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  1. Ionizing radiation-induced foci formation of mammalian Rad51 and Rad54 depends on the Rad51 paralogs, but not on Rad52

    International Nuclear Information System (INIS)

    Veelen, Lieneke R. van; Essers, Jeroen; Rakt, Mandy W.M.M. van de; Odijk, Hanny; Pastink, Albert; Zdzienicka, MaIgorzata Z.; Paulusma, Coen C.; Kanaar, Roland

    2005-01-01

    Homologous recombination is of major importance for the prevention of genomic instability during chromosome duplication and repair of DNA damage, especially double-strand breaks. Biochemical experiments have revealed that during the process of homologous recombination the RAD52 group proteins, including Rad51, Rad52 and Rad54, are involved in an essential step: formation of a joint molecule between the broken DNA and the intact repair template. Accessory proteins for this reaction include the Rad51 paralogs and BRCA2. The significance of homologous recombination for the cell is underscored by the evolutionary conservation of the Rad51, Rad52 and Rad54 proteins from yeast to humans. Upon treatment of cells with ionizing radiation, the RAD52 group proteins accumulate at the sites of DNA damage into so-called foci. For the yeast Saccharomyces cerevisiae, foci formation of Rad51 and Rad54 is abrogated in the absence of Rad52, while Rad51 foci formation does occur in the absence of the Rad51 paralog Rad55. By contrast, we show here that in mammalian cells, Rad52 is not required for foci formation of Rad51 and Rad54. Furthermore, radiation-induced foci formation of Rad51 and Rad54 is impaired in all Rad51 paralog and BRCA2 mutant cell lines tested, while Rad52 foci formation is not influenced by a mutation in any of these recombination proteins. Despite their evolutionary conservation and biochemical similarities, S. cerevisiae and mammalian Rad52 appear to differentially contribute to the DNA-damage response

  2. Rad51-Rad52 mediated maintenance of centromeric chromatin in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Sreyoshi Mitra

    2014-04-01

    Full Text Available Specification of the centromere location in most eukaryotes is not solely dependent on the DNA sequence. However, the non-genetic determinants of centromere identity are not clearly defined. While multiple mechanisms, individually or in concert, may specify centromeres epigenetically, most studies in this area are focused on a universal factor, a centromere-specific histone H3 variant CENP-A, often considered as the epigenetic determinant of centromere identity. In spite of variable timing of its loading at centromeres across species, a replication coupled early S phase deposition of CENP-A is found in most yeast centromeres. Centromeres are the earliest replicating chromosomal regions in a pathogenic budding yeast Candida albicans. Using a 2-dimensional agarose gel electrophoresis assay, we identify replication origins (ORI7-LI and ORI7-RI proximal to an early replicating centromere (CEN7 in C. albicans. We show that the replication forks stall at CEN7 in a kinetochore dependent manner and fork stalling is reduced in the absence of the homologous recombination (HR proteins Rad51 and Rad52. Deletion of ORI7-RI causes a significant reduction in the stalled fork signal and an increased loss rate of the altered chromosome 7. The HR proteins, Rad51 and Rad52, have been shown to play a role in fork restart. Confocal microscopy shows declustered kinetochores in rad51 and rad52 mutants, which are evidence of kinetochore disintegrity. CENP-ACaCse4 levels at centromeres, as determined by chromatin immunoprecipitation (ChIP experiments, are reduced in absence of Rad51/Rad52 resulting in disruption of the kinetochore structure. Moreover, western blot analysis reveals that delocalized CENP-A molecules in HR mutants degrade in a similar fashion as in other kinetochore mutants described before. Finally, co-immunoprecipitation assays indicate that Rad51 and Rad52 physically interact with CENP-ACaCse4 in vivo. Thus, the HR proteins Rad51 and Rad52

  3. Regulation of Rad51-Mediated Homologous Recombination by BRCA2, DSS1 and RAD52

    DEFF Research Database (Denmark)

    Rants, Louise Olthaver Juhl

    Homologous recombination (HR) provides a mechanism to restore integrity and maintain stability of the genetic material. HR is a major pathway for repair of DNA double-strand breaks (DSB), recovery of broken replication forks and generation of meiotic crossovers. The defining step in HR is homolog......Homologous recombination (HR) provides a mechanism to restore integrity and maintain stability of the genetic material. HR is a major pathway for repair of DNA double-strand breaks (DSB), recovery of broken replication forks and generation of meiotic crossovers. The defining step in HR...... is homologous strand exchange directed by the RecA-related recombinase Rad51. BRCA2 participates in HR by mediating Rad51 homology-directed repair. Both BRCA2 and Rad51 are essential for HR, DNA repair, and the maintenance of genome stability. In the present study, we seek to understand the mechanism of BRCA2...... with RAD52-mediated repair at sites of CPT-induced DNA damage. The synthetic lethality approach using RAD52 small molecule inhibitors in brca-deficient cancers is a promising therapeutic strategy for cancer treatment....

  4. Roles of C-Terminal Region of Yeast and Human Rad52 in Rad51-Nucleoprotein Filament Formation and ssDNA Annealing.

    Directory of Open Access Journals (Sweden)

    Nilesh V Khade

    Full Text Available Yeast Rad52 (yRad52 has two important functions at homologous DNA recombination (HR; annealing complementary single-strand DNA (ssDNA molecules and recruiting Rad51 recombinase onto ssDNA (recombination mediator activity. Its human homolog (hRAD52 has a lesser role in HR, and apparently lacks mediator activity. Here we show that yRad52 can load human Rad51 (hRAD51 onto ssDNA complexed with yeast RPA in vitro. This is biochemically equivalent to mediator activity because it depends on the C-terminal Rad51-binding region of yRad52 and on functional Rad52-RPA interaction. It has been reported that the N-terminal two thirds of both yRad52 and hRAD52 is essential for binding to and annealing ssDNA. Although a second DNA binding region has been found in the C-terminal region of yRad52, its role in ssDNA annealing is not clear. In this paper, we also show that the C-terminal region of yRad52, but not of hRAD52, is involved in ssDNA annealing. This suggests that the second DNA binding site is required for the efficient ssDNA annealing by yRad52. We propose an updated model of Rad52-mediated ssDNA annealing.

  5. Function of Rad51 paralogs in eukaryotic homologous recombinational repair

    International Nuclear Information System (INIS)

    Liu, N.; Skowronek, K.

    2003-01-01

    Full text: Homologous recombinational repair (HRR) is an important mechanism for maintaining genetic integrity and cancer prevention by accurately repair of DNA double strand breaks induced by environmental insults or occurred in DNA replication. A critical step in HRR is the polymerization of Rad51 on single stranded DNA to form nuclear protein filaments, the later conduct DNA strand paring and exchange between homologous strands. A number of proteins, including replication protein A (RPA), Rad52 and Rad51 paralogs, are suggested to modulate or facilitate the process of Rad51 filament formation. Five Rad51 paralogs, namely XRCC2, XRCC3, Rad51B, Rad51C and Rad51D have been identified in eucaryotic cells. These proteins show distant protein sequence identity to Rad51, to yeast Rad51 paralogs (Rad55 and Rad57) and to each other. Hamster or chicken mutants of Rad51 paralogs exhibit hypersensitivity to a variety of DNA damaging agents, especially cross-linking agents, and are defective in assembly of Rad51 onto HRR site after DNA damage. Recent data from our and other labs showed that Rad51 paralogs constitute two distinct complexes in cell extracts, one contains XRCC2, Rad51B, Rad51C and Rad51D, and the other contains Rad51C and XRCC3. Rad51C is involved in both complexes. Our results also showed that XRCC3-Rad51C complex interacts with Rad51 in vivo. Furthermore, overexpression of Rad52 can partially suppress the hypersensitivity of XRCC2 mutant irs1 to ionizing radiation and corrected the defects in Rad51 focus formation. These results suggest that XRCC2 and other Rad51 paralogs play a mediator function to Rad51 in the early stage of HRR

  6. Molecular anatomy of the recombination mediator function of Saccharomyces cerevisiae Rad52

    DEFF Research Database (Denmark)

    Seong, C.; Sehorn, M.G.; Plate, Iben

    2008-01-01

    A helical filament of Rad51 on single-strand DNA (ssDNA), called the presynaptic filament, catalyzes DNA joint formation during homologous recombination. Rad52 facilitates presynaptic filament assembly, and this recombination mediator activity is thought to rely on the interactions of Rad52...... with Rad51, the ssDNA-binding protein RPA, and ssDNA. The N-terminal region of Rad52, which has DNA binding activity and an oligomeric structure, is thought to be crucial for mediator activity and recombination. Unexpectedly, we find that the C-terminal region of Rad52 also harbors a DNA binding function....... Importantly, the Rad52 C-terminal portion alone can promote Rad51 presynaptic filament assembly. The middle portion of Rad52 associates with DNA-bound RPA and contributes to the recombination mediator activity. Accordingly, expression of a protein species that harbors the middle and C-terminal regions of Rad...

  7. The Molecular Basis of Double-Strand DNA Break Repair: The Critical Structure of the RAD52/RPA Complex

    National Research Council Canada - National Science Library

    Jackson, Dobra

    2001-01-01

    .... RAD52 has specific interactions with RAD51, RPA and DNA (1,2,3). The binding of RAD52 to ends of double-strand breaks has been found to be a key initiation step to DNA repair by homologous recombination...

  8. Role of teh Rad52 Amino-terminal DNA Binding Activity in DNA Strand Capture in Homologous Recombination

    DEFF Research Database (Denmark)

    Shi, Idina; Hallwyl, Swee Chuang Lim; Seong, Changhyun

    2009-01-01

    Saccharomyces cerevisiae Rad52 protein promotes homologous recombination by nucleating the Rad51 recombinase onto replication protein A-coated single-stranded DNA strands and also by directly annealing such strands. We show that the purified rad52-R70A mutant protein, with a compromised amino-ter...

  9. Recovery of deficient homologous recombination in Brca2-depleted mouse cells by wild-type Rad51 expression.

    Science.gov (United States)

    Lee, Shauna A; Roques, Céline; Magwood, Alissa C; Masson, Jean-Yves; Baker, Mark D

    2009-02-01

    The BRCA2 tumor suppressor is important in maintaining genomic stability. BRCA2 is proposed to control the availability, cellular localization and DNA binding activity of the central homologous recombination protein, RAD51, with loss of BRCA2 resulting in defective homologous recombination. Nevertheless, the roles of BRCA2 in regulating RAD51 and how other proteins implicated in RAD51 regulation, such as RAD52 and RAD54 function relative to BRCA2 is not known. In this study, we tested whether defective homologous recombination in Brca2-depleted mouse hybridoma cells could be rectified by expression of mouse Rad51 or the Rad51-interacting mouse proteins, Rad52 and Rad54. In the Brca2-depleted cells, defective homologous recombination can be restored by over-expression of wild-type mouse Rad51, but not mouse Rad52 or Rad54. Correction of the homologous recombination defect requires Rad51 ATPase activity. A sizeable fraction ( approximately 50%) of over-expressed wild-type Rad51 is nuclear localized. The restoration of homologous recombination in the presence of a low (i.e., non-functional) level of Brca2 by wild-type Rad51 over-expression is unexpected. We suggest that Rad51 may access the nuclear compartment in a Brca2-independent manner and when Rad51 is over-expressed, the normal requirement for Brca2 control over Rad51 function in homologous recombination is dispensable. Our studies support loss of Rad51 function as a critical underlying factor in the homologous recombination defect in the Brca2-depleted cells.

  10. Enhancement of the RAD51 Recombinase Activity by the Tumor Suppressor PALB2

    Energy Technology Data Exchange (ETDEWEB)

    Dray, Eloise; Etchin, Julia; Wiese, Claudia; Saro, Dorina; Williams, Gareth J.; Hammel, Michal; Yu, Xiong; Galkin, Vitold E.; Liu, Dongqing; Tsai, Miaw-Sheue; Sy, Shirley M-H.; Egelman, Edward; Chen, Junjie; Sung, Patrick; Schild, D.

    2010-08-24

    Homologous recombination mediated by the RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-stranded breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2 in the enhancement of RAD51's ability to form the D-loop. We show that PALB2 binds DNA and physically interacts with RAD51. Importantly, while PALB2 alone stimulates D-loop formation, a cooperative effect is seen with RAD51AP1, an enhancer of RAD51. This stimulation stems from PALB2's ability to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results help unveil a multi-faceted role of PALB2 in chromosome damage repair. Since PALB2 mutations can cause breast and other tumors or lead to Fanconi anemia, our findings are important for understanding the mechanism of tumor suppression in humans.

  11. RAD51B in Familial Breast Cancer

    OpenAIRE

    Pelttari, L.M.; Khan, S.; et al.,

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737\\ud and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast\\ud cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer\\ud predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the\\ud coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for\\ud identifi...

  12. RAD51B in familial breast cancer

    OpenAIRE

    Pelttari, LM; Khan, S; Vuorela, M; Kiiski, JI; Vilske, S; Nevanlinna, V; Ranta, S; Schleutker, J; Winqvist, R; Kallioniemi, A; Dörk, T; Bogdanova, NV; Figueroa, J; Pharoah, PDP; Schmidt, MK

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possi...

  13. RAD51AP2, a novel vertebrate- and meiotic-specific protein, sharesa conserved RAD51-interacting C-terminal domain with RAD51AP1/PIR51

    Energy Technology Data Exchange (ETDEWEB)

    Kovalenko, Oleg V.; Wiese, Claudia; Schild, David

    2006-07-25

    Many interacting proteins regulate and/or assist the activities of RAD51, a recombinase which plays a critical role in both DNA repair and meiotic recombination. Yeast two-hybrid screening of a human testis cDNA library revealed a new protein, RAD51AP2 (RAD51 Associated Protein 2), that interacts strongly with RAD51. A full-length cDNA clone predicts a novel vertebrate specific protein of 1159 residues, and the RAD51AP2 transcript was observed only in meiotic tissue (i.e. adult testis and fetal ovary), suggesting a meiotic-specific function for RAD51AP2. In HEK293 cells the interaction of RAD51 with an ectopically-expressed recombinant large fragment of RAD51AP2 requires the C-terminal 57 residues of RAD51AP2. This RAD51-binding region shows 81% homology to the C-terminus of RAD51AP1/PIR51, an otherwise totally unrelated RAD51-binding partner that is ubiquitously expressed. Analyses using truncations and point mutations in both RAD51AP1 and RAD51AP2 demonstrate that these proteins use the same structural motif for RAD51 binding. RAD54 shares some homology with this RAD51-binding motif, but this homologous region plays only an accessory role to the adjacent main RAD51-interacting region, which has been narrowed here to 40 amino acids. A novel protein, RAD51AP2, has been discovered that interacts with RAD51 through a C-terminal motif also present in RAD51AP1.

  14. RAD51B in Familial Breast Cancer

    DEFF Research Database (Denmark)

    Pelttari, Liisa M; Khan, Sofia; Vuorela, Mikko

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition......, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD......51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients...

  15. RAD51B in Familial Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Liisa M Pelttari

    Full Text Available Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC that were genotyped on a custom chip (iCOGS. We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259 and population controls (n = 3586 from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR: 1.15, 95% confidence interval (CI: 1.11-1.19, P = 8.88 x 10-16 and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11, compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

  16. RAD51B in Familial Breast Cancer

    Science.gov (United States)

    Pelttari, Liisa M.; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I.; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Dörk, Thilo; Bogdanova, Natalia V.; Figueroa, Jonine; Pharoah, Paul D. P.; Schmidt, Marjanka K.; Dunning, Alison M.; García-Closas, Montserrat; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Rosenberg, Efraim H.; Fasching, Peter A.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Nordestgaard, Børge G.; Benitez, Javier; González-Neira, Anna; Neuhausen, Susan L.; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Brüning, Thomas; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Van Dyck, Laurien; Janssen, Hilde; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Peterlongo, Paolo; Hallberg, Emily; Olson, Janet E.; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Schumacher, Fredrick; Simard, Jacques; Dumont, Martine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Grip, Mervi; Andrulis, Irene L.; Glendon, Gord; Devilee, Peter; Seynaeve, Caroline; Hooning, Maartje J.; Collée, Margriet; Cox, Angela; Cross, Simon S.; Shah, Mitul; Luben, Robert N.; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Couch, Fergus J.; Yannoukakos, Drakoulis; Orr, Nick; Swerdlow, Anthony; Darabi, Hatef; Li, Jingmei; Czene, Kamila; Hall, Per; Easton, Douglas F.; Mattson, Johanna; Blomqvist, Carl; Aittomäki, Kristiina; Nevanlinna, Heli

    2016-01-01

    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk. PMID:27149063

  17. Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Claudia; Dray, Eloise; Groesser, Torsten; San Filippo,Joseph; Shi, Idina; Collins, David W.; Tsai, Miaw-Sheue; Williams,Gareth; Rydberg, Bjorn; Sung, Patrick; Schild, David

    2007-04-11

    Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

  18. Correlation of RAD51 and radiosensitization of methotrexate

    International Nuclear Information System (INIS)

    Du Liqing; Bai Jianqiang; Liu Qiang; Wang Yan; Zhao Peng; Chen Fenghua; Wang Hong; Fan Feiyue

    2012-01-01

    Objective: To evaluate the correlation between homologous recombination repair protein RAD51 and methotrexate-enhanced radiosensitivity. Methods: Western blot and RT-PCR assays were used to detect RAD51 expression in HOS osteosarcoma cells exposed to γ-ray irradiation alone and in combination with methotrexate. Colony formation assay was used to test the survival fraction of HOS cells exposed to γ-rays and methotrexate. Results: Methotrexate inhibited both protein and RNA expressions of RAD51, and the combination of radiation and methotrexate enhanced the inhibition of RAD51 expression. Moreover, transfection of cells with RAD51 gene decreased cellular sensitivity to methotrexate and γ-rays. The sensitizer enhancement ratios after irradiation in combination with methotrexate were 1.51 and 0.99, respectively. Methotrexate was a preferred radiosensitizer to HOS cell. Conclusions: RAD51 might be involved in the methotrexate-enhanced radiosensitivity. (authors)

  19. DMC1 functions in a Saccharomyces cerevisiae meiotic pathway that is largely independent of the RAD51 pathway

    International Nuclear Information System (INIS)

    Dresser, M.E.; Ewing, D.J.; Conrad, M.N.; Dominguez, A.M.; Barstead, R.; Jiang, H.; Kodadek, T.

    1997-01-01

    Meiotic recombination in the yeast Saccharomyces cerevisiae requires two similar recA-like proteins, Dmc1p and Rad51p. A screen for dominant meiotic mutants provided DMC1-G126D, a dominant allele mutated in the conserved ATP-binding site (specifically, the A-loop motif) that confers a null phenotype. A recessive null allele, dmc1-K69E, was isolated as an intragenic suppressor of DMC1-G126D. Dmc1-K69Ep, unlike Dmc1p, does not interact homotypically in a two-hybrid assay, although it does interact with other fusion proteins identified by two-hybrid screen with Dmc1p. Dmc1p, unlike Rad51p, does not interact in the two-hybrid assay with Rad52p or Rad54p. However, Dmc1p does interact with Tid1p, a Rad54p homologue, with Tid4p, a Rad16p homologue, and with other fusion proteins that do not interact with Rad51p, suggesting that Dmc1p and Rad51p function in separate, though possibly overlapping, recombinational repair complexes. Epistasis analysis suggests that DMC1 and RAD51 function in separate pathways responsible for meiotic recombination. Taken together, our results are consistent with a requirement for DMC1 for meiosis-specific entry of DNA double-strand break ends into chromatin. Interestingly, the pattern on CHEF gels of chromosome fragments that result from meiotic DNA double-strand break formation is different in DMC1 mutant strains from that seen in rad50S strains. (author)

  20. Assay for Human Rad51-Mediated DNA Displacement Loop Formation

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Steven Raynard and Patrick Sung Corresponding author ([]()) ### INTRODUCTION Homologous recombination is an important mechanism for the repair of damaged chromosomes, for preventing the demise of damaged replication forks, and for several other aspects of chromosome metabolism and maintenance. The homologous recombination reaction is mediated by the Rad51 recombinase. In the presence of ATP, Rad51 polymerizes on single-stranded D...

  1. RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress

    DEFF Research Database (Denmark)

    Bhowmick, Rahul; Minocherhomji, Sheroy; Hickson, Ian D

    2016-01-01

    Homologous recombination (HR) is necessary to counteract DNA replication stress. Common fragile site (CFS) loci are particularly sensitive to replication stress and undergo pathological rearrangements in tumors. At these loci, replication stress frequently activates DNA repair synthesis in mitosis...... replication stress at CFS loci during S-phase. In contrast, MiDAS is RAD52 dependent, and RAD52 is required for the timely recruitment of MUS81 and POLD3 to CFSs in early mitosis. Our results provide further mechanistic insight into MiDAS and define a specific function for human RAD52. Furthermore, selective...

  2. RAD51 interconnects between DNA replication, DNA repair and immunity.

    Science.gov (United States)

    Bhattacharya, Souparno; Srinivasan, Kalayarasan; Abdisalaam, Salim; Su, Fengtao; Raj, Prithvi; Dozmorov, Igor; Mishra, Ritu; Wakeland, Edward K; Ghose, Subroto; Mukherjee, Shibani; Asaithamby, Aroumougame

    2017-05-05

    RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. A novel interation of nucleolin with Rad51

    International Nuclear Information System (INIS)

    De, Ananya; Donahue, Sarah L.; Tabah, Azah; Castro, Nancy E.; Mraz, Naomi; Cruise, Jennifer L.; Campbell, Colin

    2006-01-01

    Nucleolin associates with various DNA repair, recombination, and replication proteins, and possesses DNA helicase, strand annealing, and strand pairing activities. Examination of nuclear protein extracts from human somatic cells revealed that nucleolin and Rad51 co-immunoprecipitate. Furthermore, purified recombinant Rad51 associates with in vitro transcribed and translated nucleolin. Electroporation-mediated introduction of anti-nucleolin antibody resulted in a 10- to 20-fold reduction in intra-plasmid homologous recombination activity in human fibrosarcoma cells. Additionally, introduction of anti-nucleolin antibody sensitized cells to death induced by the topoisomerase II inhibitor, amsacrine. Introduction of anti-Rad51 antibody also reduced intra-plasmid homologous recombination activity and induced hypersensitivity to amsacrine-induced cell death. Co-introduction of anti-nucleolin and anti-Rad51 antibodies did not produce additive effects on homologous recombination or on cellular sensitivity to amsacrine. The association of the two proteins raises the intriguing possibility that nucleolin binding to Rad51 may function to regulate homologous recombinational repair of chromosomal DNA

  4. Lingering single-strand breaks trigger Rad51-independent homology-directed repair of collapsed replication forks in the polynucleotide kinase/phosphatase mutant of fission yeast.

    Directory of Open Access Journals (Sweden)

    Arancha Sanchez

    2017-09-01

    Full Text Available The DNA repair enzyme polynucleotide kinase/phosphatase (PNKP protects genome integrity by restoring ligatable 5'-phosphate and 3'-hydroxyl termini at single-strand breaks (SSBs. In humans, PNKP mutations underlie the neurological disease known as MCSZ, but these individuals are not predisposed for cancer, implying effective alternative repair pathways in dividing cells. Homology-directed repair (HDR of collapsed replication forks was proposed to repair SSBs in PNKP-deficient cells, but the critical HDR protein Rad51 is not required in PNKP-null (pnk1Δ cells of Schizosaccharomyces pombe. Here, we report that pnk1Δ cells have enhanced requirements for Rad3 (ATR/Mec1 and Chk1 checkpoint kinases, and the multi-BRCT domain protein Brc1 that binds phospho-histone H2A (γH2A at damaged replication forks. The viability of pnk1Δ cells depends on Mre11 and Ctp1 (CtIP/Sae2 double-strand break (DSB resection proteins, Rad52 DNA strand annealing protein, Mus81-Eme1 Holliday junction resolvase, and Rqh1 (BLM/WRN/Sgs1 DNA helicase. Coupled with increased sister chromatid recombination and Rad52 repair foci in pnk1Δ cells, these findings indicate that lingering SSBs in pnk1Δ cells trigger Rad51-independent homology-directed repair of collapsed replication forks. From these data, we propose models for HDR-mediated tolerance of persistent SSBs with 3' phosphate in pnk1Δ cells.

  5. The C-terminal region of Rad52 is essential for Rad52 nuclear and nucleolar localization, and accumulation at DNA damage sites immediately after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Manabu, E-mail: m_koike@nirs.go.jp [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Yutoku, Yasutomo [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Koike, Aki [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2013-05-31

    Highlights: •Rad52 might play a key role in the repair of DSB immediately after irradiation. •EYFP-Rad52 accumulates rapidly at DSB sites and colocalizes with Ku80. •Accumulation of Rad52 at DSB sites is independent of the core NHEJ factors. •Localization and recruitment of Rad52 to DSB sites are dependent on the Rad52 CTR. •Basic amino acids in Rad52 CTR are highly conserved among vertebrate species. -- Abstract: Rad52 plays essential roles in homologous recombination (HR) and repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae. However, in vertebrates, knockouts of the Rad52 gene show no hypersensitivity to agents that induce DSBs. Rad52 localizes in the nucleus and forms foci at a late stage following irradiation. Ku70 and Ku80, which play an essential role in nonhomologous DNA-end-joining (NHEJ), are essential for the accumulation of other core NHEJ factors, e.g., XRCC4, and a HR-related factor, e.g., BRCA1. Here, we show that the subcellular localization of EYFP-Rad52(1–418) changes dynamically during the cell cycle. In addition, EYFP-Rad52(1–418) accumulates rapidly at microirradiated sites and colocalizes with the DSB sensor protein Ku80. Moreover, the accumulation of EYFP-Rad52(1–418) at DSB sites is independent of the core NHEJ factors, i.e., Ku80 and XRCC4. Furthermore, we observed that EYFP-Rad52(1–418) localizes in nucleoli in CHO-K1 cells and XRCC4-deficient cells, but not in Ku80-deficient cells. We also found that Rad52 nuclear localization, nucleolar localization, and accumulation at DSB sites are dependent on eight amino acids (411–418) at the end of the C-terminal region of Rad52 (Rad52 CTR). Furthermore, basic amino acids on Rad52 CTR are highly conserved among mammalian, avian, and fish homologues, suggesting that Rad52 CTR is important for the regulation and function of Rad52 in vertebrates. These findings also suggest that the mechanism underlying the regulation of subcellular localization of Rad52 is

  6. FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end

    Science.gov (United States)

    Sato, Koichi; Shimomuki, Mayo; Katsuki, Yoko; Takahashi, Daisuke; Kobayashi, Wataru; Ishiai, Masamichi; Miyoshi, Hiroyuki; Takata, Minoru; Kurumizaka, Hitoshi

    2016-01-01

    The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork. PMID:27694619

  7. Molecular Basis for Enhancement of the Meiotic DMCI Recombinase by RAD51AP1

    Energy Technology Data Exchange (ETDEWEB)

    Dray, Eloise; Dunlop, Myun Hwa; Kauppi, Liisa; San Filippo, Joseph San; Wiese, Claudia; Tsai, Miaw-Sheue; Begovic, Sead; Schild, David; Jasin, Maria; Keeney, Scott; Sung, Patrick

    2010-11-05

    Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 Associated Protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific recombinase DMC1 and a stimulatory effect of RAD51AP1 on the DMC1-mediated D-loop reaction. Mechanistic studies have revealed that RAD51AP1 enhances the ability of the DMC1 presynaptic filament to capture the duplex DNA partner and to assemble the synaptic complex, in which the recombining DNA strands are homologously aligned. We also provide evidence that functional co-operation is dependent on complex formation between DMC1 and RAD51AP1, and that distinct epitopes in RAD51AP1 mediate interactions with RAD51 and DMC1. Finally, we show that RAD51AP1 is expressed in mouse testes, and that RAD51AP1 foci co-localize with a subset of DMC1 foci in spermatocytes. These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination.

  8. The SRS2 suppressor of rad6 mutations of Saccharomyces cerevisiae acts by channeling DNA lesions into the RAD52 DNA repair pathway

    International Nuclear Information System (INIS)

    Schiestl, R.H.; Prakash, S.; Prakash, L.

    1990-01-01

    rad6 mutants of Saccharomyces cerevisiae are defective in the repair of damaged DNA, DNA damage induced mutagenesis, and sporulation. In order to identify genes that can substitute for RAD6 function, the authors have isolated genomic suppressors of the UV sensitivity of rad6 deletion (rad6Δ) mutations and show that they also suppress the γ-ray sensitivity but not the UV mutagenesis or sporulation defects of rad6. The suppressors show semidominance for suppression of UV sensitivity and dominance for suppression of γ-ray sensitivity. The six suppressor mutations they isolated are all alleles of the same locus and are also allelic to a previously described suppressor of the rad6-1 nonsense mutation, SRS2. They show that suppression of rad6Δ is dependent on the RAD52 recombinational repair pathway since suppression is not observed in the rad6Δ SRS2 strain containing an additional mutation in either the RAD51, RAD52, RAD54, RAD55 or RAD57 genes. Possible mechanisms by which SRS2 may channel unrepaired DNA lesions into the RAD52 DNA repair pathway are discussed

  9. Germline RAD51B truncating mutation in a family with cutaneous melanoma

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Aoude, Lauren G; Golmard, Lisa

    2015-01-01

    Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated...... in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out...... on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While...

  10. TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity

    DEFF Research Database (Denmark)

    Moudry, Pavel; Watanabe, Kenji; Wolanin, Kamila M.

    2016-01-01

    to chromatin and formation of RAD51 foci, but without affecting the upstream HR steps of DNA end resection and RPA loading. Furthermore, TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51...

  11. Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation

    Science.gov (United States)

    Dobson, Rachel; Stockdale, Christopher; Lapsley, Craig; Wilkes, Jonathan; McCulloch, Richard

    2011-01-01

    Homologous recombination in Trypanosoma brucei is used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved recombinase, catalyses homology-directed strand exchange. In any eukaryote, RAD51-directed strand exchange in vivo is mediated by further factors, including RAD51-related proteins termed Rad51 paralogues. These appear to be ubiquitously conserved, although their detailed roles in recombination remain unclear. In T. brucei, four putative RAD51 paralogue genes have been identified by sequence homology. Here we show that all four RAD51 paralogues act in DNA repair, recombination and RAD51 subnuclear dynamics, though not equivalently, while mutation of only one RAD51 paralogue gene significantly impedes VSG switching. We also show that the T. brucei RAD51 paralogues interact, and that the complexes they form may explain the distinct phenotypes of the mutants as well as observed expression interdependency. Finally, we document the Rad51 paralogues that are encoded by a wide range of protists, demonstrating that the Rad51 paralogue repertoire in T. brucei is unusually large among microbial eukaryotes and that one member of the protein family corresponds with a key, conserved eukaryotic Rad51 paralogue. PMID:21615552

  12. Effects of the rad52 gene on recombination in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Prakash, S.; Prakash, L.; Burke, W.; Montelone, B.A.

    1979-01-01

    Effects of the rad52 mutation in Saccharomyces cerevisiae on meiotic, γ-ray-induced, uv-induced, and spontaneous mitotic recombination were studied. The rad52/rad52 diploids undergo premeiotic DNA synthesis; sporulation occurs but inviable spores are produced. Intra- and intergenic recombination during meiosis were examined in cells transferred from sporulation medium to vegetative medium at different time intervals. No intragenic recombination was observed at the hisl-1/hisl-315 and trp5-2/trp5-48 heteroalleles. Gene-centromere recombination was also not observed in rad52/rad52 diploids. No γ-ray-induced intragenic mitotic recombination is seen in rad52/rad52 diploids and uv-induced intragenic recombination is greatly reduced. However, spontaneous mitotic recombination is not similarly affected. The RAD52 gene thus functions in recombination in meiosis and in γ-ray and uv-induced mitotic recombination but not in spontaneous mitotic recombination

  13. Recruitment of RecA homologs Dmc1p and Rad51p to the double-strand break repair site initiated by meiosis-specific endonuclease VDE (PI-SceI).

    Science.gov (United States)

    Fukuda, Tomoyuki; Ohya, Yoshikazu

    2006-02-01

    During meiosis, VDE (PI-SceI), a homing endonuclease in Saccharomyces cerevisiae, introduces a double-strand break (DSB) at its recognition sequence and induces homologous recombinational repair, called homing. Meiosis-specific RecA homolog Dmc1p, as well as mitotic RecA homolog Rad51p, acts in the process of meiotic recombination, being required for strand invasion and exchange. In this study, recruitment of Dmc1p and Rad51p to the VDE-induced DSB repair site is investigated by chromatin immunoprecipitation assay. It is revealed that Dmc1p and Rad51p are loaded to the repair site in an independent manner. Association of Rad51p requires other DSB repair proteins of Rad52p, Rad55p, and Rad57p, while loading of Dmc1p is facilitated by the different protein, Sae3p. Absence of Tid1p, which can bind both RecA homologs, appears specifically to cause an abnormal distribution of Dmc1p. Lack of Hop2, Mnd1p, and Sae1p does not impair recruitment of both RecA homologs. These findings reveal the discrete functions of each strand invasion protein in VDE-initiated homing, confirm the similarity between VDE-initiated homing and Spo11p-initiated meiotic recombination, and demonstrate the availability of VDE-initiated homing for the study of meiotic recombination.

  14. Caffeine inhibits gene conversion by displacing Rad51 from ssDNA

    Science.gov (United States)

    Tsabar, Michael; Mason, Jennifer M.; Chan, Yuen-Ling; Bishop, Douglas K.; Haber, James E.

