microbial genomics

    International Nuclear Information System (INIS)

    Morrison, M.; Nelson, K.E.

    2005-01-01

    Improving microbial degradation of plant cell wall polysaccharides remains one of the highest priority goals for all livestock enterprises, including the cattle herds and draught animals of developing countries. The North American Consortium for Genomics of Fibrolytic Ruminal Bacteria was created to promote the sequencing and comparative analysis of rumen microbial genomes, offering the potential to fully assess the genetic potential in a functional and comparative fashion. It has been found that the Fibrobacter succinogenes genome encodes many more endoglucanases and cellodextrinases than previously isolated, and several new processive endoglucanases have been identified by genome and proteomic analysis of Ruminococcus albus, in addition to a variety of strategies for its adhesion to fibre. The ramifications of acquiring genome sequence data for rumen microorganisms are profound, including the potential to elucidate and overcome the biochemical, ecological or physiological processes that are rate limiting for ruminal fibre degradation. (author)

  3. Microbial Genomes Multiply

    Science.gov (United States)

    Doolittle, Russell F.

    2002-01-01

    The publication of the first complete sequence of a bacterial genome in 1995 was a signal event, underscored by the fact that the article has been cited more than 2,100 times during the intervening seven years. It was a marvelous technical achievement, made possible by automatic DNA-sequencing machines. The feat is the more impressive in that complete genome sequencing has now been adopted in many different laboratories around the world. Four years ago in these columns I examined the situation after a dozen microbial genomes had been completed. Now, with upwards of 60 microbial genome sequences determined and twice that many in progress, it seems reasonable to assess just what is being learned. Are new concepts emerging about how cells work? Have there been practical benefits in the fields of medicine and agriculture? Is it feasible to determine the genomic sequence of every bacterial species on Earth? The answers to these questions maybe Yes, Perhaps, and No, respectively.

  4. Musa sebagai Model Genom

    Directory of Open Access Journals (Sweden)

    RITA MEGIA

    2005-12-01

    Full Text Available During the meeting in Arlington, USA in 2001, the scientists grouped in PROMUSA agreed with the launching of the Global Musa Genomics Consortium. The Consortium aims to apply genomics technologies to the improvement of this important crop. These genome projects put banana as the third model species after Arabidopsis and rice that will be analyzed and sequenced. Comparing to Arabidopsis and rice, banana genome provides a unique and powerful insight into structural and in functional genomics that could not be found in those two species. This paper discussed these subjects-including the importance of banana as the fourth main food in the world, the evolution and biodiversity of this genetic resource and its parasite.

  5. The genome editing revolution

    DEFF Research Database (Denmark)

    Stella, Stefano; Montoya, Guillermo

    2016-01-01

    -Cas system has become the main tool for genome editing in many laboratories. Currently the targeted genome editing technology has been used in many fields and may be a possible approach for human gene therapy. Furthermore, it can also be used to modifying the genomes of model organisms for studying human......In the last 10 years, we have witnessed a blooming of targeted genome editing systems and applications. The area was revolutionized by the discovery and characterization of the transcription activator-like effector proteins, which are easier to engineer to target new DNA sequences than...... sequence). This ribonucleoprotein complex protects bacteria from invading DNAs, and it was adapted to be used in genome editing. The CRISPR ribonucleic acid (RNA) molecule guides to the specific DNA site the Cas9 nuclease to cleave the DNA target. Two years and more than 1000 publications later, the CRISPR...

  6. Environmentally damaging electricity trade

    International Nuclear Information System (INIS)

    Billette de Villemeur, Etienne; Pineau, Pierre-Olivier

    2010-01-01

    Electricity trade across regions is often considered welfare enhancing. We show in this paper that this should be reconsidered if environmental externalities are taken into account. We consider two cases where trade is beneficial, before accounting for environmental damages: first, when two regions with the same technology display some demand heterogeneity; second when one region endowed with hydropower arbitrages with its 'thermal' neighbor. Our results show that under reasonable demand and supply elasticities, trade comes with an additional environmental cost. This calls for integrating environmental externalities into market reforms when redesigning the electricity sector. Two North American applications illustrate our results: trade between Pennsylvania and New York, and trade between hydro-rich Quebec and New York.

  7. Vasectomy and psychosexual damage.

    Science.gov (United States)

    Savage, P M

    1972-11-01

    The director of the Family Planning Project of the San Bernardino County (California) Health Department reviews the results of a questionnaire completed by 300 husbands and their wives 6 months to 1 year after vasectomy. The replies indicated psychosexual damage from vasectomy is virtually nonexistent. 100% of the males reported an enhanced or unchanged sense of masculinity. Vasectomy clinics have been conducted by the San Bernardino County Health Department since August 1970. More than 1000 vasectomies have been completed. Vasectomies are currently being performed at a rate of 12/week. Prevasectomy group counseling should inform couples of 1) the physiological mechanisms involved, 2) the situational nature of any psychologic changes, and 3) the probability of irreversibility of the procedure.

  8. Environmentally damaging electricity trade

    Energy Technology Data Exchange (ETDEWEB)

    Billette de Villemeur, Etienne [Toulouse School of Economics (IDEI and GREMAQ) (France); Pineau, Pierre-Olivier [HEC Montreal (Canada)

    2010-03-15

    Electricity trade across regions is often considered welfare enhancing. We show in this paper that this should be reconsidered if environmental externalities are taken into account. We consider two cases where trade is beneficial, before accounting for environmental damages: first, when two regions with the same technology display some demand heterogeneity; second when one region endowed with hydropower arbitrages with its ''thermal'' neighbor. Our results show that under reasonable demand and supply elasticities, trade comes with an additional environmental cost. This calls for integrating environmental externalities into market reforms when redesigning the electricity sector. Two North American applications illustrate our results: trade between Pennsylvania and New York, and trade between hydro-rich Quebec and New York. (author)

  9. Tactical Damage Control Resuscitation.

    Science.gov (United States)

    Fisher, Andrew D; Miles, Ethan A; Cap, Andrew P; Strandenes, Geir; Kane, Shawn F

    2015-08-01

    Recently the Committee on Tactical Combat Casualty Care changed the guidelines on fluid use in hemorrhagic shock. The current strategy for treating hemorrhagic shock is based on early use of components: Packed Red Blood Cells (PRBCs), Fresh Frozen Plasma (FFP) and platelets in a 1:1:1 ratio. We suggest that lack of components to mimic whole blood functionality favors the use of Fresh Whole Blood in managing hemorrhagic shock on the battlefield. We present a safe and practical approach for its use at the point of injury in the combat environment called Tactical Damage Control Resuscitation. We describe pre-deployment preparation, assessment of hemorrhagic shock, and collection and transfusion of fresh whole blood at the point of injury. By approaching shock with goal-directed therapy, it is possible to extend the period of survivability in combat casualties. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  10. Quantitative analysis of gene-specific DNA damage in human spermatozoa

    International Nuclear Information System (INIS)

    Sawyer, Dennis E.; Mercer, Belinda G.; Wiklendt, Agnieszka M.; Aitken, R. John

    2003-01-01

    Recent studies have suggested that human spermatozoa are highly susceptible to DNA damage induced by oxidative stress. However, a detailed analysis of the precise nature of this damage and the extent to which it affects the mitochondrial and nuclear genomes has not been reported. To induce DNA damage, human spermatozoa were treated in vitro with hydrogen peroxide (H 2 O 2 ; 0-5 mM) or iron (as Fe(II)SO 4 , 0-500 μM). Quantitative PCR (QPCR) was used to measure DNA damage in individual nuclear genes (hprt, β-pol and β-globin) and mitochondrial DNA. Single strand breaks were also assessed by alkaline gel electrophoresis. H 2 O 2 was found to be genotoxic toward spermatozoa at concentrations as high as 1.25 mM, but DNA damage was not detected in these cells with lower concentrations of H 2 O 2 . The mitochondrial genome of human spermatozoa was significantly (P 2 O 2 -induced DNA damage than the nuclear genome. However, both nDNA and mtDNA in human spermatozoa were significantly (P<0.001) more resistant to damage than DNA from a variety of cell lines of germ cell and myoblastoid origin. Interestingly, significant DNA damage was also not detected in human spermatozoa treated with iron. These studies report, for the first time, quantitative measurements of DNA damage in specific genes of male germ cells, and challenge the commonly held belief that human spermatozoa are particularly vulnerable to DNA damage

  11. Multivariate pluvial flood damage models

    International Nuclear Information System (INIS)

    Van Ootegem, Luc; Verhofstadt, Elsy; Van Herck, Kristine; Creten, Tom

    2015-01-01

    Depth–damage-functions, relating the monetary flood damage to the depth of the inundation, are commonly used in the case of fluvial floods (floods caused by a river overflowing). We construct four multivariate damage models for pluvial floods (caused by extreme rainfall) by differentiating on the one hand between ground floor floods and basement floods and on the other hand between damage to residential buildings and damage to housing contents. We do not only take into account the effect of flood-depth on damage, but also incorporate the effects of non-hazard indicators (building characteristics, behavioural indicators and socio-economic variables). By using a Tobit-estimation technique on identified victims of pluvial floods in Flanders (Belgium), we take into account the effect of cases of reported zero damage. Our results show that the flood depth is an important predictor of damage, but with a diverging impact between ground floor floods and basement floods. Also non-hazard indicators are important. For example being aware of the risk just before the water enters the building reduces content damage considerably, underlining the importance of warning systems and policy in this case of pluvial floods. - Highlights: • Prediction of damage of pluvial floods using also non-hazard information • We include ‘no damage cases’ using a Tobit model. • The damage of flood depth is stronger for ground floor than for basement floods. • Non-hazard indicators are especially important for content damage. • Potential gain of policies that increase awareness of flood risks

  12. Multivariate pluvial flood damage models

    Energy Technology Data Exchange (ETDEWEB)

    Van Ootegem, Luc [HIVA — University of Louvain (Belgium); SHERPPA — Ghent University (Belgium); Verhofstadt, Elsy [SHERPPA — Ghent University (Belgium); Van Herck, Kristine; Creten, Tom [HIVA — University of Louvain (Belgium)

    2015-09-15

    Depth–damage-functions, relating the monetary flood damage to the depth of the inundation, are commonly used in the case of fluvial floods (floods caused by a river overflowing). We construct four multivariate damage models for pluvial floods (caused by extreme rainfall) by differentiating on the one hand between ground floor floods and basement floods and on the other hand between damage to residential buildings and damage to housing contents. We do not only take into account the effect of flood-depth on damage, but also incorporate the effects of non-hazard indicators (building characteristics, behavioural indicators and socio-economic variables). By using a Tobit-estimation technique on identified victims of pluvial floods in Flanders (Belgium), we take into account the effect of cases of reported zero damage. Our results show that the flood depth is an important predictor of damage, but with a diverging impact between ground floor floods and basement floods. Also non-hazard indicators are important. For example being aware of the risk just before the water enters the building reduces content damage considerably, underlining the importance of warning systems and policy in this case of pluvial floods. - Highlights: • Prediction of damage of pluvial floods using also non-hazard information • We include ‘no damage cases’ using a Tobit model. • The damage of flood depth is stronger for ground floor than for basement floods. • Non-hazard indicators are especially important for content damage. • Potential gain of policies that increase awareness of flood risks.

  13. Research for genetic instability of human genome

    Energy Technology Data Exchange (ETDEWEB)

    Hori, T.; Takahashi, E.; Tsuji, H.; Yamauchi, M. (National Inst. of Radiological Sciences, Chiba (Japan)); Murata, M.

    1992-01-01

    In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author).

  14. Research for genetic instability of human genome

    International Nuclear Information System (INIS)

    Hori, T.; Takahashi, E.; Tsuji, H.; Yamauchi, M.; Murata, M.

    1992-01-01

    In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author)

  15. DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.

    Science.gov (United States)

    Mueller, Michael M; Castells-Roca, Laia; Babu, Vipin; Ermolaeva, Maria A; Müller, Roman-Ulrich; Frommolt, Peter; Williams, Ashley B; Greiss, Sebastian; Schneider, Jennifer I; Benzing, Thomas; Schermer, Bernhard; Schumacher, Björn

    2014-12-01

    Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.

  16. Phytozome Comparative Plant Genomics Portal

    Energy Technology Data Exchange (ETDEWEB)

    Goodstein, David; Batra, Sajeev; Carlson, Joseph; Hayes, Richard; Phillips, Jeremy; Shu, Shengqiang; Schmutz, Jeremy; Rokhsar, Daniel

    2014-09-09

    The Dept. of Energy Joint Genome Institute is a genomics user facility supporting DOE mission science in the areas of Bioenergy, Carbon Cycling, and Biogeochemistry. The Plant Program at the JGI applies genomic, analytical, computational and informatics platforms and methods to: 1. Understand and accelerate the improvement (domestication) of bioenergy crops 2. Characterize and moderate plant response to climate change 3. Use comparative genomics to identify constrained elements and infer gene function 4. Build high quality genomic resource platforms of JGI Plant Flagship genomes for functional and experimental work 5. Expand functional genomic resources for Plant Flagship genomes

  17. Non-erythroid alpha spectrin prevents telomere dysfunction after DNA interstrand cross-link damage

    OpenAIRE

    Zhang, Pan; Herbig, Utz; Coffman, Frederick; Lambert, Muriel W.

    2013-01-01

    Telomere integrity is critical for telomere function and genomic stability. We previously demonstrated that non-erythroid ?-spectrin (?IISp) is present in mammalian cell nuclei where it is important in repair of DNA interstrand cross-links (ICLs) and chromosome stability. We now demonstrate that ?IISp is also important for telomere maintenance after ICL damage. It localizes to telomeres in S phase after ICL damage where it has enhanced association with TRF1 and TRF2 and is required for recrui...

  18. Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

    Directory of Open Access Journals (Sweden)

    Viktor M Pastukh

    2011-03-01

    Full Text Available Viktor M Pastukh1, Li Zhang2, Mykhaylo V Ruchko1, Olena Gorodnya1, Gina C Bardwell1, Rubin M Tuder2, Mark N Gillespie11Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL, USA; 2Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, CO, USAAbstract: Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD.Keywords: DNA damage, VEGF hypoxic response element, mtDNA, COPD

  19. Genomic instability--an evolving hallmark of cancer.

    Science.gov (United States)

    Negrini, Simona; Gorgoulis, Vassilis G; Halazonetis, Thanos D

    2010-03-01

    Genomic instability is a characteristic of most cancers. In hereditary cancers, genomic instability results from mutations in DNA repair genes and drives cancer development, as predicted by the mutator hypothesis. In sporadic (non-hereditary) cancers the molecular basis of genomic instability remains unclear, but recent high-throughput sequencing studies suggest that mutations in DNA repair genes are infrequent before therapy, arguing against the mutator hypothesis for these cancers. Instead, the mutation patterns of the tumour suppressor TP53 (which encodes p53), ataxia telangiectasia mutated (ATM) and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF) support the oncogene-induced DNA replication stress model, which attributes genomic instability and TP53 and ATM mutations to oncogene-induced DNA damage.

  20. Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index

    DEFF Research Database (Denmark)

    Suppiah, Ravi; Flossman, Oliver; Mukhtyar, Chetan

    2011-01-01

    To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis.......To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis....

  1. Global chromatin fibre compaction in response to DNA damage

    International Nuclear Information System (INIS)

    Hamilton, Charlotte; Hayward, Richard L.; Gilbert, Nick

    2011-01-01

    facilitate repair, the bulk genome becomes rapidly compacted protecting cells from further damage.

  2. Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA in the mouse heart.

    Science.gov (United States)

    Gredilla, R; Barja, G; López-Torres, M

    2001-10-01

    Oxygen radicals of mitochondrial origin are involved in oxidative damage. In order to analyze the possible relationship between metabolic rate, oxidative stress and oxidative damage, OF1 female mice were rendered hyper- and hypothyroid by chronic administration of 0.0012% L-thyroxine (T4) and 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water for 5 weeks. Hyperthyroidism significantly increased the sensitivity to lipid peroxidation in the heart, although the endogenous levels of lipid peroxidation were not altered. Thyroid hormone-induced oxidative stress also resulted in higher levels of GSSG and GSSG/GSH ratio. Oxidative damage to mitochondrial DNA was greater than that to genomic DNA. Hyperthyroidism decreased oxidative damage to genomic DNA. Hypothyroidism did not modify oxidative damage in the lipid fraction but significantly decreased GSSG and GSSG/GSH ratio and oxidative damage to mitochondrial DNA. These results indicate that thyroid hormones modulate oxidative damage to lipids and DNA, and cellular redox potential in the mouse heart. A higher oxidative stress in the hyperthyroid group is presumably neutralized in the case of nuclear DNA by an increase in repair activity, thus protecting this key molecule. Treatment with PTU, a thyroid hormone inhibitor, reduced oxidative damage in the different cell compartments.

  3. Electron damage in organic crystals

    International Nuclear Information System (INIS)

    Howitt, D.G.; Thomas, G.

    1977-01-01

    The effects of radiation damage in three crystalline organic materials (l-valine, cytosine, copper phthalocyanine) have been investigated by electron microscopy. The degradation of these materials has been found to be consistent with a gradual collapse of their crystal structures brought about by ionization damage to the comprising molecules. It is inferred that the crystallinity of these materials is destroyed by ionizing radiation because the damaged molecules cannot be incorporated into the framework of their original structures. (author)

  4. Genome-derived vaccines.

    Science.gov (United States)

    De Groot, Anne S; Rappuoli, Rino

    2004-02-01

    Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

  5. The Banana Genome Hub

    Science.gov (United States)

    Droc, Gaëtan; Larivière, Delphine; Guignon, Valentin; Yahiaoui, Nabila; This, Dominique; Garsmeur, Olivier; Dereeper, Alexis; Hamelin, Chantal; Argout, Xavier; Dufayard, Jean-François; Lengelle, Juliette; Baurens, Franc-Christophe; Cenci, Alberto; Pitollat, Bertrand; D’Hont, Angélique; Ruiz, Manuel; Rouard, Mathieu; Bocs, Stéphanie

    2013-01-01

    Banana is one of the world’s favorite fruits and one of the most important crops for developing countries. The banana reference genome sequence (Musa acuminata) was recently released. Given the taxonomic position of Musa, the completed genomic sequence has particular comparative value to provide fresh insights about the evolution of the monocotyledons. The study of the banana genome has been enhanced by a number of tools and resources that allows harnessing its sequence. First, we set up essential tools such as a Community Annotation System, phylogenomics resources and metabolic pathways. Then, to support post-genomic efforts, we improved banana existing systems (e.g. web front end, query builder), we integrated available Musa data into generic systems (e.g. markers and genetic maps, synteny blocks), we have made interoperable with the banana hub, other existing systems containing Musa data (e.g. transcriptomics, rice reference genome, workflow manager) and finally, we generated new results from sequence analyses (e.g. SNP and polymorphism analysis). Several uses cases illustrate how the Banana Genome Hub can be used to study gene families. Overall, with this collaborative effort, we discuss the importance of the interoperability toward data integration between existing information systems. Database URL: http://banana-genome.cirad.fr/ PMID:23707967

  6. Earthquake damage to underground facilities

    International Nuclear Information System (INIS)

    Pratt, H.R.; Hustrulid, W.A.; Stephenson, D.E.

    1978-11-01

    The potential seismic risk for an underground nuclear waste repository will be one of the considerations in evaluating its ultimate location. However, the risk to subsurface facilities cannot be judged by applying intensity ratings derived from the surface effects of an earthquake. A literature review and analysis were performed to document the damage and non-damage due to earthquakes to underground facilities. Damage from earthquakes to tunnels, s, and wells and damage (rock bursts) from mining operations were investigated. Damage from documented nuclear events was also included in the study where applicable. There are very few data on damage in the subsurface due to earthquakes. This fact itself attests to the lessened effect of earthquakes in the subsurface because mines exist in areas where strong earthquakes have done extensive surface damage. More damage is reported in shallow tunnels near the surface than in deep mines. In mines and tunnels, large displacements occur primarily along pre-existing faults and fractures or at the surface entrance to these facilities.Data indicate vertical structures such as wells and shafts are less susceptible to damage than surface facilities. More analysis is required before seismic criteria can be formulated for the siting of a nuclear waste repository

  7. Traditional medicine and genomics

    Directory of Open Access Journals (Sweden)

    Kalpana Joshi

    2010-01-01

    Full Text Available ′Omics′ developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics.

  8. Traditional medicine and genomics.

    Science.gov (United States)

    Joshi, Kalpana; Ghodke, Yogita; Shintre, Pooja

    2010-01-01

    'Omics' developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics.

  9. Bacillus subtilis genome diversity.

    Science.gov (United States)

    Earl, Ashlee M; Losick, Richard; Kolter, Roberto

    2007-02-01

    Microarray-based comparative genomic hybridization (M-CGH) is a powerful method for rapidly identifying regions of genome diversity among closely related organisms. We used M-CGH to examine the genome diversity of 17 strains belonging to the nonpathogenic species Bacillus subtilis. Our M-CGH results indicate that there is considerable genetic heterogeneity among members of this species; nearly one-third of Bsu168-specific genes exhibited variability, as measured by the microarray hybridization intensities. The variable loci include those encoding proteins involved in antibiotic production, cell wall synthesis, sporulation, and germination. The diversity in these genes may reflect this organism's ability to survive in diverse natural settings.

  10. Genomic taxonomy of vibrios

    Directory of Open Access Journals (Sweden)

    Iida Tetsuya

    2009-10-01

    Full Text Available Abstract Background Vibrio taxonomy has been based on a polyphasic approach. In this study, we retrieve useful taxonomic information (i.e. data that can be used to distinguish different taxonomic levels, such as species and genera from 32 genome sequences of different vibrio species. We use a variety of tools to explore the taxonomic relationship between the sequenced genomes, including Multilocus Sequence Analysis (MLSA, supertrees, Average Amino Acid Identity (AAI, genomic signatures, and Genome BLAST atlases. Our aim is to analyse the usefulness of these tools for species identification in vibrios. Results We have generated four new genome sequences of three Vibrio species, i.e., V. alginolyticus 40B, V. harveyi-like 1DA3, and V. mimicus strains VM573 and VM603, and present a broad analyses of these genomes along with other sequenced Vibrio species. The genome atlas and pangenome plots provide a tantalizing image of the genomic differences that occur between closely related sister species, e.g. V. cholerae and V. mimicus. The vibrio pangenome contains around 26504 genes. The V. cholerae core genome and pangenome consist of 1520 and 6923 genes, respectively. Pangenomes might allow different strains of V. cholerae to occupy different niches. MLSA and supertree analyses resulted in a similar phylogenetic picture, with a clear distinction of four groups (Vibrio core group, V. cholerae-V. mimicus, Aliivibrio spp., and Photobacterium spp.. A Vibrio species is defined as a group of strains that share > 95% DNA identity in MLSA and supertree analysis, > 96% AAI, ≤ 10 genome signature dissimilarity, and > 61% proteome identity. Strains of the same species and species of the same genus will form monophyletic groups on the basis of MLSA and supertree. Conclusion The combination of different analytical and bioinformatics tools will enable the most accurate species identification through genomic computational analysis. This endeavour will culminate in

  11. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  12. Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  13. Genomic signal processing

    CERN Document Server

    Shmulevich, Ilya

    2007-01-01

    Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema

  14. Radiation damage to histones

    International Nuclear Information System (INIS)

    Mee, L.K.; Adelstein, S.J.

    1985-01-01

    The damage to histones irradiated in isolation is being elaborated to aid the identification of the crosslinking sites in radiation-induced DNA-histone adducts. Histones are being examined by amino acid analysis to determine the destruction of residues and by polyacrylamide gel electrophoresis to delineate changes in conformation. For the slightly lysine-rich histone, H2A, a specific attack on selective residues has been established, the aromatic residues, tyrosine and phenylalanine, and the heterocyclic residue, histidine, being significantly destroyed. In addition, a significant increase in aspartic acid was found; this may represent a radiation product from scission of the ring in the histidine residues. The similarity of the effects on residues in nitrous oxide-saturated and nitrogen-saturated solutions suggests that OH . and e/sub aq//sup -/ are equally efficient and selective in their attack. On gel electrophoresis degradation of the histone H2A was found to be greatest for irradiations in nitrous oxide-saturated solutions, suggesting CH . is the most effective radical for producing changes in conformation; O/sub 2//sup -/ was essentially ineffective. Other histones are being examined for changes in amino acid composition, conformation, and for the formation of radiation products

  15. How life changes itself: the Read-Write (RW) genome.

    Science.gov (United States)

    Shapiro, James A

    2013-09-01

    The genome has traditionally been treated as a Read-Only Memory (ROM) subject to change by copying errors and accidents. In this review, I propose that we need to change that perspective and understand the genome as an intricately formatted Read-Write (RW) data storage system constantly subject to cellular modifications and inscriptions. Cells operate under changing conditions and are continually modifying themselves by genome inscriptions. These inscriptions occur over three distinct time-scales (cell reproduction, multicellular development and evolutionary change) and involve a variety of different processes at each time scale (forming nucleoprotein complexes, epigenetic formatting and changes in DNA sequence structure). Research dating back to the 1930s has shown that genetic change is the result of cell-mediated processes, not simply accidents or damage to the DNA. This cell-active view of genome change applies to all scales of DNA sequence variation, from point mutations to large-scale genome rearrangements and whole genome duplications (WGDs). This conceptual change to active cell inscriptions controlling RW genome functions has profound implications for all areas of the life sciences. © 2013 Elsevier B.V. All rights reserved.

  16. Shock Initiation of Damaged Explosives

    Energy Technology Data Exchange (ETDEWEB)

    Chidester, S K; Vandersall, K S; Tarver, C M

    2009-10-22

    Explosive and propellant charges are subjected to various mechanical and thermal insults that can increase their sensitivity over the course of their lifetimes. To quantify this effect, shock initiation experiments were performed on mechanically and thermally damaged LX-04 (85% HMX, 15% Viton by weight) and PBX 9502 (95% TATB, 5% Kel-F by weight) to obtain in-situ manganin pressure gauge data and run distances to detonation at various shock pressures. We report the behavior of the HMX-based explosive LX-04 that was damaged mechanically by applying a compressive load of 600 psi for 20,000 cycles, thus creating many small narrow cracks, or by cutting wedge shaped parts that were then loosely reassembled, thus creating a few large cracks. The thermally damaged LX-04 charges were heated to 190 C for long enough for the beta to delta solid - solid phase transition to occur, and then cooled to ambient temperature. Mechanically damaged LX-04 exhibited only slightly increased shock sensitivity, while thermally damaged LX-04 was much more shock sensitive. Similarly, the insensitive explosive PBX 9502 was mechanically damaged using the same two techniques. Since PBX 9502 does not undergo a solid - solid phase transition but does undergo irreversible or 'rachet' growth when thermally cycled, thermal damage to PBX 9502 was induced by this procedure. As for LX-04, the thermally damaged PBX 9502 demonstrated a greater shock sensitivity than mechanically damaged PBX 9502. The Ignition and Growth reactive flow model calculated the increased sensitivities by igniting more damaged LX-04 and PBX 9502 near the shock front based on the measured densities (porosities) of the damaged charges.

  17. Damaging the Integrated HIV Proviral DNA with TALENs.

    Directory of Open Access Journals (Sweden)

    Christy L Strong

    Full Text Available HIV-1 integrates its proviral DNA genome into the host genome, presenting barriers for virus eradication. Several new gene-editing technologies have emerged that could potentially be used to damage integrated proviral DNA. In this study, we use transcription activator-like effector nucleases (TALENs to target a highly conserved sequence in the transactivation response element (TAR of the HIV-1 proviral DNA. We demonstrated that TALENs cleave a DNA template with the HIV-1 proviral target site in vitro. A GFP reporter, under control of HIV-1 TAR, was efficiently inactivated by mutations introduced by transfection of TALEN plasmids. When infected cells containing the full-length integrated HIV-1 proviral DNA were transfected with TALENs, the TAR region accumulated indels. When one of these mutants was tested, the mutated HIV-1 proviral DNA was incapable of producing detectable Gag expression. TALEN variants engineered for degenerate recognition of select nucleotide positions also cleaved proviral DNA in vitro and the full-length integrated proviral DNA genome in living cells. These results suggest a possible design strategy for the therapeutic considerations of incomplete target sequence conservation and acquired resistance mutations. We have established a new strategy for damaging integrated HIV proviral DNA that may have future potential for HIV-1 proviral DNA eradication.

  18. Role of the Checkpoint Clamp in DNA Damage Response

    Directory of Open Access Journals (Sweden)

    Mihoko Kai

    2013-01-01

    Full Text Available DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR.

  19. MDM2 Antagonists Counteract Drug-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Anna E. Vilgelm

    2017-10-01

    Full Text Available Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.

  20. Genomics and fish adaptation

    Directory of Open Access Journals (Sweden)

    Agostinho Antunes

    2015-12-01

    Full Text Available The completion of the human genome sequencing in 2003 opened a new perspective into the importance of whole genome sequencing projects, and currently multiple species are having their genomes completed sequenced, from simple organisms, such as bacteria, to more complex taxa, such as mammals. This voluminous sequencing data generated across multiple organisms provides also the framework to better understand the genetic makeup of such species and related ones, allowing to explore the genetic changes underlining the evolution of diverse phenotypic traits. Here, recent results from our group retrieved from comparative evolutionary genomic analyses of varied fish species will be considered to exemplify how gene novelty and gene enhancement by positive selection might have been determinant in the success of adaptive radiations into diverse habitats and lifestyles.

  1. Lophotrochozoan mitochondrial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  2. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  3. Genomic definition of species

    Energy Technology Data Exchange (ETDEWEB)

    Crkvenjakov, R.; Drmanac, R.

    1991-07-01

    The subject of this paper is the definition of species based on the assumption that genome is the fundamental level for the origin and maintenance of biological diversity. For this view to be logically consistent it is necessary to assume the existence and operation of the new law which we call genome law. For this reason the genome law is included in the explanation of species phenomenon presented here even if its precise formulation and elaboration are left for the future. The intellectual underpinnings of this definition can be traced to Goldschmidt. We wish to explore some philosophical aspects of the definition of species in terms of the genome. The point of proposing the definition on these grounds is that any real advance in evolutionary theory has to be correct in both its philosophy and its science.

  4. Structural genomics in endocrinology

    NARCIS (Netherlands)

    Smit, J. W.; Romijn, J. A.

