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Sample records for replicated sister chromatids

  1. Sister chromatid cohesion and recombination in meiosis

    NARCIS (Netherlands)

    Heemst, van D.; Heyting, C.

    2000-01-01

    Sister chromatids are associated from their formation until their disjunction. Cohesion between sister chromatids is provided by protein complexes, of which some components are conserved across the kingdoms and between the mitotic and meiotic cell cycles. Sister chromatid cohesion is intimately link

  2. The origin recognition complex links replication, sister chromatid cohesion and transcriptional silencing in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Suter, Bernhard; Tong, Amy; Chang, Michael; Yu, Lisa; Brown, Grant W; Boone, Charles; Rine, Jasper

    2004-01-01

    Mutations in genes encoding the origin recognition complex (ORC) of Saccharomyces cerevisiae affect initiation of DNA replication and transcriptional repression at the silent mating-type loci. To explore the function of ORC in more detail, a screen for genetic interactions was undertaken using large

  3. Is chromatin remodeling required to build sister-chromatid cohesion?

    NARCIS (Netherlands)

    Riedel, Christian G; Gregan, Juraj; Gruber, Stephan; Nasmyth, Kim

    2004-01-01

    Chromosome segregation during mitosis and meiosis depends on the linkage of sister DNA molecules after replication. These links, known as sister-chromatid cohesion, are provided by a multi-subunit complex called cohesin. Recent papers suggest that chromatin-remodeling complexes also have a role in t

  4. Similar Sister Chromatid Arrangement in Mono- and Holocentric Plant Chromosomes.

    Science.gov (United States)

    Schubert, Veit; Zelkowski, Mateusz; Klemme, Sonja; Houben, Andreas

    2016-01-01

    Due to the X-shape formation at somatic metaphase, the arrangement of the sister chromatids is obvious in monocentric chromosomes. In contrast, the sister chromatids of holocentric chromosomes cannot be distinguished even at mitotic metaphase. To clarify their organization, we differentially labelled the sister chromatids of holocentric Luzula and monocentric rye chromosomes by incorporating the base analogue EdU during replication. Using super-resolution structured illumination microscopy (SIM) and 3D rendering, we found that holocentric sister chromatids attach to each other at their contact surfaces similar to those of monocentrics in prometaphase. We found that sister chromatid exchanges (SCEs) are distributed homogeneously along the whole holocentric chromosomes of Luzula, and that their occurrence is increased compared to monocentric rye chromosomes. The SCE frequency of supernumerary B chromosomes, present additionally to the essential A chromosome complement of rye, does not differ from that of A chromosomes. Based on these results, models of the sister chromatid arrangement in mono- and holocentric plant chromosomes are presented.

  5. Sister chromatid segregation in meiosis II

    Science.gov (United States)

    Wassmann, Katja

    2013-01-01

    Meiotic divisions (meiosis I and II) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister chromatids together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II. Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed—deprotected”—for sister chromatid segregation in meiosis II. Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection. PMID:23574717

  6. Mechanics of Sister Chromatids studied with a Polymer Model English

    Science.gov (United States)

    Zhang, Yang; Isbaner, Sebastian; Heermann, Dieter

    2013-10-01

    Sister chromatid cohesion denotes the phenomenon that sister chromatids are initially attached to each other in mitosis to guarantee the error-free distribution into the daughter cells. Cohesion is mediated by binding proteins and only resolved after mitotic chromosome condensation is completed. However, the amount of attachement points required to maintain sister chromatid cohesion while still allowing proper chromosome condensation is not known yet. Additionally the impact of cohesion on the mechanical properties of chromosomes also poses an interesting problem. In this work we study the conformational and mechanical properties of sister chromatids by means of computer simulations. We model both protein-mediated cohesion between sister chromatids and chromosome condensation with a dynamic binding mechanisms. We show in a phase diagram that only specific link concentrations lead to connected and fully condensed chromatids that do not intermingle with each other nor separate due to entropic forces. Furthermore we show that dynamic bonding between chromatids decrease the Young's modulus compared to non-bonded chromatids.

  7. Mechanics of Sister Chromatids studied with a Polymer Model

    Directory of Open Access Journals (Sweden)

    Yang eZhang

    2013-10-01

    Full Text Available Sister chromatid cohesion denotes the phenomenon that sister chromatids are initially attached to each other in mitosis to guarantee the error-free distribution into the daughter cells. Cohesion is mediated by binding proteins and only resolved after mitotic chromosome condensation is completed. However, the amount of attachement points required to maintain sister chromatid cohesion while still allowing proper chromosome condensation is not known yet. Additionally the impact of cohesion on the mechanical properties of chromosomes also poses an interesting problem. In this work we study the conformational and mechanical properties of sister chromatids by means of computer simulations. We model both protein-mediated cohesion between sister chromatids and chromosome condensation with a dynamic binding mechanisms. We show in a phase diagram that only specific link concentrations lead to connected and fully condensed chromatids that do not intermingle with each other nor separate due to entropic forces. Furthermore we show that dynamic bonding between chromatids decrease the Young's modulus compared to non-bonded chromatids.

  8. Sister chromatid segregation in meiosis II: deprotection through phosphorylation.

    Science.gov (United States)

    Wassmann, Katja

    2013-05-01

    Meiotic divisions (meiosis I and II) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister chromatids together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II. Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed--deprotected--for sister chromatid segregation in meiosis II. Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection.

  9. Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells

    NARCIS (Netherlands)

    van Wietmarschen, Niek; Lansdorp, Peter M.

    2016-01-01

    Sister chromatid exchanges (SCEs) are considered sensitive indicators of genome instability. Detection of SCEs typically requires cells to incorporate bromodeoxyuridine (BrdU) during two rounds of DNA synthesis. Previous studies have suggested that SCEs are induced by DNA replication over BrdU-subst

  10. Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells

    NARCIS (Netherlands)

    van Wietmarschen, Niek; Lansdorp, Peter M.

    2016-01-01

    Sister chromatid exchanges (SCEs) are considered sensitive indicators of genome instability. Detection of SCEs typically requires cells to incorporate bromodeoxyuridine (BrdU) during two rounds of DNA synthesis. Previous studies have suggested that SCEs are induced by DNA replication over BrdU-subst

  11. Sororin actively maintains sister chromatid cohesion.

    Science.gov (United States)

    Ladurner, Rene; Kreidl, Emanuel; Ivanov, Miroslav P; Ekker, Heinz; Idarraga-Amado, Maria Helena; Busslinger, Georg A; Wutz, Gordana; Cisneros, David A; Peters, Jan-Michael

    2016-03-15

    Cohesion between sister chromatids is established during DNA replication but needs to be maintained to enable proper chromosome-spindle attachments in mitosis or meiosis. Cohesion is mediated by cohesin, but also depends on cohesin acetylation and sororin. Sororin contributes to cohesion by stabilizing cohesin on DNA. Sororin achieves this by inhibiting WAPL, which otherwise releases cohesin from DNA and destroys cohesion. Here we describe mouse models which enable the controlled depletion of sororin by gene deletion or auxin-induced degradation. We show that sororin is essential for embryonic development, cohesion maintenance, and proper chromosome segregation. We further show that the acetyltransferases ESCO1 and ESCO2 are essential for stabilizing cohesin on chromatin, that their only function in this process is to acetylate cohesin's SMC3 subunit, and that DNA replication is also required for stable cohesin-chromatin interactions. Unexpectedly, we find that sororin interacts dynamically with the cohesin complexes it stabilizes. This implies that sororin recruitment to cohesin does not depend on the DNA replication machinery or process itself, but on a property that cohesin acquires during cohesion establishment.

  12. Precocious Sister Chromatid Separation (PSCS) in Cornelia de Lange Syndrome

    Science.gov (United States)

    Kaur, Maninder; DeScipio, Cheryl; McCallum, Jennifer; Yaeger, Dinah; Devoto, Marcella; Jackson, Laird G.; Spinner, Nancy B.; Krantz, Ian D.

    2009-01-01

    The Cornelia de Lange syndrome (CdLS) (OMIM# 122470) is a dominantly inherited multisystem developmental disorder. The phenotype consists of characteristic facial features, hirsutism, abnormalities of the upper extremities ranging from subtle changes in the phalanges and metacarpal bones to oligodactyly and phocomelia, gastroesophageal dysfunction, growth retardation, and neurodevelopmental delay. Prevalence is estimated to be as high as 1 in 10,000. Recently, mutations in NIPBL were identified in sporadic and familial CdLS cases. To date, mutations in this gene have been identified in over 45% of individuals with CdLS. NIPBL is the human homolog of the Drosophila Nipped-B gene. Although its function in mammalian systems has not yet been elucidated, sequence homologs of Nipped-B in yeast (Scc2 and Mis4) are required for sister chromatid cohesion during mitosis, and a similar role was recently demonstrated for Nipped-B in Drosophila. In order to evaluate NIPBL role in sister chromatid cohesion in humans, metaphase spreads on 90 probands (40 NIPBL mutation positive and 50 NIPBL mutation negative) with CdLS were evaluated for evidence of precocious sister chromatid separation (PSCS). We screened 50 metaphases from each proband and found evidence of PSCS in 41% (compared to 9% in control samples). These studies indicate that NIPBL may play a role in sister chromatid cohesion in humans as has been reported for its homologs in Drosophila and yeast. PMID:16100726

  13. Meiotic sister chromatid cohesion and recombination in two filamentous fungi

    NARCIS (Netherlands)

    Heemst, van D.

    2000-01-01

    Homologous recombination and sister chromatid cohesion play important roles in the maintenance of genome integrity and the fidelity of chromosome segregation in mitosis and meiosis. Within the living cell, the integrity of the DNA is threatened by various factors that cause DNA-lesions, of which DNA

  14. Functional genomics identifies a requirement of pre-mRNA splicing factors for sister chromatid cohesion.

    Science.gov (United States)

    Sundaramoorthy, Sriramkumar; Vázquez-Novelle, María Dolores; Lekomtsev, Sergey; Howell, Michael; Petronczki, Mark

    2014-11-18

    Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation during cell division. Using functional genomic screening, we identify a set of 26 pre-mRNA splicing factors that are required for sister chromatid cohesion in human cells. Loss of spliceosome subunits increases the dissociation rate of cohesin from chromatin and abrogates cohesion after DNA replication, ultimately causing mitotic catastrophe. Depletion of splicing factors causes defective processing of the pre-mRNA encoding sororin, a factor required for the stable association of cohesin with chromatin, and an associated reduction of sororin protein level. Expression of an intronless version of sororin and depletion of the cohesin release protein WAPL suppress the cohesion defect in cells lacking splicing factors. We propose that spliceosome components contribute to sister chromatid cohesion and mitotic chromosome segregation through splicing of sororin pre-mRNA. Our results highlight the loss of cohesion as an early cellular consequence of compromised splicing. This may have clinical implications because SF3B1, a splicing factor that we identify to be essential for cohesion, is recurrently mutated in chronic lymphocytic leukaemia.

  15. Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination

    NARCIS (Netherlands)

    Revenkova, E.; Eijpe, M.; Heyting, C.; Hodges, C.A.; Hunt, P.A.; Liebe, B.; Scherthan, H.; Jessberger, R.

    2004-01-01

    Sister chromatid cohesion ensures the faithful segregation of chromosomes in mitosis and in both meiotic divisions1, 2, 3, 4. Meiosis-specific components of the cohesin complex, including the recently described SMC1 isoform SMC15, were suggested to be required for meiotic sister chromatid cohesion a

  16. Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae.

    Science.gov (United States)

    Mayer, M L; Gygi, S P; Aebersold, R; Hieter, P

    2001-05-01

    We have identified and characterized an alternative RFC complex RFC(Ctf18p, Ctf8p, Dcc1p) that is required for sister chromatid cohesion and faithful chromosome transmission. Ctf18p, Ctf8p, and Dcc1p interact physically in a complex with Rfc2p, Rfc3p, Rfc4p, and Rfc5p but not with Rfc1p or Rad24p. Deletion of CTF18, CTF8, or DCC1 singly or in combination (ctf18Deltactf8Deltadcc1Delta) leads to sensitivity to microtubule depolymerizing drugs and a severe sister chromatid cohesion defect. Furthermore, temperature-sensitive mutations in RFC4 result in precocious sister chromatid separation. Our results highlight a novel function of the RFC proteins and support a model in which sister chromatid cohesion is established at the replication fork via a polymerase switching mechanism and a replication-coupled remodeling of chromatin.

  17. Sister chromatid tension and the spindle assembly checkpoint.

    Science.gov (United States)

    Nezi, Luigi; Musacchio, Andrea

    2009-12-01

    The spindle assembly checkpoint (SAC) is a feedback control system that monitors the state of kinetochore/microtubule attachment during mitosis and halts cell cycle progression until all chromosomes are properly aligned at the metaphase plate. The state of chromosome-microtubule attachment is implicated as a crucial factor in the checkpoint response. On the contrary, lack of tension in the centromere-kinetochore region of sister chromatids has been shown to regulate a pathway of correction of undesired chromosome-microtubule connections, while the presence of tension is believed to promote the stabilization of attachments. We discuss how tension-sensitive phenomena, such as attachment correction and stabilization, relate to the SAC and we speculate on the existence of a single pathway linking error correction and SAC activation.

  18. Sister chromatid exchange in Polish White improved goats (Capra hircus).

    Science.gov (United States)

    Wójcik, Ewa; Smalec, Elzbieta

    2012-01-01

    The study was aimed at evaluating the frequency of spontaneous sister chromatid exchange in Polish White Improved goats (Capra hircus). The mean number of SCEs/cell was 2.73 +/- 1.84. The effect of sex and age on SCE incidence was also investigated. No statistically significant differences in the number of SCEs/cell were observed between the males and females. On the other hand, age was found to significantly influence SCE frequency. A lower SCE frequency was observed in younger goats. A positive correlation between chromosome length and SCE number was identified. The longer the chromosome, the more exchanges occurred. The highest number of SCEs was observed in the interstitial region, the lowest in the distal area.

  19. Rfc5p regulates alternate RFC complex functions in sister chromatid pairing reactions in budding yeast

    OpenAIRE

    Maradeo, Marie E.; Garg, Anisha; Skibbens, Robert V.

    2010-01-01

    Sister chromatid pairing reactions, termed cohesion establishment, occur during S phase and appear to be regulated by replication factor C (RFC) complexes. For instance, RFCs that contain Ctf18p exhibit pro-establishment activities while those that contain Elg1p exhibit anti-establishment activities. It remains unknown whether Ctf18p-RFC and Elg1p-RFC functions are simply opposing or instead reveal complicated and non-parallel regulatory mechanisms. To better understand the nature of these no...

  20. The ELG1 clamp loader plays a role in sister chromatid cohesion.

    Directory of Open Access Journals (Sweden)

    Oren Parnas

    Full Text Available Mutations in the ELG1 gene of yeast lead to genomic instability, manifested in high levels of genetic recombination, chromosome loss, and gross chromosomal rearrangements. Elg1 shows similarity to the large subunit of the Replication Factor C clamp loader, and forms a RFC-like (RLC complex in conjunction with the 4 small RFC subunits. Two additional RLCs exist in yeast: in one of them the large subunit is Ctf18, and in the other, Rad24. Ctf18 has been characterized as the RLC that functions in sister chromatid cohesion. Here we present evidence that the Elg1 RLC (but not Rad24 also plays an important role in this process. A genetic screen identified the cohesin subunit Mcd1/Scc1 and its loader Scc2 as suppressors of the synthetic lethality between elg1 and ctf4. We describe genetic interactions between ELG1 and genes encoding cohesin subunits and their accessory proteins. We also show that defects in Elg1 lead to higher precocious sister chromatid separation, and that Ctf18 and Elg1 affect cohesion via a joint pathway. Finally, we localize both Ctf18 and Elg1 to chromatin and show that Elg1 plays a role in the recruitment of Ctf18. Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring.

  1. Smc5–Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination

    Science.gov (United States)

    De Piccoli, Giacomo; Cortes-Ledesma, Felipe; Ira, Gregory; Torres-Rosell, Jordi; Uhle, Stefan; Farmer, Sarah; Hwang, Ji-Young; Machin, Felix; Ceschia, Audrey; McAleenan, Alexandra; Cordon-Preciado, Violeta; Clemente-Blanco, Andrés; Vilella-Mitjana, Felip; Ullal, Pranav; Jarmuz, Adam; Leitao, Beatriz; Bressan, Debra; Dotiwala, Farokh; Papusha, Alma; Zhao, Xiaolan; Myung, Kyungjae; Haber, James E.; Aguilera, Andrés; Aragón, Luis

    2015-01-01

    DNA double-strand breaks (DSB) can arise during DNA replication, or after exposure to DNA-damaging agents, and their correct repair is fundamental for cell survival and genomic stability. Here, we show that the Smc5–Smc6 complex is recruited to DSBs de novo to support their repair by homologous recombination between sister chromatids. In addition, we demonstrate that Smc5–Smc6 is necessary to suppress gross chromosomal rearrangements. Our findings show that the Smc5–Smc6 complex is essential for genome stability as it promotes repair of DSBs by error-free sister-chromatid recombination (SCR), thereby suppressing inappropriate non-sister recombination events. PMID:16892052

  2. Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    M' Bemba-Meka, Prosper [Universite de Montreal, Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Main Station, P.O. Box 6128, Montreal, QC (Canada); University of Louisville, Department of Pharmacology and Toxicology, Center for Genetics and Molecular Medicine, Louisville, KY (United States); Lemieux, Nicole [Universite de Montreal, Department of Pathology and Cellular Biology, Faculty of Medicine, Main Station, P.O. Box 6128, Montreal, QC (Canada); Chakrabarti, Saroj K. [Universite de Montreal, Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Main Station, P.O. Box 6128, Montreal, QC (Canada)

    2007-02-15

    Human peripheral lymphocytes from whole blood cultures were exposed to either soluble form of nickel carbonate hydroxide (NiCH) (0-60 {mu}M), or of nickel subsulfide (Ni{sub 3}S{sub 2}) (0-120 {mu}M), or of nickel oxide (NiO) (0-120 {mu}M), or nickel sulfate (NiSO{sub 4}) (0-120 {mu}M) for a short duration of 2 h. The treatments occurred 46 h after the beginning of the cultures. The cultures were harvested after a total incubation of 72 h, and sister-chromatid exchange (SCE), replication index (RI), and mitotic index (MI) were measured for each nickel compound. The soluble form of NiCH at 30 {mu}M but those of Ni{sub 3}S{sub 2} and NiO at 120 {mu}M produced significant increase in the SCE per cell compared to the control value, whereas NiSO{sub 4} failed to produce any such significant increase. Except NiSO{sub 4}, the soluble forms of NiCH, Ni{sub 3}S{sub 2}, and NiO produced significant cell-cycle delay (as measured by the inhibition of RI) as well as significant inhibition of the MI at respective similar concentrations as mentioned above. Pretreatment of human blood lymphocytes with catalase (H{sub 2}O{sub 2} scavenger), or superoxide dismutase (superoxide anion scavenger), or dimethylthiourea (hydroxyl radical scavenger), or deferoxamine (iron chelator), or N-acetylcysteine (general antioxidant) inhibited NiCH-induced SCE, and changes in RI and MI. This suggests the participation of oxidative stress involving H{sub 2}O{sub 2}, the superoxide anion radical, the hydroxyl radical, and iron in the NiCH-induced genotoxic responses. Cotreatment of NiCH with either verapamil (inhibitor of intracellular calcium ion ([Ca{sup 2+}]{sub i}) movement through plasma membranes), or dantrolene (inhibitor of [Ca{sup 2+}]{sub i} release from sarcoplasmic reticulum), or BAPTA (Ca{sup 2+} chelator) also inhibited the NiCH-induced responses. These results suggest that [Ca{sup 2+}]{sub i} is also implicated in the genotoxicity of NiCH. Overall these data indicate that various types

  3. Sister chromatid gene conversion is a prominent double-strand break repair pathway in mammalian cells

    OpenAIRE

    Johnson, Roger D.; Jasin, Maria

    2000-01-01

    In mammalian cells, repair of DNA double-strand breaks (DSBs) occurs by both homologous and non-homologous mechanisms. By definition, homologous recombination requires a template with sufficient sequence identity to the damaged molecule in order to direct repair. We now show that the sister chromatid acts as a repair template in a substantial proportion of DSB repair events. The outcome of sister chromatid repair is primarily gene conversion unassociated with reciprocal exchange. This contras...

  4. Solution Radioactivated by Hadron Radiation Can Increase Sister Chromatid Exchanges.

    Science.gov (United States)

    Maeda, Junko; Yurkon, Charles R; Fujii, Yoshihiro; Fujisawa, Hiroshi; Kato, Sayaka; Brents, Colleen A; Uesaka, Mitsuru; Fujimori, Akira; Kitamura, Hisashi; Kato, Takamitsu A

    2015-01-01

    When energetic particles irradiate matter, it becomes activated by nuclear reactions. Radioactivation induced cellular effects are not clearly understood, but it could be a part of bystander effects. This investigation is aimed at understanding the biological effects from radioactivation in solution induced by hadron radiation. Water or phosphate buffered saline was activated by being exposed to hadron radiation including protons, carbon- and iron-ions. 1 mL of radioactivated solution was transferred to flasks with Chinese hamster ovary (CHO) cells cultured in 5 mL of complete media. The induction of sister chromatid exchanges (SCE) was used to observe any increase in DNA damage responses. The energy spectrum and the half-lives of the radioactivation were analyzed by NaI scintillation detector in order to identify generated radionuclides. In the radioactivated solution, 511 keV gamma-rays were observed, and their half-lives were approximately 2 min, 10 min, and 20 min. They respectively correspond to the beta+ decay of 15O, 13N, and 11C. The SCE frequencies in CHO cells increased depending on the amount of radioactivation in the solution. These were suppressed with a 2-hour delayed solution transfer or pretreatment with dimethyl sulfoxide (DMSO). Our results suggest that the SCE induction by radioactivated solution was mediated by free radicals produced by the annihilated gamma-rays. Since the SCE induction and DMSO modulation are also reported in radiation-induced bystander effects, our results imply that radioactivation of the solution may have some contribution to the bystander effects from hadron radiation. Further investigations are required to assess if radioactivation effects would attribute an additional level of cancer risk of the hadron radiation therapy itself.

  5. Solution Radioactivated by Hadron Radiation Can Increase Sister Chromatid Exchanges.

    Directory of Open Access Journals (Sweden)

    Junko Maeda

    Full Text Available When energetic particles irradiate matter, it becomes activated by nuclear reactions. Radioactivation induced cellular effects are not clearly understood, but it could be a part of bystander effects. This investigation is aimed at understanding the biological effects from radioactivation in solution induced by hadron radiation. Water or phosphate buffered saline was activated by being exposed to hadron radiation including protons, carbon- and iron-ions. 1 mL of radioactivated solution was transferred to flasks with Chinese hamster ovary (CHO cells cultured in 5 mL of complete media. The induction of sister chromatid exchanges (SCE was used to observe any increase in DNA damage responses. The energy spectrum and the half-lives of the radioactivation were analyzed by NaI scintillation detector in order to identify generated radionuclides. In the radioactivated solution, 511 keV gamma-rays were observed, and their half-lives were approximately 2 min, 10 min, and 20 min. They respectively correspond to the beta+ decay of 15O, 13N, and 11C. The SCE frequencies in CHO cells increased depending on the amount of radioactivation in the solution. These were suppressed with a 2-hour delayed solution transfer or pretreatment with dimethyl sulfoxide (DMSO. Our results suggest that the SCE induction by radioactivated solution was mediated by free radicals produced by the annihilated gamma-rays. Since the SCE induction and DMSO modulation are also reported in radiation-induced bystander effects, our results imply that radioactivation of the solution may have some contribution to the bystander effects from hadron radiation. Further investigations are required to assess if radioactivation effects would attribute an additional level of cancer risk of the hadron radiation therapy itself.

  6. Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells.

    Science.gov (United States)

    van Wietmarschen, Niek; Lansdorp, Peter M

    2016-08-19

    Sister chromatid exchanges (SCEs) are considered sensitive indicators of genome instability. Detection of SCEs typically requires cells to incorporate bromodeoxyuridine (BrdU) during two rounds of DNA synthesis. Previous studies have suggested that SCEs are induced by DNA replication over BrdU-substituted DNA and that BrdU incorporation alone could be responsible for the high number of SCE events observed in cells from patients with Bloom syndrome (BS), a rare genetic disorder characterized by marked genome instability and high SCE frequency. Here we show using Strand-seq, a single cell DNA template strand sequencing technique, that the presence of variable BrdU concentrations in the cell culture medium and in DNA template strands has no effect on SCE frequency in either normal or BS cells. We conclude that BrdU does not induce SCEs and that SCEs detected in either normal or BS cells reflect DNA repair events that occur spontaneously.

  7. Sororin pre-mRNA splicing is required for proper sister chromatid cohesion in human cells.

    Science.gov (United States)

    Watrin, Erwan; Demidova, Maria; Watrin, Tanguy; Hu, Zheng; Prigent, Claude

    2014-09-01

    Sister chromatid cohesion, which depends on cohesin, is essential for the faithful segregation of replicated chromosomes. Here, we report that splicing complex Prp19 is essential for cohesion in both G2 and mitosis, and consequently for the proper progression of the cell through mitosis. Inactivation of splicing factors SF3a120 and U2AF65 induces similar cohesion defects to Prp19 complex inactivation. Our data indicate that these splicing factors are all required for the accumulation of cohesion factor Sororin, by facilitating the proper splicing of its pre-mRNA. Finally, we show that ectopic expression of Sororin corrects defective cohesion caused by Prp19 complex inactivation. We propose that the Prp19 complex and the splicing machinery contribute to the establishment of cohesion by promoting Sororin accumulation during S phase, and are, therefore, essential to the maintenance of genome stability.

  8. Role of the Saccharomyces cerevisiae Rad51 paralogs in sister chromatid recombination.

    Science.gov (United States)

    Mozlin, Amy M; Fung, Cindy W; Symington, Lorraine S

    2008-01-01

    Rad51 requires a number of other proteins, including the Rad51 paralogs, for efficient recombination in vivo. Current evidence suggests that the yeast Rad51 paralogs, Rad55 and Rad57, are important in formation or stabilization of the Rad51 nucleoprotein filament. To gain further insights into the function of the Rad51 paralogs, reporters were designed to measure spontaneous or double-strand break (DSB)-induced sister or nonsister recombination. Spontaneous sister chromatid recombination (SCR) was reduced 6000-fold in the rad57 mutant, significantly more than in the rad51 mutant. Although the DSB-induced recombination defect of rad57 was suppressed by overexpression of Rad51, elevated temperature, or expression of both mating-type alleles, the rad57 defect in spontaneous SCR was not strongly suppressed by these same factors. In addition, the UV sensitivity of the rad57 mutant was not strongly suppressed by MAT heterozygosity, even though Rad51 foci were restored under these conditions. This lack of suppression suggests that Rad55 and Rad57 have different roles in the recombinational repair of stalled replication forks compared with DSB repair. Furthermore, these data suggest that most spontaneous SCR initiates from single-stranded gaps formed at stalled replication forks rather than DSBs.

  9. The Elg1-RFC clamp-loading complex performs a role in sister chromatid cohesion.

    Science.gov (United States)

    Maradeo, Marie E; Skibbens, Robert V

    2009-01-01

    It is widely accepted that of the four Replication Factor C (RFC) complexes (defined by the associations of either Rfc1p, Ctf18p, Elg1p or Rad24p with Rfc2p-Rfc5p), only Ctf18-RFC functions in sister chromatid cohesion. This model is based on findings that CTF18 deletion is lethal in combination with mutations in either CTF7(ECO1) or MCD1 sister chromatid cohesion genes and that ctf18 mutant cells exhibit cohesion defects. Here, we report that Elg1-RFC not only participates in cohesion but performs a function that is distinct from that of Ctf18-RFC. The results show that deletion of ELG1 rescues both ctf7(eco1) mutant cell temperature sensitivity and cohesion defects. Moreover, over-expression of ELG1 enhances ctf7(eco1) mutant cell phenotypes. These findings suggest that the balance of Ctf7p(Eco1p) activity depends on both Ctf18-RFC and Elg1-RFC. We also report that ELG1 deletion produces cohesion defects and intensifies the conditional phenotype of mcd1 mutant cells, further supporting a role for Elg1-RFC in cohesion. Attesting to the specificity of these interactions, deletion of RAD24 neither suppressed nor exacerbated cohesion defects in either ctf7(eco1) or mcd1 mutant cells. While parallel analyses failed to uncover a similar role in cohesion for Rad24-RFC, it is well known that Rad24-RFC, Elg1-RFC and Ctf18-RFC play key roles in DNA damage responses. We tested and found that Ctf7p(Eco1p) plays a significant role in Rad24-RFC-based DNA response pathways. In combination, these findings challenge current views and document new and distinct roles for RFC complexes in cohesion and for Ctf7p(Eco1p) in DNA repair.

  10. The Elg1-RFC clamp-loading complex performs a role in sister chromatid cohesion.

    Directory of Open Access Journals (Sweden)

    Marie E Maradeo

    Full Text Available It is widely accepted that of the four Replication Factor C (RFC complexes (defined by the associations of either Rfc1p, Ctf18p, Elg1p or Rad24p with Rfc2p-Rfc5p, only Ctf18-RFC functions in sister chromatid cohesion. This model is based on findings that CTF18 deletion is lethal in combination with mutations in either CTF7(ECO1 or MCD1 sister chromatid cohesion genes and that ctf18 mutant cells exhibit cohesion defects. Here, we report that Elg1-RFC not only participates in cohesion but performs a function that is distinct from that of Ctf18-RFC. The results show that deletion of ELG1 rescues both ctf7(eco1 mutant cell temperature sensitivity and cohesion defects. Moreover, over-expression of ELG1 enhances ctf7(eco1 mutant cell phenotypes. These findings suggest that the balance of Ctf7p(Eco1p activity depends on both Ctf18-RFC and Elg1-RFC. We also report that ELG1 deletion produces cohesion defects and intensifies the conditional phenotype of mcd1 mutant cells, further supporting a role for Elg1-RFC in cohesion. Attesting to the specificity of these interactions, deletion of RAD24 neither suppressed nor exacerbated cohesion defects in either ctf7(eco1 or mcd1 mutant cells. While parallel analyses failed to uncover a similar role in cohesion for Rad24-RFC, it is well known that Rad24-RFC, Elg1-RFC and Ctf18-RFC play key roles in DNA damage responses. We tested and found that Ctf7p(Eco1p plays a significant role in Rad24-RFC-based DNA response pathways. In combination, these findings challenge current views and document new and distinct roles for RFC complexes in cohesion and for Ctf7p(Eco1p in DNA repair.

  11. The MCM-binding protein ETG1 aids sister chromatid cohesion required for postreplicative homologous recombination repair.

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    Naoki Takahashi

    2010-01-01

    Full Text Available The DNA replication process represents a source of DNA stress that causes potentially spontaneous genome damage. This effect might be strengthened by mutations in crucial replication factors, requiring the activation of DNA damage checkpoints to enable DNA repair before anaphase onset. Here, we demonstrate that depletion of the evolutionarily conserved minichromosome maintenance helicase-binding protein ETG1 of Arabidopsis thaliana resulted in a stringent late G2 cell cycle arrest. This arrest correlated with a partial loss of sister chromatid cohesion. The lack-of-cohesion phenotype was intensified in plants without functional CTF18, a replication fork factor needed for cohesion establishment. The synergistic effect of the etg1 and ctf18 mutants on sister chromatid cohesion strengthened the impact on plant growth of the replication stress caused by ETG1 deficiency because of inefficient DNA repair. We conclude that the ETG1 replication factor is required for efficient cohesion and that cohesion establishment is essential for proper development of plants suffering from endogenous DNA stress. Cohesion defects observed upon knockdown of its human counterpart suggest an equally important developmental role for the orthologous mammalian ETG1 protein.

  12. Cell biology of cancer: BRCA1 and sister chromatid pairing reactions?

    Science.gov (United States)

    Skibbens, Robert V

    2008-02-15

    A significant portion of familial breast/ovarian cancer patients harbors a mutation in Breast Cancer Associated gene 1 (BRCA1). Cells deficient for BRCA1 exhibit chromosome aberrations such as whole chromosome duplications, translocations, inter-sister gaps and gene mis-regulation. Here, new evidence is reviewed that defects in sister chromatid cohesion may contribute directly to cancer cell phenotypes-especially those of BRCA1 mutant cells. Linking cohesion to BRCA1-dependent tumorigenesis are reports that BRCA1-associated components (DNA helicase, RFC, PCNA and genome surveillance factors) are required for efficient sister chromatid cohesion. Other cohesion factors (WAPL, EFO2/ESCO2 and hSecurin) are tightly correlated with various cell-type specific carcinogenesis, in support of a generalized model for cohesion in cancer. Recent findings further reveal that a reciprocal relationship exists in that DNA damage induces new Ctf7/Eco1-dependent sister chromatid pairing reactions that, in turn, are required for efficient DNA repair. Future research into sister chromatid pairing mechanisms are likely to provide critical new insights into the underlying causes of cancer.

  13. Mouse RAD54 Affects DNA Double-Strand Break Repair and Sister Chromatid Exchange

    Science.gov (United States)

    Dronkert, Mies L. G.; Beverloo, H. Berna; Johnson, Roger D.; Hoeijmakers, Jan H. J.; Jasin, Maria; Kanaar, Roland

    2000-01-01

    Cells can achieve error-free repair of DNA double-strand breaks (DSBs) by homologous recombination through gene conversion with or without crossover. In contrast, an alternative homology-dependent DSB repair pathway, single-strand annealing (SSA), results in deletions. In this study, we analyzed the effect of mRAD54, a gene involved in homologous recombination, on the repair of a site-specific I-SceI-induced DSB located in a repeated DNA sequence in the genome of mouse embryonic stem cells. We used six isogenic cell lines differing solely in the orientation of the repeats. The combination of the three recombination-test substrates used discriminated among SSA, intrachromatid gene conversion, and sister chromatid gene conversion. DSB repair was most efficient for the substrate that allowed recovery of SSA events. Gene conversion with crossover, indistinguishable from long tract gene conversion, preferentially involved the sister chromatid rather than the repeat on the same chromatid. Comparing DSB repair in mRAD54 wild-type and knockout cells revealed direct evidence for a role of mRAD54 in DSB repair. The substrate measuring SSA showed an increased efficiency of DSB repair in the absence of mRAD54. The substrate measuring sister chromatid gene conversion showed a decrease in gene conversion with and without crossover. Consistent with this observation, DNA damage-induced sister chromatid exchange was reduced in mRAD54-deficient cells. Our results suggest that mRAD54 promotes gene conversion with predominant use of the sister chromatid as the repair template at the expense of error-prone SSA. PMID:10757799

  14. Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance

    NARCIS (Netherlands)

    V.C. Seitan (Vlad); P.A. Banks (Peter); S. Laval (Steve); N.A. Majid (Nazia); D. Dorsett (Dale); A. Rana (Amer); J. Smith (Jeremy); A. Bateman (Alex); S. Krpic (Sanja); A. Hostert (Arnd); S.M. Rollins; H. Erdjument-Bromage (Hediye); P. Tempst (Paul); C.Y. Benard (Claire); S. Hekimi (Siegfried); S.F. Newbury (Sarah); T. Strachan (Tom)

    2006-01-01

    textabstractSaccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes emphasizes a conserved role in regulating sister chromatid cohesion, but homologs of Scc4 have not hitherto been identified outside ce

  15. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

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    Pongsavee Malinee

    2009-10-01

    Full Text Available Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI. The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

  16. SISTER-CHROMATID EXCHANGES IN CULTURED IMMATURE EMBRYOS OF WHEAT SPECIES AND REGENERANTS

    NARCIS (Netherlands)

    PIJNACKER, LP; FERWERDA, MA

    1994-01-01

    Immature embryos of Triticum aestivum (ten cultivars and lines), T. durum, T. dicoccum and T. monococcum were cultured in vitro on MS medium supplemented with 1 or 2 mg/l of 2,4-D and 20 or 30g/l of sucrose for 3 days and processed to score sister chromatid exchanges (SCEs) per chromosome. Media com

  17. Comparison of genome stability in two pig breeds by using the sister chromatid exchange (SCE test

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    V. Barbieri

    2010-01-01

    Full Text Available The sister chromatid exchange (SCE test has been used to detect genome stability in humans (Chaganti, 1974 and the main livestock species (Ciotola et al., 2004; Di Meo et al., 2000; Di Berardino et al., 1979, and to discover DNA damage caused by a variety of natural and artificial chemical compounds (Iannuzzi et al., 1990.

  18. Chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with sodium metabisulfite, a food preservative.

    Science.gov (United States)

    Rencüzogullari, E; Ila, H B; Kayraldiz, A; Topaktaş, M

    2001-02-20

    The aim of this study was to investigate the ability of sodium metabisulfite (SMB) which is used as an antimicrobial substance in food, to induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in human lymphocytes. SMB-induced CAs and SCEs at all concentrations (75, 150 and 300 microg/ml) and treatment periods (24 and 48h) dose-dependently. However, SMB decreased the replication index (RI) and the mitotic index (MI) at the concentrations of 150 and 300 microg/ml for 24 and 48h treatment periods. This decrease was dose-dependent as well.

  19. Rfc5p regulates alternate RFC complex functions in sister chromatid pairing reactions in budding yeast.

    Science.gov (United States)

    Maradeo, Marie E; Garg, Anisha; Skibbens, Robert V

    2010-11-01

    Sister chromatid pairing reactions, termed cohesion establishment, occur during S-phase and appear to be regulated by Replication Factor C (RFC) complexes. For instance, RFCs that contain Ctf18p exhibit pro-establishment activities while those that contain Elg1p exhibit anti-establishment activities. It remains unknown whether Ctf18p-RFC and Elg1p-RFC functions are simply opposing or instead reveal complicated and non-parallel regulatory mechanisms. To better understand the nature of these novel pathways, we analyzed the small RFC subunit Rfc5p that is common to both Ctf18p-RFC and Elg1p-RFC. Despite this commonality, the data show that diminished Rfc5p function rescues ctf7/eco1 mutant cell phenotypes, revealing that Rfc5p promotes anti-establishment activities. This rescue is specific to establishment pathways in that rfc5-1 greatly accentuates growth defects when expressed in scc2 (deposition), mcd1/scc1 or smc3 (cohesion maintenance) mutated cells. Our results reveal for the first time a role for small RFC subunits in directing RFC complex functions-in this case towards anti-establishment pathways. We further report that Pds5p exhibits both establishment and anti-establishment functions in cohesion. This duality suggests that categorizations of establishment and anti-establishment activities require further examination.

  20. Chiasmata Promote Monopolar Attachment of Sister Chromatids and Their Co-Segregation toward the Proper Pole during Meiosis I

    Science.gov (United States)

    Ohba, Tatsunori; Hinohara, Yumi; Matsuhara, Hirotada; Yoshida, Masashi; Itabashi, Yuta; Murakami, Hiroshi; Yamamoto, Ayumu

    2011-01-01

    The chiasma is a structure that forms between a pair of homologous chromosomes by crossover recombination and physically links the homologous chromosomes during meiosis. Chiasmata are essential for the attachment of the homologous chromosomes to opposite spindle poles (bipolar attachment) and their subsequent segregation to the opposite poles during meiosis I. However, the overall function of chiasmata during meiosis is not fully understood. Here, we show that chiasmata also play a crucial role in the attachment of sister chromatids to the same spindle pole and in their co-segregation during meiosis I in fission yeast. Analysis of cells lacking chiasmata and the cohesin protector Sgo1 showed that loss of chiasmata causes frequent bipolar attachment of sister chromatids during anaphase. Furthermore, high time-resolution analysis of centromere dynamics in various types of chiasmate and achiasmate cells, including those lacking the DNA replication checkpoint factor Mrc1 or the meiotic centromere protein Moa1, showed the following three outcomes: (i) during the pre-anaphase stage, the bipolar attachment of sister chromatids occurs irrespective of chiasma formation; (ii) the chiasma contributes to the elimination of the pre-anaphase bipolar attachment; and (iii) when the bipolar attachment remains during anaphase, the chiasmata generate a bias toward the proper pole during poleward chromosome pulling that results in appropriate chromosome segregation. Based on these results, we propose that chiasmata play a pivotal role in the selection of proper attachments and provide a backup mechanism that promotes correct chromosome segregation when improper attachments remain during anaphase I. PMID:21423721

  1. Chiasmata promote monopolar attachment of sister chromatids and their co-segregation toward the proper pole during meiosis I.

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    Yukinobu Hirose

    2011-03-01

    Full Text Available The chiasma is a structure that forms between a pair of homologous chromosomes by crossover recombination and physically links the homologous chromosomes during meiosis. Chiasmata are essential for the attachment of the homologous chromosomes to opposite spindle poles (bipolar attachment and their subsequent segregation to the opposite poles during meiosis I. However, the overall function of chiasmata during meiosis is not fully understood. Here, we show that chiasmata also play a crucial role in the attachment of sister chromatids to the same spindle pole and in their co-segregation during meiosis I in fission yeast. Analysis of cells lacking chiasmata and the cohesin protector Sgo1 showed that loss of chiasmata causes frequent bipolar attachment of sister chromatids during anaphase. Furthermore, high time-resolution analysis of centromere dynamics in various types of chiasmate and achiasmate cells, including those lacking the DNA replication checkpoint factor Mrc1 or the meiotic centromere protein Moa1, showed the following three outcomes: (i during the pre-anaphase stage, the bipolar attachment of sister chromatids occurs irrespective of chiasma formation; (ii the chiasma contributes to the elimination of the pre-anaphase bipolar attachment; and (iii when the bipolar attachment remains during anaphase, the chiasmata generate a bias toward the proper pole during poleward chromosome pulling that results in appropriate chromosome segregation. Based on these results, we propose that chiasmata play a pivotal role in the selection of proper attachments and provide a backup mechanism that promotes correct chromosome segregation when improper attachments remain during anaphase I.

  2. Bloom Helicase and DNA Topoisomerase IIIα Are Involved in the Dissolution of Sister Chromatids

    Science.gov (United States)

    Seki, Masayuki; Nakagawa, Takayuki; Seki, Takahiko; Kato, Genta; Tada, Shusuke; Takahashi, Yuriko; Yoshimura, Akari; Kobayashi, Takayuki; Aoki, Ayako; Otsuki, Makoto; Habermann, Felix A.; Tanabe, Hideyuki; Ishii, Yutaka; Enomoto, Takemi

    2006-01-01

    Bloom's syndrome (BS) is an autosomal disorder characterized by predisposition to a wide variety of cancers. The gene product whose mutation leads to BS is the RecQ family helicase BLM, which forms a complex with DNA topoisomerase IIIα (Top3α). However, the physiological relevance of the interaction between BLM and Top3α within the cell remains unclear. We show here that Top3α depletion causes accumulation of cells in G2 phase, enlargement of nuclei, and chromosome gaps and breaks that occur at the same position in sister chromatids. The transition from metaphase to anaphase is also inhibited. All of these phenomena except cell lethality are suppressed by BLM gene disruption. Taken together with the biochemical properties of BLM and Top3α, these data indicate that BLM and Top3α execute the dissolution of sister chromatids. PMID:16880537

  3. Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

    OpenAIRE

    Mihailo Mirkovic; Lukas H. Hutter; Béla Novák; Raquel A. Oliveira

    2015-01-01

    Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC), is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response r...

  4. Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

    OpenAIRE

    Mirkovic, Mihailo; Hutter, Lukas H.; Novák, Béla; Oliveira, Raquel A.

    2015-01-01

    Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC), is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response r...

  5. Increased LOH due to Defective Sister Chromatid Cohesion Is due Primarily to Chromosomal Aneuploidy and not Recombination

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    Dror Sagi

    2017-10-01

    Full Text Available Loss of heterozygosity (LOH is an important factor in cancer, pathogenic fungi, and adaptation to changing environments. The sister chromatid cohesion process (SCC suppresses aneuploidy and therefore whole chromosome LOH. SCC is also important to channel recombinational repair to sister chromatids, thereby preventing LOH mediated by allelic recombination. There is, however, insufficient information about the relative roles that the SCC pathway plays in the different modes of LOH. Here, we found that the cohesin mutation mcd1-1, and other mutations in SCC, differentially affect the various types of LOH. The greatest effect, by three orders of magnitude, was on whole chromosome loss (CL. In contrast, there was little increase in recombination-mediated LOH, even for telomeric markers. Some of the LOH events that were increased by SCC mutations were complex, i.e., they were the result of several chromosome transactions. Although these events were independent of POL32, the most parsimonious way to explain the formation of at least some of them was break-induced replication through the centromere. Interestingly, the mcd1-1 pol32Δ double mutant showed a significant reduction in the rate of CL in comparison with the mcd1-1 single mutant. Our results show that defects in SCC allow the formation of complex LOH events that, in turn, can promote drug or pesticide resistance in diploid microbes that are pathogenic to humans or plants.

  6. Rtt107 phosphorylation promotes localisation to DNA double-stranded breaks (DSBs and recombinational repair between sister chromatids.

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    Pranav Ullal

    Full Text Available Efficient repair of DNA double-stranded breaks (DSB requires a coordinated response at the site of lesion. Nucleolytic resection commits repair towards homologous recombination, which preferentially occurs between sister chromatids. DSB resection promotes recruitment of the Mec1 checkpoint kinase to the break. Rtt107 is a target of Mec1 and serves as a scaffold during repair. Rtt107 plays an important role during rescue of damaged replication forks, however whether Rtt107 contributes to the repair of DSBs is unknown. Here we show that Rtt107 is recruited to DSBs induced by the HO endonuclease. Rtt107 phosphorylation by Mec1 and its interaction with the Smc5-Smc6 complex are both required for Rtt107 loading to breaks, while Rtt107 regulators Slx4 and Rtt101 are not. We demonstrate that Rtt107 has an effect on the efficiency of sister chromatid recombination (SCR and propose that its recruitment to DSBs, together with the Smc5-Smc6 complex is important for repair through the SCR pathway.

  7. Opposing Functions of the N-terminal Acetyltransferases Naa50 and NatA in Sister-chromatid Cohesion.

    Science.gov (United States)

    Rong, Ziye; Ouyang, Zhuqing; Magin, Robert S; Marmorstein, Ronen; Yu, Hongtao

    2016-09-02

    During the cell cycle, sister-chromatid cohesion tethers sister chromatids together from S phase to the metaphase-anaphase transition and ensures accurate segregation of chromatids into daughter cells. N-terminal acetylation is one of the most prevalent protein covalent modifications in eukaryotes and is mediated by a family of N-terminal acetyltransferases (NAT). Naa50 (also called San) has previously been shown to play a role in sister-chromatid cohesion in metazoans. The mechanism by which Naa50 contributes to cohesion is not understood however. Here, we show that depletion of Naa50 in HeLa cells weakens the interaction between cohesin and its positive regulator sororin and causes cohesion defects in S phase, consistent with a role of Naa50 in cohesion establishment. Strikingly, co-depletion of NatA, a heterodimeric NAT complex that physically interacts with Naa50, rescues the sister-chromatid cohesion defects and the resulting mitotic arrest caused by Naa50 depletion, indicating that NatA and Naa50 play antagonistic roles in cohesion. Purified recombinant NatA and Naa50 do not affect each other's NAT activity in vitro Because NatA and Naa50 exhibit distinct substrate specificity, we propose that they modify different effectors and regulate sister-chromatid cohesion in opposing ways.

  8. Incorporation of deoxyuridine monophosphate into DNA increases the sister-chromatid exchange yield

    Energy Technology Data Exchange (ETDEWEB)

    Pardo, E.G.; Hernandez, P.; Gutierrez, C.

    1987-02-01

    The effect of a treatment with 5-fluoro-2'-deoxyuridine (FdUrd) in combination with 2'-deoxyuridine (dUrd) on cell proliferation, incorporation of DNA precursors into DNA and sister-chromatid exchanges (SCEs) has been analyzed in Allium cepa meristem cells. FdUrd in the range 10/sup -9/-5 x 10/sup -7/ M produced a dose- and time-dependent decrease in the amount of cells in mitosis. This inhibitory effect could be reversed by 70-80% in short-term (6 h) experiments, by exogenously supplied dUrd at a concentration of 10/sup -1/ M. However, at the highest FdUrd dose tested (10/sup -7/ M), 10/sup -4/ M dUrd could not reverse the FdUrd effect in long-term experiments as shown by analyzing the kinetics of synchronous cell populations. DNA extracted from cells pulsed with (6-/sup 3/H)dUrd in the presence of FdUrd and 6-amino-uracil (6-AU), an inhibitor of uracil-DNA glycosylase, contained a small amount of label in the form of (6-/sup 3/H)dUMP. Thus the authors conclude that under the experimental conditions, exogenously supplied dUrd may be metabolized intracellularly to 2'-deoxyuridine triphosphate (dUTP) and that this deoxynucleotide may eventually be mis-incorporated into DNA. By analyzing SCE levels in third division chromosomes of cells treated with FdUrd and dUrd during their second cycle, they has scored a 6-fold increase in the reciprocal SCE level which demonstrates that the replication of a dUMP-containing DNA template leads to a higher SCE yield.

  9. Cyclin A2 Is Required for Sister Chromatid Segregation, But Not Separase Control, in Mouse Oocyte Meiosis

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    Sandra A. Touati

    2012-11-01

    Full Text Available In meiosis, two specialized cell divisions allow the separation of paired chromosomes first, then of sister chromatids. Separase removes the cohesin complex holding sister chromatids together in a stepwise manner from chromosome arms in meiosis I, then from the centromere region in meiosis II. Using mouse oocytes, our study reveals that cyclin A2 promotes entry into meiosis, as well as an additional unexpected role; namely, its requirement for separase-dependent sister chromatid separation in meiosis II. Untimely cyclin A2-associated kinase activity in meiosis I leads to precocious sister separation, whereas inhibition of cyclin A2 in meiosis II prevents it. Accordingly, endogenous cyclin A is localized to kinetochores throughout meiosis II, but not in anaphase I. Additionally, we found that cyclin B1, but not cyclin A2, inhibits separase in meiosis I. These findings indicate that separase-dependent cohesin removal is differentially regulated by cyclin B1 and A2 in mammalian meiosis.

  10. Cyclin A2 is required for sister chromatid segregation, but not separase control, in mouse oocyte meiosis.

    Science.gov (United States)

    Touati, Sandra A; Cladière, Damien; Lister, Lisa M; Leontiou, Ioanna; Chambon, Jean-Philippe; Rattani, Ahmed; Böttger, Franziska; Stemmann, Olaf; Nasmyth, Kim; Herbert, Mary; Wassmann, Katja

    2012-11-29

    In meiosis, two specialized cell divisions allow the separation of paired chromosomes first, then of sister chromatids. Separase removes the cohesin complex holding sister chromatids together in a stepwise manner from chromosome arms in meiosis I, then from the centromere region in meiosis II. Using mouse oocytes, our study reveals that cyclin A2 promotes entry into meiosis, as well as an additional unexpected role; namely, its requirement for separase-dependent sister chromatid separation in meiosis II. Untimely cyclin A2-associated kinase activity in meiosis I leads to precocious sister separation, whereas inhibition of cyclin A2 in meiosis II prevents it. Accordingly, endogenous cyclin A is localized to kinetochores throughout meiosis II, but not in anaphase I. Additionally, we found that cyclin B1, but not cyclin A2, inhibits separase in meiosis I. These findings indicate that separase-dependent cohesin removal is differentially regulated by cyclin B1 and A2 in mammalian meiosis.

  11. Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance.

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    Vlad C Seitan

    2006-07-01

    Full Text Available Saccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes emphasizes a conserved role in regulating sister chromatid cohesion, but homologs of Scc4 have not hitherto been identified outside certain fungi. Some metazoan orthologs of Scc2 were initially identified as developmental gene regulators, such as Drosophila Nipped-B, a regulator of cut and Ultrabithorax, and delangin, a protein mutant in Cornelia de Lange syndrome. We show that delangin and Nipped-B bind previously unstudied human and fly orthologs of Caenorhabditis elegans MAU-2, a non-axis-specific guidance factor for migrating cells and axons. PSI-BLAST shows that Scc4 is evolutionarily related to metazoan MAU-2 sequences, with the greatest homology evident in a short N-terminal domain, and protein-protein interaction studies map the site of interaction between delangin and human MAU-2 to the N-terminal regions of both proteins. Short interfering RNA knockdown of human MAU-2 in HeLa cells resulted in precocious sister chromatid separation and in impaired loading of cohesin onto chromatin, indicating that it is functionally related to Scc4, and RNAi analyses show that MAU-2 regulates chromosome segregation in C. elegans embryos. Using antisense morpholino oligonucleotides to knock down Xenopus tropicalis delangin or MAU-2 in early embryos produced similar patterns of retarded growth and developmental defects. Our data show that sister chromatid cohesion in metazoans involves the formation of a complex similar to the Scc2-Scc4 interaction in the budding yeast. The very high degree of sequence conservation between Scc4 homologs in complex metazoans is consistent with increased selection pressure to conserve additional essential functions, such as regulation of cell and axon migration during development.

  12. Diagnostic insonation of extra uteri human placentas: no effect of lymphocytic sister chromatid exchange

    Energy Technology Data Exchange (ETDEWEB)

    Brulfert, A.; Ciaravino, V.; Miller, M.W.; Maulik, D.; Carstensen, E.L.

    1984-01-01

    Freshly delivered human placentas were exposed to ultrasound for 30 min using a diagnostic linear array unit. Blood was then drawn and cultured in the presence of bromodeoxyuridine, and the frequencies of sister chromatid exchanges (SCE) in the lymphocytes determined. There was no statistically significant difference in SCE frequencies between control and exposed cells; the frequencies of SCEs per cell ranged from 4.50 to 6.02 for control and from 4.66 to 6.10 for exposed cells in five separate experiments. Positive control mitomycin C treated cells were significantly affected, with more than 50 SCEs per cell. 20 references, 1 table.

  13. A proposal of a standardised nomenclature for terminal minute sister chromatid exchanges

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    Máximo E. Drets

    2006-01-01

    Full Text Available We described spontaneous minute sister chromatid exchanges (SCE in telomeric regions of human and Chinese hamster ovary (CHO chromosomes more than 10 years ago. These structures, which we called t-SCE, were detected by means of highly precise quantitative microphotometrical scanning and computer graphic image analysis. Recently, several authors using the CO-FISH method also found small SCEs in telomeric regions and called them T-SCE. The use of different terms for designating the same phenomenon should be avoided. We propose ter SCE as a uniform nomenclature for minute telomeric SCEs.

  14. The PP2A inhibitor I2PP2A is essential for sister chromatid segregation in oocyte meiosis II.

    Science.gov (United States)

    Chambon, Jean-Philippe; Touati, Sandra A; Berneau, Stéphane; Cladière, Damien; Hebras, Céline; Groeme, Rachel; McDougall, Alex; Wassmann, Katja

    2013-03-18

    Haploid gametes are generated through two consecutive meiotic divisions, with the segregation of chromosome pairs in meiosis I and sister chromatids in meiosis II. Separase-mediated stepwise removal of cohesion, first from chromosome arms and later from the centromere region, is a prerequisite for maintaining sister chromatids together until their separation in meiosis II [1]. In all model organisms, centromeric cohesin is protected from separase-dependent removal in meiosis I through the activity of PP2A-B56 phosphatase, which is recruited to centromeres by shugoshin/MEI-S332 (Sgo) [2-5]. How this protection of centromeric cohesin is removed in meiosis II is not entirely clear; we find that all the PP2A subunits remain colocalized with the cohesin subunit Rec8 at the centromere of metaphase II chromosomes. Here, we show that sister chromatid separation in oocytes depends on a PP2A inhibitor, namely I2PP2A. I2PP2A colocalizes with the PP2A enzyme at centromeres at metaphase II, independently of bipolar attachment. When I2PP2A is depleted, sister chromatids fail to segregate during meiosis II. Our findings demonstrate that in oocytes I2PP2A is essential for faithful sister chromatid segregation by mediating deprotection of centromeric cohesin in meiosis II. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Sister chromatid exchange assessment by chromosome orientation-fluorescence in situ hybridization on the bovine sex chromosomes and autosomes 16 and 26.