    2015-01-01

    Efficient repair of chromosomal double-strand breaks (DSBs) by homologous recombination relies on the formation of a Rad51 recombinase filament that forms on single-stranded DNA (ssDNA) created at DSB ends. This filament facilitates the search for a homologous donor sequence and promotes strand invasion. Recently caffeine treatment has been shown to prevent gene targeting in mammalian cells by increasing non-productive Rad51 interactions between the DSB and random regions of the genome. Here we show that caffeine treatment prevents gene conversion in yeast, independently of its inhibition of the Mec1ATR/Tel1ATM-dependent DNA damage response or caffeine's inhibition of 5′ to 3′ resection of DSB ends. Caffeine treatment results in a dosage-dependent eviction of Rad51 from ssDNA. Gene conversion is impaired even at low concentrations of caffeine, where there is no discernible dismantling of the Rad51 filament. Loss of the Rad51 filament integrity is independent of Srs2's Rad51 filament dismantling activity or Rad51's ATPase activity and does not depend on non-specific Rad51 binding to undamaged double-stranded DNA. Caffeine treatment had similar effects on irradiated HeLa cells, promoting loss of previously assembled Rad51 foci. We conclude that caffeine treatment can disrupt gene conversion by disrupting Rad51 filaments. PMID:26019181

  15. Disparate requirements for the Walker A and B ATPase motifs of human RAD51D in homologous recombination.

    Science.gov (United States)

    Wiese, Claudia; Hinz, John M; Tebbs, Robert S; Nham, Peter B; Urbin, Salustra S; Collins, David W; Thompson, Larry H; Schild, David

    2006-01-01

    In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks (ICLs). Ectopic expression of wild-type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

  16. Disparate requirements for the Walker A and B ATPase motifs ofhuman RAD51D in homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Wiese, Claudia; Hinz, John M.; Tebbs, Robert S.; Nham, Peter B.; Urbin, Salustra S.; Collins, David W.; Thompson, Larry H.; Schild, David

    2006-04-21

    In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C, and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks. Ectopic expression of wild type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

  17. Effects of the rad52 gene on recombination in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Prakash, S.; Prakash, L.; Burke, W.; Montelone, B.A.

    1980-01-01

    Effects of the rad 52 mutation in Saccharomyces cerevisiae on meiotic, γ-ray-induced, uv-induced and spontaneous mitotic recombination were studied. The rad52/rad52 diploids undergo premeiotic DNA synthesis; sporulation occurs but inviable spores are produced. Both intra and intergenic recombination during meiosis were examined in cells transferred from sporulation medium to vegetative medium at different time intervals. No intragenic recombination was observed at the his1-1/his1-315 and trp-5-2/trp5-48 heteroalleles. Gene-centromere recombination also was not observed in rad/52/rad52 diploids. No γ-ray- or uv-induced intragenic mitotic recombination is seen in rad52/rad52 diploids. The rate of spontaneous mitotic recombination is lowered five-fold at the his1-1/his1-315 and leu1-c/leu1-12 heteroalleles. Spontaneous reversion rates of both his1-1 and his1-315 were elevated 10 to 20 fold in rad52/rad52 diploids. The RAD52 gene function is required for spontaneous mitotic recombination, uv- and γ-ray-induced mitotic recombination and mitotic recombination

  18. Effect of Rad 51 overexpression on chromosomal stability and radiation sensitivity in tumour cells

    International Nuclear Information System (INIS)

    Jend, C.; Stuerzbecher, H.W.; Dikomey, E.; Borgmann, K.

    2004-01-01

    The present study was dedicated to examining the effects of Rad51 overexpression on genomic instability, expressed in terms of chromosomal aberrations in G1 and G2 phases following X-ray irradiation. For this purpose an osteosarcoma cell line (Ui-OS) which shows inducing Rad51 overexpression (UiRad5-2) after stable transfection was compared with an isogenetic line (UiLacZ) which overexpresses beta-galactosidase instead of Rad51 [de

  19. Prolonged exposure to particulate chromate inhibits RAD51 nuclear import mediator proteins.

    Science.gov (United States)

    Browning, Cynthia L; Wise, John Pierce

    2017-09-15

    Particulate hexavalent chromium (Cr(VI)) is a human lung carcinogen and a human health concern. The induction of structural chromosome instability is considered to be a driving mechanism of Cr(VI)-induced carcinogenesis. Homologous recombination repair protects against Cr(VI)-induced chromosome damage, due to its highly accurate repair of Cr(VI)-induced DNA double strand breaks. However, recent studies demonstrate Cr(VI) inhibits homologous recombination repair through the misregulation of RAD51. RAD51 is an essential protein in HR repair that facilitates the search for a homologous sequence. Recent studies show prolonged Cr(VI) exposure prevents proper RAD51 subcellular localization, causing it to accumulate in the cytoplasm. Since nuclear import of RAD51 is crucial to its function, this study investigated the effect of Cr(VI) on the RAD51 nuclear import mediators, RAD51C and BRCA2. We show acute (24h) Cr(VI) exposure induces the proper localization of RAD51C and BRCA2. In contrast, prolonged (120h) exposure increased the cytoplasmic localization of both proteins, although RAD51C localization was more severely impaired. These results correlate temporally with the previously reported Cr(VI)-induced RAD51 cytoplasmic accumulation. In addition, we found Cr(VI) does not inhibit interaction between RAD51 and its nuclear import mediators. Altogether, our results suggest prolonged Cr(VI) exposure inhibits the nuclear import of RAD51C, and to a lesser extent, BRCA2, which results in the cytoplasmic accumulation of RAD51. Cr(VI)-induced inhibition of nuclear import may play a key role in its carcinogenic mechanism since the nuclear import of many tumor suppressor proteins and DNA repair proteins is crucial to their function. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Dynamic changes in Rad51 distribution on chromatin during meiosis in male and female vertebrates.

    Science.gov (United States)

    Ashley, T; Plug, A W; Xu, J; Solari, A J; Reddy, G; Golub, E I; Ward, D C

    1995-10-01

    Antibodies against human Rad51 protein were used to examine the distribution of Rad51 on meiotic chromatin in mouse spermatocytes and oocytes as well as chicken oocytes during sequential stages of meiosis. We observed the following dynamic changes in distribution of Rad51 during meiosis: (1) in early leptotene nuclei there are multiple, apparently randomly distributed, foci that by late leptonema become organized into tracks of foci. (2) These foci persist into zygonema, but most foci are now localized on Rad51-positive axes that correspond to lateral elements of the synaptonemal complex. As homologs synapse foci from homologous axes fuse. The distribution and involvement of Rad51 foci as contact points between homologs suggest that they may be components to early recombination nodules. (3) As pachynema progresses the number of foci drops dramatically; the temporal occurrence (mice) and physical and numerical distribution of foci on axes (chickens) suggest that they may be a component of late recombination nodules. (4) In early pachynema there are numerous Rad51 foci on the single axis of the X (mouse spermatocytes) or the Z (chicken oocytes) chromosomes that neither pair, nor recombine. (5) In late pachynema in mouse spermatocytes, but not oocytes, the Rad51 signal is preferentially enhanced at both ends of all the bivalents. As bivalents in spermatocytes, but not oocytes, begin to desynapse at diplonema they are often held together at these Rad51-positive termini. These observations parallel observations that recombination rates are exceptionally high near chromosome ends in male but not female eutherian mammals. (6) From diakinesis through metaphase I, Rad51 protein is detected as low-intensity fluorescent doublets that localize with CREST-specific antigens (kinetochores), suggesting that Rad51 participates, at least as a structural component of the materials involved, in sister kinetochore cohesiveness. Finally, the changes in Rad51 distribution during meiosis

  1. Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.

    Science.gov (United States)

    Gayarre, Javier; Martín-Gimeno, Paloma; Osorio, Ana; Paumard, Beatriz; Barroso, Alicia; Fernández, Victoria; de la Hoya, Miguel; Rojo, Alejandro; Caldés, Trinidad; Palacios, José; Urioste, Miguel; Benítez, Javier; García, María J

    2017-09-26

    Despite a high prevalence of deleterious missense variants, most studies of RAD51C ovarian cancer susceptibility gene only provide in silico pathogenicity predictions of missense changes. We identified a novel deleterious RAD51C missense variant (p.Arg312Trp) in a high-risk family, and propose a criteria to prioritise RAD51C missense changes qualifying for functional analysis. To evaluate pathogenicity of p.Arg312Trp variant we used sequence homology, loss of heterozygosity (LOH) and segregation analysis, and a comprehensive functional characterisation. To define a functional-analysis prioritisation criteria, we used outputs for the known functionally confirmed deleterious and benign RAD51C missense changes from nine pathogenicity prediction algorithms. The p.Arg312Trp variant failed to correct mitomycin and olaparib hypersensitivity and to complement abnormal RAD51C foci formation according to functional assays, which altogether with LOH and segregation data demonstrated deleteriousness. Prioritisation criteria were based on the number of predictors providing a deleterious output, with a minimum of 5 to qualify for testing and a PredictProtein score greater than 33 to assign high-priority indication. Our study points to a non-negligible number of RAD51C missense variants likely to impair protein function, provides a guideline to prioritise and encourage their selection for functional analysis and anticipates that reference laboratories should have available resources to conduct such assays.

  2. OsRAD51C Is Essential for Double Strand Break Repair in Rice Meiosis

    Directory of Open Access Journals (Sweden)

    Ding eTang

    2014-05-01

    Full Text Available RAD51C is one of the RAD51 paralogs that plays an important role in DNA double-strand break repair by homologous recombination. Here, we identified and characterized OsRAD51C, the rice homolog of human RAD51C. The Osrad51c mutant plant is normal in vegetative growth but exhibits complete male and female sterility. Cytological investigation revealed that homologous pairing and synapsis were severely disrupted. Massive chromosome fragmentation occurred during metaphase I in Osrad51c meiocytes, and was fully suppressed by the CRC1 mutation. Immunofluorescence analysis showed that OsRAD51C localized onto the chromosomes from leptotene to early pachytene during prophase I, and that normal loading of OsRAD51C was dependent on OsREC8, PAIR2, and PAIR3. Additionally, ZEP1 did not localize properly in Osrad51c, indicating that OsRAD51C is required for synaptonemal complex assembly. Our study also provided evidence in support of a functional divergence in RAD51C among organisms.

  3. Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

    DEFF Research Database (Denmark)

    Gao, Min; Wei, Wei; Li, Ming Hua

    2014-01-01

    resection as well as RPA and Mre11 loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating Rad51 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or retention at DSBs...

  4. Location of RAD51-like protein during meiotic prophase in Eimeria tenella.

    Science.gov (United States)

    Del Cacho, Emilio; Gallego, Margarita; Pagés, Marc; Barbero, José Luís; Monteagudo, Luís; Sánchez-Acedo, Caridad

    2011-05-31

    This study focuses on reporting events in Eimeria tenella oocysts from early to late prophase I in terms of RAD51 protein in association with the synaptonemal complex formed between homologous chromosomes. The aim of the study was the sequential localization of RAD51 protein, which is involved in the repair of double-strand breaks (DSBs) on the eimerian chromosomes as they synapse and desynapse. Structural Maintenance of Chromosome protein SMC3, which plays a role in synaptonemal complex formation, was labeled to identify initiation and progress of chromosome synapsis and desynapsis in parallel with the appearance and disappearance of RAD51 foci. Antibodies directed against RAD51 and cohesin subunit SMC3 proteins were labeled with either fluorescence or colloidal gold to visualize RAD51 protein foci and synaptonemal complexes. RAD51 protein localization during prophase I was studied on meiotic chromosomes spreads obtained from oocysts at different points in time after the start of sporulation. The present findings showed that foci detected with the antibody directed against RAD51 protein first appeared at the pre-leptotene stage before homologous chromosomes began pairing. Subsequently, the foci were detected in association with the lateral elements at the precise sites where synapsis were in progress. These findings lead us to suggest that in E. tenella, homologous chromosome pairing was a DSB-dependent mechanism and reinforced the participation of RAD51 protein in meiotic homology search, alignment and pairing of chromosomes. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer

    DEFF Research Database (Denmark)

    Hansen, Lasse Tengbjerg; Lundin, Cecilia; Spang-Thomsen, Mogens

    2003-01-01

    Etoposide (VP16) is a potent inducer of DNA double-strand breaks (DSBs) and is efficiently used in small cell lung cancer (SCLC) therapy. However, acquired VP16 resistance remains an important barrier to effective treatment. To understand the underlying mechanisms for VP16 resistance in SCLC, we...... investigated DSB repair and cellular VP16 sensitivity of SCLC cells. VP16 sensitivity and RAD51, DNA-PK(cs), topoisomerase IIalpha and P-glycoprotein protein levels were determined in 17 SCLC cell lines. In order to unravel the role of RAD51 in VP16 resistance, we cloned the human RAD51 gene, transfected SCLC...... cells with RAD51 sense or antisense constructs and measured the VP16 resistance. Finally, we measured VP16-induced DSBs in the 17 SCLC cell lines. Two cell lines exhibited a multidrug-resistant phenotype. In the other SCLC cell lines, the cellular VP16 resistance was positively correlated with the RAD51...

  6. Regulation of homologous recombination repair protein Rad51 by Ku70

    International Nuclear Information System (INIS)

    Du Liqing; Liu Qiang; Wang Yan; Xu Chang; Cao Jia; Fu Yue; Chen Fenghua; Fan Feiyue

    2013-01-01

    Objective: To explore the regulative effect of non-homologous end joining (NHEJ)protein Ku70 on homologous recombination repair protein Rad51, and to investigate the synergistic mechanism of homologous recombination repair in combination with NHEJ. Methods: Observed Rad51 protein expression after transfect Ku70 small interfering RNA or Ku70 plasmid DNA into tumor cells using Western blot. Results: Expression of Rad51 was obviously reduced after pretreated with Ku70 small interfering RNA. And with the increasing expression of Ku70 protein after transfection of Ku70 plasmid DNA PGCsi3.0-hKu70 into tumor cell lines, the Rad51 protein expression was increased. Conclusion: Ku70 protein has regulating effect on gene expression of Rad51, and it might participate in the collaboration between homologous recombination repair and NHEJ. (authors)

  7. FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous recombination in mammalian cells

    DEFF Research Database (Denmark)

    Simandlova, Jitka; Zagelbaum, Jennifer; Payne, Miranda J

    2013-01-01

    Efficient repair of DNA double strand breaks and interstrand cross-links requires the homologous recombination (HR) pathway, a potentially error-free process that utilizes a homologous sequence as a repair template. A key player in HR is RAD51, the eukaryotic ortholog of bacterial RecA protein. RAD......51 can polymerize on DNA to form a nucleoprotein filament that facilitates both the search for the homologous DNA sequences and the subsequent DNA strand invasion required to initiate HR. Because of its pivotal role in HR, RAD51 is subject to numerous positive and negative regulatory influences...... filaments on DNA through its ssDNA translocase function. Consistent with this, a mutant mouse embryonic stem cell line with a deletion in the FBH1 helicase domain fails to limit RAD51 chromatin association and shows hyper-recombination. Our data are consistent with FBH1 restraining RAD51 DNA binding under...

  8. Rad52 forms DMA repair and recombination centers during S phase

    DEFF Research Database (Denmark)

    Lisby, M.; Rothstein, R.; Mortensen, Uffe Hasbro

    2001-01-01

    fluorescent protein (GFP) is fully functional in DNA repair and recombination. After induction of DNA double-strand breaks by gamma -irradiation, meiosis, or the HO endonuclease, Rad52-GFP relocalizes from a diffuse nuclear distribution to distinct foci. Interestingly, Rad52 foci are formed almost exclusively...

  9. RAD51C germline mutations in breast and ovarian cancer cases from high-risk families.

    Directory of Open Access Journals (Sweden)

    Jessica Clague

    Full Text Available BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5' UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001. Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene.

  10. Protein dynamics of human RPA and RAD51 on ssDNA during assembly and disassembly of the RAD51 filament.

    Science.gov (United States)

    Ma, Chu Jian; Gibb, Bryan; Kwon, YoungHo; Sung, Patrick; Greene, Eric C

    2017-01-25

    Homologous recombination (HR) is a crucial pathway for double-stranded DNA break (DSB) repair. During the early stages of HR, the newly generated DSB ends are processed to yield long single-stranded DNA (ssDNA) overhangs, which are quickly bound by replication protein A (RPA). RPA is then replaced by the DNA recombinase Rad51, which forms extended helical filaments on the ssDNA. The resulting nucleoprotein filament, known as the presynaptic complex, is responsible for pairing the ssDNA with homologous double-stranded DNA (dsDNA), which serves as the template to guide DSB repair. Here, we use single-molecule imaging to visualize the interplay between human RPA (hRPA) and human RAD51 during presynaptic complex assembly and disassembly. We demonstrate that ssDNA-bound hRPA can undergo facilitated exchange, enabling hRPA to undergo rapid exchange between free and ssDNA-bound states only when free hRPA is present in solution. Our results also indicate that the presence of free hRPA inhibits RAD51 filament nucleation, but has a lesser impact upon filament elongation. This finding suggests that hRPA exerts important regulatory influence over RAD51 and may in turn affect the properties of the assembled RAD51 filament. These experiments provide an important basis for further investigations into the regulation of human presynaptic complex assembly. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells.

    Science.gov (United States)

    King, Harry O; Brend, Tim; Payne, Helen L; Wright, Alexander; Ward, Thomas A; Patel, Karan; Egnuni, Teklu; Stead, Lucy F; Patel, Anjana; Wurdak, Heiko; Short, Susan C

    2017-01-10

    Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation. In GSCs, the small-molecule RAD51 inhibitors RI-1 and B02 prevent RAD51 focus formation, reduce DNA DSB repair, and cause significant radiosensitization. We further demonstrate that treatment with these agents combined with radiation promotes loss of stem cells defined by SOX2 expression. This indicates that RAD51-dependent repair represents an effective and specific target in GSCs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy

    KAUST Repository

    Reymer, A.; Frykholm, K.; Morimatsu, K.; Takahashi, M.; Norden, B.

    2009-01-01

    for central and N-terminal parts of pure (uncomplexed) Rad51 protein by aid of linear dichroism spectroscopy, providing angular orientations of substituted tyrosine residues of Rad51-dsDNA filaments in solution. The structure, validated by comparison

  13. Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1.

    Science.gov (United States)

    Callender, Tracy L; Laureau, Raphaelle; Wan, Lihong; Chen, Xiangyu; Sandhu, Rima; Laljee, Saif; Zhou, Sai; Suhandynata, Ray T; Prugar, Evelyn; Gaines, William A; Kwon, YoungHo; Börner, G Valentin; Nicolas, Alain; Neiman, Aaron M; Hollingsworth, Nancy M

    2016-08-01

    During meiosis, programmed double strand breaks (DSBs) are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH) bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i) phosphorylation of Rad54 by Mek1 and (ii) binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1.

  14. Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1.

    Directory of Open Access Journals (Sweden)

    Tracy L Callender

    2016-08-01

    Full Text Available During meiosis, programmed double strand breaks (DSBs are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i phosphorylation of Rad54 by Mek1 and (ii binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1.

  15. Rad51C deficiency destabilizes XRCC3, impairs recombination and radiosensitizes S/G2-phase cells

    Energy Technology Data Exchange (ETDEWEB)

    Lio, Yi-Ching; Schild, David; Brenneman, Mark A.; Redpath, J. Leslie; Chen, David J.

    2004-05-01

    The highly conserved Rad51 protein plays an essential role in repairing DNA damage through homologous recombination. In vertebrates, five Rad51 paralogs (Rad51B, Rad51C, Rad51D, XRCC2, XRCC3) are expressed in mitotically growing cells, and are thought to play mediating roles in homologous recombination, though their precise functions remain unclear. Here we report the use of RNA interference to deplete expression of Rad51C protein in human HT1080 and HeLa cells. In HT1080 cells, depletion of Rad51C by small interfering RNA caused a significant reduction of frequency in homologous recombination. The level of XRCC3 protein was also sharply reduced in Rad51C-depleted HeLa cells, suggesting that XRCC3 is dependent for its stability upon heterodimerization with Rad51C. In addition, Rad51C-depleted HeLa cells showed hypersensitivity to the DNA cross-linking agent mitomycin C, and moderately increased sensitivity to ionizing radiation. Importantly, the radiosensitivity of Rad51C-deficient HeLa cells was evident in S and G{sub 2}/M phases of the cell cycle but not in G{sub 1} phase. Together, these results provide direct cellular evidence for the importance of human Rad51C in homologous recombinational repair.

  16. Cloning of human and mouse genes homologous to RAD52, a yeast gene involved in DNA repair and recombination.

    NARCIS (Netherlands)

    D.F.R. Muris; O.Y. Bezzubova (Olga); J-M. Buerstedde; K. Vreeken; A.S. Balajee; C.J. Osgood; C. Troelstra (Christine); J.H.J. Hoeijmakers (Jan); K. Ostermann; H. Schmidt (Henning); A.T. Natarajan; J.C.J. Eeken; P.H.M. Lohmann (Paul); A. Pastink (Albert)

    1994-01-01

    textabstractThe RAD52 gene of Saccharomyces cerevisiae is required for recombinational repair of double-strand breaks. Using degenerate oligonucleotides based on conserved amino acid sequences of RAD52 and rad22, its counterpart from Schizosaccharomyces pombe, RAD52 homologs from man and mouse were

  17. The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus

    DEFF Research Database (Denmark)

    Torres-Rosell, Jordi; Sunjevaric, Ivana; De Piccoli, Giacomo

    2007-01-01

    at an extranucleolar site. The nucleolar exclusion of Rad52 recombination foci entails Mre11 and Smc5-Smc6 complexes and depends on Rad52 SUMO (small ubiquitin-related modifier) modification. Remarkably, mutations that abrogate these activities result in the formation of Rad52 foci within the nucleolus and cause r...

  18. Overexpressed of RAD51 suppresses recombination defects: a possible mechanism to reverse genomic instability

    Energy Technology Data Exchange (ETDEWEB)

    Schild, David; Wiese, Claudia

    2009-10-15

    RAD51, a key protein in the homologous recombinational DNA repair (HRR) pathway, is the major strand-transferase required for mitotic recombination. An important early step in HRR is the formation of single-stranded DNA (ss-DNA) coated by RPA (a ss-DNA binding protein). Displacement of RPA by RAD51 is highly regulated and facilitated by a number of different proteins known as the 'recombination mediators'. To assist these recombination mediators, a second group of proteins also is required and we are defining these proteins here as 'recombination co-mediators'. Defects in either recombination mediators or comediators, including BRCA1 and BRCA2, lead to impaired HRR that can genetically be complemented for (i.e. suppressed) by overexpression of RAD51. Defects in HRR have long been known to contribute to genomic instability leading to tumor development. Since genomic instability also slows cell growth, precancerous cells presumably require genomic restabilization to gain a growth advantage. RAD51 is overexpressed in many tumors, and therefore, we hypothesize that the complementing ability of elevated levels of RAD51 in tumors with initial HRR defects limits genomic instability during carcinogenic progression. Of particular interest, this model may also help explain the high frequency of TP53 mutations in human cancers, since wild-type p53 represses RAD51.

  19. RAD51 and RTEL1 compensate telomere loss in the absence of telomerase.

    Science.gov (United States)

    Olivier, Margaux; Charbonnel, Cyril; Amiard, Simon; White, Charles I; Gallego, Maria E

    2018-03-16

    Replicative erosion of telomeres is naturally compensated by telomerase and studies in yeast and vertebrates show that homologous recombination can compensate for the absence of telomerase. We show that RAD51 protein, which catalyzes the key strand-invasion step of homologous recombination, is localized at Arabidopsis telomeres in absence of telomerase. Blocking the strand-transfer activity of the RAD51 in telomerase mutant plants results in a strikingly earlier onset of developmental defects, accompanied by increased numbers of end-to-end chromosome fusions. Imposing replication stress through knockout of RNaseH2 increases numbers of chromosome fusions and reduces the survival of these plants deficient for telomerase and homologous recombination. This finding suggests that RAD51-dependent homologous recombination acts as an essential backup to the telomerase for compensation of replicative telomere loss to ensure genome stability. Furthermore, we show that this positive role of RAD51 in telomere stability is dependent on the RTEL1 helicase. We propose that a RAD51 dependent break-induced replication process is activated in cells lacking telomerase activity, with RTEL1 responsible for D-loop dissolution after telomere replication.

  20. Resolving RAD51C function in late stages of homologous recombination

    Directory of Open Access Journals (Sweden)

    Kuznetsov Sergey G

    2007-06-01

    Full Text Available Abstract DNA double strand breaks are efficiently repaired by homologous recombination. One of the last steps of this process is resolution of Holliday junctions that are formed at the sites of genetic exchange between homologous DNA. Although various resolvases with Holliday junctions processing activity have been identified in bacteriophages, bacteria and archaebacteria, eukaryotic resolvases have been elusive. Recent biochemical evidence has revealed that RAD51C and XRCC3, members of the RAD51-like protein family, are involved in Holliday junction resolution in mammalian cells. However, purified recombinant RAD51C and XRCC3 proteins have not shown any Holliday junction resolution activity. In addition, these proteins did not reveal the presence of a nuclease domain, which raises doubts about their ability to function as a resolvase. Furthermore, oocytes from infertile Rad51C mutant mice exhibit precocious separation of sister chromatids at metaphase II, a phenotype that reflects a defect in sister chromatid cohesion, not a lack of Holliday junction resolution. Here we discuss a model to explain how a Holliday junction resolution defect can lead to sister chromatid separation in mouse oocytes. We also describe other recent in vitro and in vivo evidence supporting a late role for RAD51C in homologous recombination in mammalian cells, which is likely to be resolution of the Holliday junction.

  1. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks.

    Science.gov (United States)

    Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia; Evangelou, Konstantinos; Da-Ré, Caterina; Huber, Florian; Padayachy, Laura; Tardy, Sebastien; Nicati, Noemie L; Barriot, Samia; Ochs, Fena; Lukas, Claudia; Lukas, Jiri; Gorgoulis, Vassilis G; Scapozza, Leonardo; Halazonetis, Thanos D

    2016-12-15

    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 depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci. Depletion of Rad52 by siRNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian RAD52 facilitates repair of collapsed DNA replication forks in cancer cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Identification of a breast cancer family double heterozygote for RAD51C and BRCA2 gene mutations

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Steffensen, Ane Y; Jønson, Lars

    2015-01-01

    for mutations in the RAD51C and BRCA2 genes. The RAD51C missense mutation p.Arg258His has previously been identified in a homozygous state in a patient with Fanconi anemia. This mutation is known to affect the DNA repair function of the RAD51C protein. The BRCA2 p.Leu3216Leu synonymous mutation has not been...

  3. Identification of a deoxyribonuclease controlled by the rad52 gene of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Chow, T.Y.K.; Resnick, M.A.

    1983-01-01

    We have examined deoxyribonuclease levels in extracts of wild-type and rad52 mutants and have observed no significant differences. However, major differences were observed when we employed anti-serum raised against a purified single strand DNA-binding endoexonuclease from Neurospora crassa. As much as sixty percent of the alkaline deoxyribonuclease in wild-type extracts exhibited immunocrossreactivity, whereas none was found in extracts from rad52 strains. This DNase activity was also followed through meiosis; maximum activity was observed in wild-type cells, at a time corresponding to an early stage of premeiotic DNA-synthesis and commitment to recombination. 14 references, 4 figures, 1 table

  4. Roles of Rad51 protein in homologous recombination in mammalian cells: relation with repair, replication and cell cycle

    International Nuclear Information System (INIS)

    Lambert, S.

    2001-01-01

    Homologous recombination (HR) is a fundamental process, allowing a faithful repair. In mammalian, MmRAD51, which is the homologue of Saccharomyces cerevisiae ScRAD51 key protein for HR, is an essential gene. This work is based on the characterisation of viable hyper and hypo-recombinant cell lines specifically affected in the Rad51 pathway. By expressing wild type and dominant negative forms of MmRad51, we demonstrated that Rad51 pathway participates to the repair by HR to induced DNA damages. However, inhibition of the Rad 51 pathway does not affect cell viability, spontaneously or after irradiation, whereas, radiation induced HR is inhibited. In the presence of DNA damages during late S and G2/M phase, inhibition of Rad51 pathway induced chromosomal aberrations, leading to a transient arrest in mitosis. This arrest is associated with an increased of cell death. However, a fraction of cells can escape from this transient arrest by forming tetraploid cells, associated with an absence of chromalid separation. Thus, in response to impaired Rad51 pathway, mitotic checkpoints seems to play an essential role. In line with this, we showed that the essential function of Rad51 is p53-dependent, which is in agreement with the role of p53 in tetraploidy inhibition. Our results suggest that the Rad51 protein could participate to the control of mitotic checkpoints and thus to the maintenance of genetic stability. This function could involve other Rad51 partners such as the tumour suppressors BRCA1, BRCA2 and p53. (author) [fr

  5. RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA.

    Science.gov (United States)

    Wolf, Christine; Rapp, Alexander; Berndt, Nicole; Staroske, Wolfgang; Schuster, Max; Dobrick-Mattheuer, Manuela; Kretschmer, Stefanie; König, Nadja; Kurth, Thomas; Wieczorek, Dagmar; Kast, Karin; Cardoso, M Cristina; Günther, Claudia; Lee-Kirsch, Min Ae

    2016-05-27

    Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA.

  6. Compensatory role for Rad52 during recombinational repair in Ustilago maydis

    DEFF Research Database (Denmark)

    Kojic, Milorad; Mao, Ninghui; Zhou, Qingwen

    2008-01-01

    A single Rad52-related protein is evident by blast analysis of the Ustilago maydis genome database. Mutants created by disruption of the structural gene exhibited few discernible defects in resistance to UV, ionizing radiation, chemical alkylating or cross-linking agents. No deficiency was noted...

  7. 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...... RAD52 facilitates repair of collapsed DNA replication forks in cancer cells....

  8. Rad52 multimerization is important for its nuclear localization in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Plate, Iben; Albertsen, Line; Lisby, Michael

    2008-01-01

    Rad52 is essential for all homologous recombination and DNA double strand break repair events in Saccharomyces cerevisiae. This protein is multifunctional and contains several domains that allow it to interact with DNA as well as with different repair proteins. However, it has been unclear how Rad...

  9. Roles for the yeast RAD18 and RAD52 DNA repair genes in UV mutagenesis.

    Science.gov (United States)

    Armstrong, J D; Chadee, D N; Kunz, B A

    1994-11-01

    Experimental evidence indicates that although the Saccharomyces cerevisiae RAD18 and RAD52 genes are not required for nucleotide excision repair, they function in the processing of UV-induced DNA damage in yeast. Conflicting statements regarding the UV mutability of strains deleted for RAD18 prompted us to re-examine the influence of RAD18, and RAD52, on UV mutagenesis. To do so, we characterized mutations induced by UV in SUP4-o, a yeast suppressor tRNA gene. SUP4-o was maintained on a plasmid in isogenic strains that either carried one of two different rad18 deletions (rad18 delta) or had RAD52 disrupted. Both rad18 deletions decreased the frequency of UV-induced SUP4-o mutations to levels close to those for spontaneous mutagenesis in the rad18 delta backgrounds, and prevented a net increase in mutant yield. A detailed analysis of mutations isolated after UV irradiation of one of the rad18 delta strains uncovered little evidence of the specificity features typical for UV mutagenesis in the isogenic repair-proficient (RAD) parent (e.g., predominance of G.C-->A.T transitions). Evidently, UV induction of SUP4-o mutations is highly dependent on the RAD18 gene. Compared to the RAD strain, disruption of RAD52 reduced the frequency and yield of UV mutagenesis by about two-thirds. Closer inspection revealed that 80% of this reduction was due to a decrease in the frequency of G.C-->A.T transitions. In addition, there were differences in the distributions and site specificities of single base-pair substitutions. Thus, RAD52 also participates in UV mutagenesis of a plasmid-borne gene in yeast, but to a lesser extent than RAD18.

  10. The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair.

    Science.gov (United States)

    Cukras, Scott; Lee, Euiho; Palumbo, Emily; Benavidez, Pamela; Moldovan, George-Lucian; Kee, Younghoon

    2016-10-01

    USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interaction-deficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1.

  11. The role of Rad 51 protein in radioresistance of spheroid model of Du 145 prostate carcinoma cell line

    International Nuclear Information System (INIS)

    Taghizadeh, M.; Khoei, S.; Nikoofar, A. R.; Ghamsari, L.; Goliaei, B.

    2009-01-01

    Rad 51 is a protein with critical role in double strand break repair. Down-regulation of this protein has a significant effect in radiosensitivity of some cell lines like prostate carcinoma. Compared to monolayer cell culture model, the spheroids are more resistant to radiation. The aim of the current study was to determine the Rad 51 protein level in Du 145 spheroids, and monolayer cells before and after exposure to gamma irradiation. Materials and Methods: In the present study, western blot was used to determine the level of Rad 51 protein in Du 145 cell line grown as monolayer and spheroid. Results: Western blot analysis showed that in the spheroid cells, Rad 51 had an elevated level before and after radiation in comparison with monolayer cells. Higher doses of radiation induced elevated expression of Rad 51 protein in both culture models.The level of at protein after exposure to gamma rays had been time-dependent. Conclusion: Rad 51 might act as a mediator of radiation resistance in tumor cells. Repression of Rad 51 activity could be a prominent strategy to overcome radiation resistance of tumors.