    2001-01-01

    Traditionally, endocrine research evolved from the phenotypical characterisation of endocrine disorders to the identification of underlying molecular pathophysiology. This approach has been, and still is, extremely successful. The introduction of genomics and proteomics has resulted in a reversal of

  5. Epidemiology & Genomics Research Program

    Science.gov (United States)

    The Epidemiology and Genomics Research Program, in the National Cancer Institute's Division of Cancer Control and Population Sciences, funds research in human populations to understand the determinants of cancer occurrence and outcomes.

  6. Annotating individual human genomes.

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A; Topol, Eric J; Schork, Nicholas J

    2011-10-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. ANNOTATING INDIVIDUAL HUMAN GENOMES*

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A.; Topol, Eric J.; Schork, Nicholas J.

    2014-01-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely to amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. PMID:21839162

  8. Yeast genome sequencing:

    DEFF Research Database (Denmark)

    Piskur, Jure; Langkjær, Rikke Breinhold

    2004-01-01

    For decades, unicellular yeasts have been general models to help understand the eukaryotic cell and also our own biology. Recently, over a dozen yeast genomes have been sequenced, providing the basis to resolve several complex biological questions. Analysis of the novel sequence data has shown...... of closely related species helps in gene annotation and to answer how many genes there really are within the genomes. Analysis of non-coding regions among closely related species has provided an example of how to determine novel gene regulatory sequences, which were previously difficult to analyse because...... they are short and degenerate and occupy different positions. Comparative genomics helps to understand the origin of yeasts and points out crucial molecular events in yeast evolutionary history, such as whole-genome duplication and horizontal gene transfer(s). In addition, the accumulating sequence data provide...

  9. Genetical Genomics for Evolutionary Studies

    NARCIS (Netherlands)

    Prins, J.C.P.; Smant, G.; Jansen, R.C.

    2012-01-01

    Genetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome

  10. Fatigue damage of nuclear facilities

    International Nuclear Information System (INIS)

    2001-01-01

    The conference on the fatigue damage of nuclear facilities, organized by the SFEN (french society of nuclear energy), took place at Paris the 23. of november 2000. Eleven papers were presented, showing the state of the art and the research programs in the domain of the sizing rules, safety, installations damage, examination and maintenance. (A.L.B.)

  11. Grounding Damage to Conventional Vessels

    DEFF Research Database (Denmark)

    Lützen, Marie; Simonsen, Bo Cerup

    2003-01-01

    The present paper is concerned with rational design of conventional vessels with regard to bottom damage generated in grounding accidents. The aim of the work described here is to improve the design basis, primarily through analysis of new statistical data for grounding damage. The current regula...

  12. LX-10 Explosive Damage Studies

    Science.gov (United States)

    2015-03-03

    opposite end of the vessel. The inside of the bomb is fitted with a stainless steel liner to protect the inner surface and to change the bomb...19  18. Size Fractions for Spherical LX-10 Samples Impact Damaged Between 312 and 416 ft/s...19  19. Spherical LX-10 Sample Impact Damaged at 416 ft/s ....................................... 20  20

  13. Structural Damage in Mexico City

    OpenAIRE

    Hall, John F.; Beck, James L.

    1986-01-01

    This paper describes the structural damage in Mexico City caused by the September 19, 1985 earthquake. Photographs which illustrate various features of structural behavior are included. One explanation is presented as to why buildings with fundamental periods of elastic vibration considerably below the predominant two‐second period of the ground motion were most vulnerable to damage.

  14. Damage control in vascular injury

    NARCIS (Netherlands)

    Leenen, L. P.H.

    2017-01-01

    The highest goal in damage control surgery is to stop the bleeding. Major injuries to the vessels therefore pose the major challenge in the damage control approach. Optimal care can be provided in combination with receiving and treatment rooms with CT, operative and endovascular capabilities. For

  15. The human genome project

    International Nuclear Information System (INIS)

    Worton, R.

    1996-01-01

    The Human Genome Project is a massive international research project, costing 3 to 5 billion dollars and expected to take 15 years, which will identify the all the genes in the human genome - i.e. the complete sequence of bases in human DNA. The prize will be the ability to identify genes causing or predisposing to disease, and in some cases the development of gene therapy, but this new knowledge will raise important ethical issues

  16. Decoding the human genome

    CERN Multimedia

    CERN. Geneva. Audiovisual Unit; Antonerakis, S E

    2002-01-01

    Decoding the Human genome is a very up-to-date topic, raising several questions besides purely scientific, in view of the two competing teams (public and private), the ethics of using the results, and the fact that the project went apparently faster and easier than expected. The lecture series will address the following chapters: Scientific basis and challenges. Ethical and social aspects of genomics.

  17. Molluscan Evolutionary Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Simison, W. Brian; Boore, Jeffrey L.

    2005-12-01

    In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the early 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.

  18. Human Germline Genome Editing

    OpenAIRE

    Ormond, Kelly E.; Mortlock, Douglas P.; Scholes, Derek T.; Bombard, Yvonne; Brody, Lawrence C.; Faucett, W. Andrew; Garrison, Nanibaa’ A.; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E.

    2017-01-01

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Gen...

  19. Damage growth in aerospace composites

    CERN Document Server

    2015-01-01

    This book presents novel methods for the simulation of damage evolution in aerospace composites that will assist in predicting damage onset and growth and thus foster less conservative designs which realize the promised economic benefits of composite materials. The presented integrated numerical/experimental methodologies are capable of taking into account the presence of damage and its evolution in composite structures from the early phases of the design (conceptual design) through to the detailed finite element method analysis and verification phase. The book is based on the GARTEUR Research Project AG-32, which ran from 2007 to 2012, and documents the main results of that project. In addition, the state of the art in European projects on damage evolution in composites is reviewed. While the high specific strength and stiffness of composite materials make them suitable for aerospace structures, their sensitivity to damage means that designing with composites is a challenging task. The new approaches describ...

  20. Steady State Shift Damage Localization

    DEFF Research Database (Denmark)

    Sekjær, Claus; Bull, Thomas; Markvart, Morten Kusk

    2017-01-01

    The steady state shift damage localization (S3DL) method localizes structural deterioration, manifested as either a mass or stiffness perturbation, by interrogating the damage-induced change in the steady state vibration response with damage patterns cast from a theoretical model. Damage is, thus...... the required accuracy when examining complex structures, an extensive amount of degrees of freedom (DOF) must often be utilized. Since the interrogation matrix for each damage pattern depends on the size of the system matrices constituting the FE-model, the computational time quickly becomes of first......-order importance. The present paper investigates two sub-structuring approaches, in which the idea is to employ Craig-Bampton super-elements to reduce the amount of interrogation distributions while still providing an acceptable localization resolution. The first approach operates on a strict super-element level...

  1. Radiation Damage in Scintillating Crystals

    CERN Document Server

    Zhu Ren Yuan

    1998-01-01

    Crystal Calorimetry in future high energy physics experiments faces a new challenge to maintain its precision in a hostile radiation environment. This paper discusses the effects of radiation damage in scintillating crystals, and concludes that the predominant radiation damage effect in crystal scintillators is the radiation induced absorption, or color center formation, not the loss of the scintillation light yield. The importance of maintaining crystal's light response uniformity and the feasibility to build a precision crystal calorimeter under radiation are elaborated. The mechanism of the radiation damage in scintillating crystals is also discussed. While the damage in alkali halides is found to be caused by the oxygen or hydroxyl contamination, it is the structure defects, such as oxygen vacancies, cause damage in oxides. Material analysis methods used to reach these conclusions are presented in details.

  2. RadGenomics project

    Energy Technology Data Exchange (ETDEWEB)

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu [National Inst. of Radiological Sciences, Chiba (Japan). Frontier Research Center] [and others

    2002-06-01

    Human health is determined by a complex interplay of factors, predominantly between genetic susceptibility, environmental conditions and aging. The ultimate aim of the RadGenomics (Radiation Genomics) project is to understand the implications of heterogeneity in responses to ionizing radiation arising from genetic variation between individuals in the human population. The rapid progression of the human genome sequencing and the recent development of new technologies in molecular genetics are providing us with new opportunities to understand the genetic basis of individual differences in susceptibility to natural and/or artificial environmental factors, including radiation exposure. The RadGenomics project will inevitably lead to improved protocols for personalized radiotherapy and reductions in the potential side effects of such treatment. The project will contribute to future research into the molecular mechanisms of radiation sensitivity in humans and will stimulate the development of new high-throughput technologies for a broader application of biological and medical sciences. The staff members are specialists in a variety of fields, including genome science, radiation biology, medical science, molecular biology, and informatics, and have joined the RadGenomics project from various universities, companies, and research institutes. The project started in April 2001. (author)

  3. Comparative Genome Viewer

    International Nuclear Information System (INIS)

    Molineris, I.; Sales, G.

    2009-01-01

    The amount of information about genomes, both in the form of complete sequences and annotations, has been exponentially increasing in the last few years. As a result there is the need for tools providing a graphical representation of such information that should be comprehensive and intuitive. Visual representation is especially important in the comparative genomics field since it should provide a combined view of data belonging to different genomes. We believe that existing tools are limited in this respect as they focus on a single genome at a time (conservation histograms) or compress alignment representation to a single dimension. We have therefore developed a web-based tool called Comparative Genome Viewer (Cgv): it integrates a bidimensional representation of alignments between two regions, both at small and big scales, with the richness of annotations present in other genome browsers. We give access to our system through a web-based interface that provides the user with an interactive representation that can be updated in real time using the mouse to move from region to region and to zoom in on interesting details.

  4. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  5. RadGenomics project

    International Nuclear Information System (INIS)

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu

    2002-01-01

    Human health is determined by a complex interplay of factors, predominantly between genetic susceptibility, environmental conditions and aging. The ultimate aim of the RadGenomics (Radiation Genomics) project is to understand the implications of heterogeneity in responses to ionizing radiation arising from genetic variation between individuals in the human population. The rapid progression of the human genome sequencing and the recent development of new technologies in molecular genetics are providing us with new opportunities to understand the genetic basis of individual differences in susceptibility to natural and/or artificial environmental factors, including radiation exposure. The RadGenomics project will inevitably lead to improved protocols for personalized radiotherapy and reductions in the potential side effects of such treatment. The project will contribute to future research into the molecular mechanisms of radiation sensitivity in humans and will stimulate the development of new high-throughput technologies for a broader application of biological and medical sciences. The staff members are specialists in a variety of fields, including genome science, radiation biology, medical science, molecular biology, and informatics, and have joined the RadGenomics project from various universities, companies, and research institutes. The project started in April 2001. (author)

  6. Diagnosis of Lung Cancer by Fractal Analysis of Damaged DNA

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2015-01-01

    Full Text Available Cancer starts when cells in a part of the body start to grow out of control. In fact cells become cancer cells because of DNA damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to study the cancer genes, DNA walk plots of genomes of patients with lung cancer were generated using a program written in MATLAB language. The data so obtained was checked for fractal property by computing the fractal dimension using a program written in MATLAB. Also, the correlation of damaged DNA was studied using the Hurst exponent measure. We have found that the damaged DNA sequences are exhibiting higher degree of fractality and less correlation compared with normal DNA sequences. So we confirmed this method can be used for early detection of lung cancer. The method introduced in this research not only is useful for diagnosis of lung cancer but also can be applied for detection and growth analysis of different types of cancers.

  7. Anisotropic creep damage in the framework of continuum damage mechanics

    International Nuclear Information System (INIS)

    Caboche, J.L.

    1983-01-01

    For some years, various works have shown the possibility of applying continuum mechanics to model the evolution of the damage variable, initially introduced by Kachanov. Of interest here are the complex problems posed by the anisotropy which affects both the elastic behaviour and the viscoplastic one, and also the rupture phenomenon. The main concepts of the Continuum Damage Mechanics are briefly reviewed together with some classical ways to introduce anisotropy of damage in the particular case of proportional loadings. Based on previous works, two generalizations are presented and discussed, which use different kinds of tensors to describe the anisotropy of creep damage: - The first one, by Murakami and Ohno introduces a second rank damage tensor and a net stress tensor through a net area definition. The effective stress-strain behaviour is then obtained by a fourth rank tensor. - The second theory, by the author, uses one effective stress tensor only, defined in terms of the macroscopic strain behaviour, through a fourth-order non-symmetrical damage tensor. The two theories are compared at several levels: difference and similarities are pointed out for the damage evolution during tensile creep as well as for anisotropy effects. The possibilities are discussed and compared on the basis of some existing experimental results, which leads to a partial validation of the two approaches. (orig.)

  8. DNA damage in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Coppedè, Fabio, E-mail: fabio.coppede@med.unipi.it; Migliore, Lucia, E-mail: lucia.migliore@med.unipi.it

    2015-06-15

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  9. DNA damage in neurodegenerative diseases

    International Nuclear Information System (INIS)

    Coppedè, Fabio; Migliore, Lucia

    2015-01-01

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  10. Ultrafast comparison of personal genomes

    OpenAIRE

    Mauldin, Denise; Hood, Leroy; Robinson, Max; Glusman, Gustavo

    2017-01-01

    We present an ultra-fast method for comparing personal genomes. We transform the standard genome representation (lists of variants relative to a reference) into 'genome fingerprints' that can be readily compared across sequencing technologies and reference versions. Because of their reduced size, computation on the genome fingerprints is fast and requires little memory. This enables scaling up a variety of important genome analyses, including quantifying relatedness, recognizing duplicative s...

  11. Base excision repair of oxidative DNA damage and association with cancer and aging

    DEFF Research Database (Denmark)

    Maynard, Scott; Schurman, Shepherd H; Harboe, Charlotte

    2009-01-01

    Aging has been associated with damage accumulation in the genome and with increased cancer incidence. Reactive oxygen species (ROS) are produced from endogenous sources, most notably the oxidative metabolism in the mitochondria, and from exogenous sources, such as ionizing radiation. ROS attack DNA...

  12. Genomics using the Assembly of the Mink Genome

    DEFF Research Database (Denmark)

    Guldbrandtsen, Bernt; Cai, Zexi; Sahana, Goutam

    2018-01-01

    The American Mink’s (Neovison vison) genome has recently been sequenced. This opens numerous avenues of research both for studying the basic genetics and physiology of the mink as well as genetic improvement in mink. Using genotyping-by-sequencing (GBS) generated marker data for 2,352 Danish farm...... mink runs of homozygosity (ROH) were detect in mink genomes. Detectable ROH made up on average 1.7% of the genome indicating the presence of at most a moderate level of genomic inbreeding. The fraction of genome regions found in ROH varied. Ten percent of the included regions were never found in ROH....... The ability to detect ROH in the mink genome also demonstrates the general reliability of the new mink genome assembly. Keywords: american mink, run of homozygosity, genome, selection, genomic inbreeding...

  13. Link between DNA damage and centriole disengagement/reduplication in untransformed human cells.

    Science.gov (United States)

    Douthwright, Stephen; Sluder, Greenfield

    2014-10-01

    The radiation and radiomimetic drugs used to treat human tumors damage DNA in both cancer cells and normal proliferating cells. Centrosome amplification after DNA damage is well established for transformed cell types but is sparsely reported and not fully understood in untransformed cells. We characterize centriole behavior after DNA damage in synchronized untransformed human cells. One hour treatment of S phase cells with the radiomimetic drug, Doxorubicin, prolongs G2 by at least 72 h, though 14% of the cells eventually go through mitosis in that time. By 72 h after DNA damage we observe a 52% incidence of centriole disengagement plus a 10% incidence of extra centrioles. We find that either APC/C or Plk activities can disengage centrioles after DNA damage, though they normally work in concert. All disengaged centrioles are associated with γ-tubulin and maturation markers and thus, should in principle be capable of reduplicating and organizing spindle poles. The low incidence of reduplication of disengaged centrioles during G2 is due to the p53-dependent expression of p21 and the consequent loss of Cdk2 activity. We find that 26% of the cells going through mitosis after DNA damage contain disengaged or extra centrioles. This could produce genomic instability through transient or persistent spindle multipolarity. Thus, for cancer patients the use of DNA damaging therapies raises the chances of genomic instability and evolution of transformed characteristics in proliferating normal cell populations. © 2014 Wiley Periodicals, Inc.

  14. Genome size analyses of Pucciniales reveal the largest fungal genomes.

    Science.gov (United States)

    Tavares, Sílvia; Ramos, Ana Paula; Pires, Ana Sofia; Azinheira, Helena G; Caldeirinha, Patrícia; Link, Tobias; Abranches, Rita; Silva, Maria do Céu; Voegele, Ralf T; Loureiro, João; Talhinhas, Pedro

    2014-01-01

    Rust fungi (Basidiomycota, Pucciniales) are biotrophic plant pathogens which exhibit diverse complexities in their life cycles and host ranges. The completion of genome sequencing of a few rust fungi has revealed the occurrence of large genomes. Sequencing efforts for other rust fungi have been hampered by uncertainty concerning their genome sizes. Flow cytometry was recently applied to estimate the genome size of a few rust fungi, and confirmed the occurrence of large genomes in this order (averaging 225.3 Mbp, while the average for Basidiomycota was 49.9 Mbp and was 37.7 Mbp for all fungi). In this work, we have used an innovative and simple approach to simultaneously isolate nuclei from the rust and its host plant in order to estimate the genome size of 30 rust species by flow cytometry. Genome sizes varied over 10-fold, from 70 to 893 Mbp, with an average genome size value of 380.2 Mbp. Compared to the genome sizes of over 1800 fungi, Gymnosporangium confusum possesses the largest fungal genome ever reported (893.2 Mbp). Moreover, even the smallest rust genome determined in this study is larger than the vast majority of fungal genomes (94%). The average genome size of the Pucciniales is now of 305.5 Mbp, while the average Basidiomycota genome size has shifted to 70.4 Mbp and the average for all fungi reached 44.2 Mbp. Despite the fact that no correlation could be drawn between the genome sizes, the phylogenomics or the life cycle of rust fungi, it is interesting to note that rusts with Fabaceae hosts present genomes clearly larger than those with Poaceae hosts. Although this study comprises only a small fraction of the more than 7000 rust species described, it seems already evident that the Pucciniales represent a group where genome size expansion could be a common characteristic. This is in sharp contrast to sister taxa, placing this order in a relevant position in fungal genomics research.

  15. Editorial: 3Rs tightly intertwined to maintain genome stability

    DEFF Research Database (Denmark)

    Lisby, Michael; Mortensen, Uffe H.

    2017-01-01

    , replication of damaged DNA results in stalled replication forks that await DNA damage repair before replication can be resumed. In turn, the repair of most lesions depends on processes involving DNA synthesis. At the same time, the stalled forks may engage in recombination, either as part of a controlled...... repair process or by accident, just because it can, with the risk of producing genome rearrangements and loss of heterozygosity. The set of reviews presented in this thematic issue (https://academic-oup-com.proxy.findit.dtu.dk/femsyr/pages/replication_recombination_and_repair) of FEMSYR has been selected...

  16. Genomes to Proteomes

    Energy Technology Data Exchange (ETDEWEB)

    Panisko, Ellen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Grigoriev, Igor [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Daly, Don S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Webb-Robertson, Bobbie-Jo [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baker, Scott E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-03-01

    Biologists are awash with genomic sequence data. In large part, this is due to the rapid acceleration in the generation of DNA sequence that occurred as public and private research institutes raced to sequence the human genome. In parallel with the large human genome effort, mostly smaller genomes of other important model organisms were sequenced. Projects following on these initial efforts have made use of technological advances and the DNA sequencing infrastructure that was built for the human and other organism genome projects. As a result, the genome sequences of many organisms are available in high quality draft form. While in many ways this is good news, there are limitations to the biological insights that can be gleaned from DNA sequences alone; genome sequences offer only a bird's eye view of the biological processes endemic to an organism or community. Fortunately, the genome sequences now being produced at such a high rate can serve as the foundation for other global experimental platforms such as proteomics. Proteomic methods offer a snapshot of the proteins present at a point in time for a given biological sample. Current global proteomics methods combine enzymatic digestion, separations, mass spectrometry and database searching for peptide identification. One key aspect of proteomics is the prediction of peptide sequences from mass spectrometry data. Global proteomic analysis uses computational matching of experimental mass spectra with predicted spectra based on databases of gene models that are often generated computationally. Thus, the quality of gene models predicted from a genome sequence is crucial in the generation of high quality peptide identifications. Once peptides are identified they can be assigned to their parent protein. Proteins identified as expressed in a given experiment are most useful when compared to other expressed proteins in a larger biological context or biochemical pathway. In this chapter we will discuss the automatic

  17. Experimental Induction of Genome Chaos.

    Science.gov (United States)

    Ye, Christine J; Liu, Guo; Heng, Henry H

    2018-01-01

    Genome chaos, or karyotype chaos, represents a powerful survival strategy for somatic cells under high levels of stress/selection. Since the genome context, not the gene content, encodes the genomic blueprint of the cell, stress-induced rapid and massive reorganization of genome topology functions as a very important mechanism for genome (karyotype) evolution. In recent years, the phenomenon of genome chaos has been confirmed by various sequencing efforts, and many different terms have been coined to describe different subtypes of the chaotic genome including "chromothripsis," "chromoplexy," and "structural mutations." To advance this exciting field, we need an effective experimental system to induce and characterize the karyotype reorganization process. In this chapter, an experimental protocol to induce chaotic genomes is described, following a brief discussion of the mechanism and implication of genome chaos in cancer evolution.

  18. Genome Sequences of Oryza Species

    KAUST Repository

    Kumagai, Masahiko; Tanaka, Tsuyoshi; Ohyanagi, Hajime; Hsing, Yue-Ie C.; Itoh, Takeshi

    2018-01-01

    This chapter summarizes recent data obtained from genome sequencing, annotation projects, and studies on the genome diversity of Oryza sativa and related Oryza species. O. sativa, commonly known as Asian rice, is the first monocot species whose complete genome sequence was deciphered based on physical mapping by an international collaborative effort. This genome, along with its accurate and comprehensive annotation, has become an indispensable foundation for crop genomics and breeding. With the development of innovative sequencing technologies, genomic studies of O. sativa have dramatically increased; in particular, a large number of cultivars and wild accessions have been sequenced and compared with the reference rice genome. Since de novo genome sequencing has become cost-effective, the genome of African cultivated rice, O. glaberrima, has also been determined. Comparative genomic studies have highlighted the independent domestication processes of different rice species, but it also turned out that Asian and African rice share a common gene set that has experienced similar artificial selection. An international project aimed at constructing reference genomes and examining the genome diversity of wild Oryza species is currently underway, and the genomes of some species are publicly available. This project provides a platform for investigations such as the evolution, development, polyploidization, and improvement of crops. Studies on the genomic diversity of Oryza species, including wild species, should provide new insights to solve the problem of growing food demands in the face of rapid climatic changes.

  19. Genome Sequences of Oryza Species

    KAUST Repository

    Kumagai, Masahiko

    2018-02-14

    This chapter summarizes recent data obtained from genome sequencing, annotation projects, and studies on the genome diversity of Oryza sativa and related Oryza species. O. sativa, commonly known as Asian rice, is the first monocot species whose complete genome sequence was deciphered based on physical mapping by an international collaborative effort. This genome, along with its accurate and comprehensive annotation, has become an indispensable foundation for crop genomics and breeding. With the development of innovative sequencing technologies, genomic studies of O. sativa have dramatically increased; in particular, a large number of cultivars and wild accessions have been sequenced and compared with the reference rice genome. Since de novo genome sequencing has become cost-effective, the genome of African cultivated rice, O. glaberrima, has also been determined. Comparative genomic studies have highlighted the independent domestication processes of different rice species, but it also turned out that Asian and African rice share a common gene set that has experienced similar artificial selection. An international project aimed at constructing reference genomes and examining the genome diversity of wild Oryza species is currently underway, and the genomes of some species are publicly available. This project provides a platform for investigations such as the evolution, development, polyploidization, and improvement of crops. Studies on the genomic diversity of Oryza species, including wild species, should provide new insights to solve the problem of growing food demands in the face of rapid climatic changes.

  20. Clinically Applicable Inhibitors Impacting Genome Stability.

    Science.gov (United States)

    Prakash, Anu; Garcia-Moreno, Juan F; Brown, James A L; Bourke, Emer

    2018-05-13

    Advances in technology have facilitated the molecular profiling (genomic and transcriptomic) of tumours, and has led to improved stratification of patients and the individualisation of treatment regimes. To fully realize the potential of truly personalised treatment options, we need targeted therapies that precisely disrupt the compensatory pathways identified by profiling which allow tumours to survive or gain resistance to treatments. Here, we discuss recent advances in novel therapies that impact the genome (chromosomes and chromatin), pathways targeted and the stage of the pathways targeted. The current state of research will be discussed, with a focus on compounds that have advanced into trials (clinical and pre-clinical). We will discuss inhibitors of specific DNA damage responses and other genome stability pathways, including those in development, which are likely to synergistically combine with current therapeutic options. Tumour profiling data, combined with the knowledge of new treatments that affect the regulation of essential tumour signalling pathways, is revealing fundamental insights into cancer progression and resistance mechanisms. This is the forefront of the next evolution of advanced oncology medicine that will ultimately lead to improved survival and may, one day, result in many cancers becoming chronic conditions, rather than fatal diseases.

  1. Genome position specific priors for genomic prediction

    DEFF Research Database (Denmark)

    Brøndum, Rasmus Froberg; Su, Guosheng; Lund, Mogens Sandø

    2012-01-01

    casual mutation is different between the populations but affects the same gene. Proportions of a four-distribution mixture for SNP effects in segments of fixed size along the genome are derived from one population and set as location specific prior proportions of distributions of SNP effects...... for the target population. The model was tested using dairy cattle populations of different breeds: 540 Australian Jersey bulls, 2297 Australian Holstein bulls and 5214 Nordic Holstein bulls. The traits studied were protein-, fat- and milk yield. Genotypic data was Illumina 777K SNPs, real or imputed Results...

  2. Clinical light damage to the eye

    International Nuclear Information System (INIS)

    Miller, D.

    1987-01-01

    This book contains four sections: The Nature of Light and of Light Damage to Biological Tissues; Light Damage to the Eye; Protecting the Eye from Light Damage; and Overview of Light Damage to the Eye. Some of the paper titles are: Ultraviolet-Absorbing Intraocular Lens Implants; Phototoxic Changes in the Retina; Light Damage to the Lens; and Radiation, Light, and Sight

  3. A model for damage load and its implications for the evolution of bacterial aging.

    Directory of Open Access Journals (Sweden)

    Lin Chao

    2010-08-01

    Full Text Available Deleterious mutations appearing in a population increase in frequency until stopped by natural selection. The ensuing equilibrium creates a stable frequency of deleterious mutations or the mutational load. Here I develop the comparable concept of a damage load, which is caused by harmful non-heritable changes to the phenotype. A damage load also ensues when the increase of damage is opposed by selection. The presence of a damage load favors the evolution of asymmetrical transmission of damage by a mother to her daughters. The asymmetry is beneficial because it increases fitness variance, but it also leads to aging or senescence. A mathematical model based on microbes reveals that a cell lineage dividing symmetrically is immortal if lifetime damage rates do not exceed a threshold. The evolution of asymmetry allows the lineage to persist above the threshold, but the lineage becomes mortal. In microbes with low genomic mutation rates, it is likely that the damage load is much greater than the mutational load. In metazoans with higher genomic mutation rates, the damage and the mutational load could be of the same magnitude. A fit of the model to experimental data shows that Escherichia coli cells experience a damage rate that is below the threshold and are immortal under the conditions examined. The model estimates the asymmetry level of E. coli to be low but sufficient for persisting at higher damage rates. The model also predicts that increasing asymmetry results in diminishing fitness returns, which may explain why the bacterium has not evolved higher asymmetry.

  4. 'Nothing of chemistry disappears in biology': the Top 30 damage-prone endogenous metabolites.

    Science.gov (United States)

    Lerma-Ortiz, Claudia; Jeffryes, James G; Cooper, Arthur J L; Niehaus, Thomas D; Thamm, Antje M K; Frelin, Océane; Aunins, Thomas; Fiehn, Oliver; de Crécy-Lagard, Valérie; Henry, Christopher S; Hanson, Andrew D

    2016-06-15

    Many common metabolites are intrinsically unstable and reactive, and hence prone to chemical (i.e. non-enzymatic) damage in vivo Although this fact is widely recognized, the purely chemical side-reactions of metabolic intermediates can be surprisingly hard to track down in the literature and are often treated in an unprioritized case-by-case way. Moreover, spontaneous chemical side-reactions tend to be overshadowed today by side-reactions mediated by promiscuous ('sloppy') enzymes even though chemical damage to metabolites may be even more prevalent than damage from enzyme sloppiness, has similar outcomes, and is held in check by similar biochemical repair or pre-emption mechanisms. To address these limitations and imbalances, here we draw together and systematically integrate information from the (bio)chemical literature, from cheminformatics, and from genome-scale metabolic models to objectively define a 'Top 30' list of damage-prone metabolites. A foundational part of this process was to derive general reaction rules for the damage chemistries involved. The criteria for a 'Top 30' metabolite included predicted chemical reactivity, essentiality, and occurrence in diverse organisms. We also explain how the damage chemistry reaction rules ('operators') are implemented in the Chemical-Damage-MINE (CD-MINE) database (minedatabase.mcs.anl.gov/#/top30) to provide a predictive tool for many additional potential metabolite damage products. Lastly, we illustrate how defining a 'Top 30' list can drive genomics-enabled discovery of the enzymes of previously unrecognized damage-control systems, and how applying chemical damage reaction rules can help identify previously unknown peaks in metabolomics profiles. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  5. Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells

    Directory of Open Access Journals (Sweden)

    Max Koeppel

    2015-06-01

    Full Text Available Infection with the human pathogen Helicobacter pylori (H. pylori is a major risk factor for gastric cancer. Since the bacterium exerts multiple genotoxic effects, we examined the circumstances of DNA damage accumulation and identified regions within the host genome with high susceptibility to H. pylori-induced damage. Infection impaired several DNA repair factors, the extent of which depends on a functional cagPAI. This leads to accumulation of a unique DNA damage pattern, preferentially in transcribed regions and proximal to telomeres, in both gastric cell lines and primary gastric epithelial cells. The observed pattern correlates with focal amplifications in adenocarcinomas of the stomach and partly overlaps with known cancer genes. We thus demonstrate an impact of a bacterial infection directed toward specific host genomic regions and describe underlying characteristics that make such regions more likely to acquire heritable changes during infection, which could contribute to cellular transformation.