    Science.gov (United States)

    Revay, T; King, W A

    2012-01-01

    Mammalian genome replication and maintenance are intimately coupled with the mechanisms that ensure cohesion between the resultant sister chromatids and the repair of DNA breaks. Although a sister chromatid exchange (SCE) is an error-free swapping of precisely matched and identical DNA strands, repetitive elements adjacent to the break site can act as alternative template sites and an unequal sister chromatid exchange can result, leading to structural variations and copy number change. Here we test the vulnerability for SCEs of the repeat-rich bovine Y chromosome in comparison with X, 16 and 26 chromosomes, using chromosome orientation-fluorescence in situ hybridization. The mean SCE rate of the Y chromosome (0.065 ± 0.029) was similar to that of BTA16 and BTA26 (0.065, 0.055), but was only approximately half of that of the X chromosome (0.142). As the chromosomal length affects the number of SCE events, we adjusted the SCE rates of the Y, 16, and 26 chromosomes to the length of the largest chromosome X resulting in very similar adjusted SCE (SCE(adj)) rates in all categories. Our results - based on 3 independent bulls - show that, although the cattle Y chromosome is a chest full of repeated elements, their presence and the documented activity of repeats in SCE formation does not manifest in significantly higher SCE(adj) rates and suggest the importance of the structural organization of the Y chromosome and the role of alternative mitotic DNA repair mechanisms.

  16. Investigating the in vitro effect of taurine on the infant lymphocytes by sister chromatid exchange.

    Science.gov (United States)

    Ergun, Mehmet Ali; Soysal, Yasemin; Kismet, Erol; Akay, Cemal; Dundaroz, Rusen; Ilhan, Mustafan; Imirzalioglu, Necat

    2006-06-01

    Taurine (2-aminoethane sulphonic acid) is normally present in most mammalian tissues and the most abundant free amino acid in lymphocytes. It participates in various important physiological activities including modulation of the functioning of the central nervous system, cell proliferation, viability and prevention of oxidant-induced injury in many tissues. Its levels in human milk are very high which may be the most important difference from cow's milk. In contrast, an inverse association between breast-feeding and carcinogenesis in childhood or later in life has been suggested by several studies. The study group consisted of eight healthy infants. Peripheral blood was collected and lymphocytes were cultured with either Taurine or Mitomycin C (MMC). Sister chromatid exchange in lymphocytes of the infants were calculated. Statistical differences were found between untreated and MMC-treated lymphocytes, untreated and MMC plus taurine-treated lymphocytes, and between MMC and MMC plus taurine-treated lymphocytes (P = 0.012). The results indicated that taurine plays a protective role in MMC-induced sister chromatid exchange in human lymphocytes. The authors suggest that the high levels of taurine found in human milk may induce protecting effects from breast-feeding against DNA damage and malignancy.

  17. SGO1 maintains bovine meiotic and mitotic centromeric cohesions of sister chromatids and directly affects embryo development.

    Directory of Open Access Journals (Sweden)

    Feng-Xia Yin

    Full Text Available Shugoshin (SGO is a critical factor that enforces cohesion from segregation of paired sister chromatids during mitosis and meiosis. It has been studied mainly in invertebrates. Knowledge of SGO(s in a mammalian system has only been reported in the mouse and Hela cells. In this study, the functions of SGO1 in bovine oocytes during meiotic maturation, early embryonic development and somatic cell mitosis were investigated. The results showed that SGO1 was expressed from germinal vesicle (GV to the metaphase II stage. SGO1 accumulated on condensed and scattered chromosomes from pre-metaphase I to metaphase II. The over-expression of SGO1 did not interfere with the process of homologous chromosome separation, although once separated they were unable to move to the opposing spindle poles. This often resulted in the formation of oocytes with 60 replicated chromosomes. Depletion of SGO1 in GV oocytes affected chromosomal separation resulting in abnormal chromosome alignment at a significantly higher proportion than in control oocytes. Knockdown of SGO1 expression significantly decreased the embryonic developmental rate and quality. To further confirm the function(s of SGO1 during mitosis, bovine embryonic fibroblast cells were transfected with SGO1 siRNAs. SGO1 depletion induced the premature dissociation of chromosomal cohesion at the centromere and along the chromosome arm giving rise to abnormal appearing mitotic patterns. The results of this study infer that SGO1 is involved in the centromeric cohesion of sister chromatids and chromosomal movement towards the spindle poles. Depletion of SGO1 causes arrestment of cell division in meiosis and mitosis.

  18. UV-induced chromosome aberrations, sister-chromatid exchanges and cell survival in cultured lymphocytes from malnourished children

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, P.B.; Rahiman, M.A.; Tulpule, P.G.

    1982-08-01

    Cultured lymphocytes from children with kwashiorkor and from normal children were examined for their susceptibility to ultraviolet (UV)-induced chromosome aberrations, sister-chromatid exchanges and cell survival. Cells from kwashiorkor exhibited increased chromosome aberrations, but not sister-chromatid exchanges, when exposed to higher doses of UV. Furthermore, when cells from these patients were exposed to higher doses of UV, there was a significant reduction in viability. These results indicate that, as compared to normals, cells from kwashiorkor were more sensitive to the lethal effects of UV.

  19. UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells

    DEFF Research Database (Denmark)

    Oka, Yasuyoshi; Varmark, Hanne; Vitting-Seerup, Kristoffer;

    2014-01-01

    UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency......, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions...

  20. PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis.

    Science.gov (United States)

    Nielsen, Christian F; Huttner, Diana; Bizard, Anna H; Hirano, Seiki; Li, Tian-Neng; Palmai-Pallag, Timea; Bjerregaard, Victoria A; Liu, Ying; Nigg, Erich A; Wang, Lily Hui-Ching; Hickson, Ian D

    2015-01-01

    PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH(-/-) cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localizes with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH. Purified PICH protein strongly stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH(-/-) cell line exhibits chromosome instability and chromosome condensation and decatenation defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis.

  1. Sister-chromatid exchange analysis in a rural population of Mexico exposed to pesticides.

    Science.gov (United States)

    Gómez-Arroyo, S; Noriega-Aldana, N; Osorio, A; Galicia, F; Ling, S; Villalobos-Pietrini, R

    1992-03-01

    Cytogenetic damage was evaluated by means of the analysis of sister-chromatid exchange (SCE) in a rural population of Tlaxcala, Mexico, in occupational contact with pesticides. We studied 170 men, 94 exposed and 76 not exposed. It was shown that SCE followed a normal distribution and Student's t test did not present differences between the two groups (P = 0.4). The frequency of SCE was not correlated with the duration of exposure of the rural workers (r = -0.06), the multiple covariance analysis applied to the data of duration of exposure, tobacco intake and alcohol ingestion demonstrated a lack of statistical significance. In the exposed people we observed no symptoms provoked by these compounds.

  2. Antimutagenic effect of crown ethers on heavy metal-induced sister chromatid exchanges.

    Science.gov (United States)

    Cai, M Y; Arenaz, P

    1998-01-01

    Macrocyclic polyethers (crown ethers) are a family of compounds that possess the ability to complex with and transport metal ions across membranes. Because of their unique ionophoric characteristic, they have wide application in industry and research, chemistry and biology. In the current investigation the relationship between heavy metal mutagenesis and crown ether co-mutagenicity and/or antimutagenicity in mammalian cells has been examined using sister chromatid exchange (SCE) as the cytogenetic end point. Chinese hamster ovary cells were treated with lead or cadmium, with and without selected crown ethers. Several genotoxic end points, including SCEs were scored and statistically compared. We report here that most of the crown ethers studied had little or no influence on lead- or cadmium-induced SCEs or chromosome aberrations. On the other hand, the substituted crown ether dicyclohexyl 21-crown-7 significantly decreased both spontaneous and metal-induced SCE frequencies, suggesting that this crown ether may possess antimutagenic activity.

  3. Sister chromatid exchange in human populations: the effect of smoking, drug treatment, and occupational exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, B.; Bredberg, A.; McKenzie, W.; Sten, M.

    1982-01-01

    Increased rate of sister chromatid exchange (SCE) in peripheral lymphocytes has been observed in smokers as compared to nonsmokers and in patients receiving certain cytostatic drugs. The increased SCE frequency in smokers was shown to depend on the number of cigarettes smoked per day, as well as on the duration of smoking. DNA cross-links caused by photochemotherapy against psoriasis, 8-methoxypsoralen plus UVA irradiation (PUVA), as well as by the anti-cancer chemotherapeutic agent CCNU, were shown to be more effective at inducing SCE's than other types of DNA damage caused by these treatments. These observations suggest that SCE analysis may be used as an indicator of genotoxic exposure in vivo, provided that the various types of DNA damage caused by genotoxic agents and the dose, as well as the time of exposure in relation to the time of sampling, are considered.

  4. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

    Yardimci, Hasan; Loveland, Anna B.; Habuchi, Satoshi; van Oijen, Antoine M.; Walter, Johannes C.

    2010-01-01

    The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes.

  5. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

    Yardimci, Hasan; Loveland, Anna B.; Habuchi, Satoshi; van Oijen, Antoine M.; Walter, Johannes C.

    2010-01-01

    The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes. So

  6. Regulation of the Drosophila Enhancer of split and invected-engrailed Gene Complexes by Sister Chromatid Cohesion Proteins

    NARCIS (Netherlands)

    Schaaf, Cheri A.; Misulovin, Ziva; Sahota, Gurmukh; Siddiqui, Akbar M.; Schwartz, Yuri B.; Kahn, Tatyana G.; Pirrotta, Vincenzo; Gause, Maria; Dorsett, Dale

    2009-01-01

    The cohesin protein complex was first recognized for holding sister chromatids together and ensuring proper chromosome segregation. Cohesin also regulates gene expression, but the mechanisms are unknown. Cohesin associates preferentially with active genes, and is generally absent from regions in whi

  7. An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yisong [ORNL; Giannone, Richard J [ORNL; Wu, Jun [ORNL; Gomez, Marla V [ORNL; Liu, Yie [ORNL

    2005-01-01

    Telomerase deficiency leads to a progressive loss of telomeric DNA that eventually triggers cell apoptosis in human primary cells during prolonged growth in culture. Rare survivors can maintain telomere length through either activation of telomerase or recombination-based telomere lengthening, and thus proliferate indefinitely. We have explored the possibility that telomeres may be maintained through telomere sister chromatid exchange (T-SCE) in murine telomere reverse transcriptase-deficient (mTert -/-) splenocytes and ES cells. Because telomerase deficiency leads to gradual loss of telomeric DNA in mTert -/- splenocytes and ES cells and eventually to chromosomes with telomere signal-free ends (SFEs), we examined these cell types for evidence of sister chromatid exchange at telomeres, and observed an increase in T-SCEs only in a subset of mTert -/- splenocytes or ES cells that possessed multiple SFEs. Furthermore, T-SCEs were more often detected in ES cells than in splenocytes that harbored a similar frequency of SFEs. In mTert heterozygous (mTert +/-) ES cells or splenocytes, which are known to exhibit a decrease in average telomere length but no SFEs, no increase in T-SCE was observed. In addition to T-SCE, other genomic rearrangements (i.e., SCE) were also significantly increased in mTert -/- ES cells possessing critically short telomeres, but not in splenocytes. Our results suggest that animals and cell culture differ in their ability to carry out genomic rearrangements as a means of maintaining telomere integrity when telomeres become critically shortened.

  8. Frequent and efficient use of the sister chromatid for DNA double-strand break repair during budding yeast meiosis.

    Directory of Open Access Journals (Sweden)

    Tamara Goldfarb

    Full Text Available Recombination between homologous chromosomes of different parental origin (homologs is necessary for their accurate segregation during meiosis. It has been suggested that meiotic inter-homolog recombination is promoted by a barrier to inter-sister-chromatid recombination, imposed by meiosis-specific components of the chromosome axis. Consistent with this, measures of Holliday junction-containing recombination intermediates (joint molecules [JMs] show a strong bias towards inter-homolog and against inter-sister JMs. However, recombination between sister chromatids also has an important role in meiosis. The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions, and meiotic double-strand breaks (DSBs that form within such polymorphic regions must be repaired by inter-sister recombination. Efforts to study inter-sister recombination during meiosis, in particular to determine recombination frequencies and mechanisms, have been constrained by the inability to monitor the products of inter-sister recombination. We present here molecular-level studies of inter-sister recombination during budding yeast meiosis. We examined events initiated by DSBs in regions that lack corresponding sequences on the homolog, and show that these DSBs are efficiently repaired by inter-sister recombination. This occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold yields of JMs. Loss of the meiotic-chromosome-axis-associated kinase Mek1 accelerates inter-sister DSB repair and markedly increases inter-sister JM frequencies. Furthermore, inter-sister JMs formed in mek1Δ mutants are preferentially lost, while inter-homolog JMs are maintained. These findings indicate that inter-sister recombination occurs frequently during budding yeast meiosis, with the possibility that up to one-third of all recombination events occur between sister chromatids. We suggest that a Mek1-dependent reduction in

  9. SA1 binds directly to DNA through its unique AT-hook to promote sister chromatid cohesion at telomeres.

    Science.gov (United States)

    Bisht, Kamlesh K; Daniloski, Zharko; Smith, Susan

    2013-08-01

    Sister chromatid cohesion relies on cohesin, a complex comprising a tri-partite ring and a peripheral subunit Scc3, which is found as two related isoforms SA1 and SA2 in vertebrates. There is a division of labor between the vertebrate cohesin complexes; SA1-cohesin is required at telomeres and SA2-cohesin at centromeres. Depletion of SA1 has dramatic consequences for telomere function and genome integrity, but the mechanism by which SA1-cohesin mediates cohesion at telomeres is not well understood. Here we dissect the individual contribution of SA1 and the ring subunits to telomere cohesion and show that telomeres rely heavily on SA1 and to a lesser extent on the ring for cohesion. Using chromatin immunoprecipitation we show that SA1 is highly enriched at telomeres, is decreased at mitosis when cohesion is resolved, and is increased when cohesion persists. Overexpression of SA1 alone was sufficient to induce cohesion at telomeres, independent of the cohesin ring and dependent on its unique (not found in SA2) N-terminal domain, which we show binds to telomeric DNA through an AT-hook motif. We suggest that a specialized cohesion mechanism may be required to accommodate the high level of DNA replication-associated repair at telomeres.

  10. New functions of Ctf18-RFC in preserving genome stability outside its role in sister chromatid cohesion.

    Science.gov (United States)

    Gellon, Lionel; Razidlo, David F; Gleeson, Olive; Verra, Lauren; Schulz, Danae; Lahue, Robert S; Freudenreich, Catherine H

    2011-02-10

    Expansion of DNA trinucleotide repeats causes at least 15 hereditary neurological diseases, and these repeats also undergo contraction and fragility. Current models to explain this genetic instability invoke erroneous DNA repair or aberrant replication. Here we show that CAG/CTG tracts are stabilized in Saccharomyces cerevisiae by the alternative clamp loader/unloader Ctf18-Dcc1-Ctf8-RFC complex (Ctf18-RFC). Mutants in Ctf18-RFC increased all three forms of triplet repeat instability--expansions, contractions, and fragility--with effect over a wide range of allele lengths from 20-155 repeats. Ctf18-RFC predominated among the three alternative clamp loaders, with mutants in Elg1-RFC or Rad24-RFC having less effect on trinucleotide repeats. Surprisingly, chl1, scc1-73, or scc2-4 mutants defective in sister chromatid cohesion (SCC) did not increase instability, suggesting that Ctf18-RFC protects triplet repeats independently of SCC. Instead, three results suggest novel roles for Ctf18-RFC in facilitating genomic stability. First, genetic instability in mutants of Ctf18-RFC was exacerbated by simultaneous deletion of the fork stabilizer Mrc1, but suppressed by deletion of the repair protein Rad52. Second, single-cell analysis showed that mutants in Ctf18-RFC had a slowed S phase and a striking G2/M accumulation, often with an abnormal multi-budded morphology. Third, ctf18 cells exhibit increased Rad52 foci in S phase, often persisting into G2, indicative of high levels of DNA damage. The presence of a repeat tract greatly magnified the ctf18 phenotypes. Together these results indicate that Ctf18-RFC has additional important functions in preserving genome stability, besides its role in SCC, which we propose include lesion bypass by replication forks and post-replication repair.

  11. New functions of Ctf18-RFC in preserving genome stability outside its role in sister chromatid cohesion.

    Directory of Open Access Journals (Sweden)

    Lionel Gellon

    Full Text Available Expansion of DNA trinucleotide repeats causes at least 15 hereditary neurological diseases, and these repeats also undergo contraction and fragility. Current models to explain this genetic instability invoke erroneous DNA repair or aberrant replication. Here we show that CAG/CTG tracts are stabilized in Saccharomyces cerevisiae by the alternative clamp loader/unloader Ctf18-Dcc1-Ctf8-RFC complex (Ctf18-RFC. Mutants in Ctf18-RFC increased all three forms of triplet repeat instability--expansions, contractions, and fragility--with effect over a wide range of allele lengths from 20-155 repeats. Ctf18-RFC predominated among the three alternative clamp loaders, with mutants in Elg1-RFC or Rad24-RFC having less effect on trinucleotide repeats. Surprisingly, chl1, scc1-73, or scc2-4 mutants defective in sister chromatid cohesion (SCC did not increase instability, suggesting that Ctf18-RFC protects triplet repeats independently of SCC. Instead, three results suggest novel roles for Ctf18-RFC in facilitating genomic stability. First, genetic instability in mutants of Ctf18-RFC was exacerbated by simultaneous deletion of the fork stabilizer Mrc1, but suppressed by deletion of the repair protein Rad52. Second, single-cell analysis showed that mutants in Ctf18-RFC had a slowed S phase and a striking G2/M accumulation, often with an abnormal multi-budded morphology. Third, ctf18 cells exhibit increased Rad52 foci in S phase, often persisting into G2, indicative of high levels of DNA damage. The presence of a repeat tract greatly magnified the ctf18 phenotypes. Together these results indicate that Ctf18-RFC has additional important functions in preserving genome stability, besides its role in SCC, which we propose include lesion bypass by replication forks and post-replication repair.

  12. Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

    Directory of Open Access Journals (Sweden)

    Mihailo Mirkovic

    2015-10-01

    Full Text Available Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC, is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response resulting in abnormal mitotic exit after a short delay. Quantitative live-cell imaging approaches combined with mathematical modeling indicate that weak SAC activation upon cohesion loss is caused by weak signal generation. This is further attenuated by several feedback loops in the mitotic signaling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1 gradually impair error-correction efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.

  13. In vitro genotoxicity of fipronil sister chromatid exchange, cytokinesis block micronucleus test, and comet assay.

    Science.gov (United States)

    Çelik, Ayla; Ekinci, Seda Yaprak; Güler, Gizem; Yildirim, Seda

    2014-03-01

    Fipronil (FP) is a phenylpyrazole pesticide developed by the transnational company Rhône-Poulenc Agro in 1987. Data on the genotoxicity and toxicity of FP are rather inadequate. In this study, we aimed to evaluate the potential genotoxic activity of FP using the single-cell microgel electrophoresis or comet assay, sister chromatid exchanges (SCEs), and micronuclei (MN) in human peripheral blood lymphocytes. In addition, the cytokinesis block proliferation index (CBPI) and proliferation index (PRI) were measured for cytotoxicity. In this study, three different doses of FP were used (0.7, 0.3, 0.1 μg/mL). Mitomycin C (2 μg/mL) and hydrogen peroxide were used as positive controls for SCE MN test systems, and comet assay, respectively. FP induced a statistically significant increase in the MN and SCE frequency and DNA damage in a dose-dependent manner in human peripheral blood lymphocytes (pcomet assay, we showed that all the doses of the FP induced DNA damage in human peripheral blood lymphocytes in vitro (p<0.05).

  14. A high rate of telomeric sister chromatid exchange occurs in chronic lymphocytic leukaemia B-cells.

    Science.gov (United States)

    Medves, Sandrine; Auchter, Morgan; Chambeau, Laetitia; Gazzo, Sophie; Poncet, Delphine; Grangier, Blandine; Verney, Aurélie; Moussay, Etienne; Ammerlaan, Wim; Brisou, Gabriel; Morjani, Hamid; Géli, Vincent; Palissot, Valérie; Berchem, Guy; Salles, Gilles; Wenner, Thomas

    2016-07-01

    Cancer cells protect their telomere ends from erosion through reactivation of telomerase or by using the Alternative Lengthening of Telomere (ALT) mechanism that depends on homologous recombination. Chronic lymphocytic leukaemia (CLL) B cells are characterized by almost no telomerase activity, shelterin deregulation and telomere fusions. To characterize telomeric maintenance mechanisms in B-CLL patients, we measured their telomere length, telomerase expression and the main hallmarks of the ALT activity i.e. C-circle concentration, an extra-chromosomal telomere repeat (ECTR), and the level of telomeric sister chromatid exchange (T-SCE) rate. Patients showed relative homogenous telomere length although almost no TERT transcript and nearly no C-circle were evidenced. Nevertheless, compared with normal B cells, B-CLL cells showed an increase in T-SCE rate that was correlated with a strong down-regulation of the topoisomerase III alpha (TOP3A) expression, involved in the dissolution of Holliday Junctions (HJ), together with an increased expression of SLX1A, SLX4, MUS81 and GEN1, involved in the resolution of HJ. Altogether, our results suggest that the telomere maintenance mechanism of B-CLL cells do not preferentially use telomerase or ALT. Rather, the rupture of the dissolvasome/resolvasome balance may increase telomere shuffling that could homogenize telomere length, slowing telomere erosion in this disease.

  15. Sister chromatid exchange in human lymphocytes induced by propoxur following plant activation by Vicia faba.

    Science.gov (United States)

    Gómez-Arroyo, S; Calderón-Segura, M E; Villalobos-Pietrini, R

    1995-01-01

    Because the carbamate insecticide propoxur induced sister chromatid exchanges (SCE) in Vicia faba but was ineffective in producing SCE in lymphocytes in culture, it was hardly suspected that plant metabolism was involved. Experiments were conducted in which metabolic activation was afforded by Vicia faba roots, and SCE in human lymphocytes in vitro was used to assess cytogenetic damage. Several concentrations of propoxur (250, 500, 1,000, 1,500, and 2,000 ppm) were applied for 4 hr to the roots of Vicia faba. Extracts prepared from these treatments were added to the lymphocyte cultures and a significant increase of SCE frequencies with a concentration-response relationship could be detected. The lymphocyte proliferation kinetics and the proliferation rate index (PRI) were not affected (except in the highest concentration, of 2,000 ppm). This general behavior was in agreement with the presence of an enzymatic system (S10 fraction) in Vicia roots capable of metabolizing or activating the propoxur. With 2,000 ppm, cell necrosis was produced in Vicia; therefore, this extract did not induce SCE in lymphocytes. However, lymphocyte proliferation kinetics were delayed and PRI was significantly decreased. Ethanol, a promutagen activated by this plant, was applied directly to the lymphocyte cultures as a positive control, and the response was negative. On the other hand, the extracts of roots treated with ethanol increased the SCE to more than twice that of the negative control, but the lymphocyte proliferation kinetics and PRI were not affected.

  16. Health assessment of gasoline and fuel oxygenate vapors: micronucleus and sister chromatid exchange evaluations.

    Science.gov (United States)

    Schreiner, Ceinwen A; Hoffman, Gary M; Gudi, Ramadevi; Clark, Charles R

    2014-11-01

    Micronucleus and sister chromatid exchange (SCE) tests were performed for vapor condensate of baseline gasoline (BGVC), or gasoline with oxygenates, methyl tert-butyl ether (G/MTBE), ethyl tert butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), t-butyl alcohol (TBA), or ethanol (G/EtOH). Sprague Dawley rats (the same 5/sex/group for both endpoints) were exposed to 0, 2000, 10,000, or 20,000mg/m(3) of each condensate, 6h/day, 5days/week over 4weeks. Positive controls (5/sex/test) were given cyclophosphamide IP, 24h prior to sacrifice at 5mg/kg (SCE test) and 40mg/kg (micronucleus test). Blood was collected from the abdominal aorta for the SCE test and femurs removed for the micronucleus test. Blood cell cultures were treated with 5μg/ml bromodeoxyuridine (BrdU) for SCE evaluation. No significant increases in micronucleated immature erythrocytes were observed for any test material. Statistically significant increases in SCE were observed in rats given BGVC alone or in female rats given G/MTBE. G/TAME induced increased SCE in both sexes at the highest dose only. Although DNA perturbation was observed for several samples, DNA damage was not expressed as increased micronuclei in bone marrow cells. Inclusion of oxygenates in gasoline did not increase the effects of gasoline alone or produce a cytogenetic hazard.

  17. Induction of sister chromatid exchanges by coal dust and tobacco snuff extracts in human peripheral lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J.D.; Ong, T.

    1985-01-01

    The organic solvent extracts of sub-bituminous coal dust and tobacco snuff, both together and separately, were tested for the induction of sister chromatid exchanges (SCEs) in human peripheral lymphocytes. The results indicate that these extracts induced SCEs, and that when tested together synergistically induced SCEs in two of three donors. Studies with the organic solvent extracts of all five ranks of coal indicate that the extracts of bituminous, lignite, and peat, but not anthracite, induced SCEs. Similar experiments conducted with water extracts, induced SCEs, and that anthracite was equivocal. To determine whether individuals differed in their SCE responses to coal dust extracts, lymphocytes from five donors were tested with organic solvent extracts of bituminous and sub-bituminous coal. An analysis of variance indicates that the SCE response was significantly influenced by the donor and each of the two coal extracts. The findings presented here suggest that coal dust, with or without tobacco snuff, may play a role in the elevated incidence of gastric cancer in coal miners. Because water extracts of some ranks of coal induced SCEs, there exists the possibility of adverse environmental effects due to coal leachates.

  18. Iron-mediated induction of sister-chromatid exchanges by hydrogen peroxide and superoxide anion.

    Science.gov (United States)

    Larramendy, M; Mello-Filho, A C; Martins, E A; Meneghini, R

    1987-05-01

    When Chinese hamster fibroblasts were exposed to hydrogen peroxide or to a system consisting of xanthine oxidase and hypoxanthine, which generates superoxide anion plus hydrogen peroxide, sister-chromatid exchanges (SCEs) were formed in a dose-dependent manner. When the iron-complexing agent o-phenanthroline was present in the medium, however, the production of these SCEs was completely inhibited. This fact indicates that the Fenton reaction: Fe2+ + H2O2----OH0 + OH- + Fe3+ is responsible for the production of SCEs. When O2- and H2O2 were generated inside the cell by incubation with menadione, the production of SCE was prevented by co-incubation with copper diisopropylsalicylate, a superoxide dismutase mimetic agent. The most likely role of O2- is as a reducing agent of Fe3+: O2- + Fe3+----Fe2+ + O2, so that the sum of this and the Fenton reaction, i.e., the iron-catalyzed Haber-Weiss reaction, provides an explanation for the active oxygen species-induced SCE: H2O2 + O2(-)----OH- + OH0 + O2. According to this view, the OH radical thus produced is the agent which ultimately causes SCE. These results are discussed in comparison with other mechanisms previously proposed for induction of SCE by active oxygen species.

  19. Effects of orally administered antioxidants on micronuclei and sister chromatid exchange frequency in workers professionally exposed to antineoplastic agents.

    Science.gov (United States)

    Mrđanović, Jasminka; Jungić, Saša; Šolajić, Slavica; Bogdanović, Višnja; Jurišić, Vladimir

    2012-08-01

    The widespread use of antineoplastic drugs in cancer treatment increased concern about possible hazard to workers involved in the preparation and administration of these drugs. In the present study, the effects of commercial antioxidative drug Oligogal Se on genome protection were analyzed in 15 nurses handling the antineoplastic drugs at the Oncology Department in comparison to twenty healthy volunteers. The nurses took antioxidant mixture Oligogal Se, consisting of vitamins C, E, A and selenium, one capsule per day, over a period of 6 months. Genome damage was measured in peripheral blood lymphocytes by usage of sister chromatid exchange test and the cytokinesis-block micronuclei test. The frequency of sister chromatid exchange (SCE) and micronuclei (MN) in the exposed group was significantly higher when compared to the control group (SCE, p<0.05; MN, p<0.01 respectively). After antioxidant supplementation, the frequency of sister chromatid exchange and micronuclei decreased (p<0.05) when compared with the values from the beginning of the study, but were still above the values of the control group. The effects of confounding factors such as cigarette smoking and cytostatics exposure time were also evaluated. The data indicated that Oligogal Se contributed to the decreasing of genome damages in workers handling the cytostatics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. RSC facilitates Rad59-dependent homologous recombination between sister chromatids by promoting cohesin loading at DNA double-strand breaks.

    Science.gov (United States)

    Oum, Ji-Hyun; Seong, Changhyun; Kwon, Youngho; Ji, Jae-Hoon; Sid, Amy; Ramakrishnan, Sreejith; Ira, Grzegorz; Malkova, Anna; Sung, Patrick; Lee, Sang Eun; Shim, Eun Yong

    2011-10-01

    Homologous recombination repairs DNA double-strand breaks by searching for, invading, and copying information from a homologous template, typically the homologous chromosome or sister chromatid. Tight wrapping of DNA around histone octamers, however, impedes access of repair proteins to DNA damage. To facilitate DNA repair, modifications of histones and energy-dependent remodeling of chromatin are required, but the precise mechanisms by which chromatin modification and remodeling enzymes contribute to homologous DNA repair are unknown. Here we have systematically assessed the role of budding yeast RSC (remodel structure of chromatin), an abundant, ATP-dependent chromatin-remodeling complex, in the cellular response to spontaneous and induced DNA damage. RSC physically interacts with the recombination protein Rad59 and functions in homologous recombination. Multiple recombination assays revealed that RSC is uniquely required for recombination between sister chromatids by virtue of its ability to recruit cohesin at DNA breaks and thereby promoting sister chromatid cohesion. This study provides molecular insights into how chromatin remodeling contributes to DNA repair and maintenance of chromatin fidelity in the face of DNA damage.

  1. Cis-acting determinants affecting centromere function, sister-chromatid cohesion and reciprocal recombination during meiosis in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Sears, D.D.; Hieter, P. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Shero, J.H. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)]|[Baylor College of Medicine, Houston, TX (United States); Hegemann, J.H. [Justus Liebig Universitaet, Giessen (Germany)

    1995-03-01

    We have employed a system that utilizes homologous pairs of human DNA-derived yeast artificial chromosomes (YACs) as marker chromosomes to assess the specific role(s) of conserved centromere DNA elements (CDEI, CDEII, and CDEIII) in meiotic chromosome disjunction fidelity. Thirteen different centromere (CEN) mutations were tested for their effects on meiotic centromere function. YACs containing a wild-type CEN DNA sequence segregate with high fidelity in meiosis I (99% normal segregation) and in meiosis II (96% normal segregation). YACs containing a 31-bp deletion mutation in centromere DNA element II (CDEII{Delta}31) in either a heterocentric (mutant/wild type), homocentric (mutant/mutant) or monosomic (mutant/-) YAC pair configuration exhibited high levels (16-28%) of precocious sister-chromatid segregation (PSS) and increased levels (1-6%) of nondisjunction meiosis I (NDI). YACs containing this mutation also exhibit high levels (21%) of meiosis II nondisjunction. Interestingly, significant alterations in homolog recombination frequency were observed in the exceptional PSS class of tetrads, suggesting unusual interactions between prematurely separated sister chromatids and their homologous nonsister chromatids. We also have assessed the meiotic segregation effects of rare gene conversion events occurring at sites located immediately adjacent to or distantly from the centromere region. Proximal gene conversion events were associated with extremely high levels (60%) of meiosis I segregation errors (including both PSS and NDI), whereas distal events had no apparent effect. Taken together, our results indicate a critical role for CDEII in meiosis and underscore the importance of maintaining sister-chromatid cohesion for proper recombination in meiotic prophase and for proper disjunction in meiosis I. 49 refs., 4 figs., 5 tabs.

  2. The Relationship between Dioxin Congeners in the Breast Milk of Vietnamese Women and Sister Chromatid Exchange

    Directory of Open Access Journals (Sweden)

    Hiroyuki Suzuki

    2014-04-01

    Full Text Available The aim of this study was to clarify the relationship between dioxin concentrations in breast milk and the sister chromatid exchange (SCE frequency in women from herbicide-sprayed and non sprayed areas. Blood samples were taken from 21 women with high TCDD (tetrachlorodibenzo-p-dioxin levels from sprayed areas, 23 women with moderate TCDD levels from sprayed areas, and 19 women from non sprayed areas to determine their SCE frequency. The SCE frequencies for the high and moderate TCDD groups from the sprayed area and for the non sprayed area group were 2.40, 2.19, and 1.48 per cell, respectively. Multiple regression analysis showed that the standardized β values for 1,2,3,6,7,8-hexaCDD (β = 0.60, 1,2,3,4,6,7,8-heptaCDD (β = 0.64, and octaCDD (β = 0.65 were higher than those for TCDD (β = 0.34 and 1,2,3,7,8-pentaCDD (β = 0.42. The adjusted R2 value for polyCDDs (R2 = 0.38 was higher than that for polyCDD toxic equivalents (TEQ (toxic equivalents; R2 = 0.23. This study therefore shows that levels of hexa-, hepta-, and octaCDD, which were previously regarded as being less toxic than TCDD, are closely related to SCE frequency and that the level of dioxin (pg/g lipid is potentially more useful as an indicator than TEQ value for explaining SCE frequency.

  3. A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase.

    Science.gov (United States)

    Guacci, Vincent; Stricklin, Jeremiah; Bloom, Michelle S; Guō, Xuánzōng; Bhatter, Meghna; Koshland, Douglas

    2015-01-01

    Cohesin complex mediates cohesion between sister chromatids, which promotes high-fidelity chromosome segregation. Eco1p acetylates the cohesin subunit Smc3p during S phase to establish cohesion. The current model posits that this Eco1p-mediated acetylation promotes establishment by abrogating the ability of Wpl1p to destabilize cohesin binding to chromosomes. Here we present data from budding yeast that is incompatible with this Wpl1p-centric model. Two independent in vivo assays show that a wpl1∆ fails to suppress cohesion defects of eco1∆ cells. Moreover, a wpl1∆ also fails to suppress cohesion defects engendered by blocking just the essential Eco1p acetylation sites on Smc3p (K112, K113). Thus removing WPL1 inhibition is insufficient for generating cohesion without ECO1 activity. To elucidate how ECO1 promotes cohesion, we conducted a genetic screen and identified a cohesion activator mutation in the SMC3 head domain (D1189H). Smc3-D1189H partially restores cohesion in eco1∆ wpl1∆ or eco1 mutant cells but robustly restores cohesion in cells blocked for Smc3p K112 K113 acetylation. These data support two important conclusions. First, acetylation of the K112 K113 region by Eco1p promotes cohesion establishment by altering Smc3p head function independent of its ability to antagonize Wpl1p. Second, Eco1p targets other than Smc3p K112 K113 are necessary for efficient establishment.

  4. Human RECQ1 is a DNA damage responsive protein required for genotoxic stress resistance and suppression of sister chromatid exchanges.

    Directory of Open Access Journals (Sweden)

    Sudha Sharma

    Full Text Available BACKGROUND: DNA helicases are ubiquitous enzymes that unwind DNA in an ATP-dependent and directionally specific manner. Unwinding of double-stranded DNA is essential for the processes of DNA repair, recombination, transcription, and DNA replication. Five human DNA helicases sharing sequence similarity with the E. coli RecQ helicase have been identified. Three of the human RecQ helicases are implicated in hereditary diseases (Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome which display clinical symptoms of premature aging and cancer. RECQ1 helicase is the most highly expressed of the human RecQ helicases; however, a genetic disease has yet not been linked to mutations in the RECQ1 gene, and the biological functions of human RECQ1 in cellular DNA metabolism are not known. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we report that RECQ1 becomes phosphorylated upon DNA damage and forms irradiation-induced nuclear foci that associate with chromatin in human cells. Depletion of RECQ1 renders human cells sensitive to DNA damage induced by ionizing radiation or the topoisomerase inhibitor camptothecin, and results in spontaneous gamma-H2AX foci and elevated sister chromatid exchanges, indicating aberrant repair of DNA breaks. Consistent with a role in homologous recombinational repair, endogenous RECQ1 is associated with the strand exchange protein Rad51 and the two proteins directly interact with high affinity. CONCLUSION/SIGNIFICANCE: Collectively, these results provide the first evidence for a role of human RECQ1 in the response to DNA damage and chromosomal stability maintenance and point to the vital importance of RECQ1 in genome homeostasis.

  5. Diethylstilbestrol-diphosphate induces chromosomal aberrations but not sister chromatid exchanges in murine bone marrow cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Ivett, J.L. (North Carolina State Univ., Raleigh); Tice, R.R.

    1981-01-01

    Diethylstilbestrol diphosphate (DES-dp) clastogenesis was examined in the bone marrow of C57B1/6 male and female mice. Significant and sex-related dose effects were observed for the induction of chromatid-type chromosomal aberrations and for the inhibition of cellular proliferation. Females were more sensitive to the effects of DES-dp than males when assessed for either induced chromosomal aberrations or proliferative inhibition. Contrary to other published results, we did not observe either an increase in sister chromatid exchanges or an increased incidence of aneuploidy. Ovariectomy reduced the ability of DES-dp to inhibit cellular proliferation and decreased the high degree of variability between animals at high doses of DES-dp. The results of our studies show that DES is a clastogenic agent in vivo which may relate to its carcinogenicity.

  6. Rate of sister chromatid exchanges in Bloom syndrome fibroblasts reduced by co-cultivation with normal fibroblasts.

    OpenAIRE

    1980-01-01

    Six strains of Bloom syndrome (BlS) fibroblasts responded to co-cultivation with normal fibroblasts at a 1:2 ratio by a reduced rate of sister chromatid exchanges (SCE's) from a mean of 67.5 (range = 59--78) to 28.4 (range = 21--35). The response was dose-dependent in one strain tested at 1:2, 1:1, and 2:1 ratios. In addition, quadriradial exchange figures and other signs of increased chromosomal instability were not found in BlS cells following co-cultivation with control cells. Control cell...

  7. In Vitro genotoxic and antigenotoxic studies of Thai Noni fruit juice by chromosomal aberration and sister chromatid exchange assays in human lymphocytes

    Directory of Open Access Journals (Sweden)

    Treetip Ratanavalachai

    2008-09-01

    Full Text Available The genotoxic and antigenotoxic effects of Noni fruit juice produced in Thailand have been studied in human lymphocytes for chromosome aberration assay and sister chromatid exchange (SCE assay in vitro. Treatment of Noni fruit juice(3.1-50 mg/ml alone for 3 h did not significantly induce chromosomal aberration or SCE (p<0.05. Noni fruit juice at 6.2 mg/ml is the optimum dose for cell survival and cell replication as demonstrated by the highest value of mitotic index and proliferation index (P.I.. Interestingly, pretreatment of Noni fruit juice at the same concentration of 6.2 mg/ml for 2 hfollowed by mitomycin C treatment at 3 μg/ml for 2 h significantly reduced SCE level induced by mitomycin C (p<0.05. However, these treatments did not show significant decrease in chromatid-type aberrations. Our data indicate that Thai Noni fruit juice is not genotoxic against human lymphocytes in vitro. In addition, pretreatment of Noni fruit juice at 6.2 mg/ml demonstrated no anticlastogenic effect while had some antigenotoxic effects as demonstrated by significant decrease in the SCE level induced by mitomycin C (p<0.05. Therefore, the optimum dose of Noni fruit juice used as a traditional medicine is required and needs to be studied further for the benefit of human health.

  8. Variations in dysfunction of sister chromatid cohesion in esco2 mutant zebrafish reflect the phenotypic diversity of Roberts syndrome

    Directory of Open Access Journals (Sweden)

    Stefanie M. Percival

    2015-08-01

    Full Text Available Mutations in ESCO2, one of two establishment of cohesion factors necessary for proper sister chromatid cohesion (SCC, cause a spectrum of developmental defects in the autosomal-recessive disorder Roberts syndrome (RBS, warranting in vivo analysis of the consequence of cohesion dysfunction. Through a genetic screen in zebrafish targeting embryonic-lethal mutants that have increased genomic instability, we have identified an esco2 mutant zebrafish. Utilizing the natural transparency of zebrafish embryos, we have developed a novel technique to observe chromosome dynamics within a single cell during mitosis in a live vertebrate embryo. Within esco2 mutant embryos, we observed premature chromatid separation, a unique chromosome scattering, prolonged mitotic delay, and genomic instability in the form of anaphase bridges and micronuclei formation. Cytogenetic studies indicated complete chromatid separation and high levels of aneuploidy within mutant embryos. Amongst aneuploid spreads, we predominantly observed decreases in chromosome number, suggesting that either cells with micronuclei or micronuclei themselves are eliminated. We also demonstrated that the genomic instability leads to p53-dependent neural tube apoptosis. Surprisingly, although many cells required Esco2 to establish cohesion, 10-20% of cells had only weakened cohesion in the absence of Esco2, suggesting that compensatory cohesion mechanisms exist in these cells that undergo a normal mitotic division. These studies provide a unique in vivo vertebrate view of the mitotic defects and consequences of cohesion establishment loss, and they provide a compensation-based model to explain the RBS phenotypes.

  9. Variations in dysfunction of sister chromatid cohesion in esco2 mutant zebrafish reflect the phenotypic diversity of Roberts syndrome.

    Science.gov (United States)

    Percival, Stefanie M; Thomas, Holly R; Amsterdam, Adam; Carroll, Andrew J; Lees, Jacqueline A; Yost, H Joseph; Parant, John M

    2015-08-01

    Mutations in ESCO2, one of two establishment of cohesion factors necessary for proper sister chromatid cohesion (SCC), cause a spectrum of developmental defects in the autosomal-recessive disorder Roberts syndrome (RBS), warranting in vivo analysis of the consequence of cohesion dysfunction. Through a genetic screen in zebrafish targeting embryonic-lethal mutants that have increased genomic instability, we have identified an esco2 mutant zebrafish. Utilizing the natural transparency of zebrafish embryos, we have developed a novel technique to observe chromosome dynamics within a single cell during mitosis in a live vertebrate embryo. Within esco2 mutant embryos, we observed premature chromatid separation, a unique chromosome scattering, prolonged mitotic delay, and genomic instability in the form of anaphase bridges and micronuclei formation. Cytogenetic studies indicated complete chromatid separation and high levels of aneuploidy within mutant embryos. Amongst aneuploid spreads, we predominantly observed decreases in chromosome number, suggesting that either cells with micronuclei or micronuclei themselves are eliminated. We also demonstrated that the genomic instability leads to p53-dependent neural tube apoptosis. Surprisingly, although many cells required Esco2 to establish cohesion, 10-20% of cells had only weakened cohesion in the absence of Esco2, suggesting that compensatory cohesion mechanisms exist in these cells that undergo a normal mitotic division. These studies provide a unique in vivo vertebrate view of the mitotic defects and consequences of cohesion establishment loss, and they provide a compensation-based model to explain the RBS phenotypes.

  10. Unequal sister chromatid and homolog recombination at a tandem duplication of the A1 locus in maize.

    Science.gov (United States)

    Yandeau-Nelson, Marna D; Xia, Yiji; Li, Jin; Neuffer, M Gerald; Schnable, Patrick S

    2006-08-01

    Tandemly arrayed duplicate genes are prevalent. The maize A1-b haplotype is a tandem duplication that consists of the components, alpha and beta. The rate of meiotic unequal recombination at A1-b is ninefold higher when a homolog is present than when it is absent (i.e., hemizygote). When a sequence heterologous homolog is available, 94% of recombinants (264/281) are generated via recombination with the homolog rather than with the sister chromatid. In addition, 83% (220/264) of homolog recombination events involved alpha rather than beta. These results indicate that: (1) the homolog is the preferred template for unequal recombination and (2) pairing of the duplicated segments with the homolog does not occur randomly but instead favors a particular configuration. The choice of recombination template (i.e., homolog vs. sister chromatid) affects the distribution of recombination breakpoints within a1. Rates of unequal recombination at A1-b are similar to the rate of recombination between nonduplicated a1 alleles. Unequal recombination is therefore common and is likely to be responsible for the generation of genetic variability, even within inbred lines.

  11. Regulation of centromere localization of the Drosophila Shugoshin MEI-S332 and sister-chromatid cohesion in meiosis.

    Science.gov (United States)

    Nogueira, Cristina; Kashevsky, Helena; Pinto, Belinda; Clarke, Astrid; Orr-Weaver, Terry L

    2014-07-31

    The Shugoshin (Sgo) protein family helps to ensure proper chromosome segregation by protecting cohesion at the centromere by preventing cleavage of the cohesin complex. Some Sgo proteins also influence other aspects of kinetochore-microtubule attachments. Although many Sgo members require Aurora B kinase to localize to the centromere, factors controlling delocalization are poorly understood and diverse. Moreover, it is not clear how Sgo function is inactivated and whether this is distinct from delocalization. We investigated these questions in Drosophila melanogaster, an organism with superb chromosome cytology to monitor Sgo localization and quantitative assays to test its function in sister-chromatid segregation in meiosis. Previous research showed that in mitosis in cell culture, phosphorylation of the Drosophila Sgo, MEI-S332, by Aurora B promotes centromere localization, whereas Polo phosphorylation promotes delocalization. These studies also suggested that MEI-S332 can be inactivated independently of delocalization, a conclusion supported here by localization and function studies in meiosis. Phosphoresistant and phosphomimetic mutants for the Aurora B and Polo phosphorylation sites were examined for effects on MEI-S332 localization and chromosome segregation in meiosis. Strikingly, MEI-S332 with a phosphomimetic mutation in the Aurora B phosphorylation site prematurely dissociates from the centromeres in meiosis I. Despite the absence of MEI-S332 on meiosis II centromeres in male meiosis, sister chromatids segregate normally, demonstrating that detectable levels of this Sgo are not essential for chromosome congression, kinetochore biorientation, or spindle assembly. Copyright © 2014 Nogueira et al.

  12. Absence of an effect of lead acetate on sperm morphology, sister chromatid exchanges or on micronuclei formation in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Willems, M.I.; Immel, H.R.; de Schepper, G.G.; Dietrich, A.J.J.; Wibowo, A.A.E.; Zielhuis, R.L.

    1982-07-01

    The influence of lead on sperm morphology, sister chromatid exchanges or on micronuclei formation was studied on male rabbits after exposure to doses of 0, 0.25, and 0.50 mg lead acetate/kg body weight subcutaneously injected three times a week during 14 weeks, each on a group of five rabbits. At the end of exposure phase the lead in blood concentrations of the three groups of rabbits were 0.32, 2.57, and 2.97 ..mu..mol/l respectively. The results did not show any evidence of treatment related effects on sperm count or on morphologic abnormalities of the sperms, neither on the histopathology of the testis. Statistical analysis of the number of sister chromatid exchanges per metaphase in lymphocytes indicated no differences between the groups. Also no dose dependent effect was observed on the relative number of micronuclei in bone marrow erythrocytes. The different susceptibility to lead in different organ systems of the rabbits was discussed.

  13. Further characterization of the genotoxicity of formaldehyde in vitro by the sister chromatid exchange test and co-cultivation experiments.

    Science.gov (United States)

    Neuss, Simone; Speit, Günter

    2008-09-01

    The induction of sister chromatid exchanges (SCE) was used to further characterize the genotoxic action of formaldehyde (FA) on cultured mammalian cells. FA induced SCE in V79 Chinese hamster cells and A549 human lung cells in a concentration-related manner. Addition of 5-bromodeoxyuridine (BrdUrd) for the differentiation of sister chromatids to visualize SCE 4 h after the FA treatment led to a clearly reduced induction of SCE in agreement with the repair kinetics of FA-induced DNA-protein cross-links. When A549 cells were treated with FA for 1 h and then co-cultivated with V79 cells in the presence of BrdUrd, a clear induction of SCE was measured in V79 cells. When the same experiment was performed including washing and change of medium after the FA treatment, no induction of SCE was measured in V79 cells. These results indicate that reactive FA remains in the cell culture medium for a longer time period despite the high reactivity of FA with macromolecules. However, FA that has entered a cell is not released and does not damage other cells. Possible implications for the mutagenicity of FA in vivo will be discussed.

  14. Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family conserved from fision yeast to humans.

    NARCIS (Netherlands)

    S. Parisi; M.J. McKay (Michael); M. Molnar; M.A. Thompson (Anne); P.J. van der Spek (Peter); E. van Drunen-Schoenmaker; R. Kanaar (Roland); E. Lehmann; J.H.J. Hoeijmakers (Jan); J. Kohli

    1999-01-01

    textabstractOur work and that of others defined mitosis-specific (Rad21 subfamily) and meiosis-specific (Rec8 subfamily) proteins involved in sister chromatid cohesion in several eukaryotes, including humans. Mutation of the fission yeast Schizosaccharomyces pombe rec8 gene was previously shown to

  15. Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family conserved from fision yeast to humans.

    NARCIS (Netherlands)

    S. Parisi; M.J. McKay (Michael); M. Molnar; M.A. Thompson (Anne); P.J. van der Spek (Peter); E. van Drunen-Schoenmaker; R. Kanaar (Roland); E. Lehmann; J.H.J. Hoeijmakers (Jan); J. Kohli

    1999-01-01

    textabstractOur work and that of others defined mitosis-specific (Rad21 subfamily) and meiosis-specific (Rec8 subfamily) proteins involved in sister chromatid cohesion in several eukaryotes, including humans. Mutation of the fission yeast Schizosaccharomyces pombe rec8 gene was previously shown to c

  16. Frequencies of chromosomal aberrations and sister chromatid exchanges in the benthic worm Neanthes arenaceodentata exposed to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, F.L.; Rice, D.W. Jr., Moore, D.H.

    1984-07-01

    Traditional bioassays are unsuitable for assessing sublethal effects from ocean disposal of low-level radioactive waste because mortality and phenotypic responses are not anticipated. We compared the usefulness of chromosomal aberration and sister chromatid exchange (SCE) induction as measures of low-level radiation effects in a sediment-dwelling marine worm, Neanthes arenaceodentata. The SCEs, in contrast to chromosomal aberrations, do not alter the overall chromosome morphology and in mammalian cells appear to be a more sensitive indicator of DNA alterations caused by environmental mutagens. Newly hatched larvae were exposed to two radiation-exposure regimes of either x rays at a high dose rate of 0.7 Gy (70 rad)/min for as long as 5.5 min or to /sup 60/Co gamma rays at a low dose rate of from 4.8 x 10/sup -5/ to 1.2 x 10/sup -1/ Gy (0.0048 to 12 rad)/h for 24 h. After irradiation, the larvae were exposed to 3 x 10/sup -5/M bromodeoxyuridine (BrdUrd) for 28 h (x-ray-irradiated larvae) or for 54 h (/sup 60/Co-irradiated larvae). Larval cells were examined for the proportion of cells in first, second, and third or greater division. Frequencies of chromosomal aberrations and SCEs were determined in first and second division cells, respectively. Results from x-ray irradiation indicated that dose-related increases occur in chromosome and chromatid deletions, but a dose of equal or greater 2 Gy (equal to or greater than 200 rad) was required to observe a significant increase. Worm larvae receiving /sup 60/Co irradiation showed elevated SCE frequencies with a significant increase of 0.6 Gy (60 rad). We suggest that both SCEs and chromosomal aberrations may be useful for measuring effects on genetic material induced by radiation. 56 references, 7 figures, 9 tables.

  17. Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function.

    Science.gov (United States)

    de Lange, Job; Faramarz, Atiq; Oostra, Anneke B; de Menezes, Renee X; van der Meulen, Ida H; Rooimans, Martin A; Rockx, Davy A; Brakenhoff, Ruud H; van Beusechem, Victor W; King, Randall W; de Winter, Johan P; Wolthuis, Rob M F

    2015-10-01

    Warsaw breakage syndrome (WABS) is caused by defective DDX11, a DNA helicase that is essential for chromatid cohesion. Here, a paired genome-wide siRNA screen in patient-derived cell lines reveals that WABS cells do not tolerate partial depletion of individual APC/C subunits or the spindle checkpoint inhibitor p31(comet). A combination of reduced cohesion and impaired APC/C function also leads to fatal mitotic arrest in diploid RPE1 cells. Moreover, WABS cell lines, and several cancer cell lines with cohesion defects, display a highly increased response to a new cell-permeable APC/C inhibitor, apcin, but not to the spindle poison paclitaxel. Synthetic lethality of APC/C inhibition and cohesion defects strictly depends on a functional mitotic spindle checkpoint as well as on intact microtubule pulling forces. This indicates that the underlying mechanism involves cohesion fatigue in response to mitotic delay, leading to spindle checkpoint re-activation and lethal mitotic arrest. Our results point to APC/C inhibitors as promising therapeutic agents targeting cohesion-defective cancers.

  18. Chromosome segregation: Samurai separation of Siamese sisters.

    Science.gov (United States)

    Glotzer, M

    1999-07-15

    How do cells ensure that sister chromatids are precisely partitioned in mitosis? New studies on budding yeast have revealed that sister chromatid separation at anaphase requires endoproteolytic cleavage of a protein that maintains the association between sister chromatids.

  19. Effects of chronic exposure to 2, 3, 7, 8,-tetrachlorodibenzo-p-dioxin on sister chromatid exchange levels in peripheral lymphocytes of the rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Lim, M.; Jacobson-Kram, D.; Bowman, R.E.; Williams, J.R.

    1987-01-01

    Frequencies of sister chromatid exchanges and chromosomal aberrations were examined in peripheral lymphocytes of Rhesus monkeys that had been fed a diet containing 25 parts per trillion 2,3,7,8-tetrachlorodibenzo-p-dioxin for a period of 4 years. When compared to non-exposed control animals, no significant differences were noted for either of these cytogenetic end points. In addition, there was not a significant difference in sister chromatid exchange response to a challenge dose of mitomycin C in cells from 2,3,7,8-tetrachlorodibenzo-p-dioxin exposed animals compared to controls. The results confirm the lack of genotoxic effects associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

  20. Protection of halogenated DNA from strand breakage and sister-chromatid exchange induced by the topoisomerase I inhibitor camptothecin

    Energy Technology Data Exchange (ETDEWEB)

    Orta, Manuel Luis; Mateos, Santiago; Cantero, Gloria [Department of Cell Biology, Faculty of Biology, University of Seville (Spain); Wolff, Lisa J. [Sweet Briar College, VA (United States); Cortes, Felipe [Department of Cell Biology, Faculty of Biology, University of Seville (Spain)], E-mail: cortes@us.es

    2008-01-01

    The fundamental nuclear enzyme DNA topoisomerase I (topo I), cleaves the double-stranded DNA molecule at preferred sequences within its recognition/binding sites. We have recently reported that when cells incorporate halogenated nucleosides analogues of thymidine into DNA, it interferes with normal chromosome segregation, as shown by an extraordinarily high yield of endoreduplication, and results in a protection against DNA breakage induced by the topo II poison m-AMSA [F. Cortes, N. Pastor, S. Mateos, I. Dominguez, The nature of DNA plays a role in chromosome segregation: endoreduplication in halogen-substituted chromosomes, DNA Repair 2 (2003) 719-726; G. Cantero, S. Mateos, N. Pastor; F. Cortes, Halogen substitution of DNA protects from poisoning of topoisomerase II that results in DNA double-strand breaks (DSBs), DNA Repair 5 (2006) 667-674]. In the present investigation, we have assessed whether the presence of halogenated nucleosides in DNA diminishes the frequency of interaction of topo I with DNA and thus the frequency with which the stabilisation of cleavage complexes by the topo I poison camptothecin (CPT) takes place, in such a way that it protects from chromosome breakage and sister-chromatid exchange. This protective effect is shown to parallel a loss in halogen-substituted cells of the otherwise CPT-increased catalytic activity bound to DNA.

  1. Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins.

    Directory of Open Access Journals (Sweden)

    Cheri A Schaaf

    Full Text Available The cohesin protein complex was first recognized for holding sister chromatids together and ensuring proper chromosome segregation. Cohesin also regulates gene expression, but the mechanisms are unknown. Cohesin associates preferentially with active genes, and is generally absent from regions in which histone H3 is methylated by the Enhancer of zeste [E(z] Polycomb group silencing protein. Here we show that transcription is hypersensitive to cohesin levels in two exceptional cases where cohesin and the E(z-mediated histone methylation simultaneously coat the entire Enhancer of split and invected-engrailed gene complexes in cells derived from Drosophila central nervous system. These gene complexes are modestly transcribed, and produce seven of the twelve transcripts that increase the most with cohesin knockdown genome-wide. Cohesin mutations alter eye development in the same manner as increased Enhancer of split activity, suggesting that similar regulation occurs in vivo. We propose that cohesin helps restrain transcription of these gene complexes, and that deregulation of similarly cohesin-hypersensitive genes may underlie developmental deficits in Cornelia de Lange syndrome.