  12. Evidence that a recombinationless strain, rad 51, of Saccharomyces cerevisiae lacks the budding cell resistance to γ-rays

    International Nuclear Information System (INIS)

    Hama-Inaba, Hiroko; Saeki, Tetsuya

    1975-01-01

    The radiosensitivities of a wild-type and x-ray sensitive mutant, rad 51 (defective in genetic recombination) of Saccharomyces cerevisiae to γ-rays were compared, using non-synchronized and partially synchronized cultures. The rad 51 cells, either haploid or diploid, showed only very small changes in radiosensitivity during cell growth, whereas the wild-type cells, especially haploid, showed the well-known budding resistance. The heterozygous (wild/rad 51) diploid cells showed in a survival curve a remarkable budding resistance and sigmoidal inactivation kinetics similar to those of wild-type homozygous diploid cells. (author)

  13. Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52

    Directory of Open Access Journals (Sweden)

    Chin-Chuan Chen

    2017-12-01

    Full Text Available Effective DNA repair enables cancer cells to survive DNA damage induced by chemotherapeutic or radiotherapeutic treatments. Therefore, inhibiting DNA repair pathways is a promising therapeutic strategy for increasing the efficacy of such treatments. In this study, we found that dihydrocoumarin (DHC, a flavoring agent, causes deficiencies in double-stand break (DSB repair and prolonged DNA damage checkpoint recovery in yeast. Following DNA damage, Rad52 recombinase was revealed to be inhibited by DHC, which results in deficiencies in DSB repair and prolonged DNA damage checkpoint recovery. The deletion of RPD3, a class I histone deacetylase (HDAC, was found to mimic DHC-induced suppression of Rad52 expression, suggesting that the HDAC inhibitor activity of DHC is critical to DSB repair and DNA damage sensitivity. Overall, our findings delineate the regulatory mechanisms of DHC in DSB repair and suggest that it might potentially be used as an inhibitor of the DNA repair pathway in human cells.

  14. Role of Rad52 in fractionated irradiation induced signaling in A549 lung adenocarcinoma cells

    International Nuclear Information System (INIS)

    Ghosh, Somnath; Krishna, Malini

    2012-01-01

    The effect of fractionated doses of γ-irradiation (2 Gy per fraction over 5 days), as delivered in cancer radiotherapy, was compared with acute doses of 10 and 2 Gy, in A549 cells. A549 cells were found to be relatively more radioresistant if the 10 Gy dose was delivered as a fractionated regimen. Microarray analysis showed upregulation of DNA repair and cell cycle arrest genes in the cells exposed to fractionated irradiation. There was intense activation of DNA repair pathway-associated genes (DNA-PK, ATM, Rad52, MLH1 and BRCA1), efficient DNA repair and phospho-p53 was found to be translocated to the nucleus of A549 cells exposed to fractionated irradiation. MCF-7 cells responded differently in fractionated regimen. Silencing of the Rad52 gene in fractionated group of A549 cells made the cells radiosensitive. The above result indicated increased radioresistance in A549 cells due to the activation of Rad52 gene.

  15. The gene dosage effect of the rad52 mutation on X-ray survival curves of tetraploid yeast strains

    International Nuclear Information System (INIS)

    Ho, K.S.Y.

    1975-01-01

    The mutation rad52 in the yeast Saccharomyces cerevisiae confers sensitivity to X-rays. The gene dosage effect of this mutation on X-ray survival curves of tetraploid yeast strains is shown. With increasing number of rad52 alleles, both a decrease in the survival for a given dose and a decrease in the survival curve shoulder width are observed. The generation of such a family of survival curves using three different mathematical models is discussed

  16. HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis

    DEFF Research Database (Denmark)

    Adelman, Carrie A.; Lolo, Rafal L.; Birkbak, Nicolai Juul

    2013-01-01

    Repair of interstrand crosslinks (ICLs) requires the coordinated action of the intra-S-phase checkpoint and the Fanconi anaemia pathway, which promote ICL incision, translesion synthesis and homologous recombination (reviewed in refs 1, 2). Previous studies have implicated the 3'-5' superfamily 2......, phenotype than the null, indicative of haploinsufficiency. We establish that HELQ interacts directly with the RAD51 paralogue complex BCDX2 and functions in parallel to the Fanconi anaemia pathway to promote efficient homologous recombination at damaged replication forks. Thus, our results reveal a critical...

  17. ATM/ATR-mediated phosphorylation of PALB2 promotes RAD51 function

    DEFF Research Database (Denmark)

    Ahlskog, Johanna K; Larsen, Brian D; Achanta, Kavya

    2016-01-01

    DNA damage activates the ATM and ATR kinases that coordinate checkpoint and DNA repair pathways. An essential step in homology-directed repair (HDR) of DNA breaks is the formation of RAD51 nucleofilaments mediated by PALB2-BRCA2; however, roles of ATM and ATR in this critical step of HDR are poor...... function, as the PALB2-dependent checkpoint response is normal in cells expressing the phospho-deficient PALB2 mutant. Collectively, our findings highlight a critical importance of PALB2 phosphorylation as a novel regulatory step in genome maintenance after genotoxic stress....

  18. Differential expression and requirements for Schizosaccharomyces pombe RAD52 homologs in DNA repair and recombination

    OpenAIRE

    van den Bosch, Michael; Zonneveld, José B. M.; Vreeken, Kees; de Vries, Femke A. T.; Lohman, Paul H. M.; Pastink, Albert

    2002-01-01

    In fission yeast two RAD52 homologs have been identified, rad22A+ and rad22B+. Two-hybrid experiments and GST pull-down assays revealed physical interaction between Rad22A and Rad22B, which is dependent on the N-terminal regions. Interaction with Rhp51 is dependent on the C-terminal parts of either protein. Both Rad22A and Rad22B also interact with RPA. The expression of rad22B+ in mitotically dividing cells is very low in comparison with rad22A+ but is strongly enhanced after induction of me...

  19. Differential RPA-1 and RAD-51 recruitment in vivo throughout the C. elegans germline, as revealed by laser microirradiation.

    Science.gov (United States)

    Koury, Emily; Harrell, Kailey; Smolikove, Sarit

    2018-01-25

    Studies of the repair pathways associated with DNA double strand breaks (DSBs) are numerous, and provide evidence for cell-cycle specific regulation of homologous recombination (HR) by the regulation of its associated proteins. Laser microirradiation is a well-established method to examine in vitro kinetics of repair and allows for live-imaging of DSB repair from the moment of induction. Here we apply this method to whole, live organisms, introducing an effective system to analyze exogenous, microirradiation-induced breaks in the Caenorhabditis elegans germline. Through this method we observed the sequential kinetics of the recruitment of ssDNA binding proteins RPA-1 and RAD-51 in vivo. We analyze these kinetics throughout different regions of the germline, and thus throughout a range of developmental stages of mitotic and meiotic nuclei. Our analysis demonstrates a largely conserved timing of recruitment of ssDNA binding proteins to DSBs throughout the germline, with a delay of RAD-51 recruitment at mid-pachytene nuclei. Microirradiated nuclei are viable and undergo a slow kinetics of resolution. We observe RPA-1 and RAD-51 colocalization for hours post-microirradiation throughout the germline, suggesting that there are mixed RPA-1/RAD-51 filaments. Finally, through live imaging analysis we observed RAD-51 foci movement with low frequency of coalescence. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like symptoms in zebrafish.

    Science.gov (United States)

    Botthof, Jan Gregor; Bielczyk-Maczyńska, Ewa; Ferreira, Lauren; Cvejic, Ana

    2017-05-30

    RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size. We show that some of these symptoms stem from both decreased proliferation and increased apoptosis of embryonic hematopoietic stem and progenitor cells. Comutation of p53 was able to rescue the hematopoietic defects seen in the single mutants, but led to tumor development. We further demonstrate that prolonged inflammatory stress can exacerbate the hematological impairment, leading to an additional decrease in kidney marrow cell numbers. These findings strengthen the assignment of RAD51 as a Fanconi gene and provide more evidence for the notion that aberrant p53 signaling during embryogenesis leads to the hematological defects seen later in life in FA. Further research on this zebrafish FA model will lead to a deeper understanding of the molecular basis of bone marrow failure in FA and the cellular role of RAD51.

  1. Human CST Facilitates Genome-wide RAD51 Recruitment to GC-Rich Repetitive Sequences in Response to Replication Stress.

    Science.gov (United States)

    Chastain, Megan; Zhou, Qing; Shiva, Olga; Fadri-Moskwik, Maria; Whitmore, Leanne; Jia, Pingping; Dai, Xueyu; Huang, Chenhui; Ye, Ping; Chai, Weihang

    2016-08-02

    The telomeric CTC1/STN1/TEN1 (CST) complex has been implicated in promoting replication recovery under replication stress at genomic regions, yet its precise role is unclear. Here, we report that STN1 is enriched at GC-rich repetitive sequences genome-wide in response to hydroxyurea (HU)-induced replication stress. STN1 deficiency exacerbates the fragility of these sequences under replication stress, resulting in chromosome fragmentation. We find that upon fork stalling, CST proteins form distinct nuclear foci that colocalize with RAD51. Furthermore, replication stress induces physical association of CST with RAD51 in an ATR-dependent manner. Strikingly, CST deficiency diminishes HU-induced RAD51 foci formation and reduces RAD51 recruitment to telomeres and non-telomeric GC-rich fragile sequences. Collectively, our findings establish that CST promotes RAD51 recruitment to GC-rich repetitive sequences in response to replication stress to facilitate replication restart, thereby providing insights into the mechanism underlying genome stability maintenance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Caffeine suppresses homologous recombination through interference with RAD51-mediated joint molecule formation

    Science.gov (United States)

    Zelensky, Alex N.; Sanchez, Humberto; Ristic, Dejan; Vidic, Iztok; van Rossum-Fikkert, Sari E.; Essers, Jeroen; Wyman, Claire; Kanaar, Roland

    2013-01-01

    Caffeine is a widely used inhibitor of the protein kinases that play a central role in the DNA damage response. We used chemical inhibitors and genetically deficient mouse embryonic stem cell lines to study the role of DNA damage response in stable integration of the transfected DNA and found that caffeine rapidly, efficiently and reversibly inhibited homologous integration of the transfected DNA as measured by several homologous recombination-mediated gene-targeting assays. Biochemical and structural biology experiments revealed that caffeine interfered with a pivotal step in homologous recombination, homologous joint molecule formation, through increasing interactions of the RAD51 nucleoprotein filament with non-homologous DNA. Our results suggest that recombination pathways dependent on extensive homology search are caffeine-sensitive and stress the importance of considering direct checkpoint-independent mechanisms in the interpretation of the effects of caffeine on DNA repair. PMID:23666627

  3. p53 is involved in clearance of ionizing radiation-induced RAD51 foci in a human colon cancer cell line

    International Nuclear Information System (INIS)

    Orre, Lukas M.; Stenerloew, Bo; Dhar, Sumeer; Larsson, Rolf; Lewensohn, Rolf; Lehtioe, Janne

    2006-01-01

    We have investigated p53-related differences in cellular response to DNA damaging agents, focusing on p53s effects on RAD51 protein level and sub-cellular localization post exposure to ionizing radiation. In a human colon cancer cell line, HCT116 and its isogenic p53-/- subcell line we show here p53-independent RAD51 foci formation but interestingly the resolution of RAD51 foci showed clear p53 dependence. In p53 wt cells, but not in p53-/- cells, RAD51 protein level decreased 48 h post irradiation and fluorescence immunostaining showed resolution of RAD51 foci and relocalization of RAD51 to nucleoli at time points corresponding to the decrease in RAD51 protein level. Both cell lines rejoined DNA double strand breaks efficiently with similar kinetics and p53 status did not influence sensitivity to DNA damaging agents. We suggest that p53 has a role in RAD51 clearance post DSB repair and that nucleoli might be sites of RAD51 protein degradation

  4. The recombination protein RAD52 cooperates with the excision repair protein OGG1 for the repair of oxidative lesions in mammalian cells

    DEFF Research Database (Denmark)

    de Souza-Pinto, Nadja C; Maynard, Scott; Hashiguchi, Kazunari

    2009-01-01

    number of protein interactions have been identified for OGG1, while very few appear to have functional consequences. We report here that OGG1 interacts with the recombination protein RAD52 in vitro and in vivo. This interaction has reciprocal functional consequences as OGG1 inhibits RAD52 catalytic...... knockdown, and mouse cells lacking the protein via gene knockout showed increased sensitivity to oxidative stress. Moreover, cells depleted of RAD52 show higher accumulation of oxidized bases in their genome than cells with normal levels of RAD52. Our results indicate that RAD52 cooperates with OGG1...... to repair oxidative DNA damage and enhances the cellular resistance to oxidative stress. Our observations suggest a coordinated action between these proteins that may be relevant when oxidative lesions positioned close to strand breaks impose a hindrance to RAD52 catalytic activities....

  5. Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break.

    Directory of Open Access Journals (Sweden)

    M Scott Brown

    2015-12-01

    Full Text Available The Eukaryotic RecA-like proteins Rad51 and Dmc1 cooperate during meiosis to promote recombination between homologous chromosomes by repairing programmed DNA double strand breaks (DSBs. Previous studies showed that Rad51 and Dmc1 form partially overlapping co-foci. Here we show these Rad51-Dmc1 co-foci are often arranged in pairs separated by distances of up to 400 nm. Paired co-foci remain prevalent when DSBs are dramatically reduced or when strand exchange or synapsis is blocked. Super-resolution dSTORM microscopy reveals that individual foci observed by conventional light microscopy are often composed of two or more substructures. The data support a model in which the two tracts of ssDNA formed by a single DSB separate from one another by distances of up to 400 nm, with both tracts often bound by one or more short (about 100 nt Rad51 filaments and also by one or more short Dmc1 filaments.

  6. RAD51 potentiates synergistic effects of chemotherapy with PCI-24781 and cis-diamminedichloroplatinum on gastric cancer

    Science.gov (United States)

    He, Wei-Ling; Li, Yu-Huang; Hou, Wei-Jian; Ke, Zun-Fu; Chen, Xin-Lin; Lu, Li-Ya; Cai, Shi-Rong; Song, Wu; Zhang, Chang-Hua; He, Yu-Long

    2014-01-01

    AIM: To explore the efficacy of PCI-24781, a broad-spectrum, hydroxamic acid-derived histone deacetylase inhibitor, in the treatment of gastric cancer (GC). METHODS: With or without treatment of PCI-24781 and/or cis-diamminedichloroplatinum (CDDP), GC cell lines were subjected to functional analysis, including cell growth, apoptosis and clonogenic assays. Chromatin immunoprecipitation and luciferase reporter assays were used to determine the interacting molecules and the activity of the enzyme. An in vivo study was carried out in GC xenograft mice. Cell culture-based assays were represented as mean ± SD. ANOVA tests were used to assess differences across groups. All pairwise comparisons between tumor weights among treatment groups were made using the Tukey-Kramer method for multiple comparison adjustment to control experimental-wise type I error rates. Significance was set at P PCI-24781 significantly reduced the growth of the GC cells, enhanced cell apoptosis and suppressed clonogenicity, and these effects synergized with the effects of CDDP. PCI-24781 modulated the cell cycle and significantly reduced the expression of RAD51, which is related to homologous recombination. Depletion of RAD51 augmented the biological functions of PCI-24781, CDDP and the combination treatment, whereas overexpressing RAD51 had the opposite effects. Increased binding of the transcription suppressor E2F4 on the RAD51 promoter appeared to play a major role in these processes. Furthermore, significant suppression of tumor growth and weight in vivo was obtained following PCI-24781 treatment, which synergized with the anticancer effect of CDDP. CONCLUSION: These data suggest that RAD51 potentiates the synergistic effects of chemotherapy with PCI-24781 and CDDP on GC. PMID:25110436

  7. Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability

    DEFF Research Database (Denmark)

    Galanos, Panagiotis; Pappas, George; Polyzos, Alexander

    2018-01-01

    . Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting a characteristic mutational signature landscape. Guided by the mutational signatures formed, we find that the DSBs are repaired by Rad52-dependent break...

  8. Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination.

    KAUST Repository

    Fornander, Louise H; Frykholm, Karolin; Reymer, Anna; Renodon-Corniè re, Axelle; Takahashi, Masayuki; Nordé n, Bengt

    2012-01-01

    Human RAD51 protein (HsRad51) catalyses the DNA strand exchange reaction for homologous recombination. To clarify the molecular mechanism of the reaction in vitro being more effective in the presence of Ca(2+) than of Mg(2+), we have investigated

  9. Cellular Dynamics of Rad51 and Rad54 in Response to Postreplicative Stress and DNA Damage in HeLa Cells.

    Science.gov (United States)

    Choi, Eui-Hwan; Yoon, Seobin; Hahn, Yoonsoo; Kim, Keun P

    2017-02-01

    Homologous recombination (HR) is necessary for maintenance of genomic integrity and prevention of various mutations in tumor suppressor genes and proto-oncogenes. Rad51 and Rad54 are key HR factors that cope with replication stress and DNA breaks in eukaryotes. Rad51 binds to single-stranded DNA (ssDNA) to form the presynaptic filament that promotes a homology search and DNA strand exchange, and Rad54 stimulates the strand-pairing function of Rad51. Here, we studied the molecular dynamics of Rad51 and Rad54 during the cell cycle of HeLa cells. These cells constitutively express Rad51 and Rad54 throughout the entire cell cycle, and the formation of foci immediately increased in response to various types of DNA damage and replication stress, except for caffeine, which suppressed the Rad51-dependent HR pathway. Depletion of Rad51 caused severe defects in response to postreplicative stress. Accordingly, HeLa cells were arrested at the G2-M transition although a small amount of Rad51 was steadily maintained in HeLa cells. Our results suggest that cell cycle progression and proliferation of HeLa cells can be tightly controlled by the abundance of HR proteins, which are essential for the rapid response to postreplicative stress and DNA damage stress.

  10. Brca2 C-terminus interacts with Rad51 and contributes to nuclear forcus formation in double-strand break repair of DNA

    International Nuclear Information System (INIS)

    Ochiai, Kazuhiko; Morimatsu, Masami; Yoshikawa, Yasunaga; Syuto, Bunei; Hashizume, Kazuyoshi

    2004-01-01

    In humans and mice, the interaction between the breast cancer susceptibility protein, Brca2, and Rad51 recombinase is essential for DNA repair by homologous recombination, the failure of this process can predispose to cancer. Cells with mutated Brca2 are hypersensitive to ionizing radiation (IR) and exhibit defective DNA repair. Using yeast and mammalian two-hybrid assays, we demonstrate that canine Rad51 protein interacts specifically with the C-terminus of canine Brca2. In support of the biological significance of this interaction, we found that radiation-induced focus formation of Rad51 in COS-7 cells was compromised by forced expression of the C-terminus of canine Brca2. A similar result was obtained for the murine C-terminus. These data suggest that the C-terminal domain of canine Brca2 functions to bind Rad51 and that this domain contributes to the IR-induced assembly of the Rad51 complex in vivo. (author)

  11. Rad51 expression levels predict synthetic lethality and metastatic potential in high grade breast cancers

    International Nuclear Information System (INIS)

    Wiegmans, A.P.; Al-Ejeh, F.; Khanna, K.K.

    2012-01-01

    Among women with breast cancer, 30-40% will develop metastatic disease and only achieve an overall survival of less than 5 years. Despite new-targeted therapy, breast tumors that harbour similar histology or molecular phenotype differ in their response to treatment. To uncover potential new therapeutic targets and improve outcome, we performed data mining of cancer micro array databases. We found that high expression of the homologous recombination protein, RAD51, was significantly associated with high-grade breast cancer, aggressive subtypes and increased risk of metastasis. We confirmed using immunohistochemistry that RAD5 1 was highly expressed in metastatic tumours and high-grade triple negative, HER2+ and luminal-B tumours. This provided a rationale for targeting RAD5 1 in high-grade, therapy-resistant breast cancers. Here, we report for the first time preclinical evaluation of RAD5 1 as a therapeutic target. We found that, in-vitro high RAD5 expressing cell lines were resistant to PARP inhibitor while knockdown reversed this resistance. In-vivo, knockdown of RAD5 1 inhibited metastatic progression using a syngeneic breast cancer model and the seeding of human xenografts to distant sites, including brain and lung. Concurrent PARP inhibition reduced primary tumor growth and delayed metastasis supporting synthetic lethality in-vivo. Together these insights provide pre-clinical data demonstrating RAD5 1 as a new biomarker and potential therapeutic target against aggressive metastatic breast cancer. (author)

  12. Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chen, Jyh-Cheng; Wang, Tai-Jing; Zheng, Hao-Yu; Chen, Wen-Ching; Chang, Po-Yuan; Lin, Yun-Wei

    2016-04-01

    Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination, and studies show that chemo-resistant carcinomas exhibit high levels of Rad51 expression. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Astaxanthin treatment (2.5-20 μM) decreased Rad51 expression and phospho-AKT(Ser473) protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector rescued the decreased Rad51 mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 or wortmannin) further decreased the Rad51 expression in astaxanthin-exposed A549 and H1703 cells. Knockdown of Rad51 expression by transfection with si-Rad51 RNA or cotreatment with LY294002 further enhanced the cytotoxicity and cell growth inhibition of astaxanthin. Additionally, mitomycin C (MMC) as an anti-tumor antibiotic is widely used in clinical NSCLC chemotherapy. Combination of MMC and astaxanthin synergistically resulted in cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced phospho-AKT(Ser473) level and Rad51 expression. Overexpression of AKT-CA or Flag-tagged Rad51 reversed the astaxanthin and MMC-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in astaxanthin and MMC co-treated cells. In conclusion, astaxanthin enhances MMC-induced cytotoxicity by decreasing Rad51 expression and AKT activation. These findings may provide rationale to combine astaxanthin with MMC for the treatment of NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Wang, Tai-Jing; Chang, Po-Yuan; Syu, Jhan-Jhang; Chen, Jyh-Cheng; Chen, Chien-Yu; Jian, Yun-Ting; Jian, Yi-Jun; Zheng, Hao-Yu; Chen, Wen-Ching; Lin, Yun-Wei

    2015-10-01

    Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. Our previous studies have shown that the MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In this study, minocycline treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However, combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51 expression by transfection with small interfering RNA of Rad51 enhanced the cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is typically used as a first or second line regimen to treat NSCLC. Compared to a single agent alone, MMC combined with minocycline resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced synergistic cytotoxicity. These findings may have implications for the rational design of future drug regimens incorporating minocycline and MMC for the treatment of NSCLC. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Down-regulation of Rad51 activity during meiosis in yeast prevents competition with Dmc1 for repair of double-strand breaks.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2014-01-01

    Full Text Available Interhomolog recombination plays a critical role in promoting proper meiotic chromosome segregation but a mechanistic understanding of this process is far from complete. In vegetative cells, Rad51 is a highly conserved recombinase that exhibits a preference for repairing double strand breaks (DSBs using sister chromatids, in contrast to the conserved, meiosis-specific recombinase, Dmc1, which preferentially repairs programmed DSBs using homologs. Despite the different preferences for repair templates, both Rad51 and Dmc1 are required for interhomolog recombination during meiosis. This paradox has recently been explained by the finding that Rad51 protein, but not its strand exchange activity, promotes Dmc1 function in budding yeast. Rad51 activity is inhibited in dmc1Δ mutants, where the failure to repair meiotic DSBs triggers the meiotic recombination checkpoint, resulting in prophase arrest. The question remains whether inhibition of Rad51 activity is important during wild-type meiosis, or whether inactivation of Rad51 occurs only as a result of the absence of DMC1 or checkpoint activation. This work shows that strains in which mechanisms that down-regulate Rad51 activity are removed exhibit reduced numbers of interhomolog crossovers and noncrossovers. A hypomorphic mutant, dmc1-T159A, makes less stable presynaptic filaments but is still able to mediate strand exchange and interact with accessory factors. Combining dmc1-T159A with up-regulated Rad51 activity reduces interhomolog recombination and spore viability, while increasing intersister joint molecule formation. These results support the idea that down-regulation of Rad51 activity is important during meiosis to prevent Rad51 from competing with Dmc1 for repair of meiotic DSBs.

  15. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Godthelp, Barbara C. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Wiegant, Wouter W. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands); Waisfisz, Quinten [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Medhurst, Annette L. [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Arwert, Fre [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Joenje, Hans [Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, NL-2333 AL Leiden (Netherlands) and Department of Molecular Cell Genetics, Collegium Medicum, N. Copernicus University, Bydgoszcz (Poland)]. E-mail: m.z.zdzienicka@lumc.nl

    2006-02-22

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination.

  16. Inducibility of nuclear Rad51 foci after DNA damage distinguishes all Fanconi anemia complementation groups from D1/BRCA2

    International Nuclear Information System (INIS)

    Godthelp, Barbara C.; Wiegant, Wouter W.; Waisfisz, Quinten; Medhurst, Annette L.; Arwert, Fre; Joenje, Hans; Zdzienicka, Malgorzata Z.

    2006-01-01

    Fanconi anemia (FA) is a cancer susceptibility disorder characterized by chromosomal instability and hypersensitivity to DNA cross-linking agents. So far 11 complementation groups have been identified, from which only FA-D1/BRCA2 and FA-J are defective downstream of the central FANCD2 protein as cells from these groups are capable of monoubiquitinating FANCD2. In this study we show that cells derived from patients from the new complementation groups, FA-I, FA-J and FA-L are all proficient in DNA damage induced Rad51 foci formation, making the cells from FA-D1/BRCA2 patients that are defective in this process the sole exception. Although FA-B patient HSC230 was previously reported to also have biallelic BRCA2 mutations, we found normal Rad51 foci formation in cells from this patient, consistent with the recent identification of an X-linked gene being mutated in four unrelated FA-B patients. Thus, our data show that none of the FA proteins, except BRCA2, are required to sequester Rad51 into nuclear foci. Since cells from the FA-D1 and FA-J patient groups are both able to monoubiquitinate FANCD2, the 'Rad51 foci phenotype' provides a convenient assay to distinguish between these two groups. Our results suggest that FANCJ and FANCD1/BRCA2 are part of the integrated FANC/BRCA DNA damage response pathway or, alternatively, that they represent sub-pathways in which only FANCD1/BRCA2 is directly connected to the process of homologous recombination

  17. Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy

    KAUST Repository

    Reymer, A.

    2009-07-08

    To get mechanistic insight into the DNA strand-exchange reaction of homologous recombination, we solved a filament structure of a human Rad51 protein, combining molecular modeling with experimental data. We build our structure on reported structures for central and N-terminal parts of pure (uncomplexed) Rad51 protein by aid of linear dichroism spectroscopy, providing angular orientations of substituted tyrosine residues of Rad51-dsDNA filaments in solution. The structure, validated by comparison with an electron microscopy density map and results from mutation analysis, is proposed to represent an active solution structure of the nucleo-protein complex. An inhomogeneously stretched double-stranded DNA fitted into the filament emphasizes the strategic positioning of 2 putative DNA-binding loops in a way that allows us speculate about their possibly distinct roles in nucleo-protein filament assembly and DNA strand-exchange reaction. The model suggests that the extension of a single-stranded DNA molecule upon binding of Rad51 is ensured by intercalation of Tyr-232 of the L1 loop, which might act as a docking tool, aligning protein monomers along the DNA strand upon filament assembly. Arg-235, also sitting on L1, is in the right position to make electrostatic contact with the phosphate backbone of the other DNA strand. The L2 loop position and its more ordered compact conformation makes us propose that this loop has another role, as a binding site for an incoming double-stranded DNA. Our filament structure and spectroscopic approach open the possibility of analyzing details along the multistep path of the strand-exchange reaction.

  18. Simultaneous ATM/BRCA1/RAD51 expression variations associated with prognostic factors in Iranian sporadic breast cancer patients.

    Science.gov (United States)

    Hallajian, Zeinab; Mahjoubi, Frouzandeh; Nafissi, Nahid

    2017-07-01

    DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues. Moreover, this study evaluates potential correlations among expression levels of these genes. 50 breast cancer tissues were collected and examined for BRCA1, RAD51 and ATM gene expression by Real Time PCR. Expression changes were analyzed with REST software version 2009. mRNA expression was reduced in all these three genes when compared with β-Actin as a control gene (P value  ATM, BRCA1 and RAD51 gene down expression (P value  ATM with stage (P value  < 0.05), necrosis (P value  < 0.05), perineural invasion (P value  < 0.05), vascular invasion (P value  < 0.01), malignancy (P value  ≤ 0.001), PR (P value  < 0.05) and ER status (P value  < 0.01). In addition, there was a significant association between down expression of BRCA1 with Ki67 (P value  ≤ 0.001). Moreover, there was a significant association between down expression of RAD51 with lymph node involvement (P value  < 0.01), auxiliary lymph node metastasis (P value  = 0.01), age (P = 0.001), grade (P value  < 0.05) and PR status (P value  < 0.05). This study suggests association between expression changes in several DSB repair genes in a common functional pathway in breast cancer and the significant association between abnormal expression of these genes and important clinical prognostic factors.

  19. Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament.

    KAUST Repository

    Fornander, Louise H; Renodon-Corniè re, Axelle; Kuwabara, Naoyuki; Ito, Kentaro; Tsutsui, Yasuhiro; Shimizu, Toshiyuki; Iwasaki, Hiroshi; Nordé n, Bengt; Takahashi, Masayuki

    2013-01-01

    The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand exchange reaction, a crucial step in homologous recombination. To clarify how this accessory protein acts on the strand exchange reaction, we have analyzed how the structure

  20. Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination.

    KAUST Repository

    Fornander, Louise H

    2012-02-22

    Human RAD51 protein (HsRad51) catalyses the DNA strand exchange reaction for homologous recombination. To clarify the molecular mechanism of the reaction in vitro being more effective in the presence of Ca(2+) than of Mg(2+), we have investigated the effect of these ions on the structure of HsRad51 filament complexes with single- and double-stranded DNA, the reaction intermediates. Flow linear dichroism spectroscopy shows that the two ionic conditions induce significantly different structures in the HsRad51/single-stranded DNA complex, while the HsRad51/double-stranded DNA complex does not demonstrate this ionic dependence. In the HsRad51/single-stranded DNA filament, the primary intermediate of the strand exchange reaction, ATP/Ca(2+) induces an ordered conformation of DNA, with preferentially perpendicular orientation of nucleobases relative to the filament axis, while the presence of ATP/Mg(2+), ADP/Mg(2+) or ADP/Ca(2+) does not. A high strand exchange activity is observed for the filament formed with ATP/Ca(2+), whereas the other filaments exhibit lower activity. Molecular modelling suggests that the structural variation is caused by the divalent cation interfering with the L2 loop close to the DNA-binding site. It is proposed that the larger Ca(2+) stabilizes the loop conformation and thereby the protein-DNA interaction. A tight binding of DNA, with bases perpendicularly oriented, could facilitate strand exchange.

  1. Congenital Mirror Movements Due to RAD51: Cosegregation with a Nonsense Mutation in a Norwegian Pedigree and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Oriane Trouillard

    2016-11-01

    Full Text Available Background: Autosomal dominant congenital mirror movements (CMM is a neurodevelopmental disorder characterized by early onset involuntary movements of one side of the body that mirror intentional movements on the contralateral side; these persist throughout life in the absence of other neurological symptoms. The main culprit genes responsible for this condition are RAD51 and DCC. This condition has only been reported in a few families, and the molecular mechanisms linking RAD51 mutations and mirror movements (MM are poorly understood. Methods: We collected demographic, clinical, and genetic data of a new family with CMM due to a truncating mutation of RAD51. We reviewed the literature to identify all reported patients with CMM due to RAD51 mutations. Results: We identified a heterozygous nonsense mutation c.760C>T (p.Arg254∗ in eight subjects: four with obvious and disabling MM, and four with a mild phenotype. Including our new family, we identified 32 patients from 6 families with CMM linked to RAD51 variants. Discussion: Our findings further support the involvement of RAD51 in CMM pathogenesis. Possible molecular mechanisms involved in CMM pathogenesis are discussed.

  2. Cloning, sequencing, disruption and phenotypic analysis of uvsC, an Aspergillus nidulans homologue of yeast RAD51.

    Science.gov (United States)

    van Heemst, D; Swart, K; Holub, E F; van Dijk, R; Offenberg, H H; Goosen, T; van den Broek, H W; Heyting, C

    1997-05-01

    We have cloned the uvsC gene of Aspergillus nidulans by complementation of the A. nidulans uvsC114 mutant. The predicted protein UVSC shows 67.4% sequence identity to the Saccharomyces cerevisiae Rad51 protein and 27.4% sequence identity to the Escherichia coli RecA protein. Transcription of uvsC is induced by methyl-methane sulphonate (MMS), as is transcription of RAD51 of yeast. Similar levels of uvsC transcription were observed after MMS induction in a uvsC+ strain and the uvsC114 mutant. The coding sequence of the uvsC114 allele has a deletion of 6 bp, which results in deletion of two amino acids and replacement of one amino acid in the translation product. In order to gain more insight into the biological function of the uvsC gene, a uvsC null mutant was constructed, in which the entire uvsC coding sequence was replaced by a selectable marker gene. Meiotic and mitotic phenotypes of a uvsC+ strain, the uvsC114 mutant and the uvsC null mutant were compared. The uvsC null mutant was more sensitive to both UV and MMS than the uvsC114 mutant. The uvsC114 mutant arrested in meiotic prophase-I. The uvsC null mutant arrested at an earlier stage, before the onset of meiosis. One possible interpretation of these meiotic phenotypes is that the A. nidulans homologue of Rad51 of yeast has a role both in the specialized processes preceding meiosis and in meiotic prophase I.

  3. Enhancing cytochrome P450-mediated conversions in P. pastoris through RAD52 over-expression and optimizing the cultivation conditions.