  6. Fanconi anemia: a disorder defective in the DNA damage response.

    Science.gov (United States)

    Kitao, Hiroyuki; Takata, Minoru

    2011-04-01

    Fanconi anemia (FA) is a cancer predisposition disorder characterized by progressive bone marrow failure, congenital developmental defects, chromosomal abnormalities, and cellular hypersensitivity to DNA interstrand crosslink (ICL) agents. So far mutations in 14 FANC genes were identified in FA or FA-like patients. These gene products constitute a common ubiquitin-phosphorylation network called the "FA pathway" and cooperate with other proteins involved in DNA repair and cell cycle control to repair ICL lesions and to maintain genome stability. In this review, we summarize recent exciting discoveries that have expanded our view of the molecular mechanisms operating in DNA repair and DNA damage signaling.

  7. BDS thin film damage competition

    Science.gov (United States)

    Stolz, Christopher J.; Thomas, Michael D.; Griffin, Andrew J.

    2008-10-01

    A laser damage competition was held at the 2008 Boulder Damage Symposium in order to determine the current status of thin film laser resistance within the private, academic, and government sectors. This damage competition allows a direct comparison of the current state-of-the-art of high laser resistance coatings since they are all tested using the same damage test setup and the same protocol. A normal incidence high reflector multilayer coating was selected at a wavelength of 1064 nm. The substrates were provided by the submitters. A double blind test assured sample and submitter anonymity so only a summary of the results are presented here. In addition to the laser resistance results, details of deposition processes, coating materials, and layer count will also be shared.

  8. Probabilistic Fatigue Damage Program (FATIG)

    Science.gov (United States)

    Michalopoulos, Constantine

    2012-01-01

    FATIG computes fatigue damage/fatigue life using the stress rms (root mean square) value, the total number of cycles, and S-N curve parameters. The damage is computed by the following methods: (a) traditional method using Miner s rule with stress cycles determined from a Rayleigh distribution up to 3*sigma; and (b) classical fatigue damage formula involving the Gamma function, which is derived from the integral version of Miner's rule. The integration is carried out over all stress amplitudes. This software solves the problem of probabilistic fatigue damage using the integral form of the Palmgren-Miner rule. The software computes fatigue life using an approach involving all stress amplitudes, up to N*sigma, as specified by the user. It can be used in the design of structural components subjected to random dynamic loading, or by any stress analyst with minimal training for fatigue life estimates of structural components.

  9. Kava Linked to Liver Damage

    Science.gov (United States)

    ... of these countries to remove kava from the market. Although liver damage appears to be rare, the ... are marketed to men, women, children, and the elderly. Advice to Consumers Safety is a concern for ...

  10. Civil Liability for Environmental Damages

    Directory of Open Access Journals (Sweden)

    Daniela Ciochină

    2012-05-01

    Full Text Available We debated in this article the civil liability for environmental damages as stipulated in ourlegislation with reference to Community law. The theory of legal liability in environmental law is basedon the duty of all citizens to respect and protect the environment. Considering the importance ofenvironment in which we live, the liability for environmental damages is treated by the Constitution as aprinciple and a fundamental obligation. Many human activities cause environmental damages and, in linewith the principle of sustainable development, they should be avoided. However, when this is notpossible, they must be regulated (by criminal or administrative law in order to limit their adverse effectsand, according to the polluter pays principle, to internalize in advance their externalities (through taxes,insurances or other forms of financial security products. Communication aims to analyze these issues andlegal regulations dealing with the issue of liability for environmental damage.

  11. Corneal Damage from Infrared Radiation

    National Research Council Canada - National Science Library

    McCally, Russell

    2000-01-01

    ...) laser radiation at 10.6 (micrometer) and Tm: YAG laser radiation at 2.02 (micrometer). Retinal damage from sources with rectangular irradiance distributions was also modeled. Thresholds for CO(2...

  12. DNA damage assessment by visualization and quantification of DNA damage response

    International Nuclear Information System (INIS)

    Matsuda, Shun; Matsuda, Tomonari; Ikura, Tsuyoshi

    2017-01-01

    DNA damage response (DDR) carries out signal transduction for DNA repair, activation of cell cycle checkpoint, and apoptosis to maintain genome integrity, in response to DNA damage. Many proteins and their post-translational modifications participate in the process. Especially, S139-phosphorylated histone H2AX (γH2AX), which is formed by DNA double-strand breaks (DSBs), is an important factor to bring and retain other DDR proteins to DSB sites, Thus, γH2AX is used as a good indicator of DSBs in clinical study and pharmacology for efficacy evaluation of chemotherapy and radiotherapy, detection of precancerous regions, and others. In regulatory science, γH2AX is also a useful biomarker of genotoxicity of chemicals, since a wide range of genotoxic chemicals induce γH2AX. However, conventional detection methods of γH2AX absolutely require anti-γH2AX antibody whose staining is burdensome and time-consuming, and some of these methods are not so superior in quantitativity. In this review, we introduce two new methods to overcome these limitations, involving an easy-to-use genotoxicity assay using DDR-visualizing cells and an absolute quantification method of γH2AX using liquid chromatography-tandem mass spectrometry (LC/MS/MS). (author)

  13. Radiation Damage and Dimensional Changes

    International Nuclear Information System (INIS)

    El-Barbary, A.A.; Lebda, H.I.; Kamel, M.A.

    2009-01-01

    The dimensional changes have been modeled in order to be accommodated in the reactor design. This study has major implications for the interpretation of damage in carbon based nuclear fission and fusion plant materials. Radiation damage of graphite leads to self-interstitials and vacancies defects. The aggregation of these defects causes dimensional changes. Vacancies aggregate into lines and disks which heal and contract the basal planes. Interstitials aggregate into interlayer disks which expand the dimension

  14. Apportioning liability for transborder damage

    International Nuclear Information System (INIS)

    Krause-Ablass, W.D.

    1988-01-01

    The author analyses the different legal systems applicable to transfrontier nuclear damage. Using examples, he describes the mechanisms enabling a victim of such damage to identify the competent court and the relevant law, according to whether the provisions of the Paris or the Vienna Convention come into play or whether the rules of private international law, incorporated in the various national laws are applicable (NEA) [fr

  15. Damage Atlas for Photographic materials

    Directory of Open Access Journals (Sweden)

    Kristel Van Camp

    2010-11-01

    Full Text Available La conservation des documents photographiques peut nécessiter des interventions préventives ou curatives. Ce choix est guidé par leur état de conservation. Une meilleure connaissance des détériorations est donc cruciale. Le répertoire présenté ici essaie de les classifier selon des caractéristiques spécifiques et leur niveau de gravité. Les différents types de dégradation sont illustrés et décrits avec une terminologie précise. L’auteur propose en regard de ceux-ci l’intervention qui semble la plus appropriée. Ce répertoire s’adresse à toutes les personnes concernées par la photographie, qu’ils soient dans le milieu de la conservation ou dans le domaine artistique, dans les musées ou dans les archives. In order to rescue a damaged photographic object, preventive or conservative actions are needed. Knowing the specific characteristics of different types of damage is crucial. A damage atlas can provide these characteristics. With this atlas the damage can be recognised and appropriate actions can be taken. This damage atlas offers a first attempt to such a characterisation in the field of photography. The damage atlas contains images and the necessary information about damage on photographic material. The atlas with special annotations about the terminology and the grade of the damage is meant for everybody who works with photographic material, as well in museums as in archives.

  16. Genomic rearrangement in radiation-induced murine myeloid leukemia

    International Nuclear Information System (INIS)

    Ishihara, Hiroshi

    1994-01-01

    After whole body irradiation of 3Gy X ray to C3H/He male mice, acute myeloid leukemia is induced at an incidence of 20 to 30% within 2 years. We have studied the mechanism of occurrence of this radiation-induced murine myeloid leukemia. Detection and isolation of genomic structural aberration which may be accumulated accompanied with leukemogenesis are helpful in analyzing the complicated molecular process from radiation damage to leukemogenesis. So, our research work was done in three phases. First, structures of previously characterized oncogenes and cytokine-related genes were analyzed, and abnormal structures of fms(protooncogene encoding M-CSF receptor gene)-related and myc-related genes were found in several leukemia cells. Additionally, genomic structural aberration of IL-3 gene was observed in some leukemia cells, so that construction of genomic libraries and cloning of the abnormal IL-3 genomic DNAs were performed to characterize the structure. Secondly, because the breakage of chromosome 2 that is frequently observed in myeloid leukemia locates in proximal position of IL-1 gene cluster in some cases, the copy number of IL-1 gene was determined and the gene was cloned. Lastly, the abnormal genome of leukemia cell was cloned by in-gel competence reassociation method. We discussed these findings and evaluated the analysis of the molecular process of leukemogenesis using these cloned genomic fragments. (author)

  17. Genomic legacy of the African cheetah, Acinonyx jubatus.

    Science.gov (United States)

    Dobrynin, Pavel; Liu, Shiping; Tamazian, Gaik; Xiong, Zijun; Yurchenko, Andrey A; Krasheninnikova, Ksenia; Kliver, Sergey; Schmidt-Küntzel, Anne; Koepfli, Klaus-Peter; Johnson, Warren; Kuderna, Lukas F K; García-Pérez, Raquel; Manuel, Marc de; Godinez, Ricardo; Komissarov, Aleksey; Makunin, Alexey; Brukhin, Vladimir; Qiu, Weilin; Zhou, Long; Li, Fang; Yi, Jian; Driscoll, Carlos; Antunes, Agostinho; Oleksyk, Taras K; Eizirik, Eduardo; Perelman, Polina; Roelke, Melody; Wildt, David; Diekhans, Mark; Marques-Bonet, Tomas; Marker, Laurie; Bhak, Jong; Wang, Jun; Zhang, Guojie; O'Brien, Stephen J

    2015-12-10

    Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084-12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (pcheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah's extremely high (>80 %) pleiomorphic sperm. The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species' natural history, physiological adaptations and unique reproductive disposition.

  18. Genomics of Volvocine Algae

    Science.gov (United States)

    Umen, James G.; Olson, Bradley J.S.C.

    2015-01-01

    Volvocine algae are a group of chlorophytes that together comprise a unique model for evolutionary and developmental biology. The species Chlamydomonas reinhardtii and Volvox carteri represent extremes in morphological diversity within the Volvocine clade. Chlamydomonas is unicellular and reflects the ancestral state of the group, while Volvox is multicellular and has evolved numerous innovations including germ-soma differentiation, sexual dimorphism, and complex morphogenetic patterning. The Chlamydomonas genome sequence has shed light on several areas of eukaryotic cell biology, metabolism and evolution, while the Volvox genome sequence has enabled a comparison with Chlamydomonas that reveals some of the underlying changes that enabled its transition to multicellularity, but also underscores the subtlety of this transition. Many of the tools and resources are in place to further develop Volvocine algae as a model for evolutionary genomics. PMID:25883411

  19. Genomics of Preterm Birth

    Science.gov (United States)

    Swaggart, Kayleigh A.; Pavlicev, Mihaela; Muglia, Louis J.

    2015-01-01

    The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. PMID:25646385

  20. Genomics of Salmonella Species

    Science.gov (United States)

    Canals, Rocio; McClelland, Michael; Santiviago, Carlos A.; Andrews-Polymenis, Helene

    Progress in the study of Salmonella survival, colonization, and virulence has increased rapidly with the advent of complete genome sequencing and higher capacity assays for transcriptomic and proteomic analysis. Although many of these techniques have yet to be used to directly assay Salmonella growth on foods, these assays are currently in use to determine Salmonella factors necessary for growth in animal models including livestock animals and in in vitro conditions that mimic many different environments. As sequencing of the Salmonella genome and microarray analysis have revolutionized genomics and transcriptomics of salmonellae over the last decade, so are new high-throughput sequencing technologies currently accelerating the pace of our studies and allowing us to approach complex problems that were not previously experimentally tractable.

  1. Causes of genome instability: the effect of low dose chemical exposures in modern society

    Science.gov (United States)

    Langie, Sabine A.S.; Koppen, Gudrun; Desaulniers, Daniel; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Azqueta, Amaya; Bisson, William H.; Brown, Dustin; Brunborg, Gunnar; Charles, Amelia K.; Chen, Tao; Colacci, Annamaria; Darroudi, Firouz; Forte, Stefano; Gonzalez, Laetitia; Hamid, Roslida A.; Knudsen, Lisbeth E.; Leyns, Luc; Lopez de Cerain Salsamendi, Adela; Memeo, Lorenzo; Mondello, Chiara; Mothersill, Carmel; Olsen, Ann-Karin; Pavanello, Sofia; Raju, Jayadev; Rojas, Emilio; Roy, Rabindra; Ryan, Elizabeth; Ostrosky-Wegman, Patricia; Salem, Hosni K.; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Van Schooten, Frederik J.; Valverde, Mahara; Woodrick, Jordan; Zhang, Luoping; van Larebeke, Nik; Kirsch-Volders, Micheline; Collins, Andrew R.

    2015-01-01

    Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome’s integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis. PMID:26106144

  2. RENAL DAMAGE WITH MALIGNANT NEOPLASMS

    Directory of Open Access Journals (Sweden)

    I. B. Kolina

    2015-01-01

    Full Text Available The relationship between renal damage and malignant neoplasms is one of the most actual problems of the medicine of internal diseases. Very often, exactly availability of renal damage determines the forecast of cancer patients. The range of renal pathologies associated with tumors is unusually wide: from the mechanical effect of the tumor or metastases on the kidneys and/or the urinary tract and paraneoplastic manifestations in the form of nephritis or amyloidosis to nephropathies induced with drugs or tumor lysis, etc. Thrombotic complications that develop as a result of exposure to tumor effects, side effects of certain drugs or irradiation also play an important role in the development of the kidney damage. The most frequent variants of renal damage observed in the practice of medical internists (therapists, urologists, surgeons, etc., as well as methods of diagnosis and treatment approaches are described in the article. Timely and successful prevention and treatment of tumor-associated nephropathies give hope for retaining renal functions, therefore, a higher life standard after completion of anti-tumor therapy. Even a shortterm episode of acute renal damage suffered by a cancer patient must be accompanied with relevant examination and treatment. In the caseof transformation of acute renal damage into the chronic kidney disease, such patients need systematic and weighted renoprotective therapy and correct dosing of nephrotoxic drugs.

  3. Ebolavirus comparative genomics

    Science.gov (United States)

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat; Uberbacher, Edward C.; Land, Miriam; Zhang, Qian; Wanchai, Visanu; Chai, Juanjuan; Nielsen, Morten; Trolle, Thomas; Lund, Ole; Buzard, Gregory S.; Pedersen, Thomas D.; Wassenaar, Trudy M.; Ussery, David W.

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of the same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP) and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. This information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies. This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan). PMID:26175035

  4. Brief Guide to Genomics: DNA, Genes and Genomes

    Science.gov (United States)

    ... clinic. Most new drugs based on genome-based research are estimated to be at least 10 to 15 years away, though recent genome-driven efforts in lipid-lowering therapy have considerably shortened that interval. According ...

  5. Deoxyribonucleoprotein structure and radiation injury - Cellular radiosensitivity is determined by LET-infinity-dependent DNA damage in hydrated deoxyribonucleoproteins and the extent of its repair

    Science.gov (United States)

    Lett, J. T.; Peters, E. L.

    1992-01-01

    Until recently, OH radicals formed in bulk nuclear water were believed to be the major causes of DNA damage that results in cell death, especially for sparsely ionizing radiations. That hypothesis has now been challenged, if not refuted. Lethal genomic DNA damage is determined mainly by energy deposition in deoxyribonucleoproteins, and their hydration shells, and charge (energy) transfer processes within those structures.

  6. FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage.

    Science.gov (United States)

    Bigarella, Carolina L; Li, Jianfeng; Rimmelé, Pauline; Liang, Raymond; Sobol, Robert W; Ghaffari, Saghi

    2017-02-17

    Accumulation of damaged DNA in hematopoietic stem cells (HSC) is associated with chromosomal abnormalities, genomic instability, and HSC aging and might promote hematological malignancies with age. Despite this, the regulatory pathways implicated in the HSC DNA damage response have not been fully elucidated. One of the sources of DNA damage is reactive oxygen species (ROS) generated by both exogenous and endogenous insults. Balancing ROS levels in HSC requires FOXO3, which is an essential transcription factor for HSC maintenance implicated in HSC aging. Elevated ROS levels result in defective Foxo3 -/- HSC cycling, among many other deficiencies. Here, we show that loss of FOXO3 leads to the accumulation of DNA damage in primitive hematopoietic stem and progenitor cells (HSPC), associated specifically with reduced expression of genes implicated in the repair of oxidative DNA damage. We provide further evidence that Foxo3 -/- HSPC are defective in DNA damage repair. Specifically, we show that the base excision repair pathway, the main pathway utilized for the repair of oxidative DNA damage, is compromised in Foxo3 -/- primitive hematopoietic cells. Treating mice in vivo with N -acetylcysteine reduces ROS levels, rescues HSC cycling defects, and partially mitigates HSPC DNA damage. These results indicate that DNA damage accrued as a result of elevated ROS in Foxo3 -/- mutant HSPC is at least partially reversible. Collectively, our findings suggest that FOXO3 serves as a protector of HSC genomic stability and health. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

    Science.gov (United States)

    Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

    2000-01-01

    Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

  8. Genomic Prediction in Barley

    DEFF Research Database (Denmark)

    Edriss, Vahid; Cericola, Fabio; Jensen, Jens D

    2015-01-01

    to next generation. The main goal of this study was to see the potential of using genomic prediction in a commercial Barley breeding program. The data used in this study was from Nordic Seed company which is located in Denmark. Around 350 advanced lines were genotyped with 9K Barely chip from Illumina....... Traits used in this study were grain yield, plant height and heading date. Heading date is number days it takes after 1st June for plant to head. Heritabilities were 0.33, 0.44 and 0.48 for yield, height and heading, respectively for the average of nine plots. The GBLUP model was used for genomic...

  9. Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium.

    Science.gov (United States)

    Machado, Henrique; Gram, Lone

    2017-01-01

    Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur , amino-acid usage, ANI), which allowed us to identify two misidentified strains. Genome analyses also revealed occurrence of higher and lower GC content clades, correlating with phylogenetic clusters. Pan- and core-genome analysis revealed the conservation of 25% of the genome throughout the genus, with a large and open pan-genome. The major source of genomic diversity could be traced to the smaller chromosome and plasmids. Several of the physiological traits studied in the genus did not correlate with phylogenetic data. Since horizontal gene transfer (HGT) is often suggested as a source of genetic diversity and a potential driver of genomic evolution in bacterial species, we looked into evidence of such in Photobacterium genomes. Genomic islands were the source of genomic differences between strains of the same species. Also, we found transposase genes and CRISPR arrays that suggest multiple encounters with foreign DNA. Presence of genomic exchange traits was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.

  10. CEREBRAL CORTEX DAMAGE INDUCED BY ACUTE ORAL ...

    African Journals Online (AJOL)

    2018-02-28

    Feb 28, 2018 ... This study examines alcohol-induced cerebral cortex damage and the association with oxidative ... alcohol has profound effects on the function ... Chronic use of ..... Alcohol induced brain damage and liver damage in young.

  11. Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria

    OpenAIRE

    Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

    2017-01-01

    A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compen...

  12. The current state of eukaryotic DNA base damage and repair.

    Science.gov (United States)

    Bauer, Nicholas C; Corbett, Anita H; Doetsch, Paul W

    2015-12-02

    DNA damage is a natural hazard of life. The most common DNA lesions are base, sugar, and single-strand break damage resulting from oxidation, alkylation, deamination, and spontaneous hydrolysis. If left unrepaired, such lesions can become fixed in the genome as permanent mutations. Thus, evolution has led to the creation of several highly conserved, partially redundant pathways to repair or mitigate the effects of DNA base damage. The biochemical mechanisms of these pathways have been well characterized and the impact of this work was recently highlighted by the selection of Tomas Lindahl, Aziz Sancar and Paul Modrich as the recipients of the 2015 Nobel Prize in Chemistry for their seminal work in defining DNA repair pathways. However, how these repair pathways are regulated and interconnected is still being elucidated. This review focuses on the classical base excision repair and strand incision pathways in eukaryotes, considering both Saccharomyces cerevisiae and humans, and extends to some important questions and challenges facing the field of DNA base damage repair. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Study on DNA damages induced by UV radiation

    International Nuclear Information System (INIS)

    Doan Hong Van; Dinh Ba Tuan; Tran Tuan Anh; Nguyen Thuy Ngan; Ta Bich Thuan; Vo Thi Thuong Lan; Tran Minh Quynh; Nguyen Thi Thom

    2015-01-01

    DNA damages in Escherichia coli (E. coli) exposed to UV radiation have been investigated. After 30 min of exposure to UV radiation of 5 mJ/cm"2, the growth of E. coli in LB broth medium was about only 10% in compared with non-irradiated one. This results suggested that the UV radiation caused the damages for E. coli genome resulted in reduction in its growth and survival, and those lesions can be somewhat recovered. For both solutions of plasmid DNAs and E. coli cells containing plasmid DNA, this dose also caused the breakage on single and double strands of DNA, shifted the morphology of DNA plasmid from supercoiled to circular and linear forms. The formation of pyrimidine dimers upon UV radiation significantly reduced when the DNA was irradiated in the presence of Ganoderma lucidum extract. Thus, studies on UV-induced DNA damage at molecular level are very essential to determine the UV radiation doses corresponding to the DNA damages, especially for creation and selection of useful radiation-induced mutants, as well as elucidation the protective effects of the specific compounds against UV light. (author)

  14. phiGENOME: an integrative navigation throughout bacteriophage genomes.

    Science.gov (United States)

    Stano, Matej; Klucar, Lubos

    2011-11-01

    phiGENOME is a web-based genome browser generating dynamic and interactive graphical representation of phage genomes stored in the phiSITE, database of gene regulation in bacteriophages. phiGENOME is an integral part of the phiSITE web portal (http://www.phisite.org/phigenome) and it was optimised for visualisation of phage genomes with the emphasis on the gene regulatory elements. phiGENOME consists of three components: (i) genome map viewer built using Adobe Flash technology, providing dynamic and interactive graphical display of phage genomes; (ii) sequence browser based on precisely formatted HTML tags, providing detailed exploration of genome features on the sequence level and (iii) regulation illustrator, based on Scalable Vector Graphics (SVG) and designed for graphical representation of gene regulations. Bringing 542 complete genome sequences accompanied with their rich annotations and references, makes phiGENOME a unique information resource in the field of phage genomics. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. RTEL1 maintains genomic stability by suppressing homologous recombination.

    Science.gov (United States)

    Barber, Louise J; Youds, Jillian L; Ward, Jordan D; McIlwraith, Michael J; O'Neil, Nigel J; Petalcorin, Mark I R; Martin, Julie S; Collis, Spencer J; Cantor, Sharon B; Auclair, Melissa; Tissenbaum, Heidi; West, Stephen C; Rose, Ann M; Boulton, Simon J

    2008-10-17

    Homologous recombination (HR) is an important conserved process for DNA repair and ensures maintenance of genome integrity. Inappropriate HR causes gross chromosomal rearrangements and tumorigenesis in mammals. In yeast, the Srs2 helicase eliminates inappropriate recombination events, but the functional equivalent of Srs2 in higher eukaryotes has been elusive. Here, we identify C. elegans RTEL-1 as a functional analog of Srs2 and describe its vertebrate counterpart, RTEL1, which is required for genome stability and tumor avoidance. We find that rtel-1 mutant worms and RTEL1-depleted human cells share characteristic phenotypes with yeast srs2 mutants: lethality upon deletion of the sgs1/BLM homolog, hyperrecombination, and DNA damage sensitivity. In vitro, purified human RTEL1 antagonizes HR by promoting the disassembly of D loop recombination intermediates in a reaction dependent upon ATP hydrolysis. We propose that loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer.

  16. Illuminating the Druggable Genome (IDG)

    Data.gov (United States)

    Federal Laboratory Consortium — Results from the Human Genome Project revealed that the human genome contains 20,000 to 25,000 genes. A gene contains (encodes) the information that each cell uses...

  17. National Human Genome Research Institute

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  18. Glaucomatous damage of the macula.

    Science.gov (United States)

    Hood, Donald C; Raza, Ali S; de Moraes, Carlos Gustavo V; Liebmann, Jeffrey M; Ritch, Robert

    2013-01-01

    There is a growing body of evidence that early glaucomatous damage involves the macula. The anatomical basis of this damage can be studied using frequency domain optical coherence tomography (fdOCT), by which the local thickness of the retinal nerve fiber layer (RNFL) and local retinal ganglion cell plus inner plexiform (RGC+) layer can be measured. Based upon averaged fdOCT results from healthy controls and patients, we show that: 1. For healthy controls, the average RGC+ layer thickness closely matches human histological data; 2. For glaucoma patients and suspects, the average RGC+ layer shows greater glaucomatous thinning in the inferior retina (superior visual field (VF)); and 3. The central test points of the 6° VF grid (24-2 test pattern) miss the region of greatest RGC+ thinning. Based upon fdOCT results from individual patients, we have learned that: 1. Local RGC+ loss is associated with local VF sensitivity loss as long as the displacement of RGCs from the foveal center is taken into consideration; and 2. Macular damage is typically arcuate in nature and often associated with local RNFL thinning in a narrow region of the disc, which we call the macular vulnerability zone (MVZ). According to our schematic model of macular damage, most of the inferior region of the macula projects to the MVZ, which is located largely in the inferior quadrant of the disc, a region that is particularly susceptible to glaucomatous damage. A small (cecocentral) region of the inferior macula, and all of the superior macula (inferior VF), project to the temporal quadrant, a region that is less susceptible to damage. The overall message is clear; clinicians need to be aware that glaucomatous damage to the macula is common, can occur early in the disease, and can be missed and/or underestimated with standard VF tests that use a 6° grid, such as the 24-2 VF test. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Eccentric localization of catalase to protect chromosomes from oxidative damages during meiotic maturation in mouse oocytes.

    Science.gov (United States)

    Park, Yong Seok; You, Seung Yeop; Cho, Sungrae; Jeon, Hyuk-Joon; Lee, Sukchan; Cho, Dong-Hyung; Kim, Jae-Sung; Oh, Jeong Su

    2016-09-01

    The maintenance of genomic integrity and stability is essential for the survival of every organism. Unfortunately, DNA is vulnerable to attack by a variety of damaging agents. Oxidative stress is a major cause of DNA damage because reactive oxygen species (ROS) are produced as by-products of normal cellular metabolism. Cells have developed eloquent antioxidant defense systems to protect themselves from oxidative damage along with aerobic metabolism. Here, we show that catalase (CAT) is present in mouse oocytes to protect the genome from oxidative damage during meiotic maturation. CAT was expressed in the nucleus to form unique vesicular structures. However, after nuclear envelope breakdown, CAT was redistributed in the cytoplasm with particular focus at the chromosomes. Inhibition of CAT activity increased endogenous ROS levels, but did not perturb meiotic maturation. In addition, CAT inhibition produced chromosomal defects, including chromosome misalignment and DNA damage. Therefore, our data suggest that CAT is required not only to scavenge ROS, but also to protect DNA from oxidative damage during meiotic maturation in mouse oocytes.

  20. DNA repair and the evolution of transformation in Bacillus subtilis. 3. Sex with damaged DNA

    International Nuclear Information System (INIS)

    Hoelzer, M.A.; Michod, R.E.

    1991-01-01

    Natural genetic transformation in the bacterium Bacillus subtilis provides an experimental system for studying the evolutionary function of sexual recombination. The repair hypothesis proposes that during transformation the exogenous DNA taken up by cells is used as template for recombinational repair of damages in the recipient cell's genome. Earlier results demonstrated that the population density of transformed cells (i.e., sexual cells) increases, relative to nontransformed cells (primarily asexual cells), with increasing dosage of ultraviolet irradiation, provided that the cells are transformed with undamaged homologous DNA after they have become damaged. In nature, however, donor DNA for transformation is likely to come from cells that are as damaged as the recipient cells. In order to better simulate the effects of transformation in natural populations we conducted similar experiments as those just described using damaged donor DNA. The authors document in this report that transformants continue to increase in relative density even if they are transformed with damaged donor DNA. These results suggest that sites of transformation are often damaged sites in the recipient cell's genome

  1. Genomic prediction using subsampling.

    Science.gov (United States)

    Xavier, Alencar; Xu, Shizhong; Muir, William; Rainey, Katy Martin

    2017-03-24

    Genome-wide assisted selection is a critical tool for the genetic improvement of plants and animals. Whole-genome regression models in Bayesian framework represent the main family of prediction methods. Fitting such models with a large number of observations involves a prohibitive computational burden. We propose the use of subsampling bootstrap Markov chain in genomic prediction. Such method consists of fitting whole-genome regression models by subsampling observations in each round of a Markov Chain Monte Carlo. We evaluated the effect of subsampling bootstrap on prediction and computational parameters. Across datasets, we observed an optimal subsampling proportion of observations around 50% with replacement, and around 33% without replacement. Subsampling provided a substantial decrease in computation time, reducing the time to fit the model by half. On average, losses on predictive properties imposed by subsampling were negligible, usually below 1%. For each dataset, an optimal subsampling point that improves prediction properties was observed, but the improvements were also negligible. Combining subsampling with Gibbs sampling is an interesting ensemble algorithm. The investigation indicates that the subsampling bootstrap Markov chain algorithm substantially reduces computational burden associated with model fitting, and it may slightly enhance prediction properties.

  2. The Lotus japonicus genome

    DEFF Research Database (Denmark)

    Fabaceae, groundbreaking genetic and genomic research has established a significant body of knowledge on Lotus japonicus, which was adopted as a model species more than 20 years ago. The diverse nature of legumes means that such research has a wide potential and agricultural impact, for example...

  3. Genomic taxonomy of vibrios

    DEFF Research Database (Denmark)

    Thompson, Cristiane C.; Vicente, Ana Carolina P.; Souza, Rangel C.

    2009-01-01

    BACKGROUND: Vibrio taxonomy has been based on a polyphasic approach. In this study, we retrieve useful taxonomic information (i.e. data that can be used to distinguish different taxonomic levels, such as species and genera) from 32 genome sequences of different vibrio species. We use a variety of...

  4. The Genome Atlas Resource

    DEFF Research Database (Denmark)

    Azam Qureshi, Matloob; Rotenberg, Eva; Stærfeldt, Hans Henrik

    2010-01-01

    with scripts and algorithms developed in a variety of programming languages at the Centre for Biological Sequence Analysis in order to create a three-tier software application for genome analysis. The results are made available via a web interface developed in Java, PHP and Perl CGI. User...