  2. Analysis of spontaneous and streptonigrin-induced sister chromatid exchanges in peripheral lymphocytes of aircrew members of international flights.

    Science.gov (United States)

    Sánchez, Julieta; Bianchi, Martha Susana; Ciancio, Vicente Rubén; Bolzán, Alejandro Daniel

    2008-01-01

    In this work, we extend our previous studies concerning mutagen sensitivity in flight personnel from commercial airlines by analyzing the frequency of spontaneous and streptonigrin (SN)-induced sister chromatid exchanges (SCEs) in peripheral blood lymphocytes of 18 long-haul aircrew members from Argentina and of 18 control individuals. Statistical analysis revealed no significant differences between aircrew and controls in the background level of SCEs (p > 0.05), which suggests that chronic exposure to cosmic radiation and other occupational hazards does not affect SCEs frequency in peripheral lymphocytes of aircrews. The fact that almost no correlation was found between cumulative flight hours and the yield of spontaneous SCEs in aircrews adds further support to this assumption. Therefore, the background SCEs frequency cannot be use as a valid biomarker to determine the genotoxic effects of cosmic radiation or other occupational hazards exposure in aircrews. Following SN treatment, a significant increase in the mean frequency of SCEs was observed in the control group (p aircrew group (p > 0.05), suggesting that at the population level, aircrew are more resistant to the mutagenic effects of SN than controls. The reasons of this resistance remain to be determined. Since cosmic radiation had no effect on the background SCEs frequency and no relationship was found between cumulative flight hours and SCEs inducer effect by SN in aircrews, a direct effect of cosmic radiation on SN resistance should be discarded.

  3. SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs.

    Science.gov (United States)

    van der Lelij, Petra; Stocsits, Roman R; Ladurner, Rene; Petzold, Georg; Kreidl, Emanuel; Koch, Birgit; Schmitz, Julia; Neumann, Beate; Ellenberg, Jan; Peters, Jan-Michael

    2014-11-18

    Although splicing is essential for the expression of most eukaryotic genes, inactivation of splicing factors causes specific defects in mitosis. The molecular cause of this defect is unknown. Here, we show that the spliceosome subunits SNW1 and PRPF8 are essential for sister chromatid cohesion in human cells. A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein sororin and the APC/C subunit APC2. SNW1 depletion causes cohesion defects predominantly by reducing sororin levels, which causes destabilisation of cohesin on DNA. SNW1 depletion also reduces APC/C activity and contributes to cohesion defects indirectly by delaying mitosis and causing "cohesion fatigue". Simultaneous expression of sororin and APC2 from intron-less cDNAs restores cohesion in SNW1-depleted cells. These results indicate that the spliceosome is required for mitosis because it enables expression of genes essential for cohesion. Our transcriptome-wide identification of retained introns in SNW1- and PRPF8-depleted cells may help to understand the aetiology of diseases associated with splicing defects, such as retinosa pigmentosum and cancer.

  4. Influence of retinol on carcinogen-induced sister chromatid exchangers and chromosome aberrations in V79 cells

    Energy Technology Data Exchange (ETDEWEB)

    Qin, S.; Batt, T.; Huang, C.C.

    1985-01-01

    The influence of retinol (Rol) on sister chromatid exchangers (SCE) in V79 cells induced by six indirect and two direct carcinogens, and on chromosome aberration (CA) in V79 cells induced by four indirect carcinogens were studied. The indirect carcinogens used were aflatoxin B/sub 1/ (AFB), cyclophosphamide (CPP), benzo(a)anthracene (BA), benzo(a)pyrene (BP), 9,10-dimethyl-1,2-benz(a)anthracene (DMBA), and 3-methylcholanthrene (MCA). The two direct carcinogens were ethyl methane sulfonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rol effectively inhibited SCE and CA induced by AFB and CPP in a dose-dependent manner, but it had no effect on SCE induced by BA, BP, DMBA, MCA, EMS, and MNNG. To the contrary, Rol had an enhancing effect on CA induced by BP and DMBA. The possibility that Rol exerts its anticarcinogenic effects by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of precarcinogens, such as AFB and CPP but not those enzymes required by BA, BP, DMBA, and MCA, is discussed.

  5. The Elg1 Clamp Loader Plays a Role in Sister Chromatid Cohesion

    OpenAIRE

    Oren Parnas; Adi Zipin-Roitman; Yuval Mazor; Batia Liefshitz; Shay Ben-Aroya; Martin Kupiec

    2009-01-01

    Mutations in the ELG1 gene of yeast lead to genomic instability, manifested in high levels of genetic recombination, chromosome loss, and gross chromosomal rearrangements. Elg1 shows similarity to the large subunit of the Replication Factor C clamp loader, and forms a RFC-like (RLC) complex in conjunction with the 4 small RFC subunits. Two additional RLCs exist in yeast: in one of them the large subunit is Ctf18, and in the other, Rad24. Ctf18 has been characterized as the RLC that functions ...

  6. Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Nagasawa, H; Wilson, P F; Chen, D J; Thompson, L H; Bedford, J S; Little, J B

    2007-10-26

    We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells (Nagasawa et al., Radiat. Res. 164, 141-147, 2005). In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23-0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after {alpha}-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.

  7. Effect of aging on superovulation efficiency, aneuploidy rates, and sister chromatid cohesion in mice aged up to 15 months.

    Science.gov (United States)

    Merriman, Julie A; Jennings, Phoebe C; McLaughlin, Eileen A; Jones, Keith T

    2012-02-01

    Human eggs are highly aneuploid, with female age being the only known risk factor. Here this aging phenomenon was further studied in Swiss CD1 mice aged between 1 and 15 mo. The mean number of eggs ± SEM recovered from mice following superovulation peaked at 22.5 ± 3.8 eggs/oviduct in 3-mo-old females, decreasing markedly between 6 and 9 mo old, and was only 2.1 ± 0.2 eggs/oviduct by 15 mo. Measurement of aneuploidy in these eggs revealed a low rate, ∼3-4%, in mice aged 1 and 3 mo, rising to 12.5% by 9 mo old and to 37.5% at 12 mo. Fifteen-month-old mice had the highest rate of aneuploidy, peaking at 60%. The in situ chromosome counting technique used here allowed us to measure with accuracy the distance between the kinetochores in the sister chromatids of the eggs analyzed for aneuploidy. We observed that this distance increased in eggs from older females, from 0.38 ± 0.01 μm at 1 mo old to 0.82 ± 0.03 μm by 15 mo. Furthermore, in 3- to 12-mo-old females, aneuploid eggs had significantly larger interkinetochore distances than euploid eggs from the same age, and measurements were similar to eggs from the oldest mice. However, the association between aneuploidy and interkinetochore distance was not observed at the oldest, 15-mo age, despite such measurements being maximal. We conclude that in aging CD1 mice, a reduction in the ovulated egg number precedes a rise in aneuploidy and, furthermore, except at very advanced ages, increased interkinetochore distance is associated with aneuploidy.

  8. A novel frameshift mutation in BLM gene associated with high sister chromatid exchanges (SCE) in heterozygous family members.

    Science.gov (United States)

    Ben Salah, Ghada; Hadj Salem, Ikhlas; Masmoudi, Abderrahmen; Kallabi, Fakhri; Turki, Hamida; Fakhfakh, Faiza; Ayadi, Hamadi; Kamoun, Hassen

    2014-11-01

    The Bloom syndrome (BS) is an autosomic recessive disorder comprising a wide range of abnormalities, including stunted growth, immunodeficiency, sun sensitivity and increased frequency of various types of cancer. Bloom syndrome cells display a high level of genetic instability, including a 10-fold increase in the sister chromatid exchanges (SCE) level. Bloom syndrome arises through mutations in both alleles of the BLM gene, which was identified as a member of the RecQ helicase family. In this study, we screened a Tunisian family with three BS patients. Cytogenetic analysis showed several chromosomal aberrations, and an approximately 14-fold elevated SCE frequency in BS cells. A significant increase in SCE frequency was observed in some family members but not reaching the BS patients values, leading to suggest that this could be due to the heterozygous profile. Microsatellite genotyping using four fluorescent dye-labeled microsatellite markers revealed evidence of linkage to BLM locus and the healthy members, sharing higher SCE frequency, showed heterozygous haplotypes as expected. Additionally, the direct BLM gene sequencing identified a novel homozygous frameshift mutation c.3617-3619delAA (p.K1207fsX9) in BS patients and a heterozygous BLM mutation in the family members with higher SCE frequency. Our findings suggest that this latter mutation likely leads to a reduced BLM activity explaining the homologous recombination repair defect and, therefore, the increase in SCE. Based on the present data, the screening of this mutation could contribute to the rapid diagnosis of BS. The genetic confirmation of the mutation in BLM gene provides crucial information for genetic counseling and prenatal diagnosis.

  9. Intersection between the regulators of sister chromatid cohesion establishment and maintenance in budding yeast indicates a multi-step mechanism.

    Science.gov (United States)

    Noble, Daniel; Kenna, Margaret A; Dix, Melissa; Skibbens, Robert V; Unal, Elçin; Guacci, Vincent

    2006-11-01

    Sister chromatid cohesion is established during S phase and maintained until anaphase. The cohesin complex (Mcd1p/Scc1p, Smc1p, Smc3p Irr1p/Scc3p in budding yeast) serves a structural role as it is required at all times when cohesion exists. Pds5p colocalizes temporally and spatially with cohesin on chromosomes but is thought to serve as a regulator of cohesion maintenance during mitosis. In contrast, Ctf7p/Eco1p is required during S phase for establishment but is not required during mitosis. Here we provide genetic and biochemical evidence that the pathways of cohesion establishment and maintenance are intimately linked. Our results show that mutants in ctf7 and pds5 are synthetically lethal. Moreover, over-expression of either CTF7 or PDS5 exhibits reciprocal suppression of the other mutant's temperature sensitivity. The suppression by CTF7 is specific for pds5 mutants as CTF7 over-expression increases the temperature sensitivity of an mcd1 mutant but has no effect on smc1 or smc3 mutants. Three additional findings provide new insights into the process of cohesion establishment. First, over-expression of ctf7 alleles deficient in acetylase activity exhibit significantly reduced suppression of the pds5 mutant but exacerbated toxicity to the mcd1 mutant. Second, using chromosome spreads and chromatin immuno-precipitation, we find either cohesin complex or Pds5p chromosomal localization is altered in ctf7 mutants. Finally, biochemical analysis reveals that Ctf7p and Pds5p coimmunoprecipitate, which physically links these regulators of cohesion establishment and maintenance. We propose a model whereby Ctf7p and Pds5p cooperate to facilitate efficient establishment by mediating changes in cohesin complex on chromosomes after its deposition.

  10. Mutagenicity in Salmonella and sister chromatid exchange in mice for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrenes.

    Science.gov (United States)

    Sinsheimer, J E; Giri, A K; Hooberman, B H; Jung, K Y; Gopalaswamy, R; Koreeda, M

    1991-01-01

    The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of mice was determined for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrene (DMPh) with the objective to study the relative importance of substitution at the 1 and 4 positions of this series of methylated phenanthrenes. For both tests, 1,4- DMPh was decidedly more genotoxic than the remaining regioisomers. While the well recognized role of steric crowding in the bay region is a factor in this enhanced genotoxicity, equally important is substitution at the 1 position with its potential to inhibit detoxication through 9,10-diol formation.

  11. Mutagenicity in Salmonella and sister chromatid exchange in mice for 1,4-, and 1,3-, 2,4-, and 3,4-dimethylphenanthrenes

    Energy Technology Data Exchange (ETDEWEB)

    Sinsheimer, J.E.; Giri, A.K.; Hooberman, B.H.; Jung, K.Y.; Gopalaswamy, R.; Koreeda, M. (Univ. of Michigan, Ann Arbor (United States))

    1991-01-01

    The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of mice was determined for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrene (DMPh) with the objective to study the relative importance of substitution at the 1 and 4 positions of this series of methylated phenanthrenes. For both tests, 1,4-DMPh was decidedly more genotoxic than the remaining regioisomers. While the well recognized role of steric crowding in the bay region is a factor in this enhanced genotoxicity, equally important is substitution at the 1 position with its potential to inhibit detoxication through 9,10-diol formation.

  12. Increased sister chromatid cohesion and DNA damage response factor localization at an enzyme-induced DNA double-strand break in vertebrate cells.

    LENUS (Irish Health Repository)

    Dodson, Helen

    2009-10-01

    The response to DNA damage in vertebrate cells involves successive recruitment of DNA signalling and repair factors. We used light microscopy to monitor the genetic dependencies of such localization to a single, induced DNA double strand break (DSB) in vertebrate cells. We used an inducible version of the rare-cutting I-SceI endonuclease to cut a chromosomally integrated I-SceI site beside a Tet operator array that was visualized by binding a Tet repressor-GFP fusion. Formation of gamma-H2AX foci at a single DSB was independent of ATM or Ku70. ATM-deficient cells showed normal kinetics of 53Bp1 recruitment to DSBs, but Rad51 localization was retarded. 53Bp1 and Rad51 foci formation at a single DSB was greatly reduced in H2AX-null DT40 cells. We also observed decreased inter-sister chromatid distances after DSB induction, suggesting that cohesin loading at DSBs causes elevated sister chromatid cohesion. Loss of ATM reduced DSB-induced cohesion, consistent with cohesin being an ATM target in the DSB response. These data show that the same genetic pathways control how cells respond to single DSBs and to multiple lesions induced by whole-cell DNA damage.

  13. In vitro Antigenotoxicity of Ulva rigida C.Agardh (Chlorophyceae) Extract against Induction of Chromosome Aberration,Sister Chromatid Exchange and Micronuclei by Mutagenic Agent MMC

    Institute of Scientific and Technical Information of China (English)

    SERAP CELIKLER; GAMZE YILDIZ; OZGUR VATAN; RAHMI BILALOGLU

    2008-01-01

    To determine the in vitro possible clastogenic and cytotoxic activities of Uh,a rigida crude extracts (UP,E),and identify their antigenotoxic and protective effects on chemotherapeutic agent mitomycine-C (MMC).Methods Anti-clastogenic and anti-genotoxic activities of Ulva rigida crude extracts (URE) were studied using chromosome aberration (CA),sister chromatid exchange (SCE),and micronuclei (MN) tests in human lymphocytes cultured in vitro.Results The chromosome aberration,sister chromatid exchange or micronuclei tests showed that URE at concentrations of 10,20,and 40 μg/mL had no clastogenic activity in human lymphocyte cell culture.Three doses of URE significantly decreased the number of chromosomal aberrations and the frequencies of SCE and MN when compared with the culture treated with MMC (P<0.0001).Conclusion Although URE itself is not a clastogenic or cytotoxic substance,it possesses strong antigenotoxic,anti-clastogenic,and protective effects on MMC in vitro.

  14. Genotoxic biomonitoring study of population residing in pesticide contaminated regions in Göksu Delta: micronucleus, chromosomal aberrations and sister chromatid exchanges.

    Science.gov (United States)

    Ergene, Serap; Celik, Ayla; Cavaş, Tolga; Kaya, Filiz

    2007-10-01

    Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless, exposure to pesticides represents a potential risk to humans. This paper describes a study of possible genetic damage in the people living in regions contaminated with complex mixture of pesticides in Göksu Delta. In this study, used methods were chromosomal aberration (CA), sister chromatid exchange analysis (SCE) in the peripheral blood lymphocytes, and micronucleus (MN) assay in the buccal epithelial cells. In the present investigation, 32 affected subjects consist of 16 smoking and 16 non-smokings and an equal number of control subjects were assessed for genome damage. Micronucleus (MN), Broken egg (BE), Karyorrhexis (KR), Karyolysis (KL) and Binucleus (BN) frequencies were higher in affected subjects than in controls. Smoking had a statistically significant effect on the Micronucleus, Karyorrhexis and Binucleus frequencies for both the control and the exposed group. Also smoking and exposure affected the frequency of sister chromatid exchange and chromosomal aberrations compared with control groups.

  15. Psoralen/UVA treatment and chromosomes. I. Aberrations and sister chromatid exchange in human lymphocytes in vitro and synergism with caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Waksvik, H.; Brogger, A.; Stene, J.

    1977-09-22

    Treatment of human lymphocytes in vitro with trimethylpsoralen or 8-methoxypsoralen and UVA irradiation (PUVA) induced chromosome damage, mainly constrictions and gaps, but also breaks and exchanges, and increased the frequency of sister chromatid exchange (SCE). The localization of the chromosome aberrations was nonrandom. The coincidence of many PUVA hits with mercaptoenthanol hits suggests that PUVA may have other targets in the cell than the DNA, perhaps the folding proteins of the chromosomes and the nuclear membrane/chromatin attachment organelles. Caffeine increased in a synergistic way the chromosome aberration yield if added after PUVA treatment, but there was no effect when caffeine was present before and during PUVA treatment. The SCE frequency was increased in the presence of caffeine.

  16. INVESTIGATION OF DNA REPAIR BY SISTER CHROMATID EXCHANGE (SCE) ANALYSIS AND THE ALKALINE SINGLE CELL GEL ASSAY (SCG) IN MAMMALIAN GO-LYMPHOCYTES AFTER IN VITRO EXPOSURE TO ETHYLENE OXIDE (EO)

    Science.gov (United States)

    Investigation ofDNA Repair by Sister Chromatid Exchange (SCE) Analysis and the Alkaline Single Cell Gel Assay (SCG) in Mammalian Go-Lymphocytes after In Vitro Exposure to Ethylene Oxide (EO). EO is a large volume chemical used primarily as an intermediate in manufacturing...

  17. Enhanced stimulation of chromosomal translocations and sister chromatid exchanges by either HO-induced double-strand breaks or ionizing radiation in Saccharomyces cerevisiae yku70 mutants

    Energy Technology Data Exchange (ETDEWEB)

    Fasullo, Michael [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States)]. E-mail: mfasullo@ordwayresearch.org; St Amour, Courtney [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States); Zeng Li [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States)

    2005-10-15

    DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both MAT a and MAT{alpha} inhibits NHEJ and facilitates DSB-initiated HR. We previously observed that DSB-initiated recombination between two his3 fragments, his3-{delta}5' and his3-{delta}3'::HOcs is enhanced in haploids and diploids expressing both MAT a and MAT{alpha} genes, regardless of the position or orientation of the his3 fragments. Herein, we measured frequencies of DNA damage-associated translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants, defective in NHEJ. Translocation and SCE frequencies were measured in strains containing the same his3 fragments after DSBs were made directly at trp1::his3-{delta}3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4-nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated translocations were five-fold higher in yku70 mutants compared to wild type; however, frequencies of phleomycin-associated translocations were lower in the yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated sequences on non-homologous chromosomes and sister chromatids occurs at higher frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage-associated HR in yku70 mutants depend on the DNA damaging agent.

  18. Drosophila TDP-43 RNA-Binding Protein Facilitates Association of Sister Chromatid Cohesion Proteins with Genes, Enhancers and Polycomb Response Elements.

    Directory of Open Access Journals (Sweden)

    Amanda Swain

    2016-09-01

    Full Text Available The cohesin protein complex mediates sister chromatid cohesion and participates in transcriptional control of genes that regulate growth and development. Substantial reduction of cohesin activity alters transcription of many genes without disrupting chromosome segregation. Drosophila Nipped-B protein loads cohesin onto chromosomes, and together Nipped-B and cohesin occupy essentially all active transcriptional enhancers and a large fraction of active genes. It is unknown why some active genes bind high levels of cohesin and some do not. Here we show that the TBPH and Lark RNA-binding proteins influence association of Nipped-B and cohesin with genes and gene regulatory sequences. In vitro, TBPH and Lark proteins specifically bind RNAs produced by genes occupied by Nipped-B and cohesin. By genomic chromatin immunoprecipitation these RNA-binding proteins also bind to chromosomes at cohesin-binding genes, enhancers, and Polycomb response elements (PREs. RNAi depletion reveals that TBPH facilitates association of Nipped-B and cohesin with genes and regulatory sequences. Lark reduces binding of Nipped-B and cohesin at many promoters and aids their association with several large enhancers. Conversely, Nipped-B facilitates TBPH and Lark association with genes and regulatory sequences, and interacts with TBPH and Lark in affinity chromatography and immunoprecipitation experiments. Blocking transcription does not ablate binding of Nipped-B and the RNA-binding proteins to chromosomes, indicating transcription is not required to maintain binding once established. These findings demonstrate that RNA-binding proteins help govern association of sister chromatid cohesion proteins with genes and enhancers.

  19. Holocentric plant meiosis: first sisters, then homologues.

    Science.gov (United States)

    Heckmann, Stefan; Schubert, Veit; Houben, Andreas

    2014-01-01

    Meiosis is a crucial process of sexual reproduction by forming haploid gametes from diploid precursor cells. It involves 2 subsequent divisions (meiosis I and meiosis II) after one initial round of DNA replication. Homologous monocentric chromosomes are separated during the first and sister chromatids during the second meiotic division. The faithful segregation of monocentric chromosomes is realized by mono-orientation of fused sister kinetochores at metaphase I and by bi-orientation of sister kinetochores at metaphase II. Conventionally this depends on a 2-step loss of cohesion, along chromosome arms during meiosis I and at sister centromeres during meiosis II.

  20. Chromosomal aberrations, sister-chromatid exchanges, cells with high frequency of SCE, micronuclei and comet assay parameters in 1, 3-butadiene-exposed workers.

    Science.gov (United States)

    Srám, R J; Rössner, P; Peltonen, K; Podrazilová, K; Mracková, G; Demopoulos, N A; Stephanou, G; Vlachodimitropoulos, D; Darroudi, F; Tates, A D

    1998-11-09

    The association of occupational exposure to 1,3-butadiene (BD) and induction of cytogenetic damage in peripheral lymphocytes was studied in 19 male workers from a monomer production unit and 19 control subjects from a heat production unit. The exposure to BD was measured by passive personal monitors. The following biomarkers were used: chromosomal aberrations (CA), sister chromatid exchanges (SCE), cells with a high frequency of SCE (HFC), micronuclei, comet assay parameters like tail length (TL) and percentage of DNA in tail [T (%)] and polymorphisms of GSTM1 and GSTT1 genotypes. BD exposure with a median value of 0.53 mg/m3 (range: 0.024-23.0) significantly increased (a) the percentage of cells with chromosomal aberrations in exposed vs. control groups (3.11% vs. 2.03%, P<0.01), (b) the frequency of SCE per cell (6.96 vs. 4.87, P<0.001), and (c) the percentage of HFC (19.9% vs. 4.1%, P<0.001). BD exposure had no significant effects on formation of micronuclei and on comet assay parameters. Effect of smoking was observed only for HFC in BD-exposed group. GSTM1 genotype affected chromosomal aberrations in exposed group, while GSTT1 genotype affected chromosomal aberrations in controls. No effect of GSTM1 or GSTT1 genotypes was observed on any other biomarkers used.

  1. Promutagen activation of triazine herbicides metribuzin and ametryn through Vicia faba metabolism inducing sister chromatid exchanges in human lymphocytes in vitro and in V. faba root tip meristems.

    Science.gov (United States)

    Flores-Maya, Saúl; Gómez-Arroyo, Sandra; Calderón-Segura, María Elena; Villalobos-Pietrini, Rafael; Waliszewski, Stefan M; de la Cruz, Leticia Gómez

    2005-03-01

    The aim of our study was the induction of sister chromatid exchanges (SCE) in human lymphocytes in vitro and in root tip meristems of Vicia faba to evaluate the genotoxic effects of metribuzin and ametryn. Direct treatments of these herbicides on human lymphocytes in vitro applied 24 h after the beginning of culture did not induce SCE; however, they showed a cytotoxic effect in the cultures expressed as cellular death. On the contrary, when extracts of V. faba roots, treated for 4 h with metribuzin and ametryn (in vivo activation), were added to the lymphocyte cultures, SCEs were significantly induced with an asymptotic response. Negative responses appeared with the in vitro assays, in which metribuzin and ametryn were added directly to the 48 h lymphocyte cultures for 4 h. Nevertheless, in treatments in which the S10 metabolic mix was added, the SCE frequencies were significantly different to the control, although a concentration-response relationship was only observed with metribuzin. The results showed that both herbicides needed the V. faba metabolism to produce SCE in human lymphocyte cultures. Metribuzin and ametryn applied to V. faba root tip meristems for 4 h increased SCE frequency significantly, and a concentration-response relationship was observed with both herbicides.

  2. Sister kinetochores are mechanically fused during meiosis I in yeast.

    Science.gov (United States)

    Sarangapani, Krishna K; Duro, Eris; Deng, Yi; Alves, Flavia de Lima; Ye, Qiaozhen; Opoku, Kwaku N; Ceto, Steven; Rappsilber, Juri; Corbett, Kevin D; Biggins, Sue; Marston, Adèle L; Asbury, Charles L

    2014-10-10

    Production of healthy gametes requires a reductional meiosis I division in which replicated sister chromatids comigrate, rather than separate as in mitosis or meiosis II. Fusion of sister kinetochores during meiosis I may underlie sister chromatid comigration in diverse organisms, but direct evidence for such fusion has been lacking. We used laser trapping and quantitative fluorescence microscopy to study native kinetochore particles isolated from yeast. Meiosis I kinetochores formed stronger attachments and carried more microtubule-binding elements than kinetochores isolated from cells in mitosis or meiosis II. The meiosis I-specific monopolin complex was both necessary and sufficient to drive these modifications. Thus, kinetochore fusion directs sister chromatid comigration, a conserved feature of meiosis that is fundamental to Mendelian inheritance. Copyright © 2014, American Association for the Advancement of Science.

  3. Induction of micronuclei and sister chromatid exchange in bone-marrow cells and abnormalities in sperm of Algerian mice (Mus spretus) exposed to cadmium, lead and zinc.

    Science.gov (United States)

    Tapisso, Joaquim Torres; Marques, Carla Cristina; Mathias, Maria da Luz; Ramalhinho, Maria da Graça

    2009-08-01

    As a consequence of human activities, large amounts of cadmium, lead and zinc are released in the environment, often simultaneously. The aim of this study was to investigate under experimental conditions the DNA damage induced in Algerian mice (Mus spretus) exposed to cadmium (Cd), lead (Pb) and zinc (Zn) separately, or in selected combinations. Three cytogenetic end points were considered: the frequencies of micronucleated cells (MN) and sister chromatid exchange (SCE) in the bone marrow and the frequency of sperm abnormalities. Mice were treated by intraperitoneal (i.p.) injections with 5 or 10 doses of aqueous solutions of cadmium acetate, lead acetate and zinc acetate in concentrations corresponding to 1/10 of the LD50, respectively, 21.5, 0.46 and 1.5 mg/kg bw. The control groups were injected in the same way with distilled water. With only one exception (Cd + Zn group treated with 5 doses), the results show a significant increase of MN in all groups for both treatments (5 and 10 doses). Similarly, the results concerning the SCE revealed a statistically significant increase in all treated animals, with the exception of the Zn group treated with 5 doses. The number of sperm abnormalities was significantly higher in animals treated with 5 doses, except in the group Pb + Zn. In animals treated with 10 doses the number of sperm abnormalities was always statistically higher compared with controls. This study indicates that cadmium, lead and zinc can induce MN, SCEs and sperm abnormalities in Algerian mice and that the clastogenic potential is dependent on the time of exposure and the interaction between the three elements, confirming the environmental damage that may result from the simultaneous action of several metals. Most relevant is the toxic potential for Zn, related with the dose, which may compromise its protective effect against other metal contaminations, such as cadmium.

  4. Genotoxic effects of a particular mixture of acetamiprid and alpha-cypermethrin on chromosome aberration, sister chromatid exchange, and micronucleus formation in human peripheral blood lymphocytes.

    Science.gov (United States)

    Kocaman, Ayşe Yavuz; Topaktaş, Mehmet

    2010-04-01

    The genotoxic effects of a particular mixture of acetamiprid (Acm, neonicotinoid insecticide) and alpha-cypermethrin (alpha-cyp, pyrethroid insecticide) on human peripheral lymphocytes were examined in vitro by chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronucleus (MN) tests. The human peripheral lymphocytes were treated with 12.5 + 2.5, 15 + 5, 17.5 + 7.5, and 20 + 10 microg/mL of Acm+alpha-cyp, respectively, for 24 and 48 h. The mixture of Acm+alpha-cyp induced the CAs and SCEs at all concentrations and treatment times when compared with both the control and solvent control and these increases were concentration-dependent in both treatment times. MN formation was significantly induced at 12.5 + 2.5, 15 + 5, 17.5 + 7.5, microg/mL of Acm+alpha-cyp when compared with both controls although these increases were not concentration-dependent. Binuclear cells could not be detected sufficiently in the highest concentration of the mixture (20 + 10 microg/mL) for both the 24- and 48-h treatment times. Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) significantly decreased because of the cytotoxic and cytostatic effects of the mixture, at all concentrations for two treatment periods. Significant decreases in MI and PI were concentration dependent at both treatment times. The decrease in NDI was also concentration-dependent at 48-h treatment period. In general, Acm+alpha-cyp inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC. Furthermore, in this article, the results of combined effects of Acm+alpha-cyp were compared with the results of single effects of Acm or alpha-cyp (Kocaman and Topaktas,2007,2009, respectively). In conclusion, the particular mixture of Acm+alpha-cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes.

  5. Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1,650 subjects in an Italian population: II. Contribution of sex, age, and lifestyle.

    Science.gov (United States)

    Barale, R; Chelotti, L; Davini, T; Del Ry, S; Andreassi, M G; Ballardin, M; Bulleri, M; He, J; Baldacci, S; Di Pede, F; Gemignani, F; Landi, S

    1998-01-01

    Sister chromatid exchange (SCE) and micronuclei (MN) analysis was carried out on 1,650 healthy individuals living in Pisa and in two nearby small cities, Cascina and Navacchio (Ca-Na). The effect of smoking on SCEs was linearly correlated with the number of cigarettes per day, and an increase of 7.3% SCEs was detectable for as few cigarettes as 1-10/day. Ex-smokers showed intermediate mean values of SCEs (8.09 +/- 1.88) in comparison with never smokers (7.54 +/- 1.61) and current smokers (8.45 +/- 1.94). Mean values of SCEs of ex-smokers decreased linearly with time of smoking cessation, reaching the mean values of never smokers within 8 years. The extent of SCE decrease was inversely proportional to the number of cigarettes previously smoked. No interaction between smoking habits and coffee or alcohol drinking on SCEs was observed. A borderline (P = 0.053) increase in mean SCE values in coffee drinkers (more than 3 cups/day) was found. The age effect on SCEs was remarkable in Ca-Na, but not in Pisa donors. Job type was not associated with significant modification of mean values of SCEs. Multiple logistic regression analysis revealed a statistically significant association between the proportion of high frequency cells (HCF) outliers and coffee consumption. Age and sex appeared to be by far the most important variables associated with modifications in MN frequency, which increased by 0.04 per thousand and 0.02 per thousand per year in males and females, respectively. Children and young donors (age students (+0.71 and +0.55 per thousand, respectively). Smoking did not determine any increase of MN frequency. A total lack of correlation (P = 0.913) between MN and SCEs was observed.

  6. Susceptibility to induction of chromosomal damage by metabolites of 1,3-butadiene and its relationship to 'spontaneous' sister chromatid exchange frequencies in human lymphocytes.

    Science.gov (United States)

    Wiencke, J K; Kelsey, K T

    1993-01-01

    Occupational exposure to butadiene is associated with the occurrence of lymphohaematopoietic cancers. The mutagenicity of butadiene is thought to be mediated by its mono- and diepoxide metabolites, which are capable of binding to DNA. Diepoxybutane is the most potent genotoxic metabolite and is known to produce interstrand DNA cross-links. In order to study individual differences in response to the genotoxicity of diepoxybutane, we devised a human lymphocyte culture system that involves short-term culture of T lymphocytes and measurement of sister chromatid exchange (SCE) and chromosomal aberration frequency as genotoxic end-points. We observed that when lymphocytes from healthy individuals are exposed in vitro to 6 microM of diepoxybutane, the number of SCEs induced is distributed bimodally: about 20% of 173 healthy workers studied were twice as sensitive to the induction of SCEs as the remaining 80%. Cells from sensitive individuals also contain four times more diepoxybutane-induced chromosomal deletions and exchanges. Of particular interest is the observation that diepoxybutane-sensitive individuals have higher frequencies of baseline (i.e., uninduced) SCEs. We have now examined the sensitivity of individual lymphocytes to SCE induction by another DNA cross-linking agent (nitrogen mustard) and to monoepoxybutene. The results indicate that lymphocytes sensitive to diepoxybutane-induced SCEs have normal sensitivity to nitrogen mustard and a moderately increased response to the monofunctional agent monoepoxybutene. Measurement of diepoxybutane-induced SCEs is a potential biomarker of sensitivity to the genotoxic effects of butadiene and may be useful in occupational epidemiological studies. Such studies, in combination with measures of butadiene metabolism, could be useful in ascertaining whether the sensitivity is mediated by enzyme polymorphisms.

  7. Targeting of chemical mutagens to differentiating B-lymphocytes in vivo: detection by direct DNA labeling and sister chromatid exchange induction

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, S.E.; Nanna, U.C.; Dietert, R.R.

    1987-01-01

    In vivo systems for analyzing mutagen interactions with a specific differentiating cell population are rare. Taking advantage of the unique anatomical features of the bursa of Fabricius in the chicken, the authors explored the possibility of targeting chemical mutagens to a defined differentiating cell population in the animal, namely, the B-lymphocytes series. Such cells are known to be the targets for the oncogene-activating avian leukosis virus. Targeting of chemicals to cells of the bursa was demonstrated by application of the DNA-specific fluorochrome 4'-6-diamidino-2-phenylindole (DAPI) to the anal lips of neonatal chicks. Bright nuclear fluorescence of cells in the bursa demonstrated to occur within minutes after the application of 500..mu..l of DAPI. DAPI labeling of nuclei was detected up to several days after a single application. No nuclear labeling was exhibited in cells of neighboring tissues. Methyl methanesulfonate (MMS)(10..mu..l) was applied to the anal lips of day-old chicks to study dose-response kinetics for mutagen targeting to DNA of dividing B-lymphocytes in the bursa. Since the mitotic index was found to be quite high (25-30%) in the bursa, chromosome analysis was used to assay for genome damage. Sister chromatid exchange frequencies of 3.9, 7.3, and 9.0 (baseline 2.5) per cell were obtained at MMS dosages per animal of 50 ..mu..g, 100..mu..g, and 200..mu..g, respectively. These results indicate the rapid and quantitative localization of DNA-binding chemicals to cells of the bursa, particularly the resident B-lymphocytes. The bursa should be a useful system for studying mutagen-DNA interactions in the differentiating B-lymphocyte and subsequent influences on the development of immunity and lymphoproliferative disease.

  8. Differential subcellular localizations of two human Sgo1 isoforms: implications in regulation of sister chromatid cohesion and microtubule dynamics.

    Science.gov (United States)

    Wang, Xiaoxing; Yang, Yali; Dai, Wei

    2006-03-01

    Sgo1 is an evolutionarily conserved protein that functions as a protector of centromeric cohesin during mitosis. Recent studies show that Sgo1 is kinetochorelocalized and required for accurate segregation of mitotic chromosomes because depletion of Sgo1 in mammalian cells results in precocious initiation of anaphase and mis-segregation of chromosomes. Through analysis of GFP fusion proteins, we observe that two major isoforms of human Sgo1 exhibit entirely different subcellular localization patterns. The short isoform of Sgo1 (sSgo1) that lacks exon 6 does not localize to kinetochores during any stages of the cell cycle. Instead, it is enriched at mitotic spindles. On the other hand, the longer isoform of Sgo1 primarily localizes to kinetochores during G(2) phase and mitotic prophase, metaphase, and anaphase. During late mitosis, Sgo1 does not appear to be associated with kinetochores. Intriguingly, the longer isoform of Sgo1 forms discrete foci during S phase, some of which are apparently in the nucleoli. However, a majority of these foci colocalize with CREST, a kinetochore antigen, indicating that Sgo1 is loaded onto kinetochores during or immediately after DNA replication. Together, our studies suggest that different isoforms of Sgo1 may play distinct roles during the cell cycle and that Sgo1 may have an interphase function as well.

  9. Reduction of diepoxybutane-induced sister chromatid exchanges by glutathione peroxidase and erythrocytes in transgenic Big Blue mouse and rat fibroblasts.

    Science.gov (United States)

    Erexson, G L; Tindall, K R

    2000-02-14

    We have investigated the effect of glutathione peroxidase (GSH-Px) and mammalian erythrocytes (RBCs) on spontaneous and diepoxybutane (DEB)-induced sister chromatid exchange (SCE) in primary Big Blue(R) mouse (BBM1) and Big Blue(R) rat (BBR1) fibroblasts. DEB is the putative carcinogenic metabolite of 1,3-butadiene (BD) for which inhalation exposure yields a high rate of malignancies in mice but not in rats. BD is metabolized differently in mice and rats, producing much higher levels of DEB in mice than in rats, which may partly explain the different carcinogenic responses. However, other factors may contribute to the observed differences in the rodent carcinogenic response to BD. DEB is a highly reactive compound. Upon epoxide hydrolysis, DEB can covalently bind to DNA bases. Likewise, DEB generates reactive oxygen species that, in turn, can either damage DNA or produce H(2)O(2). Reduced glutathione (GSH) is known to play a role in the metabolism and detoxification of DEB; and GSH is reduced by GSH-Px in the presence of H(2)O(2). GSH-Px is a constitutive enzyme that is found at high concentrations in mammalian RBCs. Therefore, we were interested in examining the role of RBCs and GSH-Px on DEB-induced SCE in rat and mouse cells for detection of possible differences in the species response. Transgenic BBM1 and BBR1 fibroblasts were treated with either 0, 2 or 4 microM DEB plus 0, 2 or 20 units of GSH-Px with and without 2x10(8) species-specific RBCs. DEB effectively induced SCEs in both rat and mouse cells. The relative induction of SCEs in both cell types was comparable. Both GSH-Px and RBCs alone and in combination were effective in significantly reducing DEB-induced SCEs in both mouse and rat fibroblasts, although there was more variability in the SCE response in rat cells. The present study suggests that GSH-Px may be important in the detoxification of DEB-induced DNA damage that results in the formation of SCEs.

  10. Evaluation of the persistence in the induction of Sister Chromatid Exchanges (SCE) by alkylating agents; Evaluacion de la persistencia en la induccion de Intercambio en las Cromatidas Hermanas (ICH) por agentes alquilantes

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez R, R.; Huerta V, C.; MOrales R, P.R. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2006-07-01

    The persistence in the induction of sister chromatid exchanges (SCE) by the alkylating agents methyl and ethyl-methanesulfonates (MMS and EMS) was evaluated. For it, to groups of mice its were administered a dose of these agents and later its were analyzed the induced SCE's in two periods: early and late. Both agents caused high increments of SCE in the early period and small in the late one; however, the caused lately by EMS was significantly bigger. This late induction of SCE by EMS possibly is associated with an epigenetic change or with the presence of etiladucts in the phosphodiester bonds of the DNA. (Author)

  11. Investigation of Homologous Crossing over and Sister Chromatid Exchange in the Wheat Nor-B2 Locus Coding for Rrna and Gli-B2 Locus Coding for Gliadins

    Science.gov (United States)

    Dvořák, J.; Appels, R.

    1986-01-01

    Recombination was investigated within the Nor-B2 locus of wheat chromosome 6B that contains several thousand of the 18S-5.8S-26S rRNA (rDNA) repeated units. Additionally, recombination was assessed for several chromosome regions, in arm 6Bq between the centromere and the B2 locus (awn suppressor) and in arm 6Bp between the centromere and Nor-B2, between Nor-B2 and a distal C-band and between Nor-B2 and Gli-B2 coding for gliadins. The experimental design permitted the distinction between crossing over between homologous chromosomes and exchange between sister chromatids. No homologous crossing over within the Nor-B2 locus was found in a sample of 446 chromosomes, but one exchange with the attributes of unequal sister chromatid exchange was identified. The molecular characteristics of this presumed sister chromatid exchange indicate that the spacer variants present in the Nor-B2 locus are clustered. No homologous recombination was detected within the distal Gli-B2 locus containing repeated genes coding for gliadin seed-storage proteins. Both arms of chromosome 6B showed low crossing-over frequency in the proximal regions. The distance from the centromere to Nor-B2 was only from 0.3 to 2.2 cM although it accounts for about two-thirds of the metaphase chromosome arm, which shows a great distortion of the metaphase map of the arm. The level of homologous recombination within the Nor-B2 locus is lower than in the chromosome region immediately distal to it. Whether it is comparable to that in the chromosome region proximal to it could not be determined. Recombination frequencies of different pairs of chromosome 6B in all but one interval paralleled the frequencies of their metaphase I pairing: Lower pairing at metaphase I was paralleled by lower crossing-over frequency. This relationship indicated that reduced metaphase I pairing between 6B chromosomes from different populations is due to impaired crossing-over and not due to precocious chiasma terminalization. PMID

  12. Evidence that cyclophosphamide can to induce exchanges in the sister chromatids (ICH) through secondary injuries; Evidencia de que la ciclofosfamida puede inducir intercambios en las cromatidas hermanas (ICH) a traves de lesiones secundarias

    Energy Technology Data Exchange (ETDEWEB)

    Morales R, P.; Rodriguez R, R. [Instituto Nacional de Investigaciones nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    By means of the use of destination protocol of ICH inductive injuries (DLI-ICH), it was studied if interchanges in the sister chromatids (ICH) induced by cyclophosphamide (CP), in the second post-treatment division (ICH-2) are produced by secondary injuries or by fresh injuries. For discard between these possibilities it was administered CP at different periods before of the first post-treatment division, taking as reference the administered time for high dose of bromodeoxyuridine (BrdU ) which was approximately at the beginning of this division. The ICH frequencies that occur in the first, the second and the third synthesis stages (S) were determined. It was observed that when the administered CP was four hours before BrdU , the ICH frequencies of the second and the third S were reduced. The frequency of the first ICH increased lightly in relation to those of the normal protocol (0.5 h before BrdU ) and that the supplying of CP six hours before caused almost a total reduction of ICH of second and third S and an important increment of ICH of first S.This was interpreted as evidence that the ICH-2 are product of secondary injuries. (Author)

  13. Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo; Relacion de la desmetilacion del ADN con la induccion de intercambios en las cromatidas hermanas (ICH) In vivo

    Energy Technology Data Exchange (ETDEWEB)

    Toribio E, E

    2005-07-01

    The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

  14. Kinetochores coordinate pericentromeric cohesion and early DNA replication by Cdc7-Dbf4 kinase recruitment.

    Science.gov (United States)

    Natsume, Toyoaki; Müller, Carolin A; Katou, Yuki; Retkute, Renata; Gierliński, Marek; Araki, Hiroyuki; Blow, J Julian; Shirahige, Katsuhiko; Nieduszynski, Conrad A; Tanaka, Tomoyuki U

    2013-06-01

    Centromeres play several important roles in ensuring proper chromosome segregation. Not only do they promote kinetochore assembly for microtubule attachment, but they also support robust sister chromatid cohesion at pericentromeres and facilitate replication of centromeric DNA early in S phase. However, it is still elusive how centromeres orchestrate all these functions at the same site. Here, we show that the budding yeast Dbf4-dependent kinase (DDK) accumulates at kinetochores in telophase, facilitated by the Ctf19 kinetochore complex. This promptly recruits Sld3-Sld7 replication initiator proteins to pericentromeric replication origins so that they initiate replication early in S phase. Furthermore, DDK at kinetochores independently recruits the Scc2-Scc4 cohesin loader to centromeres in G1 phase. This enhances cohesin loading and facilitates robust pericentromeric cohesion in S phase. Thus, we have found the central mechanism by which kinetochores orchestrate early S phase DNA replication and robust sister chromatid cohesion at microtubule attachment sites.

  15. Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

    Directory of Open Access Journals (Sweden)

    Stephan eSauer

    2012-11-01

    Full Text Available Ever since cloning the classic iv mutation identified the ‘left-right dynein’ (lrd gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old ‘Watson’ vs. old ‘Crick’ strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical ‘left-right axis development 1’ (‘lra1’ gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

  16. The chromosome damage induced by x-ray radiation doses. Comparison between dicentric chromosomes, micronuclei and Sister Chromatid Exchanges analyses. Valoracion de dao cromosomico originado por una dosis de rayos X. Comparacion de los analisis de cromosomas dicentricos, micronucleos e intercambios entre cromatidas hermanas

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, J.L.; Losada, C.; Losada, G.; Veiras, C. (Centro Oncologico de Galicia. La Corua (Spain)); Goyanes, V.J. (Hospital ' ' Teresa Herrera' ' . La Corua (Spain))

    1993-01-01

    Exposure to ionizing radiations is a well-known source of chromosome damage. Here we present a comparison among three different methodologies employed to recognize cytogenetic damage, after an acute exposure of human lymphocytes to 3 Gy of X-rays (100kVp). Scoring of dicentric chromosomes, present in first mitosis ''in vitro'', was the method of preference as dicentrics increased 937.5 times with respect to background. Micronucleus scoring in binucleated-cytokinesis blocked cells showed an increase of 32.5 times, while it was only of 1.46 times when Sister Chromatid Exchanges (SCEs) were analyzed. The estimated probability of an acentric fragment becoming a micronucleus was around 0.25. Intercellular distribution of dicentrics agree with Poisson, while micronucleus were overdispersed. When analyzed at second cycle after damage induction, the dicentrics yield as well as the level of cells with unstable cromosome aberrations, decreased around a half. Finally, SCEs level was similar in cells with or without unstable structural chromosome aberrations. (Author)

  17. Mechanical Link between Cohesion Establishment and DNA Replication: Ctf7p/Eco1p, a Cohesion Establishment Factor, Associates with Three Different Replication Factor C Complexes

    OpenAIRE

    Kenna, Margaret A.; Skibbens, Robert V.

    2003-01-01

    CTF7/ECO1 is an essential yeast gene required for the establishment of sister chromatid cohesion. The findings that CTF7/ECO1, POL30 (PCNA), and CHL12/CTF18 (a replication factor C [RFC] homolog) genetically interact provided the first evidence that the processes of cohesion establishment and DNA replication are intimately coupled—a link now confirmed by other studies. To date, however, it is unknown how Ctf7p/Eco1p function is coupled to DNA replication or whether Ctf7p/Eco1p physically asso...

  18. Sisters unbound is required for meiotic centromeric cohesion in Drosophila melanogaster.

    Science.gov (United States)

    Krishnan, Badri; Thomas, Sharon E; Yan, Rihui; Yamada, Hirotsugu; Zhulin, Igor B; McKee, Bruce D

    2014-11-01

    Regular meiotic chromosome segregation requires sister centromeres to mono-orient (orient to the same pole) during the first meiotic division (meiosis I) when homologous chromosomes segregate, and to bi-orient (orient to opposite poles) during the second meiotic division (meiosis II) when sister chromatids segregate. Both orientation patterns require cohesion between sister centromeres, which is established during meiotic DNA replication and persists until anaphase of meiosis II. Meiotic cohesion is mediated by a conserved four-protein complex called cohesin that includes two structural maintenance of chromosomes (SMC) subunits (SMC1 and SMC3) and two non-SMC subunits. In Drosophila melanogaster, however, the meiotic cohesion apparatus has not been fully characterized and the non-SMC subunits have not been identified. We have identified a novel Drosophila gene called sisters unbound (sunn), which is required for stable sister chromatid cohesion throughout meiosis. sunn mutations disrupt centromere cohesion during prophase I and cause high frequencies of non-disjunction (NDJ) at both meiotic divisions in both sexes. SUNN co-localizes at centromeres with the cohesion proteins SMC1 and SOLO in both sexes and is necessary for the recruitment of both proteins to centromeres. Although SUNN lacks sequence homology to cohesins, bioinformatic analysis indicates that SUNN may be a structural homolog of the non-SMC cohesin subunit stromalin (SA), suggesting that SUNN may serve as a meiosis-specific cohesin subunit. In conclusion, our data show that SUNN is an essential meiosis-specific Drosophila cohesion protein. Copyright © 2014 by the Genetics Society of America.

  19. Sisters Hope

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Worre Hallberg, Gry

    2011-01-01

    Sisters Hope invites young scholars to visit our elite-school for run-away youngsters. Maybe you will be the next one to be collected and accepted?......Sisters Hope invites young scholars to visit our elite-school for run-away youngsters. Maybe you will be the next one to be collected and accepted?...

  20. Sisters Hope

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Worre Hallberg, Gry

    2011-01-01

    I denne artikel indføres læseren i fiktionsuniverset og læringsmetoden Sisters Hope, der er inspireret af en ny tendens indenfor performancekunsten, som vi kalder "levende og relationelle fiktive paralleluniverser". Især udfoldes forskydningen af lærer- og elevrollen indenfor Sisters Hopes absurd...

  1. My sister

    Institute of Scientific and Technical Information of China (English)

    胡琪

    2004-01-01

    I have a sister.Her name is Deng Zi Jun.She's five years old.She has two big eyes,a small high nose and a small mouth.Her hair is short and black. My sister is a good student. She is good at Maths and Art.Sheis not very good at English.She likes watching TV,singing,drawing,eating,sleep-ing and playing.

  2. The Slx4-Dpb11 scaffold complex: coordinating the response to replication fork stalling in S-phase and the subsequent mitosis.

    Science.gov (United States)

    Princz, Lissa N; Gritenaite, Dalia; Pfander, Boris

    2015-01-01

    Replication fork stalling at DNA lesions is a common problem during the process of DNA replication. One way to allow the bypass of these lesions is via specific recombination-based mechanisms that involve switching of the replication template to the sister chromatid. Inherent to these mechanisms is the formation of DNA joint molecules (JMs) between sister chromatids. Such JMs need to be disentangled before chromatid separation in mitosis and the activity of JM resolution enzymes, which is under stringent cell cycle control, is therefore up-regulated in mitosis. An additional layer of control is facilitated by scaffold proteins. In budding yeast, specifically during mitosis, Slx4 and Dpb11 form a cell cycle kinase-dependent complex with the Mus81-Mms4 structure-selective endonuclease, which allows efficient JM resolution by Mus81. Furthermore, Slx4 and Dpb11 interact even prior to joining Mus81 and respond to replication fork stalling in S-phase. This S-phase complex is involved in the regulation of the DNA damage checkpoint as well as in early steps of template switch recombination. Similar interactions and regulatory principles are found in human cells suggesting that Slx4 and Dpb11 may have an evolutionary conserved role organizing the cellular response to replication fork stalling.

  3. 石油作业女性染色单体交换与习惯性流产关系研究%Study on the relationship between sister chromatid exchange and habitual abortion among the women in the petroleum operations

    Institute of Scientific and Technical Information of China (English)

    慕明涛; 霍满鹏; 蒲力群; 张静; 刘俊俊

    2012-01-01

    目的:分析石油作业女性外周血淋巴细胞姐妹染色单体互换( SCE)对习惯性流产的影响.方法:随机选择习惯性流产的石油作业女性26人为观察组和正常的育龄女性18人为对照组,检测其外周血淋巴细胞姐妹染色单体互换,记势SCE发生率.结果:观察组的外周血淋巴细胞SCE发生率为8.66 ±0.61明显高于对照组,差异有统计学意义(P<0.05).结论:SCE的发生可作为石油作业习惯性流产女性染色体结构稳定性的检测指标.石油作业环境中的某些有害物质对女性DNA损伤有一定的影响.%Objective; To analyze the effect of sister chromatid exchange (SCE) in lymphocytes in peripheral blood of the women in the petroleum operations on habitual abortion. Methods: Twenty - six women in the petroleum operations with habitual abortion and 18 normal women at childbearing age were selected randomly as observation group and control group respectively. SCE in lymphocytes in peripheral blood was detected, and the incidence was recorded. Results; The incidence of SCE in lymphocytes in peripheral blood of observation group was (8. 66 ±0. 61), which was significantly higher than that in control group (P <0. 05) . Conclusion; The occurrence of SCE can be used as a index to detect the structural stability of chromosomes in women with habitual abortion; some harmful substances in the environment in petroleum operations have a certain impact on injury of female DNA.

  4. "Pearl Sister"

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    HE Xiuying is the general manager of the Beihai Pearl Company in a small city by the Gulf of Beibu in Guangxi Zhuang Autonomous Region. Local people like to call her "Pearl Sister," because they have seen with their own eyes how He Xiuying has been transformed from an ordinary fisherwoman into a pearl expert and entrepreneur as pearl production has developed in Beihai. Born into a poor family, He Xiuying had to help her parents support her

  5. Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier

    Science.gov (United States)

    Sofueva, Sevil; Osman, Fekret; Lorenz, Alexander; Steinacher, Roland; Castagnetti, Stefania; Ledesma, Jennifer; Whitby, Matthew C.

    2011-01-01

    Most DNA double-strand breaks (DSBs) in S- and G2-phase cells are repaired accurately by Rad51-dependent sister chromatid recombination. However, a minority give rise to gross chromosome rearrangements (GCRs), which can result in disease/death. What determines whether a DSB is repaired accurately or inaccurately is currently unclear. We provide evidence that suggests that perturbing replication by a non-programmed protein–DNA replication fork barrier results in the persistence of replication intermediates (most likely regions of unreplicated DNA) into mitosis, which results in anaphase bridge formation and ultimately to DNA breakage. However, unlike previously characterised replication-associated DSBs, these breaks are repaired mainly by Rad51-independent processes such as single-strand annealing, and are therefore prone to generate GCRs. These data highlight how a replication-associated DSB can be predisposed to give rise to genome rearrangements in eukaryotes. PMID:21576223

  6. The template choice decision in meiosis: is the sister important?

    Science.gov (United States)

    Pradillo, Mónica; Santos, Juan L

    2011-10-01

    Recombination between homologous chromosomes is crucial to ensure their proper segregation during meiosis. This is achieved by regulating the choice of recombination template. In mitotic cells, double-strand break repair with the sister chromatid appears to be preferred, whereas interhomolog recombination is favoured during meiosis. However, in the last year, several studies in yeast have shown the importance of the meiotic recombination between sister chromatids. Although this thinking seems to be new, evidences for sister chromatid exchange during meiosis were obtained more than 50 years ago in non-model organisms. In this mini-review, we comment briefly on the most recent advances in this hot topic and also describe observations which suggest the existence of inter-sister repair during meiotic recombination. For instance, the behaviour of mammalian XY bivalents and that of trivalents in heterozygotes for chromosomal rearrangements are cited as examples. The "rediscovering" of the requirement for the sister template, although it seems to occur at a low frequency, will probably prompt further investigations in organisms other than yeast to understand the complexity of the partner choice during meiosis.