    Science.gov (United States)

    Wriessnegger, Tamara; Moser, Sandra; Emmerstorfer-Augustin, Anita; Leitner, Erich; Müller, Monika; Kaluzna, Iwona; Schürmann, Martin; Mink, Daniel; Pichler, Harald

    2016-04-01

    Cytochrome P450 enzymes (CYPs) play an essential role in the biosynthesis of various natural compounds by catalyzing regio- and stereospecific hydroxylation reactions. Thus, CYP activities are of great interest in the production of fine chemicals, pharmaceutical compounds or flavors and fragrances. Industrial applicability of CYPs has driven extensive research efforts aimed at improving the performance of these enzymes to generate robust biocatalysts. Recently, our group has identified CYP-mediated hydroxylation of (+)-valencene as a major bottleneck in the biosynthesis of trans-nootkatol and (+)-nootkatone in Pichia pastoris. In the current study, we aimed at enhancing CYP-mediated (+)-valencene hydroxylation by over-expressing target genes identified through transcriptome analysis in P. pastoris. Strikingly, over-expression of the DNA repair and recombination gene RAD52 had a distinctly positive effect on trans-nootkatol formation. Combining RAD52 over-expression with optimization of whole-cell biotransformation conditions, i.e. optimized media composition and cultivation at higher pH value, enhanced trans-nootkatol production 5-fold compared to the initial strain and condition. These engineering approaches appear to be generally applicable for enhanced hydroxylation of hydrophobic compounds in P. pastoris as confirmed here for two additional membrane-attached CYPs, namely the limonene-3-hydroxylase from Mentha piperita and the human CYP2D6. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination.

    Science.gov (United States)

    Inano, Shojiro; Sato, Koichi; Katsuki, Yoko; Kobayashi, Wataru; Tanaka, Hiroki; Nakajima, Kazuhiro; Nakada, Shinichiro; Miyoshi, Hiroyuki; Knies, Kerstin; Takaori-Kondo, Akifumi; Schindler, Detlev; Ishiai, Masamichi; Kurumizaka, Hitoshi; Takata, Minoru

    2017-06-01

    RFWD3 is a recently identified Fanconi anemia protein FANCW whose E3 ligase activity toward RPA is essential in homologous recombination (HR) repair. However, how RPA ubiquitination promotes HR remained unknown. Here, we identified RAD51, the central HR protein, as another target of RFWD3. We show that RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo. Phosphorylation by ATR and ATM kinases is required for this activity in vivo. RFWD3 inhibits persistent mitomycin C (MMC)-induced RAD51 and RPA foci by promoting VCP/p97-mediated protein dynamics and subsequent degradation. Furthermore, MMC-induced chromatin loading of MCM8 and RAD54 is defective in cells with inactivated RFWD3 or expressing a ubiquitination-deficient mutant RAD51. Collectively, our data reveal a mechanism that facilitates timely removal of RPA and RAD51 from DNA damage sites, which is crucial for progression to the late-phase HR and suppression of the FA phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.

    KAUST Repository

    Nomme, Julian; Renodon-Corniè re, Axelle; Asanomi, Yuya; Sakaguchi, Kazuyasu; Stasiak, Alicja Z; Stasiak, Andrzej; Norden, Bengt; Tran, Vinh; Takahashi, Masayuki

    2010-01-01

    We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.

  6. Pir51, a Rad51-interacting protein with high expression in aggressive lymphoma, controls mitomycin C sensitivity and prevents chromosomal breaks

    Energy Technology Data Exchange (ETDEWEB)

    Henson, Sarah E. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Tsai, Shih-Chang [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Malone, Cindy Sue [Department of Biology, California State University Northridge, Northridge, CA 91330 (United States); Soghomonian, Shahe V. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Ouyang, Yan [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Wall, Randolph [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Marahrens, York [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States) and Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States)]. E-mail: YMarahrens@mednet.ucla.edu; Teitell, Michael A. [Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States) and Department of Pathology and Laboratory Medicine, California NanoSystems Institute, and Institute for Stem Cell Biology and Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States)]. E-mail: mteitell@ucla.edu

    2006-10-10

    Pir51, a protein of unknown function that interacts with Rad51, was identified in a screen for genes that were highly expressed in aggressive mantle cell lymphoma (MCL) versus indolent small lymphocytic lymphoma (SLL) patient samples. We show that Pir51 is a nuclear protein expressed in a variety of cell types and that its expression is regulated during the cell cycle in a pattern nearly identical to Rad51. Also similar to Rad51, Pir51 levels did not change in response to a variety of DNA damaging agents. siRNA depletion of Pir51 did not reduce homologous recombination repair (HRR), but sensitized cells to mitomycin C (MMC)-induced DNA crosslinking and resulted in elevated levels of double-strand breaks (DSBs) in metaphase chromosome spreads and reduced colony formation. Therefore, Pir51 maintains genomic integrity and potentially connects the early response to DNA crosslinks, orchestrated by the ATR kinase and Fanconi Anemia (FA) proteins, to later stages of Rad51-dependent repair. Our results provide the first example of a Rad51-binding protein that influences DNA crosslink repair without affecting homologous recombination repair.

  7. Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.

    KAUST Repository

    Nomme, Julian

    2010-08-01

    We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.

  8. Pir51, a Rad51-interacting protein with high expression in aggressive lymphoma, controls mitomycin C sensitivity and prevents chromosomal breaks

    International Nuclear Information System (INIS)

    Henson, Sarah E.; Tsai, Shih-Chang; Malone, Cindy Sue; Soghomonian, Shahe V.; Ouyang, Yan; Wall, Randolph; Marahrens, York; Teitell, Michael A.

    2006-01-01

    Pir51, a protein of unknown function that interacts with Rad51, was identified in a screen for genes that were highly expressed in aggressive mantle cell lymphoma (MCL) versus indolent small lymphocytic lymphoma (SLL) patient samples. We show that Pir51 is a nuclear protein expressed in a variety of cell types and that its expression is regulated during the cell cycle in a pattern nearly identical to Rad51. Also similar to Rad51, Pir51 levels did not change in response to a variety of DNA damaging agents. siRNA depletion of Pir51 did not reduce homologous recombination repair (HRR), but sensitized cells to mitomycin C (MMC)-induced DNA crosslinking and resulted in elevated levels of double-strand breaks (DSBs) in metaphase chromosome spreads and reduced colony formation. Therefore, Pir51 maintains genomic integrity and potentially connects the early response to DNA crosslinks, orchestrated by the ATR kinase and Fanconi Anemia (FA) proteins, to later stages of Rad51-dependent repair. Our results provide the first example of a Rad51-binding protein that influences DNA crosslink repair without affecting homologous recombination repair

  9. Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector.

    Science.gov (United States)

    Zhang, Chao; Wang, Bing; Li, Lei; Li, Yawei; Li, Pengzhi; Lv, Guohua

    2017-09-01

    Surgery followed by radiotherapy is the standard treatment for chordomas, which are a rare but low-grade type of bone cancer arising from remnants of the embryonic notochord. However, disease recurrence following radiotherapy is common, most likely due to endogenous DNA repair mechanisms that promote cell survival upon radiation strikes. The ataxia telangiectasia mutated/ataxia telangiectasia mutated and Rad3 related (ATM/ATR)-mediated pathway has a critical role in DNA repair mechanisms; however, it has rarely been investigated in chordomas. In the present study, the expression of signal molecules related to the ATM/ATR pathway in chordoma tissues and adjacent normal tissues were initially examined using immunohistochemistry and western blot analysis. Chordoma U-CH1 and U-CH2 cells were subsequently used to investigate cell responses to ionizing radiation and the potential protective actions mediated by the ATM/ATR pathway. Phosphorylated (p)-ATM, p-ATR, γ-H2A histone family, member X (H2AX) and RAD51 were significantly upregulated in chordoma tissues relative to adjacent normal tissues (PATM, γ-H2AX and RAD51 expression in U-CH1 cells (PATM, p-ATR and RAD51 levels in U-CH2 cells (PATM/ATR pathway, in which RAD51 serves as an important downstream effector. Thus, RAD51 presents a promising therapeutic target for improving the outcome of radiotherapy treatment in chordomas.

  10. CRISPR Technology Reveals RAD(51)-ical Mechanisms of Repair in Roundworms: An Educational Primer for Use with "Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans".

    Science.gov (United States)

    Turcotte, Carolyn A; Andrews, Nicolas P; Sloat, Solomon A; Checchi, Paula M

    2016-11-01

    The mechanisms cells use to maintain genetic fidelity via DNA repair and the accuracy of these processes have garnered interest from scientists engaged in basic research to clinicians seeking improved treatment for cancer patients. Despite the continued advances, many details of DNA repair are still incompletely understood. In addition, the inherent complexity of DNA repair processes, even at the most fundamental level, makes it a challenging topic. This primer is meant to assist both educators and students in using a recent paper, "Promotion of homologous recombination by SWS-1 in complex with RAD-51 paralogs in Caenorhabditis elegans," to understand mechanisms of DNA repair. The goals of this primer are to highlight and clarify several key techniques utilized, with special emphasis on the clustered, regularly interspaced, short palindromic repeats technique and the ways in which it has revolutionized genetics research, as well as to provide questions for deeper in-class discussion. Copyright © 2016 by the Genetics Society of America.

  11. Recruitment kinetics of DNA repair proteins Mdc1 and Rad52 but not 53BP1 depend on damage complexity.

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    Volker Hable

    Full Text Available The recruitment kinetics of double-strand break (DSB signaling and repair proteins Mdc1, 53BP1 and Rad52 into radiation-induced foci was studied by live-cell fluorescence microscopy after ion microirradiation. To investigate the influence of damage density and complexity on recruitment kinetics, which cannot be done by UV laser irradiation used in former studies, we utilized 43 MeV carbon ions with high linear energy transfer per ion (LET = 370 keV/µm to create a large fraction of clustered DSBs, thus forming complex DNA damage, and 20 MeV protons with low LET (LET = 2.6 keV/µm to create mainly isolated DSBs. Kinetics for all three proteins was characterized by a time lag period T(0 after irradiation, during which no foci are formed. Subsequently, the proteins accumulate into foci with characteristic mean recruitment times τ(1. Mdc1 accumulates faster (T(0 = 17 ± 2 s, τ(1 = 98 ± 11 s than 53BP1 (T(0 = 77 ± 7 s, τ(1 = 310 ± 60 s after high LET irradiation. However, recruitment of Mdc1 slows down (T(0 = 73 ± 16 s, τ(1 = 1050 ± 270 s after low LET irradiation. The recruitment kinetics of Rad52 is slower than that of Mdc1, but exhibits the same dependence on LET. In contrast, the mean recruitment time τ(1 of 53BP1 remains almost constant when varying LET. Comparison to literature data on Mdc1 recruitment after UV laser irradiation shows that this rather resembles recruitment after high than low LET ionizing radiation. So this work shows that damage quality has a large influence on repair processes and has to be considered when comparing different studies.

  12. Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament.

    KAUST Repository

    Fornander, Louise H

    2013-12-03

    The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand exchange reaction, a crucial step in homologous recombination. To clarify how this accessory protein acts on the strand exchange reaction, we have analyzed how the structure of the primary reaction intermediate, the Rad51/single-stranded DNA (ssDNA) complex filament formed in the presence of ATP, is affected by Swi5-Sfr1. Using flow linear dichroism spectroscopy, we observe that the nucleobases of the ssDNA are more perpendicularly aligned to the filament axis in the presence of Swi5-Sfr1, whereas the bases are more randomly oriented in the absence of Swi5-Sfr1. When using a modified version of the natural protein where the N-terminal part of Sfr1 is deleted, which has no affinity for DNA but maintained ability to stimulate the strand exchange reaction, we still observe the improved perpendicular DNA base orientation. This indicates that Swi5-Sfr1 exerts its activating effect through interaction with the Rad51 filament mainly and not with the DNA. We propose that the role of a coplanar alignment of nucleobases induced by Swi5-Sfr1 in the presynaptic Rad51/ssDNA complex is to facilitate the critical matching with an invading double-stranded DNA, hence stimulating the strand exchange reaction.

  13. In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation

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    Maria Angelica Cortez

    2015-01-01

    Full Text Available MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC, among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3’ untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC.

  14. A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks

    Science.gov (United States)

    Schär, Primo; Herrmann, Gernot; Daly, Graham; Lindahl, Tomas

    1997-01-01

    Eukaryotic DNA ligases are ATP-dependent DNA strand-joining enzymes that participate in DNA replication, repair, and recombination. Whereas mammalian cells contain several different DNA ligases, encoded by at least three distinct genes, only one DNA ligase has been detected previously in either budding yeast or fission yeast. Here, we describe a newly identified nonessential Saccharomyces cerevisiae gene that encodes a DNA ligase distinct from the CDC9 gene product. This DNA ligase shares significant amino acid sequence homology with human DNA ligase IV; accordingly, we designate the yeast gene LIG4. Recombinant LIG4 protein forms a covalent enzyme-AMP complex and can join a DNA single-strand break in a DNA/RNA hybrid duplex, the preferred substrate in vitro. Disruption of the LIG4 gene causes only marginally increased cellular sensitivity to several DNA damaging agents, and does not further sensitize cdc9 or rad52 mutant cells. In contrast, lig4 mutant cells have a 1000-fold reduced capacity for correct recircularization of linearized plasmids by illegitimate end-joining after transformation. Moreover, homozygous lig4 mutant diploids sporulate less efficiently than isogenic wild-type cells, and show retarded progression through meiotic prophase I. Spore viability is normal, but lig4 mutants appear to produce a higher proportion of tetrads with only three viable spores. The mutant phenotypes are consistent with functions of LIG4 in an illegitimate DNA end-joining pathway and ensuring efficient meiosis. PMID:9271115

  15. Curcumin enhances the mitomycin C-induced cytotoxicity via downregulation of MKK1/2-ERK1/2-mediated Rad51 expression in non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Ko, Jen-Chung; Tsai, Min-Shao; Weng, Shao-Hsing; Kuo, Ya-Hsun; Chiu, Yu-Fan; Lin, Yun-Wei

    2011-01-01

    Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been reported to suppress the proliferation of a wide variety of tumor cells. Rad51 is a key protein in the homologous recombination (HR) pathway of DNA double-strand break repair, and HR represents a novel target for cancer therapy. A high expression of Rad51 has been reported in chemo- or radio-resistant carcinomas. Therefore, in the current study, we will examine whether curcumin could enhance the effects of mitomycin C (MMC), a DNA interstrand cross-linking agent, to induce cytotoxicity by decreasing Rad51 expression. Exposure of two human non-small lung cancer (NSCLC) cell lines (A549 and H1975) to curcumin could suppress MMC-induced MKK1/2-ERK1/2 signal activation and Rad51 protein expression. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) increased Rad51 protein levels in curcumin and MMC co-treated human lung cells. Moreover, the synergistic cytotoxic effect induced by curcumin combined with MMC was decreased by MKK1-CA-mediated enhancement of ERK1/2 activation by a significant degree. In contrast, MKK1/2 inhibitor, U0126 was shown to augment the cytotoxicity of curcumin and MMC through downregulation of ERK1/2 activation and Rad51 expression. Depletion of endogenous Rad51 expression by siRad51 RNA transfection significantly enhanced MMC and/or curcumin induced cell death and cell growth inhibition. In contrast, an overexpression of Rad51 protected lung cancer cells from synergistic cytotoxic effects induced by curcumin and MMC. We concluded that Rad51 inhibition may be an additional action mechanism for enhancing the chemosensitization of MMC by curcumin in NSCLC. - Highlights: → Curcumin downregulates MKK-ERK-mediated Rad51 expression. → Curcumin enhances mitomycin C-induced cytotoxicity. → Rad51 protects cells from cytotoxic effects induced by curcumin and mitomycin C. → Rad51 inhibition enhances the chemosensitization of

  16. Icotinib hydrochloride enhances chemo- and radiosensitivity by inhibiting EGFR signaling and attenuating RAD51 expression and function in Hela S3 cells

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    Wang X

    2018-03-01

    Full Text Available Xuanxuan Wang, Yanjun Gu, Hai Liu, Liming Shi, Xiaonan Sun Department of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China Background: Radiotherapy and cisplatin-based chemotherapy are currently considered as standard treatments employed for advanced cervical cancer (CC. However, patients with local recurrence or distant metastasis continue to have poor outcomes. EGFR overexpression correlated with chemo/radioresistance, and disease failure has been well proved in the previous studies. Hence, the aim of this study was to explore the therapeutic efficacy and underlying mechanism of the sensitization to radiation or cisplatin of icotinib hydrochloride (IH, a high-selective EGFR tyrosine kinase inhibitor (TKI, in the Hela S3 human CC cell line.Methods: Cell proliferation was measured with cell counting kit-8 (CCK-8 assay. Flow cytometry analysis was performed to examine cell cycle distribution and apoptosis. The phosphorylation of EGFR and its downstream signaling molecules were measured by Western blot analysis. γ-H2AX foci and RAD51 foci in the cellular nucleus were visualized using immunofluoresence staining. Expression levels of RAD51 in the whole cells and subceullar fractions were detected to demonstrate the impact of IH on DNA repair. Results: IH can significantly inhibit cell proliferation, redistribute cell cycle, enhance apoptosis and impair DNA damage response of Hela S3 cells following radiation or cisplatin treatment through suppressing the activation of the EGFR signaling pathway and attenuating the expression and function of homologous recombination (HR protein RAD51.Conclusion: This study suggests that IH is a potential sensitizer in radiotherapy and cisplatin-based chemotherapy for CC and RAD51 may serve as a prognosis biomarker for this combination treatment. Keywords: icotinib hydrochloride, cervical cancer, EGFR, radiotherapy, chemotherapy

  17. C. elegans ring finger protein RNF-113 is involved in interstrand DNA crosslink repair and interacts with a RAD51C homolog.

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    Hyojin Lee

    Full Text Available The Fanconi anemia (FA pathway recognizes interstrand DNA crosslinks (ICLs and contributes to their conversion into double-strand DNA breaks, which can be repaired by homologous recombination. Seven orthologs of the 15 proteins associated with Fanconi anemia are functionally conserved in the model organism C. elegans. Here we report that RNF-113, a ubiquitin ligase, is required for RAD-51 focus formation after inducing ICLs in C. elegans. However, the formation of foci of RPA-1 or FCD-2/FANCD2 in the FA pathway was not affected by depletion of RNF-113. Nevertheless, the RPA-1 foci formed did not disappear with time in the depleted worms, implying serious defects in ICL repair. As a result, RNF-113 depletion increased embryonic lethality after ICL treatment in wild-type worms, but it did not increase the ICL-induced lethality of rfs-1/rad51C mutants. In addition, the persistence of RPA-1 foci was suppressed in doubly-deficient rnf-113;rfs-1 worms, suggesting that there is an epistatic interaction between the two genes. These results lead us to suggest that RNF-113 and RFS-1 interact to promote the displacement of RPA-1 by RAD-51 on single-stranded DNA derived from ICLs.

  18. Homologous Recombination Repair Signaling in Chemical Carcinogenesis: Prolonged Particulate Hexavalent Chromium Exposure Suppresses the Rad51 Response in Human Lung Cells

    Science.gov (United States)

    Qin, Qin; Xie, Hong; Wise, Sandra S.; Browning, Cynthia L.; Thompson, Kelsey N.; Holmes, Amie L.; Wise, John Pierce

    2014-01-01

    The aim of this study was to focus on hexavalent chromium, [Cr(VI)], a chemical carcinogen and major public health concern, and consider its ability to impact DNA double strand break repair. We further focused on particulate Cr(VI), because it is the more potent carcinogenic form of Cr(VI). DNA double strand break repair serves to protect cells against the detrimental effects of DNA double strand breaks. For particulate Cr(VI), data show DNA double strand break repair must be overcome for neoplastic transformation to occur. Acute Cr(VI) exposures reveal a robust DNA double strand break repair response, however, longer exposures have not been considered. Using the comet assay, we found longer exposures to particulate zinc chromate induced concentration-dependent increases in DNA double strand breaks indicating breaks were occurring throughout the exposure time. Acute (24 h) exposure induced DNA double strand break repair signaling by inducing Mre11 foci formation, ATM phosphorylation and phosphorylated ATM foci formation, Rad51 protein levels and Rad51 foci formation. However, longer exposures reduced the Rad51 response. These data indicate a major chemical carcinogen can simultaneously induce DNA double strand breaks and alter their repair and describe a new and important aspect of the carcinogenic mechanism for Cr(VI). PMID:25173789

  19. Identification of cloned genes that complement the rad50-1, rad51-1, rad54-3 and rad55-3 mutations in yeast

    International Nuclear Information System (INIS)

    Calderon, I.L.; Contopoulou, C.R.; Mortimer, R.K.

    1982-01-01

    Plasmids that complement the rad50-1, rad51-1, rad54-3 and rad55-3 mutations in yeast, have been isolated. They were obtained by transforming strains, carrying the leu2-112 leu2-3 alleles and the particular rad mutation, with YEp13 plasmids containing near random yeast DNA inserts. Rad + clones were identified among the Leu + transformants. Integration by targeting into the RAD55 locus showed that the rad55-3 complementing plasmid contained the actual RAD55 gene. BamHI fragments from each of the plasmids that complement rad50-1, rad51-1 and rad54-3, all of which lacked Rad + activity, were subcloned into the integrating plasmid YIp5 and the hybrid plasmids were used to transform a Rad + Ura - strain to Ura + . By genetic mapping, the rad51 and rad54 subclones were shown to integrate at their respective loci. However, the rad50 subclones integrated at a site unlinked to the RAD50 locus. This suggests that no homology exists between this BamHI fragment and the RAD50 gene. Integration at the RAD54 locus of the rad54 subclone made the host cell Ura + but Rad - ; excision of the plasmid was shown to be x-ray inducible and to restore the Ura - Rad + phenotype. These results indicate that the BamHI fragment of the RAD54 plasmid is internal to the RAD54 gene. We can conclude also that the RAD54 gene is not essential as cells bearing a disrupted copy of this gene are able to survive. Additionally, a plasmid carrying an amber suppressor has been isolated and characterized

  20. A miR-590/Acvr2a/Rad51b Axis Regulates DNA Damage Repair during mESC Proliferation

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    Qidong Liu

    2014-12-01

    Full Text Available Embryonic stem cells (ESCs enable rapid proliferation that also causes DNA damage. To maintain genomic stabilization during rapid proliferation, ESCs must have an efficient system to repress genotoxic stress. Here, we show that withdrawal of leukemia inhibitory factor (LIF, which maintains the self-renewal capability of mouse ESCs (mESCs, significantly inhibits the cell proliferation and DNA damage of mESCs and upregulates the expression of miR-590. miR-590 promotes single-strand break (SSB and double-strand break (DSB damage repair, thus slowing proliferation of mESCs without influencing stemness. miR-590 directly targets Activin receptor type 2a (Acvr2a to mediate Activin signaling. We identified the homologous recombination-mediated repair (HRR gene, Rad51b, as a downstream molecule of the miR-590/Acvr2a pathway regulating the SSB and DSB damage repair and cell cycle. Our study shows that a miR-590/Acvr2a/Rad51b signaling axis ensures the stabilization of mESCs by balancing DNA damage repair and rapid proliferation during self-renewal.

  1. Yeast Srs2 Helicase Promotes Redistribution of Single-Stranded DNA-Bound RPA and Rad52 in Homologous Recombination Regulation

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    Luisina De Tullio

    2017-10-01

    Full Text Available Srs2 is a super-family 1 helicase that promotes genome stability by dismantling toxic DNA recombination intermediates. However, the mechanisms by which Srs2 remodels or resolves recombination intermediates remain poorly understood. Here, single-molecule imaging is used to visualize Srs2 in real time as it acts on single-stranded DNA (ssDNA bound by protein factors that function in recombination. We demonstrate that Srs2 is highly processive and translocates rapidly (∼170 nt per second in the 3′→5′ direction along ssDNA saturated with replication protein A (RPA. We show that RPA is evicted from DNA during the passage of Srs2. Remarkably, Srs2 also readily removes the recombination mediator Rad52 from RPA-ssDNA and, in doing so, promotes rapid redistribution of both Rad52 and RPA. These findings have important mechanistic implications for understanding how Srs2 and related nucleic acid motor proteins resolve potentially pathogenic nucleoprotein intermediates.

  2. Yeast Srs2 Helicase Promotes Redistribution of Single-Stranded DNA-Bound RPA and Rad52 in Homologous Recombination Regulation.

    Science.gov (United States)

    De Tullio, Luisina; Kaniecki, Kyle; Kwon, Youngho; Crickard, J Brooks; Sung, Patrick; Greene, Eric C

    2017-10-17

    Srs2 is a super-family 1 helicase that promotes genome stability by dismantling toxic DNA recombination intermediates. However, the mechanisms by which Srs2 remodels or resolves recombination intermediates remain poorly understood. Here, single-molecule imaging is used to visualize Srs2 in real time as it acts on single-stranded DNA (ssDNA) bound by protein factors that function in recombination. We demonstrate that Srs2 is highly processive and translocates rapidly (∼170 nt per second) in the 3'→5' direction along ssDNA saturated with replication protein A (RPA). We show that RPA is evicted from DNA during the passage of Srs2. Remarkably, Srs2 also readily removes the recombination mediator Rad52 from RPA-ssDNA and, in doing so, promotes rapid redistribution of both Rad52 and RPA. These findings have important mechanistic implications for understanding how Srs2 and related nucleic acid motor proteins resolve potentially pathogenic nucleoprotein intermediates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Identification of the meiotic toolkit in diatoms and exploration of meiosis-specific SPO11 and RAD51 homologs in the sexual species Pseudo-nitzschia multistriata and Seminavis robusta.

    Science.gov (United States)

    Patil, Shrikant; Moeys, Sara; von Dassow, Peter; Huysman, Marie J J; Mapleson, Daniel; De Veylder, Lieven; Sanges, Remo; Vyverman, Wim; Montresor, Marina; Ferrante, Maria Immacolata

    2015-11-14

    Sexual reproduction is an obligate phase in the life cycle of most eukaryotes. Meiosis varies among organisms, which is reflected by the variability of the gene set associated to the process. Diatoms are unicellular organisms that belong to the stramenopile clade and have unique life cycles that can include a sexual phase. The exploration of five diatom genomes and one diatom transcriptome led to the identification of 42 genes potentially involved in meiosis. While these include the majority of known meiosis-related genes, several meiosis-specific genes, including DMC1, could not be identified. Furthermore, phylogenetic analyses supported gene identification and revealed ancestral loss and recent expansion in the RAD51 family in diatoms. The two sexual species Pseudo-nitzschia multistriata and Seminavis robusta were used to explore the expression of meiosis-related genes: RAD21, SPO11-2, RAD51-A, RAD51-B and RAD51-C were upregulated during meiosis, whereas other paralogs in these families showed no differential expression patterns, suggesting that they may play a role during vegetative divisions. An almost identical toolkit is shared among Pseudo-nitzschia multiseries and Fragilariopsis cylindrus, as well as two species for which sex has not been observed, Phaeodactylum tricornutum and Thalassiosira pseudonana, suggesting that these two may retain a facultative sexual phase. Our results reveal the conserved meiotic toolkit in six diatom species and indicate that Stramenopiles share major modifications of canonical meiosis processes ancestral to eukaryotes, with important divergences in each Kingdom.

  4. Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype

    DEFF Research Database (Denmark)

    Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet

    2011-01-01

    A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer As...

  5. Sensing Conformational Changes in DNA upon Ligand Binding Using QCM-D. Polyamine Condensation and Rad51 Extension of DNA Layers

    KAUST Repository

    Sun, Lu

    2014-10-16

    © 2014 American Chemical Society. Biosensors, in which binding of ligands is detected through changes in the optical or electrochemical properties of a DNA layer confined to the sensor surface, are important tools for investigating DNA interactions. Here, we investigate if conformational changes induced in surface-attached DNA molecules upon ligand binding can be monitored by the quartz crystal microbalance with dissipation (QCM-D) technique. DNA duplexes containing 59-184 base pairs were formed on QCM-D crystals by stepwise assembly of synthetic oligonucleotides of designed base sequences. The DNA films were exposed to the cationic polyamines spermidine and spermine, known to condense DNA molecules in bulk experiments, or to the recombination protein Rad51, known to extend the DNA helix. The binding and dissociation of the ligands to the DNA films were monitored in real time by measurements of the shifts in resonance frequency (Δf) and in dissipation (ΔD). The QCM-D data were analyzed using a Voigt-based model for the viscoelastic properties of polymer films in order to evaluate how the ligands affect thickness and shear viscosity of the DNA layer. Binding of spermine shrinks all DNA layers and increases their viscosity in a reversible fashion, and so does spermidine, but to a smaller extent, in agreement with its lower positive charge. SPR was used to measure the amount of bound polyamines, and when combined with QCM-D, the data indicate that the layer condensation leads to a small release of water from the highly hydrated DNA films. The binding of Rad51 increases the effective layer thickness of a 59bp film, more than expected from the know 50% DNA helix extension. The combined results provide guidelines for a QCM-D biosensor based on ligand-induced structural changes in DNA films. The QCM-D approach provides high discrimination between ligands affecting the thickness and the structural properties of the DNA layer differently. The reversibility of the film

  6. Three new genetic loci (R1210C in CFH, variants in COL8A1 and RAD51B are independently related to progression to advanced macular degeneration.

    Directory of Open Access Journals (Sweden)

    Johanna M Seddon

    Full Text Available To assess the independent impact of new genetic variants on conversion to advanced stages of AMD, controlling for established risk factors, and to determine the contribution of genes in predictive models.In this prospective longitudinal study of 2765 individuals, 777 subjects progressed to neovascular disease (NV or geographic atrophy (GA in either eye over 12 years. Recently reported genetic loci were assessed for their independent effects on incident advanced AMD after controlling for 6 established loci in 5 genes, and demographic, behavioral, and macular characteristics. New variants which remained significantly related to progression were then added to a final multivariate model to assess their independent effects. The contribution of genes to risk models was assessed using reclassification tables by determining risk within cross-classified quintiles for alternative models.THREE NEW GENETIC VARIANTS WERE SIGNIFICANTLY RELATED TO PROGRESSION: rare variant R1210C in CFH (hazard ratio (HR 2.5, 95% confidence interval [CI] 1.2-5.3, P = 0.01, and common variants in genes COL8A1 (HR 2.0, 95% CI 1.1-3.5, P = 0.02 and RAD51B (HR 0.8, 95% CI 0.60-0.97, P = 0.03. The area under the curve statistic (AUC was significantly higher for the 9 gene model (.884 vs the 0 gene model (.873, P = .01. AUC's for the 9 vs 6 gene models were not significantly different, but reclassification analyses indicated significant added information for more genes, with adjusted odds ratios (OR for progression within 5 years per one quintile increase in risk score of 2.7, P<0.001 for the 9 vs 6 loci model, and OR 3.5, P<0.001 for the 9 vs. 0 gene model. Similar results were seen for NV and GA.Rare variant CFH R1210C and common variants in COL8A1 and RAD51B plus six genes in previous models contribute additional predictive information for advanced AMD beyond macular and behavioral phenotypes.

  7. Sensitization of Tumor to {sup 212}Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

    Energy Technology Data Exchange (ETDEWEB)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E. [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Brechbiel, Martin W., E-mail: martinwb@mail.nih.gov [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-03-15

    Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using {sup 212}Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by {sup 212}Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with {sup 212}Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. {sup 212}Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling.

  8. Epidermal growth factor receptor (EGFR mutation status and Rad51 determine the response of glioblastoma (GBM to multimodality therapy with cetuximab, temozolomide and radiation

    Directory of Open Access Journals (Sweden)

    Phyllis Rachelle Wachsberger

    2013-02-01

    Full Text Available Purpose: EGFR amplification and mutation (i.e., EGFRvIII are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuximab, an anti-EGFR inhibitor, the chemotherapeutic agent, temozolamide (TMZ and radiation therapy (RT Methods and Materials: In vitro and in vivo experiments were performed on two isogenic U87 GBM cell lines: one overexpressing wildtype EGFR (U87wtEGFR and the other overexpressing EGFRvIII (U87EGFRvIII. Results: Xenografts harboring EGFRvIII were more sensitive to TMZ alone and TMZ in combination with RT and/or cetuximab than xenografts expressing wtEGFR. In vitro experiments demonstrated that U87EGFRvIII-expressing tumors appear to harbor defective DNA homologous recombination repair in the form of Rad51 processing, Conclusions: The difference in sensitivity between EGFR-expressing and EGFRvIII-expressing tumors to combined modality treatment may help in the future tailoring of GBM therapy to subsets of patients expressing more or less of the EGFR mutant.

  9. Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients with Gastric Cancer

    Science.gov (United States)

    Sahasrabudhe, Ruta; Lott, Paul; Bohorquez, Mabel; Toal, Ted; Estrada, Ana P.; Suarez, John J.; Brea-Fernández, Alejandro; Cameselle-Teijeiro, José; Pinto, Carla; Ramos, Irma; Mantilla, Alejandra; Prieto, Rodrigo; Corvalan, Alejandro; Norero, Enrique; Alvarez, Carolina; Tapia, Teresa; Carvallo, Pilar; Gonzalez, Luz M.; Cock-Rada, Alicia; Solano, Angela; Neffa, Florencia; Valle, Adriana Della; Yau, Chris; Soares, Gabriela; Borowsky, Alexander; Hu, Nan; He, Li-Ji; Han, Xiao-You; Taylor, Philip R.; Goldstein, Alisa M.; Torres, Javier; Echeverry, Magdalena; Ruiz-Ponte, Clara; Teixeira, Manuel R.; Carvajal Carmona, Luis G.

    2016-01-01

    Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer. PMID:28024868

  10. Sensitization of Tumor to 212Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

    International Nuclear Information System (INIS)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

    2013-01-01

    Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using 212 Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by 212 Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with 212 Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. 212 Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling

  11. Budding yeast mms4 is epistatic with rad52 and the function of Mms4 can be replaced by a bacterial Holliday junction resolvase.