  5. Genomic Signatures of Reinforcement

    Directory of Open Access Journals (Sweden)

    Austin G. Garner

    2018-04-01

    Full Text Available Reinforcement is the process by which selection against hybridization increases reproductive isolation between taxa. Much research has focused on demonstrating the existence of reinforcement, yet relatively little is known about the genetic basis of reinforcement or the evolutionary conditions under which reinforcement can occur. Inspired by reinforcement’s characteristic phenotypic pattern of reproductive trait divergence in sympatry but not in allopatry, we discuss whether reinforcement also leaves a distinct genomic pattern. First, we describe three patterns of genetic variation we expect as a consequence of reinforcement. Then, we discuss a set of alternative processes and complicating factors that may make the identification of reinforcement at the genomic level difficult. Finally, we consider how genomic analyses can be leveraged to inform if and to what extent reinforcement evolved in the face of gene flow between sympatric lineages and between allopatric and sympatric populations of the same lineage. Our major goals are to understand if genome scans for particular patterns of genetic variation could identify reinforcement, isolate the genetic basis of reinforcement, or infer the conditions under which reinforcement evolved.

  6. Better chocolate through genomics

    Science.gov (United States)

    Theobroma cacao, the cacao or chocolate tree, is a tropical understory tree whose seeds are used to make chocolate. And like any important crop, cacao is the subject of much research. On September 15, 2010, scientists publicly released a preliminary sequence of the cacao genome--which contains all o...

  7. Functional genomics of tomato

    Indian Academy of Sciences (India)

    2014-10-20

    Oct 20, 2014 ... 1Repository of Tomato Genomics Resources, Department of Plant Sciences, School .... Due to its position at the crossroads of Sanger's sequencing .... replacement for the microarray-based expression profiling. .... during RNA fragmentation step prior to library construction, ...... tomato pollen as a test case.

  8. Genomic Signatures of Reinforcement

    Science.gov (United States)

    Goulet, Benjamin E.

    2018-01-01

    Reinforcement is the process by which selection against hybridization increases reproductive isolation between taxa. Much research has focused on demonstrating the existence of reinforcement, yet relatively little is known about the genetic basis of reinforcement or the evolutionary conditions under which reinforcement can occur. Inspired by reinforcement’s characteristic phenotypic pattern of reproductive trait divergence in sympatry but not in allopatry, we discuss whether reinforcement also leaves a distinct genomic pattern. First, we describe three patterns of genetic variation we expect as a consequence of reinforcement. Then, we discuss a set of alternative processes and complicating factors that may make the identification of reinforcement at the genomic level difficult. Finally, we consider how genomic analyses can be leveraged to inform if and to what extent reinforcement evolved in the face of gene flow between sympatric lineages and between allopatric and sympatric populations of the same lineage. Our major goals are to understand if genome scans for particular patterns of genetic variation could identify reinforcement, isolate the genetic basis of reinforcement, or infer the conditions under which reinforcement evolved. PMID:29614048

  9. The Nostoc punctiforme Genome

    Energy Technology Data Exchange (ETDEWEB)

    John C. Meeks

    2001-12-31

    Nostoc punctiforme is a filamentous cyanobacterium with extensive phenotypic characteristics and a relatively large genome, approaching 10 Mb. The phenotypic characteristics include a photoautotrophic, diazotrophic mode of growth, but N. punctiforme is also facultatively heterotrophic; its vegetative cells have multiple development alternatives, including terminal differentiation into nitrogen-fixing heterocysts and transient differentiation into spore-like akinetes or motile filaments called hormogonia; and N. punctiforme has broad symbiotic competence with fungi and terrestrial plants, including bryophytes, gymnosperms and an angiosperm. The shotgun-sequencing phase of the N. punctiforme strain ATCC 29133 genome has been completed by the Joint Genome Institute. Annotation of an 8.9 Mb database yielded 7432 open reading frames, 45% of which encode proteins with known or probable known function and 29% of which are unique to N. punctiforme. Comparative analysis of the sequence indicates a genome that is highly plastic and in a state of flux, with numerous insertion sequences and multilocus repeats, as well as genes encoding transposases and DNA modification enzymes. The sequence also reveals the presence of genes encoding putative proteins that collectively define almost all characteristics of cyanobacteria as a group. N. punctiforme has an extensive potential to sense and respond to environmental signals as reflected by the presence of more than 400 genes encoding sensor protein kinases, response regulators and other transcriptional factors. The signal transduction systems and any of the large number of unique genes may play essential roles in the cell differentiation and symbiotic interaction properties of N. punctiforme.

  10. Comparative Genomics of Eukaryotes.

    NARCIS (Netherlands)

    Noort, V. van

    2007-01-01

    This thesis focuses on developing comparative genomics methods in eukaryotes, with an emphasis on applications for gene function prediction and regulatory element detection. In the past, methods have been developed to predict functional associations between gene pairs in prokaryotes. The challenge

  11. Searching for genomic constraints

    Energy Technology Data Exchange (ETDEWEB)

    Lio` , P [Cambridge, Univ. (United Kingdom). Genetics Dept.; Ruffo, S [Florence, Univ. (Italy). Fac. di Ingegneria. Dipt. di Energetica ` S. Stecco`

    1998-01-01

    The authors have analyzed general properties of very long DNA sequences belonging to simple and complex organisms, by using different correlation methods. They have distinguished those base compositional rules that concern the entire genome which they call `genomic constraints` from the rules that depend on the `external natural selection` acting on single genes, i. e. protein-centered constraints. They show that G + C content, purine / pyrimidine distributions and biological complexity of the organism are the most important factors which determine base compositional rules and genome complexity. Three main facts are here reported: bacteria with high G + C content have more restrictions on base composition than those with low G + C content; at constant G + C content more complex organisms, ranging from prokaryotes to higher eukaryotes (e.g. human) display an increase of repeats 10-20 nucleotides long, which are also partly responsible for long-range correlations; work selection of length 3 to 10 is stronger in human and in bacteria for two distinct reasons. With respect to previous studies, they have also compared the genomic sequence of the archeon Methanococcus jannaschii with those of bacteria and eukaryotes: it shows sometimes an intermediate statistical behaviour.

  12. Searching for genomic constraints

    International Nuclear Information System (INIS)

    Lio', P.; Ruffo, S.

    1998-01-01

    The authors have analyzed general properties of very long DNA sequences belonging to simple and complex organisms, by using different correlation methods. They have distinguished those base compositional rules that concern the entire genome which they call 'genomic constraints' from the rules that depend on the 'external natural selection' acting on single genes, i. e. protein-centered constraints. They show that G + C content, purine / pyrimidine distributions and biological complexity of the organism are the most important factors which determine base compositional rules and genome complexity. Three main facts are here reported: bacteria with high G + C content have more restrictions on base composition than those with low G + C content; at constant G + C content more complex organisms, ranging from prokaryotes to higher eukaryotes (e.g. human) display an increase of repeats 10-20 nucleotides long, which are also partly responsible for long-range correlations; work selection of length 3 to 10 is stronger in human and in bacteria for two distinct reasons. With respect to previous studies, they have also compared the genomic sequence of the archeon Methanococcus jannaschii with those of bacteria and eukaryotes: it shows sometimes an intermediate statistical behaviour

  13. Genomic sequencing in clinical trials

    OpenAIRE

    Mestan, Karen K; Ilkhanoff, Leonard; Mouli, Samdeep; Lin, Simon

    2011-01-01

    Abstract Human genome sequencing is the process by which the exact order of nucleic acid base pairs in the 24 human chromosomes is determined. Since the completion of the Human Genome Project in 2003, genomic sequencing is rapidly becoming a major part of our translational research efforts to understand and improve human health and disease. This article reviews the current and future directions of clinical research with respect to genomic sequencing, a technology that is just beginning to fin...

  14. Statistical Methods in Integrative Genomics

    Science.gov (United States)

    Richardson, Sylvia; Tseng, George C.; Sun, Wei

    2016-01-01

    Statistical methods in integrative genomics aim to answer important biology questions by jointly analyzing multiple types of genomic data (vertical integration) or aggregating the same type of data across multiple studies (horizontal integration). In this article, we introduce different types of genomic data and data resources, and then review statistical methods of integrative genomics, with emphasis on the motivation and rationale of these methods. We conclude with some summary points and future research directions. PMID:27482531

  15. From plant genomes to phenotypes

    OpenAIRE

    Bolger, Marie; Gundlach, Heidrun; Scholz, Uwe; Mayer, Klaus; Usadel, Björn; Schwacke, Rainer; Schmutzer, Thomas; Chen, Jinbo; Arend, Daniel; Oppermann, Markus; Weise, Stephan; Lange, Matthias; Fiorani, Fabio; Spannagl, Manuel

    2017-01-01

    Recent advances in sequencing technologies have greatly accelerated the rate of plant genome and applied breeding research. Despite this advancing trend, plant genomes continue to present numerous difficulties to the standard tools and pipelines not only for genome assembly but also gene annotation and downstream analysis.Here we give a perspective on tools, resources and services necessary to assemble and analyze plant genomes and link them to plant phenotypes.

  16. DNA Damage, Mutagenesis and Cancer

    Directory of Open Access Journals (Sweden)

    Ashis K. Basu

    2018-03-01

    Full Text Available A large number of chemicals and several physical agents, such as UV light and γ-radiation, have been associated with the etiology of human cancer. Generation of DNA damage (also known as DNA adducts or lesions induced by these agents is an important first step in the process of carcinogenesis. Evolutionary processes gave rise to DNA repair tools that are efficient in repairing damaged DNA; yet replication of damaged DNA may take place prior to repair, particularly when they are induced at a high frequency. Damaged DNA replication may lead to gene mutations, which in turn may give rise to altered proteins. Mutations in an oncogene, a tumor-suppressor gene, or a gene that controls the cell cycle can generate a clonal cell population with a distinct advantage in proliferation. Many such events, broadly divided into the stages of initiation, promotion, and progression, which may occur over a long period of time and transpire in the context of chronic exposure to carcinogens, can lead to the induction of human cancer. This is exemplified in the long-term use of tobacco being responsible for an increased risk of lung cancer. This mini-review attempts to summarize this wide area that centers on DNA damage as it relates to the development of human cancer.

  17. Autophagy in DNA Damage Response

    Directory of Open Access Journals (Sweden)

    Piotr Czarny

    2015-01-01

    Full Text Available DNA damage response (DDR involves DNA repair, cell cycle regulation and apoptosis, but autophagy is also suggested to play a role in DDR. Autophagy can be activated in response to DNA-damaging agents, but the exact mechanism underlying this activation is not fully understood, although it is suggested that it involves the inhibition of mammalian target of rapamycin complex 1 (mTORC1. mTORC1 represses autophagy via phosphorylation of the ULK1/2–Atg13–FIP200 complex thus preventing maturation of pre-autophagosomal structures. When DNA damage occurs, it is recognized by some proteins or their complexes, such as poly(ADPribose polymerase 1 (PARP-1, Mre11–Rad50–Nbs1 (MRN complex or FOXO3, which activate repressors of mTORC1. SQSTM1/p62 is one of the proteins whose levels are regulated via autophagic degradation. Inhibition of autophagy by knockout of FIP200 results in upregulation of SQSTM1/p62, enhanced DNA damage and less efficient damage repair. Mitophagy, one form of autophagy involved in the selective degradation of mitochondria, may also play role in DDR. It degrades abnormal mitochondria and can either repress or activate apoptosis, but the exact mechanism remains unknown. There is a need to clarify the role of autophagy in DDR, as this process may possess several important biomedical applications, involving also cancer therapy.

  18. Radiation exposure and chromosome damage

    International Nuclear Information System (INIS)

    Lloyd, D.

    1979-01-01

    Chromosome damage is discussed as a means of biologically measuring radiation exposure to the body. Human lymphocytes are commonly used for this test since the extent of chromosome damage induced is related to the exposure dose. Several hundred lymphocytes are analysed in metaphase for chromosome damage, particularly dicentrics. The dose estimate is made by comparing the observed dicentric yield against calibration curves, previously produced by in vitro irradiation of blood samples to known doses of different types of radiation. This test is useful when there is doubt that the film badge has recorded a reasonable whole body dose and also when there is an absence of any physical data. A case of deliberate exposure is described where the chromosome damage test estimated an exposure of 152 rads. The life span of cell aberrations is also considered. Regular checks on radiotherapy patients and some accidental overdose cases have shown little reduction in the aberration levels over the first six weeks after which the damage disappears slowly with a half-life of about three years. In conclusion, chromosome studies have been shown to be of value in resolving practical problems in radiological protection. (U.K.)

  19. A Thousand Fly Genomes: An Expanded Drosophila Genome Nexus.

    Science.gov (United States)

    Lack, Justin B; Lange, Jeremy D; Tang, Alison D; Corbett-Detig, Russell B; Pool, John E

    2016-12-01

    The Drosophila Genome Nexus is a population genomic resource that provides D. melanogaster genomes from multiple sources. To facilitate comparisons across data sets, genomes are aligned using a common reference alignment pipeline which involves two rounds of mapping. Regions of residual heterozygosity, identity-by-descent, and recent population admixture are annotated to enable data filtering based on the user's needs. Here, we present a significant expansion of the Drosophila Genome Nexus, which brings the current data object to a total of 1,121 wild-derived genomes. New additions include 305 previously unpublished genomes from inbred lines representing six population samples in Egypt, Ethiopia, France, and South Africa, along with another 193 genomes added from recently-published data sets. We also provide an aligned D. simulans genome to facilitate divergence comparisons. This improved resource will broaden the range of population genomic questions that can addressed from multi-population allele frequencies and haplotypes in this model species. The larger set of genomes will also enhance the discovery of functionally relevant natural variation that exists within and between populations. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  20. Periodontal tissue damage in smokers

    Directory of Open Access Journals (Sweden)

    Hutojo Djajakusuma

    2006-09-01

    Full Text Available Dental plaque is the primary etiological factor in periodontal diseases. However, there are many factors that can modify how an individual periodontal tissue will respond to the accumulation of dental plaque. Among such risk factors, there is increasing evidence that smoking tobacco products alters the expression and rate of progression of periodontal diseases. The aim of this study was to find out the loss of periodontal tissue adhesion in smokers by measuring pocket depth using probe, and by measuring alveolar bone damage using Bone Loss Score (BLS radiographic methods on teeth 12, 11, 21, 22, 32, 31, 41, 42. Based on T Test statistical analysis, there were significant differences in pocket depth damage of alveolar bone in smokers and non smokers. In conclusion there were increasing pocket depth and alveolar bone damage in smokers.

  1. Innovative repair of subsidence damage

    International Nuclear Information System (INIS)

    Marino, G.G.

    1992-01-01

    In order to improve handling of subsidence damages the Illinois Mine Subsidence Insurance Fund supported the development of novel cost-effective methods of repair. The research in developing the repairs was directed towards the most common and costly damages that had been observed. As a result repair techniques were designed for structurally cracked foundations in the tension zone; structurally cracked foundations in the compression zone; and damaged or undamaged tilted foundations. When appropriate the postulated methods would result in: 1. significant cost savings (over conventional procedures); 2. a structural capacity greater than when the foundation was uncracked; and 3. an aesthetic appeal. All the postulated repair methodologies were laboratory and/or field tested. This paper will summarize the essentials of each technique developed and the test results

  2. Taking a Bad Turn: Compromised DNA Damage Response in Leukemia

    Directory of Open Access Journals (Sweden)

    Nadine Nilles

    2017-05-01

    Full Text Available Genomic integrity is of outmost importance for the survival at the cellular and the organismal level and key to human health. To ensure the integrity of their DNA, cells have evolved maintenance programs collectively known as the DNA damage response. Particularly challenging for genome integrity are DNA double-strand breaks (DSB and defects in their repair are often associated with human disease, including leukemia. Defective DSB repair may not only be disease-causing, but further contribute to poor treatment outcome and poor prognosis in leukemia. Here, we review current insight into altered DSB repair mechanisms identified in leukemia. While DSB repair is somewhat compromised in all leukemic subtypes, certain key players of DSB repair are particularly targeted: DNA-dependent protein kinase (DNA-PK and Ku70/80 in the non-homologous end-joining pathway, as well as Rad51 and breast cancer 1/2 (BRCA1/2, key players in homologous recombination. Defects in leukemia-related DSB repair may not only arise from dysfunctional repair components, but also indirectly from mutations in key regulators of gene expression and/or chromatin structure, such as p53, the Kirsten ras oncogene (K-RAS, and isocitrate dehydrogenase 1 and 2 (IDH1/2. A detailed understanding of the basis for defective DNA damage response (DDR mechanisms for each leukemia subtype may allow to further develop new treatment methods to improve treatment outcome and prognosis for patients.

  3. Genome-wide map of Apn1 binding sites under oxidative stress in Saccharomyces cerevisiae.

    Science.gov (United States)

    Morris, Lydia P; Conley, Andrew B; Degtyareva, Natalya; Jordan, I King; Doetsch, Paul W

    2017-11-01

    The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements. Previous studies demonstrated that a particular region of chromosome II is susceptible to chronic oxidative stress-induced chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA repair hotspots. Here we investigated the relationship between oxidative damage and genomic instability utilizing chromatin immunoprecipitation combined with DNA microarray technology to profile DNA repair sites along yeast chromosomes under different oxidative stress conditions. We targeted the major yeast AP endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1 target sequences are enriched for cytosine and guanine nucleotides. We predict that BER protects these sites in the genome because guanines and cytosines are thought to be especially susceptible to oxidative attack, thereby preventing large-scale genome destabilization from chronic accumulation of DNA damage. Information from our studies should provide insight into how regional deployment of oxidative DNA damage management systems along chromosomes protects against large-scale rearrangements. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  4. The CATDAT damaging earthquakes database

    Directory of Open Access Journals (Sweden)

    J. E. Daniell

    2011-08-01

    Full Text Available The global CATDAT damaging earthquakes and secondary effects (tsunami, fire, landslides, liquefaction and fault rupture database was developed to validate, remove discrepancies, and expand greatly upon existing global databases; and to better understand the trends in vulnerability, exposure, and possible future impacts of such historic earthquakes.

    Lack of consistency and errors in other earthquake loss databases frequently cited and used in analyses was a major shortcoming in the view of the authors which needed to be improved upon.

    Over 17 000 sources of information have been utilised, primarily in the last few years, to present data from over 12 200 damaging earthquakes historically, with over 7000 earthquakes since 1900 examined and validated before insertion into the database. Each validated earthquake includes seismological information, building damage, ranges of social losses to account for varying sources (deaths, injuries, homeless, and affected, and economic losses (direct, indirect, aid, and insured.

    Globally, a slightly increasing trend in economic damage due to earthquakes is not consistent with the greatly increasing exposure. The 1923 Great Kanto ($214 billion USD damage; 2011 HNDECI-adjusted dollars compared to the 2011 Tohoku (>$300 billion USD at time of writing, 2008 Sichuan and 1995 Kobe earthquakes show the increasing concern for economic loss in urban areas as the trend should be expected to increase. Many economic and social loss values not reported in existing databases have been collected. Historical GDP (Gross Domestic Product, exchange rate, wage information, population, HDI (Human Development Index, and insurance information have been collected globally to form comparisons.

    This catalogue is the largest known cross-checked global historic damaging earthquake database and should have far-reaching consequences for earthquake loss estimation, socio-economic analysis, and the global

  5. The CATDAT damaging earthquakes database

    Science.gov (United States)

    Daniell, J. E.; Khazai, B.; Wenzel, F.; Vervaeck, A.

    2011-08-01

    The global CATDAT damaging earthquakes and secondary effects (tsunami, fire, landslides, liquefaction and fault rupture) database was developed to validate, remove discrepancies, and expand greatly upon existing global databases; and to better understand the trends in vulnerability, exposure, and possible future impacts of such historic earthquakes. Lack of consistency and errors in other earthquake loss databases frequently cited and used in analyses was a major shortcoming in the view of the authors which needed to be improved upon. Over 17 000 sources of information have been utilised, primarily in the last few years, to present data from over 12 200 damaging earthquakes historically, with over 7000 earthquakes since 1900 examined and validated before insertion into the database. Each validated earthquake includes seismological information, building damage, ranges of social losses to account for varying sources (deaths, injuries, homeless, and affected), and economic losses (direct, indirect, aid, and insured). Globally, a slightly increasing trend in economic damage due to earthquakes is not consistent with the greatly increasing exposure. The 1923 Great Kanto (214 billion USD damage; 2011 HNDECI-adjusted dollars) compared to the 2011 Tohoku (>300 billion USD at time of writing), 2008 Sichuan and 1995 Kobe earthquakes show the increasing concern for economic loss in urban areas as the trend should be expected to increase. Many economic and social loss values not reported in existing databases have been collected. Historical GDP (Gross Domestic Product), exchange rate, wage information, population, HDI (Human Development Index), and insurance information have been collected globally to form comparisons. This catalogue is the largest known cross-checked global historic damaging earthquake database and should have far-reaching consequences for earthquake loss estimation, socio-economic analysis, and the global reinsurance field.

  6. Radiation-induced liver damage

    International Nuclear Information System (INIS)

    Marcial, V.A.; Santiago-Delpin, E.A.; Lanaro, A.E.; Castro-Vita, H.; Arroyo, G.; Moscol, J.A.; Gomez, C.; Velazquez, J.; Prado, K.

    1977-01-01

    Due to the recent increase in the use of radiation therapy in the treatment of cancer with or without chemotherapy, the risk of liver radiation damage has become a significant concern for the radiotherapist when the treated tumour is located in the upper abdomen or lower thorax. Clinically evident radiation liver damage may result in significant mortality, but at times patients recover without sequelae. The dose of 3000 rads in 3 weeks to the entire liver with 5 fractions per week of 200 rads each, seems to be tolerated well clinically by adult humans. Lower doses may lead to damage when used in children, when chemotherapy is added, as in recent hepatectomy cases, and in the presence of pre-existent liver damage. Reduced fractionation may lead to increased damage. Increased fractionation, limitation of the dose delivered to the entire liver, and restriction of the high dose irradiation volume may afford protection. With the aim of studying the problems of hepatic radiation injury in humans, a project of liver irradiation in the dog is being conducted. Mongrel dogs are being conditioned, submitted to pre-irradiation studies (haemogram, blood chemistry, liver scan and biopsy), irradiated under conditions resembling human cancer therapy, and submitted to post-irradiation evaluation of the liver. Twenty-two dogs have been entered in the study but only four qualify for the evaluation of all the study parameters. It has been found that dogs are susceptible to liver irradiation damage similar to humans. The initial mortality has been high mainly due to non-radiation factors which are being kept under control at the present phase of the study. After the initial experiences, the study will involve variations in total dose and fractionation, and the addition of anticoagulant therapy for possible prevention of radiation liver injury. (author)

  7. AKT phosphorylates H3-threonine 45 to facilitate termination of gene transcription in response to DNA damage

    OpenAIRE

    Lee, Jong-Hyuk; Kang, Byung-Hee; Jang, Hyonchol; Kim, Tae Wan; Choi, Jinmi; Kwak, Sojung; Han, Jungwon; Cho, Eun-Jung; Youn, Hong-Duk

    2015-01-01

    Post-translational modifications of core histones affect various cellular processes, primarily through transcription. However, their relationship with the termination of transcription has remained largely unknown. In this study, we show that DNA damage-activated AKT phosphorylates threonine 45 of core histone H3 (H3-T45). By genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis, H3-T45 phosphorylation was distributed throughout DNA damage-responsive gene loci, particularly ...

  8. The perennial ryegrass GenomeZipper: targeted use of genome resources for comparative grass genomics.

    Science.gov (United States)

    Pfeifer, Matthias; Martis, Mihaela; Asp, Torben; Mayer, Klaus F X; Lübberstedt, Thomas; Byrne, Stephen; Frei, Ursula; Studer, Bruno

    2013-02-01

    Whole-genome sequences established for model and major crop species constitute a key resource for advanced genomic research. For outbreeding forage and turf grass species like ryegrasses (Lolium spp.), such resources have yet to be developed. Here, we present a model of the perennial ryegrass (Lolium perenne) genome on the basis of conserved synteny to barley (Hordeum vulgare) and the model grass genome Brachypodium (Brachypodium distachyon) as well as rice (Oryza sativa) and sorghum (Sorghum bicolor). A transcriptome-based genetic linkage map of perennial ryegrass served as a scaffold to establish the chromosomal arrangement of syntenic genes from model grass species. This scaffold revealed a high degree of synteny and macrocollinearity and was then utilized to anchor a collection of perennial ryegrass genes in silico to their predicted genome positions. This resulted in the unambiguous assignment of 3,315 out of 8,876 previously unmapped genes to the respective chromosomes. In total, the GenomeZipper incorporates 4,035 conserved grass gene loci, which were used for the first genome-wide sequence divergence analysis between perennial ryegrass, barley, Brachypodium, rice, and sorghum. The perennial ryegrass GenomeZipper is an ordered, information-rich genome scaffold, facilitating map-based cloning and genome assembly in perennial ryegrass and closely related Poaceae species. It also represents a milestone in describing synteny between perennial ryegrass and fully sequenced model grass genomes, thereby increasing our understanding of genome organization and evolution in the most important temperate forage and turf grass species.

  9. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio.

    Science.gov (United States)

    Manolio, Teri A

    2016-10-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of "Genomic Medicine Meetings," under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. Published by Elsevier Ireland Ltd.

  10. Radiation damage in plastic scintillators

    International Nuclear Information System (INIS)

    Majewski, S.

    1990-01-01

    Results of radiation damage studies in plastic scintillators are reviewed and critically analyzed from the point of view of applications of plastic scintillators in calorimetric detectors for the SSC. Damage to transmission and to fluorescent yield in different conditions is discussed. New directions in R ampersand D are outlined. Several examples are given of the most recent data on the new scintillating materials made with old and new plastics and fluors, which are exhibiting significantly improved radiation resistance. With a present rate of a vigorous R D programme, the survival limits in the vicinity of 100 MRad seem to be feasible within a couple of years

  11. Atom bombs and genetic damage

    International Nuclear Information System (INIS)

    Berry, R.J.

    1982-01-01

    Comments are made on a 1981 review on genetic damage in the off-spring of the atom bomb survivors in Hiroshima and Nagasaki. The main criticisms of the review concerned, 1) the 'minimal' doubling dose value for radiation-induced mutation in man, 2) the gametic doubling dose value for sex chromosome aneuploidy and 3) the validity of trebling an observed acute doubling dose to measure the effect of chronic irradiation. The firmest conclusion which may be deduced from the studies on A-bomb survivors is that humans are fairly resistant to genetic damage from radiation. (U.K.)

  12. Applied Genomics of Foodborne Pathogens

    DEFF Research Database (Denmark)

    and customized source of information designed for and accessible to microbiologists interested in applying cutting-edge genomics in food safety and public health research. This book fills this void with a well-selected collection of topics, case studies, and bioinformatics tools contributed by experts......This book provides a timely and thorough snapshot into the emerging and fast evolving area of applied genomics of foodborne pathogens. Driven by the drastic advance of whole genome shot gun sequencing (WGS) technologies, genomics applications are becoming increasingly valuable and even essential...... at the forefront of foodborne pathogen genomics research....

  13. DNA-damage response during mitosis induces whole-chromosome missegregation.

    Science.gov (United States)

    Bakhoum, Samuel F; Kabeche, Lilian; Murnane, John P; Zaki, Bassem I; Compton, Duane A

    2014-11-01

    Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

  14. Recent Advancements in DNA Damage-Transcription Crosstalk and High-Resolution Mapping of DNA Breaks.

    Science.gov (United States)

    Vitelli, Valerio; Galbiati, Alessandro; Iannelli, Fabio; Pessina, Fabio; Sharma, Sheetal; d'Adda di Fagagna, Fabrizio

    2017-08-31

    Until recently, DNA damage arising from physiological DNA metabolism was considered a detrimental by-product for cells. However, an increasing amount of evidence has shown that DNA damage could have a positive role in transcription activation. In particular, DNA damage has been detected in transcriptional elements following different stimuli. These physiological DNA breaks are thought to be instrumental for the correct expression of genomic loci through different mechanisms. In this regard, although a plethora of methods are available to precisely map transcribed regions and transcription start sites, commonly used techniques for mapping DNA breaks lack sufficient resolution and sensitivity to draw a robust correlation between DNA damage generation and transcription. Recently, however, several methods have been developed to map DNA damage at single-nucleotide resolution, thus providing a new set of tools to correlate DNA damage and transcription. Here, we review how DNA damage can positively regulate transcription initiation, the current techniques for mapping DNA breaks at high resolution, and how these techniques can benefit future studies of DNA damage and transcription.

  15. Non coding RNA: sequence-specific guide for chromatin modification and DNA damage signaling

    Directory of Open Access Journals (Sweden)

    Sofia eFrancia

    2015-11-01

    Full Text Available Chromatin conformation shapes the environment in which our genome is transcribed into RNA. Transcription is a source of DNA damage, thus it often occurs concomitantly to DNA damage signaling. Growing amounts of evidence suggest that different types of RNAs can, independently from their protein-coding properties, directly affect chromatin conformation, transcription and splicing, as well as promote the activation of the DNA damage response (DDR and DNA repair. Therefore, transcription paradoxically functions to both threaten and safeguard genome integrity. On the other hand, DNA damage signaling is known to modulate chromatin to suppress transcription of the surrounding genetic unit. It is thus intriguing to understand how transcription can modulate DDR signaling while, in turn, DDR signaling represses transcription of chromatin around the DNA lesion. An unexpected player in this field is the RNA interference (RNAi machinery, which play roles in transcription, splicing and chromatin modulation in several organisms. Non-coding RNAs (ncRNAs and several protein factors involved in the RNAi pathway are well known master regulators of chromatin while only recent reports suggest that ncRNAs are involved in DDR signaling and homology-mediated DNA repair. Here, we discuss the experimental evidence supporting the idea that ncRNAs act at the genomic loci from which they are transcribed to modulate chromatin, DDR signaling and DNA repair.