  7. Repairability during G1 of the inductor leisure of exchanges in the sister chromatid induced by alkylating agents in DNA substituted and no substituted with BUDR, in cells of the salivary gland of mouse In vivo; Reparabilidad durante G1 de las lesiones inductoras de intercambios en las cromatidas hermanas inducidos por agentes alquilantes en ADN sustituido y no sustituido con BrdU, en celulas de la glandula salival de raton In vivo

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez B, F

    2004-07-01

    In this work you determines the repair of the lesions inductoras of Sister chromatid exchange (ICHs) generated in the cells of the salivary gland of mouse, for the treatment with the N-Methyl-N-Nitrosourea (MNU), the N-Ethyl-N-Nitrosourea (ENU), the Methyl methanesulfonate (MMS) and the Ethyl methanesulfonate (EMS) in early and slow G1 of the first one and the second cellular division, that is to say before and after the cells incorporate 5-bromine-2 -Desoxyuridine (BrdU) in the DNA. Groups witness non treaties were included with mutagen. The cells of the salivary gland repaired the generated lesions partially by the MNU, the MMS and the EMS in the 1st division, and only the lesions induced by the ENU and MMS were repaired partially in the 2nd division. The ENU generates injure that they were not repaired in the 1st division and those taken place by the EMS were little repaired in the 2nd division. The methylating agents generated but ICHs that the ethylating. One observes that the BrdU makes to the molecule of the DNA but susceptible to the damage generated by the alkylating agents that induce the formation of the ICHs. This susceptibility was incremented around 150% for the treatment with the MNU, the ENU and the MMS, on the other hand for the EMS it was 3 times minor. It is proposed that the one electronegative atom of this analog of the timine would to work as a nucleophyllic center with which the electrophyllic compounds react. (Author)

  8. Post-replicative repair involves separase-dependent removal of the kleisin subunit of cohesin.

    Science.gov (United States)

    McAleenan, Alexandra; Clemente-Blanco, Andres; Cordon-Preciado, Violeta; Sen, Nicholas; Esteras, Miguel; Jarmuz, Adam; Aragón, Luis

    2013-01-10

    DNA double-strand break repair is critical for cell viability and involves highly coordinated pathways to restore DNA integrity at the lesion. An early event during homology-dependent repair is resection of the break to generate progressively longer 3' single-strand tails that are used to identify suitable templates for repair. Sister chromatids provide near-perfect sequence homology and are therefore the preferred templates during homologous recombination. To provide a bias for the use of sisters as donors, cohesin--the complex that tethers sister chromatids together--is recruited to the break to enforce physical proximity. Here we show that DNA breaks promote dissociation of cohesin loaded during the previous S phase in budding yeast, and that damage-induced dissociation of cohesin requires separase, the protease that dissolves cohesion in anaphase. Moreover, a separase-resistant allele of the gene coding for the α-kleisin subunit of cohesin, Mcd1 (also known as Scc1), reduces double-strand break resection and compromises the efficiency of repair even when loaded during DNA damage. We conclude that post-replicative DNA repair involves cohesin dissociation by separase to promote accessibility to repair factors during the coordinated cellular response to restore DNA integrity.

  9. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

    Directory of Open Access Journals (Sweden)

    Simon Gemble

    2015-07-01

    Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

  10. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

    Directory of Open Access Journals (Sweden)

    Simon Gemble

    2015-07-01

    Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

  11. Phospho-H1 Decorates the Inter-chromatid Axis and Is Evicted along with Shugoshin by SET during Mitosis.

    Science.gov (United States)

    Krishnan, Swathi; Smits, Arne H; Vermeulen, Michiel; Reinberg, Danny

    2017-08-17

    Precise control of sister chromatid separation during mitosis is pivotal to maintaining genomic integrity. Yet, the regulatory mechanisms involved are not well understood. Remarkably, we discovered that linker histone H1 phosphorylated at S/T18 decorated the inter-chromatid axial DNA on mitotic chromosomes. Sister chromatid resolution during mitosis required the eviction of such H1S/T18ph by the chaperone SET, with this process being independent of and most likely downstream of arm-cohesin dissociation. SET also directed the disassembly of Shugoshins in a polo-like kinase 1-augmented manner, aiding centromere resolution. SET ablation compromised mitotic fidelity as evidenced by unresolved sister chromatids with marked accumulation of H1S/T18ph and centromeric Shugoshin. Thus, chaperone-assisted eviction of linker histones and Shugoshins is a fundamental step in mammalian mitotic progression. Our findings also elucidate the functional implications of the decades-old observation of mitotic linker histone phosphorylation, serving as a paradigm to explore the role of linker histones in bio-signaling processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Sisters in Dutch hospitals.

    Science.gov (United States)

    van den Bergh-Braam, A H

    1985-11-01

    This study focuses on hospital sisters in 30 Dutch hospitals. The so-called role-set approach has been adopted. In this approach the sisters are the focal persons. Direct superiors, specialists, registered nurses and student nurses acted as role-senders. The possible number of respondents is 600 (120 of each group). The response of hospital sisters is 100%, that of role-senders 88%. The study started out as an attempt to collect background information on the causes of wastage of sisters. High wastage rates are generally regarded as an indication of an unfavourable working environment. Since hospital sisters occupy a key position in hospitals, the ward problems will be studied from their angle. Although wastage rates have dropped recently, it does not necessarily follow that the working environment has improved. Wastage is known to act as a safety valve, thus allowing tensions to resolve. The threat of unemployment clogs this outlet, which increases the tensions on the hospital ward. Data from the study show that work overload is one of the major stress factors for sisters. Analyses demonstrated that there exists a relationship between work overload and tensions with the management and direct superiors, tensions in job execution, irritableness on the ward, low self-esteem, health complaints and psychological condition. Sisters with an excessive job involvement refer to work overload more often than their moderate colleagues. There is a relationship between an unfavourable working environment and irritableness of sisters.

  13. Timeless links replication termination to mitotic kinase activation.

    Science.gov (United States)

    Dheekollu, Jayaraju; Wiedmer, Andreas; Hayden, James; Speicher, David; Gotter, Anthony L; Yen, Tim; Lieberman, Paul M

    2011-05-06

    The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1). Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication.

  14. Timeless links replication termination to mitotic kinase activation.

    Directory of Open Access Journals (Sweden)

    Jayaraju Dheekollu

    Full Text Available The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1. Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication.

  15. H4K20me0 marks post-replicative chromatin and recruits the TONSL₋MMS22L DNA repair complex

    Energy Technology Data Exchange (ETDEWEB)

    Saredi, Giulia; Huang, Hongda; Hammond, Colin M.; Alabert, Constance; Bekker-Jensen, Simon; Forne, Ignasi; Reverón-Gómez, Nazaret; Foster, Benjamin M.; Mlejnkova, Lucie; Bartke, Till; Cejka, Petr; Mailand, Niels; Imhof, Axel; Patel, Dinshaw J.; Groth, Anja [UCopenhagen; (MSKCC); (ICL); (LMU); (Zurich)

    2016-06-22

    Here, we report that after DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. In this paper we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L1, 2, 3, 4 homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replication and mark post-replicative chromatin until the G2/M phase of the cell cycle. Accordingly, TONSL–MMS22L binds new histones H3–H4 both before and after incorporation into nucleosomes, remaining on replicated chromatin until late G2/M. H4K20me0 recognition is required for TONSL–MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Finally, together, these data reveal a histone-reader-based mechanism for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy.

  16. Mechanisms by which Human Cells Bypass Damaged Bases during DNA Replication after Ultraviolet Irradiation

    Directory of Open Access Journals (Sweden)

    James E. Cleaver

    2002-01-01

    Full Text Available The replication of damaged DNA involves cascading mechanisms of increasing complexity but decreasing accuracy. The most accurate mechanism uses low-fidelity DNA polymerases, Pol H and Pol I, which have active sites sufficiently large to accommodate a pyrimidine dimer. Replicative bypass of DNA damage by these polymerases produces an accurately replicated, newly synthesized strand. Pol H negative cells (XP-V cell lines either adopt a proposed secondary bypass mechanism or a recombinational mode. The mechanism of the secondary bypass is unclear, but a number of experiments suggests roles for excision repair to remove damage ahead of replication forks, hRad6/18 proteolysis to clear the blocked forks, and the Rad17-RFC and 9-1-1 complexes to establish a new replication apparatus. This alternative pathway requires functional p53. In Pol H negative cells in which p53 is also inactive, the arrested fork fragments into DNA double strand breaks. Foci containing PCNA, Mre11/Rad50/Nbs1, and gamma-H2Ax can then be detected, along with chromosomal rearrangement and high frequencies of sister chromatid exchanges. The recruitment of recombination components to the arrested forks represents the ultimate failure of replication machinery to relieve the arrested state and bypass the damage. The resulting chromosomal instability in surviving cells will contribute to malignant transformation.

  17. Elg1 forms an alternative RFC complex important for DNA replication and genome integrity.

    Science.gov (United States)

    Bellaoui, Mohammed; Chang, Michael; Ou, Jiongwen; Xu, Hong; Boone, Charles; Brown, Grant W

    2003-08-15

    Genome-wide synthetic genetic interaction screens with mutants in the mus81 and mms4 replication fork-processing genes identified a novel replication factor C (RFC) homolog, Elg1, which forms an alternative RFC complex with Rfc2-5. This complex is distinct from the DNA replication RFC, the DNA damage checkpoint RFC and the sister chromatid cohesion RFC. As expected from its genetic interactions, elg1 mutants are sensitive to DNA damage. Elg1 is redundant with Rad24 in the DNA damage response and contributes to activation of the checkpoint kinase Rad53. We find that elg1 mutants display DNA replication defects and genome instability, including increased recombination and mutation frequencies, and minichromosome maintenance defects. Mutants in elg1 show genetic interactions with pathways required for processing of stalled replication forks, and are defective in recovery from DNA damage during S phase. We propose that Elg1-RFC functions both in normal DNA replication and in the DNA damage response.

  18. ETAA1 acts at stalled replication forks to maintain genome integrity.

    Science.gov (United States)

    Bass, Thomas E; Luzwick, Jessica W; Kavanaugh, Gina; Carroll, Clinton; Dungrawala, Huzefa; Glick, Gloria G; Feldkamp, Michael D; Putney, Reid; Chazin, Walter J; Cortez, David

    2016-11-01

    The ATR checkpoint kinase coordinates cellular responses to DNA replication stress. Budding yeast contain three activators of Mec1 (the ATR orthologue); however, only TOPBP1 is known to activate ATR in vertebrates. We identified ETAA1 as a replication stress response protein in two proteomic screens. ETAA1-deficient cells accumulate double-strand breaks, sister chromatid exchanges, and other hallmarks of genome instability. They are also hypersensitive to replication stress and have increased frequencies of replication fork collapse. ETAA1 contains two RPA-interaction motifs that localize ETAA1 to stalled replication forks. It also interacts with several DNA damage response proteins including the BLM/TOP3α/RMI1/RMI2 and ATR/ATRIP complexes. It binds ATR/ATRIP directly using a motif with sequence similarity to the TOPBP1 ATR-activation domain; and like TOPBP1, ETAA1 acts as a direct ATR activator. ETAA1 functions in parallel to the TOPBP1/RAD9/HUS1/RAD1 pathway to regulate ATR and maintain genome stability. Thus, vertebrate cells contain at least two ATR-activating proteins.

  19. The Lehman Sisters Hypothesis

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2014-01-01

    markdownabstract__Abstract__ This article explores the Lehman Sisters Hypothesis. It reviews empirical literature about gender differences in behavioral, experimental, and neuro-economics as well as in other fields of behavioral research. It discusses gender differences along three dimensions of fi

  20. Analysis of Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    孙淑珍

    2004-01-01

    Chapter Ⅰ Introduction  Sitting in the rocking chair,Carrie dreams her future.This is the deep impression the novel"Sister Carrie"gives us,which is written by Theodore Dreiser(1871-1945),the great American realism writer.  ……

  1. Sister Carrie in China

    Institute of Scientific and Technical Information of China (English)

    殷希

    2015-01-01

    Sister Carrie has received many Chinese scholar's attention, and it has quantity relevance researches. Therefore, it is valuable to study why it is popular in China and it's education meaning for Chinese people. In addition, to analysis the domestic re-searches and find it's exist problems can help us make a new breakthrough from the study.

  2. Separase Is Required for Homolog and Sister Disjunction during Drosophila melanogaster Male Meiosis, but Not for Biorientation of Sister Centromeres.

    Science.gov (United States)

    Blattner, Ariane C; Chaurasia, Soumya; McKee, Bruce D; Lehner, Christian F

    2016-04-01

    Spatially controlled release of sister chromatid cohesion during progression through the meiotic divisions is of paramount importance for error-free chromosome segregation during meiosis. Cohesion is mediated by the cohesin protein complex and cleavage of one of its subunits by the endoprotease separase removes cohesin first from chromosome arms during exit from meiosis I and later from the pericentromeric region during exit from meiosis II. At the onset of the meiotic divisions, cohesin has also been proposed to be present within the centromeric region for the unification of sister centromeres into a single functional entity, allowing bipolar orientation of paired homologs within the meiosis I spindle. Separase-mediated removal of centromeric cohesin during exit from meiosis I might explain sister centromere individualization which is essential for subsequent biorientation of sister centromeres during meiosis II. To characterize a potential involvement of separase in sister centromere individualization before meiosis II, we have studied meiosis in Drosophila melanogaster males where homologs are not paired in the canonical manner. Meiosis does not include meiotic recombination and synaptonemal complex formation in these males. Instead, an alternative homolog conjunction system keeps homologous chromosomes in pairs. Using independent strategies for spermatocyte-specific depletion of separase complex subunits in combination with time-lapse imaging, we demonstrate that separase is required for the inactivation of this alternative conjunction at anaphase I onset. Mutations that abolish alternative homolog conjunction therefore result in random segregation of univalents during meiosis I also after separase depletion. Interestingly, these univalents become bioriented during meiosis II, suggesting that sister centromere individualization before meiosis II does not require separase.

  3. Separase Is Required for Homolog and Sister Disjunction during Drosophila melanogaster Male Meiosis, but Not for Biorientation of Sister Centromeres.

    Directory of Open Access Journals (Sweden)

    Ariane C Blattner

    2016-04-01

    Full Text Available Spatially controlled release of sister chromatid cohesion during progression through the meiotic divisions is of paramount importance for error-free chromosome segregation during meiosis. Cohesion is mediated by the cohesin protein complex and cleavage of one of its subunits by the endoprotease separase removes cohesin first from chromosome arms during exit from meiosis I and later from the pericentromeric region during exit from meiosis II. At the onset of the meiotic divisions, cohesin has also been proposed to be present within the centromeric region for the unification of sister centromeres into a single functional entity, allowing bipolar orientation of paired homologs within the meiosis I spindle. Separase-mediated removal of centromeric cohesin during exit from meiosis I might explain sister centromere individualization which is essential for subsequent biorientation of sister centromeres during meiosis II. To characterize a potential involvement of separase in sister centromere individualization before meiosis II, we have studied meiosis in Drosophila melanogaster males where homologs are not paired in the canonical manner. Meiosis does not include meiotic recombination and synaptonemal complex formation in these males. Instead, an alternative homolog conjunction system keeps homologous chromosomes in pairs. Using independent strategies for spermatocyte-specific depletion of separase complex subunits in combination with time-lapse imaging, we demonstrate that separase is required for the inactivation of this alternative conjunction at anaphase I onset. Mutations that abolish alternative homolog conjunction therefore result in random segregation of univalents during meiosis I also after separase depletion. Interestingly, these univalents become bioriented during meiosis II, suggesting that sister centromere individualization before meiosis II does not require separase.

  4. Bloom Helicase and DNA Topoisomerase IIIα Are Involved in the Dissolution of Sister Chromatids

    OpenAIRE

    Seki, Masayuki; Nakagawa, Takayuki; Seki, Takahiko; Kato, Genta; Tada, Shusuke; TAKAHASHI, Yuriko; Yoshimura, Akari; Kobayashi, Takayuki; Aoki, Ayako; Otsuki, Makoto; Felix A Habermann; Tanabe, Hideyuki; Ishii, Yutaka; Enomoto, Takemi

    2006-01-01

    Bloom's syndrome (BS) is an autosomal disorder characterized by predisposition to a wide variety of cancers. The gene product whose mutation leads to BS is the RecQ family helicase BLM, which forms a complex with DNA topoisomerase IIIα (Top3α). However, the physiological relevance of the interaction between BLM and Top3α within the cell remains unclear. We show here that Top3α depletion causes accumulation of cells in G2 phase, enlargement of nuclei, and chromosome gaps and breaks that occur ...

  5. Mouse RAD54 affects DNA double-strand break repair and sister chromatid exchange

    NARCIS (Netherlands)

    H.B. Beverloo (Berna); R.D. Johnson (Roger); M. Jasin (Maria); R. Kanaar (Roland); J.H.J. Hoeijmakers (Jan); M.L.G. Dronkert (Mies)

    2000-01-01

    textabstractCells can achieve error-free repair of DNA double-strand breaks (DSBs) by homologous recombination through gene conversion with or without crossover. In contrast, an alternative homology-dependent DSB repair pathway, single-strand annealing (SSA), results in deletions. In this study, we

  6. DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and suppresses sister chromatid exchange.

    Directory of Open Access Journals (Sweden)

    Hungjiun Liaw

    Full Text Available Hyperphosphorylation of RPA2 at serine 4 and serine 8 (S4, S8 has been used as a marker for activation of the DNA damage response. What types of DNA lesions cause RPA2 hyperphosphorylation, which kinase(s are responsible for them, and what is the biological outcome of these phosphorylations, however, have not been fully investigated. In this study we demonstrate that RPA2 hyperphosphorylation occurs primarily in response to genotoxic stresses that cause high levels of DNA double-strand breaks (DSBs and that the DNA-dependent protein kinase complex (DNA-PK is responsible for the modifications in vivo. Alteration of S4, S8 of RPA2 to alanines, which prevent phosphorylations at these sites, caused increased mitotic entry with concomitant increases in RAD51 foci and homologous recombination. Taken together, our results demonstrate that RPA2 hyperphosphorylation by DNA-PK in response to DSBs blocks unscheduled homologous recombination and delays mitotic entry. This pathway thus permits cells to repair DNA damage properly and increase cell viability.

  7. 40 CFR 79.65 - In vivo sister chromatid exchange assay.

    Science.gov (United States)

    2010-07-01

    ... least five female and five male animals per experimental and control group shall be used. The use of a... PROGRAMS (CONTINUED) REGISTRATION OF FUELS AND FUEL ADDITIVES Testing Requirements for Registration § 79.65... days to three or more concentrations of a test substance in air. Groups of animals are sacrificed at...

  8. Linking Sister Chromatid Cohesion to Apoptosis and Aneuploidy in the Development of Breast Cancer

    Science.gov (United States)

    2005-07-01

    instead ofa pituitary isograft as in the original specific optical filters TRI, TR2, and TR3 (Chroma Technology, Brattleboro, experiment. A pituitary... isograft results in marked increases in the circulating VT). Quantitative evaluation of the hybridization was performed using a levels of prolactin and...transcription start sites Untreated 9/50(18) 49.2 16 6/10 Pituitary isograft 7/50(14) 41.4 14 7/7using Genomatix Suite and a neural network promoter prediction

  9. Review of the international symposium, sister chromatid exchanges: twenty-five years of experimental research

    Energy Technology Data Exchange (ETDEWEB)

    Tice, R.R.; Lambert, B.; Morimoto, Kanehisa; Hollaender, A.

    1983-01-01

    The purpose of this symposium was to honor initial research at Brookhaven by bringing internationally recognized leaders in the fields of genetics, cytogenetics, carcinogenesis, mutagenesis, radiation biology, toxicology, and environmental health together into an open forum to present and discuss: (1) current knowledge of the induction and formation of SCEs and their relationship to other biological endpoints, including carcinogenesis, mutagenesis, transformation, clastogenesis, DNA damage and repair, and cellular toxicity; (2) the optimal strategies for the utilization of SCEs in genetic toxicology testing schemes involving in vitro and in vivo exposure situations; (3) the most valid statistical methods for analyzing SCE data obtained from cells in culture, from cells in intact organisms, and from cells in humans; (4) the relevance of SCEs as an indicator of human disease states, both inherited and acquired, and of progress in disease treatment; and (5) the use of SCEs as an indicator of human exposure to genotoxic agents and their relevance as a prognosticator of future adverse health outcomes. This report summarizes the presentations. 7 references. (ACR)

  10. Fanconi anaemia proteins are associated with sister chromatid bridging in mitosis

    DEFF Research Database (Denmark)

    Ying, Songmin; Hickson, Ian D

    2011-01-01

    that specifically occur during chromosome segregation in mitosis. The BS protein, BLM, was shown recently to define a novel class of anaphase DNA bridge structures that, in some cases, also contain FA proteins. We will discuss the possible source of these bridges and the role that FA proteins and BLM might play...

  11. PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

    DEFF Research Database (Denmark)

    Nielsen, Christian Thomas Friberg; Huttner, Diana; Bizard, Anna H

    2015-01-01

    PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural......-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis....

  12. Homologous recombination, sister chromatid cohesion, and chromosome condensation in mammalian meiosis

    NARCIS (Netherlands)

    Eijpe, M.

    2002-01-01

    In the life cycle of sexually reproducing eukaryotes, haploid and diploid generations of cells alternate. Two types of cell division occur in such a life cycle: mitosis and meiosis. They are compared in chapter 1 . Haploid and diploid cells can multiply by mitoses.

  13. BRCA1 controls homologous recombination at Tus/Ter-stalled mammalian replication forks.

    Science.gov (United States)

    Willis, Nicholas A; Chandramouly, Gurushankar; Huang, Bin; Kwok, Amy; Follonier, Cindy; Deng, Chuxia; Scully, Ralph

    2014-06-26

    Replication fork stalling can promote genomic instability, predisposing to cancer and other diseases. Stalled replication forks may be processed by sister chromatid recombination (SCR), generating error-free or error-prone homologous recombination (HR) outcomes. In mammalian cells, a long-standing hypothesis proposes that the major hereditary breast/ovarian cancer predisposition gene products, BRCA1 and BRCA2, control HR/SCR at stalled replication forks. Although BRCA1 and BRCA2 affect replication fork processing, direct evidence that BRCA gene products regulate homologous recombination at stalled chromosomal replication forks is lacking, due to a dearth of tools for studying this process. Here we report that the Escherichia coli Tus/Ter complex can be engineered to induce site-specific replication fork stalling and chromosomal HR/SCR in mouse cells. Tus/Ter-induced homologous recombination entails processing of bidirectionally arrested forks. We find that the Brca1 carboxy (C)-terminal tandem BRCT repeat and regions of Brca1 encoded by exon 11-two Brca1 elements implicated in tumour suppression-control Tus/Ter-induced homologous recombination. Inactivation of either Brca1 or Brca2 increases the absolute frequency of 'long-tract' gene conversions at Tus/Ter-stalled forks, an outcome not observed in response to a site-specific endonuclease-mediated chromosomal double-strand break. Therefore, homologous recombination at stalled forks is regulated differently from homologous recombination at double-strand breaks arising independently of a replication fork. We propose that aberrant long-tract homologous recombination at stalled replication forks contributes to genomic instability and breast/ovarian cancer predisposition in BRCA mutant cells.

  14. Chromatids segregate without centrosomes during Caenorhabditis elegans mitosis in a Ran- and CLASP-dependent manner.

    Science.gov (United States)

    Nahaboo, Wallis; Zouak, Melissa; Askjaer, Peter; Delattre, Marie

    2015-06-01

    During mitosis, chromosomes are connected to a microtubule-based spindle. Current models propose that displacement of the spindle poles and/or the activity of kinetochore microtubules generate mechanical forces that segregate sister chromatids. Using laser destruction of the centrosomes during Caenorhabditis elegans mitosis, we show that neither of these mechanisms is necessary to achieve proper chromatid segregation. Our results strongly suggest that an outward force generated by the spindle midzone, independently of centrosomes, is sufficient to segregate chromosomes in mitotic cells. Using mutant and RNAi analysis, we show that the microtubule-bundling protein SPD-1/MAP-65 and BMK-1/kinesin-5 act as a brake opposing the force generated by the spindle midzone. Conversely, we identify a novel role for two microtubule-growth and nucleation agents, Ran and CLASP, in the establishment of the centrosome-independent force during anaphase. Their involvement raises the interesting possibility that microtubule polymerization of midzone microtubules is continuously required to sustain chromosome segregation during mitosis.

  15. Alleles of the homologous recombination gene, RAD59, identify multiple responses to disrupted DNA replication in Saccharomyces cerevisiae.

    Science.gov (United States)

    Liddell, Lauren C; Manthey, Glenn M; Owens, Shannon N; Fu, Becky X H; Bailis, Adam M

    2013-10-14

    In Saccharomyces cerevisiae, Rad59 is required for multiple homologous recombination mechanisms and viability in DNA replication-defective rad27 mutant cells. Recently, four rad59 missense alleles were found to have distinct effects on homologous recombination that are consistent with separation-of-function mutations. The rad59-K166A allele alters an amino acid in a conserved α-helical domain, and, like the rad59 null allele diminishes association of Rad52 with double-strand breaks. The rad59-K174A and rad59-F180A alleles alter amino acids in the same domain and have genetically similar effects on homologous recombination. The rad59-Y92A allele alters a conserved amino acid in a separate domain, has genetically distinct effects on homologous recombination, and does not diminish association of Rad52 with double-strand breaks. In this study, rad59 mutant strains were crossed with a rad27 null mutant to examine the effects of the rad59 alleles on the link between viability, growth and the stimulation of homologous recombination in replication-defective cells. Like the rad59 null allele, rad59-K166A was synthetically lethal in combination with rad27. The rad59-K174A and rad59-F180A alleles were not synthetically lethal in combination with rad27, had effects on growth that coincided with decreased ectopic gene conversion, but did not affect mutation, unequal sister-chromatid recombination, or loss of heterozygosity. The rad59-Y92A allele was not synthetically lethal when combined with rad27, stimulated ectopic gene conversion and heteroallelic recombination independently from rad27, and was mutually epistatic with srs2. Unlike rad27, the stimulatory effect of rad59-Y92A on homologous recombination was not accompanied by effects on growth rate, cell cycle distribution, mutation, unequal sister-chromatid recombination, or loss of heterozygosity. The synthetic lethality conferred by rad59 null and rad59-K166A alleles correlates with their inhibitory effect on association

  16. Sisters Hope - the exposed self

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Hallberg, Gry Worre

    Sisters Hope is an art-educational method and a practice-led research tool, rooted in the construction of a fictional parallel universe revolving around the twin sisters Coco and Coca Pebber. Our work is rooted in the ambition to democratize the aesthetic dimension through ‘affective engineering......’ and the establishment of fictional spaces outside the institutional art context. In the Unfolding Academia-context Sisters Hope investigates new forms of research and (re)presentation through the creation of interactive and affective learning-spaces. At Collective Futures Sisters Hope explored questions such as: How...

  17. Sister-sister incest: data from an anonymous computerized survey.

    Science.gov (United States)

    Stroebel, Sandra S; O'Keefe, Stephen L; Griffee, Karen; Kuo, Shih-Ya; Beard, Keith W; Kommor, Martin J

    2013-01-01

    Retrospective data were entered anonymously by 1,521 adult women using a computer-assisted self-interview. Thirty-one participants were victims of sister-sister incest, 40 were victims of brother-sister incest, 19 were victims of father-daughter incest, 8 were victims of sexual abuse by an adult female (including one mother), and 232 were victims of sexual abuse by an adult male other than their father before reaching 18 years of age. The rest (1,203) served as controls. The victims of sister-sister incest had significantly more problematic outcomes than controls on many measures as adults. Victims of sister-sister incest were more depressed and more likely than controls to be distant from the perpetrator-sister and to have traded sex for money, experienced an unplanned pregnancy, engaged in four different types of masturbation, and engaged in 13 different same-sex behaviors. Our findings were consistent with other reports of early eroticization and persistent hypereroticization of incest victims.

  18. The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants.

    Science.gov (United States)

    Imamura, Osamu; Campbell, Judith L

    2003-07-08

    Bloom syndrome is a disorder of profound and early cancer predisposition in which cells become hypermutable, exhibit high frequency of sister chromatid exchanges, and show increased micronuclei. BLM, the gene mutated in Bloom syndrome, has been cloned previously, and the BLM protein is a member of the RecQ family of DNA helicases. Many lines of evidence suggest that BLM is involved either directly in DNA replication or in surveillance during DNA replication, but its specific roles remain unknown. Here we show that hBLM can suppress both the temperature-sensitive growth defect and the DNA damage sensitivity of the yeast DNA replication mutant dna2-1. The dna2-1 mutant is defective in a helicase-nuclease that is required either to coordinate with the crucial Saccharomyces cerevisiae (sc) FEN1 nuclease in Okazaki fragment maturation or to compensate for scFEN1 when its activity is impaired. We show that human BLM interacts with both scDna2 and scFEN1 by using coimmunoprecipitation from yeast extracts, suggesting that human BLM participates in the same steps of DNA replication or repair as scFEN1 and scDna2.

  19. Enhanced G2 chromatid radiosensitivity in dyskeratosis congenita fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    DeBauche, D.M.; Pai, G.S.; Stanley, W.S. (Medical Univ. of South Carolina, Charleston (USA))

    1990-02-01

    Dyskeratosis congenita (DC) is an inherited disorder characterized by reticular pigmentation of the skin, dystrophic nails, mucosal leukoplakia, and a predisposition to cancer in early adult life. In the majority of cases, DC is an X-linked recessive trait. However, one or more autosomal form(s) of DC may exist. Although excessive spontaneous chromatid breakage has been reported in DC, it is not a consistent cytological marker for this disorder. We examined the frequency and specificity of X-irradiation-induced G2 chromatid breakage in fibroblasts from three unrelated DC patients (two males and one female). Metaphase cells from DC patients had significantly more chromatid breaks (16-18-fold and 17-26-fold at 50 and 100 rad X-irradiation, respectively) and chromatid gaps (10-12-fold and 6-7-fold at 50 and 100 rad, respectively) than those from two different controls. Analysis of banded chromosomes revealed a nonrandom distribution of chromatid aberrations in DC but not in controls, a distribution corresponding to some of the known breakpoints for cancer-specific rearrangements, constitutive fragile sites, and/or loci for cellular proto-oncogenes. The significance of this finding for cancer predisposition in DC patients is uncertain, but the increased susceptibility of X-irradiation-induced chromatid breakage may serve as a cellular marker of diagnostic value.

  20. Where are Sedna's Sisters?

    Science.gov (United States)

    Bartlett, D. F.

    2005-05-01

    Simulations of the formation of the Oort cloud from the Kuiper Belt typically are presented as an animated scatter diagram. Here the orbit of each object appears as a point of perihelion distance q and semi-major axis a. (eg. Levison, Morbidelli, & Dones 2004). These plots show a conspicuous void, bounded by the inequalities: q 50 AU, and a Bermuda Triangle". The only present occupant is Sedna (q=76 AU, a=501 AU). Brown, Trujillo, & Rabinowitz , the discovers of Sedna, have challenged others to explain how Sedna got inside the triangle and to predict where similar objects might be found. Sedna could not have simply formed in its current orbit by the accumulation of smaller objects (Stern 2005). Several authors have suggested that a passing star scattered Sedna into the triangle shortly after the birth of the solar system. Here I offer an alternative which uses the very strong galactic tidal forces of the Sinusoidal potential (Bartlett 2001, 2004). In this potential, the numerator of Newton's law is replaced by GM cos(ko r) where ko = 2 π / lambdao and the 'wavelength' λ o is 425 pc. The 20 radial oscillations between the sun and the center of the Galaxy give tidal forces that are 120 times as big as generally expected. I will show how this tidal force, acting over the lifetime of the solar system, could move the perihelion of Sedna from about 40 to 76 AU. Sedna's sisters are likely to have still larger q & a and to have perihelia in two specific quadrants of the ecliptic plane.

  1. NIPBL rearrangements in Cornelia de Lange syndrome: evidence for replicative mechanism and genotype–phenotype correlation

    Science.gov (United States)

    Pehlivan, Davut; Hullings, Melanie; Carvalho, Claudia M.B.; Gonzaga-Jauregui, Claudia G.; Loy, Elizabeth; Jackson, Laird G.; Krantz, Ian D.; Deardorff, Matthew A.; Lupski, James R.

    2013-01-01

    Purpose Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder characterized by mental retardation, limb abnormalities, distinctive facial features, and hirsutism. Mutations in three genes involved in sister chromatid cohesion, NIPBL, SMC1A, and SMC3, account for ~55% of CdLS cases. The molecular etiology of a significant fraction of CdLS cases remains unknown. We hypothesized that large genomic rearrangements of cohesin complex subunit genes may play a role in the molecular etiology of this disorder. Methods Custom high-resolution oligonucleotide array comparative genomic hybridization analyses interrogating candidate cohesin genes and breakpoint junction sequencing of identified genomic variants were performed. Results Of the 162 patients with CdLS, for whom mutations in known CdLS genes were previously negative by sequencing, deletions containing NIPBL exons were observed in 7 subjects (~5%). Breakpoint sequences in five patients implicated microhomology-mediated replicative mechanisms—such as serial replication slippage and fork stalling and template switching/microhomology-mediated break-induced replication—as a potential predominant contributor to these copy number variations. Most deletions are predicted to result in haploinsuflciency due to heterozygous loss-of-function mutations; such mutations may result in a more severe CdLS phenotype. Conclusion Our findings suggest a potential clinical utility to testing for copy number variations involving NIPBL when clinically diagnosed CdLS cases are mutation-negative by DNA-sequencing studies. PMID:22241092

  2. Overexpression of SETβ, a protein localizing to centromeres, causes precocious separation of chromatids during the first meiosis of mouse oocytes.

    Science.gov (United States)

    Qi, Shu-Tao; Wang, Zhen-Bo; Ouyang, Ying-Chun; Zhang, Qing-Hua; Hu, Meng-Wen; Huang, Xin; Ge, Zhaojia; Guo, Lei; Wang, Ya-Peng; Hou, Yi; Schatten, Heide; Sun, Qing-Yuan

    2013-04-01

    Chromosome segregation in mammalian oocyte meiosis is an error-prone process, and any mistake in this process may result in aneuploidy, which is the main cause of infertility, abortion and many genetic diseases. It is now well known that shugoshin and protein phosphatase 2A (PP2A) play important roles in the protection of centromeric cohesion during the first meiosis. PP2A can antagonize the phosphorylation of rec8, a member of the cohesin complex, at the centromeres and thus prevent cleavage of rec8 and so maintain the cohesion of chromatids. SETβ is a protein that physically interacts with shugoshin and inhibits PP2A activity. We thus hypothesized that SETβ might regulate cohesion protection and chromosome segregation during oocyte meiotic maturation. Here we report for the first time the expression, subcellular localization and functions of SETβ during mouse oocyte meiosis. Immunoblotting analysis showed that the expression level of SETβ was stable from the germinal vesicle stage to the MII stage of oocyte meiosis. Immunofluorescence analysis showed SETβ accumulation in the nucleus at the germinal vesicle stage, whereas it was targeted mainly to the inner centromere area and faintly localized to the interchromatid axes from germinal vesicle breakdown to MI stages. At the MII stage, SETβ still localized to the inner centromere area, but could relocalize to kinetochores in a process perhaps dependent on the tension on the centromeres. SETβ partly colocalized with PP2A at the inner centromere area. Overexpression of SETβ in mouse oocytes caused precocious separation of sister chromatids, but depletion of SETβ by RNAi showed little effects on the meiotic maturation process. Taken together, our results suggest that SETβ, even though it localizes to centromeres, might not be essential for chromosome separation during mouse oocyte meiotic maturation, although its forced overexpression causes premature chromatid separation.

  3. Naturalistic Elements in Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    刘艳晖

    2007-01-01

    @@ Theodore Dreiser is considered to be a controversial writer.His first novel.Sister Carrie makes a new way of presenting re-ality.This paper discusses the naturalistic elements from the de-tailed description of the environment in that society.

  4. A Brief Analysis of Sister Carrie's Character

    Science.gov (United States)

    Yu, Hanying

    2010-01-01

    Carrie is always dreaming while the rocking chair is rocking again and again, this is the deep impression on us after we read "Sister Carrie" which is the first novel of Theodore Dreiser. In this novel the protagonist Sister Carrie is a controversial person. This paper tries to analyze the character of Sister Carrie in order to find out…

  5. Abnormal centromere-chromatid apposition (ACCA) and Peters' anomaly.

    Science.gov (United States)

    Wertelecki, W; Dev, V G; Superneau, D W

    1985-08-01

    Abnormal centromere-chromatid apposition (ACCA) was noted in a patient with Peters' anomaly. Previous reports of ACCA emphasized its association with tetraphocomelia and other congenital malformations (Roberts, SC Phocomelia, Pseudothalidomide Syndromes). This report expands the array of congenital malformations associated with ACCA and emphasizes the diagnostic importance of ocular defects for the ascertainment of additional cases of ACCA and its possible relationship with abnormal cell division.

  6. Field Verification Program (Aquatic Disposal). Sister Chromatid Exchange in Marine Polychaetes Exposed to Black Rock Harbor Sediment.

    Science.gov (United States)

    1985-07-01

    improbable that relationships would be detected given the variability inherent in the data. With a sample size of seven, the correlation coefficient would have...strain TA2637) with metabolic activation (Tikkanen, Matsushima, and Natori 1983), possibly via the generation of active oxygen (Brown 1980; Chesis ...Exchange as an Indicator of Mutagenesis," Nature (London), Vol 2- , p 551-553. Chesi , P. I., Levin, D. E., Smith, M. T., Ernster, L., and Ames, B. N. 1984

  7. A study of sister chromatid exchange and somatic cell mutation in hospital workers exposed to ethylene oxide.

    OpenAIRE

    Tomkins, D J; T. Haines; Lawrence, M.; Rosa, N

    1993-01-01

    To investigate the risks of exposure to ethylene oxide (EO) at current permissible levels and at past higher levels, an inception cohort of sterilizer operators and supervisors from the Central Processing Department (CPD), respiratory therapists, and engineers exposed to EO were identified at the McMaster University Medical Centre. A comparison group from Nutrition Services (NUTR) were matched with the CPD workers on the basis of sex, age, and smoking habit. The present report is based on gen...

  8. A study of sister chromatid exchange and somatic cell mutation in hospital workers exposed to ethylene oxide.

    Science.gov (United States)

    Tomkins, D J; Haines, T; Lawrence, M; Rosa, N

    1993-10-01

    To investigate the risks of exposure to ethylene oxide (EO) at current permissible levels and at past higher levels, an inception cohort of sterilizer operators and supervisors from the Central Processing Department (CPD), respiratory therapists, and engineers exposed to EO were identified at the McMaster University Medical Centre. A comparison group from Nutrition Services (NUTR) were matched with the CPD workers on the basis of sex, age, and smoking habit. The present report is based on genetic test results for the 94 CPD and matched NUTR workers only. Statistical analysis based on the mean SCE frequency in the top 5, top 10, and all cells (50 cells scored per individual) and high frequency cells (HFC) based on the 95th percentile for nonsmoking control subjects showed a direct association with current smoking but not with EO exposure. Similarly, statistical analysis of the somatic cell mutation (SCMT) variant frequencies did not demonstrate an association with EO exposure, nor with smoking. Regression analysis indicated that sex was the only other covariate that significantly affected SCE. Age was weakly associated with SCMT. A statistically significant interaction between occupational exposure and smoking habits was observed only for the mean SCE frequency of the top 5 and top 10 cells when the 11 current CPD/NUTR pairs were not included. Thus, this interaction should be interpreted with caution.

  9. Discovering non-random segregation of sister chromatids: The naïve treatment of a premature discovery

    Directory of Open Access Journals (Sweden)

    Karl G. Lark

    2013-02-01

    Full Text Available The discovery of non-random chromosome segregation is discussed from the perspective of what was known in1965 and1966. The distinction between daughter, parent or grandparent strands of DNA was developed in a bacterial system and led to the discovery that multiple copies of DNA elements of bacteria are not distributed randomly with respect to the age of the template strand. Experiments with higher eukaryotic cells demonstrated that during mitosis Mendel’s laws were violated; and the initial serendipitous choice of eukaryotic cell system led to the striking example of non-random segregation of parent and grand-parent DNA template strands in primary cultures of cells derived from mouse embryos. Attempts to extrapolate these findings to established TC lines demonstrated that the property could be lost. Experiments using plant root tips demonstrated that the phenomenon exists in plants and that it was, at some level, under genetic control. Despite publication in major journals and symposia (Lark et al. (1966a; Lark (1967a; 1967b; 1969, 1969a; 1969b the potential implications of these findings were ignored for several decades. Here we explore possible reasons for the pre-maturity (Stent, 1972 of this discovery.

  10. Parallel increases in sister chromatid exchanges at base level and with UV treatment in human opiate users

    Energy Technology Data Exchange (ETDEWEB)

    Shafer, D.A.; Falek, A.; Madden, J.J.; Tadayon, F.; Pline, M. (Georgia Mental Health Inst., Atlanta (USA). Human Genetics Research Lab.; Emory Univ., Atlanta, GA (USA). Dept. of Psychiatry); Bokos, P.J. (Interventions, Chicago, IL (USA)); Kuehnle, J.C.; Mendelson, J. (McLean Hospital, Belmont, MA (USA). Alcohol and Drug Abuse Research Center)

    1983-04-01

    The SCE base level frequency and SCE levels induced by far-UV (254 nm) treatment of cells in early G/sub 1/ and early S phases of the cell cycle were significantly higher in leukocytes from heroin addicts as compared to controls. The increased SCE levels in addicts was greatest at base level and smallest after UV irradiation of cells in S phase. These results corrobate and extend our previous findings of increased chromosome damage and reduced DNA-repair synthesis in heroin users. Since opiates do not directly damage DNA, the elevated cytogenetic effects associated with opiate use probably arise from secondary promotional effects related to opiate-mediated alterations in leukocyte metabolism.

  11. Onderzoek naar de inductie van chromosoomafwijkingen en "sister- chromatid exchanges" door acrylamide met Chinese hamster cellen in vitro

    NARCIS (Netherlands)

    Knaap; A.G.A.C.; Bergkamp; W.G.M.; Groot; M.G.

    1986-01-01

    Acrylamide bleek een clastogene werking te hebben in een test op chromosoomafwijkingen met Chinese hamster cellen in vitro vanaf 0,1 mg/ml (1,4 mmol/l), zowel in aan- als afwezigheid van een systeem voor metaboliosche activering (S9). Tevens induceerde acrylamide in deze cellen een significante

  12. 78 FR 45061 - Safety Zone; Sister Bay Marina Fest Fireworks and Ski Show, Sister Bay, WI

    Science.gov (United States)

    2013-07-26

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Sister Bay Marina Fest Fireworks and Ski... intended to restrict vessels from a portion of Sister Bay due to a fireworks display and ski show. This... with the fireworks display and ski show in Sister Bay on August 31, 2013. DATES: This rule is...

  13. A FEMINIST READING OF SISTER CARRIE

    Institute of Scientific and Technical Information of China (English)

    高陈科

    2011-01-01

    In the history of American literature, Sister Carrie has always been a controversial character. The critics regard Carrie either as a "fallen woman" or as a "new women". This thesis aims to offer a feminist reading of the image of Sister Carrie in the con

  14. Unique geometry of sister kinetochores in human oocytes during meiosis I may explain maternal age-associated increases in chromosomal abnormalities.

    Science.gov (United States)

    Patel, Jessica; Tan, Seang Lin; Hartshorne, Geraldine M; McAinsh, Andrew D

    2015-12-30

    The first meiotic division in human oocytes is highly error-prone and contributes to the uniquely high incidence of aneuploidy observed in human pregnancies. A successful meiosis I (MI) division entails separation of homologous chromosome pairs and co-segregation of sister chromatids. For this to happen, sister kinetochores must form attachments to spindle kinetochore-fibres emanating from the same pole. In mouse and budding yeast, sister kinetochores remain closely associated with each other during MI, enabling them to act as a single unified structure. However, whether this arrangement also applies in human meiosis I oocytes was unclear. In this study, we perform high-resolution imaging of over 1900 kinetochores in human oocytes, to examine the geometry and architecture of the human meiotic kinetochore. We reveal that sister kinetochores in MI are not physically fused, and instead individual kinetochores within a pair are capable of forming independent attachments to spindle k-fibres. Notably, with increasing female age, the separation between kinetochores increases, suggesting a degradation of centromeric cohesion and/or changes in kinetochore architecture. Our data suggest that the differential arrangement of sister kinetochores and dual k-fibre attachments may explain the high proportion of unstable attachments that form in MI and thus indicate why human oocytes are prone to aneuploidy, particularly with increasing maternal age.

  15. Unique geometry of sister kinetochores in human oocytes during meiosis I may explain maternal age-associated increases in chromosomal abnormalities

    Directory of Open Access Journals (Sweden)

    Jessica Patel

    2016-02-01

    Full Text Available The first meiotic division in human oocytes is highly error-prone and contributes to the uniquely high incidence of aneuploidy observed in human pregnancies. A successful meiosis I (MI division entails separation of homologous chromosome pairs and co-segregation of sister chromatids. For this to happen, sister kinetochores must form attachments to spindle kinetochore-fibres emanating from the same pole. In mouse and budding yeast, sister kinetochores remain closely associated with each other during MI, enabling them to act as a single unified structure. However, whether this arrangement also applies in human meiosis I oocytes was unclear. In this study, we perform high-resolution imaging of over 1900 kinetochores in human oocytes, to examine the geometry and architecture of the human meiotic kinetochore. We reveal that sister kinetochores in MI are not physically fused, and instead individual kinetochores within a pair are capable of forming independent attachments to spindle k-fibres. Notably, with increasing female age, the separation between kinetochores increases, suggesting a degradation of centromeric cohesion and/or changes in kinetochore architecture. Our data suggest that the differential arrangement of sister kinetochores and dual k-fibre attachments may explain the high proportion of unstable attachments that form in MI and thus indicate why human oocytes are prone to aneuploidy, particularly with increasing maternal age.

  16. All in the Family: The Sister Study

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues All in the Family: The Sister Study Past Issues / ... that may ultimately eliminate this dreaded disease. We all know that breast cancer does not discriminate. Whether ...

  17. A Naturalistic Reading of Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    谈月

    2016-01-01

    Sister Carrie is well known as the works in which naturalism attained maturity in America. Up until now, the relevant research on Dreiser and his Sister Carrie abroad and at home is primarily concerned with the frustration of American dream, the naturalistic thoughts and pessimism. The paper attempts to study it from naturalistic point of view and explain how environmental, hereditary factors and the idea of“survival of the fittest”influence Carrie’s fate.

  18. [Two Dutch sisters in analysis with Freud].

    Science.gov (United States)

    Stroeken, Harry

    2010-01-01

    The author provides persuasive or at least plausible data for the identity of two patients recorded by Freud in his working season of 1910/11. They were two sisters, living in The Hague/Leiden, who came from a rich banker's family, the van der Lindens. Whereas the treatment does not seem to have led to any decisive improvement for the older of the two, it may have encouraged the younger sister to seek divorce.

  19. Cut1/separase-dependent roles of multiple phosphorylation of fission yeast cohesion subunit Rad21 in post-replicative damage repair and mitosis.

    Science.gov (United States)

    Adachi, Yoh; Kokubu, Aya; Ebe, Masahiro; Nagao, Koji; Yanagida, Mitsuhiro

    2008-03-15

    Cohesin is a multiprotein complex essential for sister-chromatid cohesion. It plays a pivotal role in proper chromosome segregation and DNA damage repair. The mitotic behavior of cohesin is controlled through its phosphorylation, which possibly induces the dissociation of cohesin from chromosomes and enhances its susceptibility to separase. Here, we report using mass spectrometry and anti-phospho antibodies that the central domain of Rad21, the separase-target subunit of Schizosaccharomyces pombe cohesin, is regulated by various kinase-induced phosphorylation at nine residues, indicating the multiple roles for S. pombe cohesin. In vegetative and non-dividing G(0) cells, Rad21 is phosphorylated by unknown S/TP-consensus kinases, in mitotic and non-mitotic cells by polo/Plo1 and CDK, and in DNA-damaged cells by Rad3/ATR. While mitotic phosphorylation is implicated in the dissociation of Rad21 and its cleavage by separase in anaphase, the Rad3/ATR-dependent damage-induced phosphorylation occurs intensively at the time of repair completion, and only in post-replicative cells. This damage-induced Rad21 phosphorylation is involved in the recovery process of cells from checkpoint arrest, and needed for the removal of cohesin by separase after the completion of damage repair. These complex phospho-regulations of Rad21 indicate the functional significance of cohesin in cell adaptation to a variety of cellular conditions.

  20. Long range chromosome organization in Escherichia coli: The position of the replication origin defines the non-structured regions and the Right and Left macrodomains

    Science.gov (United States)

    2017-01-01

    The Escherichia coli chromosome is organized into four macrodomains (Ori, Ter, Right and Left) and two non-structured regions. This organization influences the segregation of sister chromatids, the mobility of chromosomal DNA, and the cellular localization of the chromosome. The organization of the Ter and Ori macrodomains relies on two specific systems, MatP/matS for the Ter domain and MaoP/maoS for the Ori domain, respectively. Here by constructing strains with chromosome rearrangements to reshuffle the distribution of chromosomal segments, we reveal that the difference between the non-structured regions and the Right and Left lateral macrodomains relies on their position on the chromosome. A change in the genetic location of oriC generated either by an inversion within the Ori macrodomain or by the insertion of a second oriC modifies the position of Right and Left macrodomains, as the chromosome region the closest to oriC are always non-structured while the regions further away behave as macrodomain regardless of their DNA sequence. Using fluorescent microscopy we estimated that loci belonging to a non-structured region are significantly closer to the Ori MD than loci belonging to a lateral MD. Altogether, our results suggest that the origin of replication plays a prominent role in chromosome organization in E. coli, as it determines structuring and localization of macrodomains in growing cell. PMID:28486476

  1. Dynamics of Escherichia coli chromosome segregation during multifork replication.

    Science.gov (United States)

    Nielsen, Henrik J; Youngren, Brenda; Hansen, Flemming G; Austin, Stuart

    2007-12-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive cohesion of sister DNA regions was seen at any growth rate. We conclude that segregation is driven by the progression of the replication forks.

  2. SUMO modification regulates BLM and RAD51 interaction at damaged replication forks.

    Directory of Open Access Journals (Sweden)

    Karen J Ouyang

    2009-12-01

    Full Text Available The gene mutated in Bloom's syndrome, BLM, is important in the repair of damaged replication forks, and it has both pro- and anti-recombinogenic roles in homologous recombination (HR. At damaged forks, BLM interacts with RAD51 recombinase, the essential enzyme in HR that catalyzes homology-dependent strand invasion. We have previously shown that defects in BLM modification by the small ubiquitin-related modifier (SUMO cause increased gamma-H2AX foci. Because the increased gamma-H2AX could result from defective repair of spontaneous DNA damage, we hypothesized that SUMO modification regulates BLM's function in HR repair at damaged forks. To test this hypothesis, we treated cells that stably expressed a normal BLM (BLM+ or a SUMO-mutant BLM (SM-BLM with hydroxyurea (HU and examined the effects of stalled replication forks on RAD51 and its DNA repair functions. HU treatment generated excess gamma-H2AX in SM-BLM compared to BLM+ cells, consistent with a defect in replication-fork repair. SM-BLM cells accumulated increased numbers of DNA breaks and were hypersensitive to DNA damage. Importantly, HU treatment failed to induce sister-chromatid exchanges in SM-BLM cells compared to BLM+ cells, indicating a specific defect in HR repair and suggesting that RAD51 function could be compromised. Consistent with this hypothesis, RAD51 localization to HU-induced repair foci was impaired in SM-BLM cells. These data suggested that RAD51 might interact noncovalently with SUMO. We found that in vitro RAD51 interacts noncovalently with SUMO and that it interacts more efficiently with SUMO-modified BLM compared to unmodified BLM. These data suggest that SUMOylation controls the switch between BLM's pro- and anti-recombinogenic roles in HR. In the absence of BLM SUMOylation, BLM perturbs RAD51 localization at damaged replication forks and inhibits fork repair by HR. Conversely, BLM SUMOylation relieves its inhibitory effects on HR, and it promotes RAD51 function.

  3. Stable interaction between the human proliferating cell nuclear antigen loader complex Ctf18-replication factor C (RFC) and DNA polymerase {epsilon} is mediated by the cohesion-specific subunits, Ctf18, Dcc1, and Ctf8.

    Science.gov (United States)

    Murakami, Takeshi; Takano, Ryuji; Takeo, Satoshi; Taniguchi, Rina; Ogawa, Kaori; Ohashi, Eiji; Tsurimoto, Toshiki

    2010-11-05

    One of the proliferating cell nuclear antigen loader complexes, Ctf18-replication factor C (RFC), is involved in sister chromatid cohesion. To examine its relationship with factors involved in DNA replication, we performed a proteomics analysis of Ctf18-interacting proteins. We found that Ctf18 interacts with a replicative DNA polymerase, DNA polymerase ε (pol ε). Co-immunoprecipitation with recombinant Ctf18-RFC and pol ε demonstrated that their binding is direct and mediated by two distinct interactions, one weak and one stable. Three subunits that are specifically required for cohesion in yeast, Ctf18, Dcc1, and Ctf8, formed a trimeric complex (18-1-8) and together enabled stable binding with pol ε. The C-terminal 23-amino acid stretch of Ctf18 was necessary for the trimeric association of 18-1-8 and was required for the stable interaction. The weak interaction was observed with alternative loader complexes including Ctf18-RFC(5), which lacks Dcc1 and Ctf8, suggesting that the common loader structures, including the RFC small subunits (RFC2-5), are responsible for the weak interaction. The two interaction modes, mediated through distinguishable structures of Ctf18-RFC, both occurred through the N-terminal half of pol ε, which includes the catalytic domain. The addition of Ctf18-RFC or Ctf18-RFC(5) to the DNA synthesis reaction caused partial inhibition and stimulation, respectively. Thus, Ctf18-RFC has multiple interactions with pol ε that promote polymorphic modulation of DNA synthesis. We propose that their interaction alters the DNA synthesis mode to enable the replication fork to cooperate with the establishment of cohesion.

  4. Sisters Hope - Protected by the Fiction

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Hallberg, Gry Worre

    2011-01-01

    In this article we will introduce the fictional and art-pedagogical universe of Sisters Hope and describe how it in different ways transcends into contexts beyond the art world and thus functions as a tool to democratize the aesthetic dimension and mode of being within high schools, academia...

  5. Comments on the image of Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    张楠

    2016-01-01

    Thedore Oreiser was one of America's greatest writers and one of his famous masterpieces is Sister Carrie. the heroin of the novel was a country girl who struggled for success and finally became a movie star. Analysis on the image of Carrie is of practical significance to the country girls swarming into the city nowdays in our country.

  6. Sisters Hope - Protected by the Fiction

    DEFF Research Database (Denmark)

    Lawaetz, Anna; Hallberg, Gry Worre

    2011-01-01

    In this article we will introduce the fictional and art-pedagogical universe of Sisters Hope and describe how it in different ways transcends into contexts beyond the art world and thus functions as a tool to democratize the aesthetic dimension and mode of being within high schools, academia...

  7. Database Replication

    CERN Document Server

    Kemme, Bettina

    2010-01-01

    Database replication is widely used for fault-tolerance, scalability and performance. The failure of one database replica does not stop the system from working as available replicas can take over the tasks of the failed replica. Scalability can be achieved by distributing the load across all replicas, and adding new replicas should the load increase. Finally, database replication can provide fast local access, even if clients are geographically distributed clients, if data copies are located close to clients. Despite its advantages, replication is not a straightforward technique to apply, and

  8. Crocodile Talk: Attributions of Incestuously Abused and Nonabused Sisters.

    Science.gov (United States)

    Monahan, Kathleen

    1997-01-01

    This qualitative study analyzed the retrospective attributions of adult sisters (five abused sister dyads, and five abused and nonabused sister dyads) who grew up in incestuous families. It examined the attributions of subjects regarding the general sibling group; victim selection and nonselection; and attributions regarding jealousy, protection,…

  9. [CHL15--a new gene controlling the replication of chromosomes in saccharomycetes yeast: cloning, physical mapping, sequencing, and sequence analysis].

    Science.gov (United States)

    Kuprina, N Iu; Krol', E S; Koriabin, M Iu; Shestopalov, B V; Bliskovskiĭ, V V; Bannikov, V M; Gizatullin, R Z; Kirillov, A V; Kravtsov, V Iu; Zakhar'ev, V M

    1993-01-01

    We have analyzed the CHL15 gene, earlier identified in a screen for yeast mutants with increased loss of chromosome III and artificial circular and linear chromosomes in mitosis. Mutations in the CHL15 gene lead to a 100-fold increase in the rate of chromosome III loss per cell division and a 200-fold increase in the rate of marker homozygosis on this chromosome by mitotic recombination. Analysis of segregation of artificial circular minichromosome and artificially generated nonessential marker chromosome fragment indicated that sister chromatid loss (1:0 segregation) is a main reason of chromosome destabilization in the chl15-1 mutant. A genomic clone of CHL15 was isolated and used to map its physical position on chromosome XVI. Nucleotide sequence analysis of CHL15 revealed a 2.8-kb open reading frame with a 105-kD predicted protein sequence. At the N-terminal region of the protein sequences potentially able to form DNA-binding domains defined as zinc-fingers were found. The C-terminal region of the predicted protein displayed a similarity to sequence of regulatory proteins known as the helix-loop-helix (HLH) proteins. Data on partial deletion analysis suggest that the HLH domain is essential for the function of the CHL15 gene product. Analysis of the upstream untranslated region of CHL15 revealed the presence of the hexamer element, ACGCGT (an MluI restriction site) controlling both the periodic expression and coordinate regulation of the DNA synthesis genes in budding yeast. Deletion in the RAD52 gene, the product of which is involved in double-strand break/recombination repair and replication, leads to a considerable decrease in the growth rate of the chl15 mutant. We suggest that CHL15 is a new DNA synthesis gene in the yeast Saccharomyces cerevisiae.