    Science.gov (United States)

    Odagiri, Nao; Seki, Masayuki; Onoda, Fumitoshi; Yoshimura, Akari; Watanabe, Sei; Enomoto, Takemi

    2003-03-01

    MMS4 of Saccharomyces cerevisiae was originally identified as the gene responsible for one of the collection of methyl methanesulfonate (MMS)-sensitive mutants, mms4. Recently it was identified as a synthetic lethal gene with an SGS1 mutation. Epistatic analyses revealed that MMS4 is involved in a pathway leading to homologous recombination requiring Rad52 or in the recombination itself, in which SGS1 is also involved. MMS sensitivity of mms4 but not sgs1, was suppressed by introducing a bacterial Holliday junction (HJ) resolvase, RusA. The frequencies of spontaneously occurring unequal sister chromatid recombination (SCR) and loss of marker in the rDNA in haploid mms4 cells and interchromosomal recombination between heteroalleles in diploid mms4 cells were essentially the same as those of wild-type cells. Although UV- and MMS-induced interchromosomal recombination was defective in sgs1 diploid cells, hyper-induction of interchromosomal recombination was observed in diploid mms4 cells, indicating that the function of Mms4 is dispensable for this type of recombination.

  12. Three new genetic loci (R1210C in CFH, variants in COL8A1 and RAD51B) are independently related to progression to advanced macular degeneration.

    Science.gov (United States)

    Seddon, Johanna M; Reynolds, Robyn; Yu, Yi; Rosner, Bernard

    2014-01-01

    To assess the independent impact of new genetic variants on conversion to advanced stages of AMD, controlling for established risk factors, and to determine the contribution of genes in predictive models. In this prospective longitudinal study of 2765 individuals, 777 subjects progressed to neovascular disease (NV) or geographic atrophy (GA) in either eye over 12 years. Recently reported genetic loci were assessed for their independent effects on incident advanced AMD after controlling for 6 established loci in 5 genes, and demographic, behavioral, and macular characteristics. New variants which remained significantly related to progression were then added to a final multivariate model to assess their independent effects. The contribution of genes to risk models was assessed using reclassification tables by determining risk within cross-classified quintiles for alternative models. THREE NEW GENETIC VARIANTS WERE SIGNIFICANTLY RELATED TO PROGRESSION: rare variant R1210C in CFH (hazard ratio (HR) 2.5, 95% confidence interval [CI] 1.2-5.3, P = 0.01), and common variants in genes COL8A1 (HR 2.0, 95% CI 1.1-3.5, P = 0.02) and RAD51B (HR 0.8, 95% CI 0.60-0.97, P = 0.03). The area under the curve statistic (AUC) was significantly higher for the 9 gene model (.884) vs the 0 gene model (.873), P = .01. AUC's for the 9 vs 6 gene models were not significantly different, but reclassification analyses indicated significant added information for more genes, with adjusted odds ratios (OR) for progression within 5 years per one quintile increase in risk score of 2.7, Padvanced AMD beyond macular and behavioral phenotypes.

  13. Specific inhibition of Wee1 kinase and Rad51 recombinase: A strategy to enhance the sensitivity of leukemic T-cells to ionizing radiation-induced DNA double-strand breaks

    International Nuclear Information System (INIS)

    Havelek, Radim; Cmielova, Jana; Kralovec, Karel; Bruckova, Lenka; Bilkova, Zuzana; Fousova, Ivana; Sinkorova, Zuzana; Vavrova, Jirina; Rezacova, Martina

    2014-01-01

    Highlights: • Pre-treatment with the inhibitors increased the sensitivity of Jurkat cells to irradiation. • Combining both inhibitors together resulted in a G2 cell cycle arrest abrogation in Jurkat. • Jurkat cells pre-treated with inhibitors were positive for γH2AX foci 24 h upon irradiation. • Pre-treatment with Rad51 RI-1 had no effect on apoptosis induction in MOLT-4 cells. • When dosed together, the combination decreased MOLT-4 cell survival. - Abstract: Present-day oncology sees at least two-thirds of cancer patients receiving radiation therapy as a part of their anticancer treatment. The objectives of the current study were to investigate the effects of the small molecule inhibitors of Wee1 kinase II (681641) and Rad51 (RI-1) on cell cycle progression, DNA double-strand breaks repair and apoptosis following ionizing radiation exposure in human leukemic T-cells Jurkat and MOLT-4. Pre-treatment with the Wee1 681641 or Rad51 RI-1 inhibitor alone increased the sensitivity of Jurkat cells to irradiation, however combining both inhibitors together resulted in a further enhancement of apoptosis. Jurkat cells pre-treated with inhibitors were positive for γH2AX foci 24 h upon irradiation. MOLT-4 cells were less affected by inhibitors application prior to ionizing radiation exposure. Pre-treatment with Rad51 RI-1 had no effect on apoptosis induction; however Wee1 681641 increased ionizing radiation-induced cell death in MOLT-4 cells

  14. Cloning of an E. coli RecA and yeast RAD51 homolog, radA, an allele of the uvsC in Aspergillus nidulans and its mutator effects.

    Science.gov (United States)

    Seong, K Y; Chae, S K; Kang, H S

    1997-04-30

    An E. coli RecA and yeast RAD51 homolog from Aspergillus nidulans, radA, has been cloned by screening genomic and cDNA libraries with a PCR-amplified probe. This probe was generated using primers carrying the conserved sequences of eukaryotic RecA homologs. The deduced amino acid sequence revealed two conserved Walker-A and -B type nucleotide-binding domains and exhibited 88%, 60%, and 53% identity with Mei-3 of Neurospora crassa, rhp51+ of Schizosaccharomyces pombe, and Rad51 of Saccharomyces cerevisiae, respectively. radA null mutants constructed by replacing the whole coding region with a selection marker showed high methyl methanesulfonate (MMS) sensitivity. Heterozygous diploids of radA disruptant with the uvsC114 mutant failed to complement with respect to MMS-sensitivity, indicating that radA is an allele of uvsC. In selecting spontaneous forward selenate resistant mutations, mutator effects were observed in radA null mutants similarly to those shown in uvsC114 mutant strains.

  15. Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype

    DEFF Research Database (Denmark)

    Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet

    2011-01-01

    for tumors of lower grade (case-only P= 6.7 × 10(-3)) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling......A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer......10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11...

  16. DNA repair genes RAD52 and SRS2, a cell wall synthesis regulator gene SMI1, and the membrane sterol synthesis scaffold gene ERG28 are important in efficient Agrobacterium-mediated yeast transformation with chromosomal T-DNA.

    Science.gov (United States)

    Ohmine, Yuta; Satoh, Yukari; Kiyokawa, Kazuya; Yamamoto, Shinji; Moriguchi, Kazuki; Suzuki, Katsunori

    2016-04-02

    Plant pathogenic Agrobacterium strains can transfer T-DNA regions of their Ti plasmids to a broad range of eukaryotic hosts, including fungi, in vitro. In the recent decade, the yeast Saccharomyces cerevisiae is used as a model host to reveal important host proteins for the Agrobacterium-mediated transformation (AMT). Further investigation is required to understand the fundamental mechanism of AMT, including interaction at the cell surface, to expand the host range, and to develop new tools. In this study, we screened a yeast mutant library for low AMT mutant strains by advantage of a chromosome type T-DNA, which transfer is efficient and independent on integration into host chromosome. By the mutant screening, we identified four mutant strains (srs2Δ, rad52Δ, smi1Δ and erg28Δ), which showed considerably low AMT efficiency. Structural analysis of T-DNA product replicons in AMT colonies of mutants lacking each of the two DNA repair genes, SRS2 and RAD52, suggested that the genes act soon after T-DNA entry for modification of the chromosomal T-DNA to stably maintain them as linear replicons and to circularize certain T-DNA simultaneously. The cell wall synthesis regulator SMI1 might have a role in the cell surface interaction between the donor and recipient cells, but the smi1Δ mutant exhibited pleiotropic effect, i.e. low effector protein transport as well as low AMT for the chromosomal T-DNA, but relatively high AMT for integrative T-DNAs. The ergosterol synthesis regulator/enzyme-scaffold gene ERG28 probably contributes by sensing a congested environment, because growth of erg28Δ strain was unaffected by the presence of donor bacterial cells, while the growth of the wild-type and other mutant yeast strains was suppressed by their presence. RAD52 and the DNA helicase/anti-recombinase gene SRS2 are necessary to form and maintain artificial chromosomes through the AMT of chromosomal T-DNA. A sterol synthesis scaffold gene ERG28 is important in the high

  17. An integrated in silico approach to analyze the involvement of single amino acid polymorphisms in FANCD1/BRCA2-PALB2 and FANCD1/BRCA2-RAD51 complex.

    Science.gov (United States)

    Doss, C George Priya; Nagasundaram, N

    2014-11-01

    Fanconi anemia (FA) is an autosomal recessive human disease characterized by genomic instability and a marked increase in cancer risk. The importance of FANCD1 gene is manifested by the fact that deleterious amino acid substitutions were found to confer susceptibility to hereditary breast and ovarian cancers. Attaining experimental knowledge about the possible disease-associated substitutions is laborious and time consuming. The recent introduction of genome variation analyzing in silico tools have the capability to identify the deleterious variants in an efficient manner. In this study, we conducted in silico variation analysis of deleterious non-synonymous SNPs at both functional and structural level in the breast cancer and FA susceptibility gene BRCA2/FANCD1. To identify and characterize deleterious mutations in this study, five in silico tools based on two different prediction methods namely pathogenicity prediction (SIFT, PolyPhen, and PANTHER), and protein stability prediction (I-Mutant 2.0 and MuStab) were analyzed. Based on the deleterious scores that overlap in these in silico approaches, and the availability of three-dimensional structures, structure analysis was carried out with the major mutations that occurred in the native protein coded by FANCD1/BRCA2 gene. In this work, we report the results of the first molecular dynamics (MD) simulation study performed to analyze the structural level changes in time scale level with respect to the native and mutated protein complexes (G25R, W31C, W31R in FANCD1/BRCA2-PALB2, and F1524V, V1532F in FANCD1/BRCA2-RAD51). Analysis of the MD trajectories indicated that predicted deleterious variants alter the structural behavior of BRCA2-PALB2 and BRCA2-RAD51 protein complexes. In addition, statistical analysis was employed to test the significance of these in silico tool predictions. Based on these predictions, we conclude that the identification of disease-related SNPs by in silico methods, in combination with MD

  18. Games Uniforms Unveiled

    Institute of Scientific and Technical Information of China (English)

    Linda

    2008-01-01

    The uniforms for Beijing Olympics’ workers, technical staff and volunteers have been unveiled to mark the 200-day countdown to the Games. The uniforms feature the key element of the clouds of promise and will be in three colors:red for Beijing Olympic Games Committee staff, blue

  19. Lord Shiva Statue Unveiled

    CERN Multimedia

    2004-01-01

    On 18 June, CERN unveiled an unusual new landmark, a 2m tall statue of the Indian deity Lord Shiva. The Director-General and Dr. Kakodkar watch as Mr.Chandrasekhar signs the Guest Book. The statue is a gift from India, celebrating CERN's long association with India which started in the 1960's and continues strongly today. It was unveiled by the Director General, Dr Robert Aymar, His Excellency Mr K. M. Chandrasekhar, Ambassador (WTO-Geneva) and Dr Anil Kakodkar, Chairman of the Atomic Energy Commission and Secretary, Dept of Atomic Energy, India. In the Hindu religion, this form of the dancing Lord Shiva is known as the Nataraj and symbolises Shakti, or life force. As a plaque alongside the statue explains, the belief is that Lord Shiva danced the Universe into existence, motivates it, and will eventually extinguish it. Carl Sagan drew the metaphor between the cosmic dance of the Nataraj and the modern study of the 'cosmic dance' of subatomic particles. The statue was made in India. The original sculpture was...

  20. Protein dynamics during presynaptic complex assembly on individual ssDNA molecules

    OpenAIRE

    Gibb, Bryan; Ye, Ling F.; Kwon, YoungHo; Niu, Hengyao; Sung, Patrick; Greene, Eric C.

    2014-01-01

    Homologous recombination is a conserved pathway for repairing double?stranded breaks, which are processed to yield single?stranded DNA overhangs that serve as platforms for presynaptic complex assembly. Here we use single?molecule imaging to reveal the interplay between Saccharomyce cerevisiae RPA, Rad52, and Rad51 during presynaptic complex assembly. We show that Rad52 binds RPA?ssDNA and suppresses RPA turnover, highlighting an unanticipated regulatory influence on protein dynamics. Rad51 b...

  1. Molecular Pathways

    Science.gov (United States)

    Lok, Benjamin H.; Powell, Simon N.

    2012-01-01

    The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

  2. Contribution of Germline Mutations in the RAD51B>, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population

    DEFF Research Database (Denmark)

    Song, Honglin; Dicks, Ed; Ramus, Susan J

    2015-01-01

    Screening Study (UK_FOCSS) after quality-control analysis. RESULTS: In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P

  3. Localization of recombination proteins and Srs2 reveals anti-recombinase function in vivo

    DEFF Research Database (Denmark)

    Burgess, Rebecca C; Lisby, Michael; Altmannova, Veronika

    2009-01-01

    , and surprisingly, can form in the absence of Rad52 mediation. However, these Rad51 foci do not represent repair-proficient filaments, as determined by recombination assays. Antagonistic roles for Rad52 and Srs2 in Rad51 filament formation are also observed in vitro. Furthermore, we provide evidence that Srs2......Homologous recombination (HR), although an important DNA repair mechanism, is dangerous to the cell if improperly regulated. The Srs2 "anti-recombinase" restricts HR by disassembling the Rad51 nucleoprotein filament, an intermediate preceding the exchange of homologous DNA strands. Here, we...... removes Rad51 indiscriminately from DNA, while the Rad52 protein coordinates appropriate filament reformation. This constant breakdown and rebuilding of filaments may act as a stringent quality control mechanism during HR....

  4. Protein dynamics during presynaptic complex assembly on individual ssDNA molecules

    Science.gov (United States)

    Gibb, Bryan; Ye, Ling F.; Kwon, YoungHo; Niu, Hengyao; Sung, Patrick; Greene, Eric C.

    2014-01-01

    Homologous recombination is a conserved pathway for repairing double–stranded breaks, which are processed to yield single–stranded DNA overhangs that serve as platforms for presynaptic complex assembly. Here we use single–molecule imaging to reveal the interplay between Saccharomyce cerevisiae RPA, Rad52, and Rad51 during presynaptic complex assembly. We show that Rad52 binds RPA–ssDNA and suppresses RPA turnover, highlighting an unanticipated regulatory influence on protein dynamics. Rad51 binding extends the ssDNA, and Rad52–RPA clusters remain interspersed along the presynaptic complex. These clusters promote additional binding of RPA and Rad52. Together, our work illustrates the spatial and temporal progression of RPA and Rad52 association with the presynaptic complex, and reveals a novel RPA–Rad52Rad51–ssDNA intermediate, which has implications for understanding how the activities of Rad52 and RPA are coordinated with Rad51 during the later stages recombination. PMID:25195049

  5. France: the programme of festivities is unveiled

    CERN Multimedia

    2004-01-01

    The programme of events to be held in the local French area in honour of CERN's fiftieth anniversary was unveiled in the CMS hall on 26 April at a ceremony attended by many local authority representatives.

  6. Rad52 SUMOylation affects the efficiency of the DNA repair

    DEFF Research Database (Denmark)

    Altmannova, Veronika; Eckert-Boulet, Nadine; Arneric, Milica

    2010-01-01

    Homologous recombination (HR) plays a vital role in DNA metabolic processes including meiosis, DNA repair, DNA replication and rDNA homeostasis. HR defects can lead to pathological outcomes, including genetic diseases and cancer. Recent studies suggest that the post-translational modification by ...

  7. Georges Charpak street sign unveiled

    CERN Multimedia

    Paola Catapano

    2011-01-01

    While it might not be the only French street named in honour of the late Georges Charpak, who passed away in September 2010 at the age of 87, the street chosen by the mayor of Saint-Genis-Pouilly is certainly the only one located directly opposite the CERN "campus". The road overlooks buildings on the CERN Meyrin site, where Georges Charpak spent most of his career as a physicist, conducting the research that won him the Nobel Prize in Physics in 1992.   From left to right: Sigurd Lettow, Dominique Charpak and the mayor of Saint-Genis-Pouilly. The unveiling took place on 17 October and was organised by the mayor of Saint-Genis-Pouilly. George Charpak’s wife, Dominique, and Sigurd Lettow, CERN Director of Administration and General Infrastructure, attended what was an intimate and touching ceremony. The mayor’s speech at the event praised Georges’ commitment to scientific education. The highlight of the event, however, was a witty and humorous ...

  8. Split dose recovery studies using homologous recombination deficient gene knockout chicken B lymphocyte cells

    International Nuclear Information System (INIS)

    Rao, B.S.S.; Tano, Kaori; Utsumi, Hiroshi; Takeda, Shunichi

    2007-01-01

    To understand the role of proteins involved in double strand breaks (DSB) repair modulating sublethal damage (SLD) recovery, chicken B lymphoma (DT 40) cell lines either proficient or deficient in RAD52, XRCC2, XRCC3, RAD51C and RAD51D were subjected to fractionated irradiation and their survival curves charted. Survival curves of both WT DT40 and RAD52 -/- cells had a big shoulder while all the other cells exhibited small shoulders. However, at the higher doses of radiation, RAD51C -/- cells displayed hypersensitivity comparable to the data obtained for the homologous recombination deficient RAD54 -/- cells. Repair of SLD was measured as an increase in survival after a split dose irradiation with an interval of incubation between the radiation doses. All the cell lines (parental DT40 and genetic knockout cell lines viz., RAD52 -/- , XRCC2 -/- XRCC3 -/- RAD51C -/- and RAD51D -/- ) used in this study demonstrated a typical split-dose recovery capacity with a specific peak, which varied depending on the cell type. The maximum survival of WT DT40 and RAD52 -/- was reached at about 1-2 hours after the first dose of radiation and then decreased to a minimum thereafter (5 h). The increase in the survival peaked once again by about 8 hours. The survival trends observed in XRCC2 -/- , XRCC3 -/- , RAD51C -/- and RAD51D -/- knockout cells were also similar, except for the difference in the initial delay of a peak survival for RAD51D -/- and lower survival ratios. The second phase of increase in the survival in these cell lines was much slower in XRCC2 -/- , XRCC3 -/- , RAD51C -/- nd RAD51D -/- and further delayed when compared with that of RAD52 -/- and parental DT40 cells suggesting a dependence on their cell cycle kinetics. This study demonstrates that the participation of RAD52, XRCC2, XRCC3, RAD51C and RAD51D in the DSB repair via homologous recombination is of less importance in comparison to RAD54, as RAD54 deficient cells demonstrated complete absence of SLD recovery

  9. Germany unveils €18bn research plan

    Science.gov (United States)

    Banks, Michael

    2009-07-01

    The German government has unveiled an ambitious plan to inject a total of €18bn into teaching and research over the next decade. The German chancellor Angela Merkel, who has a degree in physics, announced that she was releasing the funds despite concerns from her social-democrat coalition partners that financing the package could be difficult in the economic downturn.

  10. Cash boost to Great British science unveiled

    CERN Multimedia

    2002-01-01

    "Trade and Industry Secretary, Patricia Hewitt today unveiled new plans for the DTI's record science budget over the next three years, to keep Britain at the forefront of world science. The plans include funding to develop life saving new health techniques, to seek alternative energy sources, to help our rural economy, to develop the computers of tomorrow and boost business with the next generation of leading edge technologies" (1 page).

  11. Unveiling DNA structural properties of promoter regions of ...

    Indian Academy of Sciences (India)

    Aditya Kumar

    Unveiling DNA structural properties of promoter regions of prokaryotic transcriptome and their role in gene expression. Aditya Kumar. Assistant Professor. Molecular Biology & Biotechnology. Tezpur University. Tezpur – 784028, Assam ...

  12. Cumulative dosage effect of a RAD51L1/HMGA2 fusion and RAD51L1 loss in a case of pseudo-Meigs' syndrome.

    NARCIS (Netherlands)

    Amant, F.; Debiec-Rychter, M.; Schoenmakers, E.F.P.M.; Hagemeijer-Hausman, A.; Vergote, I.

    2001-01-01

    Uterine leiomyoma presenting with ascites and pleural fluid is referred to as pseudo-Meigs' syndrome. It is unclear whether common uterine leiomyomas and uterine leiomyomas causing pseudo-Meigs' syndrome are cytogenetically related or whether functionally different primary pathogenetic triggers are

  13. Unveiling Reality of the Mind: Cultural Arbitrary of Consumerism

    Science.gov (United States)

    Choi, Su-Jin

    2012-01-01

    This paper discusses the cultural arbitrary of consumerism by focusing on a personal realm. That is, I discuss what consumerism appeals to and how it flourishes in relation to our minds. I argue that we need to unveil reality of the mind, be aware of ourselves in relation to the perpetuation of consumerism, in order to critically intervene in the…

  14. Book review: Unveiling the Whale: Discourses on Whales and Whaling

    Science.gov (United States)

    John Schelhas

    2012-01-01

    Whaling represents one of the most internationally controversial and highly polarized environmental issues of recent times. Arne Kalland, in Unveiling the Whale: Discourses on Whales and Whaling, examines the whaling issue from the perspective of a pro-whaling country with an emphasis on analysis of discourse in international arenas, primarily the International Whaling...

  15. Proofpoint unveils the industry's most advanced anti-spam laboratory

    CERN Multimedia

    2003-01-01

    "Proofpoint, Inc., the leader in large enterprise anti-spam solutions, today unveiled its Anti-Spam Laboratory, the world's most advanced center for spam research and analysis, and the first to be based on advanced Machine Learning science" (1 page).

  16. First National Picture of Trends in the Humanities Is Unveiled

    Science.gov (United States)

    Howard, Jennifer

    2009-01-01

    When it comes to hard data about what they do, policy makers and educators in the humanities have been mostly left out in the cold, forced to rely on isolated statistics that do not give an overview of the field. That changed this month, as the American Academy of Arts and Sciences unveiled the prototype of its long-awaited Humanities Indicators…

  17. Universe unveiled the cosmos in my bubble bath

    CERN Document Server

    Vishveshwara, C V

    2015-01-01

    The bubbles were swirling all around me, massaging my body. As I luxuriated in this fantastic bath, I gasped realizing that those bubbles carried with them miniature galaxies bringing the entire Cosmos into my bathtub... Alfie is back. And so are George and other characters from the author’s previous book Einstein’s Enigma or Black Holes in My Bubble Bath. While the present book, Universe Unveiled - The Cosmos in My Bubble Bath, is completely independent, its storyline can be considered a sequel to the previous one. The scientific content spanning ancient world models to the most recent mysteries of cosmology is presented in an entirely nontechnical and descriptive style through the discussions between Alfie, the enlightened learner, and George, professor of astrophysics. Fantasies, based on these discussions that cover the scientific facts, are created by the magical bubble baths taken by Alfie. Universe Unveiled blends accurate science with philosophy, drama, humour, and fantasy to create an exciting co...

  18. ESA Unveils Its New Comet Chaser.

    Science.gov (United States)

    1999-07-01

    The objective is to study one of these primordial objects at close quarters by placing a lander on its surface and chasing, with an orbiter, the comet for millions of kilometres through space. Comets - among the oldest (4.6 billion years!) and last altered objects in the solar system - are regarded as the building blocks from which the planets formed. Thus the Rosetta's discoveries will allow the scientists to learn more about birth and evolution of the planets and about the origin of life on the Earth. The final design of the Rosetta orbiter will be revealed for the first time at the Royal Society in London on 1 July when a 1:4 scale model will be unveiled by ESA's Director of Science, Prof.. Roger Bonnet. (The full size version of the spacecraft is 32 metres across, so large that it would stretch the entire width of a football pitch. Almost 90 of this is accounted for by the giant solar panels which are needed to provide electrical power in the dark depths of the Solar System). "Rosetta is a mission of major scientific importance," said Prof. Bonnet. "It will build on the discoveries made by Giotto and confirm ESA's leading role in the exploration of the Solar System and the Universe as a whole." The timing of this event has been chosen to coincide with the London meeting of the Rosetta Science Working Team and the second Earth flyby of the now non-operational Giotto spacecraft. In addition, the opening of the British Museum's 'Cracking Codes' Exhibition, for which the Rosetta Stone is the centrepiece, is set to take place on 10 July. The Rosetta mission. Rosetta is the third Cornerstone in ESA's 'Horizon 2000' long-term scientific programme. It will be launched by Ariane 5 rocket from Kourou spaceport in French Guiana in January 2003. In order to gain sufficient speed to reach the distant comet, Rosetta will require gravity assists from the Earth (twice) and Mars. After swinging around Mars in May 2005, Rosetta will return to Earth's vicinity in October 2005 and

  19. A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51

    NARCIS (Netherlands)

    Ameziane, Najim; May, Patrick; Haitjema, Anneke; van de Vrugt, Henri J.; van Rossum-Fikkert, Sari E.; Ristic, Dejan; Williams, Gareth J.; Balk, Jesper; Rockx, Davy; Li, Hong; Rooimans, Martin A.; Oostra, Anneke B.; Velleuer, Eunike; Dietrich, Ralf; Bleijerveld, Onno B.; Maarten Altelaar, A. F.; Meijers-Heijboer, Hanne; Joenje, Hans; Glusman, Gustavo; Roach, Jared; Hood, Leroy; Galas, David; Wyman, Claire; Balling, Rudi; den Dunnen, Johan; de Winter, Johan P.; Kanaar, Roland; Gelinas, Richard; Dorsman, Josephine C.

    2015-01-01

    Fanconi anaemia (FA) is a hereditary disease featuring hypersensitivity to DNA cross-linker-induced chromosomal instability in association with developmental abnormalities, bone marrow failure and a strong predisposition to cancer. A total of 17 FA disease genes have been reported, all of which act

  20. Physical interaction of RECQ5 helicase with RAD51 facilitates its anti-recombinase activity

    Czech Academy of Sciences Publication Activity Database

    Schwendener, S.; Raynard, S.; Paliwal, S.; Cheng, A.; Kanagaraj, R.; Shevelev, Igor; Stark, J.M.; Sung, P.; Janscak, P.

    2010-01-01

    Roč. 285, č. 21 (2010), s. 15739-15745 ISSN 0021-9258 Grant - others:NIH(US) R01CA120954; NIH(US) ES015632; SNSF(CH) 3100A0-116008 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA helicase * double-strand breaks * homologous recombination Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.328, year: 2010

  1. FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51

    DEFF Research Database (Denmark)

    Chu, Wai Kit; Payne, Miranda J; Beli, Petra

    2015-01-01

    Unscheduled homologous recombination (HR) can lead to genomic instability, which greatly increases the threat of neoplastic transformation in humans. The F-box DNA helicase 1 (FBH1) is a 3'-5' DNA helicase with a putative function as a negative regulator of HR. It is the only known DNA helicase t...

  2. FBH1 Helicase Disrupts RAD51 Filaments in Vitro and Modulates Homologous Recombination in Mammalian Cells

    Czech Academy of Sciences Publication Activity Database

    Šimandlová, Jitka; Zagelbaum, J.; Payne, M.J.; Chu, W.K.; Shevelev, Igor; Hanada, K.; Chatterjee, S.; Reid, D.A.; Liu, Y.; Janščák, Pavel; Rothenberg, E.; Hickson, I.D.

    2013-01-01

    Roč. 288, č. 47 (2013), s. 34168-34180 ISSN 0021-9258 R&D Projects: GA ČR GAP305/10/0281 Institutional support: RVO:68378050 Keywords : DNA damage * DNA helicase * DNA recombination * DNA repair * DNA replication Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.600, year: 2013

  3. Inactivation of RAD52 and HDF1 DNA repair genes leads to ...

    Indian Academy of Sciences (India)

    Silvia Mercado-Sáenz

    2017-04-18

    Apr 18, 2017 ... such as water or synthetic dextrose complete (SDC). (Fabrizio et al. ..... (ANOVA) (treatment x time) and the Student's t-test. P- values reported are ..... Madeo F, Frohlich E, Ligr M, Grey M, Sigrist SJ, Wolf DH and. Frohlich KU ...

  4. Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre

    DEFF Research Database (Denmark)

    Lisby, M.; Mortensen, Uffe Hasbro; Rothstein, R.

    2003-01-01

    DNA double-strand break repair (DSBR) is an essential process for preserving genomic integrity in all organisms. To investigate this process at the cellular level, we engineered a system of fluorescently marked DNA double-strand breaks (DSBs) in the yeast Saccharomyces cerevisiae to visualize in ...

  5. SUMOylation of Rad52-Rad59 synergistically change the outcome of mitotic recombination

    DEFF Research Database (Denmark)

    Silva, Sonia; Altmannova, Veronika; Eckert-Boulet, Nadine

    2016-01-01

    Homologous recombination (HR) is essential for maintenance of genome stability through double-strand break (DSB) repair, but at the same time HR can lead to loss of heterozygosity and uncontrolled recombination can be genotoxic. The post-translational modification by SUMO (small ubiquitin...

  6. RPA mediates recombination repair during replication stress and is displaced from DNA by checkpoint signalling in human cells

    DEFF Research Database (Denmark)

    Sleeth, Kate M; Sørensen, Claus Storgaard; Issaeva, Natalia

    2007-01-01

    The replication protein A (RPA) is involved in most, if not all, nuclear metabolism involving single-stranded DNA. Here, we show that RPA is involved in genome maintenance at stalled replication forks by the homologous recombination repair system in humans. Depletion of the RPA protein inhibited...... the formation of RAD51 nuclear foci after hydroxyurea-induced replication stalling leading to persistent unrepaired DNA double-strand breaks (DSBs). We demonstrate a direct role of RPA in homology directed recombination repair. We find that RPA is dispensable for checkpoint kinase 1 (Chk1) activation...... and that RPA directly binds RAD52 upon replication stress, suggesting a direct role in recombination repair. In addition we show that inhibition of Chk1 with UCN-01 decreases dissociation of RPA from the chromatin and inhibits association of RAD51 and RAD52 with DNA. Altogether, our data suggest a direct role...

  7. Resolving the Gordian Knot: Srs2 Strips Intermediates Formed during Homologous Recombination.

    Science.gov (United States)

    Ghodke, Harshad; Lewis, Jacob S; van Oijen, Antoine M

    2018-03-01

    Cells use a suite of specialized enzymes to repair chromosomal double-strand breaks (DSBs). Two recent studies describe how single-molecule fluorescence imaging techniques are used in the direct visualization of some of the key molecular steps involved. De Tullio et al. and Kaniecki et al. watch individual Srs2 helicase molecules disrupt repair intermediates formed by RPA, Rad51, and Rad52 on DNA during homologous recombination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. 'THE UNVEILED HEART' a teaching program in cardiovascular nuclear medicine

    International Nuclear Information System (INIS)

    Itti, Roland; Merabet, Yasmina; Roca, Ramona; Bontemps, Laurence; Itti, Emmanuel

    2004-01-01

    The functional investigation of cardiac diseases using nuclear techniques involves several variables, such as myocardial perfusion, cellular viability or mechanical contraction. The combined, topographical and quantitative assessment of these variables can characterize the functional state of the heart in terms of normal myocardium, ischemia, hibernation or necrosis. The teaching program, 'The Unveiled Heart', has been designed in order to help nuclear physicians or cardiologists approaching these concepts and their implications for diagnosis of coronary artery disease, optimization of therapeutic strategies and prognosis evaluation. Anatomical correlations with coronary angiographic results obtained during balloon occlusion at the time of coronary angioplasty demonstrate the complementary role of imaging techniques and highlight the patient to patient variability of risk areas. A sectorial model derived from a polar projection of the myocardium presents for each sector the probability of involvement of a given coronary artery

  9. Photonic integrated circuits unveil crisis-induced intermittency.

    Science.gov (United States)

    Karsaklian Dal Bosco, Andreas; Akizawa, Yasuhiro; Kanno, Kazutaka; Uchida, Atsushi; Harayama, Takahisa; Yoshimura, Kazuyuki

    2016-09-19

    We experimentally investigate an intermittent route to chaos in a photonic integrated circuit consisting of a semiconductor laser with time-delayed optical feedback from a short external cavity. The transition from a period-doubling dynamics to a fully-developed chaos reveals a stage intermittently exhibiting these two dynamics. We unveil the bifurcation mechanism underlying this route to chaos by using the Lang-Kobayashi model and demonstrate that the process is based on a phenomenon of attractor expansion initiated by a particular distribution of the local Lyapunov exponents. We emphasize on the crucial importance of the distribution of the steady-state solutions introduced by the time-delayed feedback on the existence of this intermittent dynamics.

  10. Dynamic organization of genetic recombination proteins and chromosomes

    International Nuclear Information System (INIS)

    Essers, J.; Van Cappellen, G.; Van Drunen, E.; Theil, A.; Jaspers, N.N.G.J.; Houtsmuller, A.B.; Vermeulen, W.; Kanaar, R.