  16. Evolution of small prokaryotic genomes

    Directory of Open Access Journals (Sweden)

    David José Martínez-Cano

    2015-01-01

    Full Text Available As revealed by genome sequencing, the biology of prokaryotes with reduced genomes is strikingly diverse. These include free-living prokaryotes with ~800 genes as well as endosymbiotic bacteria with as few as ~140 genes. Comparative genomics is revealing the evolutionary mechanisms that led to these small genomes. In the case of free-living prokaryotes, natural selection directly favored genome reduction, while in the case of endosymbiotic prokaryotes neutral processes played a more prominent role. However, new experimental data suggest that selective processes may be at operation as well for endosymbiotic prokaryotes at least during the first stages of genome reduction. Endosymbiotic prokaryotes have evolved diverse strategies for living with reduced gene sets inside a host-defined medium. These include utilization of host-encoded functions (some of them coded by genes acquired by gene transfer from the endosymbiont and/or other bacteria; metabolic complementation between co-symbionts; and forming consortiums with other bacteria within the host. Recent genome sequencing projects of intracellular mutualistic bacteria showed that previously believed universal evolutionary trends like reduced G+C content and conservation of genome synteny are not always present in highly reduced genomes. Finally, the simplified molecular machinery of some of these organisms with small genomes may be used to aid in the design of artificial minimal cells. Here we review recent genomic discoveries of the biology of prokaryotes endowed with small gene sets and discuss the evolutionary mechanisms that have been proposed to explain their peculiar nature.

  17. Informational laws of genome structures

    Science.gov (United States)

    Bonnici, Vincenzo; Manca, Vincenzo

    2016-06-01

    In recent years, the analysis of genomes by means of strings of length k occurring in the genomes, called k-mers, has provided important insights into the basic mechanisms and design principles of genome structures. In the present study, we focus on the proper choice of the value of k for applying information theoretic concepts that express intrinsic aspects of genomes. The value k = lg2(n), where n is the genome length, is determined to be the best choice in the definition of some genomic informational indexes that are studied and computed for seventy genomes. These indexes, which are based on information entropies and on suitable comparisons with random genomes, suggest five informational laws, to which all of the considered genomes obey. Moreover, an informational genome complexity measure is proposed, which is a generalized logistic map that balances entropic and anti-entropic components of genomes and is related to their evolutionary dynamics. Finally, applications to computational synthetic biology are briefly outlined.

  18. Toward genome-enabled mycology.

    Science.gov (United States)

    Hibbett, David S; Stajich, Jason E; Spatafora, Joseph W

    2013-01-01

    Genome-enabled mycology is a rapidly expanding field that is characterized by the pervasive use of genome-scale data and associated computational tools in all aspects of fungal biology. Genome-enabled mycology is integrative and often requires teams of researchers with diverse skills in organismal mycology, bioinformatics and molecular biology. This issue of Mycologia presents the first complete fungal genomes in the history of the journal, reflecting the ongoing transformation of mycology into a genome-enabled science. Here, we consider the prospects for genome-enabled mycology and the technical and social challenges that will need to be overcome to grow the database of complete fungal genomes and enable all fungal biologists to make use of the new data.

  19. Radiation-induced damage of membranes

    International Nuclear Information System (INIS)

    Yonei, Shuji

    1977-01-01

    An outline of membranous structure was stated, and radiation-induced damage of membranes were surveyed. By irradiation, permeability of membranes, especially passive transportation mechanism, was damaged, and glycoprotein in the surface layers of cells and the surface layer structures were changed. The intramembranous damage was induced by decrease of electrophoresis of nuclear mambranes and a quantitative change of cytochrome P450 of microsomal membranes of the liver, and peroxidation of membranous lipid and SH substitute damage of membranous protein were mentioned as the mechanism of membranous damage. Recovery of membranous damage depends on radiation dose and temperature, and membranous damage participates largely in proliferation death. (tsunoda, M.)

  20. Genomic research perspectives in Kazakhstan

    Directory of Open Access Journals (Sweden)

    Ainur Akilzhanova

    2014-01-01

    Full Text Available Introduction: Technological advancements rapidly propel the field of genome research. Advances in genetics and genomics such as the sequence of the human genome, the human haplotype map, open access databases, cheaper genotyping and chemical genomics, have transformed basic and translational biomedical research. Several projects in the field of genomic and personalized medicine have been conducted at the Center for Life Sciences in Nazarbayev University. The prioritized areas of research include: genomics of multifactorial diseases, cancer genomics, bioinformatics, genetics of infectious diseases and population genomics. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures for cancer diagnosis and prognosis, genome-guided therapy, and dose selection of therapeutic drugs are the important issues in personalized medicine. Results: To further develop genomic and biomedical projects at Center for Life Sciences, the development of bioinformatics research and infrastructure and the establishment of new collaborations in the field are essential. Widespread use of genetic tools will allow the identification of diseases before the onset of clinical symptoms, the individualization of drug treatment, and could induce individual behavioral changes on the basis of calculated disease risk. However, many challenges remain for the successful translation of genomic knowledge and technologies into health advances, such as medicines and diagnostics. It is important to integrate research and education in the fields of genomics, personalized medicine, and bioinformatics, which will be possible with opening of the new Medical Faculty at Nazarbayev University. People in practice and training need to be educated about the key concepts of genomics and engaged so they can effectively apply their knowledge in a matter that will bring the era of genomic medicine to patient care. This requires the development of well

  1. Identification of candidate new cancer susceptibility genes using yeast genomics

    International Nuclear Information System (INIS)

    Brown, M.; Brown, J.A.; Game, J.C.

    2003-01-01

    A large proportion of cancer susceptibility syndromes are the result of mutations in genes in DNA repair or in cell-cycle checkpoints in response to DNA damage, such as ataxia telangiectasia (AT), Fanconi's anemia (FA), Bloom's syndrome (BS), Nijmegen breakage syndrome (NBS), and xeroderma pigmentosum (XP). Mutations in these genes often cause gross chromosomal instability leading to an increased mutation rate of all genes including those directly responsible for cancer. We have proposed that because the orthologs of these genes in budding yeast, S. cerevisiae, confer protection against killing by DNA damaging agents it should be possible to identify new cancer susceptibility genes by identifying yeast genes whose deletion causes sensitivity to DNA damage. We therefore screened the recently completed collection of individual gene deletion mutants to identify genes that affect sensitivity to DNA-damaging agents. Screening for sensitivity in this obtained up to now with the F98 glioma model othe fact that each deleted gene is replaced by a cassette containing two molecular 'barcodes', or 20-mers, that uniquely identify the strain when DNA from a pool of strains is hybridized to an oligonucleotide array containing the complementary sequences of the barcodes. We performed the screen with UV, IR, H 2 0 2 and other DNA damaging agents. In addition to identifying genes already known to confer resistance to DNA damaging agents we have identified, and individually confirmed, several genes not previously associated with resistance. Several of these are of unknown function. We have also examined the chromosomal stability of selected strains and found that IR sensitive strains often but not always exhibit genomic instability. We are presently constructing a yeast artificial chromosome to globally interrogate all the genes in the deletion pool for their involvement in genomic stability. This work shows that budding yeast is a valuable eukaryotic model organism to identify

  2. Mycobacteriophage genome database.

    Science.gov (United States)

    Joseph, Jerrine; Rajendran, Vasanthi; Hassan, Sameer; Kumar, Vanaja

    2011-01-01

    Mycobacteriophage genome database (MGDB) is an exclusive repository of the 64 completely sequenced mycobacteriophages with annotated information. It is a comprehensive compilation of the various gene parameters captured from several databases pooled together to empower mycobacteriophage researchers. The MGDB (Version No.1.0) comprises of 6086 genes from 64 mycobacteriophages classified into 72 families based on ACLAME database. Manual curation was aided by information available from public databases which was enriched further by analysis. Its web interface allows browsing as well as querying the classification. The main objective is to collect and organize the complexity inherent to mycobacteriophage protein classification in a rational way. The other objective is to browse the existing and new genomes and describe their functional annotation. The database is available for free at http://mpgdb.ibioinformatics.org/mpgdb.php.

  3. Precision genome editing

    DEFF Research Database (Denmark)

    Steentoft, Catharina; Bennett, Eric P; Schjoldager, Katrine Ter-Borch Gram

    2014-01-01

    Precise and stable gene editing in mammalian cell lines has until recently been hampered by the lack of efficient targeting methods. While different gene silencing strategies have had tremendous impact on many biological fields, they have generally not been applied with wide success in the field...... of glycobiology, primarily due to their low efficiencies, with resultant failure to impose substantial phenotypic consequences upon the final glycosylation products. Here, we review novel nuclease-based precision genome editing techniques enabling efficient and stable gene editing, including gene disruption...... by introducing single or double-stranded breaks at a defined genomic sequence. We here compare and contrast the different techniques and summarize their current applications, highlighting cases from the field of glycobiology as well as pointing to future opportunities. The emerging potential of precision gene...

  4. Alignment of whole genomes.

    Science.gov (United States)

    Delcher, A L; Kasif, S; Fleischmann, R D; Peterson, J; White, O; Salzberg, S L

    1999-01-01

    A new system for aligning whole genome sequences is described. Using an efficient data structure called a suffix tree, the system is able to rapidly align sequences containing millions of nucleotides. Its use is demonstrated on two strains of Mycoplasma tuberculosis, on two less similar species of Mycoplasma bacteria and on two syntenic sequences from human chromosome 12 and mouse chromosome 6. In each case it found an alignment of the input sequences, using between 30 s and 2 min of computation time. From the system output, information on single nucleotide changes, translocations and homologous genes can easily be extracted. Use of the algorithm should facilitate analysis of syntenic chromosomal regions, strain-to-strain comparisons, evolutionary comparisons and genomic duplications. PMID:10325427

  5. eGenomics: Cataloguing Our Complete Genome Collection III

    Directory of Open Access Journals (Sweden)

    Dawn Field

    2007-01-01

    Full Text Available This meeting report summarizes the proceedings of the “eGenomics: Cataloguing our Complete Genome Collection III” workshop held September 11–13, 2006, at the National Institute for Environmental eScience (NIEeS, Cambridge, United Kingdom. This 3rd workshop of the Genomic Standards Consortium was divided into two parts. The first half of the three-day workshop was dedicated to reviewing the genomic diversity of our current and future genome and metagenome collection, and exploring linkages to a series of existing projects through formal presentations. The second half was dedicated to strategic discussions. Outcomes of the workshop include a revised “Minimum Information about a Genome Sequence” (MIGS specification (v1.1, consensus on a variety of features to be added to the Genome Catalogue (GCat, agreement by several researchers to adopt MIGS for imminent genome publications, and an agreement by the EBI and NCBI to input their genome collections into GCat for the purpose of quantifying the amount of optional data already available (e.g., for geographic location coordinates and working towards a single, global list of all public genomes and metagenomes.

  6. Genomics Portals: integrative web-platform for mining genomics data.

    Science.gov (United States)

    Shinde, Kaustubh; Phatak, Mukta; Johannes, Freudenberg M; Chen, Jing; Li, Qian; Vineet, Joshi K; Hu, Zhen; Ghosh, Krishnendu; Meller, Jaroslaw; Medvedovic, Mario

    2010-01-13

    A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems. Genomics Portals platform integrates access to an extensive knowledge base and a large database of human, mouse, and rat genomics data with basic analytical visualization tools. It provides the context for analyzing and interpreting new experimental data and the tool for effective mining of a large number of publicly available genomics datasets stored in the back-end databases. The uniqueness of this platform lies in the volume and the diversity of genomics data that can be accessed and analyzed (gene expression, ChIP-chip, ChIP-seq, epigenomics, computationally predicted binding sites, etc), and the integration with an extensive knowledge base that can be used in such analysis. The integrated access to primary genomics data, functional knowledge and analytical tools makes Genomics Portals platform a unique tool for interpreting results of new genomics experiments and for mining the vast amount of data stored in the Genomics Portals backend databases. Genomics Portals can be accessed and used freely at http://GenomicsPortals.org.

  7. Genomics Portals: integrative web-platform for mining genomics data

    Directory of Open Access Journals (Sweden)

    Ghosh Krishnendu

    2010-01-01

    Full Text Available Abstract Background A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems. Results Genomics Portals platform integrates access to an extensive knowledge base and a large database of human, mouse, and rat genomics data with basic analytical visualization tools. It provides the context for analyzing and interpreting new experimental data and the tool for effective mining of a large number of publicly available genomics datasets stored in the back-end databases. The uniqueness of this platform lies in the volume and the diversity of genomics data that can be accessed and analyzed (gene expression, ChIP-chip, ChIP-seq, epigenomics, computationally predicted binding sites, etc, and the integration with an extensive knowledge base that can be used in such analysis. Conclusion The integrated access to primary genomics data, functional knowledge and analytical tools makes Genomics Portals platform a unique tool for interpreting results of new genomics experiments and for mining the vast amount of data stored in the Genomics Portals backend databases. Genomics Portals can be accessed and used freely at http://GenomicsPortals.org.

  8. Family genome browser: visualizing genomes with pedigree information.

    Science.gov (United States)

    Juan, Liran; Liu, Yongzhuang; Wang, Yongtian; Teng, Mingxiang; Zang, Tianyi; Wang, Yadong

    2015-07-15

    Families with inherited diseases are widely used in Mendelian/complex disease studies. Owing to the advances in high-throughput sequencing technologies, family genome sequencing becomes more and more prevalent. Visualizing family genomes can greatly facilitate human genetics studies and personalized medicine. However, due to the complex genetic relationships and high similarities among genomes of consanguineous family members, family genomes are difficult to be visualized in traditional genome visualization framework. How to visualize the family genome variants and their functions with integrated pedigree information remains a critical challenge. We developed the Family Genome Browser (FGB) to provide comprehensive analysis and visualization for family genomes. The FGB can visualize family genomes in both individual level and variant level effectively, through integrating genome data with pedigree information. Family genome analysis, including determination of parental origin of the variants, detection of de novo mutations, identification of potential recombination events and identical-by-decent segments, etc., can be performed flexibly. Diverse annotations for the family genome variants, such as dbSNP memberships, linkage disequilibriums, genes, variant effects, potential phenotypes, etc., are illustrated as well. Moreover, the FGB can automatically search de novo mutations and compound heterozygous variants for a selected individual, and guide investigators to find high-risk genes with flexible navigation options. These features enable users to investigate and understand family genomes intuitively and systematically. The FGB is available at http://mlg.hit.edu.cn/FGB/. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Human Germline Genome Editing.

    Science.gov (United States)

    Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T; Bombard, Yvonne; Brody, Lawrence C; Faucett, W Andrew; Garrison, Nanibaa' A; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E

    2017-08-03

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  10. Damage limits of accelerator equipment

    CERN Document Server

    Rosell, Gemma

    2014-01-01

    Beam losses occur in particle accelerators for various reasons. The effect of lost particles on accelerator equipment becomes more severe with the increasing energies and intensities. The present study is focused on the damage potential of the proton beam as a function of particle energy and beam size. Injection and extraction energies of different accelerators at CERN were considered.

  11. DNA damage by Auger emitters

    International Nuclear Information System (INIS)

    Martin, R.F.; d'Cunha, Glenn; Gibbs, Richard; Murray, Vincent; Pardee, Marshall; Allen, B.J.

    1988-01-01

    125 I atoms can be introduced at specific locations along a defined DNA target molecule, either by site-directed incorporation of an 125 I-labelled deoxynucleotide or by binding of an 125 I-labelled sequence-selective DNA ligand. After allowing accumulation of 125 I decay-induced damage to the DNA, application of DNA sequencing techniques enables positions of strand breaks to be located relative to the site of decay, at a resolution corresponding to the distance between adjacent nucleotides [0.34 nm]. Thus, DNA provides a molecular framework to analyse the extent of damage following [averaged] individual decay events. Results can be compared with energy deposition data generated by computer-simulation methods developed by Charlton et al. The DNA sequencing technique also provides information about the chemical nature of the termini of the DNA chains produced following Auger decay-induced damage. In addition to reviewing the application of this approach to the analysis of 125 I decay induced DNA damage, some more recent results obtained by using 67 Ga are also presented. (author)

  12. Preparation of bubble damage detectors

    International Nuclear Information System (INIS)

    Tu Caiqing; Guo Shilun; Wang Yulan; Hao Xiuhong; Chen Changmao; Su Jingling

    1997-01-01

    Bubble damage detectors have been prepared by using polyacrylamide as detector solid and freon as detector liquid. Tests show that the prepared detectors are sensitive to fast neutrons and have proportionality between bubble number and neutron fluence within a certain range of neutron fluence. Therefore, it can be used as a fast neutron detector and a dosimeter

  13. Genomic Prediction from Whole Genome Sequence in Livestock: The 1000 Bull Genomes Project

    DEFF Research Database (Denmark)

    Hayes, Benjamin J; MacLeod, Iona M; Daetwyler, Hans D

    Advantages of using whole genome sequence data to predict genomic estimated breeding values (GEBV) include better persistence of accuracy of GEBV across generations and more accurate GEBV across breeds. The 1000 Bull Genomes Project provides a database of whole genome sequenced key ancestor bulls....... In a dairy data set, predictions using BayesRC and imputed sequence data from 1000 Bull Genomes were 2% more accurate than with 800k data. We could demonstrate the method identified causal mutations in some cases. Further improvements will come from more accurate imputation of sequence variant genotypes...

  14. Genomic technologies in neonatology

    Directory of Open Access Journals (Sweden)

    L. N. Chernova

    2017-01-01

    Full Text Available In recent years, there has been a tremendous trend toward personalized medicine. Advances in the field forced clinicians, including neonatologists, to take a fresh look at prevention, tactics of management and therapy of various diseases. In the center of attention of foreign, and increasingly Russian, researchers and doctors, there are individual genomic data that allow not only to assess the risks of some form of pathology, but also to successfully apply personalized strategies of prediction, prevention and targeted treatment. This article provides a brief review of the latest achievements of genomic technologies in newborns, examines the problems and potential applications of genomics in promoting the concept of personalized medicine in neonatology. The increasing amount of personalized data simply impossible to analyze only by the human mind. In this connection, the need of computers and bioinformatics is obvious. The article reveals the role of translational bioinformatics in the analysis and integration of the results of the accumulated fundamental research into complete clinical decisions. The latest advances in neonatal translational bioinformatics such as clinical decision support systems are considered. It helps to monitor vital parameters of newborns influencing the course of a particular disease, to calculate the increased risks of the development of various pathologies and to select the drugs.

  15. Value-based genomics.

    Science.gov (United States)

    Gong, Jun; Pan, Kathy; Fakih, Marwan; Pal, Sumanta; Salgia, Ravi

    2018-03-20

    Advancements in next-generation sequencing have greatly enhanced the development of biomarker-driven cancer therapies. The affordability and availability of next-generation sequencers have allowed for the commercialization of next-generation sequencing platforms that have found widespread use for clinical-decision making and research purposes. Despite the greater availability of tumor molecular profiling by next-generation sequencing at our doorsteps, the achievement of value-based care, or improving patient outcomes while reducing overall costs or risks, in the era of precision oncology remains a looming challenge. In this review, we highlight available data through a pre-established and conceptualized framework for evaluating value-based medicine to assess the cost (efficiency), clinical benefit (effectiveness), and toxicity (safety) of genomic profiling in cancer care. We also provide perspectives on future directions of next-generation sequencing from targeted panels to whole-exome or whole-genome sequencing and describe potential strategies needed to attain value-based genomics.

  16. DNA Damage Repair System in Plants: A Worldwide Research Update.

    Science.gov (United States)

    Gimenez, Estela; Manzano-Agugliaro, Francisco

    2017-10-30

    Living organisms are usually exposed to various DNA damaging agents so the mechanisms to detect and repair diverse DNA lesions have developed in all organisms with the result of maintaining genome integrity. Defects in DNA repair machinery contribute to cancer, certain diseases, and aging. Therefore, conserving the genomic sequence in organisms is key for the perpetuation of life. The machinery of DNA damage repair (DDR) in prokaryotes and eukaryotes is similar. Plants also share mechanisms for DNA repair with animals, although they differ in other important details. Plants have, surprisingly, been less investigated than other living organisms in this context, despite the fact that numerous lethal mutations in animals are viable in plants. In this manuscript, a worldwide bibliometric analysis of DDR systems and DDR research in plants was made. A comparison between both subjects was accomplished. The bibliometric analyses prove that the first study about DDR systems in plants (1987) was published thirteen years later than that for other living organisms (1975). Despite the increase in the number of papers about DDR mechanisms in plants in recent decades, nowadays the number of articles published each year about DDR systems in plants only represents 10% of the total number of articles about DDR. The DDR research field was done by 74 countries while the number of countries involved in the DDR & Plant field is 44. This indicates the great influence that DDR research in the plant field currently has, worldwide. As expected, the percentage of studies published about DDR systems in plants has increased in the subject area of agricultural and biological sciences and has diminished in medicine with respect to DDR studies in other living organisms. In short, bibliometric results highlight the current interest in DDR research in plants among DDR studies and can open new perspectives in the research field of DNA damage repair.

  17. Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium

    DEFF Research Database (Denmark)

    Machado, Henrique; Gram, Lone

    2017-01-01

    was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.......Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand...... the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur, amino-acid usage, ANI), which allowed us to identify two...

  18. Genome update: the 1000th genome - a cautionary tale

    DEFF Research Database (Denmark)

    Lagesen, Karin; Ussery, David; Wassenaar, Gertrude Maria

    2010-01-01

    conclusions for example about the largest bacterial genome sequenced. Biological diversity is far greater than many have thought. For example, analysis of multiple Escherichia coli genomes has led to an estimate of around 45 000 gene families more genes than are recognized in the human genome. Moreover......There are now more than 1000 sequenced prokaryotic genomes deposited in public databases and available for analysis. Currently, although the sequence databases GenBank, DNA Database of Japan and EMBL are synchronized continually, there are slight differences in content at the genomes level...... for a variety of logistical reasons, including differences in format and loading errors, such as those caused by file transfer protocol interruptions. This means that the 1000th genome will be different in the various databases. Some of the data on the highly accessed web pages are inaccurate, leading to false...

  19. Efficient Breeding by Genomic Mating.

    Science.gov (United States)

    Akdemir, Deniz; Sánchez, Julio I

    2016-01-01

    Selection in breeding programs can be done by using phenotypes (phenotypic selection), pedigree relationship (breeding value selection) or molecular markers (marker assisted selection or genomic selection). All these methods are based on truncation selection, focusing on the best performance of parents before mating. In this article we proposed an approach to breeding, named genomic mating, which focuses on mating instead of truncation selection. Genomic mating uses information in a similar fashion to genomic selection but includes information on complementation of parents to be mated. Following the efficiency frontier surface, genomic mating uses concepts of estimated breeding values, risk (usefulness) and coefficient of ancestry to optimize mating between parents. We used a genetic algorithm to find solutions to this optimization problem and the results from our simulations comparing genomic selection, phenotypic selection and the mating approach indicate that current approach for breeding complex traits is more favorable than phenotypic and genomic selection. Genomic mating is similar to genomic selection in terms of estimating marker effects, but in genomic mating the genetic information and the estimated marker effects are used to decide which genotypes should be crossed to obtain the next breeding population.

  20. Implementation of an anisotropic damage material model using general second order damage tensor

    NARCIS (Netherlands)

    Niazi, Muhammad Sohail; Mori, K.; Wisselink, H.H.; Pietrzyk, M.; Kusiak, J.; Meinders, Vincent T.; ten Horn, Carel; Majta, J.; Hartley, P.; Lin, J.

    2010-01-01

    Damage in metals is mainly the process of the initiation and growth of voids. With the growing complexity in materials and forming proc-esses, it becomes inevitable to include anisotropy in damage (tensorial damage variable). Most of the anisotropic damage models define the damage tensor in the

  1. Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium

    OpenAIRE

    Henrique Machado; Henrique Machado; Lone Gram

    2017-01-01

    Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationship...

  2. Genome Surfing As Driver of Microbial Genomic Diversity.

    Science.gov (United States)

    Choudoir, Mallory J; Panke-Buisse, Kevin; Andam, Cheryl P; Buckley, Daniel H

    2017-08-01

    Historical changes in population size, such as those caused by demographic range expansions, can produce nonadaptive changes in genomic diversity through mechanisms such as gene surfing. We propose that demographic range expansion of a microbial population capable of horizontal gene exchange can result in genome surfing, a mechanism that can cause widespread increase in the pan-genome frequency of genes acquired by horizontal gene exchange. We explain that patterns of genetic diversity within Streptomyces are consistent with genome surfing, and we describe several predictions for testing this hypothesis both in Streptomyces and in other microorganisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Genome U-Plot: a whole genome visualization.

    Science.gov (United States)

    Gaitatzes, Athanasios; Johnson, Sarah H; Smadbeck, James B; Vasmatzis, George

    2018-05-15

    The ability to produce and analyze whole genome sequencing (WGS) data from samples with structural variations (SV) generated the need to visualize such abnormalities in simplified plots. Conventional two-dimensional representations of WGS data frequently use either circular or linear layouts. There are several diverse advantages regarding both these representations, but their major disadvantage is that they do not use the two-dimensional space very efficiently. We propose a layout, termed the Genome U-Plot, which spreads the chromosomes on a two-dimensional surface and essentially quadruples the spatial resolution. We present the Genome U-Plot for producing clear and intuitive graphs that allows researchers to generate novel insights and hypotheses by visualizing SVs such as deletions, amplifications, and chromoanagenesis events. The main features of the Genome U-Plot are its layered layout, its high spatial resolution and its improved aesthetic qualities. We compare conventional visualization schemas with the Genome U-Plot using visualization metrics such as number of line crossings and crossing angle resolution measures. Based on our metrics, we improve the readability of the resulting graph by at least 2-fold, making apparent important features and making it easy to identify important genomic changes. A whole genome visualization tool with high spatial resolution and improved aesthetic qualities. An implementation and documentation of the Genome U-Plot is publicly available at https://github.com/gaitat/GenomeUPlot. vasmatzis.george@mayo.edu. Supplementary data are available at Bioinformatics online.

  4. Genomic Data Commons and Genomic Cloud Pilots - Google Hangout

    Science.gov (United States)

    Join us for a live, moderated discussion about two NCI efforts to expand access to cancer genomics data: the Genomic Data Commons and Genomic Cloud Pilots. NCI subject matters experts will include Louis M. Staudt, M.D., Ph.D., Director Center for Cancer Genomics, Warren Kibbe, Ph.D., Director, NCI Center for Biomedical Informatics and Information Technology, and moderated by Anthony Kerlavage, Ph.D., Chief, Cancer Informatics Branch, Center for Biomedical Informatics and Information Technology. We welcome your questions before and during the Hangout on Twitter using the hashtag #AskNCI.

  5. Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis.

    Science.gov (United States)

    Pushpavalli, Sreerangam N C V L; Sarkar, Arpita; Ramaiah, M Janaki; Chowdhury, Debabani Roy; Bhadra, Utpal; Pal-Bhadra, Manika

    2013-01-24

    In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk) is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof¹/+; mnkp⁶/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using Drosophila as model system and carry out the interaction of MOF

  6. Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis

    Directory of Open Access Journals (Sweden)

    Pushpavalli Sreerangam NCVL

    2013-01-01

    Full Text Available Abstract Background In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Results Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof1/+; mnkp6/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. Conclusion mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using

  7. [Studies on the repair of damaged DNA in bacteriophage, bacterial and mammalian systems]: Final report

    International Nuclear Information System (INIS)

    Friedberg, E.C.

    1987-08-01

    This study sought to exploit the use of uv radiation as a source of genomic damage. We explored the molecular mechanism of the repair of DNA damage at a number of different levels of biological organization, by investigating bacteriophage, bacterial, yeast and mammalian cells. Not only have observations obtained in one biological system suggested specific experimental approaches in others, but we have also learned that some biochemical pathways for DNA repair are unique to specific organisms. Our studies are summarized in terms of 4 major areas of research activity that span the past 16 years. 86 refs

  8. Analysis of localized damage in creep rupture

    International Nuclear Information System (INIS)

    Wang Zhengdong; Wu Dongdi

    1992-01-01

    Continuum Damage Mechanics studies the effect of distributed defects, whereas the failure of engineering structures is usually caused by local damage. In this paper, an analysis of localized damage in creep rupture is carried out. The material tested is a 2 1/4Cr-1Mo pressure vessel steel and the material constants necessary for damage analysis are evaluated. Notched specimens are used to reflect localized damage in creep rupture and the amount of damage is measured using DCPD method. Through FEM computation, stress components and effective stress in the region of notch root are evaluated and it is found that the von Mises effective stress can represent the damage effective stress in the analysis of localized creep damage. It is possible to develop a method for the assessment of safety of pressure vessels under creep through localized creep damage analysis. (orig.)

  9. Ultraviolet Radiations: Skin Defense-Damage Mechanism.

    Science.gov (United States)

    Mohania, Dheeraj; Chandel, Shikha; Kumar, Parveen; Verma, Vivek; Digvijay, Kumar; Tripathi, Deepika; Choudhury, Khushboo; Mitten, Sandeep Kumar; Shah, Dilip

    2017-01-01

    UV-radiations are the invisible part of light spectra having a wavelength between visible rays and X-rays. Based on wavelength, UV rays are subdivided into UV-A (320-400 nm), UV-B (280-320 nm) and UV-C (200-280 nm). Ultraviolet rays can have both harmful and beneficial effects. UV-C has the property of ionization thus acting as a strong mutagen, which can cause immune-mediated disease and cancer in adverse cases. Numbers of genetic factors have been identified in human involved in inducing skin cancer from UV-radiations. Certain heredity diseases have been found susceptible to UV-induced skin cancer. UV radiations activate the cutaneous immune system, which led to an inflammatory response by different mechanisms. The first line of defense mechanism against UV radiation is melanin (an epidermal pigment), and UV absorbing pigment of skin, which dissipate UV radiation as heat. Cell surface death receptor (e.g. Fas) of keratinocytes responds to UV-induced injury and elicits apoptosis to avoid malignant transformation. In addition to the formation of photo-dimers in the genome, UV also can induce mutation by generating ROS and nucleotides are highly susceptible to these free radical injuries. Melanocortin 1 receptor (MC1R) has been known to be implicated in different UV-induced damages such as pigmentation, adaptive tanning, and skin cancer. UV-B induces the formation of pre-vitamin D3 in the epidermal layer of skin. UV-induced tans act as a photoprotection by providing a sun protection factor (SPF) of 3-4 and epidermal hyperplasia. There is a need to prevent the harmful effects and harness the useful effects of UV radiations.