  10. Nonrecurrent MECP2 duplications mediated by genomic architecture-driven DNA breaks and break-induced replication repair.

    Science.gov (United States)

    Bauters, Marijke; Van Esch, Hilde; Friez, Michael J; Boespflug-Tanguy, Odile; Zenker, Martin; Vianna-Morgante, Angela M; Rosenberg, Carla; Ignatius, Jaakko; Raynaud, Martine; Hollanders, Karen; Govaerts, Karen; Vandenreijt, Kris; Niel, Florence; Blanc, Pierre; Stevenson, Roger E; Fryns, Jean-Pierre; Marynen, Peter; Schwartz, Charles E; Froyen, Guy

    2008-06-01

    Recurrent submicroscopic genomic copy number changes are the result of nonallelic homologous recombination (NAHR). Nonrecurrent aberrations, however, can result from different nonexclusive recombination-repair mechanisms. We previously described small microduplications at Xq28 containing MECP2 in four male patients with a severe neurological phenotype. Here, we report on the fine-mapping and breakpoint analysis of 16 unique microduplications. The size of the overlapping copy number changes varies between 0.3 and 2.3 Mb, and FISH analysis on three patients demonstrated a tandem orientation. Although eight of the 32 breakpoint regions coincide with low-copy repeats, none of the duplications are the result of NAHR. Bioinformatics analysis of the breakpoint regions demonstrated a 2.5-fold higher frequency of Alu interspersed repeats as compared with control regions, as well as a very high GC content (53%). Unexpectedly, we obtained the junction in only one patient by long-range PCR, which revealed nonhomologous end joining as the mechanism. Breakpoint analysis in two other patients by inverse PCR and subsequent array comparative genomic hybridization analysis demonstrated the presence of a second duplicated region more telomeric at Xq28, of which one copy was inserted in between the duplicated MECP2 regions. These data suggest a two-step mechanism in which part of Xq28 is first inserted near the MECP2 locus, followed by breakage-induced replication with strand invasion of the normal sister chromatid. Our results indicate that the mechanism by which copy number changes occur in regions with a complex genomic architecture can yield complex rearrangements.

  11. Replication and recombination factors contributing to recombination-dependent bypass of DNA lesions by template switch.

    Directory of Open Access Journals (Sweden)

    Fabio Vanoli

    2010-11-01

    Full Text Available Damage tolerance mechanisms mediating damage-bypass and gap-filling are crucial for genome integrity. A major damage tolerance pathway involves recombination and is referred to as template switch. Template switch intermediates were visualized by 2D gel electrophoresis in the proximity of replication forks as X-shaped structures involving sister chromatid junctions. The homologous recombination factor Rad51 is required for the formation/stabilization of these intermediates, but its mode of action remains to be investigated. By using a combination of genetic and physical approaches, we show that the homologous recombination factors Rad55 and Rad57, but not Rad59, are required for the formation of template switch intermediates. The replication-proficient but recombination-defective rfa1-t11 mutant is normal in triggering a checkpoint response following DNA damage but is impaired in X-structure formation. The Exo1 nuclease also has stimulatory roles in this process. The checkpoint kinase, Rad53, is required for X-molecule formation and phosphorylates Rad55 robustly in response to DNA damage. Although Rad55 phosphorylation is thought to activate recombinational repair under conditions of genotoxic stress, we find that Rad55 phosphomutants do not affect the efficiency of X-molecule formation. We also examined the DNA polymerase implicated in the DNA synthesis step of template switch. Deficiencies in translesion synthesis polymerases do not affect X-molecule formation, whereas DNA polymerase δ, required also for bulk DNA synthesis, plays an important role. Our data indicate that a subset of homologous recombination factors, together with DNA polymerase δ, promote the formation of template switch intermediates that are then preferentially dissolved by the action of the Sgs1 helicase in association with the Top3 topoisomerase rather than resolved by Holliday Junction nucleases. Our results allow us to propose the choreography through which different

  12. DNA replication arrest in XP variant cells after UV exposure is diverted into an Mre11-dependent recombination pathway by the kinase inhibitor wortmannin

    Energy Technology Data Exchange (ETDEWEB)

    Limoli, C.L.; Laposa, R.; Cleaver, J.E

    2002-12-29

    Ultraviolet (UV) irradiation produces DNA photoproducts that are blocks to DNA replication by normal replicative polymerases. A specialized, damage-specific, distributive polymerase, Pol H or Pol h, that is the product of the hRad30A gene, is required for replication past these photoproducts. This polymerase is absent from XP variant (XP-V) cells that must employ other mechanisms to negotiate blocks to DNA replication. These mechanisms include the use of alternative polymerases or recombination between sister chromatids. Replication forks arrested by UV damage in virus transformed XP-V cells degrade into DNA double strand breaks that are sites for recombination, but in normal cells arrested forks may be protected from degradation by p53 protein. These breaks are sites for binding a protein complex, hMre11/hRad50/Nbs1, that colocalizes with H2AX and PCNA, and can be visualized as immunofluorescent foci. The protein complexes need phosphorylation to activate their DNA binding capacity. Incubation of UV irradiated XP-V cells with the irreversible kinase inhibitor wortmannin, however, increased the yield of Mre11 focus-positive cells. One interpretation of this observation is that two classes of kinases are involved after UV irradiation. One would be a wortmannin-resistant kinase that phosphorylates the Mre11 complex. The other would be a wortmannin-sensitive kinase that phosphorylates and activates the p53/large T in SV40 transformed XP-V cells. The sensitive class corresponds to the PI3-kinases of ATM, ATR, and DNA-PK, but the resistant class remains to be identified. Alternatively, the elevated yield of Mre11 foci positive cells following wortmannin treatment may reflect an overall perturbation to the signaling cascades regulated by wortmannin-sensitive PI3 related kinases. In this scenario, wortmannin could compromise damage inducible-signaling pathways that maintain the stability of stalled forks, resulting in a further destabilization of stalled forks that then

  13. Two Sisters with Idiopathic Pulmonary Hemosiderosis

    Directory of Open Access Journals (Sweden)

    Mehmet Gencer

    2007-01-01

    Full Text Available Idiopathic pulmonary hemosiderosis (IPH is a rare cause of diffuse alveolar hemorrhage with unknown etiology. In the present report, the presentations of two sisters are described: one sister had IPH, eosinophilia and a high serum immunoglobulin E (IgE level; and the other had IPH, pneumothorax, eosinophilia and a high serum IgE level. Both cases had quite unusual presentations. The first patient was 23 years of age, and had suffered from dry cough and progressive dyspnea for four years. Her hemoglobin level was 60 g/L, total serum IgE level was 900 U/mL and eosinophilia was 9%. Her chest radiography revealed diffuse infiltration. She died due to respiratory failure. The second patient was 18 years of age. She had also suffered from dry cough and gradually increasing dyspnea for two years. She had partial pneumothorax in the right lung and diffuse infiltration in other pulmonary fields on chest radiography. Her hemoglobin level was 99 g/L, total serum IgE level was 1200 U/mL and eosinophilia was 8%. IPH was diagnosed by open lung biopsy. All these findings suggested that familial or allergic factors, as well as immunological factors, might have contributed to the etiology of IPH.

  14. Effects of caffeine on sister chromatid exchange (SCE) after exposure to uv light or triaziquone studied with a fluorescence plus giemsa (FPG) technique

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, W.; Bauknecht, T.

    1978-01-19

    Studies are reported that are designed to analyze the mechanism by which caffeine reduces the induction of SCE by uv light or alkylating agents. The substantial points are (1) caffeine does not inhibit SCE formatin, and (2) the caffeine-mediated apparent decrease of SCE induction after uv or triaziquone, exposure is due to a selective destruction of those metaphases otherwise exhibiting a high number of SCE. These findings and their relevance to the ascertainment of the SCE-forming process are discussed.

  15. Cold-sensitive and caffeine-supersensitive mutants of the Schizosaccharomyces pombe dis genes implicated in sister chromatid separation during mitosis.

    OpenAIRE

    Ohkura,H.; Adachi, Y.; Kinoshita, N; Niwa, O; TODA, T.; Yanagida, M

    1988-01-01

    We isolated novel classes of Schizosaccharomyces pombe cold-sensitive dis mutants that block mitotic chromosome separation (nine mapped in the dis1 gene and one each in the dis2 and dis3 genes). Defective phenotype at restrictive temperature is similar among the mutants; the chromosomes condense and anomalously move to the cell ends in the absence of their disjoining so that they are unequally distributed at the two cell ends. Synchronous culture analyses indicate that the cells can enter int...

  16. 12. Chromosomal aberrations and sister chromatid exchanges in the symptomatic individuals exposed to arsenic through drinking water in West Bengal, India

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@In the seven districts of West Bengal, India arsenic in ground water has been found to be above the permissible limit. The concentrations of arsenic is ranging from 200-800 (g/l according to latest reports. More than 200,000 people have already shown different types of arsenical skin lesions in these seven districts of West Bengal. It has been regarded as the biggest arsenic calamity in the world. However, there is

  17. EarthLabs Meet Sister Corita Kent

    Science.gov (United States)

    Quartini, E.; Ellins, K. K.; Cavitte, M. G.; Thirumalai, K.; Ledley, T. S.; Haddad, N.; Lynds, S. E.

    2013-12-01

    The EarthLabs project provides a framework to enhance high school students' climate literacy and awareness of climate change. The project provides climate science curriculum and teacher professional development, followed by research on students' learning as teachers implement EarthLabs climate modules in the classroom. The professional development targets high school teachers whose professional growth is structured around exposure to current climate science research, data observation collection and analysis. During summer workshops in Texas and Mississippi, teachers work through the laboratories, experiments, and hand-on activities developed for their students. In summer 2013, three graduate students from the University of Texas at Austin Institute for Geophysics with expertise in climate science participated in two weeklong workshops. The graduate students partnered with exemplary teacher leaders to provide scientific content and lead the EarthLabs learning activities. As an experiment, we integrated a visit to the Blanton Museum and an associated activity in order to motivate participants to think creatively, as well as analytically, about science. This exercise was inspired by the work and educational philosophy of Sister Corita Kent. During the visit to the Blanton Museum, we steered participants towards specific works of art pre-selected to emphasize aspects of the climate of Texas and to draw participants' attention to ways in which artists convey different concepts. For example, artists use of color, lines, and symbols conjure emotional responses to imagery in the viewer. The second part of the exercise asked participants to choose a climate message and to convey this through a collage. We encouraged participants to combine their experience at the museum with examples of Sister Corita Kent's artwork. We gave them simple guidelines for the project based on techniques and teaching of Sister Corita Kent. Evaluation results reveal that participants enjoyed the

  18. Sister Carrie, an Adherent of Desires

    Institute of Scientific and Technical Information of China (English)

    裴水妹

    2007-01-01

    Sister Carrie is one of the most controversial characters in American literature.Thought as a "fallen woman" firstly,she was defined as a "new woman" by some critics later. However, by digging into the motivaton behind the whole process of Carrie's "success", the relationship between Carrie and her creator (the author), the social conditions of then American, it can be found that Carrie has never been free-standing on her thought and she has never found her real-sdf even after becoming a famous actress. In a society dominated by mass consumerism Carrie is only an adherent of her own desires. She also is a representative of all those country girls flooded into cities, a symbol and a sacrifice of the urbanization of America in a time countryside was overcome by cities.

  19. Sister Carrie:A Material Pursuer

    Institute of Scientific and Technical Information of China (English)

    马春花

    2015-01-01

    Sister Carrie dramatized by Dreiser is totally a material pursuer. She is selfish and accumulates money in a crazy way. What she does inevitably centers on materials. Living with Drouet and later Hurstwood, Carrie gets what she wants and enjoys the luxurious life in an easy way. However, with the satisfaction of some of her desires, Carrie ’s desires grow and expand. With enough food and clothes, she needs luxury. Hurstwood’s failure in business leads Carrie to the stage and finally she makes a suc⁃cess and becomes a famous actress in Broadway. She gets more money, but her desires grow even higher. Nothing can satisfy her. In this essay, the author tries to analyze Carrie according to Freud’s and Guo Weilu’s theories and prove that Carrie is totally a material pursuer.

  20. A Feminist Reading of Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    Wang; Jiatong

    2015-01-01

    In the history of American literature,Sister Carrie is the first novel of Theodore Dreiser,it impresses people deeply.Carrie,a poor country girl,becomes a famous star in a big city.She has totally changed from her hard experiences,and she becomes financially independent as a new woman when she goes through hesitation.In he whole novel,the author has planted some strong points of Carrie’s character.At the end of this paper,it analyzes woman’s status in modern time from two aspects of the improvement of female’s social status and the comparison between men and women.

  1. Interpretations of the Image of Caroline in Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    钱绘

    2014-01-01

    In the history of American naturalistic literature, Sister Carrie is a representative work of this literary genre. And the protagonist of this novel Caroline has always been a controversial character. Based on Sister Carrie and the social background of that period in America, this paper discussed the various interpretations of the image of Carrie from different aspects.

  2. The Disillusion of American Dream in Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    张晴

    2016-01-01

    Dreiser is a generally acknowledged writer as one of American's literary naturalists. In Sister Carrie, the author skillfully used the naturalistic writing style which incisively and vividly showed the society environment at that time. The paper states the process that how the American dream in Sister Carrie disillusioned gradually.

  3. Hypersensitivity to G/sub 2/ chromatid radiation damage in familial dysplastic naevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Sanford, K.K.; Tarone, R.E.; Parshad, Ram; Tucker, M.A.; Greene, M.H.; Jones, G.M.

    1987-11-14

    Skin fibroblasts from 25 members of nine kindreds with familial dysplastic naevus syndrome (DNS), 12 apparently normal spouses, and 11 additional unrelated normal individuals were tested for G/sub 2/ cell-cycle phase sensitivity to ionising radiation. The cells from individuals with DNS or hereditary cutaneous malignant melanoma with DNS (HCMM/DNS) had significantly more chromatid breaks and gaps when entering metaphase 0.5-1.5 h after G/sub 2/ phase X-irradiation (1 Gy) than those from unaffected controls. In two cases, the test results positively identified individuals before the clinical diagnosis of DNS. A clinically normal obligate carrier of the HCMM/DNS gene showed the enhanced G/sub 2/ radiosensitivity. Moreover, in a test on 1 proband, the sensitivity was apparent in peripheral blood lymphoblasts. Enhanced G/sub 2/ chromatid radiosensitivity may be a marker of genetic susceptibility to HCMM/DNS.

  4. Short telomere length and breast cancer risk: a study in sister sets.

    Science.gov (United States)

    Shen, Jing; Terry, Mary Beth; Gurvich, Irina; Liao, Yuyan; Senie, Ruby T; Santella, Regina M

    2007-06-01

    Telomeres consist of a tandem repeats of the sequence TTAGGG at the ends of chromosomes and play a key role in the maintenance of chromosomal stability. Previous studies indicated that short telomeres are associated with increased risk for human bladder, head and neck, lung, and renal cell cancer. We investigated the association between white blood cell telomere length and breast cancer risk among 268 family sets (287 breast cancer cases and 350 sister controls). Telomere length was assessed by quantitative PCR. The mean telomere length was shorter in cases (mean, 0.70; range, 0.03-1.95) than in unaffected control sisters (mean, 0.74; range, 0.03-2.29), but no significant difference was observed (P = 0.11). When subjects were categorized according to the median telomere length in controls (0.70), affected sisters had shorter telomeres compared with unaffected sisters after adjusting for age at blood donation and smoking status [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.9-1.8], but the association was not statistically significant. The association by quartile of telomere length (Q4 shortest versus Q1 longest) also supported an increase in risk from shorter telomere length, although the association was not statistically significant (OR, 1.6; 95% CI, 0.9-2.7). This association was more pronounced among premenopausal women (OR, 2.1; 95% CI, 0.8-5.5) than postmenopausal women (OR, 1.3; 95% CI, 0.5-3.6 for Q4 versus Q1). If these associations are replicated in larger studies, they provide modest epidemiologic evidence that shortened telomere length may be associated with breast cancer risk.

  5. Sister Cities and Economic Development: A New Zeeland Perspective

    Directory of Open Access Journals (Sweden)

    Brian CROSS

    2010-06-01

    Full Text Available Sister City relationships, originally built on cultural understanding and peace through citizen diplomacy, are evolving in today’s society. Politicians increasingly demand real returns where local government is actively involved. Meaningful sister city links are an asset for any community and its nation. However full utilisation requires skills and commitment talked about but often lacking in delivery. Increased emphasis on economic development as primary motivator for having sister cities provides opportunities, but also presents risks as policy emphasis shifts from relationship-building to pragmatic, shorter term goals. New Zealand’s portfolio of sister cities reflect its place on the Pacific Rim and its political/ economic positioning as “part of Asia”. An upsurge in interest from and in China as the place to do business has coincided with a levelling off of sister city activities when they should be increasing. The reasons are varied, but demonstrate the challenges New Zealand faces in continuing as a front-runner in the sister city movement. Sister city policies require honest assessment. Limited resources demand better investment where opportunities are identified or disassociation where they are not. Success requires robust policy development, professionalism and an effective public relations campaign informing communities concerned of the possibilities their international links can present.

  6. Creating Sister Cities: An Exchange Across Hemispheres

    Science.gov (United States)

    Adams, M. T.; Cabezon, S. A.; Hardy, E.; Harrison, R. J.

    2008-06-01

    Sponsored by Associated Universities, Inc. (AUI) and the National Radio Astronomy Observatory (NRAO), this project creates a cultural and educational exchange program between communities in South and North America, linking San Pedro de Atacama in Chile and Magdalena, New Mexico in the United States. Both communities have similar demographics, are in relatively undeveloped regions of high-elevation desert, and are located near major international radio astronomy research facilities. The Atacama Large Millimeter/submillimeter Array (ALMA) is just 40 km east of San Pedro; the Very Large Array (VLA) is just 40 km west of Magdalena. In February 2007, the Mayor of San Pedro and two teachers visited Magdalena for two weeks; in July 2007 three teachers from Magdalena will visit San Pedro. These visits enable the communities to lay the foundation for a permanent, unique partnership. The teachers are sharing expertise and teaching methodologies for physics and astronomy. In addition to creating science education opportunities, this project offers students linguistic and cultural connections. The town of San Pedro, Chile, hosts nearly 100,000 tourists per year, and English language skills are highly valued by local students. Through exchanges enabled by email and distance conferencing, San Pedro and Magdalena students will improve English and Spanish language skills while teaching each other about science and their respective cultures. This poster describes the AUI/NRAO Sister Cities program, including the challenges of cross-cultural communication and the rewards of interpersonal exchanges between continents and cultures.

  7. Mars' atmosphere: Earth's sister and statistical twin

    Science.gov (United States)

    Chen, Wilbur; Lovejoy, Shaun; Muller, Jan-Peter

    2016-04-01

    Satellite-based Martian re-analyses have allowed unprecedented comparisons between our atmosphere and that of our sister planet, underlining various similarities and differences in their respective dynamics. Yet by focusing on large scale structures and deterministic mechanisms they have improved our understanding of the dynamics only over fairly narrow ranges of (near) planetary scales. However, the Reynolds numbers of the flows on both planets are larger than 1011 and dissipation only occurs at centimetric (Mars) or millimetric scales (Earth) so that over most of their scale ranges, the dynamics are fully turbulent. In this presentation, we therefore examine the high level, statistical, turbulent laws for the temperature, horizontal wind and surface pressure, finding that Earth and Mars have virtually identical statistical exponents: their statistics are very similar over wide ranges. Therefore, it would seem that with the exception of certain aspects of the largest scales (such as the role of dust in atmospheric heating on Mars, or of water in its various phases on Earth), that the nonlinear dynamics are very similar. We argue that this is a prediction of the classical laws of turbulence when extended to planetary scales, and that it supports our use of turbulent laws on both planetary atmospheres.

  8. Horsetails are the sister group to all other monilophytes and Marattiales are sister to leptosporangiate ferns.

    Science.gov (United States)

    Knie, Nils; Fischer, Simon; Grewe, Felix; Polsakiewicz, Monika; Knoop, Volker

    2015-09-01

    The "Monilophyte" clade comprising ferns, horsetails and whisk ferns receives unequivocal support from molecular data as the sister clade to seed plants. However, the branching order of its earliest emerging lineages, the Equisetales (horsetails), the Marattiales, the Ophioglossales/Psilotales and the large group of leptosporangiate ferns has remained dubious. We investigated the mitochondrial nad2 and rpl2 genes as two new, intron-containing loci for a wide sampling of taxa. We found that both group II introns - nad2i542g2 and rpl2i846g2 - are universally present among monilophytes. Both introns have orthologues in seed plants where nad2i542g2 has evolved into a trans-arrangement. In contrast and despite substantial size extensions to more than 5kb in Psilotum, nad2i542g2 remains cis-arranged in the monilophytes. For phylogenetic analyses, we filled taxonomic gaps in previously investigated mitochondrial (atp1, nad5) and chloroplast (atpA, atpB, matK, rbcL, rps4) loci and created a 9-gene matrix that also included the new mitochondrial nad2 and rpl2 loci. We extended the taxon sampling with two taxa each for all land plant outgroups (liverworts, mosses, hornworts, lycophytes and seed plants) to minimize the risk of phylogenetic artefacts. We ultimately obtained a well-supported molecular phylogeny placing Marattiales as sister to leptosporangiate ferns and horsetails as sister to all remaining monilophytes. In addition, an indel in an exon of the here introduced rpl2 locus independently supports the placement of horsetails. We conclude that under dense taxon sampling, phylogenetic information from a prudent choice of loci is currently superior to character-rich phylogenomic approaches at low taxon sampling. As here shown the selective choice of loci and taxa enabled us to resolve the long-enigmatic diversifications of the earliest monilophyte lineages.

  9. Developing skills in clinical leadership for ward sisters.

    Science.gov (United States)

    Fenton, Katherine; Phillips, Natasha

    The Francis report has called for a strengthening of the ward sister's role. It recommends that sisters should operate in a supervisory capacity and should not be office bound. Effective ward leadership has been recognised as being vital to high-quality patient care and experience, resource management and interprofessional working. However, there is evidence that ward sisters are ill equipped to lead effectively and lack confidence in their ability to do so. University College London Hospitals Foundation Trust has recognised that the job has become almost impossible in increasingly large and complex organisations. Ward sisters spend less than 40% of their time on clinical leadership and the trust is undertaking a number of initiatives to support them in this role.

  10. CPAFFC Delegation Attends Annual Conference Of Australia Sister Cities Association

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    <正>At the invitation of the Australia Sister Cities Association(ASCA),the CPAFFC delegation visited Australia and attended the Annual Conference of ASCA in Devonport of Tasmania State from November 11 to 22,2006.

  11. Keynote: Sisters Academy. Intervenerende performancepraksis og sanselig uddannelse

    DEFF Research Database (Denmark)

    Hallberg, Gry Worre

    2016-01-01

    Med udgangspunkt i egen intervenerende performancepraksis forankret i visionen om et mere sanseligt samfund, og mere specifikt med det performative uddannelsesudviklingsprojekt Sisters Academy som case, belyses og diskuteres det, hvordan vi kan bruge performancekunst, som en eksperimenterende...

  12. Sister Callista Roy适应模式的应用

    Institute of Scientific and Technical Information of China (English)

    邢映影

    2002-01-01

    @@ 麻省Boston学院的护士理论家Sister Callista Roy,RN,Ph,D曾发表了、和等著作,提出并讨论了Sister Callista Roy适应模式.本文对该模式简单介绍并举例说明其应用,提出一点体会,供学习和应用借鉴.

  13. Two sisters resembling Gorlin-Chaudhry-Moss syndrome.

    Science.gov (United States)

    Aravena, Teresa; Passalacqua, Cristóbal; Pizarro, Oscar; Aracena, Mariana

    2011-10-01

    The Gorlin-Chaudhry-Moss syndrome (GCMS), was describe initially by Gorlin et al. [Gorlin et al. (1960)] in two sisters with craniosynostosis, hypertrichosis, hypoplastic labia majora, dental defects, eye anomalies, patent ductus arteriosus, and normal intelligence. Two other sporadic instances have been documented. Here, we report on two sisters with a condition with some similarities to GCMS as well as some differences, which could represent either previously unreported variability in GCMS, or it may represent a novel disorder.

  14. Sisters of St. Dorothy: an answer? (1866-1910

    Directory of Open Access Journals (Sweden)

    Ir. Diana Barbosa

    2016-12-01

    Full Text Available Implantation of the Congregation of the Sisters of St.  Dorothy inPortugal. Initial difficulties. New answers. Paula Frassinetti visits the Sisters. Development of the Institute inPortugal. Foundations: 1875-1910. Development of theCollegeofQuelhas.The Religious Persecution of 1901. The Revolution of October 1910 and the expulsion. Dispersion.Keywords  Dorothy;Portugal; Education;  Expansion.

  15. Archaeal DNA replication.

    Science.gov (United States)

    Kelman, Lori M; Kelman, Zvi

    2014-01-01

    DNA replication is essential for all life forms. Although the process is fundamentally conserved in the three domains of life, bioinformatic, biochemical, structural, and genetic studies have demonstrated that the process and the proteins involved in archaeal DNA replication are more similar to those in eukaryal DNA replication than in bacterial DNA replication, but have some archaeal-specific features. The archaeal replication system, however, is not monolithic, and there are some differences in the replication process between different species. In this review, the current knowledge of the mechanisms governing DNA replication in Archaea is summarized. The general features of the replication process as well as some of the differences are discussed.

  16. Geographic variance of cardiovascular risk factors among community women: the national Sister to Sister campaign.

    Science.gov (United States)

    Jarvie, Jennifer L; Johnson, Caitlin E; Wang, Yun; Wan, Yun; Aslam, Farhan; Athanasopoulos, Leonidas V; Pollin, Irene; Foody, JoAnne M

    2011-01-01

    There are substantial variations in cardiovascular disease (CVD) risk and outcomes among women. We sought to determine geographic variation in risk factor prevalence in a contemporary sample of U.S. women. Using 2008-2009 Sister to Sister (STS) free heart screening data from 17 U.S. cities, we compared rates of obesity (body mass index [BMI] ≥30 kg/m(2)), hypertension (HTN ≥140/90 mm Hg), low high-density lipoprotein cholesterol (HDL-C national rates. In 18,892 women (mean age 49.8 ± 14.3 years, 37% black, 32% white, 14% Hispanic), compared to overall STS rates, significantly higher rates were observed for obesity in Baltimore (42.4%), Atlanta (40.0%), Dallas (37.9%), and Jacksonville (36.0%); for HTN in Atlanta (43.9%), Baltimore (42.5%), and New York (39.1%); for hyperglycemia in Jacksonville (20.3%), Philadelphia (18.1%), and Tampa (17.8%); and for HDL-C national American Heart Association (AHA) 2010 update rates, most STS cities had higher rates of hyperglycemia and low HDL-C. In a large, community-based sample of women nationwide, this comprehensive analysis shows remarkable geographic variation in risk factors, which provides opportunities to improve and reduce a woman's CVD risk. Further investigation is required to understand the reasons behind such variation, which will provide insight toward tailoring preventive interventions to narrow gaps in CVD risk reduction in women.

  17. Teenage pregnancy: the impact of maternal adolescent childbearing and older sister's teenage pregnancy on a younger sister.

    Science.gov (United States)

    Wall-Wieler, Elizabeth; Roos, Leslie L; Nickel, Nathan C

    2016-05-25

    Risk factors for teenage pregnancy are linked to many factors, including a family history of teenage pregnancy. This research examines whether a mother's teenage childbearing or an older sister's teenage pregnancy more strongly predicts teenage pregnancy. This study used linkable administrative databases housed at the Manitoba Centre for Health Policy (MCHP). The original cohort consisted of 17,115 women born in Manitoba between April 1, 1979 and March 31, 1994, who stayed in the province until at least their 20(th) birthday, had at least one older sister, and had no missing values on key variables. Propensity score matching (1:2) was used to create balanced cohorts for two conditional logistic regression models; one examining the impact of an older sister's teenage pregnancy and the other analyzing the effect of the mother's teenage childbearing. The adjusted odds of becoming pregnant between ages 14 and 19 for teens with at least one older sister having a teenage pregnancy were 3.38 (99 % CI 2.77-4.13) times higher than for women whose older sister(s) did not have a teenage pregnancy. Teenage daughters of mothers who had their first child before age 20 had 1.57 (99 % CI 1.30-1.89) times higher odds of pregnancy than those whose mothers had their first child after age 19. Educational achievement was adjusted for in a sub-population examining the odds of pregnancy between ages 16 and 19. After this adjustment, the odds of teenage pregnancy for teens with at least one older sister who had a teenage pregnancy were reduced to 2.48 (99 % CI 2.01-3.06) and the odds of pregnancy for teen daughters of teenage mothers were reduced to 1.39 (99 % CI 1.15-1.68). Although both were significant, the relationship between an older sister's teenage pregnancy and a younger sister's teenage pregnancy is much stronger than that between a mother's teenage childbearing and a younger daughter's teenage pregnancy. This study contributes to understanding of the broader topic "who is

  18. little sister: An Afro-Temporal Solo-Play.

    Science.gov (United States)

    De Berry, Misty

    2016-09-12

    little sister: An Afro-Temporal Solo-Play is at once a memory-scape and a mytho-biography set to poetry, movement, and mixed media. A performance poem spanning from the Antebellum South to present-moment Chicago, it tells the story of a nomadic spirit named little-she who shape-shifts through the memories and imaginings of her sister, the narrator. Through the characters little-she and the narrator, the solo-performance explores embodied ways to rupture and relieve the impact of macro forms of violence in the micro realm of the everyday. To this end, little sister witnesses and disrupts the legacy of violence in the lives of queer Black women through a trans-temporal navigation of everyday encounters within familial, small groups and intimate partner spaces.

  19. Familial acromegaly - case study of two sisters with acromegaly.

    Science.gov (United States)

    Malicka, Joanna; Świrska, Joanna; Nowakowski, Andrzej

    2011-01-01

    In the majority of cases, acromegaly is sporadic. However, it can also occur in a familial setting as a component of MEN-1, MEN-4, Carney complex (CNC) or as the extremely rare syndrome of isolated familial somatotropinoma (IFS), the latter belonging to familial isolated pituitary adenomas (FIPA). The diagnosis of IFS is based on the recognition of acromegaly/gigantism in at least two family members, given that the family is not affected by MEN-1, MEN-4 or CNC. The authors present a case study of two sisters: a 56 year-old patient (case no. 1) and a 61 year-old patient (case no. 2). In both sisters, acromegaly was recognised in the course of pituitary macroadenoma. Neither of the sisters showed features of MEN-1, MEN-4 or Carney complex. The authors suppose that the presented cases are manifestations of IFS. However, this diagnosis has not been confirmed yet because of the poor availability of genetic tests.

  20. [Florence Nightingale and charity sisters: revisiting the history].

    Science.gov (United States)

    Padilha, Maria Itayra Coelho de Souza; Mancia, Joel Rolim

    2005-01-01

    This study presents an historical analysis on the links between the nursing practice and the influence received from various religious orders/associations along the times, especially from Saint Vincent Paul's charity sisters. The professional nursing which was pioneered by Florence Nightingale in the XlXth century, was directly influenced by the teachings of love and fraternity. In addition, other contributions from the religious orders/associations were the concepts of altruism, valorization of an adequate environment for the care of patients, and the division of work in nursing. The study shows the influence of Charity Sisters on Florence Nightingale.

  1. Links between DNA Replication, Stem Cells and Cancer

    Directory of Open Access Journals (Sweden)

    Alex Vassilev

    2017-01-01

    Full Text Available Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in early embryos give rise to all of the cell lineages in the embryo and adult, but when they mislocate to ectopic sites, they produce tumors. Remarkably, pluripotent stem cells, like many cancer cells, depend on the Geminin protein to prevent excess DNA replication from triggering DNA damage-dependent apoptosis. This link between the control of DNA replication during early development and germ cell neoplasia reveals Geminin as a potential chemotherapeutic target in the eradication of cancer progenitor cells.

  2. Links between DNA Replication, Stem Cells and Cancer.

    Science.gov (United States)

    Vassilev, Alex; DePamphilis, Melvin L

    2017-01-25

    Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in early embryos give rise to all of the cell lineages in the embryo and adult, but when they mislocate to ectopic sites, they produce tumors. Remarkably, pluripotent stem cells, like many cancer cells, depend on the Geminin protein to prevent excess DNA replication from triggering DNA damage-dependent apoptosis. This link between the control of DNA replication during early development and germ cell neoplasia reveals Geminin as a potential chemotherapeutic target in the eradication of cancer progenitor cells.

  3. Letters from a suicide: Van Gogh and his sister.

    Science.gov (United States)

    Lester, David

    2010-04-01

    An analysis of trends over a 3-yr. period in the letters of Vincent Van Gogh to his sister as the time of his suicide approached identified 8 trends, including an increase in words concerned with anxiety and words concerned with the past.

  4. Sister M. Madeleva Wolff, C.S.C.

    Science.gov (United States)

    Petit, M. Loretta

    2006-01-01

    Sister M. Madeleva Wolff, C.S.C., teacher, essayist, poet, and college administrator, through her creative ability and innovative practices made possible major contributions to Catholic education in her lifetime. Without her strong personality and boundless energy, many of her dreams for an ideal college curriculum would not have come to fruition.…

  5. Some Effects of Having a Brother or Sister.

    Science.gov (United States)

    Leventhal, Gerald S.

    The data indicate that the influence of a brother or sister is considerably greater upon the second born than upon the first born. The magnitude of the sex of sibling effect is probably dependent upon whether a sibling is present during the first few years of life, a period during which many enduring response patterns are being acquired. The…

  6. El naturalismo americano: Theodore Dreiser y Sister Carrie

    Directory of Open Access Journals (Sweden)

    Dolores G. ALONSO MULAS

    2009-08-01

    Full Text Available Para situar a un escritor, como Theodore Dreiser, y especialmente su novela Sister Carrie dentro de un movimiento literario y de una etapa determinada de la historia americana, es necesario dar un breve repaso al naturalismo, llegado a América a través de Stephen Crane

  7. Freud on Brothers and Sisters: A Neglected Topic

    Science.gov (United States)

    Sherwin-White, Susan

    2007-01-01

    This paper explores Freud's developing thought on brothers and sisters, and their importance in his psychoanalytical writings and clinical work. Freud's work on sibling psychology has been seriously undervalued. This paper aims to give due recognition to Freud's work in this area. (Contains 1 note.)

  8. The Lehman Sisters Hypothesis: an exploration of literature and bankers

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2012-01-01

    textabstractThis article tests the Lehman Sisters Hypothesis in two complementary, although incomplete ways. It reviews the diverse empirical literature in behavioural, experimental, and neuroeconomics as well as related fields of behavioural research. And it presents the findings from an explorativ

  9. The Lehman Sisters Hypothesis: an exploration of literature and bankers

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2012-01-01

    textabstractAbstract This article tests the Lehman Sisters Hypothesis in two complementary, although incomplete ways. It reviews the diverse empirical literature in behavioral, experimental, and neuroeconomics as well as related fields of behavioral research. And it presents the findings from an exp

  10. 写作风景线 My Sister

    Institute of Scientific and Technical Information of China (English)

    尹姗姗; 高现华; 刘占华

    2004-01-01

    I ave a pretty sister.She’s fourteen years old.Shestudies hard.So she sets agood example to me.Shersgetting on well with her class-mates and her teachers. Shelikes maths and Chinese,andshe's good at them.She likesdancing and music very much.

  11. The Lehman Sisters Hypothesis: an exploration of literature and bankers

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2012-01-01

    textabstractThis article tests the Lehman Sisters Hypothesis in two complementary, although incomplete ways. It reviews the diverse empirical literature in behavioural, experimental, and neuroeconomics as well as related fields of behavioural research. And it presents the findings from an

  12. The Lehman Sisters Hypothesis: an exploration of literature and bankers

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2012-01-01

    textabstractAbstract This article tests the Lehman Sisters Hypothesis in two complementary, although incomplete ways. It reviews the diverse empirical literature in behavioral, experimental, and neuroeconomics as well as related fields of behavioral research. And it presents the findings from an

  13. The Broken American Dream Based on Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    Dong Wenjuan

    2012-01-01

      Sister Carrie is the first work of Theodore Dreiser, It tells us how a country maiden becomes a famous star in Broadway. In the novel, Dreiser describes the living conditions and emotion changes of Carrie very vividly. Sister Carrie takes true realism as its distinctive feature, reflects the tragic fact that people pursue American dream fanatically in the early twentieth century. This paper exposes the theme of instinct, which drives people to enjoy but disillusion finally, and illustrates that it is impossible to possess true happiness in a money-oriented capitalism society%  Sister Carrie is the first work of Theodore Dreiser, Ittells us how a country maiden becomes a famous star in Broadway.In the novel, Dreiser describes the living conditions and emotion changes of Carrie very vividly. Sister Carrie takes true realism as itsdistinctive feature, reflects the tragic fact that people pursue Americandream fanatically in the early twentieth century. This paper exposes the theme of instinct, which drives people to enjoy but disillusion finally, and illustrates that it is impossible to possess true happiness in a money-oriented capitalism society

  14. Adult Sibling Relationships with Brothers and Sisters with Severe Disabilities

    Science.gov (United States)

    Rossetti, Zach; Hall, Sarah

    2015-01-01

    The purpose of this qualitative study was to examine perceptions of adult sibling relationships with a brother or sister with severe disabilities and the contexts affecting the relationships. Adult siblings without disabilities (N = 79) from 19 to 72 years of age completed an online survey with four open-ended questions about their relationship…

  15. Freud on Brothers and Sisters: A Neglected Topic

    Science.gov (United States)

    Sherwin-White, Susan

    2007-01-01

    This paper explores Freud's developing thought on brothers and sisters, and their importance in his psychoanalytical writings and clinical work. Freud's work on sibling psychology has been seriously undervalued. This paper aims to give due recognition to Freud's work in this area. (Contains 1 note.)

  16. Replication Restart in Bacteria.

    Science.gov (United States)

    Michel, Bénédicte; Sandler, Steven J

    2017-07-01

    In bacteria, replication forks assembled at a replication origin travel to the terminus, often a few megabases away. They may encounter obstacles that trigger replisome disassembly, rendering replication restart from abandoned forks crucial for cell viability. During the past 25 years, the genes that encode replication restart proteins have been identified and genetically characterized. In parallel, the enzymes were purified and analyzed in vitro, where they can catalyze replication initiation in a sequence-independent manner from fork-like DNA structures. This work also revealed a close link between replication and homologous recombination, as replication restart from recombination intermediates is an essential step of DNA double-strand break repair in bacteria and, conversely, arrested replication forks can be acted upon by recombination proteins and converted into various recombination substrates. In this review, we summarize this intense period of research that led to the characterization of the ubiquitous replication restart protein PriA and its partners, to the definition of several replication restart pathways in vivo, and to the description of tight links between replication and homologous recombination, responsible for the importance of replication restart in the maintenance of genome stability. Copyright © 2017 American Society for Microbiology.

  17. Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.

    Directory of Open Access Journals (Sweden)

    Jessica Hopkins

    2014-07-01

    Full Text Available Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3 proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β, two α-kleisins (RAD21L and REC8 and one STAG protein (STAG3 that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC. From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8 is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis

  18. Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.

    Science.gov (United States)

    Hopkins, Jessica; Hwang, Grace; Jacob, Justin; Sapp, Nicklas; Bedigian, Rick; Oka, Kazuhiro; Overbeek, Paul; Murray, Steve; Jordan, Philip W

    2014-07-01

    Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3) proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG) protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β), two α-kleisins (RAD21L and REC8) and one STAG protein (STAG3) that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC). From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8) is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis-specific cohesin

  19. Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.

    Directory of Open Access Journals (Sweden)

    Jessica Hopkins

    2014-07-01

    Full Text Available Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3 proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β, two α-kleisins (RAD21L and REC8 and one STAG protein (STAG3 that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC. From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8 is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis

  20. Mercury poisoning in two 13-year-old twin sisters

    OpenAIRE

    Ezzat Khodashenas; Mohammadhassan Aelami; Mahdi Balali-Mood

    2015-01-01

    Mercury (Hg) is a toxic agent that evaporates in room temperature and its inhalation may cause poisoning. Due to the nonspecific symptoms, diagnosis is difficult in special circumstances with no initial history of Hg exposure. We report two such cases of Hg poisoning. The patients were two sisters, presenting with pain in extremities, itchy rashes, sweating, salivation, weakness, and mood changes. They have used a compound that contains mercury, for treatment of pedicullosis three months befo...

  1. The Construction of Social Darwinism in Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    薛晶晶; 秦素华

    2014-01-01

    Social Darwinism is an important theory reflected in Sister Carrie. This thesis is to interpret the characters’fates with Social Darwinism.“Survival of the fittest”is an important theme. Carrie is the winner of life and Hurtwood is the loser. Their adjustability to the environment determines their future. It is hoped to help the readers construct a better understanding on this theory.

  2. Autosomal recessive limb girdle myasthenia in two sisters.

    Directory of Open Access Journals (Sweden)

    Shankar A

    2002-10-01

    Full Text Available Limb girdle myasthenic syndromes are rare genetic disorders described under the broad heterogeneous group known as congenital myasthenic syndromes and present with mixed features of myasthenia and myopathy. The familial limb girdle myasthenia has been described as one with selective weakness of pectoral and pelvic girdles, showing a positive response to edrophonium chloride. A report of two sisters affected by this disorder is presented.

  3. Cell killing and chromatid damage in primary human bronchial epithelial cells irradiated with accelerated 56Fe ions

    Science.gov (United States)

    Suzuki, M.; Piao, C.; Hall, E. J.; Hei, T. K.

    2001-01-01

    We examined cell killing and chromatid damage in primary human bronchial epithelial cells irradiated with high-energy 56Fe ions. Cells were irradiated with graded doses of 56Fe ions (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at Brookhaven National Laboratory. The survival curves for cells plated 1 h after irradiation (immediate plating) showed little or no shoulder. However, the survival curves for cells plated 24 h after irradiation (delayed plating) had a small initial shoulder. The RBE for 56Fe ions compared to 137Cs gamma rays was 1.99 for immediate plating and 2.73 for delayed plating at the D10. The repair ratio (delayed plating/immediate plating) was 1.67 for 137Cs gamma rays and 1.22 for 56Fe ions. The dose-response curves for initially measured and residual chromatid fragments detected by the Calyculin A-mediated premature chromosome condensation technique showed a linear response. The results indicated that the induction frequency for initially measured fragments was the same for 137Cs gamma rays and 56Fe ions. On the other hand, approximately 85% of the fragments induced by 137Cs gamma rays had rejoined after 24 h of postirradiation incubation; the corresponding amount for 56Fe ions was 37%. Furthermore, the frequency of chromatid exchanges induced by gamma rays measured 24 h after irradiation was higher than that induced by 56Fe ions. No difference in the amount of chromatid damage induced by the two types of radiations was detected when assayed 1 h after irradiation. The results suggest that high-energy 56Fe ions induce a higher frequency of complex, unrepairable damage at both the cellular and chromosomal levels than 137Cs gamma rays in the target cells for radiation-induced lung cancers.

  4. DNA asymmetry in stem cells - immortal or mortal?

    Science.gov (United States)

    Yadlapalli, Swathi; Yamashita, Yukiko M

    2013-09-15

    The immortal strand hypothesis proposes that stem cells retain a template copy of genomic DNA (i.e. an 'immortal strand') to avoid replication-induced mutations. An alternative hypothesis suggests that certain cells segregate sister chromatids non-randomly to transmit distinct epigenetic information. However, this area of research has been highly controversial, with conflicting data even from the same cell types. Moreover, historically, the same term of 'non-random sister chromatid segregation' or 'biased sister chromatid segregation' has been used to indicate distinct biological processes, generating a confusion in the biological significance and potential mechanism of each phenomenon. Here, we discuss the models of non-random sister chromatid segregation, and we explore the strengths and limitations of the various techniques and experimental model systems used to study this question. We also describe our recent study on Drosophila male germline stem cells, where sister chromatids of X and Y chromosomes are segregated non-randomly during cell division. We aim to integrate the existing evidence to speculate on the underlying mechanisms and biological relevance of this long-standing observation on non-random sister chromatid segregation.

  5. Broad phylogenomic sampling and the sister lineage of land plants.

    Directory of Open Access Journals (Sweden)

    Ruth E Timme

    Full Text Available The tremendous diversity of land plants all descended from a single charophyte green alga that colonized the land somewhere between 430 and 470 million years ago. Six orders of charophyte green algae, in addition to embryophytes, comprise the Streptophyta s.l. Previous studies have focused on reconstructing the phylogeny of organisms tied to this key colonization event, but wildly conflicting results have sparked a contentious debate over which lineage gave rise to land plants. The dominant view has been that 'stoneworts,' or Charales, are the sister lineage, but an alternative hypothesis supports the Zygnematales (often referred to as "pond scum" as the sister lineage. In this paper, we provide a well-supported, 160-nuclear-gene phylogenomic analysis supporting the Zygnematales as the closest living relative to land plants. Our study makes two key contributions to the field: 1 the use of an unbiased method to collect a large set of orthologs from deeply diverging species and 2 the use of these data in determining the sister lineage to land plants. We anticipate this updated phylogeny not only will hugely impact lesson plans in introductory biology courses, but also will provide a solid phylogenetic tree for future green-lineage research, whether it be related to plants or green algae.

  6. Genomic sister-disorders of neurodevelopment: an evolutionary approach.

    Science.gov (United States)

    Crespi, Bernard; Summers, Kyle; Dorus, Steve

    2009-02-01

    Genomic sister-disorders are defined here as diseases mediated by duplications versus deletions of the same region. Such disorders can provide unique information concerning the genomic underpinnings of human neurodevelopment because effects of diametric variation in gene copy number on cognitive and behavioral phenotypes can be inferred. We describe evidence from the literature on deletions versus duplications for the regions underlying the best-known human neurogenetic sister-disorders, including Williams syndrome, Velocardiofacial syndrome, and Smith-Magenis syndrome, as well as the X-chromosomal conditions Klinefelter and Turner syndromes. These data suggest that diametric copy-number alterations can, like diametric alterations to imprinted genes, generate contrasting phenotypes associated with autistic-spectrum and psychotic-spectrum conditions. Genomically based perturbations to the development of the human social brain are thus apparently mediated to a notable degree by effects of variation in gene copy number. We also conducted the first analyses of positive selection for genes in the regions affected by these disorders. We found evidence consistent with adaptive evolution of protein-coding genes, or selective sweeps, for three of the four sets of sister-syndromes analyzed. These studies of selection facilitate identification of candidate genes for the phenotypes observed and lend a novel evolutionary dimension to the analysis of human cognitive architecture and neurogenetic disorders.

  7. Strain gradients and melt pathways, Twin Sisters complex, Washington State

    Science.gov (United States)

    Kruckenberg, S. C.; Newman, J.; Tikoff, B.; Toy, V. G.

    2009-12-01

    The Twin Sisters complex in the North Cascades of Washington state is a large (~6 by 16 km), virtually unaltered ultramafic body that provides information about the relationships between the formation of compositional layering, structural fabrics and the formation of inferred melt pathways in naturally deforming peridotites. Compositional layering is largely defined by alternating layers of orthopyroxene-absent dunite (>95% olivine) and orthopyroxene-present (~15% orthopyroxene; ~85% olivine) harzburgite aligned parallel to a roughly N-S striking and steeply dipping foliation. Orthopyroxene- and clinopyroxene-bearing dikes occur throughout the Twin Sisters and crosscut the host dunite and harzburgite layering. Orthopyroxene dikes range in thickness from 1 cm to >1 m and are variably oriented and may be folded. Clinopyroxene-bearing dikes are thinner, more consistently oriented (~N-S), and generally more tabular than the orthopyroxene dikes. In the Twin Sisters, cm- to m-scale zones of porphyroclastic dunite cross-cut the main dunite-harzburgite compositional layering and display a variety of relationships with pyroxene dikes in the region. These porphyroclastic dunite bands locally contain single olivine grains >10 cm and likely represent former pathways of melt migration. Transect mapping along an E-W traverse across the Twin Sisters massif reveals that these inferred melt channels form at various angles relative to the main dunite-harzburgite layering. In the west, porphyroclastic olivine layers form at low angle to the main foliation and compositional layering. These zone form at systematically higher angles across the structural section of the Twin Sisters massif to the east and commonly form conjugate cross-cutting sets at high-angle to the main N-S dunite-harzburgite layering. This change in band angle correlates broadly with changes in the intensity of folding of orthopyroxene-bearing dikes, with more intensely deformed dikes in the west to more planar dikes

  8. Mutagen sensitivity as measured by induced chromatid breakage as a marker of cancer risk.

    Science.gov (United States)

    Wu, Xifeng; Zheng, Yun-Ling; Hsu, T C

    2014-01-01

    Risk assessment is now recognized as a multidisciplinary process, extending beyond the scope of traditional epidemiologic methodology to include biological evaluation of interindividual differences in carcinogenic susceptibility. Modulation of environmental exposures by host genetic factors may explain much of the observed interindividual variation in susceptibility to carcinogenesis. These genetic factors include, but are not limited to, carcinogen metabolism and DNA repair capacity. This chapter describes a standardized method for the functional assessment of mutagen sensitivity. This in vitro assay measures the frequency of mutagen-induced breaks in the chromosomes of peripheral blood lymphocytes. Mutagen sensitivity assessed by this method has been shown to be a significant risk factor for tobacco-related maladies, especially those of the upper aerodigestive tract. Mutagen sensitivity may therefore be a useful member of a panel of susceptibility markers for defining high-risk subgroups for chemoprevention trials. This chapter describes methods for and discusses results from studies of mutagen sensitivity as measured by quantifying chromatid breaks induced by clastogenic agents, such as the γ-radiation mimetic DNA cross-linking agent bleomycin and chemicals that form so-called bulky DNA adducts, such as 4-nitroquinoline and the tobacco smoke constituent benzo[a]pyrene, in short-term cultured peripheral blood lymphocytes.

  9. DNA replication and cancer

    DEFF Research Database (Denmark)

    Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

    2016-01-01

    A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways...... causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy....

  10. Chiasmatic and achiasmatic inverted meiosis of plants with holocentric chromosomes

    Science.gov (United States)

    Cabral, Gabriela; Marques, André; Schubert, Veit; Pedrosa-Harand, Andrea; Schlögelhofer, Peter

    2014-01-01

    Meiosis is a specialized cell division in sexually reproducing organisms before gamete formation. Following DNA replication, the canonical sequence in species with monocentric chromosomes is characterized by reductional segregation of homologous chromosomes during the first and equational segregation of sister chromatids during the second meiotic division. Species with holocentric chromosomes employ specific adaptations to ensure regular disjunction during meiosis. Here we present the analysis of two closely related plant species with holocentric chromosomes that display an inversion of the canonical meiotic sequence, with the equational division preceding the reductional. In-depth analysis of the meiotic divisions of Rhynchospora pubera and R. tenuis reveals that during meiosis I sister chromatids are bi-oriented, display amphitelic attachment to the spindle and are subsequently separated. During prophase II, chromatids are connected by thin chromatin threads that appear instrumental for the regular disjunction of homologous non-sister chromatids in meiosis II. PMID:25295686

  11. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  12. ATPase-Dependent Control of the Mms21 SUMO Ligase during DNA Repair

    NARCIS (Netherlands)

    M. Bermúdez-López (Marcelino); I. Pociño-Merino (Irene); H. Sanchez (Humberto); A. Bueno (Andrés); C. Guasch (Clàudia); S. Almedawar (Seba); S. Bru-Virgili (Sergi); E. Garí (Eloi); C. Wyman (Claire); D. Reverter (David); N. Colomina (Neus); J. Torres-Rosell (Jordi)

    2015-01-01

    textabstractModification of proteins by SUMO is essential for the maintenance of genome integrity. During DNA replication, the Mms21-branch of the SUMO pathway counteracts recombination intermediates at damaged replication forks, thus facilitating sister chromatid disjunction. The Mms21 SUMO ligase

  13. Obstetric prognosis in sisters of preeclamptic women – implications for genetic linkage studies

    Directory of Open Access Journals (Sweden)

    Heinonen Seppo

    2003-02-01

    Full Text Available Abstract Background To investigate obstetric prognosis in sisters of preeclamptic women. Methods We identified consecutive 635 sib pairs from the Birth Registry data of Kuopio University Hospital who had their first delivery between January 1989 and December 1999 in our institution. Of these, in 530 pairs both sisters had non-preeclamptic pregnancies (the reference group, in 63 pairs one of the sisters had preeclampsia and the unaffected sisters were studied (study group I. In 42 pairs both sister's first delivery was affected (study group II. Pregnancy outcome measures in these groups were compared. Results Unaffected sisters of the index patients had uncompromised fetal growth in their pregnancies, and overall, as good obstetric outcomes as in the reference group. The data on affected sisters of the index patients showed an increased prematurity rate, and increased incidences of low birth weight and small-for-gestational age infants, as expected. Conclusion Unaffected sisters of the index patients had no signs of utero-placental insufficiency and they were at low risk with regard to adverse obstetric outcome, whereas affected sisters were high-risk. Clinically, affected versus unaffected status appears to be clear-cut in first-degree relatives regardless of their genetic susceptibility and unaffected sisters do not need special antepartum surveillance.

  14. Reflection of Naturalism and Darwinism in Dreiser' s Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    王静

    2009-01-01

    Naturalism is a significant school of literature in American literary history. This thesis mainly reviews the background, development, and characteristic of the realism and naturalism literature, and states the significant person in Naturalism literature-Dreiser and his. important literary position and analyzes the reflection of naturalism and Darwinism in Sister Carrie. Through the analysis of determinism, desire, ethics and detail description, a conclusion is made: the factors affecting the novel' s writing not only include the author' s own experiences but also the main social ideology in his living years.

  15. Dealing with conflict - The role of the ward sister

    Directory of Open Access Journals (Sweden)

    L.M. Cremer

    1980-09-01

    Full Text Available In the course of her duties, the ward sister has to contend with many forms of conflict, discord and dissension. These involve conflict of the intrapersonal, interpersonal and intergroup varieties. Conflict is in the main, disruptive and dysfunctional. Skilful management, however, embodying cooperative effort in its reduction can produce constructive and positive results. Conflict management strategies are therefore either restrictive or constructive. Persons in serious conflict suffer varied degrees of personality disequilibrium, which necessitates emotional first aid or crisis intervention. Such primary preventive care is applicable to patients, their relatives, and members of the nursing staff in such need.

  16. The Replication Recipe: What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't

    2014-01-01

    Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

  17. Cortical Pathology in RRMS: Taking a Cue from Four Sisters

    Directory of Open Access Journals (Sweden)

    Massimiliano Calabrese

    2012-01-01

    Full Text Available Background. Although grey matter pathology is a relevant aspect of multiple sclerosis (MS both with physical and cognitive rebounds, its pathogenesis is still under investigation. To what extent the familial and sporadic cases of MS differ in cortical pathology has not been elucidated yet. Here we present a multiple case report of four sisters affected by MS, all of them having a very high burden of cortical pathology. Methods. The clinical and grey matter MRI parameters of the patients were compared with those of twenty-five-aged matched healthy women and 25 women affected by sporadic MS (matched for age, disease duration, EDSS, and white matter lesion load. Results. Despite their short disease duration (<5 years, the four sisters showed a significant cortical thinning compared to healthy controls ( and sporadic MS ( and higher CLs number ( and volume ( compared to sporadic MS. Discussion. Although limited to a single family, our observation is worth of interest since it suggests that familial factors may account for a peculiar involvement of the cortex in MS pathology. This hypothesis should be further evaluated in a large number of multiplex MS families.

  18. Modeling DNA Replication.

    Science.gov (United States)

    Bennett, Joan

    1998-01-01

    Recommends the use of a model of DNA made out of Velcro to help students visualize the steps of DNA replication. Includes a materials list, construction directions, and details of the demonstration using the model parts. (DDR)

  19. Eukaryotic DNA Replication Fork.

    Science.gov (United States)

    Burgers, Peter M J; Kunkel, Thomas A

    2017-06-20

    This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.