    2003-01-01

    Homologous recombination requires the co-ordinated action of the RAD52 group proteins, including Rad51, Rad52 and Rad54. Upon treatment of mammalian cells with ionizing radiation, these proteins accumulate into foci at sites of DSB induction. We probed the nature of the DNA damage-induced foci in living cells with the use of photobleaching techniques. These foci are not static assemblies of DNA repair proteins. Instead, they are dynamic structures of which Rad51 is a stable core component, while Rad52 and Rad54 reversibly interact with the structure. Furthermore, even though the RAD52 group proteins colocalize in the DNA damage-induced foci, the majority of the proteins are not part of the same multi-protein complex in the absence of DNA damage. Executing DNA transactions through dynamic multi-protein complexes, rather than stable holo-complexes, allows greater flexibility during the transaction. In case of DNA repair, for example, it allows cross talk between different DNA repair pathways and coupling to other DNA transactions, such as replication. In addition to the behavior of proteins in living cells, we have tracked chromosomes during cell division. Our results suggest that the relative position of chromosomes in the mother cell is conserved in its daughter cells

  11. Traditional Islamic cities unveiled: the quest for urban design regularity

    Directory of Open Access Journals (Sweden)

    Jorge Correia

    2015-08-01

    Full Text Available Traditional Islamic cities have generally gathered orientalized gazes and perspectives, picking up from misconceptions and stereotypes that during the second half af the 19th century andwere perpectuated by colonialism. More recent scholarship has shed light on the urban organizationand composition of such tissues; most of them confined to old quarters or historical centres ofthriving contemporary cities within the Arab-Muslim world. In fact, one of the most striking featureshas been the unveiling of layered urban assemblages where exterior agents have somehowlaunched or interrupted an apparent islamicized continuum. Primarly, this paper wishes to search forexternal political factors that have designed regularly geometrized patterns in medium-sized Arabtowns. For that, two case studies from different geographies - Maghreb and the Near East - will bemorphologically analysed through updated urban surveys. Whereas Nablus (Palestine ows the urbanmatrix of its old town to its Roman past, in Azemmour’s medina (Morocco it is still possible to trackthe thin European early-modern colonial stratum. However, both cases show how regularity patternschallenge Western concepts of geometrical design to embrace levels of rationality related to tradionalIslamic urban forms, societal configurations and built environment. Urban morphology becomes afundamental tool for articulating the history with me processes of sedimentation and evolution in orderto read current urban prints and dynamics. Thus, the paper will also interpret alternative logics ofrational urban display in Azemmour and Nablus, linked to ways of living within the Islamic sphere.

  12. Tempo and mode of genomic mutations unveil human evolutionary history.

    Science.gov (United States)

    Hara, Yuichiro

    2015-01-01

    Mutations that have occurred in human genomes provide insight into various aspects of evolutionary history such as speciation events and degrees of natural selection. Comparing genome sequences between human and great apes or among humans is a feasible approach for inferring human evolutionary history. Recent advances in high-throughput or so-called 'next-generation' DNA sequencing technologies have enabled the sequencing of thousands of individual human genomes, as well as a variety of reference genomes of hominids, many of which are publicly available. These sequence data can help to unveil the detailed demographic history of the lineage leading to humans as well as the explosion of modern human population size in the last several thousand years. In addition, high-throughput sequencing illustrates the tempo and mode of de novo mutations, which are producing human genetic variation at this moment. Pedigree-based human genome sequencing has shown that mutation rates vary significantly across the human genome. These studies have also provided an improved timescale of human evolution, because the mutation rate estimated from pedigree analysis is half that estimated from traditional analyses based on molecular phylogeny. Because of the dramatic reduction in sequencing cost, sequencing on-demand samples designed for specific studies is now also becoming popular. To produce data of sufficient quality to meet the requirements of the study, it is necessary to set an explicit sequencing plan that includes the choice of sample collection methods, sequencing platforms, and number of sequence reads.

  13. Hidden temporal order unveiled in stock market volatility variance

    Directory of Open Access Journals (Sweden)

    Y. Shapira

    2011-06-01

    Full Text Available When analyzed by standard statistical methods, the time series of the daily return of financial indices appear to behave as Markov random series with no apparent temporal order or memory. This empirical result seems to be counter intuitive since investor are influenced by both short and long term past market behaviors. Consequently much effort has been devoted to unveil hidden temporal order in the market dynamics. Here we show that temporal order is hidden in the series of the variance of the stocks volatility. First we show that the correlation between the variances of the daily returns and means of segments of these time series is very large and thus cannot be the output of random series, unless it has some temporal order in it. Next we show that while the temporal order does not show in the series of the daily return, rather in the variation of the corresponding volatility series. More specifically, we found that the behavior of the shuffled time series is equivalent to that of a random time series, while that of the original time series have large deviations from the expected random behavior, which is the result of temporal structure. We found the same generic behavior in 10 different stock markets from 7 different countries. We also present analysis of specially constructed sequences in order to better understand the origin of the observed temporal order in the market sequences. Each sequence was constructed from segments with equal number of elements taken from algebraic distributions of three different slopes.

  14. Unveiling protein functions through the dynamics of the interaction network.

    Directory of Open Access Journals (Sweden)

    Irene Sendiña-Nadal

    Full Text Available Protein interaction networks have become a tool to study biological processes, either for predicting molecular functions or for designing proper new drugs to regulate the main biological interactions. Furthermore, such networks are known to be organized in sub-networks of proteins contributing to the same cellular function. However, the protein function prediction is not accurate and each protein has traditionally been assigned to only one function by the network formalism. By considering the network of the physical interactions between proteins of the yeast together with a manual and single functional classification scheme, we introduce a method able to reveal important information on protein function, at both micro- and macro-scale. In particular, the inspection of the properties of oscillatory dynamics on top of the protein interaction network leads to the identification of misclassification problems in protein function assignments, as well as to unveil correct identification of protein functions. We also demonstrate that our approach can give a network representation of the meta-organization of biological processes by unraveling the interactions between different functional classes.

  15. Called to respond: The potential of unveiling hiddens

    Directory of Open Access Journals (Sweden)

    Alison L Black

    2014-12-01

    Full Text Available Interested in exploring how personal stories and aesthetic modes of representing experiences can nudge open academic and educational spaces, this article/collection of particles seeks to document our encounters of being affected and called to respond to things the other has written and represented. As a way of engaging with questions about what research and research data might be and become, our attention has been drawn to stories and images from our lives that we have not shaken off – and to how, as we have opened these to the other, making once private moments public, our hiddens have morphed tenderly into a shared knowing and being. As we have acted on the call we have felt to respond we have found ourselves entering spaces of collaboration, communion, contemplation, and conversation – spaces illuminated by what we have not been able to – and cannot – set aside. Using visual and poetic materials we explore heartfelt and heartbroken aspects of our educational worlds and lives, to be present with each other and our (reemerging personal and professional meanings. We see the shared body (of work, of writing, of image that develops from the taking of brave steps and the risky slipping off of academic masks and language, as a manifestation of the trusted and nurturing spaces that can be generated through collaborative opportunities to gather together. These steps towards unveiling hiddens are producing in us and of us a friendship, fluency, and fluidity as we write new ways of becoming. In turn, we hope the uncovering and revealing of our dialogue in the public gathering of this journal might supports readers’ telling of their own life stories through what calls them to respond.

  16. Functions and structures of eukaryotic recombination proteins

    International Nuclear Information System (INIS)

    Ogawa, Tomoko

    1994-01-01

    We have found that Rad51 and RecA Proteins form strikingly similar structures together with dsDNA and ATP. Their right handed helical nucleoprotein filaments extend the B-form DNA double helixes to 1.5 times in length and wind the helix. The similarity and uniqueness of their structures must reflect functional homologies between these proteins. Therefore, it is highly probable that similar recombination proteins are present in various organisms of different evolutional states. We have succeeded to clone RAD51 genes from human, mouse, chicken and fission yeast genes, and found that the homologues are widely distributed in eukaryotes. The HsRad51 and MmRad51 or ChRad51 proteins consist of 339 amino acids differing only by 4 or 12 amino acids, respectively, and highly homologous to both yeast proteins, but less so to Dmcl. All of these proteins are homologous to the region from residues 33 to 240 of RecA which was named ''homologous core. The homologous core is likely to be responsible for functions common for all of them, such as the formation of helical nucleoprotein filament that is considered to be involved in homologous pairing in the recombination reaction. The mouse gene is transcribed at a high level in thymus, spleen, testis, and ovary, at lower level in brain and at a further lower level in some other tissues. It is transcribed efficiently in recombination active tissues. A clear functional difference of Rad51 homologues from RecA was suggested by the failure of heterologous genes to complement the deficiency of Scrad51 mutants. This failure seems to reflect the absence of a compatible partner, such as ScRad52 protein in the case of ScRad51 protein, between different species. Thus, these discoveries play a role of the starting point to understand the fundamental gene targeting in mammalian cells and in gene therapy. (J.P.N.)

  17. Nasa Unveils Cosmic Images Book in Braille for Blind Readers

    Science.gov (United States)

    2008-01-01

    BALTIMORE - At a Tuesday ceremony at the National Federation of the Blind, NASA unveiled a new book that brings majestic images taken by its Great Observatories to the fingertips of the blind. "Touch the Invisible Sky" is a 60-page book with color images of nebulae, stars, galaxies and some of the telescopes that captured the original pictures. Each image is embossed with lines, bumps and other textures. These raised patterns translate colors, shapes and other intricate details of the cosmic objects, allowing visually impaired people to experience them. Braille and large-print descriptions accompany each of the book's 28 photographs, making the book's design accessible to readers of all visual abilities. Sample page Sample page The book contains spectacular images from the Hubble Space Telescope, Chandra X-ray Observatory, Spitzer Space Telescope and powerful ground-based telescopes. The celestial objects are presented as they appear through visible-light telescopes and different spectral regions invisible to the naked eye, from radio to infrared, visible, ultraviolet and X-ray light. The book introduces the concept of light and the spectrum and explains how the different observatories complement each others' findings. Readers take a cosmic journey beginning with images of the sun, and travel out into the galaxy to visit relics of exploding and dying stars, as well as the Whirlpool galaxy and colliding Antennae galaxies. People Who Read This Also Read... Chandra Data Reveal Rapidly Whirling Black Holes Jet Power and Black Hole Assortment Revealed in New Chandra Image Action Replay of Powerful Stellar Explosion Black Holes Are The Rhythm at The Heart of Galaxies "Touch the Invisible Sky" was written by astronomy educator and accessibility specialist Noreen Grice of You Can Do Astronomy LLC and the Museum of Science, Boston, with authors Simon Steel, an astronomer with the Harvard-Smithsonian Center for Astrophysics in Cambridge, Mass., and Doris Daou, an astronomer

  18. Rec2 Interplay with both Brh2 and Rad51 Balances Recombinational Repair in Ustilago maydis

    DEFF Research Database (Denmark)

    Kojic, M.; Zhou, Q.; Lisby, M.

    2006-01-01

    and allelic recombination are elevated. The Dss1-independent Brh2-RPA70 fusion protein is also active in restoring radiation sensitivity of rec2 but is hyperactive to an extreme degree in allelic recombination and in suppressing the meiotic block of rec2. However, the high frequency of chromosome...

  19. Old Wine in New Wine Skins: Tombstone Unveiling as a Case of ...

    African Journals Online (AJOL)

    This article reflects on the practice of Tombstone Unveiling, a recent phenomenon among Shona Christians in Zimbabwe, as a case of religious change. Historically, many church doctrines and practices have been negative towards African Traditional Religions (ATRs). Shona Christians have reacted by trying to ...

  20. Atomic Force Microscopy - A Tool to Unveil the Mystery of Biological ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 15; Issue 7. Atomic Force Microscopy - A Tool to Unveil the Mystery of Biological Systems ... Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 ...

  1. Unveiling EFL and Self-Contained Teachers’ Discourses on Bilingualism Within the Context of Professional Development

    Directory of Open Access Journals (Sweden)

    Jennyfer Paola Camargo Cely

    2018-01-01

    Full Text Available Throughout time, the predominant use of certain languages has allowed some nations to take control over others and assure for them a privileged position. This study unveiled how certain practices and ideologies in regard to bilingualism have influenced teachers’ professional development. Data were collected through discussion group sessions, reflective journals, and protocols from five teachers from a private K-11 school in Bogota. Analysis indicated participants’ discourses drew on hegemonic, colonial, and manipulative ideas. Nevertheless, when dialoguing and peer coaching, a discourse of resistance was constituted. The study suggested further research into teachers’ professional growth, bilingualism, and bilingual education in monolingual contexts as the Colombian one.

  2. Uzbekistan unveiled

    International Nuclear Information System (INIS)

    Mazurkevich, A.P.

    1993-01-01

    Through centuries of revolution, war and strife, the people of Uzbekistan have built a reputation as skilled and tenacious merchants. Since antiquity, when the Silk Road from China turned toward Europe at Smarakand, they have been master traders of such valuable commodities as cotton, fruits, vegetables, spices and gold. Now, they're about to introduce another of their specialties to the world: Uranium. Uranium mining in the country is controlled by a new, independent company, the Kizilkumredmetzoloto, parent of the Navoi Mining ampersand Metallurgy Combine [NMMC]. Established in 1958 at the height of the Cold War, when uranium mining for military stockpiles got started in earnest, Navoi was wholly owned by the USSR's Ministry of Medium Machine Building. Up until 1991, virtually all of Navoi's uranium production, strictly in the form of uranium concentrates, was used for either military purposes or for nuclear power plants within the former Soviet Union. The republic exerted no control over the final destination of its uranium. All production and operating decisions for Navoi's mines were dictated by the Soviet Union's Ministry of Atomic Power ampersand Industry [MAPI], which developed annual quotas for uranium production in each republic of the country. Uranium from the republics was sold to Techsnabexport [Tenex], the distribution and marketing arm of MAPI. Exports to other countries were handled strictly by Tenex

  3. From Multilatina to Global Latina: Unveiling the corporate-level international strategy choices of Grupo Nutresa

    Directory of Open Access Journals (Sweden)

    MARIA A DE VILLA

    Full Text Available Research on Multilatinas has underexplored multinationals from Colombia and their corporate-level international strategy choices to develop into Global Latinas. Building on interviews, documents, and archival data about Grupo Nutresa -Colombia's most international firm in manufactured goods-, this study unveils and discusses this firm's corporate-level international strategy choices between 1960 and 2014. A prevailing notion is that most multinationals from Latin America continue to target international operations to focus mainly on their home region through an export, multidomestic or transnational corporate-level international strategy. In contrast, data show that Grupo Nutresa chose to evolve through a sequential approach from an export to a transnational corporate-level international strategy while its international operations were able to transcend its home region to reach North America, Asia, Europe, Africa, and Oceania. These results add to international business research on emergent market multinational companies (EMNCs from Latin America by unveiling the corporate-level international strategy choices of a Colombian origin Multilatina that transformed into a Global Latina.

  4. Expectations and satisfaction of pregnant women: unveiling prenatal care in primary care.

    Science.gov (United States)

    Aparecida Maciel Cardelli, Alexandrina; Li Marrero, Tai; Aparecida Pimenta Ferrari, Rosângela; Trevisan Martins, Júlia; Serafim, Deise

    2016-06-01

    To analyze the perception of primiparous women about prenatal care in Basic Health Units in a municipality in southern Brazil. This is a qualitative research from the perspective of Social Representation Theory, from the following question: How has been the pre-natal care for you? Eighteen pregnant women were interviewed. The analysis resulted in three categories: Expectation representation about prenatal care; Rescuing the care offered in prenatal consultation; Unveiling the (dis) satisfaction with prenatal consultation. The prenatal care was apprehended as an essential moment for safe pregnancy, although centered on the doctor's figure and guarantee access to early laboratory and imaging tests. On the other hand, dissatisfaction was revealed from the reception at the entrance to the health unit to the consultations access, although some statements suggest timely satisfaction. Prenatal care did not meet the specific expectations of the study group and unveiled that the nurse did not supply it, as a member of the multidisciplinary team. The organization of the nursing work process in primary care, related to prenatal care, needs to be revisited to promote the effectiveness of its actions.

  5. Expectations and satisfaction of pregnant women: unveiling prenatal care in primary care

    Directory of Open Access Journals (Sweden)

    Alexandrina Aparecida Maciel Cardelli

    Full Text Available Objective.To analyze the perception of primiparous women about prenatal care in Basic Health Units in a municipality in southern Brazil. Methods. This is a qualitative research from the perspective of Social Representation Theory, from the following question: How has been the pre-natal care for you? Eighteen pregnant women were interviewed. Results. The analysis resulted in three categories: Expectation representation about prenatal care; Rescuing the care offered in prenatal consultation; Unveiling the (dis satisfaction with prenatal consultation. The prenatal care was apprehended as an essential moment for safe pregnancy, although centered on the doctor's figure and guarantee access to early laboratory and imaging tests. On the other hand, dissatisfaction was revealed from the reception at the entrance to the health unit to the consultations access, although some statements suggest timely satisfaction. Conclusion. Prenatal care did not meet the specific expectations of the study group and unveiled that the nurse did not supply it, as a member of the multidisciplinary team. The organization of the nursing work process in primary care, related to prenatal care, needs to be revisited to promote the effectiveness of its actions.

  6. Data analysis unveils a new stylized fact in foreign currency markets

    Science.gov (United States)

    Nacher, J. C.; Ochiai, T.

    2012-09-01

    The search for stylized facts (i.e., simplified empirical facts) is of capital importance in econophysics because the stylized facts constitute the experimental empirical body on which theories and models should be tested. At the moment they are too few and this is an important limitation to the progress in the field. In this work, we unveil a new stylized fact, which consists of resistance effect and breaking-acceleration effect that implicitly requires a long memory feature in price movement. By analyzing a vast amount of historical data, we demonstrate that the financial market tends to exceed a past (historical) extreme price less often than expected by a classic short-memory model (e.g., Black-Scholes model). We call it resistance effect. However, when the market does it, we predict that the average volatility at that time point will be much higher (accelerates more). It means, in average, volatility accelerates more when the price breaks the highest (lowest) value. We refer to this as breaking-acceleration effect. These observed empirical facts are actually an effect which may arise from technical trading and psychological effects. Taken together, these results indicate that, beyond the predictive capability of this unveiled stylized fact, traditional short-memory models do not faithfully capture the market dynamics.

  7. NASA's Great Observatories Celebrate the International Year of Astronomy With a National Unveiling of Spectacular Images

    Science.gov (United States)

    2009-02-01

    In 1609, Galileo first turned his telescope to the heavens and gave birth to modern astronomy. To commemorate four hundred years of exploring the universe, 2009 is designated the International Year of Astronomy. NASA's Great Observatories - the Hubble Space Telescope, Spitzer Space Telescope, and Chandra X-ray Observatory - are marking the occasion with the release of a suite of images at over 100 planetariums, museums, nature centers, and schools across the country in conjunction with Galileo's birthday on February 15. The selected sites will unveil a large 9-square-foot print of the spiral galaxy Messier 101 that combines the optical view of Hubble, the infrared view of Spitzer, and the X-ray view of Chandra into one multi-wavelength picture. "It's like using your eyes, night vision goggles, and X-ray vision all at the same time," says Dr. Hashima Hasan, lead scientist for the International Year of Astronomy at NASA Headquarters in Washington. Cas A animation Chandra X-ray Image of M101 Participating institutions also will display a matched trio of Hubble, Spitzer, and Chandra images of Messier 101. Each image shows a different wavelength view of the galaxy that illustrates not only the different science uncovered by each observatory, but also just how far astronomy has come since Galileo. Messier 101 is a face-on spiral galaxy about 22 million light-years away in the constellation Ursa Major. It is in many ways similar to, but larger than, our own Milky Way galaxy. Hubble's visible light view shows off the swirls of bright stars and glowing gas that give the galaxy its nickname the Pinwheel Galaxy. In contrast, Spitzer's infrared-light image sees into the spiral arms and reveals the glow of dust lanes where dense clouds can collapse to form new stars. Chandra's X-ray picture uncovers the high-energy features in the galaxy, such as remnants of exploded stars or matter zooming around black holes. The juxtaposition of observations from these three telescopes

  8. White House Unveils America's College Promise Proposal: Tuition-Free Community College for Responsible Students. Fact Sheet

    Science.gov (United States)

    The White House, 2015

    2015-01-01

    In January, 2015, the President unveiled the America's College Promise proposal, which would make two years of community college free for responsible students, letting students earn the first half of a bachelor's degree and earn skills needed in the workforce at no cost. This proposal will require everyone to do their part: community colleges must…

  9. Unveiling EFL and Self-Contained Teachers' Discourses on Bilingualism within the Context of Professional Development

    Science.gov (United States)

    Camargo Cely, Jennyfer Paola

    2018-01-01

    Throughout time, the predominant use of certain languages has allowed some nations to take control over others and assure for them a privileged position. This study unveiled how certain practices and ideologies in regard to bilingualism have influenced teachers' professional development. Data were collected through discussion group sessions,…

  10. Unveiling non-stationary coupling between Amazon and ocean during recent extreme events

    Science.gov (United States)

    Ramos, Antônio M. de T.; Zou, Yong; de Oliveira, Gilvan Sampaio; Kurths, Jürgen; Macau, Elbert E. N.

    2018-02-01

    The interplay between extreme events in the Amazon's precipitation and the anomaly in the temperature of the surrounding oceans is not fully understood, especially its causal relations. In this paper, we investigate the climatic interaction between these regions from 1999 until 2012 using modern tools of complex system science. We identify the time scale of the coupling quantitatively and unveil the non-stationary influence of the ocean's temperature. The findings show consistently the distinctions between the coupling in the recent major extreme events in Amazonia, such as the two droughts that happened in 2005 and 2010 and the three floods during 1999, 2009 and 2012. Interestingly, the results also reveal the influence over the anomalous precipitation of Southwest Amazon has become increasingly lagged. The analysis can shed light on the underlying dynamics of the climate network system and consequently can improve predictions of extreme rainfall events.

  11. Unveiling the molecular bipolar outflow of the peculiar red supergiant VY Canis Majoris

    Science.gov (United States)

    Shinnaga, Hiroko; Claussen, Mark J.; Lim, Jeremy; Dinh-van-Trung; Tsuboi, Masato

    2003-04-01

    We carried out polarimetric spectral-line imaging of the molecular outflow of the peculiar red supergiant VY Canis Majoris in SiO J=1-0 line in the ground vibrational state, which contains highly linearly-polarized velocity components, using the Very Large Array. We succeeded in unveiling the highly linearly polarized bipolar outflow for the first time at subarcsecond spatial resolution. The results clearly show that the direction of linear polarization of the brightest maser components is parallel to the outflow axis. The results strongly suggest that the linear polarization of the SiO maser is closely related to the outflow phenomena of the star. Furthermore, the results indicate that the linear polarization observed in the optical and infrared also occur due to the outflow phenomena.

  12. The Green Bank Ammonia Survey: Unveiling the Dynamics of the Barnard 59 Star-forming Clump

    Science.gov (United States)

    Redaelli, E.; Alves, F. O.; Caselli, P.; Pineda, J. E.; Friesen, R. K.; Chacón-Tanarro, A.; Matzner, C. D.; Ginsburg, A.; Rosolowsky, E.; Keown, J.; Offner, S. S. R.; Di Francesco, J.; Kirk, H.; Myers, P. C.; Hacar, A.; Cimatti, A.; Chen, H. H.; Chen, M. C.; Lee, K. I.; Seo, Y. M.

    2017-12-01

    Understanding the early stages of star formation is a research field of ongoing development, both theoretically and observationally. In this context, molecular data have been continuously providing observational constraints on the gas dynamics at different excitation conditions and depths in the sources. We have investigated the Barnard 59 core, the only active site of star formation in the Pipe Nebula, to achieve a comprehensive view of the kinematic properties of the source. This information was derived by simultaneously fitting ammonia inversion transition lines (1, 1) and (2, 2). Our analysis unveils the imprint of protostellar feedback, such as increasing line widths, temperature, and turbulent motions in our molecular data. Combined with complementary observations of dust thermal emission, we estimate that the core is gravitationally bound following a virial analysis. If the core is not contracting, another source of internal pressure, most likely the magnetic field, is supporting it against gravitational collapse and limits its star formation efficiency.

  13. Understanding the mechanism of catalytic fast pyrolysis by unveiling reactive intermediates in heterogeneous catalysis

    Science.gov (United States)

    Hemberger, Patrick; Custodis, Victoria B. F.; Bodi, Andras; Gerber, Thomas; van Bokhoven, Jeroen A.

    2017-06-01

    Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes.

  14. Loss of heterozygosity and DNA damage repair in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Daigaku, Yasukazu [Graduate School of Life Sciences, Tohoku University, Sendai 980-8577 (Japan); Endo, Kingo [Graduate School of Life Sciences, Tohoku University, Sendai 980-8577 (Japan); Watanabe, Eri [Graduate School of Life Sciences, Tohoku University, Sendai 980-8577 (Japan); Ono, Tetsuya [Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan); Yamamoto, Kazuo [Graduate School of Life Sciences, Tohoku University, Sendai 980-8577 (Japan)]. E-mail: yamamot@mail.tains.tohoku.ac.jp

    2004-11-22

    Loss of heterozygosity (LOH) of tumor suppressor genes is a crucial step in the development of sporadic and hereditary cancer. Understanding how LOH events arise may provide an opportunity for the prevention or early intervention of cancer development. In an effort to investigate the source of LOH events, we constructed MAT{alpha} can1{delta}::LEU2 and MATa CAN1 haploid yeast strains and examined canavanine-resistance mutations in a MATa CAN1/MAT{alpha} can1{delta}::LEU2 heterozygote formed by mating UV-irradiated and nonirradiated haploids. An increase in LOH was observed when the irradiated CAN1 haploid was mated with nonirradiated can1{delta}::LEU2, while reversed irradiation only marginally increased LOH. In the rad51{delta} background, allelic crossover type LOH increased following UV irradiation but not gene conversion. In the rad52{delta} background, neither type of LOH increased. The chromosome structure following LOH and the requirement for Rad51 and Rad52 proteins indicated the involvement of gene conversion, allelic crossover and break-induced replication. We argued that LOH events could have occurred during the repair of double-strand breaks on a functional (damaged) but not nonfunctional (undamaged) chromosome through recombination.

  15. Body Covering and Body Image: A Comparison of Veiled and Unveiled Muslim Women, Christian Women, and Atheist Women Regarding Body Checking, Body Dissatisfaction, and Eating Disorder Symptoms.

    Science.gov (United States)

    Wilhelm, Leonie; Hartmann, Andrea S; Becker, Julia C; Kişi, Melahat; Waldorf, Manuel; Vocks, Silja

    2018-02-21

    Although Islam is the fastest growing religion worldwide, only few studies have investigated body image in Muslim women, and no study has investigated body checking. Therefore, the present study examined whether body image, body checking, and disordered eating differ between veiled and unveiled Muslim women, Christian women, and atheist women. While the groups did not differ regarding body dissatisfaction, unveiled Muslim women reported more checking than veiled Muslim and Christian women, and higher bulimia scores than Christian. Thus, prevention against eating disorders should integrate all women, irrespective of religious affiliation or veiling, with a particular focus on unveiled Muslim women.

  16. Codon-triplet context unveils unique features of the Candida albicans protein coding genome

    Directory of Open Access Journals (Sweden)

    Oliveira José L

    2007-11-01

    Full Text Available Abstract Background The evolutionary forces that determine the arrangement of synonymous codons within open reading frames and fine tune mRNA translation efficiency are not yet understood. In order to tackle this question we have carried out a large scale study of codon-triplet contexts in 11 fungal species to unravel associations or relationships between codons present at the ribosome A-, P- and E-sites during each decoding cycle. Results Our analysis unveiled high bias within the context of codon-triplets, in particular strong preference for triplets of identical codons. We have also identified a surprisingly large number of codon-triplet combinations that vanished from fungal ORFeomes. Candida albicans exacerbated these features, showed an unbalanced tRNA population for decoding its pool of codons and used near-cognate decoding for a large set of codons, suggesting that unique evolutionary forces shaped the evolution of its ORFeome. Conclusion We have developed bioinformatics tools for large-scale analysis of codon-triplet contexts. These algorithms identified codon-triplets context biases, allowed for large scale comparative codon-triplet analysis, and identified rules governing codon-triplet context. They could also detect alterations to the standard genetic code.

  17. A strategy to unveil transient sources of ultra-high-energy cosmic rays

    Directory of Open Access Journals (Sweden)

    Takami Hajime

    2013-06-01

    Full Text Available Transient generation of ultra-high-energy cosmic rays (UHECRs has been motivated from promising candidates of UHECR sources such as gamma-ray bursts, flares of active galactic nuclei, and newly born neutron stars and magnetars. Here we propose a strategy to unveil transient sources of UHECRs from UHECR experiments. We demonstrate that the rate of UHECR bursts and/or flares is related to the apparent number density of UHECR sources, which is the number density estimated on the assumption of steady sources, and the time-profile spread of the bursts produced by cosmic magnetic fields. The apparent number density strongly depends on UHECR energies under a given rate of the bursts, which becomes observational evidence of transient sources. It is saturated at the number density of host galaxies of UHECR sources. We also derive constraints on the UHECR burst rate and/or energy budget of UHECRs per source as a function of the apparent source number density by using models of cosmic magnetic fields. In order to obtain a precise constraint of the UHECR burst rate, high event statistics above ∼ 1020 eV for evaluating the apparent source number density at the highest energies and better knowledge on cosmic magnetic fields by future observations and/or simulations to better estimate the time-profile spread of UHECR bursts are required. The estimated rate allows us to constrain transient UHECR sources by being compared with the occurrence rates of known energetic transient phenomena.

  18. Surprisal analysis of Glioblastoma Multiform (GBM) microRNA dynamics unveils tumor specific phenotype.

    Science.gov (United States)

    Zadran, Sohila; Remacle, Francoise; Levine, Raphael

    2014-01-01

    Gliomablastoma multiform (GBM) is the most fatal form of all brain cancers in humans. Currently there are limited diagnostic tools for GBM detection. Here, we applied surprisal analysis, a theory grounded in thermodynamics, to unveil how biomolecule energetics, specifically a redistribution of free energy amongst microRNAs (miRNAs), results in a system deviating from a non-cancer state to the GBM cancer -specific phenotypic state. Utilizing global miRNA microarray expression data of normal and GBM patients tumors, surprisal analysis characterizes a miRNA system response capable of distinguishing GBM samples from normal tissue biopsy samples. We indicate that the miRNAs contributing to this system behavior is a disease phenotypic state specific to GBM and is therefore a unique GBM-specific thermodynamic signature. MiRNAs implicated in the regulation of stochastic signaling processes crucial in the hallmarks of human cancer, dominate this GBM-cancer phenotypic state. With this theory, we were able to distinguish with high fidelity GBM patients solely by monitoring the dynamics of miRNAs present in patients' biopsy samples. We anticipate that the GBM-specific thermodynamic signature will provide a critical translational tool in better characterizing cancer types and in the development of future therapeutics for GBM.

  19. Unveiling the biotransformation mechanism of indole in a Cupriavidus sp. strain.

    Science.gov (United States)

    Qu, Yuanyuan; Ma, Qiao; Liu, Ziyan; Wang, Weiwei; Tang, Hongzhi; Zhou, Jiti; Xu, Ping

    2017-12-01

    Indole, an important signaling molecule as well as a typical N-heterocyclic aromatic pollutant, is widespread in nature. However, the biotransformation mechanisms of indole are still poorly studied. Here, we sought to unlock the genetic determinants of indole biotransformation in strain Cupriavidus sp. SHE based on genomics, proteomics and functional studies. A total of 177 proteins were notably altered (118 up- and 59 downregulated) in cells grown in indole mineral salt medium when compared with that in sodium citrate medium. RT-qPCR and gene knockout assays demonstrated that an indole oxygenase gene cluster was responsible for the indole upstream metabolism. A functional indole oxygenase, termed IndA, was identified in the cluster, and its catalytic efficiency was higher than those of previously reported indole oxidation enzymes. Furthermore, the indole downstream metabolism was found to proceed via the atypical CoA-thioester pathway rather than conventional gentisate and salicylate pathways. This unusual pathway was catalyzed by a conserved 2-aminobenzoyl-CoA gene cluster, among which the 2-aminobenzoyl-CoA ligase initiated anthranilate transformation. This study unveils the genetic determinants of indole biotransformation and will provide new insights into our understanding of indole biodegradation in natural environments and its functional studies. © 2017 John Wiley & Sons Ltd.

  20. Unveiling the water-associated conformational mobility in the active site of ascorbate peroxidase.

    Science.gov (United States)

    Chao, Wei-Chih; Lin, Li-Ju; Lu, Jyh-Feng; Wang, Jinn-Shyan; Lin, Tzu-Chieh; Chen, Yi-Han; Chen, Yi-Ting; Yang, Hsiao-Ching; Chou, Pi-Tai

    2018-03-01

    We carried out comprehensive spectroscopic studies of wild type and mutants of ascorbate peroxidase (APX) to gain understanding of the conformational mobility of the active site. In this approach, three unnatural tryptophans were applied to replace the distal tryptophan (W41) in an aim to probe polarity/water environment near the edge of the heme-containing active site. 7-azatryptophan ((7-aza)Trp) is sensitive to environment polarity, while 2,7-azatryptophan ((2,7-aza)Trp) and 2,6-diazatryptophan ((2,6-aza)Trp) undergo excited-state water-catalyzed double and triple proton transfer, respectively, and are sensitive to the water network. The combination of their absorption, emission bands and the associated relaxation dynamics of these fluorescence probes, together with the Soret-band difference absorption and resonance Raman spectroscopy, lead us to unveil the water associated conformational mobility in the active site of APX. The results are suggestive of the existence of equilibrium between two different environments surrounding W41 in APX, i.e., the water-rich and water-scant forms with distinct fluorescence relaxation. Our results thus demonstrate for the first time the power of integrating multiple sensors (7-aza)Trp, (2,7-aza)Trp and (2,6-aza)Trp in probing the water environment of a specifically targeted Trp in proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Cellular therapies for heart disease: unveiling the ethical and public policy challenges.

    Science.gov (United States)

    Raval, Amish N; Kamp, Timothy J; Hogle, Linda F

    2008-10-01

    Cellular therapies have emerged as a potential revolutionary treatment for cardiovascular disease. Promising preclinical results have resulted in a flurry of basic research activity and spawned multiple clinical trials worldwide. However, the optimal cell type and delivery mode have not been determined for target patient populations. Nor have the mechanisms of benefit for the range of cellular interventions been clearly defined. Experiences to date have unveiled a myriad of ethical and public policy challenges which will affect the way researchers and clinicians make decisions for both basic and clinical research. Stem cells derived from embryos are at the forefront of the ethical and political debate, raising issues of which derivation methods are morally and socially permissible to pursue, as much as which are technically feasible. Adult stem cells are less controversial; however, important challenges exist in determining study design, cell processing, delivery mode, and target patient population. Pathways to successful commercialization and hence broad accessibility of cellular therapies for heart disease are only beginning to be explored. Comprehensive, multi-disciplinary and collaborative networks involving basic researchers, clinicians, regulatory officials and policymakers are required to share information, develop research, regulatory and policy standards and enable rational and ethical cell-based treatment approaches.