  10. Ensembl 2002: accommodating comparative genomics.

    Science.gov (United States)

    Clamp, M; Andrews, D; Barker, D; Bevan, P; Cameron, G; Chen, Y; Clark, L; Cox, T; Cuff, J; Curwen, V; Down, T; Durbin, R; Eyras, E; Gilbert, J; Hammond, M; Hubbard, T; Kasprzyk, A; Keefe, D; Lehvaslaiho, H; Iyer, V; Melsopp, C; Mongin, E; Pettett, R; Potter, S; Rust, A; Schmidt, E; Searle, S; Slater, G; Smith, J; Spooner, W; Stabenau, A; Stalker, J; Stupka, E; Ureta-Vidal, A; Vastrik, I; Birney, E

    2003-01-01

    The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

  11. The Ensembl genome database project.

    Science.gov (United States)

    Hubbard, T; Barker, D; Birney, E; Cameron, G; Chen, Y; Clark, L; Cox, T; Cuff, J; Curwen, V; Down, T; Durbin, R; Eyras, E; Gilbert, J; Hammond, M; Huminiecki, L; Kasprzyk, A; Lehvaslaiho, H; Lijnzaad, P; Melsopp, C; Mongin, E; Pettett, R; Pocock, M; Potter, S; Rust, A; Schmidt, E; Searle, S; Slater, G; Smith, J; Spooner, W; Stabenau, A; Stalker, J; Stupka, E; Ureta-Vidal, A; Vastrik, I; Clamp, M

    2002-01-01

    The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.

  12. Comparative Genomics in Homo sapiens.

    Science.gov (United States)

    Oti, Martin; Sammeth, Michael

    2018-01-01

    Genomes can be compared at different levels of divergence, either between species or within species. Within species genomes can be compared between different subpopulations, such as human subpopulations from different continents. Investigating the genomic differences between different human subpopulations is important when studying complex diseases that are affected by many genetic variants, as the variants involved can differ between populations. The 1000 Genomes Project collected genome-scale variation data for 2504 human individuals from 26 different populations, enabling a systematic comparison of variation between human subpopulations. In this chapter, we present step-by-step a basic protocol for the identification of population-specific variants employing the 1000 Genomes data. These variants are subsequently further investigated for those that affect the proteome or RNA splice sites, to investigate potentially biologically relevant differences between the populations.

  13. Genetic damage following nuclear war

    International Nuclear Information System (INIS)

    Oftedal, P.

    1984-01-01

    Genetic damage may be caused by ionizing radiation from the exploding bomb itself, or from radioactive nuclides released or formed in the explosion. Long-wave radiation in the heat flash and physical force do not contribute. Thus only a small fraction of the energy of the explosion - fission or fusion- can cause genetic damage. Neutron irradiation is generally found to be 5-20 times more efficient than gamma irradiation for the same absorbed dose. Fetuses and children are generally more radiosensitive than adults. Exposure of gonads during the proliferative stage of gonad growth may conceivably lead to a ''fluctuation test'' effect, so that a gonad may contain a sector of cells carrying identical mutations. A corresponding development may take place if the gonad stem cell population has been severely depleted by an acute exposure and recovers

  14. Apportioning liability for transborder damages

    International Nuclear Information System (INIS)

    Krause-Ablass, W.-D.

    1988-01-01

    The legal situation in the case of cross border damage being caused by reactor accidents or transportation of nuclear material through more than one country is analysed. Two questions have to be asked - which country's courts have jurisdiction over the claims for damage? and which law is applicable? In considering the jurisdiction problem, the Paris and Vienna Conventions are discussed and also other rules of jurisdiction. The way the law is applicable is discussed in the second section. When the action for liability is based on the Paris or Vienna Convention the issue of reciprocity may arise and this is discussed. After a nuclear incident a potential plaintiff may have a choice amongst various jurisdictions and various available laws. Success may depend on the right choice of the forum chosen. This is illustrated by two examples. (U.K.)

  15. Genetic doping and health damages.

    Science.gov (United States)

    Fallahi, Aa; Ravasi, Aa; Farhud, Dd

    2011-01-01

    Use of genetic doping or gene transfer technology will be the newest and the lethal method of doping in future and have some unpleasant consequences for sports, athletes, and outcomes of competitions. The World Anti-Doping Agency (WADA) defines genetic doping as "the non-therapeutic use of genes, genetic elements, and/or cells that have the capacity to enhance athletic performance ". The purpose of this review is to consider genetic doping, health damages and risks of new genes if delivered in athletes. This review, which is carried out by reviewing relevant publications, is primarily based on the journals available in GOOGLE, ELSEVIER, PUBMED in fields of genetic technology, and health using a combination of keywords (e.g., genetic doping, genes, exercise, performance, athletes) until July 2010. There are several genes related to sport performance and if they are used, they will have health risks and sever damages such as cancer, autoimmunization, and heart attack.

  16. Civil liability for nuclear damage

    International Nuclear Information System (INIS)

    1963-01-01

    An international Convention on Civil Liability for Nuclear Damage was adopted in Vienna on 19 May 1963 by a sixty-nation conference convened by the International Atomic Energy Agency. The Convention, which is subject to ratification by the States signing it, will come into force three months after the deposit of the fifth instrument of ratification. The Convention is designee only to establish minimum rules regarding civil liability for nuclear damage; it may thus well be described as a framework convention, the main provisions of which represent the essential common denomination acceptable to as many States as possible. It leaves wide scope for national legislation and regional arrangements with a view to implementing these provisions The Convention does not purport to create a uniform civil law in this field, but it contains the minimal essential for protection of the public and forms the legal basis for uniform world-wide liability rules

  17. Damaging brands through market research:

    DEFF Research Database (Denmark)

    Horn, C.; Brem, Alexander; Ivens, B.

    2014-01-01

    Purpose – The purpose of this paper is to investigate the possibility of using the new marketing research tool of prediction markets (PMs), which integrates customers to into the marketing research process. The research questions are: does taking part in PMs influence customers’ brand perception......? Is there a danger of damaging a brand through this tool? Design/methodology/approach – The paper uses a series of five short-term (less than one hour) and five long-term (three weeks) experimental online PMs where customers are integrated into marketing research and apply a series of online-surveys before and after...... taking part as virtual stock market traders. Subjects of research are taken from the sporting goods industry. Findings – The paper shows that PMs can be used by marketing researchers without the danger of damaging the brand of the products that are subject of the PMs, although customers are being...

  18. Radiation damage in biomolecular systems

    CERN Document Server

    Fuss, Martina Christina

    2012-01-01

    Since the discovery of X-rays and radioactivity, ionizing radiations have been widely applied in medicine both for diagnostic and therapeutic purposes. The risks associated with radiation exposure and handling led to the parallel development of the field of radiation protection. Pioneering experiments done by Sanche and co-workers in 2000 showed that low-energy secondary electrons, which are abundantly generated along radiation tracks, are primarily responsible for radiation damage through successive interactions with the molecular constituents of the medium. Apart from ionizing processes, which are usually related to radiation damage, below the ionization level low-energy electrons can induce molecular fragmentation via dissociative processes such as internal excitation and electron attachment. This prompted collaborative projects between different research groups from European countries together with other specialists from Canada,  the USA and Australia. This book summarizes the advances achieved by these...

  19. A damage-tolerant glass.

    Science.gov (United States)

    Demetriou, Marios D; Launey, Maximilien E; Garrett, Glenn; Schramm, Joseph P; Hofmann, Douglas C; Johnson, William L; Ritchie, Robert O

    2011-02-01

    Owing to a lack of microstructure, glassy materials are inherently strong but brittle, and often demonstrate extreme sensitivity to flaws. Accordingly, their macroscopic failure is often not initiated by plastic yielding, and almost always terminated by brittle fracture. Unlike conventional brittle glasses, metallic glasses are generally capable of limited plastic yielding by shear-band sliding in the presence of a flaw, and thus exhibit toughness-strength relationships that lie between those of brittle ceramics and marginally tough metals. Here, a bulk glassy palladium alloy is introduced, demonstrating an unusual capacity for shielding an opening crack accommodated by an extensive shear-band sliding process, which promotes a fracture toughness comparable to those of the toughest materials known. This result demonstrates that the combination of toughness and strength (that is, damage tolerance) accessible to amorphous materials extends beyond the benchmark ranges established by the toughest and strongest materials known, thereby pushing the envelope of damage tolerance accessible to a structural metal.

  20. genome-wide association and metabolic pathway analysis of corn earworm resistance in maize

    Science.gov (United States)

    Marilyn L. Warburton; Erika D. Womack; Juliet D. Tang; Adam Thrash; J. Spencer Smith; Wenwei Xu; Seth C. Murray; W. Paul Williams

    2018-01-01

    Maize (Zea mays mays L.) is a staple crop of economic, industrial, and food security importance. Damage to the growing ears by corn earworm [Helicoverpa zea (Boddie)] is a major economic burden and increases secondary fungal infections and mycotoxin levels. To identify biochemical pathways associated with native resistance mechanisms, a genome-wide...

  1. Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions

    DEFF Research Database (Denmark)

    Martín-Pardillos, Ana; Tsaalbi-Shtylik, Anastasia; Chen, Si

    2017-01-01

    -distorting nucleotide lesions, resulted in the perinatal loss of hematopoietic stem cells, progressive loss of bone marrow, and fatal aplastic anemia between 3 and 4 months of age. This was associated with replication stress, genomic breaks, DNA damage signaling, senescence, and apoptosis in bone marrow. Surprisingly...

  2. Nucleotide excision repair : complexes and complexities : a study of global genome repair in human cells

    NARCIS (Netherlands)

    Volker, Marcel

    2006-01-01

    Of all exogenous agents that damage genomic DNA and hence threaten its integrity, the ultraviolet B (UVB) component of sunlight is highly relevant because of its abundance. UVB induces predominantly cyclobutane pyrimidine dimers and 6-4 photoproducts. In humans, these photolesions are repaired by

  3. Nucleotide excision repair : a multi-step mechanism required to maintain genome integrity

    NARCIS (Netherlands)

    Moser, Jill

    2010-01-01

    DNA is continuously exposed to exogenous and genotoxic insults including ionizing and ultraviolet radiation as well as chemical agents. DNA damage can compromise the integrity of the genome and have potentially deleterious effects. Ultraviolet light (UV) can induce the formation of helix distorting

  4. The genome of Arabidopsis thaliana.

    OpenAIRE

    Goodman, H M; Ecker, J R; Dean, C

    1995-01-01

    Arabidopsis thaliana is a small flowering plant that is a member of the family cruciferae. It has many characteristics--diploid genetics, rapid growth cycle, relatively low repetitive DNA content, and small genome size--that recommend it as the model for a plant genome project. The current status of the genetic and physical maps, as well as efforts to sequence the genome, are presented. Examples are given of genes isolated by using map-based cloning. The importance of the Arabidopsis project ...

  5. Advances in editing microalgae genomes

    OpenAIRE

    Daboussi, Fayza

    2017-01-01

    There have been significant advances in microalgal genomics over the last decade. Nevertheless, there are still insufficient tools for the manipulation of microalgae genomes and the development of microalgae as industrial biofactories. Several research groups have recently contributed to progress by demonstrating that particular nucleases can be used for targeted and stable modifications of the genomes of some microalgae species. The nucleases include Meganucleases, Zinc Finger nucleases, TAL...

  6. Genomic selection in plant breeding.

    Science.gov (United States)

    Newell, Mark A; Jannink, Jean-Luc

    2014-01-01

    Genomic selection (GS) is a method to predict the genetic value of selection candidates based on the genomic estimated breeding value (GEBV) predicted from high-density markers positioned throughout the genome. Unlike marker-assisted selection, the GEBV is based on all markers including both minor and major marker effects. Thus, the GEBV may capture more of the genetic variation for the particular trait under selection.

  7. Smart accelerometer. [vibration damage detection

    Science.gov (United States)

    Bozeman, Richard J., Jr. (Inventor)

    1994-01-01

    The invention discloses methods and apparatus for detecting vibrations from machines which indicate an impending malfunction for the purpose of preventing additional damage and allowing for an orderly shutdown or a change in mode of operation. The method and apparatus is especially suited for reliable operation in providing thruster control data concerning unstable vibration in an electrical environment which is typically noisy and in which unrecognized ground loops may exist.

  8. Damage-resistant brittle coatings

    Energy Technology Data Exchange (ETDEWEB)

    Lawn, B.R.; Lee, K.S. [National Inst. of Stand. and Technol., Gaithersburg, MD (United States). Mater. Sci. and Eng. Lab.; Chai, H. [Tel Aviv Univ. (Israel). Faculty of Engineering; Pajares, A. [Universidad de Extremadura, Badajoz (Spain). Dept. de Fisica; Kim, D.K. [Korea Advanced Inst. of Science and Technolgy, Taejon (Korea). Dept. of Materials Science and Engineering; Wuttiphan, S. [National Metal and Materials Technology Center, Bangkok (Thailand); Peterson, I.M. [Corning Inc., NY (United States); Hu Xiaozhi [Western Australia Univ., Nedlands, WA (Australia). Dept. of Mechanical and Materials Engineering

    2000-11-01

    Laminate structures consisting of hard, brittle coatings and soft, tough substrates are important in a wide variety of engineering applications, biological structures, and traditional pottery. In this study the authors introduce a new approach to the design of damage-resistant brittle coatings, based on a combination of new and existing relations for crack initiation in well-defined contact-induced stress fields. (orig.)

  9. Analysis of radiation damaged nanocrystals

    International Nuclear Information System (INIS)

    Sitek, J.; Dekan, J.; Sedlackova, K.; Sagatova, A.

    2014-01-01

    Ribbon-shaped specimens of the master alloy were prepared by planar flow casting. The ribbons with nominal composition of (Fe_1_-_xN_x)_8_1Nb_7B_1_2 (x = 0, 0.25, 0.5, 0.75) were about 25 μm thick and 10 mm wide. To achieve nanocrystalline state, the amorphous ribbons were annealed in vacuum at the temperature of 550 grad C for 1 hour. Samples were irradiated by neutrons in nuclear reactor with fluence of 10"1"6 n/cm"2 and 10"1"7 n/cm"2. and by electrons in linear accelerator with dose 1 MGy at the Slovak Medical University. Moessbauer spectra were collected in transmission geometry by a conventional constant-acceleration spectrometer with a "5"7Co(Rh) source. All spectra were measured at room temperature and evaluated by the CONFIT program, which allows simultaneous treatment of crystalline and residual amorphous phase by means of individual lines and distribution of hyperfine components. After summarizing all obtained results, the fluence 10"1"6 n/cm"2 is still not sufficiently high significantly damage amorphous and crystalline structure. This fluence more or less modify the structure than damage. After fluence 10"17"n/cm"2 we observed beginning of the. structural damage. Our results show, that high electron dose also modify the structure of nanocrystaline alloys. In further study of this alloy it would be necessary to find the limit of electron dose under that the alloy is resistant against electron's damage. From point of view Moessbauer spectroscopy the most sensitive parameter is direction of net magnetic moment. (authors)

  10. Quantification of thermal damage in skin tissue

    Institute of Scientific and Technical Information of China (English)

    Xu Feng; Wen Ting; Lu Tianjian; Seffen Keith

    2008-01-01

    Skin thermal damage or skin burns are the most commonly encountered type of trauma in civilian and military communities. Besides, advances in laser, microwave and similar technologies have led to recent developments of thermal treatments for disease and damage involving skin tissue, where the objective is to induce thermal damage precisely within targeted tissue structures but without affecting the surrounding, healthy tissue. Further, extended pain sensation induced by thermal damage has also brought great problem for burn patients. Thus, it is of great importance to quantify the thermal damage in skin tissue. In this paper, the available models and experimental methods for quantification of thermal damage in skin tissue are discussed.

  11. Biologically important radiation damage in DNA

    International Nuclear Information System (INIS)

    Ward, J.F.

    1994-01-01

    Most DNA damage by the hydroxyl radical is confined to the bases, and this base damage represents an important component of locally multiply demanded sites (LMOS). The yields of the major damaged bases have been determined by gas chromatography mass spectrometry. For our propose, it was necessary to convert a known fraction of these damaged bases to strand breaks and then assay these labile sites as the increase in strand break yield over the normally observed level. Three potential agents by which this strategy of conversion of base damage to strand break could be implemented were identified in the original application: 1, Sl nuclease; 2, piperidine; and 3, base damage specific enzymes

  12. Economic measurement of environment damages

    Energy Technology Data Exchange (ETDEWEB)

    Krawiec, F.

    1980-05-01

    The densities, energy consumption, and economic development of the increasing population exacerbate environmental degradation. Air and water pollution is a major environmental problem affecting life and health, outdoor recreation, household soiling, vegetation, materials, and production. The literature review indicated that numerous studies have assessed the physical and monetary damage to populations at risk from excessive concentrations of major air and water pollutants-sulfur dioxide, total suspended particulate matter, oxidants, and carbon monoxide in air; and nutrients, oil, pesticides, and toxic metals and others in water. The measurement of the damages was one of the most controversial issues in pollution abatement. The methods that have been used to estimate the societal value of pollution abatement are: (1) chain of effects, (2) market approaches, and (3) surveys. National gross damages of air pollution of $20.2 billion and of water pollution of $11.1 billion for 1973 are substantial. These best estimates, updated for the economic and demographic conditions, could provide acceptable control totals for estimating and predicting benefits and costs of abating air and water pollution emissions. The major issues to be resolved are: (1) lack of available noneconomic data, (2) theoretical and empirical difficulties of placing a value on human life and health and on benefits such as aesthetics, and (3) lack of available demographic and economic data.

  13. Radiation damage of structural materials

    International Nuclear Information System (INIS)

    Koutsky, J.; Kocik, J.

    1994-01-01

    Maintaining the integrity of nuclear power plants (NPP) is critical in the prevention or control of severe accidents. This monograph deals with both basic groups of structural materials used in the design of light-water nuclear reactors, making the primary safety barriers of NPPs. Emphasis is placed on materials used in VVER-type nuclear reactors: Cr-Mo-V and Cr-Ni-Mo-V steel for reactor pressure vessels (RPV) and Zr-Nb alloys for fuel element cladding. The book is divided into seven main chapters, with the exception of the opening one and the chapter providing phenomenological background for the subject of radiation damage. Chapters 3-6 are devoted to RPV steels and chapters 7-9 to zirconium alloys, analyzing their radiation damage structure, changes of mechanical properties due to neutron irradiation as well as factors influencing the degree of their performance degradation. The recovery of damaged materials is also discussed. Considerable attention is paid to a comparison of VVER-type and western-type light-water materials

  14. Damage-induced tensile instability

    International Nuclear Information System (INIS)

    Hult, J.

    1975-01-01

    The paper presents a unified description of ductile and brittle rupture phenomena in structural components under tensile loading with particular emphasis on creep rupture. Two structural elements are analyzed in detail: 1) the uniform tensile bar subject to a Heaviside history of tensile force and superimposed such loadings, i.e. staircase histories, and 2) the thinwalled spherical pressure vessel subject to a Heaviside history of internal pressure. For both these structures the conditions for instantaneous as well as delayed rupture are analysed. It is shown that a state of mechanical instability will be reached at a certain load or after a certain time. The cases of purely ductile rupture and purely brittle fracture are identified as two limiting cases of this general instability phenomenon. The Kachanov-Rabotnov damage law implies that a structural component will fail in tension only when it has reached a state of complete damage, i.e. zero load carrying capacity. The extended law predicts failure at an earlier stage of the deterioration process and is therefore more compatible with experimental observation. Further experimental support is offered by predictions for staircase loading histories, both step-up and step-down type. The presented damage theory here predicts strain histories which are in closer agreement with test data than predictions based on other phenomenological theories

  15. The Nucleolus: In Genome Maintenance and Repair.

    Science.gov (United States)

    Tsekrekou, Maria; Stratigi, Kalliopi; Chatzinikolaou, Georgia

    2017-07-01

    The nucleolus is the subnuclear membrane-less organelle where rRNA is transcribed and processed and ribosomal assembly occurs. During the last 20 years, however, the nucleolus has emerged as a multifunctional organelle, regulating processes that go well beyond its traditional role. Moreover, the unique organization of rDNA in tandem arrays and its unusually high transcription rates make it prone to unscheduled DNA recombination events and frequent RNA:DNA hybrids leading to DNA double strand breaks (DSBs). If not properly repaired, rDNA damage may contribute to premature disease onset and aging. Deregulation of ribosomal synthesis at any level from transcription and processing to ribosomal subunit assembly elicits a stress response and is also associated with disease onset. Here, we discuss how genome integrity is maintained within nucleoli and how such structures are functionally linked to nuclear DNA damage response and repair giving an emphasis on the newly emerging roles of the nucleolus in mammalian physiology and disease.

  16. Genomic Feature Models

    DEFF Research Database (Denmark)

    Sørensen, Peter; Edwards, Stefan McKinnon; Rohde, Palle Duun

    -additive genetic mechanisms. These modeling approaches have proven to be highly useful to determine population genetic parameters as well as prediction of genetic risk or value. We present a series of statistical modelling approaches that use prior biological information for evaluating the collective action......Whole-genome sequences and multiple trait phenotypes from large numbers of individuals will soon be available in many populations. Well established statistical modeling approaches enable the genetic analyses of complex trait phenotypes while accounting for a variety of additive and non...... regions and gene ontologies) that provide better model fit and increase predictive ability of the statistical model for this trait....

  17. Genomic dairy cattle breeding

    DEFF Research Database (Denmark)

    Mark, Thomas; Sandøe, Peter

    2010-01-01

    the thoughts of breeders and other stakeholders on how to best make use of genomic breeding in the future. Intensive breeding has played a major role in securing dramatic increases in milk yield since the Second World War. Until recently, the main focus in dairy cattle breeding was on production traits...... it less accountable to the concern of private farmers for the welfare of their animals. It is argued that there is a need to mobilise a wide range of stakeholders to monitor developments and maintain pressure on breeding companies so that they are aware of the need to take precautionary measures to avoid...

  18. Organizational heterogeneity of vertebrate genomes.

    Science.gov (United States)

    Frenkel, Svetlana; Kirzhner, Valery; Korol, Abraham

    2012-01-01

    Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS) analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers) in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM) allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

  19. Organizational heterogeneity of vertebrate genomes.

    Directory of Open Access Journals (Sweden)

    Svetlana Frenkel

    Full Text Available Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

  20. Genome engineering in Vibrio cholerae

    DEFF Research Database (Denmark)

    Val, Marie-Eve; Skovgaard, Ole; Ducos-Galand, Magaly

    2012-01-01

    Although bacteria with multipartite genomes are prevalent, our knowledge of the mechanisms maintaining their genome is very limited, and much remains to be learned about the structural and functional interrelationships of multiple chromosomes. Owing to its bi-chromosomal genome architecture and its....... This difficulty was surmounted using a unique and powerful strategy based on massive rearrangement of prokaryotic genomes. We developed a site-specific recombination-based engineering tool, which allows targeted, oriented, and reciprocal DNA exchanges. Using this genetic tool, we obtained a panel of V. cholerae...

  1. Genome Writing: Current Progress and Related Applications

    Directory of Open Access Journals (Sweden)

    Yueqiang Wang

    2018-02-01

    Full Text Available The ultimate goal of synthetic biology is to build customized cells or organisms to meet specific industrial or medical needs. The most important part of the customized cell is a synthetic genome. Advanced genomic writing technologies are required to build such an artificial genome. Recently, the partially-completed synthetic yeast genome project represents a milestone in this field. In this mini review, we briefly introduce the techniques for de novo genome synthesis and genome editing. Furthermore, we summarize recent research progresses and highlight several applications in the synthetic genome field. Finally, we discuss current challenges and future prospects. Keywords: Synthetic biology, Genome writing, Genome editing, Bioethics, Biosafety

  2. Comparative genomics of Lactobacillus and other LAB

    DEFF Research Database (Denmark)

    Wassenaar, Trudy M.; Lukjancenko, Oksana

    2014-01-01

    that of the others, with the two Streptococcus species having the shortest genomes. The widest distribution in genome content was observed for Lactobacillus. The number of tRNA and rRNA gene copies varied considerably, with exceptional high numbers observed for Lb. delbrueckii, while these numbers were relatively......The genomes of 66 LABs, belonging to five different genera, were compared for genome size and gene content. The analyzed genomes included 37 Lactobacillus genomes of 17 species, six Lactococcus lactis genomes, four Leuconostoc genomes of three species, six Streptococcus genomes of two species...

  3. Genome Update: alignment of bacterial chromosomes

    DEFF Research Database (Denmark)

    Ussery, David; Jensen, Mette; Poulsen, Tine Rugh

    2004-01-01

    There are four new microbial genomes listed in this month's Genome Update, three belonging to Gram-positive bacteria and one belonging to an archaeon that lives at pH 0; all of these genomes are listed in Table 1⇓. The method of genome comparison this month is that of genome alignment and, as an ...

  4. DNA Repair and Genome Maintenance in Bacillus subtilis

    Science.gov (United States)

    Lenhart, Justin S.; Schroeder, Jeremy W.; Walsh, Brian W.

    2012-01-01

    Summary: From microbes to multicellular eukaryotic organisms, all cells contain pathways responsible for genome maintenance. DNA replication allows for the faithful duplication of the genome, whereas DNA repair pathways preserve DNA integrity in response to damage originating from endogenous and exogenous sources. The basic pathways important for DNA replication and repair are often conserved throughout biology. In bacteria, high-fidelity repair is balanced with low-fidelity repair and mutagenesis. Such a balance is important for maintaining viability while providing an opportunity for the advantageous selection of mutations when faced with a changing environment. Over the last decade, studies of DNA repair pathways in bacteria have demonstrated considerable differences between Gram-positive and Gram-negative organisms. Here we review and discuss the DNA repair, genome maintenance, and DNA damage checkpoint pathways of the Gram-positive bacterium Bacillus subtilis. We present their molecular mechanisms and compare the functions and regulation of several pathways with known information on other organisms. We also discuss DNA repair during different growth phases and the developmental program of sporulation. In summary, we present a review of the function, regulation, and molecular mechanisms of DNA repair and mutagenesis in Gram-positive bacteria, with a strong emphasis on B. subtilis. PMID:22933559

  5. Genome Stability Maintenance in Naked Mole-Rat.

    Science.gov (United States)

    Petruseva, I O; Evdokimov, A N; Lavrik, O I

    2017-01-01

    The naked mole-rat ( Heterocephalus glaber ) is one of the most promising models used to study genome maintenance systems, including the effective repair of damage to DNA. The naked mole-rat is the longest lived rodent species, which is extraordinarily resistant to cancer and has a number of other unique phenotypic traits. For at least 80% of its lifespan, this animal shows no signs of aging or any increased likelihood of death and retains the ability to reproduce. The naked mole-rat draws the heightened attention of researchers who study the molecular basis of lengthy lifespan and cancer resistance. Despite the fact that the naked mole-rat lives under genotoxic stress conditions (oxidative, etc.), the main characteristics of its genome and proteome are a high stability and effective functioning. Replicative senescence in the somatic cells of naked mole-rats is missing, while an additional p53/pRb-dependent mechanism of early contact inhibition has been revealed in its fibroblasts, which controls cell proliferation and its mechanism of arf- dependent aging. The unique traits of phenotypic and molecular adaptations found in the naked mole-rat speak to a high stability and effective functioning of the molecular machinery that counteract damage accumulation in its genome. This review analyzes existing results in the study of the molecular basis of longevity and high cancer resistance in naked mole-rats.

  6. Proteomics insights into DNA damage response and translating this knowledge to clinical strategies

    DEFF Research Database (Denmark)

    von Stechow, Louise; Olsen, Jesper V

    2017-01-01

    Genomic instability is a critical driver in the process of cancer formation. At the same time, inducing DNA damage by irradiation or genotoxic compounds constitutes a key therapeutic strategy to kill fast-dividing cancer cells. Sensing of DNA lesions initiates a complex set of signalling pathways......) in the DDR. Finally, we provide an outlook on how proteomics studies of the DDR could aid clinical developments on multiple levels. This article is protected by copyright. All rights reserved....

  7. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    OpenAIRE

    Sterpone, Silvia; Cozzi, Renata

    2010-01-01

    It is well known that ionizing radiation (IR) can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to de...

  8. DNA damage response is hijacked by human papillomaviruses to complete their life cycle

    OpenAIRE

    Hong, Shi-yuan

    2017-01-01

    The DNA damage response (DDR) is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and cell cycle regulation. Human papillomaviruses (HPVs) are the main etiological agents of cervical cancer. Cervical cancer ranks as the fourth most common cancer among women and the second most frequent cause of cancer-related death worldwide. Over 200 types of HPVs have been identifi...

  9. Damages induced in lambda phage DNA by enzyme-generated triplet acetone

    International Nuclear Information System (INIS)

    Menck, C.F.; Cabral Neto, J.B.; Gomes, R.A.; Faljoni-Alario, A.

    1985-01-01

    Exposure of lambda phage to triplet acetone, generated during the aerobic oxidation of isobutanal by peroxidase, leads to genome lesions. The majority of these lesions are detected as DNA single-strand breaks only in alkaline conditions, so true breaks were not observed. Also, no sites sensitive to UV-endonuclease from Micrococcus luteus were found in DNA from treated phage. The participation of triplet acetone in the generation of such DNA damage is discussed. (Author) [pt

  10. Insights into structural variations and genome rearrangements in prokaryotic genomes.

    Science.gov (United States)

    Periwal, Vinita; Scaria, Vinod

    2015-01-01

    Structural variations (SVs) are genomic rearrangements that affect fairly large fragments of DNA. Most of the SVs such as inversions, deletions and translocations have been largely studied in context of genetic diseases in eukaryotes. However, recent studies demonstrate that genome rearrangements can also have profound impact on prokaryotic genomes, leading to altered cell phenotype. In contrast to single-nucleotide variations, SVs provide a much deeper insight into organization of bacterial genomes at a much better resolution. SVs can confer change in gene copy number, creation of new genes, altered gene expression and many other functional consequences. High-throughput technologies have now made it possible to explore SVs at a much refined resolution in bacterial genomes. Through this review, we aim to highlight the importance of the less explored field of SVs in prokaryotic genomes and their impact. We also discuss its potential applicability in the emerging fields of synthetic biology and genome engineering where targeted SVs could serve to create sophisticated and accurate genome editing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Comparative genomics reveals insights into avian genome evolution and adaptation

    DEFF Research Database (Denmark)

    Zhang, Guojie; Li, Cai; Li, Qiye

    2014-01-01

    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, ...

  12. Air pollution and genomic instability: The role of particulate matter in lung carcinogenesis

    International Nuclear Information System (INIS)

    Santibáñez-Andrade, Miguel; Quezada-Maldonado, Ericka Marel; Osornio-Vargas, Álvaro; Sánchez-Pérez, Yesennia; García-Cuellar, Claudia M.