  20. Abiotic self-replication.

    Science.gov (United States)

    Meyer, Adam J; Ellefson, Jared W; Ellington, Andrew D

    2012-12-18

    The key to the origins of life is the replication of information. Linear polymers such as nucleic acids that both carry information and can be replicated are currently what we consider to be the basis of living systems. However, these two properties are not necessarily coupled. The ability to mutate in a discrete or quantized way, without frequent reversion, may be an additional requirement for Darwinian evolution, in which case the notion that Darwinian evolution defines life may be less of a tautology than previously thought. In this Account, we examine a variety of in vitro systems of increasing complexity, from simple chemical replicators up to complex systems based on in vitro transcription and translation. Comparing and contrasting these systems provides an interesting window onto the molecular origins of life. For nucleic acids, the story likely begins with simple chemical replication, perhaps of the form A + B → T, in which T serves as a template for the joining of A and B. Molecular variants capable of faster replication would come to dominate a population, and the development of cycles in which templates could foster one another's replication would have led to increasingly complex replicators and from thence to the initial genomes. The initial genomes may have been propagated by RNA replicases, ribozymes capable of joining oligonucleotides and eventually polymerizing mononucleotide substrates. As ribozymes were added to the genome to fill gaps in the chemistry necessary for replication, the backbone of a putative RNA world would have emerged. It is likely that such replicators would have been plagued by molecular parasites, which would have been passively replicated by the RNA world machinery without contributing to it. These molecular parasites would have been a major driver for the development of compartmentalization/cellularization, as more robust compartments could have outcompeted parasite-ridden compartments. The eventual outsourcing of metabolic

  1. Adenovirus DNA Replication

    OpenAIRE

    Hoeben, Rob C.; Uil, Taco G.

    2013-01-01

    Adenoviruses have attracted much attention as probes to study biological processes such as DNA replication, transcription, splicing, and cellular transformation. More recently these viruses have been used as gene-transfer vectors and oncolytic agents. On the other hand, adenoviruses are notorious pathogens in people with compromised immune functions. This article will briefly summarize the basic replication strategy of adenoviruses and the key proteins involved and will deal with the new deve...

  2. Minichromosome replication in vitro: inhibition of re-replication by replicatively assembled nucleosomes.

    Science.gov (United States)

    Krude, T; Knippers, R

    1994-08-19

    Single-stranded circular DNA, containing the SV40 origin sequence, was used as a template for complementary DNA strand synthesis in cytosolic extracts from HeLa cells. In the presence of the replication-dependent chromatin assembly factor CAF-1, defined numbers of nucleosomes were assembled during complementary DNA strand synthesis. These minichromosomes were then induced to semiconservatively replicate by the addition of the SV40 initiator protein T antigen (re-replication). The results indicate that re-replication of minichromosomes appears to be inhibited by two independent mechanisms. One acts at the initiation of minichromosome re-replication, and the other affects replicative chain elongation. To directly demonstrate the inhibitory effect of replicatively assembled nucleosomes, two types of minichromosomes were prepared: (i) post-replicative minichromosomes were assembled in a reaction coupled to replication as above; (ii) pre-replicative minichromosomes were assembled independently of replication on double-stranded DNA. Both types of minichromosomes were used as templates for DNA replication under identical conditions. Replicative fork movement was found to be impeded only on post-replicative minichromosome templates. In contrast, pre-replicative minichromosomes allowed one unconstrained replication cycle, but re-replication was inhibited due to a block in fork movement. Thus, replicatively assembled chromatin may have a profound influence on the re-replication of DNA.

  3. Narcolepsy with cataplexy mimicry: the strange case of two sisters.

    Science.gov (United States)

    Pizza, Fabio; Vandi, Stefano; Poli, Francesca; Moghadam, Keivan Kaveh; Franceschini, Christian; Bellucci, Claudia; Cipolli, Carlo; Ingravallo, Francesca; Natalini, Giuliana; Mignot, Emmanuel; Plazzi, Giuseppe

    2013-06-15

    We report on two sisters, 17 and 12 years of age, with clinical features suggesting narcolepsy with cataplexy (NC): daytime sleepiness, spontaneous and emotionally triggered sudden falls to the ground, and overweight/obesity. MSLT showed borderline sleep latency, with 1 and 0 sleep onset REM periods. HLA typing disclosed the DQB1*0602 allele. Video-polygraphy of the spells ruled out NC diagnosis by demonstrating their easy elicitation by suggestion, with wake EEG, electromyographic persistence of muscle tone, and stable presence of tendon reflexes (i.e., pseudo-cataplexy), together with normal cerebrospinal hypocretin-1 levels. Our cases emphasize the need of a clear depiction of cataplexy pattern at the different ages, the usefulness of examining ictal neurophysiology, and collecting all available disease markers in ambiguous cases.

  4. Mercury poisoning in two 13-year-old twin sisters.

    Science.gov (United States)

    Khodashenas, Ezzat; Aelami, Mohammadhassan; Balali-Mood, Mahdi

    2015-03-01

    Mercury (Hg) is a toxic agent that evaporates in room temperature and its inhalation may cause poisoning. Due to the nonspecific symptoms, diagnosis is difficult in special circumstances with no initial history of Hg exposure. We report two such cases of Hg poisoning. The patients were two sisters, presenting with pain in extremities, itchy rashes, sweating, salivation, weakness, and mood changes. They have used a compound that contains mercury, for treatment of pedicullosis three months before admission. This compound was purchased from a herbal shop and was applied locally on the scalps for 2 days. Their urinary mercury concentrations were 50 and 70 mg/L. They were successfully treated by D-penicillamine and gabapentin. In a patient with any kind of bone and joint pain, skin rash erythema and peripheral neuropathy, mercury poisoning should be considered as a differential diagnosis.

  5. Mercury poisoning in two 13-year-old twin sisters

    Directory of Open Access Journals (Sweden)

    Ezzat Khodashenas

    2015-01-01

    Full Text Available Mercury (Hg is a toxic agent that evaporates in room temperature and its inhalation may cause poisoning. Due to the nonspecific symptoms, diagnosis is difficult in special circumstances with no initial history of Hg exposure. We report two such cases of Hg poisoning. The patients were two sisters, presenting with pain in extremities, itchy rashes, sweating, salivation, weakness, and mood changes. They have used a compound that contains mercury, for treatment of pedicullosis three months before admission. This compound was purchased from a herbal shop and was applied locally on the scalps for 2 days. Their urinary mercury concentrations were 50 and 70 mg/L. They were successfully treated by D-penicillamine and gabapentin. In a patient with any kind of bone and joint pain, skin rash erythema and peripheral neuropathy, mercury poisoning should be considered as a differential diagnosis.

  6. A Bangladeshi family with three sisters 'Bombay' or Oh phenotype.

    Science.gov (United States)

    Rahman, M; Abdullah, A Z; Husain, M; Hague, K M; Hossain, M M

    1990-12-01

    Three sisters in a same family (MIAH FAMILY) are of 'Bombay' phenotype. These being the first known female examples of 'Bombay' blood group have been detected in Bangladesh. As predicted by current theory their red cells are Le(a+b-) and their saliva do not contain any of the antigens A, B and H except Lea substance. Family studies showed that individuals with 'Bombay' or Oh phenotype may have A or B gene which are not expressed. This very particular type of blood is one of the rarest in any other parts of world except in India. Due to the presence of anti-H antibody in the plasma of Oh phenotype, when considering such patients for transfusion only blood of identical Bombay type can be safely transfused.

  7. Investigating variation in replicability: A "Many Labs" replication project

    NARCIS (Netherlands)

    Klein, R.A.; Ratliff, K.A.; Vianello, M.; Adams, R.B.; Bahnik, S.; Bernstein, M.J.; Bocian, K.; Brandt, M.J.; Brooks, B.; Brumbaugh, C.C.; Cemalcilar, Z.; Chandler, J.; Cheong, W.; Davis, W.E.; Devos, T.; Eisner, M.; Frankowska, N.; Furrow, D.; Galliani, E.M.; Hasselman, F.W.; Hicks, J.A.; Hovermale, J.F.; Hunt, S.J.; Huntsinger, J.R.; IJzerman, H.; John, M.S.; Joy-Gaba, J.A.; Kappes, H.B.; Krueger, L.E.; Kurtz, J.; Levitan, C.A.; Mallett, R.K.; Morris, W.L.; Nelson, A.J.; Nier, J.A.; Packard, G.; Pilati, R.; Rutchick, A.M.; Schmidt, K.; Skorinko, J.L.M.; Smith, R.; Steiner, T.G.; Storbeck, J.; Van Swol, L.M.; Thompson, D.; Veer, A.E. van 't; Vaughn, L.A.; Vranka, M.; Wichman, A.L.; Woodzicka, J.A.; Nosek, B.A.

    2014-01-01

    Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently.

  8. Hepatitis B virus replication

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Hepadnaviruses, including human hepatitis B virus (HBV), replicate through reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription: it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA,ε, as template, and depends on cellular chaperones;moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids.This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV (DHBV),now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately,not be complemented by three-dimensional structural information on the involved components. However, at least for the s RNA element such information is emerging,raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal,will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.

  9. Psychology, replication & beyond.

    Science.gov (United States)

    Laws, Keith R

    2016-06-01

    Modern psychology is apparently in crisis and the prevailing view is that this partly reflects an inability to replicate past findings. If a crisis does exists, then it is some kind of 'chronic' crisis, as psychologists have been censuring themselves over replicability for decades. While the debate in psychology is not new, the lack of progress across the decades is disappointing. Recently though, we have seen a veritable surfeit of debate alongside multiple orchestrated and well-publicised replication initiatives. The spotlight is being shone on certain areas and although not everyone agrees on how we should interpret the outcomes, the debate is happening and impassioned. The issue of reproducibility occupies a central place in our whig history of psychology.

  10. Sister Mary Joseph Nodule as a Presenting Sign of Pancreatobiliary Adenocarcinoma

    OpenAIRE

    2012-01-01

    Sister Mary Joseph nodules represent metastatic cancer of the umbilicus. These malignancies are usually associated with the ovary and gastrointestinal tract. The authors report the case of a Sister Mary Joseph nodule originating from the bifurcation of the common hepatic duct. Umbilical nodules should prompt clinical evaluations, as these tumors are usually associated with poor prognosis.

  11. Sister Mary joseph nodule as a presenting sign of pancreatobiliary adenocarcinoma.

    Science.gov (United States)

    Shelling, Michael L; Vitiello, Magalys; Lanuti, Emma L; Rodriguez, Senen; Kerdel, Francisco A

    2012-10-01

    Sister Mary Joseph nodules represent metastatic cancer of the umbilicus. These malignancies are usually associated with the ovary and gastrointestinal tract. The authors report the case of a Sister Mary Joseph nodule originating from the bifurcation of the common hepatic duct. Umbilical nodules should prompt clinical evaluations, as these tumors are usually associated with poor prognosis.

  12. Contrastive Analysis of Two Sisters in Sense and Sensibility Based on“Melancholy Philosophy”

    Institute of Scientific and Technical Information of China (English)

    陈元元

    2014-01-01

    Sense and Sensibility, one of Jane Austen’s masterpieces, has undergone a long time study and the two sisters in the book-Elinor and Marianne have been researched from various kinds of perspectives except“melancholy philosophy”. This pa-per aims to analyze the two sisters in Sense and Sensibility under the guidance of“melancholy philosophy”.

  13. 76 FR 315 - Sisters Ranger District; Deschutes National Forest; Oregon; Popper Vegetation Management Project

    Science.gov (United States)

    2011-01-04

    ... comments-pacificnorthwest-deschutes-sisters@fs.fed.us . Please put ``Popper Vegetation Management Project... effects will take place. The Popper Vegetation Management Project decision and the reasons for the... Forest Service Sisters Ranger District; Deschutes National Forest; Oregon; Popper Vegetation Management...

  14. DNA adenine methylation is required to replicate both Vibrio cholerae chromosomes once per cell cycle.

    Directory of Open Access Journals (Sweden)

    Gaëlle Demarre

    2010-05-01

    Full Text Available DNA adenine methylation is widely used to control many DNA transactions, including replication. In Escherichia coli, methylation serves to silence newly synthesized (hemimethylated sister origins. SeqA, a protein that binds to hemimethylated DNA, mediates the silencing, and this is necessary to restrict replication to once per cell cycle. The methylation, however, is not essential for replication initiation per se but appeared so when the origins (oriI and oriII of the two Vibrio cholerae chromosomes were used to drive plasmid replication in E. coli. Here we show that, as in the case of E. coli, methylation is not essential for oriI when it drives chromosomal replication and is needed for once-per-cell-cycle replication in a SeqA-dependent fashion. We found that oriII also needs SeqA for once-per-cell-cycle replication and, additionally, full methylation for efficient initiator binding. The requirement for initiator binding might suffice to make methylation an essential function in V. cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication.

  15. The role of brothers and sisters in the gender development of preschool children.

    Science.gov (United States)

    Rust, J; Golombok, S; Hines, M; Johnston, K; Golding, J

    2000-12-01

    The study examined whether the sex of older siblings influences the gender role development of younger brothers and sisters of age 3 years. Data on the Pre-School Activities Inventory, a measure of gender role behavior that discriminates within as well as between the sexes, were obtained in a general population study for 527 girls and 582 boys with an older sister, 500 girls and 561 boys with an older brother, and 1665 singleton girls and 1707 singleton boys. It was found that boys with older brothers and girls with older sisters were more sex-typed than same-sex singletons who, in turn, were more sex-typed than children with other-sex siblings. Having an older brother was associated with more masculine and less feminine behavior in both boys and girls, whereas boys with older sisters were more feminine but not less masculine and girls with older sisters were less masculine but not more feminine.

  16. Monitoring the exposure of rats to 2-acetylaminofluorene by the estimation of mutagenic activity in excreta, sister-chromatid exchanges in peripheral blood cells and DNA adducts in peripheral blood, liver and spleen

    NARCIS (Netherlands)

    Willems, M.I.; Raat, W.K.de; Baan, R.A.; Wilmer, J.W.G.M.; Lansbergen, M.J.; Lohman, P.H.M.

    1987-01-01

    The sensitivity of various methods suitable for biomonitoring the exposure to genotoxicants was compared in an animal model. The results were related to the presence of genotoxic effects in the target organ. Groups of male Wistar rats were given one oral dose of 0, 0.1, 1, 10 or 200 mg 2-acetylamino

  17. DNA replication origins in archaea

    OpenAIRE

    Zhenfang eWu; Jingfang eLiu; Haibo eYang; Hua eXiang

    2014-01-01

    DNA replication initiation, which starts at specific chromosomal site (known as replication origins), is the key regulatory stage of chromosome replication. Archaea, the third domain of life, use a single or multiple origin(s) to initiate replication of their circular chromosomes. The basic structure of replication origins is conserved among archaea, typically including an AT-rich unwinding region flanked by several conserved repeats (origin recognition box, ORB) that are located adjacent to ...

  18. The geography and ecology of plant speciation: range overlap and niche divergence in sister species.

    Science.gov (United States)

    Anacker, Brian L; Strauss, Sharon Y

    2014-03-07

    A goal of evolutionary biology is to understand the roles of geography and ecology in speciation. The recent shared ancestry of sister species can leave a major imprint on their geographical and ecological attributes, possibly revealing processes involved in speciation. We examined how ecological similarity, range overlap and range asymmetry are related to time since divergence of 71 sister species pairs in the California Floristic Province (CFP). We found that plants exhibit strikingly different age-range correlation patterns from those found for animals; the latter broadly support allopatric speciation as the primary mode of speciation. By contrast, plant sisters in the CFP were sympatric in 80% of cases and range sizes of sisters differed by a mean of 10-fold. Range overlap and range asymmetry were greatest in younger sisters. These results suggest that speciation mechanisms broadly grouped under 'budding' speciation, in which a larger ranged progenitor gives rise to a smaller ranged derivative species, are probably common. The ecological and reproductive similarity of sisters was significantly greater than that of sister-non-sister congeners for every trait assessed. However, shifts in at least one trait were present in 93% of the sister pairs; habitat and soil shifts were especially common. Ecological divergence did not increase with range overlap contrary to expectations under character displacement in sympatry. Our results suggest that vicariant speciation is more ubiquitous in animals than plants, perhaps owing to the sensitivity of plants to fine-scale environmental heterogeneity. Despite high levels of range overlap, ecological shifts in the process of budding speciation may result in low rates of fine-scale spatial co-occurrence. These results have implications for ecological studies of trait evolution and community assembly; despite high levels of sympatry, sister taxa and potentially other close relatives, may be missing from local communities.

  19. Replication studies in longevity

    DEFF Research Database (Denmark)

    Varcasia, O; Garasto, S; Rizza, T

    2001-01-01

    In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20...

  20. Replication-Fork Dynamics

    NARCIS (Netherlands)

    Duderstadt, Karl E.; Reyes-Lamothe, Rodrigo; van Oijen, Antoine M.; Sherratt, David J.

    2014-01-01

    The proliferation of all organisms depends on the coordination of enzymatic events within large multiprotein replisomes that duplicate chromosomes. Whereas the structure and function of many core replisome components have been clarified, the timing and order of molecular events during replication re

  1. Coronavirus Attachment and Replication

    Science.gov (United States)

    1988-03-28

    synthesis during RNA replication of vesicular stomatitis virus. J. Virol. 49:303-309. Pedersen, N.C. 1976a. Feline infectious peritonitis: Something old...receptors on intestinal brush border membranes from normal host species were developed for canine (CCV), feline (FIPV), porcine (TGEV), human (HCV...gastroenteritis receptor on pig BBMs ...... ................. ... 114 Feline infectious peritonitis virus receptor on cat BBMs ... .............. 117 Human

  2. Replication Banding Patterns in Human Chromosomes Detected Using 5-ethynyl-2'-deoxyuridine Incorporation.

    Science.gov (United States)

    Hoshi, Osamu; Ushiki, Tatsuo

    2011-10-26

    A novel technique using the incorporation of 5-ethynyl-2'-deoxyuridine (EdU) into replicating DNA is described for the analysis of replicating banding patterns of human metaphase chromosomes. Human lymphocytes were synchronized with excess thymidine and treated with EdU during the late S phase of the cell cycle. The incorporated EdU was then detected in metaphase chromosomes using Alexa Fluor® 488 azides, through the 1,3-dipolar cycloaddition reaction of organic azides with the terminal acetylene group of EdU. Chromosomes with incorporated EdU showed a banding pattern similar to G-banding of normal human chromosomes. Imaging by atomic force microscopy (AFM) in liquid conditions showed that the structure of the chromosomes was well preserved even after EdU treatment. Comparison between fluorescence microscopy and AFM images of the same chromosome 1 indicated the presence of ridges and grooves in the chromatid arm, features that have been previously reported in relation to G-banding. These results suggest an intimate relationship between EdU-induced replication bands and G- or R-bands in human chromosomes. This technique is thus useful for analyzing the structure of chromosomes in relation to their banding patterns following DNA replication in the S phase.

  3. Concordance of ulcerative colitis in monozygotic twin sisters

    Institute of Scientific and Technical Information of China (English)

    Madoka Horiya; Masatomo Mori; Satoru Kakizaki; Katsunobu Teshigawara; Yuki Kikuchi; Tetsu Hashida; Yoshio Tomizawa; Tomohiro Iida; Takashige Masuo; Hitoshi Takagi

    2005-01-01

    The etiology of inflammatory bowel disease is multifacto rial and appears to combine both genetic and environmental factors. We experienced here a rare occurrence of woman monozygotic twins with ulcerative colitis (UC). A 45-year-old woman (the elder monozygotic twin) was admitted to our hospital because of bloody diarrhea occurring over 10 times per day, abdominal pain and fever. She was diagnosed as UC at the age of 22, and repeated the relapse and remission. She was diagnosed as relapse of UC and total colitis type. Her younger monozygotic twin sister also suffered from UC at the age of 22. Human leukocyte antigen was examined serologically with DNA type in both patients. DRB1*1502, which was previously shown to be dominant in Japanese patients with UC, was not observed in this case. Although the concordance in monozygotic twin in UC is reported to be 6.3-18.8%, the concordant case like this is relatively rare. We report this rare case of UC and the previously reported cases are also discussed.

  4. The unforgotten sisters female astronomers and scientists before Caroline Herschel

    CERN Document Server

    Bernardi, Gabriella

    2016-01-01

    Taking inspiration from Siv Cedering’s poem in the form of a fictional letter from Caroline Herschel that refers to “my long, lost sisters, forgotten in the books that record our science”, this book tells the lives of twenty-five female scientists, with specific attention to astronomers and mathematicians. Each of the presented biographies is organized as a kind of "personal file" which sets the biographee’s life in its historical context, documents her main works, highlights some curious facts, and records citations about her. The selected figures are among the most representative of this neglected world, including such luminaries as Hypatia of Alexandra, Hildegard of Bingen, Elisabetha Hevelius, and Maria Gaetana Agnesi. They span a period of about 4000 years, from En HeduAnna, the Akkadian princess, who was one of the first recognized female astronomers, to the dawn of the era of modern astronomy with Caroline Herschel and Mary Somerville. The book will be of interest to all who wish to learn more ...

  5. The bacterial nucleoid: nature, dynamics and sister segregation.

    Science.gov (United States)

    Kleckner, Nancy; Fisher, Jay K; Stouf, Mathieu; White, Martin A; Bates, David; Witz, Guillaume

    2014-12-01

    Recent studies reveal that the bacterial nucleoid has a defined, self-adherent shape and an underlying longitudinal organization and comprises a viscoelastic matrix. Within this shape, mobility is enhanced by ATP-dependent processes and individual loci can undergo ballistic off-equilibrium movements. In Escherichia coli, two global dynamic nucleoid behaviors emerge pointing to nucleoid-wide accumulation and relief of internal stress. Sister segregation begins with local splitting of individual loci, which is delayed at origin, terminus and specialized interstitial snap regions. Globally, as studied in several systems, segregation is a multi-step process in which internal nucleoid state plays critical roles that involve both compaction and expansion. The origin and terminus regions undergo specialized programs partially driven by complex ATP burning mechanisms such as a ParAB Brownian ratchet and a septum-associated FtsK motor. These recent findings reveal strong, direct parallels among events in different systems and between bacterial nucleoids and mammalian chromosomes with respect to physical properties, internal organization and dynamic behaviors.

  6. Benign multicystic mesothelioma: a case report of three sisters

    Directory of Open Access Journals (Sweden)

    Thomas Rutherford

    2009-12-01

    Full Text Available Benign multicystic mesothelioma (BMCM is a rare tumor of the abdomen-peritoneum of unknown etiology. This benign tumor was initially described by Plaut in 1928 when he observed loose cysts in the pelvis during a surgery for a uterine leiomyoma.2 The mesothelial origin was later confirmed by electron micro-scopy by Mennemeyer and Smith in 1979.3 To date, there are approximately 140 cases of BMCM reported in the literature.4 This disease primarily occurs in pre-menopausal women and is associated with a history of pelvic inflammatory disease, prior abdominal surgery, and endometriosis.4,5 The pathogenesis of this disease remains controversial, with possible etiologies including a neoplastic versus a reactive process.5 In the literature, a few case reports discuss a possible genetic or familial association with BMCM.6 Specifically, one report describes a man with familial Mediterranean fever who developed BMCM. Although familial Mediter-ranean fever is associated with malignant mesothelioma, he had only BMCM, and did not suffer from malignant mesothelioma.6 A genetic evaluation and chromosomal analysis were not able to identify a specific genetic cause of the family’s pattern of disease. This case report describes two female siblings diagnosed with BMCM. In addition, a third sister also had findings consistent with BMCM, however, the discrete histological diagnosis was never confirmed.

  7. Chloroplast phylogenomics indicates that Ginkgo biloba is sister to cycads.

    Science.gov (United States)

    Wu, Chung-Shien; Chaw, Shu-Miaw; Huang, Ya-Yi

    2013-01-01

    Molecular phylogenetic studies have not yet reached a consensus on the placement of Ginkgoales, which is represented by the only living species, Ginkgo biloba (common name: ginkgo). At least six discrepant placements of ginkgo have been proposed. This study aimed to use the chloroplast phylogenomic approach to examine possible factors that lead to such disagreeing placements. We found the sequence types used in the analyses as the most critical factor in the conflicting placements of ginkgo. In addition, the placement of ginkgo varied in the trees inferred from nucleotide (NU) sequences, which notably depended on breadth of taxon sampling, tree-building methods, codon positions, positions of Gnetopsida (common name: gnetophytes), and including or excluding gnetophytes in data sets. In contrast, the trees inferred from amino acid (AA) sequences congruently supported the monophyly of a ginkgo and Cycadales (common name: cycads) clade, regardless of which factors were examined. Our site-stripping analysis further revealed that the high substitution saturation of NU sequences mainly derived from the third codon positions and contributed to the variable placements of ginkgo. In summary, the factors we surveyed did not affect results inferred from analyses of AA sequences. Congruent topologies in our AA trees give more confidence in supporting the ginkgo-cycad sister-group hypothesis.

  8. Narrative research on mental health recovery: two sister paradigms.

    Science.gov (United States)

    Spector-Mersel, Gabriela; Knaifel, Evgeny

    2017-06-24

    Despite the breadth of narrative studies on individuals with severe mental illness, the suitability of narrative inquiry to exploring mental health recovery (MHR) has not been examined. (1) Examining the appropriateness of narrative inquiry to studying MHR; (2) assessing the extent to which narrative studies on MHR conform to the unique features of narrative research, as a distinctive form of qualitative inquiry. Review of empirical, theoretical and methodological literature on recovery and narrative inquiry. Considering the perspectives of recovery and narrative as paradigms, the similarity between their ontology and epistemology is shown, evident in 10 common emphases: meaning, identity, change and development, agency, holism, culture, uniqueness, context, language and giving voice. The resemblance between these "sister" paradigms makes narrative methodology especially fruitful for accessing the experiences of individuals in recovery. Reviewing narrative studies on MHR suggests that, currently, narrative research's uniqueness, centered on the holistic principle, is blurred on the philosophical, methodological and textual levels. Well-established narrative research has major implications for practice and policy in recovery-oriented mental health care. The narrative inquiry paradigm offers a possible path to enhancing the distinctive virtues of this research, realizing its potential in understanding and promoting MHR.

  9. Reversible Switching of Cooperating Replicators

    Science.gov (United States)

    Urtel, Georg C.; Rind, Thomas; Braun, Dieter

    2017-02-01

    How can molecules with short lifetimes preserve their information over millions of years? For evolution to occur, information-carrying molecules have to replicate before they degrade. Our experiments reveal a robust, reversible cooperation mechanism in oligonucleotide replication. Two inherently slow replicating hairpin molecules can transfer their information to fast crossbreed replicators that outgrow the hairpins. The reverse is also possible. When one replication initiation site is missing, single hairpins reemerge from the crossbreed. With this mechanism, interacting replicators can switch between the hairpin and crossbreed mode, revealing a flexible adaptation to different boundary conditions.

  10. Interphase cell cycle dynamics of a late-replicating, heterochromatic homogeneously staining region: precise choreography of condensation/decondensation and nuclear positioning.

    Science.gov (United States)

    Li, G; Sudlow, G; Belmont, A S

    1998-03-09

    Recently we described a new method for in situ localization of specific DNA sequences, based on lac operator/repressor recognition (Robinett, C.C., A. Straight, G. Li, C. Willhelm, G. Sudlow, A. Murray, and A.S. Belmont. 1996. J. Cell Biol. 135:1685-1700). We have applied this methodology to visualize the cell cycle dynamics of an approximately 90 Mbp, late-replicating, heterochromatic homogeneously staining region (HSR) in CHO cells, combining immunostaining with direct in vivo observations. Between anaphase and early G1, the HSR extends approximately twofold to a linear, approximately 0.3-mum-diam chromatid, and then recondenses to a compact mass adjacent to the nuclear envelope. No further changes in HSR conformation or position are seen through mid-S phase. However, HSR DNA replication is preceded by a decondensation and movement of the HSR into the nuclear interior 4-6 h into S phase. During DNA replication the HSR resolves into linear chromatids and then recondenses into a compact mass; this is followed by a third extension of the HSR during G2/ prophase. Surprisingly, compaction of the HSR is extremely high at all stages of interphase. Preliminary ultrastructural analysis of the HSR suggests at least three levels of large-scale chromatin organization above the 30-nm fiber.

  11. Monopolin subunit Csm1 associates with MIND complex to establish monopolar attachment of sister kinetochores at meiosis I.

    Science.gov (United States)

    Sarkar, Sourav; Shenoy, Rajesh T; Dalgaard, Jacob Z; Newnham, Louise; Hoffmann, Eva; Millar, Jonathan B A; Arumugam, Prakash

    2013-01-01

    Sexually reproducing organisms halve their cellular ploidy during gametogenesis by undergoing a specialized form of cell division known as meiosis. During meiosis, a single round of DNA replication is followed by two rounds of nuclear divisions (referred to as meiosis I and II). While sister kinetochores bind to microtubules emanating from opposite spindle poles during mitosis, they bind to microtubules originating from the same spindle pole during meiosis I. This phenomenon is referred to as mono-orientation and is essential for setting up the reductional mode of chromosome segregation during meiosis I. In budding yeast, mono-orientation depends on a four component protein complex referred to as monopolin which consists of two nucleolar proteins Csm1 and Lrs4, meiosis-specific protein Mam1 of unknown function and casein kinase Hrr25. Monopolin complex binds to kinetochores during meiosis I and prevents bipolar attachments. Although monopolin associates with kinetochores during meiosis I, its binding site(s) on the kinetochore is not known and its mechanism of action has not been established. By carrying out an imaging-based screen we have found that the MIND complex, a component of the central kinetochore, is required for monopolin association with kinetochores during meiosis. Furthermore, we demonstrate that interaction of monopolin subunit Csm1 with the N-terminal domain of MIND complex subunit Dsn1, is essential for both the association of monopolin with kinetochores and for monopolar attachment of sister kinetochores during meiosis I. As such this provides the first functional evidence for a monopolin-binding site at the kinetochore.

  12. Geometry and force behind kinetochore orientation: lessons from meiosis.

    Science.gov (United States)

    Watanabe, Yoshinori

    2012-05-16

    During mitosis, replicated chromosomes (sister chromatids) become attached at the kinetochore by spindle microtubules emanating from opposite poles and segregate equationally. In the first division of meiosis, however, sister chromatids become attached from the same pole and co-segregate, whereas homologous chromosomes connected by chiasmata segregate to opposite poles. Disorder in this specialized chromosome attachment in meiosis is the leading cause of miscarriage in humans. Recent studies have elucidated the molecular mechanisms determining chromosome orientation, and consequently segregation, in meiosis. Comparative studies of meiosis and mitosis have led to the general principle that kinetochore geometry and tension exerted by microtubules synergistically generate chromosome orientation.

  13. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  14. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  15. Initiation of adenovirus DNA replication.

    OpenAIRE

    Reiter, T; Fütterer, J; Weingärtner, B; Winnacker, E L

    1980-01-01

    In an attempt to study the mechanism of initiation of adenovirus DNA replication, an assay was developed to investigate the pattern of DNA synthesis in early replicative intermediates of adenovirus DNA. By using wild-type virus-infected cells, it was possible to place the origin of adenovirus type 2 DNA replication within the terminal 350 to 500 base pairs from either of the two molecular termini. In addition, a variety of parameters characteristic of adenovirus DNA replication were compared ...

  16. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    Stability and function of eukaryotic genomes are closely linked to chromatin structure and organization. During cell division the entire genome must be accurately replicated and the chromatin landscape reproduced on new DNA. Chromatin and nuclear structure influence where and when DNA replication...... initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  17. Replication Research and Special Education

    Science.gov (United States)

    Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.

    2016-01-01

    Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…

  18. Replication Research and Special Education

    Science.gov (United States)

    Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.

    2016-01-01

    Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…

  19. Regulation of rDNA stability by sumoylation

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine; Lisby, Michael

    2009-01-01

    , the eukaryotic cell has evolved mechanisms to favor equal sister chromatid exchange (SCE) and suppress unequal SCE, single-strand annealing and break-induced replication. In the budding yeast Saccharomyces cerevisiae, the tight regulation of homologous recombination at the rDNA locus is dependent on the Smc5-Smc...

  20. Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination

    NARCIS (Netherlands)

    K. Kikuchi (Koji); T. Narita (Takeo); V.C. Pham (Van Ca); J. Iijima (Junko); T. Hirota (Tomomitsu); I.S. Keka (Islam Shamima); Mohiuddin; K. Okawa (Katsuya); T. Hori (Toshiyuki); T. Fukagawa (Tatsuo); J. Essers (Jeroen); R. Kanaar (Roland); M.C. Whitby (Matthew); K. Sugasawa (Kaoru); Y. Taniguchi (Yoshihito); K. Kitagawa; S. Takeda (Shiunichi)

    2013-01-01

    textabstractDNA double-strand breaks (DSB) occur frequently during replication in sister chromatids and are dramatically increased when cells are exposed to chemotherapeutic agents including camptothecin. Such DSBs are efficiently repaired specifically by homologous recombination (HR) with the intac

  1. Andrographia paniculata a Miracle Herbs for cancer treatment: In vivo and in vitro studies against Aflatoxin B1 Toxicity

    Directory of Open Access Journals (Sweden)

    Md. Sultan Ahmad

    2014-04-01

    Conclusion: In conclusion A. paniculata extracts significantly reduced the number of aberrant cells and frequencies of aberration per cell at each concentration and duration of exposure in vivo; similarly it reduced chromosomal aberrations and sister chromatid exchanges and replication index was enhanced in vitro that was statistically significant at <0.05 level.

  2. Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination

    NARCIS (Netherlands)

    K. Kikuchi (Koji); T. Narita (Takeo); V.C. Pham (Van Ca); J. Iijima (Junko); T. Hirota (Tomomitsu); I.S. Keka (Islam Shamima); Mohiuddin; K. Okawa (Katsuya); T. Hori (Toshiyuki); T. Fukagawa (Tatsuo); J. Essers (Jeroen); R. Kanaar (Roland); M.C. Whitby (Matthew); K. Sugasawa (Kaoru); Y. Taniguchi (Yoshihito); K. Kitagawa; S. Takeda (Shiunichi)

    2013-01-01

    textabstractDNA double-strand breaks (DSB) occur frequently during replication in sister chromatids and are dramatically increased when cells are exposed to chemotherapeutic agents including camptothecin. Such DSBs are efficiently repaired specifically by homologous recombination (HR) with the intac

  3. The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility

    NARCIS (Netherlands)

    A. Herrán; C. Gutierréz-Caballero; M. Sáanchez-Martin; T. Hernández; A. Viera; J.L. Barbero; E. de Álava; D.G. de Rooij; J. Ángel Suja; E. Llano; A.M. Pendas

    2011-01-01

    The cohesin complex is a ring-shaped proteinaceous structure that entraps the two sister chromatids after replication until the onset of anaphase when the ring is opened by proteolytic cleavage of its alpha-kleisin subunit (RAD21 at mitosis and REC8 at meiosis) by separase. RAD21L is a recently iden

  4. Cohesin is required for higher-order chromatin conformation at the imprinted IGF2-H19 locus

    NARCIS (Netherlands)

    R. Nativio (Raffaella); K.S. Wendt (Kerstin); Y. Ito (Yoko); J.E. Huddleston (Joanna); S. Uribe-Lewis (Santiago); K. Woodfine (Kathryn); C. Krueger (Christel); W. Reik (Wolf); J.M. Peters; A. Murrell (Adele)

    2009-01-01

    textabstractCohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. Cohesin also has important roles in gene regulation, but the mechanistic basis of this function is poorly understood. In mammalian genomes, cohesin

  5. Replication data collection highlights value in diversity of replication attempts

    Science.gov (United States)

    DeSoto, K. Andrew; Schweinsberg, Martin

    2017-01-01

    Researchers agree that replicability and reproducibility are key aspects of science. A collection of Data Descriptors published in Scientific Data presents data obtained in the process of attempting to replicate previously published research. These new replication data describe published and unpublished projects. The different papers in this collection highlight the many ways that scientific replications can be conducted, and they reveal the benefits and challenges of crucial replication research. The organizers of this collection encourage scientists to reuse the data contained in the collection for their own work, and also believe that these replication examples can serve as educational resources for students, early-career researchers, and experienced scientists alike who are interested in learning more about the process of replication. PMID:28291224

  6. Competitive avoidance not edaphic specialization drives vertical niche partitioning among sister species of ectomycorrhizal fungi

    National Research Council Canada - National Science Library

    Mujic, Alija B; Durall, Daniel M; Spatafora, Joseph W; Kennedy, Peter G

    2016-01-01

    .... In three bioassay experiments, we tested the role of vertical soil heterogeneity in determining the distributions and competitive outcomes of the EM sister species Rhizopogon vinicolor and Rhizopogon vesiculosus...

  7. Extensive range overlap between heliconiine sister species: evidence for sympatric speciation in butterflies?

    National Research Council Canada - National Science Library

    Rosser, Neil; Kozak, Krzysztof M; Phillimore, Albert B; Mallet, James

    2015-01-01

    .... We here quantify geographic overlap of sister species of heliconiine butterflies, and use age-range correlations and spatial simulations of the geography of speciation to infer the frequency of sympatric speciation...

  8. Chromosomal differentiation and speciation in sister-species of Grammatidae (Perciformes) from the Western Atlantic

    National Research Council Canada - National Science Library

    Molina, Wagner Franco; da Costa, Gideão Wagner Werneck Felix; de Bello Cioffi, Marcelo; Bertollo, Luiz Antonio Carlos

    2012-01-01

    ... brasiliensis, endemic in Brazil, and its Caribbean counterpart Gramma loreto. Morphological and molecular studies have helped establish evolutionary patterns that sister-species of these two marine habitats are subjected...

  9. West Sister Island National Wildlife Refuge Wilderness Character Monitoring Back-end Database

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This is the back-end data file for the West Sister Island Wilderness Character Monitoring Application. User interface and lookup databases are required for use (see...

  10. 2 SISTERS WITH MENTAL-RETARDATION, CATARACT, ATAXIA, PROGRESSIVE HEARING-LOSS, AND POLYNEUROPATHY

    NARCIS (Netherlands)

    BEGEER, JH; SCHOLTE, FA; VANESSEN, AJ

    1991-01-01

    Two sisters are described with a disorder characterised by mental retardation, congenital cataract, progressive spinocerebellar ataxia, sensorineural deafness, and signs of peripheral neuropathy. Progressive hearing loss, ataxia, and polyneuropathy became evident in the third decade. The differentia

  11. 2 SISTERS WITH MENTAL-RETARDATION, CATARACT, ATAXIA, PROGRESSIVE HEARING-LOSS, AND POLYNEUROPATHY

    NARCIS (Netherlands)

    BEGEER, JH; SCHOLTE, FA; VANESSEN, AJ

    1991-01-01

    Two sisters are described with a disorder characterised by mental retardation, congenital cataract, progressive spinocerebellar ataxia, sensorineural deafness, and signs of peripheral neuropathy. Progressive hearing loss, ataxia, and polyneuropathy became evident in the third decade. The

  12. Psychopathology, childhood trauma, and personality traits in patients with borderline personality disorder and their sisters.

    Science.gov (United States)

    Laporte, Lise; Paris, Joel; Guttman, Herta; Russell, Jennifer

    2011-08-01

    The aim of this study was to document and compare adverse childhood experiences, and personality profiles in women with borderline personality disorder (BPD) and their sisters, and to determine how these factors impact current psychopathology. Fifty-six patients with BPD and their sisters were compared on measures assessing psychopathology, personality traits, and childhood adversities. Most sisters showed little evidence of psychopathology. Both groups reported dysfunctional parent-child relationships and a high prevalence of childhood trauma. Subjects with BPD reported experiencing more emotional abuse and intrafamilial sexual abuse, but more similarities than differences between probands and sisters were found. In multilevel analyses, personality traits of affective instability and impulsivity predicted DIB-R scores and SCL-90-R scores, above and beyond trauma. There were few relationships between childhood adversities and other measures of psychopathology. Sensitivity to adverse experiences, as reflected in the development of psychopathology, appears to be influenced by personality trait profiles.

  13. [The work of Moscow communities of Sisters of Charity in own medical institutions].

    Science.gov (United States)

    Zorin, K V

    2011-01-01

    The article analyses the medical activities of Moscow communities of Sisters of Charity in curative and educational institutions organized by the communities themselves. The social ministration of communities on the territory of Moscow is considered.

  14. Endovascular Repair of Internal Mammary Artery Aneurysms in Two Sisters with SMAD3 Mutation.

    Science.gov (United States)

    Nevidomskyte, Daiva; Shalhub, Sherene; Aldea, Gabriel S; Byers, Peter H; Schwarze, Ulrike; Murray, Mitzi L; Starnes, Benjamin

    2017-03-07

    True aneurysms of the internal mammary artery are rare and have been described in association with vasculitis or connective tissue disorders. Herein we describe two cases of familial internal mammary artery aneurysms in two sisters with SMAD3 mutation. The older sister presented at the age of 54 with an incidental diagnosis of a multilobed right internal mammary artery aneurysm (IMA) and the younger sister presented several years earlier with a ruptured left IMA aneurysm at the age of 49. Both sisters had Debakey type I aortic dissections prior to the IMA aneurysm presentation. To our knowledge this is the first time IMA aneurysms has been described in siblings with SMAD3 mutation. In our experience endovascular repair is a feasible and safe treatment option. An assessment of the entire arterial tree is recommended in patients diagnosed with SMAD3 mutations.

  15. Anatomy of Mammalian Replication Domains

    Science.gov (United States)

    Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

    2017-01-01

    Genetic information is faithfully copied by DNA replication through many rounds of cell division. In mammals, DNA is replicated in Mb-sized chromosomal units called “replication domains.” While genome-wide maps in multiple cell types and disease states have uncovered both dynamic and static properties of replication domains, we are still in the process of understanding the mechanisms that give rise to these properties. A better understanding of the molecular basis of replication domain regulation will bring new insights into chromosome structure and function. PMID:28350365

  16. Genomic data do not support comb jellies as the sister group to all other animals.

    Science.gov (United States)

    Pisani, Davide; Pett, Walker; Dohrmann, Martin; Feuda, Roberto; Rota-Stabelli, Omar; Philippe, Hervé; Lartillot, Nicolas; Wörheide, Gert

    2015-12-15

    Understanding how complex traits, such as epithelia, nervous systems, muscles, or guts, originated depends on a well-supported hypothesis about the phylogenetic relationships among major animal lineages. Traditionally, sponges (Porifera) have been interpreted as the sister group to the remaining animals, a hypothesis consistent with the conventional view that the last common animal ancestor was relatively simple and more complex body plans arose later in evolution. However, this premise has recently been challenged by analyses of the genomes of comb jellies (Ctenophora), which, instead, found ctenophores as the sister group to the remaining animals (the "Ctenophora-sister" hypothesis). Because ctenophores are morphologically complex predators with true epithelia, nervous systems, muscles, and guts, this scenario implies these traits were either present in the last common ancestor of all animals and were lost secondarily in sponges and placozoans (Trichoplax) or, alternatively, evolved convergently in comb jellies. Here, we analyze representative datasets from recent studies supporting Ctenophora-sister, including genome-scale alignments of concatenated protein sequences, as well as a genomic gene content dataset. We found no support for Ctenophora-sister and conclude it is an artifact resulting from inadequate methodology, especially the use of simplistic evolutionary models and inappropriate choice of species to root the metazoan tree. Our results reinforce a traditional scenario for the evolution of complexity in animals, and indicate that inferences about the evolution of Metazoa based on the Ctenophora-sister hypothesis are not supported by the currently available data.

  17. Ecological divergence and speciation between lemur (Eulemur) sister species in Madagascar.

    Science.gov (United States)

    Blair, M E; Sterling, E J; Dusch, M; Raxworthy, C J; Pearson, R G

    2013-08-01

    Understanding ecological niche evolution over evolutionary timescales is crucial to elucidating the biogeographic history of organisms. Here, we used, for the first time, climate-based ecological niche models (ENMs) to test hypotheses about ecological divergence and speciation processes between sister species pairs of lemurs (genus Eulemur) in Madagascar. We produced ENMs for eight species, all of which had significant validation support. Among the four sister species pairs, we found nonequivalent niches between sisters, varying degrees of niche overlap in ecological and geographic space, and support for multiple divergence processes. Specifically, three sister-pair comparisons supported the null model that niches are no more divergent than the available background region. These findings are consistent with an allopatric speciation model, and for two sister pairs (E. collaris-E. cinereiceps and E. rufus-E. rufifrons), a riverine barrier has been previously proposed for driving allopatric speciation. However, for the fourth sister pair E. flavifrons-E. macaco, we found support for significant niche divergence, and consistent with their parapatric distribution on an ecotone and the lack of obvious geographic barriers, these findings most strongly support a parapatric model of speciation. These analyses thus suggest that various speciation processes have led to diversification among closely related Eulemur species.

  18. Loss of Cell Cycle Checkpoint Control in Drosophila Rfc4 Mutants

    OpenAIRE

    Krause, S A; Loupart, M L; Vass, S.; Schoenfelder, S; Harrison, S; Heck, M M S

    2001-01-01

    Two alleles of the Drosophila melanogaster Rfc4 (DmRfc4) gene, which encodes subunit 4 of the replication factor C (RFC) complex, cause striking defects in mitotic chromosome cohesion and condensation. These mutations produce larval phenotypes consistent with a role in DNA replication but also result in mitotic chromosomal defects appearing either as premature chromosome condensation-like or precocious sister chromatid separation figures. Though the DmRFC4 protein localizes to all replicating...

  19. Modeling inhomogeneous DNA replication kinetics.

    Directory of Open Access Journals (Sweden)

    Michel G Gauthier

    Full Text Available In eukaryotic organisms, DNA replication is initiated at a series of chromosomal locations called origins, where replication forks are assembled proceeding bidirectionally to replicate the genome. The distribution and firing rate of these origins, in conjunction with the velocity at which forks progress, dictate the program of the replication process. Previous attempts at modeling DNA replication in eukaryotes have focused on cases where the firing rate and the velocity of replication forks are homogeneous, or uniform, across the genome. However, it is now known that there are large variations in origin activity along the genome and variations in fork velocities can also take place. Here, we generalize previous approaches to modeling replication, to allow for arbitrary spatial variation of initiation rates and fork velocities. We derive rate equations for left- and right-moving forks and for replication probability over time that can be solved numerically to obtain the mean-field replication program. This method accurately reproduces the results of DNA replication simulation. We also successfully adapted our approach to the inverse problem of fitting measurements of DNA replication performed on single DNA molecules. Since such measurements are performed on specified portion of the genome, the examined DNA molecules may be replicated by forks that originate either within the studied molecule or outside of it. This problem was solved by using an effective flux of incoming replication forks at the model boundaries to represent the origin activity outside the studied region. Using this approach, we show that reliable inferences can be made about the replication of specific portions of the genome even if the amount of data that can be obtained from single-molecule experiments is generally limited.

  20. Replicated Spectrographs in Astronomy

    CERN Document Server

    Hill, Gary J

    2014-01-01

    As telescope apertures increase, the challenge of scaling spectrographic astronomical instruments becomes acute. The next generation of extremely large telescopes (ELTs) strain the availability of glass blanks for optics and engineering to provide sufficient mechanical stability. While breaking the relationship between telescope diameter and instrument pupil size by adaptive optics is a clear path for small fields of view, survey instruments exploiting multiplex advantages will be pressed to find cost-effective solutions. In this review we argue that exploiting the full potential of ELTs will require the barrier of the cost and engineering difficulty of monolithic instruments to be broken by the use of large-scale replication of spectrographs. The first steps in this direction have already been taken with the soon to be commissioned MUSE and VIRUS instruments for the Very Large Telescope and the Hobby-Eberly Telescope, respectively. MUSE employs 24 spectrograph channels, while VIRUS has 150 channels. We compa...

  1. SUMO and KSHV Replication

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Pei-Ching [Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan (China); Kung, Hsing-Jien, E-mail: hkung@nhri.org.tw [Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan (China); Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616 (United States); UC Davis Cancer Center, University of California, Davis, CA 95616 (United States); Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan (China)

    2014-09-29

    Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis.

  2. IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister

    Directory of Open Access Journals (Sweden)

    Sills Eric

    2010-03-01

    Full Text Available Abstract Background Premature ovarian failure (POF remains a clinically challenging entity because in vitro fertilisation (IVF with donor oocytes is currently the only treatment known to be effective. Methods A 33 year-old nulligravid patient with a normal karyotype was diagnosed with POF; she had a history of failed fertility treatments and had an elevated serum FSH (42 mIU/ml. Oocytes donated by her dizygotic twin sister were used for IVF. The donor had already completed a successful pregnancy herself and subsequently produced a total of 10 oocytes after a combined FSH/LH superovulation regime. These eggs were fertilised with sperm from the recipient's husband via intracytoplasmic injection and two fresh embryos were transferred to the recipient on day three. Results A healthy twin pregnancy resulted from IVF; two boys were delivered by caesarean section at 39 weeks' gestation. Additionally, four embryos were cryopreserved for the recipient's future use. The sister-donor achieved another natural pregnancy six months after oocyte retrieval, resulting in a healthy singleton delivery. Conclusion POF is believed to affect approximately 1% of reproductive age females, and POF patients with a sister who can be an oocyte donor for IVF are rare. Most such IVF patients will conceive from treatment using oocytes from an anonymous oocyte donor. This is the first report of births following sister-donor oocyte IVF in Ireland. Indeed, while sister-donor IVF has been successfully undertaken by IVF units elsewhere, this is the only known case where oocyte donation involved twin sisters. As with all types of donor gamete therapy, pre-treatment counselling is important in the circumstance of sister oocyte donation.

  3. IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister.

    LENUS (Irish Health Repository)

    Sills, Eric Scott

    2010-01-01

    BACKGROUND: Premature ovarian failure (POF) remains a clinically challenging entity because in vitro fertilisation (IVF) with donor oocytes is currently the only treatment known to be effective. METHODS: A 33 year-old nulligravid patient with a normal karyotype was diagnosed with POF; she had a history of failed fertility treatments and had an elevated serum FSH (42 mIU\\/ml). Oocytes donated by her dizygotic twin sister were used for IVF. The donor had already completed a successful pregnancy herself and subsequently produced a total of 10 oocytes after a combined FSH\\/LH superovulation regime. These eggs were fertilised with sperm from the recipient\\'s husband via intracytoplasmic injection and two fresh embryos were transferred to the recipient on day three. RESULTS: A healthy twin pregnancy resulted from IVF; two boys were delivered by caesarean section at 39 weeks\\' gestation. Additionally, four embryos were cryopreserved for the recipient\\'s future use. The sister-donor achieved another natural pregnancy six months after oocyte retrieval, resulting in a healthy singleton delivery. CONCLUSION: POF is believed to affect approximately 1% of reproductive age females, and POF patients with a sister who can be an oocyte donor for IVF are rare. Most such IVF patients will conceive from treatment using oocytes from an anonymous oocyte donor. This is the first report of births following sister-donor oocyte IVF in Ireland. Indeed, while sister-donor IVF has been successfully undertaken by IVF units elsewhere, this is the only known case where oocyte donation involved twin sisters. As with all types of donor gamete therapy, pre-treatment counselling is important in the circumstance of sister oocyte donation.

  4. Efficient usage of Adabas replication

    CERN Document Server

    Storr, Dieter W

    2011-01-01

    In today's IT organization replication becomes more and more an essential technology. This makes Software AG's Event Replicator for Adabas an important part of your data processing. Setting the right parameters and establishing the best network communication, as well as selecting efficient target components, is essential for successfully implementing replication. This book provides comprehensive information and unique best-practice experience in the field of Event Replicator for Adabas. It also includes sample codes and configurations making your start very easy. It describes all components ne

  5. Solving the Telomere Replication Problem

    Science.gov (United States)

    Maestroni, Laetitia; Matmati, Samah; Coulon, Stéphane

    2017-01-01

    Telomeres are complex nucleoprotein structures that protect the extremities of linear chromosomes. Telomere replication is a major challenge because many obstacles to the progression of the replication fork are concentrated at the ends of the chromosomes. This is known as the telomere replication problem. In this article, different and new aspects of telomere replication, that can threaten the integrity of telomeres, will be reviewed. In particular, we will focus on the functions of shelterin and the replisome for the preservation of telomere integrity. PMID:28146113

  6. Identifying possible sister groups of Cryptocercidae+Isoptera: a combined molecular and morphological phylogeny of Dictyoptera.

    Science.gov (United States)

    Djernæs, Marie; Klass, Klaus-Dieter; Eggleton, Paul

    2015-03-01

    Termites (Isoptera) offer an alternative model for the development of eusociality which is not dependent on a high degree of relatedness as found between sisters in hymenopterans (bees, wasps, ants). Recent phylogenetic studies have established that termites belong within the cockroaches as sister to the subsocial Cryptocercidae. Cryptocercidae shares several important traits with termites, thus we need to understand the phylogenetic position of Cryptocercidae+Isoptera to determine how these traits evolved. However, placement of Cryptocercidae+Isoptera is still uncertain. We used both molecular (12S, 16S, COII, 18S, 28S, H3) and morphological characters to reconstruct the phylogeny of Dictyoptera. We included all previously suggested sister groups of Cryptocercidae+Isoptera as well as taxa which might represent additional major cockroach lineages. We used Bayes factors to test different sister groups for Cryptocercidae+Isoptera and assessed character support for the consensus tree based on morphological characters and COII amino acid data. We used the molecular data and fossil calibration to estimate divergence times. We found the most likely sister groups of Cryptocercidae+Isoptera to be Tryonicidae, Anaplecta or Tryonicidae+Anaplecta. Anaplecta has never previously been suggested as sister group or even close to Cryptocercidae+Isoptera, but was formerly placed in Blaberoidea as sister to the remaining taxa. Topological tests firmly supported our new placement of Anaplecta. We discuss the morphological characters (e.g. retractable genitalic hook) that have contributed to the previous placement of Anaplecta in Blaberoidea as well as the factors that might have contributed to a parallel development of genitalic features in Anaplecta and Blaberoidea. Cryptocercidae+Isoptera is placed in a clade with Tryonicidae, Anaplecta and possibly Lamproblattidae. Based on this, we suggest that wood-feeding, and the resultant need to conserve nitrogen, may have been an important

  7. Digital Data for Volcano Hazards of the Three Sisters Region, Oregon

    Science.gov (United States)

    Schilling, S.P.; Doelger, S.; Scott, W.E.; Iverson, R.M.

    2008-01-01

    Three Sisters is one of three active volcanic centers that lie close to rapidly growing communities and resort areas in Central Oregon. The major composite volcanoes of this area are clustered near the center of the region and include South Sister, Middle Sister, and Broken Top. Additionally, hundreds of mafic volcanoes are scattered throughout the Three Sisters area. These range from small cinder cones to large shield volcanoes like North Sister and Belknap Crater. Hazardous events include landslides from the steep flanks of large volcanoes and floods, which need not be triggered by eruptions, as well as eruption-triggered events such as fallout of tephra (volcanic ash) and lava flows. A proximal hazard zone roughly 20 kilometers (12 miles) in diameter surrounding the Three Sisters and Broken Top could be affected within minutes of the onset of an eruption or large landslide. Distal hazard zones that follow river valleys downstream from the Three Sisters and Broken Top could be inundated by lahars (rapid flows of water-laden rock and mud) generated either by melting of snow and ice during eruptions or by large landslides. Slow-moving lava flows could issue from new mafic volcanoes almost anywhere within the region. Fallout of tephra from eruption clouds can affect areas hundreds of kilometers (miles) downwind, so eruptions at volcanoes elsewhere in the Cascade Range also contribute to volcano hazards in Central Oregon. Scientists at the Cascades Volcano Observatory created a geographic information system (GIS) data set which depicts proximal and distal lahar hazard zones as well as a regional lava flow hazard zone for Three Sisters (USGS Open-File Report 99-437, Scott and others, 1999). The various distal lahar zones were constructed from LaharZ software using 20, 100, and 500 million cubic meter input flow volumes. Additionally, scientists used the depositional history of past events in the Three Sisters Region as well as experience and judgment derived from the

  8. The management of professionals: the preferences of hospital sisters and charge nurses.

    Science.gov (United States)

    Foster, D

    1995-05-01

    This analysis of the preferences of how sisters and charge nurses are managed is the result of a two centre descriptive study using theoretical models of professionalism, developing preferences and exercising situational leadership. It was conducted to determine if the management structure preferred by sisters and charge nurses, in a general acute hospital setting, supported the professionalism of nursing. The outcomes were intended to help develop a strategic plan for the future of nursing and the management of nurses. The research instruments were a self-completed questionnaire (19 were returned, a response rate of 31.1%) and four semi-structured interviews. The findings disclosed some dissatisfaction with the present management arrangements. The sisters and charge nurses felt that their priorities for practice and professional issues were better supported by clinically involved, ward-based senior nurses than by unit-based senior nurses with a general management function. However, sisters' and charge nurses' discussions with ward-based senior nurses were apparently less effective than discussions in peer groups which led to influential collegial autonomy. This preferred management style can be supported by the use of situational leadership theory which would enhance collegial autonomy and professional satisfaction. Recognition of the sisters and charge nurses preferences and adjustment of their management would therefore enable them to participate effectively in organizational decision-making.