  2. Unveiling the geography of historical patents in the United States from 1836 to 1975

    Science.gov (United States)

    Petralia, Sergio; Balland, Pierre-Alexandre; Rigby, David L.

    2016-01-01

    It is clear that technology is a key driver of economic growth. Much less clear is where new technologies are produced and how the geography of U.S. invention has changed over the last two hundred years. Patent data report the geography, history, and technological characteristics of invention. However, those data have only recently become available in digital form and at the present time there exists no comprehensive dataset on the geography of knowledge production in the United States prior to 1975. The database presented in this paper unveils the geography of historical patents granted by the United States Patent and Trademark Office (USPTO) from 1836 to 1975. This historical dataset, HistPat, is constructed using digitalized records of original patent documents that are publicly available. We describe a methodological procedure that allows recovery of geographical information on patents from the digital records. HistPat can be used in different disciplines ranging from geography, economics, history, network science, and science and technology studies. Additionally, it is easily merged with post-1975 USPTO digital patent data to extend it until today. PMID:27576103

  3. Unveiling the development of intracranial injury using dynamic brain EIT: an evaluation of current reconstruction algorithms.

    Science.gov (United States)

    Li, Haoting; Chen, Rongqing; Xu, Canhua; Liu, Benyuan; Tang, Mengxing; Yang, Lin; Dong, Xiuzhen; Fu, Feng

    2017-08-21

    Dynamic brain electrical impedance tomography (EIT) is a promising technique for continuously monitoring the development of cerebral injury. While there are many reconstruction algorithms available for brain EIT, there is still a lack of study to compare their performance in the context of dynamic brain monitoring. To address this problem, we develop a framework for evaluating different current algorithms with their ability to correctly identify small intracranial conductivity changes. Firstly, a simulation 3D head phantom with realistic layered structure and impedance distribution is developed. Next several reconstructing algorithms, such as back projection (BP), damped least-square (DLS), Bayesian, split Bregman (SB) and GREIT are introduced. We investigate their temporal response, noise performance, location and shape error with respect to different noise levels on the simulation phantom. The results show that the SB algorithm demonstrates superior performance in reducing image error. To further improve the location accuracy, we optimize SB by incorporating the brain structure-based conductivity distribution priors, in which differences of the conductivities between different brain tissues and the inhomogeneous conductivity distribution of the skull are considered. We compare this novel algorithm (called SB-IBCD) with SB and DLS using anatomically correct head shaped phantoms with spatial varying skull conductivity. Main results and Significance: The results showed that SB-IBCD is the most effective in unveiling small intracranial conductivity changes, where it can reduce the image error by an average of 30.0% compared to DLS.

  4. Distinct roles of FANCO/RAD51C in DNA damage signaling and repair: implications for fanconi anemia and breast cancer susceptibility

    International Nuclear Information System (INIS)

    Nagaraju, G.; Somyajit, K.; Subramanya, S.

    2012-01-01

    Unrepaired or misrepaired chromosomal double-strand breaks (DSBs) can cause gross chromosomal rearrangements which eventually can lead to tumorigenesis through inactivation of tumor suppressor genes or activation of oncogenes. There are two major mechanisms of DSB repair: non-homologous end joining (NHEJ) and homologous recombination (HR). DSBs that are generated during S and G2 phase of the cell are preferentially repaired by sister chromatid recombination (SCR), an HR pathway that utilizes neighboring sister chromatid as a template. Since the copied information is accurate, SCR is potentially an error-free pathway. HR also plays a critical role in the repair of daughter strand gaps (DSGs) that arise as a result of replication fork stalling and facilitates replication fork recovery. Furthermore, in collaboration with nucleotide excision repair and translesion synthesis, HR is involved in the repair of DNA interstrand cross-links (ICLs). Thus, HR is important for the maintenance of genome integrity and its dysfunction can lead to various genetic disorders and cancer

  5. Sensing Conformational Changes in DNA upon Ligand Binding Using QCM-D. Polyamine Condensation and Rad51 Extension of DNA Layers

    KAUST Repository

    Sun, Lu; Frykholm, Karolin; Fornander, Louise H.; Svedhem, Sofia; Westerlund, Fredrik; Å kerman, Bjö rn

    2014-01-01

    © 2014 American Chemical Society. Biosensors, in which binding of ligands is detected through changes in the optical or electrochemical properties of a DNA layer confined to the sensor surface, are important tools for investigating DNA interactions

  6. Wukong Sharpens Its Eyes and Unveils the Nature of Dark Matter

    Science.gov (United States)

    Cong, Kun-Lin

    2016-07-01

    Dark matter does not emit light or reflect electromagnetic radiation, but its existence can be inferred from the effects of measurements such as gravity and mass. Unveiling the nature of dark matter is one of the biggest mysteries of modern science. Exploration of dark matter could give scientists a clearer understanding of the past and future of galaxies and the universe. Chinese scientists have been engaged actively in dark matter research in recent years, and made some significant achievements in theoretical studies, numerical simulations, and experimental investigation. The Dark Matter Particles Explorer Satellite (DAMPE) was launched by LM launch vehicle on 17th December 2015. It was constructed as a scientific satellite that has four major parts - a plastic scintillator array detector, a silicon array detector, a BGO calorimeter and a neutron detector - together comprising about 76,000 minor detectors. The main scientific purpose of DAMPE is to investigate dark matter particle from deep space, via high resolution observation of gamma-rays and electrons spectra, and its space distribution. It will also help scientists study the transportation and acceleration of cosmic rays in the galaxy by measuring the energy spectra of heavy ions. DAMPE was dubbed Wukong after the Monkey King character from the Chinese classic legend Journey to the West. "Wu" means becoming aware of through the senses, and "Kong" refers to the space. The figurative meaning of "Wukong" is to know and comprehend the nature of the space. DAMPE is the most sensitive and accurate detectors designed for dark matter with the highest performance among the similar explorers. It will find the evidence that can certify the existence of dark matter.

  7. Microevolution analysis of Bacillus coahuilensis unveils differences in phosphorus acquisition strategies and their regulation

    Directory of Open Access Journals (Sweden)

    Zulema eGómez-Lunar

    2016-02-01

    Full Text Available Bacterial genomes undergo numerous events of gene losses and gains that generate genome variability among strains of the same species (microevolution. Our aim was to compare the genomes and relevant phenotypes of three Bacillus coahuilensis strains from two oligotrophic hydrological systems in the Cuatro Ciénegas Basin (México, to unveil the environmental challenges that this species cope with, and the microevolutionary differences in these genotypes. Since the strains were isolated from a low P environment, we placed emphasis on the search of different phosphorus acquisition strategies. The three B. coahuilensis strains exhibited similar numbers of coding DNA sequences, of which 82% (2, 893 constituted the core genome, and 18% corresponded to accessory genes. Most of the genes in this last group were associated with mobile genetic elements or were annotated as hypothetical proteins. Ten percent of the pangenome consisted of strain-specific genes. Alignment of the three B. coahuilensis genomes indicated a high level of synteny and revealed the presence of several genomic islands. Unexpectedly, one of these islands contained genes that encode the 2-keto-3-deoxymannooctulosonic acid (Kdo biosynthesis enzymes, a feature associated to cell walls of Gram-negative bacteria. Some microevolutionary changes were clearly associated with mobile genetic elements. Our analysis revealed inconsistencies between phenotype and genotype, which we suggest result from the impossibility to map regulatory features to genome analysis. Experimental results revealed variability in the types and numbers of auxotrophies between the strains that could not consistently be explained by in silico metabolic models. Several intraspecific differences in preferences for carbohydrate and phosphorus utilization were observed. Regarding phosphorus recycling, scavenging, and storage, variations were found between the three genomes. The three strains exhibited differences regarding

  8. Unveiled Risks in a Telecoupled Arena Dependent on Agricultural Commodity Trade

    Science.gov (United States)

    Batistella, M.; Silva, R. F. B. D.; Liu, J.; Moran, E. F.; Torres, S.; Dou, Y.

    2017-12-01

    In less than five years, a new field of interdisciplinary research has been widely developed within the coupled human-natural systems (CHANS) community. Based on well-known concepts acting over long distances, such as teleconnections for biophysical sciences and globalization for human sciences, the telecoupling framework states that long distant CHANS may be integrated through flows of capital, information, and matter, shaping environmental and socioeconomic changes within local systems. An international project including researchers from Brazil, China, United Kingdom (UK), and United States of America (USA) is using such a framework to study the flows of agricultural commodities between sending systems such as Brazil and the USA, and receiving systems such as China with soybean trade as a case in point. Many findings have already shown that these dynamics are intrinsically connected and changes in environmental conditions in one system may affect economic conditions in other systems. In the case of the double-crop practice (i.e., soybean followed by maize, two crops year round) used in some regions of Brazil, maize production is strongly connected with soybean production through the supply chain, logistics, producer regions, and farmers. Consequently, maize has been displaced to second-crop status, making it more vulnerable to rain shortfalls. The use of the telecoupling framework has also unveiled a possible threat for soybean production in the long run if it only relies on international demand and inputs. The telecoupled soybean production system has put some Brazilian farmers at economic risk, and is pushing them towards diversification and alternative production practices (e.g., non-GMO crops, biological control, in-farm seed production) to reduce their risk. This, in turn, may affect the demand-consumption relationship among traditional trading partners. With this paper, we also highlight the role of cascading effects and spillover systems of telecoupling in

  9. Unveiling the UHE Universe from space: the JEM-EUSO mission

    Energy Technology Data Exchange (ETDEWEB)

    Santangelo, A.; Fenu, F. [Institute of Astronomy and Astrophysics, Kepler Center for Astro and Particle Physics, Eberhard-Karls-Universitaet, Sand 1, 72076, Tuebingen (Germany); RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako 351-0198 (Japan); Ebisuzaki, T.; Shinozaki, K. [RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako 351-0198 (Japan)

    2011-03-15

    The Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO) is an international mission designed to explore the origin and nature of the of ultra high-energy cosmic rays (UHECR), with energies E>5.5x10{sup 19} eV, aiming at an integrated exposure of {approx}10{sup 6} km{sup 2} sr yr at E>10{sup 20} eV. Consisting of a near-UV 2.65 m diameter telescope with a field of view of 60{sup o}, JEM-EUSO looks down from space, monitoring the dark side of the Earth, to detect the fluorescence and Cherenkov light emitted along the linear track generated by a cosmic particle traversing the atmosphere. The energy and the arrival direction of each particle will be measured while the all 4{pi} sky is monitored. The primary science goal of the mission is to identify the sources of the highest energy particles, and to measure their flux and spectrum, to unveil the mechanisms for the production, acceleration, and in situ propagation of these extreme particles. Other exploratory objectives of the mission include the study of the galactic and local extragalactic magnetic field; the detection of high-energy gamma rays and neutrinos, and tests of relativity and quantum gravity effects at extreme energies. Other aspects of fundamental physics that will be studied include the top-down models and the behavior of the neutrino cross sections at extreme energies. JEM-EUSO is also expected to conduct a systematic survey of the not yet well known energetic phenomena of the Earth's atmosphere. The mission is currently in the phase A study by JAXA and has been included in the ELIPS research pool of the European Space Agency. JEM-EUSO will be launched by an H2B rocket in the Japanese fiscal year 2016 and will be transferred to the ISS by an H2 Transfer Vehicle (HTV). It will be attached to the external experiment platform of the Japanese 'KIBO' module of the ISS. In this paper we summarize the science case, the science objectives, the technological and

  10. Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Xie L

    2016-11-01

    Full Text Available Lisha Xie,1,* Tiancen Zhao,1,2,* Jing Cai,1 You Su,1 Zehua Wang,1 Weihong Dong1 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2Department of Obstetrics and Gynecology, Central Hospital of Wuhan, Wuhan, China *These authors contributed equally to this work Objective: The objective of this study was to investigate the mechanism of sensitivity to methotrexate (MTX in human choriocarcinoma cells regarding DNA damage response. Methods: Two choriocarcinoma cancer cell lines, JAR and JEG-3, were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX-resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical adenocarcinoma cell line Hela served as controls. Cell viability assay was carried out to assess MTX sensitivity of cell lines. MTX-induced DNA damage was evaluated by comet assay. Quantitative reverse transcription polymerase chain reaction was used to detect the mRNA levels of BRCA1, BRCA2, RAD51 and RAD52. The protein levels of γH2AX, RAD 51 and p53 were analyzed by Western blot. Results: Remarkable DNA strand breaks were observed in MTX-sensitive cell lines (JAR, JEG-3 and MG63 but not in MTX-resistant cancer cells (A2780 and Hela after 48 h of MTX treatment. Only in the choriocarcinoma cells, the expression of homologous recombination (HR repair gene RAD51 was dramatically suppressed by MTX in a dose- and time-dependent manner, accompanied with the increase in p53. Conclusion: The MTX-induced DNA strand breaks accompanied by deficiencies in HR repair may contribute to the hypersensitivity to chemotherapy in choriocarcinoma. Keywords: choriocarcinoma, chemotherapy hypersensitivity, DNA double-strand break, RAD51, p53

  11. Schizosaccharomyces pombe Rad22A and Rad22B have similar biochemical properties and form multimeric structures

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Femke A.T. de [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Zonneveld, Jose B.M. [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Groot, Anton J. de [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Koning, Roman I. [Department of Molecular Cell Biology, Leiden University Medical Center, Leiden (Netherlands); Zeeland, Albert A. van [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands); Pastink, Albert [Department of Toxicogenetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)]. E-mail: A.Pastink@lumc.nl

    2007-02-03

    The Saccharomyces cerevisiae Rad52 protein has a crucial role in the repair of DNA double-strand breaks by homologous recombination. In vitro, Rad52 displays DNA binding and strand annealing activities and promotes Rad51-mediated strand exchange. Schizosaccharomyces pombe has two Rad52 homologues, Rad22A and Rad22B. Whereas rad22A deficient strains exhibit severe defects in repair and recombination, rad22B mutants have a much less severe phenotype. To better understand the role of Rad22A and Rad22B in double-strand break repair, both proteins were purified to near homogeneity. Using gel retardation and filter binding assays, binding of Rad22A and Rad22B to short single-stranded DNAs was demonstrated. Binding of Rad22A to double-stranded oligonucleotides or linearized plasmid molecules containing blunt ends or short single-stranded overhangs could not be detected. Rad22B also does not bind efficiently to short duplex oligonucleotides but binds readily to DNA fragments containing 3'-overhangs. Rad22A as well as Rad22B efficiently promote annealing of complementary single-stranded DNAs. In the presence of Rad22A annealing of complementary DNAs is almost 90%. Whereas in reactions containing Rad22B the maximum level of annealing is 60%, most likely due to inhibition of the reaction by duplex DNA. Gel-filtration experiments and electron microscopic analyses indicate self-association of Rad22A and Rad22B and the formation of multimeric structures as has been observed for Rad52 in yeast and man.

  12. Unveiling topographical changes using LiDAR mapping capability: case study of Belaga in Sarawak, East-Malaysia

    Science.gov (United States)

    Ganendra, T. R.; Khan, N. M.; Razak, W. J.; Kouame, Y.; Mobarakeh, E. T.

    2016-06-01

    The use of Light Detection and Ranging (LiDAR) remote sensing technology to scan and map landscapes has proven to be one of the most popular techniques to accurately map topography. Thus, LiDAR technology is the ultimate method of unveiling the surface feature under dense vegetation, and, this paper intends to emphasize the diverse techniques that can be utilized to elucidate topographical changes over the study area, using multi-temporal airborne full waveform LiDAR datasets collected in 2012 and 2014. Full waveform LiDAR data offers access to an almost unlimited number of returns per shot, which enables the user to explore in detail topographical changes, such as vegetation growth measurement. The study also found out topography changes at the study area due to earthwork activities contributing to soil consolidation, soil erosion and runoff, requiring cautious monitoring. The implications of this study not only concurs with numerous investigations undertaken by prominent researchers to improve decision making, but also corroborates once again that investigations employing multi-temporal LiDAR data to unveil topography changes in vegetated terrains, produce more detailed and accurate results than most other remote sensing data.

  13. Dilemmas in the (un)veiling of the diagnosis of Alzheimer's disease: walking an ethical and professional tight rope.

    Science.gov (United States)

    Karnieli-Miller, Orit; Werner, Perla; Aharon-Peretz, Judith; Eidelman, Shmuel

    2007-08-01

    To enhance the understanding and effect of physician's difficulties, attitudes and communication styles on the disclosure of the diagnosis of AD in practice. Qualitative, phenomenological study, combining pre-encounter interviews with physicians, observations of actual encounters of diagnosis disclosure of AD, and post-encounter interviews. There were various ways or tactics to (un)veil the bad news that may be perceived as different ways of dulling the impact and avoiding full and therefore problematic statements. In the actual encounters this was accomplished by keeping encounters short, avoiding elaboration, confirmation of comprehension and explicit terminology and using fractured sentences. The present study's findings highlight the difficulties encountered in breaking the news about AD, in the way it is actually done, and the problems that may arise from this way of un/veiling the news. The main problem is that the reluctance to make a candid disclosure of the diagnosis as was demonstrated in this study may violate basic moral and legal rights and may also deprive patients and caregivers of some of the benefits of early disclosure of diagnosis. There is a need for assisting physicians to cope with their personal difficulties, problems and pitfalls in breaking the news.

  14. IEEE Milestone at CERN - W Cleon Anderson (right), president of the Institute of Electrical and Electronics Engineers, unveils the Milestone plaque at CERN, together with Georges Charpak

    CERN Multimedia

    Maximilien Brice

    2005-01-01

    At a ceremony on 26 September at CERN, W Cleon Anderson, president of the Institute of Electrical and Electronics Engineers (IEEE), formally dedicated a "Milestone" plaque in recognition of the invention of electronic particle detectors at CERN. The plaque was unveiled by Anderson and Georges Charpak, the Nobel-prize winning inventor of wire-chamber technology at CERN.

  15. Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming.

    Science.gov (United States)

    Islam, Mohammed M; Smith, Derek K; Niu, Wenze; Fang, Sanhua; Iqbal, Nida; Sun, Guoqiang; Shi, Yanhong; Zhang, Chun-Li

    2015-11-10

    The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming.

  16. Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming

    Science.gov (United States)

    Islam, Mohammed M.; Smith, Derek K.; Niu, Wenze; Fang, Sanhua; Iqbal, Nida; Sun, Guoqiang; Shi, Yanhong; Zhang, Chun-Li

    2015-01-01

    Summary The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming. PMID:26607952

  17. Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming

    Directory of Open Access Journals (Sweden)

    Mohammed M. Islam

    2015-11-01

    Full Text Available The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming.

  18. Unveiling the strangeness secrets: low-energy kaon-nucleon/nuclei interactions studies at DAΦNE

    Directory of Open Access Journals (Sweden)

    Curceanu C.

    2014-03-01

    Full Text Available The DAΦNE electron-positron collider at the Laboratori Nazionali di Frascati of INFN, Italy has made available a unique quality low-energy negatively charged kaons “beam”, which is used to unveil the secrets of the kaon-nucleon/nuclei interactions at low energies by the SIDDHARTA-2 and AMADEUS experiments. SIDDHARTA has already performed unprecedented precision measurements of kaonic atoms, and is being presently upgraded, as SIDDHARTA-2, to approach new frontiers. The AMADEUS experiment plans to perform in the coming years precision measurements on kaon-nuclei interactions at low-energies, to study the possible formation of kaonic nuclei, of the Λ(1405 and of many other processes involving strangeness.

  19. Social Networking Sites in the Classroom: Unveiling New Roles for Teachers and New Approaches to Online Course Design

    Directory of Open Access Journals (Sweden)

    Jorge Eduardo Pineda Hoyos

    2014-12-01

    Full Text Available Web 2.0 tools in general and social networking sites in particular are very popular today in everyday life. However, their use in education has not been explored. This paper reports the findings of the implementation of a web 2.0 tool namely a social networking site as a web support for a face-to-face course. The findings show that the implementation of a web-based environment in a face-to-face course can be viewed from 5 different managerial areas: (1 logistics management, (2 information/knowledge management, (3 communication management, (4 class work extension management and (5 web-based environment easiness of accessibility. The conclusions of the study show that the implementation of the web-based environment unveils new roles for teachers and new approaches to design online or blended courses.

  20. Mechanism of Homologous Recombination and Implications for Aging-Related Deletions in Mitochondrial DNA

    Science.gov (United States)

    2013-01-01

    SUMMARY Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of double-strand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin in mitochondria, which operates by a single-strand annealing mechanism independent of the canonical RecA/Rad51-type recombinases. Increasing evidence supports the notion that, like in bacteriophages, mtDNA inheritance is a coordinated interplay between recombination, repair, and replication. These findings could have profound implications for understanding the mechanism of mtDNA inheritance and the generation of mtDNA deletions in aging cells. PMID:24006472

  1. Use of orthogonal field alternational gel electrophoresis (OFAGE) for studying DNA double strand breakage and repair

    International Nuclear Information System (INIS)

    Contopoulou, C.R.; Cook, V.; Mortimer, R.K.

    1987-01-01

    The study of DNA double strand breakage and repair has normally been carried by using neutral sucrose gradient or neutral elution techniques. The authors have applied OFAGE procedures to study x-ray induced double strand breaks and repair. Breakage of chromosomes is seen by a decrease in intensity of individual chromosome bands; as expected, this decrease becomes more pronounced as chromosome size increases. The fragments of broken chromosomes appears as a broad smear in the size range 100 kb to 1000 kb. Following repair, these fragments partially disappear and the chromosomal bands increase in intensity. In four repair deficient mutants, rad51, rad52, rad54, rad55, no increase in chromosomal band intensity was seen. These results have been confirmed by blotting for a specific chromosome

  2. Her Excellency Mrs Sarah Gillett Her Majesty's Ambassador to the Swiss Confederation United Kingdom of Great Britain and Northern Ireland on the occasion of the Antony Gormley sculpture unveiling ceremony Wednesday 7th December 2011

    CERN Document Server

    Maximilien Brice

    2011-01-01

    Her Excellency Mrs Sarah Gillett Her Majesty's Ambassador to the Swiss Confederation United Kingdom of Great Britain and Northern Ireland on the occasion of the Antony Gormley sculpture unveiling ceremony Wednesday 7th December 2011

  3. A novel pathogenic aviadenovirus from red-bellied parrots (Poicephalus rufiventris) unveils deep recombination events among avian host lineages

    International Nuclear Information System (INIS)

    Das, Shubhagata; Fearnside, Kathleen; Sarker, Subir; Forwood, Jade K.; Raidal, Shane R.

    2017-01-01

    Competing roles of coevolution, selective pressure and recombination are an emerging interest in virus evolution. We report a novel aviadenovirus from captive red-bellied parrots (Poicephalus rufiventris) that uncovers evidence of deep recombination among aviadenoviruses. The sequence identity of the virus was most closely related to Turkey adenovirus D (42% similarity) and other adenoviruses in chickens, turkeys and pigeons. Sequencing and comparative analysis showed that the genome comprised 40,930 nucleotides containing 42 predicted open reading frames (ORFs) 19 of which had strong similarity with genes from other adenovirus species. The new genome unveiled a lineage that likely participated in deep recombination events across the genus Aviadenovirus accounting for an ancient evolutionary relationship. We hypothesize frequent host switch events and recombination among adenovirus progenitors in Galloanserae hosts caused the radiation of extant aviadenoviruses and the newly assembled Poicephalus adenovirus genome points to a potentially broader host range of these viruses among birds. - Highlights: •Shows how a single new genome can change overall phylogeny. •Reveals host switch events among adenovirus progenitors in Galloanserae hosts. •Points to a potentially broader host range of adenoviruses among birds and wildlife .

  4. A novel pathogenic aviadenovirus from red-bellied parrots (Poicephalus rufiventris) unveils deep recombination events among avian host lineages

    Energy Technology Data Exchange (ETDEWEB)

    Das, Shubhagata, E-mail: sdas@csu.edu.au [School of Animal and Veterinary Sciences, Faculty of Science, Charles Sturt University, New South Wales 2678 (Australia); Fearnside, Kathleen, E-mail: kathyfearnside@exemail.com.au [Hills District Veterinary Hospital, Unit 1, 276 New Line Road, Dural, NSW 2158 (Australia); Sarker, Subir, E-mail: S.Sarker@latrobe.edu.au [Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC 3086 (Australia); Forwood, Jade K., E-mail: jforwood@csu.edu.au [School of Biomedical Sciences, Faculty of Science, Charles Sturt University, Wagga Wagga, NSW 2650 (Australia); Raidal, Shane R., E-mail: shraidal@csu.edu.au [School of Animal and Veterinary Sciences, Faculty of Science, Charles Sturt University, New South Wales 2678 (Australia)

    2017-02-15

    Competing roles of coevolution, selective pressure and recombination are an emerging interest in virus evolution. We report a novel aviadenovirus from captive red-bellied parrots (Poicephalus rufiventris) that uncovers evidence of deep recombination among aviadenoviruses. The sequence identity of the virus was most closely related to Turkey adenovirus D (42% similarity) and other adenoviruses in chickens, turkeys and pigeons. Sequencing and comparative analysis showed that the genome comprised 40,930 nucleotides containing 42 predicted open reading frames (ORFs) 19 of which had strong similarity with genes from other adenovirus species. The new genome unveiled a lineage that likely participated in deep recombination events across the genus Aviadenovirus accounting for an ancient evolutionary relationship. We hypothesize frequent host switch events and recombination among adenovirus progenitors in Galloanserae hosts caused the radiation of extant aviadenoviruses and the newly assembled Poicephalus adenovirus genome points to a potentially broader host range of these viruses among birds. - Highlights: •Shows how a single new genome can change overall phylogeny. •Reveals host switch events among adenovirus progenitors in Galloanserae hosts. •Points to a potentially broader host range of adenoviruses among birds and wildlife .

  5. Endogenous and ectopic expression of telomere regulating genes in chicken embryonic fibroblasts

    International Nuclear Information System (INIS)

    Michailidis, Georgios; Saretzki, Gabriele; Hall, Judith

    2005-01-01

    In this study, we compared the endogenous expression of genes encoding telomere regulating proteins in cultured chicken embryonic fibroblasts (CEFs) and 10-day-old chicken embryos. CEFs maintained in vitro senesced and senescence was accompanied by reduced telomere length, telomerase activity, and expression of the chicken (c) TRF1 gene. There was no change in TRF2 gene expression although the major TRF2 transcript identified in 10-day-old chicken embryos encoded a truncated TRF2 protein (TRF2'), containing an N-terminal dimerisation domain but lacking a myb-related DNA binding domain and nuclear localisation signal. Senescence of the CEFs in vitro was associated with the loss of the TRF2' transcript, indicative of a novel function for the encoded protein. Senescence was also coupled with decreased expression of RAD51, but increased RAD52 expression. These data support that RAD51 independent recombination mechanisms do not function in vitro to maintain chicken telomeres. To attempt to rescue the CEFs from replicative senescence, we stably transfected passage 3 CEFs with the human telomerase reverse transcriptase (hTERT) catalytic subunit. While hTERT expression was detected in the stable transfectants neither telomerase activity nor the stabilisation of telomere length was observed, and the transfectant cells senesced at the same passage number as the untransfected cells. These data indicate that the human TERT is incompatible with the avian telomere maintenance apparatus and suggest the functioning of a species specific telomere system in the avian

  6. The caregiver burden in lupus: findings from UNVEIL, a national online lupus survey in the United States.

    Science.gov (United States)

    Al Sawah, S; Daly, R P; Foster, S A; Naegeli, A N; Benjamin, K; Doll, H; Bond, G; Moshkovich, O; Alarcón, G S

    2017-01-01

    Lupus imposes a substantial burden on patients; however, little is known about its impact on those caring for patients with the disease. In this study, we examined the impact 'caring for patients with lupus' has on caregivers from their own perspective. UNVEIL was a one-time online national cross-sectional survey developed in partnership with the Lupus Foundation of America and fielded targeting the US Lupus Foundation of America constituents in 2014. Eligible caregivers were adults who self-identified as unpaid caregivers of patients with lupus. Eligible caregivers had to complete a series of sociodemographic questions as well as a series of well established outcome measures, such as the Short Form 12v2 Health Survey, the Work Productivity and Activity Index, the Caregiver Burden Inventory, and the Perceived Benefits of Caregiving Scale. A total of 253 caregivers completed the survey. The majority of caregivers (90.1%) were aged 60 years or younger, more than half (54.2%) were men, and more than half (59.7%) identified themselves as either a spouse or a partner to the patient with lupus they were caring for. Overall health-related quality of life was close to the norm mean of the general US population. Caregivers who were employed missed an average of 12.8% of paid work time due to caregiving responsibilities and reported a 33.5% reduction in on-the-job effectiveness. Nearly half of the caregivers surveyed (49.4%) indicated that their caregiving responsibilities impacted their ability to socialize with friends, and almost all caregivers (97.6%) reported experiencing increased anxiety and stress in relation to their caregiving role. Caregiving for patients with lupus has a substantial impact on the work productivity and the social and emotional functioning of caregivers. Healthcare professionals and policymakers should continually assess the impact of healthcare decisions on the well-being of those caring for patients with lupus. © The Author(s) 2016.

  7. The effect of post-mastectomy radiation therapy on breast implants: Unveiling biomaterial alterations with potential implications on capsular contracture

    Energy Technology Data Exchange (ETDEWEB)

    Ribuffo, Diego; Lo Torto, Federico [Department of Plastic Surgery, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Giannitelli, Sara M. [Tissue Engineering Unit, Department of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome (Italy); Urbini, Marco; Tortora, Luca [Surface Analysis Laboratory, Department of Mathematics and Physics, University “Roma Tre”, Via della Vasca Navale 84, 00146 Rome (Italy); INFN — National Institute of Nuclear Physics, Section of Roma Tre, Via della Vasca Navale 84, 00146 Rome (Italy); Mozetic, Pamela; Trombetta, Marcella [Tissue Engineering Unit, Department of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome (Italy); Basoli, Francesco; Licoccia, Silvia [Department of Chemical Science and Technologies, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00173 Rome (Italy); Tombolini, Vincenzo [Department of Radiation Oncology, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Spencer-Lorillard Foundation, Viale Regina Elena 291, 00161 Rome (Italy); Cassese, Raffaele [Department of Radiation Oncology, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Scuderi, Nicolò [Department of Plastic Surgery, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); and others

    2015-12-01

    Post-mastectomy breast reconstruction with expanders and implants is recognized as an integral part of breast cancer treatment. Its main complication is represented by capsular contracture, which leads to poor expansion, breast deformation, and pain, often requiring additional surgery. In such a scenario, the debate continues as to whether the second stage of breast reconstruction should be performed before or after post-mastectomy radiation therapy, in light of potential alterations induced by irradiation to silicone biomaterial. This work provides a novel, multi-technique approach to unveil the role of radiotherapy in biomaterial alterations, with potential involvement in capsular contracture. Following irradiation, implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, Attenuated Total Reflectance Fourier Transform InfraRed spectroscopy (ATR/FTIR), Scanning Electron Microscopy (SEM), high resolution stylus profilometry, and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Our findings are consistent with radiation-induced modifications of silicone that, although not detectable at the microscale, can be evidenced by more sophisticated nanoscale surface analyses. In light of these results, biomaterial irradiation cannot be ruled out as one of the possible co-factors underlying capsular contracture. - Highlights: • The debate continues whether to perform breast reconstruction before or after PMRT. • Radiation therapy may alter implant material, concurring to capsular contracture. • In this work, irradiated implants were investigated by a multi-technique approach. • Radiation-induced alterations could be evidenced by ATR/FTIR and ToF-SIMS. • Reported alteration might represent a co-factor underlying capsular contracture.

  8. Unveiling the Aggregation of Lycopene in Vitro and in Vivo: UV-Vis, Resonance Raman, and Raman Imaging Studies.

    Science.gov (United States)

    Ishigaki, Mika; Meksiarun, Phiranuphon; Kitahama, Yasutaka; Zhang, Leilei; Hashimoto, Hideki; Genkawa, Takuma; Ozaki, Yukihiro

    2017-08-31

    The present study investigates the structure of lycopene aggregates both in vitro and in vivo using ultraviolet-visible (UV-vis) and Raman spectroscopies. The electronic absorption bands of the J- and H-aggregates in vitro shift to lower and higher energies, respectively, compared to that of the lycopene monomer. Along with these results, the frequencies of the ν 1 Raman bands were shifted to lower and higher frequencies, respectively. By plotting the frequencies of the ν 1 Raman band against the S 0 → S 2 transition energy, a linear relationship between the data set with different aggregation conformations can be obtained. Therefore, the band positions depending on the different conformations can be explained based on the idea that the effective conjugated C═C chain lengths within lycopene molecules are different due to the environmental effect (site-shift effect) caused by the aggregation conformation. Applying this knowledge to the in vivo measurement of a tomato fruit sample, the relationship between the aggregation conformation of lycopene and the spectral patterns observed in the UV-vis as well as Raman spectra in different parts of tomato fruits was discussed in detail. The results showed that the concentration of lycopene (particularly that of the J-aggregate) specifically increased, whereas that of chlorophyll decreased, with ripening. Furthermore, Raman imaging indicated that lycopene with different aggregate conformations was distributed inhomogeneously, even within one sample. The layer formation in tomato tissues with high concentrations of J- and H-aggregates was successfully visualized. In this manner, the presence of lycopene distributions with different aggregate conformations was unveiled in vivo.