    2017-01-01

    In this review, we summarize and discuss the evidence regarding the interaction between air pollution, especially particulate matter (PM), and genomic instability. PM has been widely studied in the context of several diseases, and its role in lung carcinogenesis gained relevance due to an increase in cancer cases for which smoking does not seem to represent the main risk factor. According to epidemiological and toxicological evidence, PM acts as a carcinogenic factor in humans, inducing high rates of genomic alterations. Here, we discuss not only how PM is capable of inducing genomic instability during the carcinogenic process but also how our genetic background influences the response to the sources of damage. - Highlights: • Air pollution represents a worldwide problem with impact on human health. • Particulate matter (PM) has a recognized carcinogenic potential in humans. • Lung cancer susceptibility depends on gene-environment interactions. • Epidemiological and experimental evidence links PM exposure to genomic instability. • PM and genomic instability are co-dependent factors during cancer continuum. - We summarize the association between particulate matter (a component of air pollution) and genomic instability as well as discuss how new strategies to study the impact of air pollution on genomic instability and lung-cancer development could improve our understanding of the lung-cancer genome.

  13. Identification of a large genomic region in UV-irradiated human cells which has fewer cyclobutane pyrimidine dimers than most genomic regions

    International Nuclear Information System (INIS)

    Kantor, G.J.; Deiss-Tolbert, D.M.

    1995-01-01

    Size separation after UV-endonuclease digestion of DNA from UV-irradiated human cells using denaturing conditions fractionates the genome based on cyclobutane pyrimidine dimer content. We have examined the largest molecules available (50-80 kb; about 5% of the DNA) after fractionation and those of average size (5-15 kb) for content of some specific genes. We find that the largest molecules are not a representative sampling of the genome. Three contiguous genes located in a G+C-rich isochore (tyrosine hydroxylase, insulin, insulin-like growth factor II) have concentrations two to three times greater in the largest molecules. This shows that this genomic region has fewer pyrimidine dimers than most other genomic regions. In contrast, the β-actin genomic region, which has a similar G+C content, has an equal concentration in both fractions as do the p53 and β-globin genomic regions, which are A+T-rich. These data show that DNA damage in the form of cyclobutane pyrimidine dimers occurs with different probabilities in specific isochores. Part of the reason may be the relative G-C content, but other factors must play a significant role. We also report that the transcriptionally inactive insulin region is repaired at the genome-overall rate in normal cells and is not repaired in xeroderma pigmentosum complementation group C cells. (author)

  14. Genomic instability and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Little, John B [Harvard School of Public Health, Boston, MA 02115 (United States)

    2003-06-01

    Genomic instability is a hallmark of cancer cells, and is thought to be involved in the process of carcinogenesis. Indeed, a number of rare genetic disorders associated with a predisposition to cancer are characterised by genomic instability occurring in somatic cells. Of particular interest is the observation that transmissible instability can be induced in somatic cells from normal individuals by exposure to ionising radiation, leading to a persistent enhancement in the rate at which mutations and chromosomal aberrations arise in the progeny of the irradiated cells after many generations of replication. If such induced instability is involved in radiation carcinogenesis, it would imply that the initial carcinogenic event may not be a rare mutation occurring in a specific gene or set of genes. Rather, radiation may induce a process of instability in many cells in a population, enhancing the rate at which the multiple gene mutations necessary for the development of cancer may arise in a given cell lineage. Furthermore, radiation could act at any stage in the development of cancer by facilitating the accumulation of the remaining genetic events required to produce a fully malignant tumour. The experimental evidence for such induced instability is reviewed. (review)

  15. Genomic instability and radiation

    International Nuclear Information System (INIS)

    Little, John B

    2003-01-01

    Genomic instability is a hallmark of cancer cells, and is thought to be involved in the process of carcinogenesis. Indeed, a number of rare genetic disorders associated with a predisposition to cancer are characterised by genomic instability occurring in somatic cells. Of particular interest is the observation that transmissible instability can be induced in somatic cells from normal individuals by exposure to ionising radiation, leading to a persistent enhancement in the rate at which mutations and chromosomal aberrations arise in the progeny of the irradiated cells after many generations of replication. If such induced instability is involved in radiation carcinogenesis, it would imply that the initial carcinogenic event may not be a rare mutation occurring in a specific gene or set of genes. Rather, radiation may induce a process of instability in many cells in a population, enhancing the rate at which the multiple gene mutations necessary for the development of cancer may arise in a given cell lineage. Furthermore, radiation could act at any stage in the development of cancer by facilitating the accumulation of the remaining genetic events required to produce a fully malignant tumour. The experimental evidence for such induced instability is reviewed. (review)

  16. DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Marchetti, Francesco; Wryobek, Andrew J

    2008-02-21

    The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7- 1 dbf). Analysis of chromosomalaberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

  17. DNA Repair Decline During Mouse Spermiogenesis Results in the Accumulation of Heritable DNA Damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Marchetti, Francesco; Wyrobek, Andrew J.

    2007-12-01

    The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

  18. DNA damage by carbonyl stress in human skin cells

    International Nuclear Information System (INIS)

    Roberts, Michael J.; Wondrak, Georg T.; Laurean, Daniel Cervantes; Jacobson, Myron K.; Jacobson, Elaine L.

    2003-01-01

    Reactive carbonyl species (RCS) are potent mediators of cellular carbonyl stress originating from endogenous chemical processes such as lipid peroxidation and glycation. Skin deterioration as observed in photoaging and diabetes has been linked to accumulative protein damage from glycation, but the effects of carbonyl stress on skin cell genomic integrity are ill defined. In this study, the genotoxic effects of acute carbonyl stress on HaCaT keratinocytes and CF3 fibroblasts were assessed. Administration of the α-dicarbonyl compounds glyoxal and methylglyoxal as physiologically relevant RCS inhibited skin cell proliferation, led to intra-cellular protein glycation as evidenced by the accumulation of N ε -(carboxymethyl)-L-lysine (CML) in histones, and caused extensive DNA strand cleavage as assessed by the comet assay. These effects were prevented by treatment with the carbonyl scavenger D-penicillamine. Both glyoxal and methylglyoxal damaged DNA in intact cells. Glyoxal caused DNA strand breaks while methylglyoxal produced extensive DNA-protein cross-linking as evidenced by pronounced nuclear condensation and total suppression of comet formation. Glycation by glyoxal and methylglyoxal resulted in histone cross-linking in vitro and induced oxygen-dependent cleavage of plasmid DNA, which was partly suppressed by the hydroxyl scavenger mannitol. We suggest that a chemical mechanism of cellular DNA damage by carbonyl stress occurs in which histone glycoxidation is followed by reactive oxygen induced DNA stand breaks. The genotoxic potential of RCS in cultured skin cells and its suppression by a carbonyl scavenger as described in this study have implications for skin damage and carcinogenesis and its prevention by agents selective for carbonyl stress

  19. DNA damage by carbonyl stress in human skin cells

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Michael J.; Wondrak, Georg T.; Laurean, Daniel Cervantes; Jacobson, Myron K.; Jacobson, Elaine L

    2003-01-28

    Reactive carbonyl species (RCS) are potent mediators of cellular carbonyl stress originating from endogenous chemical processes such as lipid peroxidation and glycation. Skin deterioration as observed in photoaging and diabetes has been linked to accumulative protein damage from glycation, but the effects of carbonyl stress on skin cell genomic integrity are ill defined. In this study, the genotoxic effects of acute carbonyl stress on HaCaT keratinocytes and CF3 fibroblasts were assessed. Administration of the {alpha}-dicarbonyl compounds glyoxal and methylglyoxal as physiologically relevant RCS inhibited skin cell proliferation, led to intra-cellular protein glycation as evidenced by the accumulation of N{sup {epsilon}}-(carboxymethyl)-L-lysine (CML) in histones, and caused extensive DNA strand cleavage as assessed by the comet assay. These effects were prevented by treatment with the carbonyl scavenger D-penicillamine. Both glyoxal and methylglyoxal damaged DNA in intact cells. Glyoxal caused DNA strand breaks while methylglyoxal produced extensive DNA-protein cross-linking as evidenced by pronounced nuclear condensation and total suppression of comet formation. Glycation by glyoxal and methylglyoxal resulted in histone cross-linking in vitro and induced oxygen-dependent cleavage of plasmid DNA, which was partly suppressed by the hydroxyl scavenger mannitol. We suggest that a chemical mechanism of cellular DNA damage by carbonyl stress occurs in which histone glycoxidation is followed by reactive oxygen induced DNA stand breaks. The genotoxic potential of RCS in cultured skin cells and its suppression by a carbonyl scavenger as described in this study have implications for skin damage and carcinogenesis and its prevention by agents selective for carbonyl stress.

  20. DNA damage and repair in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Zaras, Magdalena [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Wozniak, Katarzyna [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Szaflik, Jerzy [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Blasiak, Janusz, E-mail: januszb@biol.uni.lodz.pl [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2009-10-02

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  1. DNA damage and repair in age-related macular degeneration

    International Nuclear Information System (INIS)

    Szaflik, Jacek P.; Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika; Zaras, Magdalena; Wozniak, Katarzyna; Szaflik, Jerzy; Blasiak, Janusz

    2009-01-01

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  2. Theory of microbial genome evolution

    Science.gov (United States)

    Koonin, Eugene

    Bacteria and archaea have small genomes tightly packed with protein-coding genes. This compactness is commonly perceived as evidence of adaptive genome streamlining caused by strong purifying selection in large microbial populations. In such populations, even the small cost incurred by nonfunctional DNA because of extra energy and time expenditure is thought to be sufficient for this extra genetic material to be eliminated by selection. However, contrary to the predictions of this model, there exists a consistent, positive correlation between the strength of selection at the protein sequence level, measured as the ratio of nonsynonymous to synonymous substitution rates, and microbial genome size. By fitting the genome size distributions in multiple groups of prokaryotes to predictions of mathematical models of population evolution, we show that only models in which acquisition of additional genes is, on average, slightly beneficial yield a good fit to genomic data. Thus, the number of genes in prokaryotic genomes seems to reflect the equilibrium between the benefit of additional genes that diminishes as the genome grows and deletion bias. New genes acquired by microbial genomes, on average, appear to be adaptive. Evolution of bacterial and archaeal genomes involves extensive horizontal gene transfer and gene loss. Many microbes have open pangenomes, where each newly sequenced genome contains more than 10% `ORFans', genes without detectable homologues in other species. A simple, steady-state evolutionary model reveals two sharply distinct classes of microbial genes, one of which (ORFans) is characterized by effectively instantaneous gene replacement, whereas the other consists of genes with finite, distributed replacement rates. These findings imply a conservative estimate of at least a billion distinct genes in the prokaryotic genomic universe.

  3. Genomic selection: genome-wide prediction in plant improvement.

    Science.gov (United States)

    Desta, Zeratsion Abera; Ortiz, Rodomiro

    2014-09-01

    Association analysis is used to measure relations between markers and quantitative trait loci (QTL). Their estimation ignores genes with small effects that trigger underpinning quantitative traits. By contrast, genome-wide selection estimates marker effects across the whole genome on the target population based on a prediction model developed in the training population (TP). Whole-genome prediction models estimate all marker effects in all loci and capture small QTL effects. Here, we review several genomic selection (GS) models with respect to both the prediction accuracy and genetic gain from selection. Phenotypic selection or marker-assisted breeding protocols can be replaced by selection, based on whole-genome predictions in which phenotyping updates the model to build up the prediction accuracy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Parasite Genome Projects and the Trypanosoma cruzi Genome Initiative

    Directory of Open Access Journals (Sweden)

    Wim Degrave

    1997-11-01

    Full Text Available Since the start of the human genome project, a great number of genome projects on other "model" organism have been initiated, some of them already completed. Several initiatives have also been started on parasite genomes, mainly through support from WHO/TDR, involving North-South and South-South collaborations, and great hopes are vested in that these initiatives will lead to new tools for disease control and prevention, as well as to the establishment of genomic research technology in developing countries. The Trypanosoma cruzi genome project, using the clone CL-Brener as starting point, has made considerable progress through the concerted action of more than 20 laboratories, most of them in the South. A brief overview of the current state of the project is given

  5. A Taste of Algal Genomes from the Joint Genome Institute

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Alan; Grigoriev, Igor

    2012-06-17

    Algae play profound roles in aquatic food chains and the carbon cycle, can impose health and economic costs through toxic blooms, provide models for the study of symbiosis, photosynthesis, and eukaryotic evolution, and are candidate sources for bio-fuels; all of these research areas are part of the mission of DOE's Joint Genome Institute (JGI). To date JGI has sequenced, assembled, annotated, and released to the public the genomes of 18 species and strains of algae, sampling almost all of the major clades of photosynthetic eukaryotes. With more algal genomes currently undergoing analysis, JGI continues its commitment to driving forward basic and applied algal science. Among these ongoing projects are the pan-genome of the dominant coccolithophore Emiliania huxleyi, the interrelationships between the 4 genomes in the nucleomorph-containing Bigelowiella natans and Guillardia theta, and the search for symbiosis genes of lichens.

  6. Modeling damage in concrete pavements and bridges.

    Science.gov (United States)

    2010-09-01

    This project focused on micromechanical modeling of damage in concrete under general, multi-axial loading. A : continuum-level, three-dimensional constitutive model based on micromechanics was developed. The model : accounts for damage in concrete by...

  7. Nerve damage from diabetes - self-care

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000326.htm Nerve damage from diabetes - self-care To use the ... or at other unusual times. Treating and Preventing Nerve Damage from Diabetes Treating diabetic neuropathy can make ...

  8. Damage Models for Soft Tissues: A Survey.

    Science.gov (United States)

    Li, Wenguang

    Damage to soft tissues in the human body has been investigated for applications in healthcare, sports, and biomedical engineering. This paper reviews and classifies damage models for soft tissues to summarize achievements, identify new directions, and facilitate finite element analysis. The main ideas of damage modeling methods are illustrated and interpreted. A few key issues related to damage models, such as experimental data curve-fitting, computational effort, connection between damage and fractures/cracks, damage model applications, and fracture/crack extension simulation, are discussed. Several new challenges in the field are identified and outlined. This review can be useful for developing more advanced damage models and extending damage modeling methods to a variety of soft tissues.

  9. Effective elastic properties of damaged isotropic solids

    International Nuclear Information System (INIS)

    Lee, U Sik

    1998-01-01

    In continuum damage mechanics, damaged solids have been represented by the effective elastic stiffness into which local damage is smoothly smeared. Similarly, damaged solids may be represented in terms of effective elastic compliances. By virtue of the effective elastic compliance representation, it may become easier to derive the effective engineering constants of damaged solids from the effective elastic compliances, all in closed form. Thus, in this paper, by using a continuum modeling approach based on both the principle of strain energy equivalence and the equivalent elliptical micro-crack representation of local damage, the effective elastic compliance and effective engineering constants are derived in terms of the undamaged (virgin) elastic properties and a scalar damage variable for both damaged two-and three-dimensional isotropic solids

  10. OryzaGenome: Genome Diversity Database of Wild Oryza Species

    KAUST Repository

    Ohyanagi, Hajime

    2015-11-18

    The species in the genus Oryza, encompassing nine genome types and 23 species, are a rich genetic resource and may have applications in deeper genomic analyses aiming to understand the evolution of plant genomes. With the advancement of next-generation sequencing (NGS) technology, a flood of Oryza species reference genomes and genomic variation information has become available in recent years. This genomic information, combined with the comprehensive phenotypic information that we are accumulating in our Oryzabase, can serve as an excellent genotype-phenotype association resource for analyzing rice functional and structural evolution, and the associated diversity of the Oryza genus. Here we integrate our previous and future phenotypic/habitat information and newly determined genotype information into a united repository, named OryzaGenome, providing the variant information with hyperlinks to Oryzabase. The current version of OryzaGenome includes genotype information of 446 O. rufipogon accessions derived by imputation and of 17 accessions derived by imputation-free deep sequencing. Two variant viewers are implemented: SNP Viewer as a conventional genome browser interface and Variant Table as a textbased browser for precise inspection of each variant one by one. Portable VCF (variant call format) file or tabdelimited file download is also available. Following these SNP (single nucleotide polymorphism) data, reference pseudomolecules/ scaffolds/contigs and genome-wide variation information for almost all of the closely and distantly related wild Oryza species from the NIG Wild Rice Collection will be available in future releases. All of the resources can be accessed through http://viewer.shigen.info/oryzagenome/.

  11. Specific transcripts are elevated in Saccharomyces cerevisiae in response to DNA damage

    International Nuclear Information System (INIS)

    McClanahan, T.; McEntee, K.

    1984-01-01

    Differential hybridization has been used to identify genes in Saccharomyces cerevisiae displaying increased transcript levels after treatment of cells with UV irradiation or with the mutagen/carcinogen 4-nitroquinoline-1-oxide (NQO). The authors describe the isolation and characterization of four DNA damage responsive genes obtained from screening ca. 9000 yeast genomic clones. Two of these clones, lambda 78A and pBR178C, contain repetitive elements in the yeast genome as shown by Southern hybridization analysis. Although the genomic hybridization pattern is distinct for each of these two clones, both of these sequences hybridize to large polyadenylated transcripts ca. 5 kilobases in length. Two other DNA damage responsive sequences, pBRA2 and pBR3016B, are single-copy genes and hybridize to 0.5- and 3.2-kilobase transcripts, respectively. Kinetic analysis of the 0.5-kilobase transcript homologous to pBRA2 indicates that the level of this RNA increases more than 15-fold within 20 min after exposure to 4-nitroquinoline-1-oxide. Moreover, the level of this transcript is significantly elevated in cells containing the rad52-1 mutation which are deficient in DNA strand break repair and gene conversion. These results provide some of the first evidence that DNA damage stimulates transcription of specific genes in eucaryotic cells

  12. Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage

    Directory of Open Access Journals (Sweden)

    Robert L. Eoff

    2010-01-01

    Full Text Available DNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and disease in multi-cellular organisms. Investigations into the chemical and biological aspects of DNA damage have identified multi-tiered and overlapping cellular systems that have evolved as a means of stabilizing the genome. One of these pathways supports DNA replication events by in a sense adopting the mantra that one must “make the best of a bad situation” and tolerating covalent modification to DNA through less accurate copying of the damaged region. Part of this so-called DNA damage tolerance pathway involves the recruitment of specialized DNA polymerases to sites of stalled or collapsed replication forks. These enzymes have unique structural and functional attributes that often allow bypass of adducted template DNA and successful completion of genomic replication. What follows is a selective description of the salient structural features and bypass properties of specialized DNA polymerases with an emphasis on Y-family members.

  13. Quantification of thermal damage in skin tissue

    Institute of Scientific and Technical Information of China (English)

    徐峰; 文婷; 卢天健; Seffen; Keith

    2008-01-01

    Skin thermal damage or skin burns are the most commonly encountered type of trauma in civilian and military communities. Besides, advances in laser, microwave and similar technologies have led to recent developments of thermal treatments for disease and damage involving skin tissue, where the objective is to induce thermal damage precisely within targeted tissue structures but without affecting the surrounding, healthy tissue. Further, extended pain sensation induced by thermal damage has also brought great...

  14. Large area damage testing of optics

    International Nuclear Information System (INIS)

    Sheehan, L.; Kozlowski, M.; Stolz, C.

    1996-01-01

    The damage threshold specifications for the National Ignition Facility will include a mixture of standard small-area tests and new large-area tests. During our studies of laser damage and conditioning processes of various materials we have found that some damage morphologies are fairly small and this damage does not grow with further illumination. This type of damage might not be detrimental to the laser performance. We should therefore assume that some damage can be allowed on the optics, but decide on a maximum damage allowance of damage. A new specification of damage threshold termed open-quotes functional damage thresholdclose quotes was derived. Further correlation of damage size and type to system performance must be determined in order to use this measurement, but it is clear that it will be a large factor in the optics performance specifications. Large-area tests have verified that small-area testing is not always sufficient when the optic in question has defect-initiated damage. This was evident for example on sputtered polarizer and mirror coatings where the defect density was low enough that the features could be missed by standard small- area testing. For some materials, the scale-length at which damage non-uniformities occur will effect the comparison of small-area and large-area tests. An example of this was the sub-aperture tests on KD*P crystals on the Beamlet test station. The tests verified the large-area damage threshold to be similar to that found when testing a small-area. Implying that for this KD*P material, the dominate damage mechanism is of sufficiently small scale-length that small-area testing is capable of determining the threshold. The Beamlet test station experiments also demonstrated the use of on-line laser conditioning to increase the crystals damage threshold

  15. Percutaneous penetration through slightly damaged skin

    DEFF Research Database (Denmark)

    Nielsen, Jesper B

    2005-01-01

    with human skin. A slight damage to the barrier integrity was induced by pre-treatment of the skin with sodium lauryl sulphate (SLS) before pesticide exposure. The experimental model with 3 h pre-treatment with SLS (0.1% or 0.3%) assured a significant but controlled damage to the barrier integrity, a damage...

  16. Cocoa/Cotton Comparative Genomics

    Science.gov (United States)

    With genome sequence from two members of the Malvaceae family recently made available, we are exploring syntenic relationships, gene content, and evolutionary trajectories between the cacao and cotton genomes. An assembly of cacao (Theobroma cacao) using Illumina and 454 sequence technology yielded ...

  17. Genomic selection in dairy cattle

    NARCIS (Netherlands)

    Roos, de A.P.W.

    2011-01-01

    The objectives of this Ph.D. thesis were (1) to optimise genomic selection in dairy cattle with respect to the accuracy of predicting total genetic merit and (2) to optimise a dairy cattle breeding program using genomic selection. The study was performed using a combination of real data sets and

  18. Cloud computing for comparative genomics

    Directory of Open Access Journals (Sweden)

    Pivovarov Rimma

    2010-05-01

    Full Text Available Abstract Background Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward. To test this, we redesigned a typical comparative genomics algorithm, the reciprocal smallest distance algorithm (RSD, to run within Amazon's Elastic Computing Cloud (EC2. We then employed the RSD-cloud for ortholog calculations across a wide selection of fully sequenced genomes. Results We ran more than 300,000 RSD-cloud processes within the EC2. These jobs were farmed simultaneously to 100 high capacity compute nodes using the Amazon Web Service Elastic Map Reduce and included a wide mix of large and small genomes. The total computation time took just under 70 hours and cost a total of $6,302 USD. Conclusions The effort to transform existing comparative genomics algorithms from local compute infrastructures is not trivial. However, the speed and flexibility of cloud computing environments provides a substantial boost with manageable cost. The procedure designed to transform the RSD algorithm into a cloud-ready application is readily adaptable to similar comparative genomics problems.

  19. Cloud computing for comparative genomics.

    Science.gov (United States)

    Wall, Dennis P; Kudtarkar, Parul; Fusaro, Vincent A; Pivovarov, Rimma; Patil, Prasad; Tonellato, Peter J

    2010-05-18

    Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward. To test this, we redesigned a typical comparative genomics algorithm, the reciprocal smallest distance algorithm (RSD), to run within Amazon's Elastic Computing Cloud (EC2). We then employed the RSD-cloud for ortholog calculations across a wide selection of fully sequenced genomes. We ran more than 300,000 RSD-cloud processes within the EC2. These jobs were farmed simultaneously to 100 high capacity compute nodes using the Amazon Web Service Elastic Map Reduce and included a wide mix of large and small genomes. The total computation time took just under 70 hours and cost a total of $6,302 USD. The effort to transform existing comparative genomics algorithms from local compute infrastructures is not trivial. However, the speed and flexibility of cloud computing environments provides a substantial boost with manageable cost. The procedure designed to transform the RSD algorithm into a cloud-ready application is readily adaptable to similar comparative genomics problems.

  20. The promise of insect genomics

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, Cornelis J P; Cazzamali, Giuseppe; Williamson, Michael

    2007-01-01

    Insects are the largest animal group in the world and are ecologically and economically extremely important. This importance of insects is reflected by the existence of currently 24 insect genome projects. Our perspective discusses the state-of-the-art of these genome projects and the impacts...

  1. Bioinformatics of genomic association mapping

    NARCIS (Netherlands)

    Vaez Barzani, Ahmad

    2015-01-01

    In this thesis we present an overview of bioinformatics-based approaches for genomic association mapping, with emphasis on human quantitative traits and their contribution to complex diseases. We aim to provide a comprehensive walk-through of the classic steps of genomic association mapping

  2. Radiation damage in lithium orthosilicate

    Energy Technology Data Exchange (ETDEWEB)

    Noda, K.; Nakazawa, T.; Ishii, Y.; Fukai, K.; Watanabe, H. (Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment); Matsui, H.; Vollath, D.

    1993-11-01

    Radiation damage in lithium orthosilicate (Li[sub 4]SiO[sub 4]) and Al-doped Li[sub 4]SiO[sub 4] (Li[sub 3.7]Al[sub 0.1]SiO[sub 4]) irradiated with oxygen ions was studied with ionic conductivity measurements, Raman spectroscopy, Fourier transform infrared photo-acoustic spectroscopy (FT-IR PAS) and transmission electron microscopy. It was seen from the ionic conductivity measurements that lithium-ion vacancies were introduced as irradiation defects for Li-ions sites in both materials due to the irradiation. By the Raman spectroscopy, oxygen atoms in SiO[sub 4] tetrahedra were considered to be preferentially displaced due to the irradiation for Li[sub 4]SiO[sub 4], although only a decrease of the number of SiO[sub 4] tetrahedra occurred for Li[sub 3.7]Al[sub 0.1]SiO[sub 4] by displacement of both silicon and oxygen atoms. Decomposition of SiO[sub 4] tetrahedra and formation of some new phases having Si-O-Si and Si-O bonds were found to take place for both Li[sub 4]SiO[sub 4] and Li[sub 3.7]Al[sub 0.1]SiO[sub 4] by FT-IR PAS. In the electron microscopy, damage microstructure consisting of many voids or cavities and amorphization were observed for Li[sub 4]SiO[sub 4] irradiated with oxygen ions. The recovery behavior of radiation damage mentioned above was also investigated. (author).

  3. Damage instability and Earthquake nucleation

    Science.gov (United States)

    Ionescu, I. R.; Gomez, Q.; Campillo, M.; Jia, X.

    2017-12-01

    Earthquake nucleation (initiation) is usually associated to the loss of the stability of the geological structure under a slip-weakening friction acting on the fault. The key parameters involved in the stability of the fault are the stress drop, the critical slip distance but also the elastic stiffness of the surrounding materials (rocks). We want to explore here how the nucleation phenomena are correlated to the material softening during damage accumulation by dynamic and/or quasi-static processes. Since damage models are describing micro-cracks growth, which is generally an unstable phenomenon, it is natural to expect some loss of stability on the associated micro-mechanics based models. If the model accurately captures the material behavior, then this can be due to the unstable nature of the brittle material itself. We obtained stability criteria at the microscopic scale, which are related to a large class of damage models. We show that for a given continuous strain history the quasi-static or dynamic problems are instable or ill-posed (multiplicity of material responses) and whatever the selection rule is adopted, shocks (time discontinuities) will occur. We show that the quasi-static equilibria chosen by the "perfect delay convention" is always stable. These stability criteria are used to analyze how NIC (Non Interacting Crack) effective elasticity associated to "self similar growth" model work in some special configurations (one family of micro-cracks in mode I, II and III and in plane strain or plain stress). In each case we determine a critical crack density parameter and critical micro-crack radius (length) which distinguish between stable and unstable behaviors. This critical crack density depends only on the chosen configuration and on the Poisson ratio.

  4. A biological-based model that links genomic instability, bystander effects, and adaptive response

    International Nuclear Information System (INIS)

    Scott, B.R.

    2004-01-01

    This paper links genomic instability, bystander effects, and adaptive response in mammalian cell communities via a novel biological-based, dose-response model called NEOTRANS 3 . The model is an extension of the NEOTRANS 2 model that addressed stochastic effects (genomic instability, mutations, and neoplastic transformation) associated with brief exposure to low radiation doses. With both models, ionizing radiation produces DNA damage in cells that can be associated with varying degrees of genomic instability. Cells with persistent problematic instability (PPI) are mutants that arise via misrepair of DNA damage. Progeny of PPI cells also have PPI and can undergo spontaneous neoplastic transformation. Unlike NEOTRANS 2 , with NEOTRANS 3 newly induced mutant PPI cells and their neoplastically transformed progeny can be suppressed via our previously introduced protective apoptosis-mediated (PAM) process, which can be activated by low linear energy transfer (LET) radiation. However, with NEOTRANS 3 (which like NEOTRANS 2 involves cross-talk between nongenomically compromised [e.g., nontransformed, nonmutants] and genomically compromised [e.g., mutants, transformants, etc.] cells), it is assumed that PAM is only activated over a relatively narrow, dose-rate-dependent interval (D PAM ,D off ); where D PAM is a small stochastic activation threshold, and D off is the stochastic dose above which PAM does not occur. PAM cooperates with activated normal DNA repair and with activated normal apoptosis in guarding against genomic instability. Normal repair involves both error-free repair and misrepair components. Normal apoptosis and the error-free component of normal repair protect mammals by preventing the occurrence of mutant cells. PAM selectively removes mutant cells arising via the misrepair component of normal repair, selectively removes existing neoplastically transformed cells, and probably selectively removes other genomically compromised cells when it is activated

  5. Radiation damage of structural materials

    CERN Document Server

    Koutsky, Jaroslav

    1994-01-01

    Maintaining the integrity of nuclear power plants is critical in the prevention or control of severe accidents. This monograph deals with both basic groups of structural materials used in the design of light-water nuclear reactors, making the primary safety barriers of NPPs. Emphasis is placed on materials used in VVER-type nuclear reactors: Cr-Mo-V and Cr-Ni-Mo-V steel for RPV and Zr-Nb alloys for fuel element cladding. The book is divided into 7 main chapters, with the exception of the opening one and the chapter providing a phenomenological background for the subject of radiation damage. Ch

  6. Radiation damage in silicon detectors

    CERN Document Server

    Lindström, G

    2003-01-01

    Radiation damage effects in silicon detectors under severe hadron and gamma-irradiation are surveyed, focusing on bulk effects. Both macroscopic detector properties (reverse current, depletion voltage and charge collection) as also the underlying microscopic defect generation are covered. Basic results are taken from the work done in the CERN-RD48 (ROSE) collaboration updated by results of recent work. Preliminary studies on the use of dimerized float zone and Czochralski silicon as detector material show possible benefits. An essential progress in the understanding of the radiation-induced detector deterioration had recently been achieved in gamma irradiation, directly correlating defect analysis data with the macroscopic detector performance.

  7. The ischemic perinatal brain damage

    International Nuclear Information System (INIS)

    Crisi, G.; Mauri, C.; Canossi, G.; Della Giustina, E.