  9. Neuropsychological profiles of three sisters homozygous for the fragile X premutation

    Energy Technology Data Exchange (ETDEWEB)

    Mazzocco, M.M.M. [Johns Hopkins School of Medicine, Baltimore, MD (United States); Holden, J.J.A. [Ongwanada Resource Centre, Kingston, Ontario (Canada)

    1996-08-09

    Fragile X syndrome (fraX) is associated with an amplification of a CGG repeat within the fraX mental retardation (FMR-1) gene. We describe an exceptional family in which 3 adult sisters are homozygous for the FMR-1 premutation. Each sister inherited 2 premutation alleles (ca. 80 CGG repeats) from their biologically unrelated parents. The 3 sisters were administered measures of executive function, visual spatial, memory, and verbal skills. Deficiencies in the first 2 of these domains have been reported among females with the full mutation. The sisters` performances were compared with available normative data and with published group means for females affected by fraX. These women did not appear to have verbal or memory difficulties. None of the women demonstrated a global executive function deficit, and none had global deficits in spatial ability. The profiles of these sisters are consistent with reports that the fragile X premutation does not affect cognitive performance. 31 refs., 1 fig., 4 tabs.

  10. Investigating the etiology of multiple tooth agenesis in three sisters with severe oligodontia.

    Science.gov (United States)

    Swinnen, S; Bailleul-Forestier, I; Arte, S; Nieminen, P; Devriendt, K; Carels, C

    2008-02-01

    To describe the dentofacial phenotypes of three sisters with severe non-syndromic oligodontia, to report on the mutation analysis in three genes, previously shown to cause various phenotypes of non-syndromic oligodontia and in two other suspected genes. Based on the phenotypes in the pedigree of this family, the different possible patterns of transmission are discussed. Anamnestic data and a panoramic radiograph were taken to study the phenotype of the three sisters and their first-degree relatives. Blood samples were also taken to obtain their karyotypes and DNA samples. Mutational screening was performed for the MSX1, PAX9, AXIN2, DLX1 and DLX2 genes. The probands' pedigree showed evidence for a recessive or multifactorial inheritance pattern. Normal chromosomal karyotypes were found and - despite the severe oligodontia present in all three sisters - no mutation appeared to be present in the five genes studied so far in these patients. In the three sisters reported, their common oligodontia phenotype is not caused by mutations in the coding regions of MSX1, PAX9, AXIN2, DLX1 or DLX2 genes, but genetic factors most probably play a role as all three sisters were affected. Environmental and epigenetic factors as well as genes regulating odontogenesis need further in vivo and in vitro investigation to explain the phenotypic heterogeneity and to increase our understanding of the odontogenic processes.

  11. Yeast Interacting Proteins Database: YCL029C, YER016W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available rotubules and kinetochore, involved in sister chromatid separation; essential in polyploid cells but not in ...le-associated protein, component of the interface between microtubules and kinetochore, involved in sister chromatid separation

  12. Yeast Interacting Proteins Database: YDL089W, YML008C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available rDNA repeat stability; null mutant causes increase in unequal sister-chromatid exchange; GFP-fusion protein...peat stability; null mutant causes increase in unequal sister-chromatid exchange; GFP-fusion protein localiz

  13. Sequence Classification: 893950 [

    Lifescience Database Archive (English)

    Full Text Available associated protein, required for sister chromatid cohesion; interacts with DNA polymerase alpha (Pol1p) and ...may link DNA synthesis to sister chromatid cohesion; Ctf4p || http://www.ncbi.nlm.nih.gov/protein/6325393 ...

  14. Sequence Classification: 893838 [

    Lifescience Database Archive (English)

    Full Text Available sion complex; maintains cohesion between sister chromatids during meiosis I; maintains cohesion...TMB Non-TMH TMB TMB TMB TMB >gi|6325264|ref|NP_015332.1| Meiosis-specific component of sister chromatid cohe

  15. Charter School Replication. Policy Guide

    Science.gov (United States)

    Rhim, Lauren Morando

    2009-01-01

    "Replication" is the practice of a single charter school board or management organization opening several more schools that are each based on the same school model. The most rapid strategy to increase the number of new high-quality charter schools available to children is to encourage the replication of existing quality schools. This policy guide…

  16. Sexual and physical abuse: a comparison between lesbians and their heterosexual sisters.

    Science.gov (United States)

    Stoddard, Joel P; Dibble, Suzanne L; Fineman, Norman

    2009-01-01

    The purpose of this study was to investigate similarities and differences in the incidence and patterns of abuse experienced by lesbians and their heterosexual sisters. In a matched sample of 324 lesbian/heterosexual sister pairs, the lesbians reported a greater incidence than their sisters of childhood physical and sexual abuse, as well as adult sexual abuse. Both groups identified male relatives as the most common perpetrator of both childhood physical and sexual abuse. Male relatives were most commonly identified as perpetrators of adult physical abuse and male strangers were most commonly identified as adult sexual abusers. Our results demonstrate that both sexual and physical abuse are common experiences for lesbian and heterosexual women; however, since the context of these experiences is different, each group will have special needs for services and treatment.

  17. A Feminist Reading of Sister Carrie: Carrie——the Aspiring Cinderella

    Institute of Scientific and Technical Information of China (English)

    殷娟

    2008-01-01

    Like Cinderella in the fairy tale Cinderella, Carrie is beautiful, innocent and poor. But unlike the traditional Cinderella who mindlessly waits around for a handsome prince to come to her rescue, Carrie, the aspiring Cinderella, resolvedly leaves the men she ever depended on and eventually becomes a successful actress. Sister Carrie, the most impressive heroine of Theodore Dreiser, is a contradictory character. Some accuse her of realizing her ambition with immoral means. However, some others take sympathy with her courage, determination, and aspiration. By analyzing the most distinguished quality of Sister Carrie - her aspiration, this essay is to illustrate from the perspective of feminism that women are not limited by their sex. Ignoring her own sex as well as the conventional attitude toward women in a male-dominated society, sister Carrie, full of aspiration, takes an active pan in creating and determining her own lives and her own futures..

  18. Causes of the Disillusionment of Sister Carrie’s American Dream

    Institute of Scientific and Technical Information of China (English)

    谭佳

    2013-01-01

    Theodore Dreiser’s novel Sister Carrie is the representative of studying the disillusionment of the American Dream. Since the publication of Sister Carrie,there have been many critics who commented on this work, and its main character Sister Carrie is a controversial person. Dreiser was criticized by critics and readers because he didn ’t give any comment on her degener-ation. This thesis tries to analyze the causes of this tragedy.In the end, the paper draws the conclusion:the American Dream looks beautiful, but to some extent it is not reliable, just like the foam of soap. It only gives people an illusion. So Carrie ’s tragedy is in-evitable.

  19. Osteological evidence for sister group relationship between pseudo-toothed birds (Aves: Odontopterygiformes) and waterfowls (Anseriformes)

    Science.gov (United States)

    Bourdon, Estelle

    2005-12-01

    The phylogenetic affinities of the extinct pseudo-toothed birds have remained controversial. Some authors noted that they resemble both pelicans and allies (Pelecaniformes) and tube-nosed birds (Procellariiformes), but assigned them to a distinct taxon, the Odontopterygiformes. In most recent studies, the pseudo-toothed birds are referred to the family Pelagornithidae inside the Pelecaniformes. Here, I perform a cladistic analysis with five taxa of the pseudo-toothed birds including two undescribed new species from the Early Tertiary of Morocco. The present hypothesis strongly supports a sister group relationship of pseudo-toothed birds (Odontopterygiformes) and waterfowls (Anseriformes). The Odontoanserae (Odontopterygiformes plus Anseriformes) are the sister group of Neoaves. The placement of the landfowls (Galliformes) as the sister taxon of all other neognathous birds does not support the consensus view that the Galloanserae (Galliformes plus Anseriformes) are monophyletic.

  20. LHCb experience with LFC replication

    CERN Document Server

    Bonifazi, F; Perez, E D; D'Apice, A; dell'Agnello, L; Düllmann, D; Girone, M; Re, G L; Martelli, B; Peco, G; Ricci, P P; Sapunenko, V; Vagnoni, V; Vitlacil, D

    2008-01-01

    Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.

  1. DATABASE REPLICATION IN HETEROGENOUS PLATFORM

    Directory of Open Access Journals (Sweden)

    Hendro Nindito

    2014-01-01

    Full Text Available The application of diverse database technologies in enterprises today is increasingly a common practice. To provide high availability and survavibality of real-time information, a database replication technology that has capability to replicate databases under heterogenous platforms is required. The purpose of this research is to find the technology with such capability. In this research, the data source is stored in MSSQL database server running on Windows. The data will be replicated to MySQL running on Linux as the destination. The method applied in this research is prototyping in which the processes of development and testing can be done interactively and repeatedly. The key result of this research is that the replication technology applied, which is called Oracle GoldenGate, can successfully manage to do its task in replicating data in real-time and heterogeneous platforms.

  2. LHCb experience with LFC replication

    CERN Document Server

    Carbone, Angelo; Dafonte Perez, Eva; D'Apice, Antimo; dell'Agnello, Luca; Duellmann, Dirk; Girone, Maria; Lo Re, Giuseppe; Martelli, Barbara; Peco, Gianluca; Ricci, Pier Paolo; Sapunenko, Vladimir; Vagnoni, Vincenzo; Vitlacil, Dejan

    2007-01-01

    Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informations (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.

  3. Protein (Viridiplantae): 356522276 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available 3847:837 PREDICTED: sister chromatid cohesion protein PDS5-like Glycine max MYFSAAYEFWKLELLLSSLDQEPTKPIQESLV...PAMKALISDELLRHTDGDVKISVTSCINEITRITAPDVPYDDEQMKEIFKLTVASFEKLSHISGRGYEKALTILDNANKVRLCLVMLDLECNDLVIEMFQHFLRYIRHPPIAKVYVRKIGKGSRTLGFTWALRKIVEITISDI ...

  4. Ukrainian and European Baroque in the Context of “Sister Arts” Idea

    Directory of Open Access Journals (Sweden)

    Olga Shikirinskaya

    2015-08-01

    Full Text Available The article deals with the “Sister Arts” tradition as the interrelationship of various art forms (poetry, fiction, painting, theatre, music etc. relative to the Baroque period. “Sister Arts” criticism, based on E.G. Lessing essay “Laocoön…” uses the inter-art analogies to appreciate the importance of literature in the Arts, as well as to comprehend aspects of the modern approach to the synthesis of the arts. The article presents the aesthetic concept of Baroque art and its realization in architecture, sculpture, decorative and applied arts, music and literature on the background of the European and Ukrainian cultural tradition.

  5. On the major Characteristics of Writing in Dreiser’s Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    张含

    2014-01-01

    Dreiser’s Sister Carrie has been controverted for a long time. It is still consummate today and as alive and valid as when it was written. First, the description of the psychology plays an important role in revealing the personalities of the major characters and deepens the theme. The second is Dreiser’s usage of comparison. Finally Dreiser uses the method of realism like Balzac. Sister Carrie is the exact reflection and the mirror of the society. Its special characteristics and the realistic writing style start a new field in American literature.

  6. Synergistic convergence and split pons in horizontal gaze palsy and progressive scoliosis in two sisters

    Directory of Open Access Journals (Sweden)

    Jain Nitin

    2011-01-01

    Full Text Available Synergistic convergence is an ocular motor anomaly where on attempted abduction or on attempted horizontal gaze, both the eyes converge. It has been related to peripheral causes such as congenital fibrosis of extraocular muscles (CFEOM, congenital cranial dysinnervation syndrome, ocular misinnervation or rarely central causes like horizontal gaze palsy with progressive scoliosis, brain stem dysplasia. We hereby report the occurrence of synergistic convergence in two sisters. Both of them also had kyphoscoliosis. Magnetic resonance imaging (MRI brain and spine in both the patients showed signs of brain stem dysplasia (split pons sign differing in degree (younger sister had more marked changes.

  7. The Influence of Sister Carrie’s Female Consciousness on Chinese Women

    Institute of Scientific and Technical Information of China (English)

    张佳

    2015-01-01

    Since Sister Carrie’s publication, it has attracted various criticism and comments on Carrie. There are many studies to explore Sister Carrie from various perspectives. The influence of Carrie’s female consciousness on Chinese women is the focus to discuss in the thesis. From Carrie, we realize Carrie is brave and successful in that “survival for the fittest” world. We cannot deny that Carrie is of great importance in present China in enlightening people’s value and women’s social position.

  8. NACSA Charter School Replication Guide: The Spectrum of Replication Options. Authorizing Matters. Replication Brief 1

    Science.gov (United States)

    O'Neill, Paul

    2010-01-01

    One of the most important and high-profile issues in public education reform today is the replication of successful public charter school programs. With more than 5,000 failing public schools in the United States, there is a tremendous need for strong alternatives for parents and students. Replicating successful charter school models is an…

  9. Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome.

    Science.gov (United States)

    Chabosseau, Pauline; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Lambert, Sarah; Debatisse, Michelle; Brison, Olivier; Amor-Guéret, Mounira

    2011-06-28

    Defects in DNA replication are associated with genetic instability and cancer development, as illustrated in Bloom syndrome. Features of this syndrome include a slowdown in replication speed, defective fork reactivation and high rates of sister chromatid exchange, with a general predisposition to cancer. Bloom syndrome is caused by mutations in the BLM gene encoding a RecQ helicase. Here we report that BLM deficiency is associated with a strong cytidine deaminase defect, leading to pyrimidine pool disequilibrium. In BLM-deficient cells, pyrimidine pool normalization leads to reduction of sister chromatid exchange frequency and is sufficient for full restoration of replication fork velocity but not the fork restart defect, thus identifying the part of the Bloom syndrome phenotype because of pyrimidine pool imbalance. This study provides new insights into the molecular basis of control of replication speed and the genetic instability associated with Bloom syndrome. Nucleotide pool disequilibrium could be a general phenomenon in a large spectrum of precancerous and cancer cells.

  10. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

    to local environments and under the impact of new learning. To illuminate these issues, we draw on a longitudinal in-depth study of Swedish home furnishing giant IKEA, involving more than 70 interviews. We find that IKEA has developed organizational mechanisms that support an ongoing learning process aimed......, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (“flexible replication”). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator....

  11. The Psychology of Replication and Replication in Psychology.

    Science.gov (United States)

    Francis, Gregory

    2012-11-01

    Like other scientists, psychologists believe experimental replication to be the final arbiter for determining the validity of an empirical finding. Reports in psychology journals often attempt to prove the validity of a hypothesis or theory with multiple experiments that replicate a finding. Unfortunately, these efforts are sometimes misguided because in a field like experimental psychology, ever more successful replication does not necessarily ensure the validity of an empirical finding. When psychological experiments are analyzed with statistics, the rules of probability dictate that random samples should sometimes be selected that do not reject the null hypothesis, even if an effect is real. As a result, it is possible for a set of experiments to have too many successful replications. When there are too many successful replications for a given set of experiments, a skeptical scientist should be suspicious that null or negative findings have been suppressed, the experiments were run improperly, or the experiments were analyzed improperly. This article describes the implications of this observation and demonstrates how to test for too much successful replication by using a set of experiments from a recent research paper.

  12. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

    Preserving genome integrity is essential for cell survival. To this end, mechanisms that supervise DNA replication and respond to replication perturbations have evolved. One such mechanism is the replication checkpoint, which responds to DNA replication stress and acts to ensure replication pausing...

  13. Sister Mary Joseph Nodules on 99mTc HYNIC-TOC scintigraphy in patients with neuroendocrine tumors.

    Science.gov (United States)

    Jing, Hongli; Zhang, Yingqiang; Li, Fang

    2015-02-01

    A Sister Mary Joseph nodule represents an umbilical metastasis, which is more commonly caused by a primary malignancy in gastrointestinal tract or from reproductive system. We report Sister Mary Joseph nodules caused by neuroendocrine tumor and revealed on Tc HYNIC-TOC scintigraphy.

  14. 77 FR 66851 - Submission for OMB Review; Comment Request The Sister Study: A Prospective Study of the Genetic...

    Science.gov (United States)

    2012-11-07

    ...: A Prospective Study of the Genetic and Environmental Risk Factors for Breast Cancer SUMMARY: Under... Collection: Title: The Sister Study: A Prospective Study of the Genetic and Environmental Risk Factors for...: This is to continue the Phase II follow-up of the Sister Study -- a study of genetic and...

  15. 77 FR 48993 - Proposed Collection; Comment Request; The Sister Study: A Prospective Study of the Genetic and...

    Science.gov (United States)

    2012-08-15

    ... Proposed Collection; Comment Request; The Sister Study: A Prospective Study of the Genetic and... Prospective Study of the Genetic and Environmental Risk Factors for Breast Cancer. Type of Information...-up of the Sister Study--a study of genetic and environmental risk factors for the development...

  16. Empirical Psycho-Aesthetics and Her Sisters: Substantive and Methodological Issues--Part II

    Science.gov (United States)

    Konecni, Vladimir J.

    2013-01-01

    Empirical psycho-aesthetics is approached in this two-part article from two directions. Part I, which appeared in the Winter 2012 issue of "JAE," addressed definitional and organizational issues, including the field's origins, its relation to "sister" disciplines (experimental philosophy, cognitive neuroscience of art, and neuroaesthetics), and…

  17. Study on Sister Carrie’s Purity from the Society and Her Nature

    Institute of Scientific and Technical Information of China (English)

    Wu Yu-xia; Dong Ting-jian

    2014-01-01

    Dreiser’s Sister Carrie often has negative comments, while her pursuit of happiness and ideal with pure faith under the dark social environment deserve study. Her characters shown in the struggle of life and her love affairs has been stated, which proves Carrie’purity in chasing dreams in the dirty society.

  18. Study on Sister Carrie’s Purity from the Society and Her Nature

    Institute of Scientific and Technical Information of China (English)

    Wu; Yu-xia; Dong; Ting-jian

    2014-01-01

    Dreiser’s Sister Carrie often has negative comments,while her pursuit of happiness and ideal with pure faith under the dark social environment deserve study.Her characters shown in the struggle of life and her love affairs has been stated,which proves Carrie’purity in chasing dreams in the dirty society.

  19. Brother-Sister Incest: Data from Anonymous Computer-Assisted Self Interviews

    Science.gov (United States)

    Stroebel, Sandra S.; O'Keefe, Stephen L.; Beard, Keith W.; Kuo, Shih-Ya; Swindell, Samuel; Stroupe, Walter

    2013-01-01

    Retrospective data were entered anonymously by 1,521 adult women using computer-assisted self interview. Forty were classified as victims of brother-sister incest, 19 were classified as victims of father-daughter incest, and 232 were classified as victims of sexual abuse by an adult other than their father before reaching 18 years of age. The…

  20. PERRAULT'S SYNDROME: A CLINICAL AND GENETIC INVESTIGATION OF THREE SISTERS

    Directory of Open Access Journals (Sweden)

    P. Mehdipour

    1999-07-01

    Full Text Available Perrault's syndrome (P.S. is rare. The combination of gonadal dysgenesis and hearing loss was accompanied by 46,XXkaryotype in three sisters with parental consanguineous marriage. Genetic investigation revealed normal female karyotype, positive liarr and negative fluorescence iPj-bodies, which was confirmed by molecular study on the basis of fluorescence in situ hybridization (PISH, with application of Keen probe, showing the presence of two signals in 95% of the cells of these 3 Iranian sisters. The pedigree showed parental consanguinity (first cousin with an autosomal mode of inheritance for both Perrault's syndrome and hearing loss. These findings together with normal thyroid function, serum prolactin, high level of .serum gonadotropins is similar to the menopausal period in all 3 sisters. Estrogen and progesterone were recommended for all 3 sisters. This combined therapy led to mensturation and after a few montfis their breasts were normally developed. Tor further management cochlear implantation, speech therapy and training courses were suggested in order to improve hearing and intellectual abilities.

  1. Subcortical laminar heterotopia in two sisters and their mother : MRI, clinical findings and pathogenesis

    NARCIS (Netherlands)

    van der Valk, PHM; Snoeck, [No Value; Meiners, LC; des Portes, [No Value; Chelly, J; Pinard, JM; Ippel, PF; van Nieuwenhuizen, O

    1999-01-01

    MR imaging, clinical data and underlying pathogenesis of subcortical laminar heterotopia (SCLH), also known as band heterotopia, in two sisters and their mother are presented. On MR imaging a different degree of SCLH was found in all three affected family-members. The inversion recovery sequence was

  2. "Brothers and Sisters": A Novel Way to Teach Human Resources Management.

    Science.gov (United States)

    Bumpus, Minnette

    2000-01-01

    The novel "Brothers and Sisters" by Bebe Moore Campbell was used in a management course to explore human resource management issues, concepts, and theories. The course included prereading and postreading surveys, lecture, book review, and examination. Most of the students (92%) felt the novel was an appropriate way to meet course objectives. (SK)

  3. A sister group metabolomic contrast delineates the biochemical regulation underlying desiccation tolerance in Sporobolus stapfianus

    Science.gov (United States)

    Understanding how plant cells tolerate dehydration is a vital prerequisite for developing strategies for improving drought tolerance. The desiccation tolerant grass Sporobolus stapfianus and the desiccation sensitive S. pyramidalis were used to form a sister-group contrast to reveal adaptive metabo...

  4. Three Sisters: Lessons of Traditional Story Honored in Assessment and Accreditation

    Science.gov (United States)

    Chenault, Venida S.

    2008-01-01

    The three sisters story is shared across many tribes. It explains the practice of planting corn, beans, and squash together. The corn stalks provide support for the bean vines; the beans provide nitrogen for the corn; and the squash prevents weed growth between the mounds. Such stories explain not only the science of agricultural methods in tribal…

  5. Analyzing of Sister Carrie's Independence Process from the Perspective of Feminism

    Institute of Scientific and Technical Information of China (English)

    姜新新

    2015-01-01

    "Sister Carrie" is published when the American society is in the transition from traditional industry to modern industry.Modern industrial not only provide opportunity to the development of city,but also offer some employment opportunities to the people,while the survival pressure for living is also increased.People's thought also undergo a tremendous change.They even feel puzzled andconfused.

  6. Food Yields and Nutrient Analyses of the Three Sisters: A Haudenosaunee Cropping System

    Directory of Open Access Journals (Sweden)

    Jane Mt.Pleasant

    2016-11-01

    Full Text Available Scholars have studied The Three Sisters, a traditional cropping system of the Haudenosaunee (Iroquois, from multiple perspectives. However, there is no research examining food yields, defined as the quantities of energy and protein produced per unit land area, from the cropping system within Iroquoia. This article compares food yields and other nutrient contributions from the Three Sisters, comprised of interplanted maize, bean and pumpkin, with monocultures of these same crops. The Three Sisters yields more energy (12.25 x 106 kcal/ha and more protein (349 kg/ha than any of the crop monocultures or mixtures of monocultures planted to the same area. The Three Sisters supplies 13.42 people/ha/yr. with energy and 15.86 people/ha/yr. with protein. Nutrient contents of the crops are further enhanced by nixtamalization, a traditional processing technique where maize is cooked in a high alkaline solution. This process increases calcium, protein quality, and niacin in maize.

  7. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... with their chronological age and present health status, help define their current rate of aging and contribute to establish personalized therapy plans to reduce, counteract or even avoid the appearance of aging biomarkers....

  8. Nucleotide Metabolism and DNA Replication.

    Science.gov (United States)

    Warner, Digby F; Evans, Joanna C; Mizrahi, Valerie

    2014-10-01

    The development and application of a highly versatile suite of tools for mycobacterial genetics, coupled with widespread use of "omics" approaches to elucidate the structure, function, and regulation of mycobacterial proteins, has led to spectacular advances in our understanding of the metabolism and physiology of mycobacteria. In this article, we provide an update on nucleotide metabolism and DNA replication in mycobacteria, highlighting key findings from the past 10 to 15 years. In the first section, we focus on nucleotide metabolism, ranging from the biosynthesis, salvage, and interconversion of purine and pyrimidine ribonucleotides to the formation of deoxyribonucleotides. The second part of the article is devoted to DNA replication, with a focus on replication initiation and elongation, as well as DNA unwinding. We provide an overview of replication fidelity and mutation rates in mycobacteria and summarize evidence suggesting that DNA replication occurs during states of low metabolic activity, and conclude by suggesting directions for future research to address key outstanding questions. Although this article focuses primarily on observations from Mycobacterium tuberculosis, it is interspersed, where appropriate, with insights from, and comparisons with, other mycobacterial species as well as better characterized bacterial models such as Escherichia coli. Finally, a common theme underlying almost all studies of mycobacterial metabolism is the potential to identify and validate functions or pathways that can be exploited for tuberculosis drug discovery. In this context, we have specifically highlighted those processes in mycobacterial DNA replication that might satisfy this critical requirement.

  9. Plasmid Rolling-Circle Replication.

    Science.gov (United States)

    Ruiz-Masó, J A; MachóN, C; Bordanaba-Ruiseco, L; Espinosa, M; Coll, M; Del Solar, G

    2015-02-01

    Plasmids are DNA entities that undergo controlled replication independent of the chromosomal DNA, a crucial step that guarantees the prevalence of the plasmid in its host. DNA replication has to cope with the incapacity of the DNA polymerases to start de novo DNA synthesis, and different replication mechanisms offer diverse solutions to this problem. Rolling-circle replication (RCR) is a mechanism adopted by certain plasmids, among other genetic elements, that represents one of the simplest initiation strategies, that is, the nicking by a replication initiator protein on one parental strand to generate the primer for leading-strand initiation and a single priming site for lagging-strand synthesis. All RCR plasmid genomes consist of a number of basic elements: leading strand initiation and control, lagging strand origin, phenotypic determinants, and mobilization, generally in that order of frequency. RCR has been mainly characterized in Gram-positive bacterial plasmids, although it has also been described in Gram-negative bacterial or archaeal plasmids. Here we aim to provide an overview of the RCR plasmids' lifestyle, with emphasis on their characteristic traits, promiscuity, stability, utility as vectors, etc. While RCR is one of the best-characterized plasmid replication mechanisms, there are still many questions left unanswered, which will be pointed out along the way in this review.

  10. Mutant analysis, protein-protein interactions and subcellular localization of the Arabidopsis B sister (ABS) protein.

    Science.gov (United States)

    Kaufmann, Kerstin; Anfang, Nicole; Saedler, Heinz; Theissen, Günter

    2005-09-01

    Recently, close relatives of class B floral homeotic genes, termed B(sister) genes, have been identified in both angiosperms and gymnosperms. In contrast to the B genes themselves, B(sister) genes are exclusively expressed in female reproductive organs, especially in the envelopes or integuments surrounding the ovules. This suggests an important ancient function in ovule or seed development for B(sister) genes, which has been conserved for about 300 million years. However, investigation of the first loss-of-function mutant for a B(sister) gene (ABS/TT16 from Arabidopsis) revealed only a weak phenotype affecting endothelium formation. Here, we present an analysis of two additional mutant alleles, which corroborates this weak phenotype. Transgenic plants that ectopically express ABS show changes in the growth and identity of floral organs, suggesting that ABS can interact with floral homeotic proteins. Yeast-two-hybrid and three-hybrid analyses indicated that ABS can form dimers with SEPALLATA (SEP) floral homeotic proteins and multimeric complexes that also include the AGAMOUS-like proteins SEEDSTICK (STK) or SHATTERPROOF1/2 (SHP1, SHP2). These data suggest that the formation of multimeric transcription factor complexes might be a general phenomenon among MIKC-type MADS-domain proteins in angiosperms. Heterodimerization of ABS with SEP3 was confirmed by gel retardation assays. Fusion proteins tagged with CFP (Cyan Fluorescent Protein) and YFP (Yellow Fluorescent Protein) in Arabidopsis protoplasts showed that ABS is localized in the nucleus. Phylogenetic analysis revealed the presence of a structurally deviant, but closely related, paralogue of ABS in the Arabidopsis genome. Thus the evolutionary developmental genetics of B(sister) genes can probably only be understood as part of a complex and redundant gene network that may govern ovule formation in a conserved manner, which has yet to be fully explored.

  11. Extensive range overlap between heliconiine sister species: evidence for sympatric speciation in butterflies?

    Science.gov (United States)

    Rosser, Neil; Kozak, Krzysztof M; Phillimore, Albert B; Mallet, James

    2015-06-30

    Sympatric speciation is today generally viewed as plausible, and some well-supported examples exist, but its relative contribution to biodiversity remains to be established. We here quantify geographic overlap of sister species of heliconiine butterflies, and use age-range correlations and spatial simulations of the geography of speciation to infer the frequency of sympatric speciation. We also test whether shifts in mimetic wing colour pattern, host plant use and climate niche play a role in speciation, and whether such shifts are associated with sympatry. Approximately a third of all heliconiine sister species pairs exhibit near complete range overlap, and analyses of the observed patterns of range overlap suggest that sympatric speciation contributes 32%-95% of speciation events. Müllerian mimicry colour patterns and host plant choice are highly labile traits that seem to be associated with speciation, but we find no association between shifts in these traits and range overlap. In contrast, climatic niches of sister species are more conserved. Unlike birds and mammals, sister species of heliconiines are often sympatric and our inferences using the most recent comparative methods suggest that sympatric speciation is common. However, if sister species spread rapidly into sympatry (e.g. due to their similar climatic niches), then assumptions underlying our methods would be violated. Furthermore, although we find some evidence for the role of ecology in speciation, ecological shifts did not show the associations with range overlap expected under sympatric speciation. We delimit species of heliconiines in three different ways, based on "strict and " "relaxed" biological species concepts (BSC), as well as on a surrogate for the widely-used "diagnostic" version of the phylogenetic species concept (PSC). We show that one reason why more sympatric speciation is inferred in heliconiines than in birds may be due to a different culture of species delimitation in the two

  12. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.

  13. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis

    2008-01-01

    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  14. Shell Separation for Mirror Replication

    Science.gov (United States)

    1999-01-01

    NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery, and materials to replicate electro-formed nickel mirrors. Optics replication uses reusable forms, called mandrels, to make telescope mirrors ready for final finishing. MSFC optical physicist Bill Jones monitors a device used to chill a mandrel, causing it to shrink and separate from the telescope mirror without deforming the mirror's precisely curved surface.

  15. Personality and Academic Motivation: Replication, Extension, and Replication

    Science.gov (United States)

    Jones, Martin H.; McMichael, Stephanie N.

    2015-01-01

    Previous work examines the relationships between personality traits and intrinsic/extrinsic motivation. We replicate and extend previous work to examine how personality may relate to achievement goals, efficacious beliefs, and mindset about intelligence. Approximately 200 undergraduates responded to the survey with a 150 participants replicating…

  16. RNase-dependent discontinuities associated with the crossovers of spontaneously formed joint DNA molecules in Physarum polycephalum.

    Science.gov (United States)

    Maric, Chrystelle; Bénard, Marianne; Pierron, Gérard

    2010-12-01

    Transient four stranded joint DNA molecules bridging sister chromatids constitute an intriguing feature of replicating genomes. Here, we studied their structure and frequency of formation in Physarum polycephalum. By "3D gels", we evidenced that they are not made of four continuous DNA strands. Discontinuities, which do not interfere with the unique propensity of the joint DNA molecules to branch migrate in vitro, are linked to the crossover, enhanced by RNaseA, and affect at most half of the DNA strands. We propose a structural model of joint DNA molecules containing ribonucleotides inserted within one strand, a gapped strand, and two continuous DNA strands. We further show that spontaneous joint DNA molecules are short-lived and are as abundant as replication forks. Our results emphasize the highly frequent formation of joint DNA molecules involving newly replicated DNA in an untreated cell and uncover a transitory mechanism connecting the sister chromatids during S phase.

  17. The use of convent archival records in medical research: the School Sisters of Notre Dame archives and the nun study.

    Science.gov (United States)

    Patzwald, Gari-Anne; Wildt, Sister Carol Marie

    2004-01-01

    The School Sisters of Notre Dame (SSND) archives program in a cooperative system for the arrangement and preservation of the records of the SSND provinces in North America, including records of individual sisters. Archival records include autobiographies, school and college transcripts, employment histories, and family socioeconomic data. The Nun Study, a longitudinal study of Alzheimer's disease and aging in 678 SSND sisters, compares data extracted from these records with data on late-life cognitive and physical function and postmortem brain neuropathology to explore early life factor that may affect late-life cognitive function and longevity.

  18. Self-healing photo-neuropathy and cervical spinal arthrosis in four sisters with brachioradial pruritus

    Directory of Open Access Journals (Sweden)

    Wallengren Joanna

    2009-11-01

    Full Text Available Abstract The cause of brachioradial pruritus (a localized itching on the arms or shoulders is controversial. The role of sun and cervical spine disease has been discussed. This is a report on four sisters suffering from brachioradial pruritus recurring every summer. The sisters spent much time outdoors and exposed themselves extensively to the sun. They also had occupations requiring heavy lifting. Cervical radiographs indicated arthrosis. The density of sensory nerve fibers in the skin biopsies from the itchy skin of the arms, visualized by antibodies against a pan-neuronal marker, protein gene product 9.5, was reduced compared with biopsies from the same skin region during the symptom-free period in the winter. This data exemplifies that brachioradial pruritus is a self healing photoneuropathy occurring in middle aged adults predisposed by cervical arthrosis.

  19. [Egon Erwin Kisch and the Blazek sisters. A contribution to the history of teratology].

    Science.gov (United States)

    Schierhorn, H

    1985-01-01

    A century ago, on April 29th 1885, the "Raving Reporter" Egon Erwin Kisch was born in Prague. On this occasion his news-reporting about the conjoined Bohemian twins Rosa and Josefa Blazek (born 1878) is appreciated and compared respectively contrasted with the observations and papers of contemporary physicians, among them the famous neuropathologist Richard Henneberg from Berlin and the important gynaecologists Breisky and Pitha from Prague and Schauta from Vienna. Kisch's report "The conjoined sisters" was published in his book "Sensation fair" during his antifascistic exile firstly 1941 in New York in English, a year later in Mexico-City in the German language. In spite of his stunt-making style Kisch's declining opposite the capitalistic marketing and opposite the disgracing people's exhibition (in this case of the Bohemian pygopage sisters) is articulated. Kisch, the founder of the socialistic literary report, died in 1948 in Prague, Czechoslovakia.

  20. [WILSON-KONOVALOV'S DISEASE IN TWO SISTERS: DIFFERENCES IN THE CLINICAL PICTURE AND SUCCESSFUL THERAPY].

    Science.gov (United States)

    Ignatova, T M; Solov'eva O V; Arion, E A; Balashova, M S; Rozina, T P

    2016-01-01

    Wilson-Konovalov's disease is a rare genetic pathology of copper metabolism that in the first place affects liver and CNS. Due to autosomal-recessive inheritance of this condition, it most frequently occurs in sibs. We report a case of Wilson-Konovalov's disease in two sisters differing in its clinical course: severe abdominal variant in the younger sister and largely neurologic form in the elder one. This observation demonstrates clinical variability of Wilson-Konovalov's disease, the possibility of its late clinical manifestation (at the age 45 years), the necessity of examination of all sibs of a proband regardless of age, and the possibility of radical improvement of prognosis even when the disease is diagnosed at the stage of decompensated liver cirrhosis.

  1. The first record of a trans-oceanic sister-group relationship between obligate vertebrate troglobites.

    Directory of Open Access Journals (Sweden)

    Prosanta Chakrabarty

    Full Text Available We show using the most complete phylogeny of one of the most species-rich orders of vertebrates (Gobiiformes, and calibrations from the rich fossil record of teleost fishes, that the genus Typhleotris, endemic to subterranean karst habitats in southwestern Madagascar, is the sister group to Milyeringa, endemic to similar subterranean systems in northwestern Australia. Both groups are eyeless, and our phylogenetic and biogeographic results show that these obligate cave fishes now found on opposite ends of the Indian Ocean (separated by nearly 7,000 km are each others closest relatives and owe their origins to the break up of the southern supercontinent, Gondwana, at the end of the Cretaceous period. Trans-oceanic sister-group relationships are otherwise unknown between blind, cave-adapted vertebrates and our results provide an extraordinary case of Gondwanan vicariance.

  2. The first record of a trans-oceanic sister-group relationship between obligate vertebrate troglobites.

    Science.gov (United States)

    Chakrabarty, Prosanta; Davis, Matthew P; Sparks, John S

    2012-01-01

    We show using the most complete phylogeny of one of the most species-rich orders of vertebrates (Gobiiformes), and calibrations from the rich fossil record of teleost fishes, that the genus Typhleotris, endemic to subterranean karst habitats in southwestern Madagascar, is the sister group to Milyeringa, endemic to similar subterranean systems in northwestern Australia. Both groups are eyeless, and our phylogenetic and biogeographic results show that these obligate cave fishes now found on opposite ends of the Indian Ocean (separated by nearly 7,000 km) are each others closest relatives and owe their origins to the break up of the southern supercontinent, Gondwana, at the end of the Cretaceous period. Trans-oceanic sister-group relationships are otherwise unknown between blind, cave-adapted vertebrates and our results provide an extraordinary case of Gondwanan vicariance.

  3. An Unusual Cause for Sister Mary Joseph’s Nodule: A Case Report

    Directory of Open Access Journals (Sweden)

    Yasser Aljehani

    2014-11-01

    Full Text Available Sister Mary Joseph’s nodule refers to palpable nodules bulging into the umbilicus as a result of metastasis from malignancy in the abdomen or pelvis. The most common primaries are in the gastrointestinal or genital tract, while other origins are considered rare. We recently treated a 71-year-old man who presented with painless umbilical swelling. Further investigation, including laboratory, radiological and histopathological exam, confirmed the diagnosis of a metastatic neuroendocrine tumor. The peculiarity of this case is that the umbilical swelling was the initial presentation of a neuroendocrine tumor and, to our knowledge, this is the first to be reported. This case demonstrates that neuroendocrine tumor is a rare cause of Sister Mary Joseph’s nodule.

  4. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

    facilitate replication recovery after MMS-induced replication stress. Our data reveal that control of Mrc1 turnover through the interplay between posttranslational modifications and INQ localization adds another layer of regulation to the replication checkpoint. We also add replication recovery to the list...... is mediated by Mrc1, which ensures Mec1 presence at the stalled replication fork thus facilitating Rad53 phosphorylation. When replication can be resumed safely, the replication checkpoint is deactivated and replication forks restart. One mechanism for checkpoint deactivation is the ubiquitin......-targeted proteasomal degradation of Mrc1. In this study, we describe a novel nuclear structure, the intranuclear quality control compartment (INQ), which regulates protein turnover and is important for recovery after replication stress. We find that upon methyl methanesulfonate (MMS)-induced replication stress, INQ...

  5. 最后消息:Bodies of JFK Jr.,Wife,Sister-in-Law Found

    Institute of Scientific and Technical Information of China (English)

    Tony; Munroe

    1999-01-01

    Searchers have found the bodies of John F. Kennedy Jr., his wife CarolynBessette Kennedy and her sister Lauren as well as a large piece of their crashedplane off the coast of Martha’s Vineyard, officials said Wednesday. Massachusetts Sen. Edward Kennedy and his two sons headed for the crashsite on a U. S. Coast Guard vessel after the bodies and wreckage (残骸) were

  6. Analysis of Interpersonal Relationship in the Consumer Society Context in Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    张恩秀

    2009-01-01

    Carrie's characterization is a familiar topic in the criticism in Sister Carrie. However, how it could be re-viewed in the context of the consumer society is relalively a new issue. This paper attempts to analyze the interpersonal relationship in the context of a consumer society. It explores the consumer society's influences on the lovers and family. In addition, it points out Dreiser's ambivalent attitude towards consumer ideology.

  7. Analyzing of Sister Carrie’s Independence Process from the Perspective of Feminism

    Institute of Scientific and Technical Information of China (English)

    姜新新

    2015-01-01

    "Sister Carrie" is published when the American society is in the transition from traditional industry to modern industry.Modern industrial not only provide opportunity to the development of city,but also offer some employment opportunities to the people,while the survival pressure for living is also increased.People’s thought also undergo a tremendous change.They even feel puzzled and confused.

  8. Arrangement of nuclear structures is not transmitted through mitosis but is identical in sister cells.

    Science.gov (United States)

    Orlova, Darya Yu; Stixová, Lenka; Kozubek, Stanislav; Gierman, Hinco J; Šustáčková, Gabriela; Chernyshev, Andrei V; Medvedev, Ruslan N; Legartová, Soňa; Versteeg, Rogier; Matula, Pavel; Stoklasa, Roman; Bártová, Eva

    2012-11-01

    Although it is well known that chromosomes are non-randomly organized during interphase, it is not completely clear whether higher-order chromatin structure is transmitted from mother to daughter cells. Therefore, we addressed the question of how chromatin is rearranged during interphase and whether heterochromatin pattern is transmitted after mitosis. We additionally tested the similarity of chromatin arrangement in sister interphase nuclei. We noticed a very active cell rotation during interphase, especially when histone hyperacetylation was induced or transcription was inhibited. This natural phenomenon can influence the analysis of nuclear arrangement. Using photoconversion of Dendra2-tagged core histone H4 we showed that the distribution of chromatin in daughter interphase nuclei differed from that in mother cells. Similarly, the nuclear distribution of heterochromatin protein 1β (HP1β) was not completely identical in mother and daughter cells. However, identity between mother and daughter cells was in many cases evidenced by nucleolar composition. Moreover, morphology of nucleoli, HP1β protein, Cajal bodies, chromosome territories, and gene transcripts were identical in sister cell nuclei. We conclude that the arrangement of interphase chromatin is not transmitted through mitosis, but the nuclear pattern is identical in naturally synchronized sister cells. It is also necessary to take into account the possibility that cell rotation and the degree of chromatin condensation during functionally specific cell cycle phases might influence our view of nuclear architecture.

  9. An Eco-feminist Comparison between Sister Carrie and My Antonia

    Institute of Scientific and Technical Information of China (English)

    刘翌

    2014-01-01

    According to human history, there are varieties of ways through which the feminine aspect of nature faced and in many cases, overcame oppression. One of the ways this phenomenon displays itself is in the literary works that we deem as realis⁃tic and an expression of the norms and customs of the society in question. Sister Carrie and My Antonia are two such literary pieces that embody the struggles and triumphs of women in the 19th and most of the early 20th century. In creating such monu⁃mental and naturalistic adaptations, both authors are able to present the case of two migratory women from different backgrounds but confined by the norms and mannerisms of the society around them. The struggles that each of these characters undergoes is an expression of the underlying constraints that the paternal and chauvinistic society of their time places upon both women and the natural world. The eco-feminist agenda, however, gets a more elaborate representation in My Antonia than in Sister Carrie due to a variety of factors that serve to illuminate the differences between these two iconic stories. This paper makes a thorough comparison between two literary works—Sister Carrie by Theodore Dreiser and My Antonia by Willa Cather from the perspec⁃tive of eco-feminism.

  10. Secret Sisters: Women Religious under European Communism Collection at the Catholic Theological Union

    Directory of Open Access Journals (Sweden)

    Vincent P. Tinerella

    2010-10-01

    Full Text Available After the fall of Communism in Eastern Europe, Pope John Paul II asked Catholics around the world to assist members of the Church who had suffered under the yoke of communist oppression as a result of their commitment to Catholicism. Sr. Margaret Savoie, and Sr. Margaret Nacke, Sisters of St. Joseph, Concordia, Kansas, decided that the experiences of Catholic women in religious communities – “surviving sisters” – was an important story that needed to be documented, preserved, and made available for future generations and researchers. In 2003, Sisters Mary and Margaret began their research, recording the plight of Catholic sisters in eight countries, Bulgaria, Czech Republic, Hungary, Lithuania, Romania, Slovakia, and the Ukraine, from the rise of Stalin until the collapse of European communism. Over 200 testimonials now reside at the Paul Bechtold Library at the Catholic Theological Union in Chicago under the auspices of the library’s archivist, Dr. Kenneth O’Malley, C.P. , and their work has been made into a national and award-winning documentary film. .

  11. Hyperthermia stimulates HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Ferdinand Roesch

    Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  12. Hyperthermia stimulates HIV-1 replication.

    Science.gov (United States)

    Roesch, Ferdinand; Meziane, Oussama; Kula, Anna; Nisole, Sébastien; Porrot, Françoise; Anderson, Ian; Mammano, Fabrizio; Fassati, Ariberto; Marcello, Alessandro; Benkirane, Monsef; Schwartz, Olivier

    2012-01-01

    HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  13. Cellular Responses to Replication Problems

    NARCIS (Netherlands)

    M. Budzowska (Magdalena)

    2008-01-01

    textabstractDuring every S-phase cells need to duplicate their genomes so that both daughter cells inherit complete copies of genetic information. It is a tremendous task, given the large sizes of mammalian genomes and the required precision of DNA replication. A major threat to the accuracy and eff

  14. Covert Reinforcement: A Partial Replication.

    Science.gov (United States)

    Ripstra, Constance C.; And Others

    A partial replication of an investigation of the effect of covert reinforcement on a perceptual estimation task is described. The study was extended to include an extinction phase. There were five treatment groups: covert reinforcement, neutral scene reinforcement, noncontingent covert reinforcement, and two control groups. Each subject estimated…

  15. Crinivirus replication and host interactions

    Directory of Open Access Journals (Sweden)

    Zsofia A Kiss

    2013-05-01

    Full Text Available Criniviruses comprise one of the genera within the family Closteroviridae. Members in this family are restricted to the phloem and rely on whitefly vectors of the genera Bemisia and/or Trialeurodes for plant-to-plant transmission. All criniviruses have bipartite, positive-sense ssRNA genomes, although there is an unconfirmed report of one having a tripartite genome. Lettuce infectious yellows virus (LIYV is the type species of the genus, the best studied so far of the criniviruses and the first for which a reverse genetics system was available. LIYV RNA 1 encodes for proteins predicted to be involved in replication, and alone is competent for replication in protoplasts. Replication results in accumulation of cytoplasmic vesiculated membranous structures which are characteristic of most studied members of the Closteroviridae. These membranous structures, often referred to as BYV-type vesicles, are likely sites of RNA replication. LIYV RNA 2 is replicated in trans when co-infecting cells with RNA 1, but is temporally delayed relative to RNA1. Efficient RNA 2 replication also is dependent on the RNA 1-encoded RNA binding protein, P34. No LIYV RNA 2-encoded proteins have been shown to affect RNA replication, but at least four, CP, CPm, Hsp70h, and p59 are virion structural components and CPm is a determinant of whitefly transmissibility. Roles of other LIYV RNA 2-encoded proteins are largely as yet unknown, but P26 is a non-virion protein that accumulates in cells as characteristic plasmalemma deposits which in plants are localized within phloem parenchyma and companion cells over plasmodesmata connections to sieve elements. The two remaining crinivirus-conserved RNA 2-encoded proteins are P5 and P9. P5 is 39 amino acid protein and is encoded at the 5’ end of RNA 2 as ORF1 and is part of the hallmark closterovirus gene array. The orthologous gene in BYV has been shown to play a role in cell-to-cell movement and indicated to be localized to the

  16. Three wise centromere functions: see no error, hear no break, speak no delay.

    Science.gov (United States)

    Tanaka, Tomoyuki U; Clayton, Lesley; Natsume, Toyoaki

    2013-12-01

    The main function of the centromere is to promote kinetochore assembly for spindle microtubule attachment. Two additional functions of the centromere, however, are becoming increasingly clear: facilitation of robust sister-chromatid cohesion at pericentromeres and advancement of replication of centromeric regions. The combination of these three centromere functions ensures correct chromosome segregation during mitosis. Here, we review the mechanisms of the kinetochore-microtubule interaction, focusing on sister-kinetochore bi-orientation (or chromosome bi-orientation). We also discuss the biological importance of robust pericentromeric cohesion and early centromere replication, as well as the mechanisms orchestrating these two functions at the microtubule attachment site.

  17. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1983

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa NWR, Cedar Point NWR, and West Sister Island NWR outlines Refuge accomplishments during the 1983 calendar year. The report...

  18. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1979

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa NWR, Cedar Point NWR, West Sister Island NWR, Navarre Marsh, and Darby Marsh outlines Refuge accomplishments during the 1979...

  19. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1985

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa NWR, Cedar Point NWR, and West Sister Island NWR outlines Refuge accomplishments during the 1985 calendar year. The report...

  20. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1987

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa NWR, Cedar Point NWR, and West Sister Island NWR outlines Refuge accomplishments during the 1987 calendar year. The report...

  1. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1986

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa NWR, Cedar Point NWR, and West Sister Island NWR outlines Refuge accomplishments during the 1986 calendar year. The report...

  2. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1989

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa, Cedar Point, and West Sister Island National Wildlife Refuges outlines Refuge accomplishments during the 1989 calendar year....

  3. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1982

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa NWR, Cedar Point NWR, and West Sister Island NWR outlines Refuge accomplishments during the 1982 calendar year. The report...

  4. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1980

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa NWR, Cedar Point NWR, West Sister Island NWR, Navarre Marsh, and Darby Marsh outlines Refuge accomplishments during the 1980...

  5. Ottawa National Wildlife Refuge Complex (Ottawa, Cedar Point, West Sister Island NWR's): Annual narrative report: Calendar year 1981

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Ottawa NWR, Cedar Point NWR, and West Sister Island NWR outlines Refuge accomplishments during the 1981 calendar year. The report...

  6. Replication-Uncoupled Histone Deposition during Adenovirus DNA Replication

    OpenAIRE

    Komatsu, Tetsuro; Nagata, Kyosuke

    2012-01-01

    In infected cells, the chromatin structure of the adenovirus genome DNA plays critical roles in its genome functions. Previously, we reported that in early phases of infection, incoming viral DNA is associated with both viral core protein VII and cellular histones. Here we show that in late phases of infection, newly synthesized viral DNA is also associated with histones. We also found that the knockdown of CAF-1, a histone chaperone that functions in the replication-coupled deposition of his...

  7. REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

    DEFF Research Database (Denmark)

    2016-01-01

    structured master surface (3a, 3b, 3c, 3d) having a lateral master pattern and a vertical master profile. The microscale structured master surface (3a, 3b, 3c, 3d) has been provided by localized pulsed laser treatment to generate microscale phase explosions. A method for producing a part with microscale......The invention relates to a replication tool (1, 1a, 1b) for producing a part (4) with a microscale textured replica surface (5a, 5b, 5c, 5d). The replication tool (1, 1a, 1b) comprises a tool surface (2a, 2b) defining a general shape of the item. The tool surface (2a, 2b) comprises a microscale...... energy directors on flange portions thereof uses the replication tool (1, 1a, 1b) to form an item (4) with a general shape as defined by the tool surface (2a, 2b). The formed item (4) comprises a microscale textured replica surface (5a, 5b, 5c, 5d) with a lateral arrangement of polydisperse microscale...

  8. Replicator dynamics in value chains

    DEFF Research Database (Denmark)

    Cantner, Uwe; Savin, Ivan; Vannuccini, Simone

    2016-01-01

    The pure model of replicator dynamics though providing important insights in the evolution of markets has not found much of empirical support. This paper extends the model to the case of firms vertically integrated in value chains. We show that i) by taking value chains into account, the replicator...... dynamics may revert its effect. In these regressive developments of market selection, firms with low fitness expand because of being integrated with highly fit partners, and the other way around; ii) allowing partner's switching within a value chain illustrates that periods of instability in the early...... stage of industry life-cycle may be the result of an 'optimization' of partners within a value chain providing a novel and simple explanation to the evidence discussed by Mazzucato (1998); iii) there are distinct differences in the contribution to market selection between the layers of a value chain...

  9. Therapeutic targeting of replicative immortality

    OpenAIRE

    Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo

    2015-01-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persis...

  10. Alphavirus polymerase and RNA replication.

    Science.gov (United States)

    Pietilä, Maija K; Hellström, Kirsi; Ahola, Tero

    2017-01-16

    Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4), initially produced as a polyprotein P1234. nsP4 is the core RNA-dependent RNA polymerase but all four nsPs are required for RNA synthesis. The early replication complex (RC) formed by the polyprotein P123 and nsP4 synthesizes minus RNA strands, and the late RC composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus strands. Different parts of nsP4 recognize the promoters for minus and plus strands but the binding also requires the other nsPs. The alphavirus polymerase has been purified and is capable of de novo RNA synthesis only in the presence of the other nsPs. The purified nsP4 also has terminal adenylyltransferase activity, which may generate the poly(A) tail at the 3' end of the genome. Membrane association of the nsPs is vital for replication, and alphaviruses induce membrane invaginations called spherules, which form a microenvironment for RNA synthesis by concentrating replication components and protecting double-stranded RNA intermediates. The RCs isolated as crude membrane preparations are active in RNA synthesis in vitro, but high-resolution structure of the RC has not been achieved, and thus the arrangement of viral and possible host components remains unknown. For some alphaviruses, Ras-GTPase-activating protein (Src-homology 3 (SH3) domain)-binding proteins (G3BPs) and amphiphysins have been shown to be essential for RNA replication and are present in the RCs. Host factors offer an additional target for antivirals, as only few alphavirus polymerase inhibitors have been described.

  11. Dynamic replication of Web contents

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The phenomenal growth of the World Wide Web has brought huge increase in the traffic to the popular web sites.Long delays and denial of service experienced by the end-users,especially during the peak hours,continues to be the common problem while accessing popular sites.Replicating some of the objects at multiple sites in a distributed web-server environment is one of the possible solutions to improve the response time/Iatency. The decision of what and where to replicate requires solving a constraint optimization problem,which is NP-complete in general.In this paper, we consider the problem of placing copies of objects in a distributed web server system to minimize the cost of serving read and write requests when the web servers have Iimited storage capacity.We formulate the problem as a 0-1 optimization problem and present a polynomial time greedy algorithm with backtracking to dynamically replicate objects at the appropriate sites to minimize a cost function.To reduce the solution search space,we present necessary condi tions for a site to have a replica of an object jn order to minimize the cost function We present simulation resuIts for a variety of problems to illustrate the accuracy and efficiency of the proposed algorithms and compare them with those of some well-known algorithms.The simulation resuIts demonstrate the superiority of the proposed algorithms.

  12. Evaluating replicability of laboratory experiments in economics.

    Science.gov (United States)

    Camerer, Colin F; Dreber, Anna; Forsell, Eskil; Ho, Teck-Hua; Huber, Jürgen; Johannesson, Magnus; Kirchler, Michael; Almenberg, Johan; Altmejd, Adam; Chan, Taizan; Heikensten, Emma; Holzmeister, Felix; Imai, Taisuke; Isaksson, Siri; Nave, Gideon; Pfeiffer, Thomas; Razen, Michael; Wu, Hang

    2016-03-25

    The replicability of some scientific findings has recently been called into question. To contribute data about replicability in economics, we replicated 18 studies published in the American Economic Review and the Quarterly Journal of Economics between 2011 and 2014. All of these replications followed predefined analysis plans that were made publicly available beforehand, and they all have a statistical power of at least 90% to detect the original effect size at the 5% significance level. We found a significant effect in the same direction as in the original study for 11 replications (61%); on average, the replicated effect size is 66% of the original. The replicability rate varies between 67% and 78% for four additional replicability indicators, including a prediction market measure of peer beliefs.

  13. Adenovirus sequences required for replication in vivo.

    OpenAIRE

    Wang, K.; Pearson, G D

    1985-01-01

    We have studied the in vivo replication properties of plasmids carrying deletion mutations within cloned adenovirus terminal sequences. Deletion mapping located the adenovirus DNA replication origin entirely within the first 67 bp of the adenovirus inverted terminal repeat. This region could be further subdivided into two functional domains: a minimal replication origin and an adjacent auxillary region which boosted the efficiency of replication by more than 100-fold. The minimal origin occup...