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis

  8. Damages by radiation in glasses

    International Nuclear Information System (INIS)

    Olguin, F.; Gutierrez, C.; Cisniega, G.; Flores, J.H.; Golzarri, J.I.; Espinoza, G.

    1997-01-01

    As a part of the works carried out to characterize the electrons beam from the Pelletron accelerator of the Mexican Nuclear Center aluminium-silicate glass samples were irradiated. The purpose of these irradiations is to cause alterations in the amorphous microstructure of the material by means of the creation of color centers. The population density of these defects, consequence to the irradiation, is function of the exposure time which varied from 1 to 30 minutes, with an electronic beam energy of 400 keV, doing the irradiations at free atmosphere. the obtained spectra are correlated by damage which the radiation produced. (Author)

  9. Air pollution damage to plants

    Energy Technology Data Exchange (ETDEWEB)

    Daly, G T

    1974-01-01

    The effects of the most important air pollutants on plants are described in detail. The include: smoke and particulates, sulfur dioxide, fluorides, peroxyacetyl nitrate, nitrogen oxides, and ozone. An attempt is made to show that plant injury by air pollution can be recognized and evaluated in the presence of effects from insect, fungal, bacterial, viral pathogens and the symptoms of nutrient and enviromental stress. All plants are more or less affected by toxic gases and metals absorbed from the air. For each plant and each pollutant there is a critical concentration above which damage occurs, and below which growth is normal.

  10. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call...

  11. Pathophysiology of MDS: genomic aberrations.

    Science.gov (United States)

    Ichikawa, Motoshi

    2016-01-01

    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  12. Chemical biology on the genome.

    Science.gov (United States)

    Balasubramanian, Shankar

    2014-08-15

    In this article I discuss studies towards understanding the structure and function of DNA in the context of genomes from the perspective of a chemist. The first area I describe concerns the studies that led to the invention and subsequent development of a method for sequencing DNA on a genome scale at high speed and low cost, now known as Solexa/Illumina sequencing. The second theme will feature the four-stranded DNA structure known as a G-quadruplex with a focus on its fundamental properties, its presence in cellular genomic DNA and the prospects for targeting such a structure in cels with small molecules. The final topic for discussion is naturally occurring chemically modified DNA bases with an emphasis on chemistry for decoding (or sequencing) such modifications in genomic DNA. The genome is a fruitful topic to be further elucidated by the creation and application of chemical approaches. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. IMA Genome-F 5G

    OpenAIRE

    Wingfield, Brenda D.; Barnes, Irene; Wilhelm de Beer, Z.; De Vos, Lieschen; Duong, Tuan A.; Kanzi, Aquillah M.; Naidoo, Kershney; Nguyen, Hai D.T.; Santana, Quentin C.; Sayari, Mohammad; Seifert, Keith A.; Steenkamp, Emma T.; Trollip, Conrad; van der Merwe, Nicolaas A.; van der Nest, Magriet A.

    2015-01-01

    The genomes of Ceratocystis eucalypticola, Chrysoporthe cubensis, Chrysoporthe deuterocubensis, Davidsoniella virescens, Fusarium temperatum, Graphilbum fragrans, Penicillium nordicum and Thielaviopsis musarum are presented in this genome announcement. These seven genomes are from plant pathogens and otherwise economically important fungal species. The genome sizes range from 28 Mb in the case of T. musarum to 45 Mb for Fusarium temperatum. These genomes include the first reports of genomes f...

  14. [Preface for genome editing special issue].

    Science.gov (United States)

    Gu, Feng; Gao, Caixia

    2017-10-25

    Genome editing technology, as an innovative biotechnology, has been widely used for editing the genome from model organisms, animals, plants and microbes. CRISPR/Cas9-based genome editing technology shows its great value and potential in the dissection of functional genomics, improved breeding and genetic disease treatment. In the present special issue, the principle and application of genome editing techniques has been summarized. The advantages and disadvantages of the current genome editing technology and future prospects would also be highlighted.

  15. Privacy in the Genomic Era.

    Science.gov (United States)

    Naveed, Muhammad; Ayday, Erman; Clayton, Ellen W; Fellay, Jacques; Gunter, Carl A; Hubaux, Jean-Pierre; Malin, Bradley A; Wang, Xiaofeng

    2015-09-01

    Genome sequencing technology has advanced at a rapid pace and it is now possible to generate highly-detailed genotypes inexpensively. The collection and analysis of such data has the potential to support various applications, including personalized medical services. While the benefits of the genomics revolution are trumpeted by the biomedical community, the increased availability of such data has major implications for personal privacy; notably because the genome has certain essential features, which include (but are not limited to) (i) an association with traits and certain diseases, (ii) identification capability (e.g., forensics), and (iii) revelation of family relationships. Moreover, direct-to-consumer DNA testing increases the likelihood that genome data will be made available in less regulated environments, such as the Internet and for-profit companies. The problem of genome data privacy thus resides at the crossroads of computer science, medicine, and public policy. While the computer scientists have addressed data privacy for various data types, there has been less attention dedicated to genomic data. Thus, the goal of this paper is to provide a systematization of knowledge for the computer science community. In doing so, we address some of the (sometimes erroneous) beliefs of this field and we report on a survey we conducted about genome data privacy with biomedical specialists. Then, after characterizing the genome privacy problem, we review the state-of-the-art regarding privacy attacks on genomic data and strategies for mitigating such attacks, as well as contextualizing these attacks from the perspective of medicine and public policy. This paper concludes with an enumeration of the challenges for genome data privacy and presents a framework to systematize the analysis of threats and the design of countermeasures as the field moves forward.

  16. Privacy in the Genomic Era

    Science.gov (United States)

    NAVEED, MUHAMMAD; AYDAY, ERMAN; CLAYTON, ELLEN W.; FELLAY, JACQUES; GUNTER, CARL A.; HUBAUX, JEAN-PIERRE; MALIN, BRADLEY A.; WANG, XIAOFENG

    2015-01-01

    Genome sequencing technology has advanced at a rapid pace and it is now possible to generate highly-detailed genotypes inexpensively. The collection and analysis of such data has the potential to support various applications, including personalized medical services. While the benefits of the genomics revolution are trumpeted by the biomedical community, the increased availability of such data has major implications for personal privacy; notably because the genome has certain essential features, which include (but are not limited to) (i) an association with traits and certain diseases, (ii) identification capability (e.g., forensics), and (iii) revelation of family relationships. Moreover, direct-to-consumer DNA testing increases the likelihood that genome data will be made available in less regulated environments, such as the Internet and for-profit companies. The problem of genome data privacy thus resides at the crossroads of computer science, medicine, and public policy. While the computer scientists have addressed data privacy for various data types, there has been less attention dedicated to genomic data. Thus, the goal of this paper is to provide a systematization of knowledge for the computer science community. In doing so, we address some of the (sometimes erroneous) beliefs of this field and we report on a survey we conducted about genome data privacy with biomedical specialists. Then, after characterizing the genome privacy problem, we review the state-of-the-art regarding privacy attacks on genomic data and strategies for mitigating such attacks, as well as contextualizing these attacks from the perspective of medicine and public policy. This paper concludes with an enumeration of the challenges for genome data privacy and presents a framework to systematize the analysis of threats and the design of countermeasures as the field moves forward. PMID:26640318

  17. Online imaging of initial DNA damages at the PTB microbeam

    International Nuclear Information System (INIS)

    Giesen, U.; Langner, F.; Mielke, C.; Mosconi, M.; Dirks, W. G.

    2011-01-01

    In an inter-disciplinary collaboration of Physikalisch-Technische Bundesanstalt (PTB), German Collection of Microorganisms and Cell Cultures (DSMZ) and Heinrich-Heine Univ., live-cell imaging has been established at the charged-particle microbeam facility of PTB. Candidate genes participating in DNA strand-break repair pathways such as PARP-1, MRE11, MSH2, MDC1 and p53BP1 have been modified to generate fluorescent fusion proteins. Using multi-cistronic expression vectors, stable genomic integration was achieved in HT-1080 fibroblasts. The aim of this study is to characterise and use these highly reliable cell lines for studying initial steps of DNA damage responses and kinetics of repair after microbeam irradiation with high- and low-linear energy transfer (LET) particles in living cells at physiological conditions. (authors)

  18. Repair of DNA damage in the human metallothionein gene family

    International Nuclear Information System (INIS)

    Leadon, S.A.; Snowden, M.M.

    1987-01-01

    In order to distinguish enhanced repair of a sequence due to its transcriptional activity from enhanced repair due to chromatin alterations brought about by integration of a sequence into the genome, we have investigated the repair of damage both in endogenous genes and in cell lines that contain an integrated gene with an inducible promoter. The endogenous genes we are studying are the metallothioneins (MTs), a multigene family in man consisting of about 10-12 members. Cultured cells were exposed to 10-J/m 2 uv light and allowed to repair in the presence of bromodeoxyuridine. The DNA was then isolated, digested with Eco RI, and fully hybrid density DNA made by semiconservative synthesis was separated from unreplicated DNA by centrifugation in CsCl density gradients. Unreplicated, parental-density DNA was then reacted with a monoclonal antibody against bromouracil. 1 ref., 1 fig., 1 tab

  19. HSV-I and the cellular DNA damage response.

    Science.gov (United States)

    Smith, Samantha; Weller, Sandra K

    2015-04-01

    Peter Wildy first observed genetic recombination between strains of HSV in 1955. At the time, knowledge of DNA repair mechanisms was limited, and it has only been in the last decade that particular DNA damage response (DDR) pathways have been examined in the context of viral infections. One of the first reports addressing the interaction between a cellular DDR protein and HSV-1 was the observation by Lees-Miller et al . that DNA-dependent protein kinase catalytic subunit levels were depleted in an ICP0-dependent manner during Herpes simplex virus 1 infection. Since then, there have been numerous reports describing the interactions between HSV infection and cellular DDR pathways. Due to space limitations, this review will focus predominantly on the most recent observations regarding how HSV navigates a potentially hostile environment to replicate its genome.

  20. The AID-induced DNA damage response in chromatin

    DEFF Research Database (Denmark)

    Daniel, Jeremy A; Nussenzweig, André

    2013-01-01

    Chemical modifications to the DNA and histone protein components of chromatin can modulate gene expression and genome stability. Understanding the physiological impact of changes in chromatin structure remains an important question in biology. As one example, in order to generate antibody diversity...... with somatic hypermutation and class switch recombination, chromatin must be made accessible for activation-induced cytidine deaminase (AID)-mediated deamination of cytosines in DNA. These lesions are recognized and removed by various DNA repair pathways but, if not handled properly, can lead to formation...... of oncogenic chromosomal translocations. In this review, we focus the discussion on how chromatin-modifying activities and -binding proteins contribute to the native chromatin environment in which AID-induced DNA damage is targeted and repaired. Outstanding questions remain regarding the direct roles...

  1. The genomes and comparative genomics of Lactobacillus delbrueckii phages.

    Science.gov (United States)

    Riipinen, Katja-Anneli; Forsman, Päivi; Alatossava, Tapani

    2011-07-01

    Lactobacillus delbrueckii phages are a great source of genetic diversity. Here, the genome sequences of Lb. delbrueckii phages LL-Ku, c5 and JCL1032 were analyzed in detail, and the genetic diversity of Lb. delbrueckii phages belonging to different taxonomic groups was explored. The lytic isometric group b phages LL-Ku (31,080 bp) and c5 (31,841 bp) showed a minimum nucleotide sequence identity of 90% over about three-fourths of their genomes. The genomic locations of their lysis modules were unique, and the genomes featured several putative overlapping transcription units of genes. LL-Ku and c5 virions displayed peptidoglycan hydrolytic activity associated with a ~36-kDa protein similar in size to the endolysin. Unexpectedly, the 49,433-bp genome of the prolate phage JCL1032 (temperate, group c) revealed a conserved gene order within its structural genes. Lb. delbrueckii phages representing groups a (a phage LL-H), b and c possessed only limited protein sequence homology. Genomic comparison of LL-Ku and c5 suggested that diversification of Lb. delbrueckii phages is mainly due to insertions, deletions and recombination. For the first time, the complete genome sequences of group b and c Lb. delbrueckii phages are reported.

  2. Genomics technologies to study structural variations in the grapevine genome

    Directory of Open Access Journals (Sweden)

    Cardone Maria Francesca

    2016-01-01

    Full Text Available Grapevine is one of the most important crop plants in the world. Recently there was great expansion of genomics resources about grapevine genome, thus providing increasing efforts for molecular breeding. Current cultivars display a great level of inter-specific differentiation that needs to be investigated to reach a comprehensive understanding of the genetic basis of phenotypic differences, and to find responsible genes selected by cross breeding programs. While there have been significant advances in resolving the pattern and nature of single nucleotide polymorphisms (SNPs on plant genomes, few data are available on copy number variation (CNV. Furthermore association between structural variations and phenotypes has been described in only a few cases. We combined high throughput biotechnologies and bioinformatics tools, to reveal the first inter-varietal atlas of structural variation (SV for the grapevine genome. We sequenced and compared four table grape cultivars with the Pinot noir inbred line PN40024 genome as the reference. We detected roughly 8% of the grapevine genome affected by genomic variations. Taken into account phenotypic differences existing among the studied varieties we performed comparison of SVs among them and the reference and next we performed an in-depth analysis of gene content of polymorphic regions. This allowed us to identify genes showing differences in copy number as putative functional candidates for important traits in grapevine cultivation.

  3. Marine Bacterial Genomics

    DEFF Research Database (Denmark)

    Machado, Henrique

    For decades, terrestrial microorganisms have been used as sources of countless enzymes and chemical compounds that have been produced by pharmaceutical and biotech companies and used by mankind. There is a need for new chemical compounds, including antibiotics,new enzymatic activities and new...... microorganisms to be used as cell factories for production. Therefore exploitation of new microbial niches and use of different strategies is an opportunity to boost discoveries. Even though scientists have started to explore several habitats other than the terrestrial ones, the marine environment stands out...... as a hitherto under-explored niche. This thesis work uses high-throughput sequencing technologies on a collection of marine bacteria established during the Galathea 3 expedition, with the purpose of unraveling new biodiversity and new bioactivities. Several tools were used for genomic analysis in order...

  4. The South Asian genome.

    Directory of Open Access Journals (Sweden)

    John C Chambers

    Full Text Available The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.

  5. Comparative RNA genomics

    DEFF Research Database (Denmark)

    Backofen, Rolf; Gorodkin, Jan; Hofacker, Ivo L.

    2018-01-01

    Over the last two decades it has become clear that RNA is much more than just a boring intermediate in protein expression. Ancient RNAs still appear in the core information metabolism and comprise a surprisingly large component in bacterial gene regulation. A common theme with these types of mostly...... small RNAs is their reliance of conserved secondary structures. Large scale sequencing projects, on the other hand, have profoundly changed our understanding of eukaryotic genomes. Pervasively transcribed, they give rise to a plethora of large and evolutionarily extremely flexible noncoding RNAs...... that exert a vastly diverse array of molecule functions. In this chapter we provide a—necessarily incomplete—overview of the current state of comparative analysis of noncoding RNAs, emphasizing computational approaches as a means to gain a global picture of the modern RNA world....

  6. Materials Genome Initiative

    Science.gov (United States)

    Vickers, John

    2015-01-01

    The Materials Genome Initiative (MGI) project element is a cross-Center effort that is focused on the integration of computational tools to simulate manufacturing processes and materials behavior. These computational simulations will be utilized to gain understanding of processes and materials behavior to accelerate process development and certification to more efficiently integrate new materials in existing NASA projects and to lead to the design of new materials for improved performance. This NASA effort looks to collaborate with efforts at other government agencies and universities working under the national MGI. MGI plans to develop integrated computational/experimental/ processing methodologies for accelerating discovery and insertion of materials to satisfy NASA's unique mission demands. The challenges include validated design tools that incorporate materials properties, processes, and design requirements; and materials process control to rapidly mature emerging manufacturing methods and develop certified manufacturing processes

  7. Inheritance of the yeast mitochondrial genome

    DEFF Research Database (Denmark)

    Piskur, Jure

    1994-01-01

    Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast......Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast...

  8. Shaped input distributions for structural damage localization

    DEFF Research Database (Denmark)

    Ulriksen, Martin Dalgaard; Bernal, Dionisio; Damkilde, Lars

    2018-01-01

    localization method is cast that operates on the premise of shaping inputs—whose spatial distribution is fixed—by use of a model, such that these inputs, in one structural subdomain at a time, suppress certain steady-state vibration quantities (depending on the type of damage one seeks to interrogate for......). Accordingly, damage is localized when the vibration signature induced by the shaped inputs in the damaged state corresponds to that in the reference state, hereby implying that the approach does not point directly to damage. Instead, it operates with interrogation based on postulated damage patterns...

  9. Plantagora: modeling whole genome sequencing and assembly of plant genomes.

    Directory of Open Access Journals (Sweden)

    Roger Barthelson

    Full Text Available BACKGROUND: Genomics studies are being revolutionized by the next generation sequencing technologies, which have made whole genome sequencing much more accessible to the average researcher. Whole genome sequencing with the new technologies is a developing art that, despite the large volumes of data that can be produced, may still fail to provide a clear and thorough map of a genome. The Plantagora project was conceived to address specifically the gap between having the technical tools for genome sequencing and knowing precisely the best way to use them. METHODOLOGY/PRINCIPAL FINDINGS: For Plantagora, a platform was created for generating simulated reads from several different plant genomes of different sizes. The resulting read files mimicked either 454 or Illumina reads, with varying paired end spacing. Thousands of datasets of reads were created, most derived from our primary model genome, rice chromosome one. All reads were assembled with different software assemblers, including Newbler, Abyss, and SOAPdenovo, and the resulting assemblies were evaluated by an extensive battery of metrics chosen for these studies. The metrics included both statistics of the assembly sequences and fidelity-related measures derived by alignment of the assemblies to the original genome source for the reads. The results were presented in a website, which includes a data graphing tool, all created to help the user compare rapidly the feasibility and effectiveness of different sequencing and assembly strategies prior to testing an approach in the lab. Some of our own conclusions regarding the different strategies were also recorded on the website. CONCLUSIONS/SIGNIFICANCE: Plantagora provides a substantial body of information for comparing different approaches to sequencing a plant genome, and some conclusions regarding some of the specific approaches. Plantagora also provides a platform of metrics and tools for studying the process of sequencing and assembly

  10. Genomes in turmoil: quantification of genome dynamics in prokaryote supergenomes.

    Science.gov (United States)

    Puigbò, Pere; Lobkovsky, Alexander E; Kristensen, David M; Wolf, Yuri I; Koonin, Eugene V

    2014-08-21

    Genomes of bacteria and archaea (collectively, prokaryotes) appear to exist in incessant flux, expanding via horizontal gene transfer and gene duplication, and contracting via gene loss. However, the actual rates of genome dynamics and relative contributions of different types of event across the diversity of prokaryotes are largely unknown, as are the sizes of microbial supergenomes, i.e. pools of genes that are accessible to the given microbial species. We performed a comprehensive analysis of the genome dynamics in 35 groups (34 bacterial and one archaeal) of closely related microbial genomes using a phylogenetic birth-and-death maximum likelihood model to quantify the rates of gene family gain and loss, as well as expansion and reduction. The results show that loss of gene families dominates the evolution of prokaryotes, occurring at approximately three times the rate of gain. The rates of gene family expansion and reduction are typically seven and twenty times less than the gain and loss rates, respectively. Thus, the prevailing mode of evolution in bacteria and archaea is genome contraction, which is partially compensated by the gain of new gene families via horizontal gene transfer. However, the rates of gene family gain, loss, expansion and reduction vary within wide ranges, with the most stable genomes showing rates about 25 times lower than the most dynamic genomes. For many groups, the supergenome estimated from the fraction of repetitive gene family gains includes about tenfold more gene families than the typical genome in the group although some groups appear to have vast, 'open' supergenomes. Reconstruction of evolution for groups of closely related bacteria and archaea reveals an extremely rapid and highly variable flux of genes in evolving microbial genomes, demonstrates that extensive gene loss and horizontal gene transfer leading to innovation are the two dominant evolutionary processes, and yields robust estimates of the supergenome size.

  11. Air pollution and brain damage.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Azzarelli, Biagio; Acuna, Hilda; Garcia, Raquel; Gambling, Todd M; Osnaya, Norma; Monroy, Sylvia; DEL Tizapantzi, Maria Rosario; Carson, Johnny L; Villarreal-Calderon, Anna; Rewcastle, Barry

    2002-01-01

    Exposure to complex mixtures of air pollutants produces inflammation in the upper and lower respiratory tract. Because the nasal cavity is a common portal of entry, respiratory and olfactory epithelia are vulnerable targets for toxicological damage. This study has evaluated, by light and electron microscopy and immunohistochemical expression of nuclear factor-kappa beta (NF-kappaB) and inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF-kappaB and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks; subsequent damage included alterations of the blood-brain barrier (BBB), degenerating cortical neurons, apoptotic glial white matter cells, deposition of apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and pericytes, nonneuritic plaques, and neurofibrillary tangles. Persistent pulmonary inflammation and deteriorating olfactory and respiratory barriers may play a role in the neuropathology observed in the brains of these highly exposed canines. Neurodegenerative disorders such as Alzheimer's may begin early in life with air pollutants playing a crucial role.

  12. Ultrasonic wave damage detecting device

    International Nuclear Information System (INIS)

    Miura, Yuichi; Nagao, Tetsuya; Nishi, Yuji; Kubota, Keisuke; Maruyama, Takayuki.

    1994-01-01

    Upon detecting a damage for a joint between a connecting nozzle at the outer circumference of a reactor pressure vessel and pipelines, the present invention greatly shortens the operation time. That is, it is noted that the connecting nozzle has a tapered portion and a small-diameter portion in view of strength. A main magnetic wheel supported on a base of a running vehicle is attracted to the small-diameter portion and an auxiliary magnet wheel is attracted to the tapered portion respectively and they are rolled. This regulate the deviation of the position of the base of the running vehicle in axial direction of the nozzle by the small-diameter portion and the tapered portion. Accordingly, the running vehicle can be circulated along a predetermined course on the outer circumference of the connecting nozzle without using tracks such as an existent ring track. The test can be performed conveniently only by placing the damage detecting device on the connecting nozzle. As a result, preparation time required before the test can remarkably be shortened. (I.S.)

  13. DNA damage repair and radiosensitivity

    International Nuclear Information System (INIS)

    Suzuki, Norio

    2003-01-01

    Tailored treatment is not new in radiotherapy; it has been the major subject for the last 20-30 years. Radiation responses and RBE (relative biological effectiveness) depend on assay systems, endpoints, type of tissues and tumors, radiation quality, dose rate, dose fractionation, physiological and environmental factors etc, Latent times to develop damages also differ among tissues and endpoints depending on doses and radiation quality. Recent progress in clarification of radiation induced cell death, especially of apoptotic cell death, is quite important for understanding radiosensitivity of tumor cure process as well as of tumorigenesis. Apoptotic cell death as well as dormant cells had been unaccounted and missed into a part of reproductive cell death. Another area of major progress has been made in clarifying repair mechanisms of radiation damage, i.e., non-homologous end joining (NHEJ) and homologous recombinational repair (HRR). New approaches and developments such as cDNA or protein micro arrays and so called informatics in addition to basic molecular biological analysis are expected to aid identifying molecules and their roles in signal transduction pathways, which are multi-factorial and interactive each other being involved in radiation responses. (authors)

  14. 1000 Bull Genomes - Toward genomic Selectionf from whole genome sequence Data in Dairy and Beef Cattle

    NARCIS (Netherlands)

    Hayes, B.; Daetwyler, H.D.; Fries, R.; Guldbrandtsen, B.; Mogens Sando Lund, M.; Didier A. Boichard, D.A.; Stothard, P.; Veerkamp, R.F.; Hulsegge, B.; Rocha, D.; Tassell, C.; Mullaart, E.; Gredler, B.; Druet, T.; Bagnato, A.; Goddard, M.E.; Chamberlain, H.L.

    2013-01-01

    Genomic prediction of breeding values is now used as the basis for selection of dairy cattle, and in some cases beef cattle, in a number of countries. When genomic prediction was introduced most of the information was to thought to be derived from linkage disequilibrium between markers and causative

  15. Gene polymorphisms and increased DNA damage in morbidly obese women.

    Science.gov (United States)

    Luperini, B C O; Almeida, D C; Porto, M P; Marcondes, J P C; Prado, R P; Rasera, I; Oliveira, M R M; Salvadori, D M F

    2015-06-01

    Obesity is characterized by increased adipose tissue mass resulting from a chronic imbalance between energy intake and expenditure. Furthermore, there is a clearly defined relationship among fat mass expansion, chronic low-grade systemic inflammation and reactive oxygen species (ROS) generation; leading to ROS-related pathological events. In the past years, genome-wide association studies have generated convincing evidence associating genetic variation at multiple regions of the genome with traits that reflect obesity. Therefore, the present study aimed to evaluate the relationships among the gene polymorphisms ghrelin (GHRL-rs26802), ghrelin receptor (GHSR-rs572169), leptin (LEP-rs7799039), leptin receptor (LEPR-rs1137101) and fat mass and obesity-associated (FTO-rs9939609) and obesity. The relationships among these gene variants and the amount of DNA damage were also investigated. Three hundred Caucasian morbidly obese and 300 eutrophic (controls) women were recruited. In summary, the results demonstrated that the frequencies of the GHRL, GHSR, LEP and LEPR polymorphisms were not different between Brazilian white morbidly obese and eutrophic women. Exceptions were the AA-FTO genotype and allele A, which were significantly more frequent in obese women than in the controls (0.23% vs. 0.10%; 0.46 vs. 0.36, respectively), and the TT-FTO genotype and the T allele, which were less frequent in morbidly obese women (p<0.01). Furthermore, significant differences in the amount of genetic lesions associated with FTO variants were observed only in obese women. In conclusion, this study demonstrated that the analyzed SNPs were not closely associated with morbid obesity, suggesting they are not the major contributors to obesity. Therefore, our data indicated that these gene variants are not good biomarkers for predicting risk susceptibility for obesity, whereas ROS generated by the inflammatory status might be one of the causes of DNA damage in obese women, favoring

  16. DNA methylation in human fibroblasts following DNA damage and repair

    International Nuclear Information System (INIS)

    Kastan, M.B.

    1984-01-01

    Methylation of deoxycytidine (dCyd) incorporated by DNA excision repair synthesis in human diploid fibroblasts following damage with ultraviolet radiation (UV), N-methyl-N-nitrosourea, or N-acetoxy-2-acetylaminofluorene was studied utilizing [6- 3 H]dCyd to label repaired DNA specifically and high performance liquid chromatographic analysis to quantify the percentage of deoxycytidine converted to 5-methyldeoxycytidine (m 5 dCyd). In confluent, nondividing cells, methylation in repair patches induced by all three agents is slow and incomplete. Whereas after DNA replication a level of 3.4% m 5 dCyd is reached in less than 2 hours, following UV-stimulated repair synthesis in confluent cells it takes about 3 days to reach a level of approx.2.0% m 5 dCyd in the repair patch. This undermethylation of repair patches occurs throughout the genome. In cells from cultures in logarithmic-phase growth, m 5 dCyd formation in UV-induced repair patches occurs faster and to a greater extent, reaching a level of approx.2.7% in 10-20 hours. Pre-existing hypomethylated repair patches in confluent cells are methylated further when the cells are stimulated to divide; however, the repair patch may still not be fully methylated before cell division occurs. Thus DNA damage and repair may lead to heritable loss of methylation at some sites. The distribution within chromatin of m 5 dCyd in repair patches was also investigated. Over a wide range of extents of digestion by staphylococcal nuclease or deoxyribonuclease I, the level of hypomethylation in repaired DNA in nuclease sensitive and resistant regions of chromatin was constant relative to the genomic level of methylation in these regions. Similar conclusions were reached in experiments with isolated mononucleosomes

  17. Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

    Science.gov (United States)

    Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki

    2014-12-01

    Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  18. Ex vivo irradiation of human blood to determine DNA damage using molecular techniques

    International Nuclear Information System (INIS)

    Montes, Angel; Agapito, Juan

    2014-01-01

    Biological dosimetry is the assessment of absorbed dose in individuals exposed to ionizing radiation from blood samples based on the radiation induced damage in cellular DNA. The aim of this study was to determine the damage in the DNA through the assessment of an experimental ex vivo assay using irradiated samples of human blood cells. For this purpose, blood samples were irradiated at low doses (<100 mGy) considering the following parameters: blood volume (3mL), temperature (37 °C) and incubation time (0.5, 2, 4, 8 and 24 h). Dose values were: 0, 12.5, 25 and 50 mGy using Cesium -137 gamma rays at 662 keV and a dose rate of 38.46 mGy/h. The qualitative damage in the genomic DNA was determined using agarose gel electrophoresis and polymerase chain reaction (PCR) for the p53 gene in a sequence of 133 pb of exon 7, related to the protein that acts in the cell repair process. The results of the qualitative analysis showed no degradation of genomic DNA; also an increase in the DNA concentration was observed up to the fourth hour of incubation, finding maximum values for all doses in the two samples. As a conclusion, the effects of ionizing radiation at doses used in this experiment do not generate a detectable damage, by means of molecular techniques such as those used in the present study. (authors).

  19. Micronutrient special issue: Coenzyme Q10 requirements for DNA damage prevention

    International Nuclear Information System (INIS)

    Schmelzer, Constance; Döring, Frank

    2012-01-01

    Coenzyme Q 10 (CoQ 10 ) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ 10 (ubiquinol, Q 10 H 2 ) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ 10 supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ 10 on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ 10 provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ 10 on oxidative stress biomarkers, CoQ 10 intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ 10 on prevention of DNA damage.

  20. Micronutrient special issue: Coenzyme Q{sub 10} requirements for DNA damage prevention

    Energy Technology Data Exchange (ETDEWEB)

    Schmelzer, Constance, E-mail: schmelzer@fbn-dummerstorf.de [Leibniz Institute for Farm Animal Biology (FBN), Nutritional Physiology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf (Germany); Doering, Frank [University of Kiel, Institute of Human Nutrition and Food Science, Molecular Prevention, Heinrich-Hecht-Platz 10, 24118 Kiel (Germany)

    2012-05-01

    Coenzyme Q{sub 10} (CoQ{sub 10}) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ{sub 10} (ubiquinol, Q{sub 10}H{sub 2}) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ{sub 10} supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ{sub 10} on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ{sub 10} provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ{sub 10} on oxidative stress biomarkers, CoQ{sub 10} intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ{sub 10} on prevention of DNA damage.