  14. Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and cell cycle regulation.

    Science.gov (United States)

    Strzalka, Wojciech; Ziemienowicz, Alicja

    2011-05-01

    PCNA (proliferating cell nuclear antigen) has been found in the nuclei of yeast, plant and animal cells that undergo cell division, suggesting a function in cell cycle regulation and/or DNA replication. It subsequently became clear that PCNA also played a role in other processes involving the cell genome. This review discusses eukaryotic PCNA, with an emphasis on plant PCNA, in terms of the protein structure and its biochemical properties as well as gene structure, organization, expression and function. PCNA exerts a tripartite function by operating as (1) a sliding clamp during DNA synthesis, (2) a polymerase switch factor and (3) a recruitment factor. Most of its functions are mediated by its interactions with various proteins involved in DNA synthesis, repair and recombination as well as in regulation of the cell cycle and chromatid cohesion. Moreover, post-translational modifications of PCNA play a key role in regulation of its functions. Finally, a phylogenetic comparison of PCNA genes suggests that the multi-functionality observed in most species is a product of evolution. Most plant PCNAs exhibit features similar to those found for PCNAs of other eukaryotes. Similarities include: (1) a trimeric ring structure of the PCNA sliding clamp, (2) the involvement of PCNA in DNA replication and repair, (3) the ability to stimulate the activity of DNA polymerase δ and (4) the ability to interact with p21, a regulator of the cell cycle. However, many plant genomes seem to contain the second, probably functional, copy of the PCNA gene, in contrast to PCNA pseudogenes that are found in mammalian genomes.

  15. Three sisters with very-late-onset major depression and parkinsonism.

    Science.gov (United States)

    Sechi, GianPietro; Antonio Cocco, Giovanni; Errigo, Alessandra; Deiana, Luca; Rosati, Giulio; Agnetti, Virgilio; Stephen Paulus, Kay; Mario Pes, Giovanni

    2007-03-01

    Familiar Parkinson's disease has an age of onset from the second to the sixth decade, whereas Wilson's disease (WD) usually presents in the first decade of life. We studied three sisters with a form of very-late-onset major depression and parkinsonism with probable linkage to ATP7B gene. Molecular studies demonstrated a nucleotide deletion at the 5'UTR region in a single allele of ATP7B gene. They did not have a family history of WD, or markers indicative for copper deposition in peripheral tissues. We suggest that single allele mutations of ATP7B gene may confer a susceptibility for late-onset major depression and parkinsonism.

  16. Two Cases of Endometrial Cancer in Twin Sisters with Myotonic Dystrophy

    Directory of Open Access Journals (Sweden)

    Ezra Y. Koh

    2016-01-01

    Full Text Available We describe two cases of endometrial cancer (EC occurring in nulligravid twin sisters with myotonic dystrophy. Both tested negative for Lynch syndrome and both were treated with laparoscopic hysterectomy with bilateral salpingooophorectomy and adjuvant radiotherapy. Although EC tends to run in families, the diagnosis in itself is not considered sufficient cause for screening or prophylactic measures in close relatives. However, the presence of additional risk factors, such as nulligravidity and myotonic dystrophy in the underlying cases, may call for extra vigilance in first-degree family members.

  17. Shigella strains are not clones of Escherichia coli but sister species in the genus Escherichia.

    Science.gov (United States)

    Zuo, Guanghong; Xu, Zhao; Hao, Bailin

    2013-02-01

    Shigella species and Escherichia coli are closely related organisms. Early phenotyping experiments and several recent molecular studies put Shigella within the species E. coli. However, the whole-genome-based, alignment-free and parameter-free CVTree approach shows convincingly that four established Shigella species, Shigella boydii, Shigella sonnei, Shigella felxneri and Shigella dysenteriae, are distinct from E. coli strains, and form sister species to E. coli within the genus Escherichia. In view of the overall success and high resolution power of the CVTree approach, this result should be taken seriously. We hope that the present report may promote further in-depth study of the Shigella-E. coli relationship.

  18. The Naturalism in Tess of the D'Urbervilles and Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    原燕婷

    2010-01-01

    @@ Nowadays, literature study is almost perfectly and profoundly cultivated by scholars and educators all around the world, thus, the exploration in this field is progressing much slower, and comparison literature is raising its head steadily in modern literature circles. Accordingly, the comparison between Tess of the d'Urbervilles and Sister Carrie is rarely done, although the naturalism in the two novels has been colossally studied and nearly reached the peak of its maxim, the author still feel obliged to connect them through the clue-"naturalism" to attain a unique but unanimous effect of literature study.

  19. Emergence of ethnochoreology internationally: The Janković sisters, Maud Karpeles, and Gertrude Kurath

    Directory of Open Access Journals (Sweden)

    Dunin Elsie Ivancich

    2014-01-01

    Full Text Available A fifty-year (1962-2012 period has been shown as a history of ethnochoreology supported by living memories of members of the International Council for Traditional Music (ICTM Study Group on Ethnochoreology. Recently uncovered and juxtapositioned correspondence of three predecessors within earlier years of the International Folk Music Council (IFMC broadens the history. This article reveals the emergence of ethnochoreology during the 1950s with publications of the two Janković sisters in Serbia with that of Gertrude Kurath in the United States, alongside correspondence with Maud Karpeles, the unheralded founder of the IFMC.

  20. Diet transiently improves migraine in two twin sisters: possible role of ketogenesis?

    Science.gov (United States)

    Di Lorenzo, Cherubino; Currà, Antonio; Sirianni, Giulio; Coppola, Gianluca; Bracaglia, Martina; Cardillo, Alessandra; De Nardis, Lorenzo; Pierelli, Francesco

    2013-01-01

    The ketogenic diet is a high-fat, low-carbohydrate diet long used to treat refractory epilepsy; ketogenesis (ketone body formation) is a physiological phenomenon also observed in patients following lowcarbohydrate, low-calorie diets prescribed for rapid weight loss. We report the case of a pair of twin sisters, whose high-frequency migraine improved during a ketogenic diet they followed in order to lose weight. The observed time-lock between ketogenesis and migraine improvement provides some insight into how ketones act to improve migraine.

  1. [Partial lipodystrophy in two HLA identical sisters with hypocomplementemia and nephropathy].

    Science.gov (United States)

    Peces, R

    2002-01-01

    Partial lipodystrophy is a rare disorder with both autosomal recessive and familial forms. The cutaneous findings, which are often subtle, consist of gradual loss of subcutaneous fat from the face and upper body. Low levels of C3 and the presence of C3NeF help to identify these patients. Associated systemic abnormalities include the development of membranoproliferative glomerulonephritis, insulin resistance and an increased incidence of autoimmune diseases. We report here two HLA identical sisters with the typical features of partial lipodystrophy associated with recurrent infections, low levels of C3, and nephropathy. Our data suggest an autosomal recessive transmission. We discuss the genetic and molecular basis of this rare association.

  2. The Conflict Between the Traditional Value and Reality In Sister Carrie

    Institute of Scientific and Technical Information of China (English)

    顾庆媛; 陈飞; 孙胜强; 常利娜; 张罗斌

    2009-01-01

    Theodore Dreiser relates a story of Carrie's rise from a poor country girl to a Broadway star in Sister Carrie.An attempt is rnade in this paper to analyze the cold society.Byway of analyzing this unequal and cruel reality to prove:in the world only the fittest can survive.the standards and requirements of morality are challenged and the traditional value is suspected.In the cold reality.any way that Can protect oneself or survivein the wodd is sensible,morality and traditional value are weak and mcaningless.

  3. Replication Origin Specification Gets a Push.

    Science.gov (United States)

    Plosky, Brian S

    2015-12-03

    During the gap between G1 and S phases when replication origins are licensed and fired, it is possible that DNA translocases could disrupt pre-replicative complexes (pre-RCs). In this issue of Molecular Cell, Gros et al. (2015) find that pre-RCs can be pushed along DNA and retain the ability to support replication.

  4. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard

    2015-01-01

    DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms...

  5. Replication of micro and nano surface geometries

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Hocken, R.J.; Tosello, Guido

    2011-01-01

    : manufacture of net-shape micro/nano surfaces, tooling (i.e. master making), and surface quality control (metrology, inspection). Replication processes and methods as well as the metrology of surfaces to determine the degree of replication are presented and classified. Examples from various application areas...... are given including replication for surface texture measurements, surface roughness standards, manufacture of micro and nano structured functional surfaces, replicated surfaces for optical applications (e.g. optical gratings), and process chains based on combinations of repeated surface replication steps....

  6. Replication of prions in differentiated muscle cells.

    Science.gov (United States)

    Herbst, Allen; Aiken, Judd M; McKenzie, Debbie

    2014-01-01

    We have demonstrated that prions accumulate to high levels in non-proliferative C2C12 myotubes. C2C12 cells replicate as myoblasts but can be differentiated into myotubes. Earlier studies indicated that C2C12 myoblasts are not competent for prion replication. (1) We confirmed that observation and demonstrated, for the first time, that while replicative myoblasts do not accumulate PrP(Sc), differentiated post-mitotic myotube cultures replicate prions robustly. Here we extend our observations and describe the implication and utility of this system for replicating prions.

  7. FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs

    Directory of Open Access Journals (Sweden)

    Zhao Hongyu

    2008-01-01

    Full Text Available Abstract Background FTO is a gene located in chromosome region 16q12.2. Recently two studies have found associations of several single nucleotide polymorphisms (SNPs in FTO with body mass index (BMI and obesity, particularly rs1421085, rs17817449, and rs9939609. Methods We examined these three SNPs in 583 extremely obese women with current BMI greater than 35 kg/m2 and lifetime BMI greater than 40 kg/m2, and 544 controls who were currently normal weight (BMI2 and had never been overweight during their lifetimes. Results We detected highly significant associations of obesity with alleles in all three SNPs (p -9. The strongest association was with rs1421085 (p = 3.04 × 10-10, OR = 1.75, CI = 1.47–2.08. A subset of 99 cases had extremely discordant sisters with BMI2. The discordant sisters differed in allele and genotype frequencies in parallel with the overall case and control sample. The strongest association was with rs17817449 (z = 3.57, p = 3.6 × 10-4. Conclusion These results suggest common variability in FTO is associated with increased obesity risk or resistance and may in part account for differences between closely related individuals.

  8. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: variable phenotypic expression in three affected sisters from Mexican ancestry.

    Science.gov (United States)

    Arteaga, María E; Hunziker, Walter; Teo, Audrey S M; Hillmer, Axel M; Mutchinick, Osvaldo M

    2015-02-01

    Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal disease caused by mutations in genes for the tight junction transmembrane proteins Claudin-16 (CLDN16) and Claudin-19 (CLDN19). We present the first case report of a Mexican family with three affected sisters carrying a p.Gly20Asp mutation in CLDN19 whose heterozygous mother showed evident hypercalciuria and normal low magnesemia without any other clinical, laboratory, and radiological symptoms of renal disease making of her an unsuitable donor. The affected sisters showed variable phenotypic expression including age of first symptoms, renal urinary tract infections, nephrolithiasis, nephrocalcinosis, and eye symptoms consisting in retinochoroiditis, strabismus, macular scars, bilateral anisocoria, and severe myopia and astigmatism. End stage renal disease due to renal failure needed kidney transplantation in the three of them. Interesting findings were a heterozygous mother with asymptomatic hypercalciuria warning on the need of carefully explore clinical, laboratory, kidney ultrasonograpy, and mutation status in first degree asymptomatic relatives to avoid inappropriate kidney donors; an evident variable phenotypic expression among patients; the identification of a mutation almost confined to Spanish cases and a 3.5 Mb block of genomic homozygosis strongly suggesting a common remote parental ancestor for the gene mutation reported.

  9. Exploring the origin of the latitudinal diversity gradient: Contrasting the sister fern genera Phegopteris and Pseudophegopteris

    Institute of Scientific and Technical Information of China (English)

    Harald SCHNEIDER; Li-Juan HE; Jeannine MARQUARDT; Li WANG; Jochen HEINRICHS; Sabine HENNEQUIN; Xian-Chun ZHANG

    2013-01-01

    The origin of the latitudinal biodiversity gradient has been studied using various approaches.Here,we employ a comparative phylogenetic approach to infer evidence for the hypothesis that differences in diversification rates are one of the main factors contributing to the assembly of this gradient.We infer the phylogeny of the two sister genera Phegopteris and Pseudophegopteris.The two genera are distinct in their species richness (4 vs.20 spp.) and their preferences to temperate to subtropical (Phegopteris) or tropical climates (Pseudophegopteris).Using sequences of three plastid DNA regions,we confirm the monophyly of each genus and infer the inter-and intra-generic phylogenetic differentiation of the sister clades.We recover evidence for distinct net-diversification rate between the two genera,which may be caused either by a higher extinction risk of temperate Phegopteris or a higher speciation rate of tropical Pseudophegopteris.We discuss our results in the context of our current knowledge on the speciation processes of ferns.We conclude on the crucial influence of other factors such as the rise of the Himalaya on the diversification of these fems.

  10. Three Sisters Mountain Village development transformation of old coal mine properties into modern day use

    Energy Technology Data Exchange (ETDEWEB)

    Fox, B. [Golder Paste Technology Ltd., Sudbury, ON (Canada)

    2006-07-01

    This paper discussed the development of the Three Sisters Mountain Village, located close to Canmore, Alberta. The paper provided the history and background of the mining and development of the site. It discussed underground mining methodology and planned housing and industrial development. The village included plans for 10,000 residential homes, 2 golf courses, a wellness centre, a school, commercial buildings and wildlife corridors. Environmental concerns were also addressed, as Canmore contains a series of natural wildlife corridors, which act as migration and travelling routes for elk and deer as well as cougars, grizzly bears, and other animals. These routes are essential for the survival of the different herds and animal species. The development progress strategy was discussed. The Three Sisters Mountain Village Development commissioned Golder Associates Ltd. to study and address the environmental concerns of the stakeholders regarding the migrating routes of wildlife. Mining works mitigation, including mapping of the constraint zones, knowledge of subsidence issues and the effects of subsidence on structural stress and the ability to analysis field data to predict potential problems was also presented along with a methodology for mitigation and choice of backfill material to be used to fill the mine workings. The advantages of using concrete paste backfill were also identified.

  11. Different parasite faunas in sympatric populations of sister hedgehog species in a secondary contact zone.

    Directory of Open Access Journals (Sweden)

    Miriam Pfäffle

    Full Text Available Providing descriptive data on parasite diversity and load in sister species is a first step in addressing the role of host-parasite coevolution in the speciation process. In this study we compare the parasite faunas of the closely related hedgehog species Erinaceus europaeus and E. roumanicus from the Czech Republic where both occur in limited sympatry. We examined 109 hedgehogs from 21 localities within this secondary contact zone. Three species of ectoparasites and nine species of endoparasites were recorded. Significantly higher abundances and prevalences were found for Capillaria spp. and Brachylaemus erinacei in E. europaeus compared to E. roumanicus and higher mean infection rates and prevalences for Hymenolepis erinacei, Physaloptera clausa and Nephridiorhynchus major in E. roumanicus compared to E. europaeus. Divergence in the composition of the parasite fauna, except for Capillaria spp., which seem to be very unspecific, may be related to the complicated demography of their hosts connected with Pleistocene climate oscillations and consequent range dynamics. The fact that all parasite species with different abundances in E. europaeus and E. roumanicus belong to intestinal forms indicates a possible diversification of trophic niches between both sister hedgehog species.

  12. A novel sister clade to the enterobacteria microviruses (family Microviridae) identified in methane seep sediments.

    Science.gov (United States)

    Bryson, Samuel Joseph; Thurber, Andrew R; Correa, Adrienne M S; Orphan, Victoria J; Vega Thurber, Rebecca

    2015-10-01

    Methane seep microbial communities perform a key ecosystem service by consuming the greenhouse gas methane prior to its release into the hydrosphere, minimizing the impact of marine methane sources on our climate. Although previous studies have examined the ecology and biochemistry of these communities, none has examined viral assemblages associated with these habitats. We employed virus particle purification, genome amplification, pyrosequencing and gene/genome reconstruction and annotation on two metagenomic libraries, one prepared for ssDNA and the other for all DNA, to identify the viral community in a methane seep. Similarity analysis of these libraries (raw and assembled) revealed a community dominated by phages, with a significant proportion of similarities to the Microviridae family of ssDNA phages. We define these viruses as the Eel River Basin Microviridae (ERBM). Assembly and comparison of 21 ERBM closed circular genomes identified five as members of a novel sister clade to the Microvirus genus of Enterobacteria phages. Comparisons among other metagenomes and these Microviridae major-capsid sequences indicated that this clade of phages is currently unique to the Eel River Basin sediments. Given this ERBM clade's relationship to the Microviridae genus Microvirus, we define this sister clade as the candidate genus Pequeñovirus.

  13. DNA replication stress: causes, resolution and disease.

    Science.gov (United States)

    Mazouzi, Abdelghani; Velimezi, Georgia; Loizou, Joanna I

    2014-11-15

    DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Replication Stress: A Lifetime of Epigenetic Change

    Directory of Open Access Journals (Sweden)

    Simran Khurana

    2015-09-01

    Full Text Available DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs and has been linked to both genome instability and irreversible cell cycle arrest (senescence. Recent technological advances have elucidated many of the factors that contribute to the sensing and repair of stalled or broken replication forks. In addition to bona fide repair factors, these efforts highlight a range of chromatin-associated changes at and near sites of replication stress, suggesting defects in epigenome maintenance as a potential outcome of aberrant DNA replication. Here, we will summarize recent insight into replication stress-induced chromatin-reorganization and will speculate on possible adverse effects for gene expression, nuclear integrity and, ultimately, cell function.

  15. Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster (CHO) Cells With and Without Metabolic Activation, Test Acticle: Ethylenediamine Dinitrate (EDDN)

    Science.gov (United States)

    2010-02-25

    chromosomes leading to four-armed configurations. This could be asymmetrical with formation of a dicentric and an acentric chromatid, ifunion is complete, or...a shortened monocentric chromosome , and where there is no sister chromatid union. Dicentric - an asymmetrical exchange between two chromosomes ...a shortened monocentric chromosome , and where there is no sister chromatid union. Dicentric - an asymmetrical exchange between two chromosomes

  16. Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation

    OpenAIRE

    Measday, Vivien; Baetz, Kristin; Guzzo, Julie; Yuen, Karen; Kwok, Teresa; Sheikh, Bilal; Ding, Huiming; Ueta, Ryo; Hoac, Trinh; Cheng, Benjamin; Pot, Isabelle; Tong, Amy; Yamaguchi-Iwai, Yuko; Boone, Charles; Hieter, Phil

    2005-01-01

    Accurate chromosome segregation requires the execution and coordination of many processes during mitosis, including DNA replication, sister chromatid cohesion, and attachment of chromosomes to spindle microtubules via the kinetochore complex. Additional pathways are likely involved because faithful chromosome segregation also requires proteins that are not physically associated with the chromosome. Using kinetochore mutants as a starting point, we have identified genes with roles in chromosom...

  17. Terminalia catappa, an anticlastogenic agent against MMS induced genotoxicity in the human lymphocyte culture and in bone marrow cells of Albino mice

    Directory of Open Access Journals (Sweden)

    Mohammad Sultan Ahmad

    2014-07-01

    Conclusion: Extracts of T. catappa significantly reduced chromosomal aberrations up to 11.65% to 40.30% at different dosages against MMS induced toxicity, similarly sister chromatid exchange was reduced and replication index enhanced in vitro. Similarly in the in vivo experiments, the effective reduction in clastogeny ranges from 19.70% to 40.90%. Their reducing potential was time and dose dependant.

  18. Three wise centromere functions: see no error, hear no break, speak no delay.

    OpenAIRE

    Tanaka, Tomoyuki U; Clayton, Lesley; Natsume, Toyoaki

    2013-01-01

    The main function of the centromere is to promote kinetochore assembly for spindle microtubule attachment. Two additional functions of the centromere, however, are becoming increasingly clear: facilitation of robust sister-chromatid cohesion at pericentromeres and advancement of replication of centromeric regions. The combination of these three centromere functions ensures correct chromosome segregation during mitosis. Here, we review the mechanisms of the kinetochore–microtubule interaction,...

  19. DNA topoisomerase II must act at mitosis to prevent nondisjunction and chromosome breakage.

    OpenAIRE

    Holm, C.; Stearns, T.; Botstein, D

    1989-01-01

    The hypothesis that DNA topoisomerase II facilitates the separation of replicated sister chromatids was tested by examining the consequences of chromosome segregation in the absence of topoisomerase II activity. We observed a substantial elevation in the rate of nondisjunction in top2/top2 cells incubated at the restrictive temperature for one generation time. In contrast, only a minor increase in the amount of chromosome breakage was observed by either physical or genetic assays. These resul...

  20. Novel HPS6 mutations identified by whole-exome sequencing in two Japanese sisters with suspected ocular albinism.

    Science.gov (United States)

    Miyamichi, Daisuke; Asahina, Miki; Nakajima, Junya; Sato, Miho; Hosono, Katsuhiro; Nomura, Takahito; Negishi, Takashi; Miyake, Noriko; Hotta, Yoshihiro; Ogata, Tsutomu; Matsumoto, Naomichi

    2016-09-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction and ceroid deposition. We report suspected ocular albinism in two Japanese sisters, caused by mutations in the HPS6 (Hermansky-Pudlak syndrome 6) gene. Trio-based whole-exome sequencing (WES) identified novel compound heterozygous mutations in HPS6 (c.1898delC: mother origin and c.2038C>T: father origin) in the two sisters. To date, 10 associated mutations have been detected in HPS6. Although we detected no general manifestations, including platelet dysfunction, in the sisters, even in long-term follow-up, we established a diagnosis of HPS type 6 based on the HPS6 mutations and absence of dense bodies in the platelets, indicating that WES can identify cases of HPS type 6. To the best of our knowledge, this is the first report of HPS6 mutations in Japanese patients.

  1. Self-replication of DNA rings

    Science.gov (United States)

    Kim, Junghoon; Lee, Junwye; Hamada, Shogo; Murata, Satoshi; Ha Park, Sung

    2015-06-01

    Biology provides numerous examples of self-replicating machines, but artificially engineering such complex systems remains a formidable challenge. In particular, although simple artificial self-replicating systems including wooden blocks, magnetic systems, modular robots and synthetic molecular systems have been devised, such kinematic self-replicators are rare compared with examples of theoretical cellular self-replication. One of the principal reasons for this is the amount of complexity that arises when you try to incorporate self-replication into a physical medium. In this regard, DNA is a prime candidate material for constructing self-replicating systems due to its ability to self-assemble through molecular recognition. Here, we show that DNA T-motifs, which self-assemble into ring structures, can be designed to self-replicate through toehold-mediated strand displacement reactions. The inherent design of these rings allows the population dynamics of the systems to be controlled. We also analyse the replication scheme within a universal framework of self-replication and derive a quantitative metric of the self-replicability of the rings.

  2. DNA Replication via Entanglement Swapping

    CERN Document Server

    Pusuluk, Onur

    2010-01-01

    Quantum effects are mainly used for the determination of molecular shapes in molecular biology, but quantum information theory may be a more useful tool to understand the physics of life. Molecular biology assumes that function is explained by structure, the complementary geometries of molecules and weak intermolecular hydrogen bonds. However, both this assumption and its converse are possible if organic molecules and quantum circuits/protocols are considered as hardware and software of living systems that are co-optimized during evolution. In this paper, we try to model DNA replication as a multiparticle entanglement swapping with a reliable qubit representation of nucleotides. In the model, molecular recognition of a nucleotide triggers an intrabase entanglement corresponding to a superposition state of different tautomer forms. Then, base pairing occurs by swapping intrabase entanglements with interbase entanglements.

  3. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. Copyright © 2015 The Authors

  4. Cytogenetic studies in human populations exposed to gas leak at Bhopal, India

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, B.B.; Sengupta, S.; Roy, A.; Maity, S.; Ghosh, S.; Talukder, G.; Sharma, A. (Univ. of Calcutta (India))

    1990-06-01

    Frequencies of chromosomal abnormalities, sister chromatid exchanges, and replicative index were assessed following peripheral lymphocyte culture in 129 individuals from Bhopal, India. Of these, 83 persons (40 male and 43 female) had been exposed directly to the methyl isocyanate (MIC) gas after the accident at the Union Carbide plant on December 2 and 3, 1984. The remaining 46 samples were taken from age-matched unexposed persons in the same city. Chromosome aberrations were recorded at first cycle metaphase (M{sub 1}) and sister chromatid exchanges, at second cycle metaphase (M{sub 2}), following standard schedule. The frequency of chromosomal aberrations was, in general, higher in individuals from the exposed populations, with the females showing a higher incidence. Nondisjunction of chromosomes or laggard was rare. The frequencies of sister chromatid exchanges and depression in mitotic and replicative indices could not be related to exposure or sex. The persistence of chromosomal abnormalities in the form of replicating minutes and exchange configurations, even 1,114 days after exposure to the gas, may indicate a residual effect on T-cell precursors.

  5. Wanita Penjaja Agama Kepemimpinan Sister Aimee Semple McPherson dalam Novel: Elmer Gentry, Oil!, dan The Loved One

    Directory of Open Access Journals (Sweden)

    Nursaktiningrum Nursaktiningrum

    2010-06-01

    Full Text Available This article studies how three famous American writers portray Sister McPherson (1890-1944, a controversial female religious leader, in their novels. Placing the novels written by Lewis, Sinclair, and Waugh in the context of American society, this study aims to reveal how Sister McPherson crossed gender boundaries and reinvented tradition in American religious institutions. By combining religious teachings and the advancement of popular culture, she broke the old religious tradition and succeeded in popularizing the religion she embraced.

  6. Pseudoxanthoma elasticum: clinical, histologic, and genetic studies--a report of two sisters.

    Science.gov (United States)

    Kaimbo, Dieudonne Kaimbo Wa; Mutosh, Anne; Leys, Anita; Parys-van Ginderdeuren, Rita; Bergen, A A B

    2011-01-01

    CASE 1: A 24-year-old black woman was referred to our clinic in September 1999 by the department of dermatology. She was referred to confirm the diagnosis of pseudoxanthoma elasticum (PXE). Her medical history was normal. Dermatologic examination revealed confluent papules that gave the skin a "plucked chicken" appearance on the flexural surfaces in the neck, axillae, clavicle, thigh, and periumbilical area (Figure 1). The patient stated that the changes in her skin had begun in the periumbilical region at about 5 years of age and had since been slowly progressive. Physical examination showed brownish black pigmentation on the left side of the face, left eyelid, and left sclera, which was diagnosed as Nevus of Ota (Figure 2). Her visual acuity was 20/10 in both eyes, with no afferent pupillary defect. Intraocular pressure in both eyes was normal. Slit lamp examination showed no abnormalities. Findings from fundus examination revealed angioid streaks that formed an incomplete ring around the optic disc and anteriorly radiated toward the equator of the globe, multiple calcified drusen-like structures, and "peau d'orange" changes. Skin biopsy (skin tissue from the neck) was taken and the diagnosis of PXE was confirmed. Histopathologic findings revealed calcification of the elastic fibers and abnormalities of the collagen (Figure 3). The patient was not known to have sickle cell anemia or sickle cell trait, and her blood pressure levels had never elevated. Other systemic causes of angioid streaks were excluded by findings from extensive laboratory examination. Her relatives were asked to come in for examination but lived far away. One of the patient's sisters lived in Kinshasa, Africa, however, and is presented in case 2. CASE 2: The 27-year-old sister of the previous patient was examined on April 19, 2000. At examination, she was found to have PXE. Her medical history was significant for systemic hypertension since 1998 and genital hemorrhage. She underwent an

  7. Regulation of Unperturbed DNA Replication by Ubiquitylation

    Directory of Open Access Journals (Sweden)

    Sara Priego Moreno

    2015-06-01

    Full Text Available Posttranslational modification of proteins by means of attachment of a small globular protein ubiquitin (i.e., ubiquitylation represents one of the most abundant and versatile mechanisms of protein regulation employed by eukaryotic cells. Ubiquitylation influences almost every cellular process and its key role in coordination of the DNA damage response is well established. In this review we focus, however, on the ways ubiquitylation controls the process of unperturbed DNA replication. We summarise the accumulated knowledge showing the leading role of ubiquitin driven protein degradation in setting up conditions favourable for replication origin licensing and S-phase entry. Importantly, we also present the emerging major role of ubiquitylation in coordination of the active DNA replication process: preventing re-replication, regulating the progression of DNA replication forks, chromatin re-establishment and disassembly of the replisome at the termination of replication forks.

  8. Chromosome replication and segregation in bacteria.

    Science.gov (United States)

    Reyes-Lamothe, Rodrigo; Nicolas, Emilien; Sherratt, David J

    2012-01-01

    In dividing cells, chromosome duplication once per generation must be coordinated with faithful segregation of newly replicated chromosomes and with cell growth and division. Many of the mechanistic details of bacterial replication elongation are well established. However, an understanding of the complexities of how replication initiation is controlled and coordinated with other cellular processes is emerging only slowly. In contrast to eukaryotes, in which replication and segregation are separate in time, the segregation of most newly replicated bacterial genetic loci occurs sequentially soon after replication. We compare the strategies used by chromosomes and plasmids to ensure their accurate duplication and segregation and discuss how these processes are coordinated spatially and temporally with growth and cell division. We also describe what is known about the three conserved families of ATP-binding proteins that contribute to chromosome segregation and discuss their inter-relationships in a range of disparate bacteria.

  9. Semiconservative replication in the quasispecies model

    Science.gov (United States)

    Tannenbaum, Emmanuel; Deeds, Eric J.; Shakhnovich, Eugene I.

    2004-06-01

    This paper extends Eigen’s quasispecies equations to account for the semiconservative nature of DNA replication. We solve the equations in the limit of infinite sequence length for the simplest case of a static, sharply peaked fitness landscape. We show that the error catastrophe occurs when μ , the product of sequence length and per base pair mismatch probability, exceeds 2 ln [2/ ( 1+1/k ) ] , where k>1 is the first-order growth rate constant of the viable “master” sequence (with all other sequences having a first-order growth rate constant of 1 ). This is in contrast to the result of ln k for conservative replication. In particular, as k→∞ , the error catastrophe is never reached for conservative replication, while for semiconservative replication the critical μ approaches 2 ln 2 . Semiconservative replication is therefore considerably less robust than conservative replication to the effect of replication errors. We also show that the mean equilibrium fitness of a semiconservatively replicating system is given by k ( 2 e-μ/2 -1 ) below the error catastrophe, in contrast to the standard result of k e-μ for conservative replication (derived by Kimura and Maruyama in 1966). From this result it is readily shown that semiconservative replication is necessary to account for the observation that, at sufficiently high mutagen concentrations, faster replicating cells will die more quickly than more slowly replicating cells. Thus, in contrast to Eigen’s original model, the semiconservative quasispecies equations are able to provide a mathematical basis for explaining the efficacy of mutagens as chemotherapeutic agents.

  10. Incestuous sisters: mate preference for brothers over unrelated males in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Adeline Loyau

    Full Text Available The literature is full of examples of inbreeding avoidance, while recent mathematical models predict that inbreeding tolerance or even inbreeding preference should be expected under several realistic conditions like e.g. polygyny. We investigated male and female mate preferences with respect to relatedness in the fruit fly D. melanogaster. Experiments offered the choice between a first order relative (full-sibling or parent and an unrelated individual with the same age and mating history. We found that females significantly preferred mating with their brothers, thus supporting inbreeding preference. Moreover, females did not avoid mating with their fathers, and males did not avoid mating with their sisters, thus supporting inbreeding tolerance. Our experiments therefore add empirical evidence for inbreeding preference, which strengthens the prediction that inbreeding tolerance and preference can evolve under specific circumstances through the positive effects on inclusive fitness.

  11. Sibling recognition and the development of identity: intersubjective consequences of sibling differentiation in the sister relationship.

    Science.gov (United States)

    Vivona, Jeanine M

    2013-01-01

    Identity is, among other things, a means to adapt to the others around whom one must fit. Psychoanalytic theory has highlighted ways in which the child fits in by emulating important others, especially through identification. Alternately, the child may fit into the family and around important others through differentiation, an unconscious process that involves developing or accentuating qualities and desires in oneself that are expressly different from the perceived qualities of another person and simultaneously suppressing qualities and desires that are perceived as similar. With two clinical vignettes centered on the sister relationship, the author demonstrates that recognition of identity differences that result from sibling differentiation carries special significance in the sibling relationship and simultaneously poses particular intersubjective challenges. To the extent that the spotlight of sibling recognition delimits the lateral space one may occupy, repeatedly frustrated desires for sibling recognition may have enduring consequences for one's sense of self-worth and expectations of relationships with peers and partners.

  12. Early Development of Squamous Cell Carsinoma in Two Sister Cases with pidermodysplasia Verruciformis

    Directory of Open Access Journals (Sweden)

    Ömer Çalka

    2010-06-01

    Full Text Available Epidermodysplasia verruciformis (Lewandowsky-Lutz syndrome is an uncommon disease characterized by multiple plane warts, pityriasis versicolor-like lesions, defects of cell-mediated immunity, and tendency to develop skin malignancies, primarily on sun-exposed areas. Most commonly it is inherited as an autosomal recessive trait. Squamous cell carcinoma is the most common type of skin cancer found in patient with epidermodysplasia verruciformis. Human papilloma virus 5, 8, and 47 are found in more than 90% of epidermodysplasia verruciformis skin cancers. Treatment for epidermodysplasia verruciformis consists largely of preventive measures. Photoprotection remains essential for management. In this report, two sister case of epidermodisplasia verruciformis with plane warts, pityriasis versicolor-like lesions, and squamous cell carcinomas on sun-exposed areas of skin was presented for it is a rarely encountered disease and associated with early development of malignancy.

  13. The Brotherhood of Freemason Sisters. Gender, Secrecy, and Fraternity in Italian Masonic Lodges

    OpenAIRE

    Bounissou, Cédric

    2017-01-01

    Lilith Mahmud, The Brotherhood of Freemason Sisters. Gender, Secrecy, and Fraternity in Italian Masonic Lodges, Chicago-London, University of Chicago Press, 2014, 250 p., bibl., index Depuis sa création au xviiie siècle, la franc-maçonnerie a joué un rôle important dans la formation de la démocratie moderne, en favorisant l’émergence de l’espace public tel que le définit Jürgen Habermas (p. 8). En décrivant la franc-maçonnerie comme « la société secrète occidentale par excellence, celle qui, ...

  14. Comparing methods of estimating strength parameters for fissured clays at Seven Sisters Generating Station

    Energy Technology Data Exchange (ETDEWEB)

    Dubois, D.P.; Yereniuk, V.A. [Manitoba Hydro, Winnipeg, MB (Canada)

    2003-07-01

    Some instabilities have been observed at several dyke locations at the Seven Sisters Generating Station, Manitoba since construction in the late 1940s. The foundations of the dykes are fissured plastic clays. Slope stabilizing methods have been proposed by a number of researchers since the late 1970s for estimating strength parameters for fissured plastic clays. This paper reports on four methods which were used for estimating Mohr-Coulomb strength parameters for stability analyses involving nine dyke locations where instability has been reported in the past. Correlation is established between the calculated safety factors and observed performance in an effort to determine the most appropriate method for this site. It was determined that the most appropriate method was that proposed by P.J. Rivard and Y.Lu in the late 1970s. 16 refs., 1 tab., 7 figs.

  15. Two sisters with macular dystrophy caused by the 3243A>G mitochondrial DNA mutation.

    Science.gov (United States)

    Sánchez-Gutiérrez, V; García-Montesinos, J; Pardo-Muñoz, A

    2016-05-01

    Two sisters of 54 and 60years old, with a history of diabetes and deafness, consulted for decreased visual acuity (VA). Funduscopic examination revealed patchy areas of chorioretinal atrophy with annular arrangement around the fovea. Genetic study identified the heteroplasmic mutation 3243A>G in mitochondrial DNA, which supports syndrome maternally inherited diabetes and deafness (MIDD) or Ballinger-Wallace disease. The finding of such macular disorders, especially in the presence of diabetes mellitus and deafness, should suggest the performing of a mitochondrial genome screening to identify this unusual syndrome. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Regulation of chromosomal replication in Caulobacter crescentus.

    Science.gov (United States)

    Collier, Justine

    2012-03-01

    The alpha-proteobacterium Caulobacter crescentus is characterized by its asymmetric cell division, which gives rise to a replicating stalked cell and a non-replicating swarmer cell. Thus, the initiation of chromosomal replication is tightly regulated, temporally and spatially, to ensure that it is coordinated with cell differentiation and cell cycle progression. Waves of DnaA and CtrA activities control when and where the initiation of DNA replication will take place in C. crescentus cells. The conserved DnaA protein initiates chromosomal replication by directly binding to sites within the chromosomal origin (Cori), ensuring that DNA replication starts once and only once per cell cycle. The CtrA response regulator represses the initiation of DNA replication in swarmer cells and in the swarmer compartment of pre-divisional cells, probably by competing with DnaA for binding to Cori. CtrA and DnaA are controlled by multiple redundant regulatory pathways that include DNA methylation-dependent transcriptional regulation, temporally regulated proteolysis and the targeting of regulators to specific locations within the cell. Besides being critical regulators of chromosomal replication, CtrA and DnaA are also master transcriptional regulators that control the expression of many genes, thus connecting DNA replication with other events of the C. crescentus cell cycle. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Comparison of three replication strategies in complex multicellular organisms: Asexual replication, sexual replication with identical gametes, and sexual replication with distinct sperm and egg gametes

    Science.gov (United States)

    Tannenbaum, Emmanuel

    2008-01-01

    This paper studies the mutation-selection balance in three simplified replication models. The first model considers a population of organisms replicating via the production of asexual spores. The second model considers a sexually replicating population that produces identical gametes. The third model considers a sexually replicating population that produces distinct sperm and egg gametes. All models assume diploid organisms whose genomes consist of two chromosomes, each of which is taken to be functional if equal to some master sequence, and defective otherwise. In the asexual population, the asexual diploid spores develop directly into adult organisms. In the sexual populations, the haploid gametes enter a haploid pool, where they may fuse with other haploids. The resulting immature diploid organisms then proceed to develop into mature organisms. Based on an analysis of all three models, we find that, as organism size increases, a sexually replicating population can only outcompete an asexually replicating population if the adult organisms produce distinct sperm and egg gametes. A sexual replication strategy that is based on the production of large numbers of sperm cells to fertilize a small number of eggs is found to be necessary in order to maintain a sufficiently low cost for sex for the strategy to be selected for over a purely asexual strategy. We discuss the usefulness of this model in understanding the evolution and maintenance of sexual replication as the preferred replication strategy in complex, multicellular organisms.

  18. Ice Volumes on Cascade Volcanoes: Mount Rainier, Mount Hood, Three Sisters, and Mount Shasta

    Science.gov (United States)

    Driedger, Carolyn L.; Kennard, Paul M.

    1986-01-01

    During the eruptions of Mount St. Helens the occurrence of floods and mudflows made apparent the need for predictive water-hazard analysis of other Cascade volcanoes. A basic requirement for such analysis is information about the volumes and distributions of snow and ice on other volcanoes. A radar unit contained in a backpack was used to make point measurements of ice thickness on major glaciers of Mount Rainier, Wash.; Mount Hood, Oreg.; the Three Sisters, Oreg.; and Mount Shasta, Calif. The measurements were corrected for slope and were used to develop subglacial contour maps from which glacier volumes were measured. These values were used to develop estimation methods for finding volumes of unmeasured glaciers. These methods require a knowledge of glacier slope, altitude, and area and require an estimation of basal shear stress, each estimate derived by using topographic maps updated by aerial photographs. The estimation methods were found to be accurate within ?20 percent on measured glaciers and to be within ?25 percent when applied to unmeasured glaciers on the Cascade volcanoes. The estimation methods may be applicable to other temperate glaciers in similar climatic settings. Areas and volumes of snow and ice are as follows: Mount Rainier, 991 million ft2, 156 billion ft3; Mount Hood, 145 million ft2, 12 billion ft3; Three Sisters, 89 million ft2, 6 billion ft3; and Mount Shasta, 74 million ft2, 5 billion ft3. The distribution of ice and firn patches within 58 glacierized basins on volcanoes is mapped and listed by altitude and by watershed to facilitate water-hazard analysis.

  19. EPRI/DOE High Burnup Fuel Sister Pin Test Plan Simplification and Visualization

    Energy Technology Data Exchange (ETDEWEB)

    Saltzstein, Sylvia J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sorenson, Ken B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hanson, Brady [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Billone, Mike [Argonne National Lab. (ANL), Argonne, IL (United States); Scaglione, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Montgomery, Rose [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bevard, Bruce [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-07-01

    The EPRI/DOE High Burnup Confirmatory Data Project (herein called the "Demo") is a multi-year, multi-entity confirmation demonstration test with the purpose of providing quantitative and qualitative data to show how high-burnup fuel ages in dry storage over a ten-year period. The Demo involves obtaining 32 assemblies of high-burnup PWR fuel of four common cladding alloys from the North Anna Nuclear Power Plant, drying them according to standard plant procedures, and then storing them in an NRC-licensed TN-3 2B cask on the North Anna dry storage pad for ten years. After the ten-year storage time, the cask will be opened and the rods will be examined for signs of aging. Twenty-five rods from assemblies of similar claddings, in-reactor placement, and burnup histories (herein called "sister rods") have been shipped from the North Anna Nuclear Power Plant and are currently being nondestructively tested at Oak Ridge National Laboratory. After the non-destructive testing has been completed for each of the twenty-five rods, destructive analysis will be performed at ORNL, PNNL, and ANL to obtain mechanical data. Opinions gathered from the expert interviews, ORNL and PNNL Sister Rod Test Plans, and numerous meetings has resulted in the Simplified Test Plan described in this document. Some of the opinions and discussions leading to the simplified test plan are included here. Detailed descriptions and background are in the ORNL and PNNL plans in the appendices . After the testing described in this simplified test plan h as been completed , the community will review all the collected data and determine if additional testing is needed.

  20. Phylogenomic analyses support the position of turtles as the sister group of birds and crocodiles (Archosauria

    Directory of Open Access Journals (Sweden)

    Chiari Ylenia

    2012-07-01

    Full Text Available Abstract Background The morphological peculiarities of turtles have, for a long time, impeded their accurate placement in the phylogeny of amniotes. Molecular data used to address this major evolutionary question have so far been limited to a handful of markers and/or taxa. These studies have supported conflicting topologies, positioning turtles as either the sister group to all other reptiles, to lepidosaurs (tuatara, lizards and snakes, to archosaurs (birds and crocodiles, or to crocodilians. Genome-scale data have been shown to be useful in resolving other debated phylogenies, but no such adequate dataset is yet available for amniotes. Results In this study, we used next-generation sequencing to obtain seven new transcriptomes from the blood, liver, or jaws of four turtles, a caiman, a lizard, and a lungfish. We used a phylogenomic dataset based on 248 nuclear genes (187,026 nucleotide sites for 16 vertebrate taxa to resolve the origins of turtles. Maximum likelihood and Bayesian concatenation analyses and species tree approaches performed under the most realistic models of the nucleotide and amino acid substitution processes unambiguously support turtles as a sister group to birds and crocodiles. The use of more simplistic models of nucleotide substitution for both concatenation and species tree reconstruction methods leads to the artefactual grouping of turtles and crocodiles, most likely because of substitution saturation at third codon positions. Relaxed molecular clock methods estimate the divergence between turtles and archosaurs around 255 million years ago. The most recent common ancestor of living turtles, corresponding to the split between Pleurodira and Cryptodira, is estimated to have occurred around 157 million years ago, in the Upper Jurassic period. This is a more recent estimate than previously reported, and questions the interpretation of controversial Lower Jurassic fossils as being part of the extant turtles radiation

  1. Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

    Science.gov (United States)

    Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

    1994-07-01

    We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

  2. Yeast Interacting Proteins Database: YDR267C, YHR122W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available ister chromatid cohesion; synthetically lethal with RFC5, an RF-C subunit that links...uired for establishment of sister chromatid cohesion; synthetically lethal with RFC5, an RF-C subunit that links

  3. Using ecological niche models and niche analyses to understand speciation patterns: the case of sister neotropical orchid bees.

    Directory of Open Access Journals (Sweden)

    Daniel P Silva

    Full Text Available The role of past connections between the two major South American forested biomes on current species distribution has been recognized a long time ago. Climatic oscillations that further separated these biomes have promoted parapatric speciation, in which many species had their continuous distribution split, giving rise to different but related species (i.e., different potential distributions and realized niche features. The distribution of many sister species of orchid bees follow this pattern. Here, using ecological niche models and niche analyses, we (1 tested the role of ecological niche differentiation on the divergence between sister orchid-bees (genera Eulaema and Eufriesea from the Amazon and Atlantic forests, and (2 highlighted interesting areas for new surveys. Amazonian species occupied different realized niches than their Atlantic sister species. Conversely, species of sympatric but distantly related Eulaema bees occupied similar realized niches. Amazonian species had a wide potential distribution in South America, whereas Atlantic Forest species were more limited to the eastern coast of the continent. Additionally, we identified several areas in need of future surveys. Our results show that the realized niche of Atlantic-Amazonian sister species of orchid bees, which have been previously treated as allopatric populations of three species, had limited niche overlap and similarity. These findings agree with their current taxonomy, which treats each of those populations as distinct valid species.

  4. Using ecological niche models and niche analyses to understand speciation patterns: the case of sister neotropical orchid bees.

    Science.gov (United States)

    Silva, Daniel P; Vilela, Bruno; De Marco, Paulo; Nemésio, André

    2014-01-01

    The role of past connections between the two major South American forested biomes on current species distribution has been recognized a long time ago. Climatic oscillations that further separated these biomes have promoted parapatric speciation, in which many species had their continuous distribution split, giving rise to different but related species (i.e., different potential distributions and realized niche features). The distribution of many sister species of orchid bees follow this pattern. Here, using ecological niche models and niche analyses, we (1) tested the role of ecological niche differentiation on the divergence between sister orchid-bees (genera Eulaema and Eufriesea) from the Amazon and Atlantic forests, and (2) highlighted interesting areas for new surveys. Amazonian species occupied different realized niches than their Atlantic sister species. Conversely, species of sympatric but distantly related Eulaema bees occupied similar realized niches. Amazonian species had a wide potential distribution in South America, whereas Atlantic Forest species were more limited to the eastern coast of the continent. Additionally, we identified several areas in need of future surveys. Our results show that the realized niche of Atlantic-Amazonian sister species of orchid bees, which have been previously treated as allopatric populations of three species, had limited niche overlap and similarity. These findings agree with their current taxonomy, which treats each of those populations as distinct valid species.

  5. Historical biogeography and diversification of truffles in the Tuberaceae and their newly identified Southern hemisphere sister lineage

    Science.gov (United States)

    Gregory Bonito; Matthew E. Smith; Michael Nowak; Rosanne A. Healy; Gonzalo Guevara; Efren Cazares; Akihiko Kinoshita; Eduardo R. Nouhra; Laura S. Dominguez; Leho Tedersoo; Claude Murat; Yun Wang; Baldomero Arroyo Moreno; Donald H. Pfister; Kazuhide Nara; Alessandra Zambonelli; James M. Trappe; Rytas. Vilgalys

    2013-01-01

    In this study we reassessed the biogeography and origin of the Tuberaceae and their relatives using multiple loci and a global sampling of taxa. Multiple independent transitions from an aboveground to a belowground truffie fruiting body form have occurred in the Tuberaceae and in its newly recognized sister lineage...

  6. Lost Women in Social Transitional Period-A Comparative Study of the Tragic Fate of Sister Carrie and Guo Haizao

    Institute of Scientific and Technical Information of China (English)

    陈晶晶

    2014-01-01

    Sister Carrie and Dwelling depict two heroines who share similarities in many aspects. They all live in the social transi-tional period and suffer a lot. This paper will make a comparison about the two ladies’tragic fates and aims to investigate the im-pact on females brought about by the social transition.

  7. Phylogenetic analysis of seven WRKY genes across the palm subtribe Attaleinae (Areceaceae) identifies Syagrus as sister to the coconut

    Science.gov (United States)

    The origins of the coconut (Cocos nucifera) have been one of the "abominable mysteries" of palm systematics for decades. Previous studies with predominantly plastid genes have indicated an American ancestry for the coconut but with weak support and ambiguous sister relationships. We used primers d...

  8. Comparative phylogeography of sympatric sister species, Clevelandia ios and Eucyclogobius newberryi (Teleostei, Gobiidae), across the California Transition Zone.

    Science.gov (United States)

    Dawson, M N; Louie, K D; Barlow, M; Jacobs, D K; Swift, C C

    2002-06-01

    It is paradigmatic in marine species that greater dispersal ability often, but not always, results in greater gene flow and less population structure. Some of the exceptions may be attributable to studies confounded by comparison of species with dissimilar evolutionary histories, i.e. co-occurring species that are not closely related or species that are closely related but allopatric. Investigation of sympatric sister species, in contrast, should allow differences in phylogeographic structure to be attributed reliably to recently derived differences in dispersal ability. Here, using mitochondrial DNA control region sequence, we first confirm that Clevelandia ios and Eucyclogobius newberryi are sympatric sister taxa, then demonstrate considerably shallower phylogeographic structure in C. ios than in E. newberryi. This shallower phylogeographic structure is consistent with the higher dispersal ability of C. ios, which most likely results from the interaction of habitat and life-history differences between the species. We suggest that the paradigm will be investigated most rigorously by similar studies of other sympatric sister species, appended by thorough ecological studies, and by extending this sister-taxon approach to comparative phylogeographic studies of monophyletic clades of sympatric species.

  9. An Evaluation of Parental Assessment of the Big Brothers/Big Sisters Program in New York City.

    Science.gov (United States)

    Frecknall, Peter; Luks, Alan

    1992-01-01

    Parents rated impact of Big Brother/Big Sister program on children along variables of school attendance, grades, family relationship, friendship, self-esteem, staying out of trouble, being responsible, frequency of contact, and length of time in program. Although children were rated as benefiting significantly from program, children's frequency of…

  10. A Case of Maternal Half-sisters Sharing Alleles at 18 X-chromosomal Short Tandem Repeat Loci

    Directory of Open Access Journals (Sweden)

    Qiu-Ling Liu

    2016-01-01

    Full Text Available Analysis of X-chromosome short tandem repeats (STRs is very helpful in deficiency paternity testing. Here, we reported a case of kinship analysis that showed a potentially erroneous inclusion of paternal sisters between two women. The two women shared alleles at 18 X-chromosomal STR loci spanned from 14.76cM (DXS6807 to 184.19cM (DXS7423. When their relatives were not available for testing, biostatistical analysis for the 18 X-chromosomal STR loci and 24 autosomal STR loci revealed the most possible relationship between the two women was paternal sisters. However, when the father of one woman was available, the other father-daughter possibility was excluded. In the end, the likelihood ratio of STR marker and mitochondrial DNA (mtDNA sequences confirmed the two women were maternal sisters. This case emphasizes a cautionary interpretation of X chromosomal marker in deficiency paternity cases with female offspring. Even though large parts of the X-chromosome haplotypes shared by two females, additional relatives and extended DNA typing (such as mtDNA may be needed further to ascertain whether they are paternal or maternal sisters.

  11. ‘‘‘Sister to the tailor’: Guilds, gender and the needle trades in eighteenth-century Europe’

    DEFF Research Database (Denmark)

    Simonton, Deborah

    2017-01-01

    Milliners, and their sisters, mantuamakers, modistes and marchandes de mode, were skilled artisans, businesswomen and tradeswomen. During the eighteenth century, they commandeered the high-class sewing that set fashion and created stars of their most famous, like Rose Bertrand, milliner to Marie...

  12. Surface micro topography replication in injection moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf

    of the mechanisms controlling topography replication. Surface micro topography replication in injection moulding depends on the main elements of  Process conditions  Plastic material  Mould topography In this work, the process conditions is the main factor considered, but the impact of plastic material...

  13. Replication and Robustness in Developmental Research

    Science.gov (United States)

    Duncan, Greg J.; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J.

    2014-01-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…

  14. Completion of DNA replication in Escherichia coli.

    Science.gov (United States)

    Wendel, Brian M; Courcelle, Charmain T; Courcelle, Justin

    2014-11-18

    The mechanism by which cells recognize and complete replicated regions at their precise doubling point must be remarkably efficient, occurring thousands of times per cell division along the chromosomes of humans. However, this process remains poorly understood. Here we show that, in Escherichia coli, the completion of replication involves an enzymatic system that effectively counts pairs and limits cellular replication to its doubling point by allowing converging replication forks to transiently continue through the doubling point before the excess, over-replicated regions are incised, resected, and joined. Completion requires RecBCD and involves several proteins associated with repairing double-strand breaks including, ExoI, SbcDC, and RecG. However, unlike double-strand break repair, completion occurs independently of homologous recombination and RecA. In some bacterial viruses, the completion mechanism is specifically targeted for inactivation to allow over-replication to occur during lytic replication. The results suggest that a primary cause of genomic instabilities in many double-strand-break-repair mutants arises from an impaired ability to complete replication, independent from DNA damage.

  15. Replication and Robustness in Developmental Research

    Science.gov (United States)

    Duncan, Greg J.; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J.

    2014-01-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…

  16. Using Replication Projects in Teaching Research Methods

    Science.gov (United States)

    Standing, Lionel G.; Grenier, Manuel; Lane, Erica A.; Roberts, Meigan S.; Sykes, Sarah J.

    2014-01-01

    It is suggested that replication projects may be valuable in teaching research methods, and also address the current need in psychology for more independent verification of published studies. Their use in an undergraduate methods course is described, involving student teams who performed direct replications of four well-known experiments, yielding…

  17. How frog embryos replicate their DNA reliably

    Science.gov (United States)

    Bechhoefer, John; Marshall, Brandon

    2007-03-01

    Frog embryos contain three billion base pairs of DNA. In early embryos (cycles 2-12), DNA replication is extremely rapid, about 20 min., and the entire cell cycle lasts only 25 min., meaning that mitosis (cell division) takes place in about 5 min. In this stripped-down cell cycle, there are no efficient checkpoints to prevent the cell from dividing before its DNA has finished replication - a disastrous scenario. Even worse, the many origins of replication are laid down stochastically and are also initiated stochastically throughout the replication process. Despite the very tight time constraints and despite the randomness introduced by origin stochasticity, replication is extremely reliable, with cell division failing no more than once in 10,000 tries. We discuss a recent model of DNA replication that is drawn from condensed-matter theories of 1d nucleation and growth. Using our model, we discuss different strategies of replication: should one initiate all origins as early as possible, or is it better to hold back and initiate some later on? Using concepts from extreme-value statistics, we derive the distribution of replication times given a particular scenario for the initiation of origins. We show that the experimentally observed initiation strategy for frog embryos meets the reliability constraint and is close to the one that requires the fewest resources of a cell.

  18. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks

    DEFF Research Database (Denmark)

    Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia

    2016-01-01

    Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depl...

  19. Rescue from replication stress during mitosis.

    Science.gov (United States)

    Fragkos, Michalis; Naim, Valeria

    2017-04-03

    Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

  20. A New Replication Norm for Psychology

    Directory of Open Access Journals (Sweden)

    Etienne P LeBel

    2015-10-01

    Full Text Available In recent years, there has been a growing concern regarding the replicability of findings in psychology, including a mounting number of prominent findings that have failed to replicate via high-powered independent replication attempts. In the face of this replicability “crisis of confidence”, several initiatives have been implemented to increase the reliability of empirical findings. In the current article, I propose a new replication norm that aims to further boost the dependability of findings in psychology. Paralleling the extant social norm that researchers should peer review about three times as many articles that they themselves publish per year, the new replication norm states that researchers should aim to independently replicate important findings in their own research areas in proportion to the number of original studies they themselves publish per year (e.g., a 4:1 original-to-replication studies ratio. I argue this simple approach could significantly advance our science by increasing the reliability and cumulative nature of our empirical knowledge base, accelerating our theoretical understanding of psychological phenomena, instilling a focus on quality rather than quantity, and by facilitating our transformation toward a research culture where executing and reporting independent direct replications is viewed as an ordinary part of the research process. To help promote the new norm, I delineate (1 how each of the major constituencies of the research process (i.e., funders, journals, professional societies, departments, and individual researchers can incentivize replications and promote the new norm and (2 any obstacles each constituency faces in supporting the new norm.