  9. The crystal structures of the tryparedoxin-tryparedoxin peroxidase couple unveil the structural determinants of Leishmania detoxification pathway.

    Directory of Open Access Journals (Sweden)

    Annarita Fiorillo

    Full Text Available Leishmaniasis is a neglected disease caused by Leishmania, an intracellular protozoan parasite which possesses a unique thiol metabolism based on trypanothione. Trypanothione is used as a source of electrons by the tryparedoxin/tryparedoxin peroxidase system (TXN/TXNPx to reduce the hydroperoxides produced by macrophages during infection. This detoxification pathway is not only unique to the parasite but is also essential for its survival; therefore, it constitutes a most attractive drug target. Several forms of TXNPx, with very high sequence identity to one another, have been found in Leishmania strains, one of which has been used as a component of a potential anti-leishmanial polyprotein vaccine. The structures of cytosolic TXN and TXNPx from L. major (LmTXN and LmTXNPx offer a unique opportunity to study peroxide reduction in Leishmania parasites at a molecular level, and may provide new tools for multienzyme inhibition-based drug discovery. Structural analyses bring out key structural features to elucidate LmTXN and LmTXNPx function. LmTXN displays an unusual N-terminal α-helix which allows the formation of a stable domain-swapped dimer. In LmTXNPx, crystallized in reducing condition, both the locally unfolded (LU and fully folded (FF conformations, typical of the oxidized and reduced protein respectively, are populated. The structural analysis presented here points to a high flexibility of the loop that includes the peroxidatic cysteine which facilitates Cys52 to form an inter-chain disulfide bond with the resolving cysteine (Cys173, thereby preventing over-oxidation which would inactivate the enzyme. Analysis of the electrostatic surface potentials of both LmTXN and LmTXNPx unveils the structural elements at the basis of functionally relevant interaction between the two proteins. Finally, the structural analysis of TXNPx allows us to identify the position of the epitopes that make the protein antigenic and therefore potentially suitable

  10. Eyeball Pressure Stimulation Unveils Subtle Autonomic Cardiovascular Dysfunction in Persons with a History of Mild Traumatic Brain Injury.

    Science.gov (United States)

    Hilz, Max J; Aurnhammer, Felix; Flanagan, Steven R; Intravooth, Tassanai; Wang, Ruihao; Hösl, Katharina M; Pauli, Elisabeth; Koehn, Julia

    2015-11-15

    After mild traumatic brain injury (mTBI), patients have increased long-term mortality rates, persisting even beyond 13 years. Pathophysiology is unclear. Yet, central autonomic network dysfunction may contribute to cardiovascular dysregulation and increased mortality. Purely parasympathetic cardiovascular challenge by eyeball pressure stimulation (EP), might unveil subtle autonomic dysfunction in post-mTBI patients. We investigated whether mild EP shows autonomic cardiovascular dysregulation in post-mTBI patients. In 24 patients (34 ± 12 years; 5-86 months post-injury) and 27 controls (30 ± 11 years), we monitored respiration, electrocardiographic RR intervals (RRI), systolic and diastolic blood pressure (BPsys, BPdia) before and during 2 min of 30 mm Hg EP, applied by an ophthalmologic ocular pressure device (Okulopressor(®)). We calculated spectral powers of RRI in the mainly sympathetic low frequency (LF; 0.04-0.15 Hz) and parasympathetic high frequency (HF; 0.15-0.5 Hz) ranges, and of BP in the sympathetic LF range, the RRI-LF/HF ratio as index of the sympathetic-parasympathetic balance, normalized (nu) RRI-LF- and HF-powers, and LF- and HF-powers after natural logarithmic transformation (ln). Parameters before and during EP in post-mTBI patients and controls were compared by repeated measurement analysis of variance with post hoc analysis (p < 0.05). During EP, BPsys and BPdia increased in post-mTBI patients. Only in controls but not in post-mTBI patients, EP increased RRI-HFnu-powers and decreased RRI-LF-powers, RRI-LFnu-powers, BPsys-LF-powers, BPsys-lnLF-powers and BPdia-lnLF-powers. RRI-LF/HF ratios slightly increased in post-mTBI patients but slightly decreased in controls upon EP. Even with only mild EP, our controls showed normal EP responses and shifted sympathetic-parasympathetic balance towards parasympathetic predominance. In contrast, our post-mTBI patients could not increase parasympathetic heart rate modulation but

  11. Uncertainty analysis in Titan ionospheric simulated ion mass spectra: unveiling a set of issues for models accuracy improvement

    Science.gov (United States)

    Hébrard, Eric; Carrasco, Nathalie; Dobrijevic, Michel; Pernot, Pascal

    present semi-coupled model of Titan's ionosphere. We will eventually unveil a set of different issues limiting the current accuracy and, as one can expect, the predictivity of Titan photochemical models.

  12. Unveiling the Gap

    DEFF Research Database (Denmark)

    Jensson, Pall; Rokkjær, Ole; Nørgaard, Bente

    by the EU Leonardo da Vinci Partnership program. The project had two objectives. The first objective was to use the European Qualification Framework (EQF) as a benchmark against the National Qualification Framework (NQF) of the partner countries and the IE educations offered by the partner institutions...

  13. LHCb unveils new particles

    CERN Multimedia

    Stefania Pandolfi

    2016-01-01

    The LHCb collaboration announces the observation of four “exotic” particles from its analysis of the LHC data.   The LHCb experimental cavern. On 28 June, the LHCb collaboration reported the observation of three new "exotic" particles and confirmation of the existence of a fourth one in data from the LHC. These particles each appear to be formed by four quarks (the fundamental constituents of the matter inside all the atoms of the universe): two quarks and two antiquarks (that is, a tetraquark). Due to their non-standard quark content, the newly observed particles have been included in the broad category of so-called exotic particles, although their exact theoretical interpretation is still under study.            The quark model, proposed by Murray Gell-Mann and George Zweig in 1964, is considered to be the most valid scheme for the classification of hadrons (all the composite particles) that has been fou...

  14. Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics

    DEFF Research Database (Denmark)

    Gresner, Peter; Gromadzinska, Jolanta; Jablonska, Ewa

    2014-01-01

    affect the unselected BrC risk. Contrary to this, carriers of rs12946522, rs16943176, rs12946397 and rs17222691 rare-alleles were found to present significantly increased level of blood plasma TBARS compared to respective wild-type homozygotes (p... decreased fraction of oxidatively generated DNA damage (34% of total damaged DNA) in favor of DNA strand breakage, with no effect on total DNA damage, unlike respective wild-types, among which more evenly distributed proportions between oxidatively damaged DNA (48% of total DNA damage) and DNA strand...

  15. Indian gift unveiled at CERN: the statue of the Indian deity Shiva was unveiled by His Excellency K M Chandrasekhar, ambassador (WTO Geneva), shown above signing the visitors' book, Anil Kakodkar, chairman of the Atomic Energy Commission and secretary of the Indian Department of Energy, and CERN's director-general, Robert Aymar.

    CERN Multimedia

    Maximilien Brice

    2004-01-01

    On 18 June CERN unveiled an unusual new landmark - a statue of the Indian deity Shiva. The statue is a gift from CERN's Indian collaborators to celebrate CERN's long association with India, which began in the 1960s. The statue was made in India in the traditional style. The original sculpture was a wax model, around which a soil mould was made. Melting the wax left a hollow into which liquid metal was poured, and once cooled the mould was split and the statue polished and given its antique finish.

  16. Large scale comparative codon-pair context analysis unveils general rules that fine-tune evolution of mRNA primary structure.

    Directory of Open Access Journals (Sweden)

    Gabriela Moura

    Full Text Available BACKGROUND: Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. METHODOLOGIES/PRINCIPAL FINDINGS: We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. CONCLUSIONS: The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage.

  17. "Is political behavior a viable coping strategy to perceived organizational politics? Unveiling the underlying resource dynamics": Correction to Sun and Chen (2017).

    Science.gov (United States)

    2017-10-01

    Reports an error in "Is Political Behavior a Viable Coping Strategy to Perceived Organizational Politics? Unveiling the Underlying Resource Dynamics" by Shuhua Sun and Huaizhong Chen ( Journal of Applied Psychology , Advanced Online Publication, May 22, 2017, np). In the article, Table 1 contained a formatting error. Correlation coefficient values in the last four cells of column 6 were misplaced with correlation coefficient values in the last four cells of column 7. All versions of this article have been corrected. (The following abstract of the original article appeared in record 2017-22542-001.) We conduct a theory-driven empirical investigation on whether political behavior, as a coping strategy to perceived organizational politics, creates resource trade-offs in moderating the relationship between perceived organizational politics and task performance. Drawing on conservation of resources theory, we hypothesize that political behavior mitigates the adverse effect of perceived organizational politics on task performance via psychological empowerment, yet exacerbates its adverse effect on task performance via emotional exhaustion. Three-wave multisource data from a sample of 222 employees and their 75 supervisors were collected for hypothesis testing. Findings supported our hypotheses. Our study enhances understandings of the complex resource dynamics of using political behavior to cope with perceived organizational politics and highlights the need to move stress-coping research from a focus on the stress-buffering effect of coping on outcomes to a focus on the underlying competing resource dynamics. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Srs2 and Mus81-Mms4 Prevent Accumulation of Toxic Inter-Homolog Recombination Intermediates.

    Directory of Open Access Journals (Sweden)

    Kenji Keyamura

    2016-07-01

    Full Text Available Homologous recombination is an evolutionally conserved mechanism that promotes genome stability through the faithful repair of double-strand breaks and single-strand gaps in DNA, and the recovery of stalled or collapsed replication forks. Saccharomyces cerevisiae ATP-dependent DNA helicase Srs2 (a member of the highly conserved UvrD family of helicases has multiple roles in regulating homologous recombination. A mutation (srs2K41A resulting in a helicase-dead mutant of Srs2 was found to be lethal in diploid, but not in haploid, cells. In diploid cells, Srs2K41A caused the accumulation of inter-homolog joint molecule intermediates, increased the levels of spontaneous Rad52 foci, and induced gross chromosomal rearrangements. Srs2K41A lethality and accumulation of joint molecules were suppressed by inactivating Rad51 or deleting the Rad51-interaction domain of Srs2, whereas phosphorylation and sumoylation of Srs2 and its interaction with sumoylated proliferating cell nuclear antigen (PCNA were not required for lethality. The structure-specific complex of crossover junction endonucleases Mus81 and Mms4 was also required for viability of diploid, but not haploid, SRS2 deletion mutants (srs2Δ, and diploid srs2Δ mus81Δ mutants accumulated joint molecule intermediates. Our data suggest that Srs2 and Mus81-Mms4 have critical roles in preventing the formation of (or in resolving toxic inter-homolog joint molecules, which could otherwise interfere with chromosome segregation and lead to genetic instability.

  19. Exploring the oxidation and iron binding profile of a cyclodextrin encapsulated quercetin complex unveiled a controlled complex dissociation through a chemical stimulus.

    Science.gov (United States)

    Diamantis, Dimitrios A; Ramesova, Sarka; Chatzigiannis, Christos M; Degano, Ilaria; Gerogianni, Paraskevi S; Karadima, Constantina; Perikleous, Sonia; Rekkas, Dimitrios; Gerothanassis, Ioannis P; Galaris, Dimitrios; Mavromoustakos, Thomas; Valsami, Georgia; Sokolova, Romana; Tzakos, Andreas G

    2018-06-07

    Flavonoids possess a rich polypharmacological profile and their biological role is linked to their oxidation state protecting DNA from oxidative stress damage. However, their bioavailability is hampered due to their poor aqueous solubility. This can be surpassed through encapsulation to supramolecular carriers as cyclodextrin (CD). A quercetin- 2HP-β-CD complex has been formerly reported by us. However, once the flavonoid is in its 2HP-β-CD encapsulated state its oxidation potential, its decomplexation mechanism, its potential to protect DNA damage from oxidative stress remained elusive. To unveil this, an array of biophysical techniques was used. The quercetin-2HP-β-CD complex was evaluated through solubility and dissolution experiments, electrochemical and spectroelectrochemical studies (Cyclic Voltammetry) UV-Vis spectroscopy, HPLC-ESI-MS/MS and HPLC-DAD, fluorescence spectroscopy, NMR Spectroscopy, theoretical calculations (density functional theory (DFT)) and biological evaluation of the protection offered against H 2 O 2 -induced DNA damage. Encapsulation of quercetin inside the supramolecule's cavity enhanced its solubility and oxidation profile is retained in its encapsulated state. Although the protective ability of the quercetin-2HP-β-CD complex against H 2 O 2 was diminished, iron serves as a chemical stimulus to dissociate the complex and release quercetin. We found that in a quercetin-2HP-β-CD inclusion complex quercetin retains its oxidation profile similarly to its native state, while iron can operate as a chemical stimulus to release quercetin from its host cavity. The oxidation profile of a natural product once it is encapsulated in a supramolecular cyclodextrin carrier as also it was discovered that decomplexation can be triggered by a chemical stimulus. Copyright © 2018. Published by Elsevier B.V.

  20. Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex

    Science.gov (United States)

    Zhou, Mowei; Yan, Jing; Romano, Christine A.; Tebo, Bradley M.; Wysocki, Vicki H.; Paša-Tolić, Ljiljana

    2018-01-01

    Manganese oxidation is an important biogeochemical process that is largely regulated by bacteria through enzymatic reactions. However, the detailed mechanism is poorly understood due to challenges in isolating and characterizing these unknown enzymes. A manganese oxidase, Mnx, from Bacillus sp. PL-12 has been successfully overexpressed in active form as a protein complex with a molecular mass of 211 kDa. We have recently used surface induced dissociation (SID) and ion mobility-mass spectrometry (IM-MS) to release and detect folded subcomplexes for determining subunit connectivity and quaternary structure. The data from the native mass spectrometry experiments led to a plausible structural model of this multicopper oxidase, which has been difficult to study by conventional structural biology methods. It was also revealed that each Mnx subunit binds a variable number of copper ions. Becasue of the heterogeneity of the protein and limited mass resolution, ambiguities in assigning some of the observed peaks remained as a barrier to fully understanding the role of metals and potential unknown ligands in Mnx. In this study, we performed SID in a modified Fourier transform-ion cyclotron resonance (FTICR) mass spectrometer. The high mass accuracy and resolution offered by FTICR unveiled unexpected artificial modifications on the protein that had been previously thought to be iron bound species based on lower resolution spectra. Additionally, isotopically resolved spectra of the released subcomplexes revealed the metal binding stoichiometry at different structural levels. This method holds great potential for in-depth characterization of metalloproteins and protein-ligand complexes. [Figure not available: see fulltext.

  1. Systems biology and genome-wide approaches to unveil the molecular players involved in the pre-germinative metabolism: implications on seed technology traits.

    Science.gov (United States)

    Macovei, Anca; Pagano, Andrea; Leonetti, Paola; Carbonera, Daniela; Balestrazzi, Alma; Araújo, Susana S

    2017-05-01

    The pre-germinative metabolism is among the most fascinating aspects of seed biology. The early seed germination phase, or pre-germination, is characterized by rapid water uptake (imbibition), which directs a series of dynamic biochemical events. Among those are enzyme activation, DNA damage and repair, and use of reserve storage compounds, such as lipids, carbohydrates and proteins. Industrial seedling production and intensive agricultural production systems require seed stocks with high rate of synchronized germination and low dormancy. Consequently, seed dormancy, a quantitative trait related to the activation of the pre-germinative metabolism, is probably the most studied seed trait in model species and crops. Single omics, systems biology, QTLs and GWAS mapping approaches have unveiled a list of molecules and regulatory mechanisms acting at transcriptional, post-transcriptional and post-translational levels. Most of the identified candidate genes encode for regulatory proteins targeting ROS, phytohormone and primary metabolisms, corroborating the data obtained from simple molecular biology approaches. Emerging evidences show that epigenetic regulation plays a crucial role in the regulation of these mentioned processes, constituting a still unexploited strategy to modulate seed traits. The present review will provide an up-date of the current knowledge on seed pre-germinative metabolism, gathering the most relevant results from physiological, genetics, and omics studies conducted in model and crop plants. The effects exerted by the biotic and abiotic stresses and priming are also addressed. The possible implications derived from the modulation of pre-germinative metabolism will be discussed from the point of view of seed quality and technology.

  2. Unveiling the Antarctic subglacial landscape.

    Science.gov (United States)

    Warner, Roland; Roberts, Jason

    2010-05-01

    Better knowledge of the subglacial landscape of Antarctica is vital to reducing uncertainties regarding prediction of the evolution of the ice sheet. These uncertainties are associated with bedrock geometry for ice sheet dynamics, including possible marine ice sheet instabilities and subglacial hydrological pathways (e.g. Wright et al., 2008). Major collaborative aerogeophysics surveys motivated by the International Polar Year (e.g. ICECAP and AGAP), and continuing large scale radar echo sounding campaigns (ICECAP and NASA Ice Bridge) are significantly improving the coverage. However, the vast size of Antarctica and logistic difficulties mean that data gaps persist, and ice thickness data remains spatially inhomogeneous. The physics governing large scale ice sheet flow enables ice thickness, and hence bedrock topography, to be inferred from knowledge of ice sheet surface topography and considerations of ice sheet mass balance, even in areas with sparse ice thickness measurements (Warner and Budd, 2000). We have developed a robust physically motivated interpolation scheme, based on these methods, and used it to generate a comprehensive map of Antarctic bedrock topography, using along-track ice thickness data assembled for the BEDMAP project (Lythe et al., 2001). This approach reduces ice thickness biases, compared to traditional inverse distance interpolation schemes which ignore the information available from considerations of ice sheet flow. In addition, the use of improved balance fluxes, calculated using a Lagrangian scheme, eliminates the grid orientation biases in ice fluxes associated with finite difference methods (Budd and Warner, 1996, Le Brocq et al., 2006). The present map was generated using a recent surface DEM (Bamber et al., 2009, Griggs and Bamber, 2009) and accumulation distribution (van de Berg et al., 2006). Comparing our results with recent high resolution regional surveys gives confidence that all major subglacial topographic features are revealed by this approach, and we advocate its consideration in future ice thickness data syntheses. REFERENCES Budd, W.F., and R.C. Warner, 1996. A computer scheme for rapid calculations of balance-flux distributions. Annals of Glaciology 23, 21-27. Bamber, J.L., J.L. Gomez Dans and J.A. Griggs, 2009. A new 1 km digital elevation model of the Antarctic derived from combined satellite radar and laser data. Part I: Data and methods. The Cryosphere 3 (2), 101-111. Griggs, J.A., and J.L. Bamber, 2009. A new digital elevation model of Antarctica derived from combined radar and laser altimetry data. Part II: Validation and error estimates, The Cryosphere, 3(2), 113-123. Le Brocq, A.M., A.J. Payne and M.J. Siegert, 2006. West Antarctic balance calculations: Impact of flux-routing algorithm, smoothing algorithm and topography. Computers and Geosciences 23(10): 1780-1795. Lythe, M. B., D.G. Vaughan, and the BEDMAP Consortium 2001, BEDMAP: A new ice thickness and subglacial topographic model of Antarctica, J. of Geophys. Res., 106(B6),11,335-11,351. van de Berg, W.J., M.R. van den Broeke, C.H. Reijmer, and E. van Meijgaard, 2006. Reassessment of the Antarctic surface mass balance using calibrated output of a regional atmospheric climate model, J. Geophys. Res., 111, D11104,doi:10.1029/2005JD006495. Warner, R.C., and W.F. Budd, 2000. Derivation of ice thickness and bedrock topography in data-gap regions over Antarctica, Annals of Glaciology, 31, 191-197. Wright, A.P., M.J. Siegert, A.M. Le Brocq, and D.B. Gore, 2008. High sensitivity of subglacial hydrological pathways in Antarctica to small ice-sheet changes, Geophys. Res. Lett., 35, L17504, doi:10.1029/2008GL034937.

  3. Unveiling the dynamics of reading

    International Nuclear Information System (INIS)

    Posner, M.; Abdullaev, Y.

    1996-01-01

    What happens in our brain when we read isolated words? Are some particular areas of cortex stimulated when these words make sense? Does the reading practice induce others areas? And what about the new senses research? Some studies carried out for a century show that two regions of the left cerebral hemisphere: the Broca and the Wernicke areas are involved. By visualizing in vivo an elementary thought as what is for instance the function of a hammer, the functional cerebral imagery (positron computed tomography, NMR imaging, electro-encephalography) allows to deepen and to explain the analysis. It reveals an areas network called semantic, in the right hemisphere too. Their activation would take place according to a very fast sequence in order to direct the eye movements during the reading. (O.M.)

  4. Unveiling Cebuano Traditional Healing Practices

    Directory of Open Access Journals (Sweden)

    ZachiaRaiza Joy S. Berdon

    2016-02-01

    Full Text Available This study aims to identify the features of Cebuano’s traditional healing practices. Specifically, it also answers the following objectives: analyze traditional healing in Cebuano’s perspectives, explain the traditional healing process practiced in terms of the traditional healers’ belief, and extrapolate perceptions of medical practitioners toward traditional healing. This study made use of qualitative approach, among five traditional healers who performed healing for not less than ten years, in the mountain barangays of Cebu City. These healers served as the primary informants who were selected because of their popularity in healing. The use of open-ended interview in local dialect and naturalistic observation provided a free listing of their verbatim accounts were noted and as primary narratives. Participation in the study was voluntary and participants were interviewed privately after obtaining their consent. The Cebuano traditional healing practices or “panambal” comprise the use of “himolso” (pulse-checking, “palakaw” (petition, “pasubay” (determining what causes the sickness and its possible means of healing, “pangalap” (searching of medicinal plants for “palina” (fumigation, “tayhop” (gentle-blowing, “tutho” (saliva-blowing,“tuob” (boiling, “orasyon” (mystical prayers, “hilot” (massage, and “barang” (sorcery. Though traditional with medical science disapproval, it contributes to a mystical identity of Cebuano healers, as a manifestation of folk Catholicism belief, in order to do a good legacy to the community that needs help. For further study, researchers may conduct further the studies on the: curative effects of medicinal plants in Cebu, psychological effect pulsechecking healed persons by the mananambal, and unmasking the other features of traditional healing.

  5. Ireland unveils petroleum tax measures

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that Ireland's government has introduced detailed petroleum tax legislation designed to boost offshore exploration and development. The petroleum tax measures, published last week and included in the government's omnibus finance bill for 1992, will provide Ireland for the first time a comprehensive petroleum tax regime. They include elements which, in tax terms, will make Ireland a most attractive location for oil and gas exploration and development, the Irish Energy Minister Robert Molloy. He the, Exploration companies will now have the benefit of the certainty of a detailed tax framework and attractive tax rates. Debate on the finance bill has begun in the Irish Dail (parliament). Under Ireland's constitution, the budget bill must be approved and signed by the president by the end of May. Failure to approve a budget bill within that time would mean the current government's collapse

  6. Unveiling the Secrets of Archimedes

    International Nuclear Information System (INIS)

    Turner, Manisha

    2008-01-01

    Progress has been made at the Stanford Linear Accelerator Center (SLAC) toward deciphering the remaining 10-20% of ancient Greek text contained in the Archimedes palimpsest. The text is known to contain valuable works by the mathematician, including the Method of Mechanical Theorems, the Equilibrium of Planes, On Floating Bodies, and several diagrams. The only surviving copy of the text was recycled into a prayer book in the Middle Ages. The ink used to write on the goat skin parchment is partly composed of iron, which is visible by x-ray radiation. To image the palimpsest pages, the parchment was framed and placed in a stage that moved according to the raster method. When an x-ray beam was incident upon the parchment the iron in the ink was detected by a germanium detector. The resultant signal was converted to a gray-scale image. It was extremely important that each line of data was well aligned with the line that came before it. The objectives of this experiment were to determine the best parameters for producing well-aligned images and to reduce the scanning time. Imaging half a page of parchment during previous beam time for this project was achieved in thirty hours. Equations were produced to evaluate count time, shutter time, and the number of pixels in this experiment. On Beamline 6-2 at the Stanford Synchrotron Radiation Laboratory (SSRL), actual scanning time was reduced by one fourth. The remaining pages were successfully imaged and sent to ancient Greek experts for translation

  7. Unveiling Privilege to Broaden Participation

    Science.gov (United States)

    Scherr, Rachel E.; Robertson, Amy D.

    2017-10-01

    The underrepresentation of women and people of color in physics has been attributed to a wide variety of factors ranging from society-wide conditions such as income inequality and sparse role models, to daily interpersonal interactions that disadvantage or discourage women and people of color from pursuing physics. These factors may be seen as manifestations of White and/or male privilege: social, economic, educational, or political advantages that are made available to Whites and males on the basis of their social identity. White male privilege pervades the discipline of physics as well as the classrooms in which physics is taught and learned. For example, physics is portrayed in textbooks as the product of individual great men, independent of all social or political contexts, rather than as being shaped by the culture of the European Enlightenment (among other cultures) or the conditions during specific international conflicts.

  8. Unveiling the Mobile Learning Paradox.

    Science.gov (United States)

    Mather, Carey; Cummings, Elizabeth

    2015-01-01

    A mobile learning paradox exists in Australian healthcare settings. Although it is increasingly acknowledged that timely, easy, and convenient access to health information using mobile learning technologies can enhance care and improve patient outcomes, currently there is an inability for nurses to access information at the point of care. Rapid growth in the use of mobile technology has created challenges for learning and teaching in the workplace. Easy access to educational resources via mobile devices challenges traditional strategies of knowledge and skill acquisition. Redesign of learning and teaching in the undergraduate curriculum and the development of policies to support the use of mobile learning at point of care is overdue. This study explored mobile learning opportunities used by clinical supervisors in tertiary and community-based facilities in two Australian States. Individual, organisation and systems level governance were sub-themes of professionalism that emerged as the main theme and impacts on learning and teaching in situ in healthcare environments. It is imperative healthcare work redesign includes learning and teaching that supports professional identity formation of students during work integrated learning.

  9. Astronomers Unveiling Life's Cosmic Origins

    Science.gov (United States)

    2009-02-01

    Processes that laid the foundation for life on Earth -- star and planet formation and the production of complex organic molecules in interstellar space -- are yielding their secrets to astronomers armed with powerful new research tools, and even better tools soon will be available. Astronomers described three important developments at a symposium on the "Cosmic Cradle of Life" at the annual meeting of the American Association for the Advancement of Science in Chicago, IL. Chemistry Cycle The Cosmic Chemistry Cycle CREDIT: Bill Saxton, NRAO/AUI/NSF Full Size Image Files Chemical Cycle Graphic (above image, JPEG, 129K) Graphic With Text Blocks (JPEG, 165K) High-Res TIFF (44.2M) High-Res TIFF With Text Blocks (44.2M) In one development, a team of astrochemists released a major new resource for seeking complex interstellar molecules that are the precursors to life. The chemical data released by Anthony Remijan of the National Radio Astronomy Observatory (NRAO) and his university colleagues is part of the Prebiotic Interstellar Molecule Survey, or PRIMOS, a project studying a star-forming region near the center of our Milky Way Galaxy. PRIMOS is an effort of the National Science Foundation's Center for Chemistry of the Universe, started at the University of Virginia (UVa) in October 2008, and led by UVa Professor Brooks H. Pate. The data, produced by the NSF's Robert C. Byrd Green Bank Telescope (GBT) in West Virginia, came from more than 45 individual observations totalling more than nine GigaBytes of data and over 1.4 million individual frequency channels. Scientists can search the GBT data for specific radio frequencies, called spectral lines -- telltale "fingerprints" -- naturally emitted by molecules in interstellar space. "We've identified more than 720 spectral lines in this collection, and about 240 of those are from unknown molecules," Remijan said. He added, "We're making available to all scientists the best collection of data below 50 GHz ever produced for the study of interstellar chemistry," Remijan said. Astronomers have already identified more than 150 molecules in interstellar space in the past 40 years, including complex organic compounds such as sugars and alcohols. "This is a major change in how we search for molecules in space," Remijan explained. "Before, people decided beforehand which molecules they were looking for, then searched in a very narrow band of radio frequencies emitted by those molecules. In this GBT survey, we've observed a wide range of frequencies, collected the data and immediately made it publicly available. Scientists anywhere can 'mine' this resource to find new molecules," he said. Another key development, presented by Crystal Brogan of the NRAO, showed that highly-detailed images of "protoclusters" of massive young stars reveal a complex mix of stars in different stages of formation, complicated gas motions, and numerous chemical clues to the physical conditions in such stellar nurseries. "We saw a much more complex picture than we had expected and now have new questions to answer," she said. Using the Smithsonian Astrophysical Observatory's Submillimeter Array (SMA) in Hawaii, Brogan and her colleagues studied a nebula 5,500 light-years from Earth in the constellation Scorpius where stars significantly more massive than our Sun are forming. "It's essential to understand what's going on in systems like this because most stars, Sun-like stars included, form in clusters," Brogan said. "The most massive stars in the cluster have a tremendous impact on the formation and environment of the rest of the cluster, including the less-massive stars and their planets," Brogan said, adding that "if we want to understand how solar systems that could support life form and evolve, we need to know how these giant stars affect their environment." Also, Brogan said, the massive young stars are surrounded by "hot cores" that include copious organic material that later may be spewed into interstellar space by stellar winds and other processes. This can help "seed" star-forming regions with some of the chemicals found by the GBT and other telescopes. Narrowing in on the problem of how planets form around young stars, David Wilner of the Harvard-Smithsonian Center for Astrophysics presented observations with the SMA that revealed new details of solar systems in the earliest stages of their formation. Wilner and his colleagues studied nine dusty disks surrounding young stars in a region in the constellation Ophiuchus. "These are the most detailed images of such disks made at these wavelengths," Wilner said. The images show the distribution of material on the same size scale as our own Solar System, and indicate that these disks are capable of producing planetary systems. Two of the disks show large central cavities where young planets may already have swept out the material from their neighborhoods. "Before, we knew that such disks have enough material to form solar systems. These new images tell us that material is in the right places to form solar systems. We're getting a tantalizing peek at the very earliest stages of planet formation," said Sean Andrews, a Hubble Fellow at the CfA. All three areas of study are poised for major advances with the impending arrival of powerful new radio-telescope facilities such as the Atacama Large Millimeter/submillimeter Array (ALMA) and the Expanded Very Large Array (EVLA), and new capabilities for the GBT. Studies of protoplanetary disks and young solar systems will benefit greatly from the groundbreaking new capabilities of ALMA, Wilner said. "While we've been able to study a few of these objects so far, ALMA will be able to give us highly-detailed images of many more that we can't study today," he said. Wilner added that ALMA also will likely provide new information on the chemicals in those still-forming planetary systems. The complex motions and chemistry of Brogan's protoclusters of young, massive stars, also will become much clearer with ALMA. "Both the detail of the images and the ability to find molecular spectral lines will improve by a factor of at least 25 with ALMA," she said. In addition, the increased power of the EVLA will give astronomers a far better look into the inner regions of the disks around young stars -- regions obscured to telescopes operating at shorter wavelengths. "We know that complex chemicals exist in interstellar space before stars and planets form. With the new research tools coming in the next few years, we're on the verge of learning how the chemistry of the interstellar clouds, the young stars and their environments, and the disks from which planets are formed is all linked together to provide the chemical basis for life on those planets," Remijan explained. Astrophysicist Neil deGrasse Tyson of the American Museum of Natural History noted, "Like no other science, astrophysics cross-pollinates the expertise of chemists, biologists, geologists and physicists, all to discover the past, present, and future of the cosmos -- and our humble place within it."

  10. Unveiling the Knowledge Sharing Culture

    NARCIS (Netherlands)

    Hendriks, P.H.J.

    2009-01-01

    It is generally acknowledged that organisation culture affects how knowledge processes such as knowledge-sharing evolve. Despite the growing attention to the aspects of culture, the knowledge management debate has not paid systematic attention to the assessment or measurement of a knowledge-sharing

  11. RNA-processing proteins regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA.

    Science.gov (United States)

    Manfrini, Nicola; Trovesi, Camilla; Wery, Maxime; Martina, Marina; Cesena, Daniele; Descrimes, Marc; Morillon, Antonin; d'Adda di Fagagna, Fabrizio; Longhese, Maria Pia

    2015-02-01

    Eukaryotic cells respond to DNA double-strand breaks (DSBs) by activating a checkpoint that depends on the protein kinases Tel1/ATM and Mec1/ATR. Mec1/ATR is activated by RPA-coated single-stranded DNA (ssDNA), which arises upon nucleolytic degradation (resection) of the DSB. Emerging evidences indicate that RNA-processing factors play critical, yet poorly understood, roles in genomic stability. Here, we provide evidence that the Saccharomyces cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA. The lack of Xrn1 inhibits ssDNA generation at the DSB by preventing the loading of the MRX complex. By contrast, DSB resection is not affected in the absence of Rrp6 or Trf4, but their lack impairs the recruitment of RPA, and therefore of Mec1, to the DSB. Rrp6 and Trf4 inactivation affects neither Rad51/Rad52 association nor DSB repair by homologous recombination (HR), suggesting that full Mec1 activation requires higher amount of RPA-coated ssDNA than HR-mediated repair. Noteworthy, deep transcriptome analyses do not identify common misregulated gene expression that could explain the observed phenotypes. Our results provide a novel link between RNA processing and genome stability. © 2014 The Authors.

  12. Homologous recombination and non-homologous end-joining repair pathways in bovine embryos with different developmental competence

    International Nuclear Information System (INIS)

    Henrique Barreta, Marcos; Garziera Gasperin, Bernardo; Braga Rissi, Vitor; Cesaro, Matheus Pedrotti de; Ferreira, Rogério; Oliveira, João Francisco de; Gonçalves, Paulo Bayard Dias; Bordignon, Vilceu

    2012-01-01

    This study investigated the expression of genes controlling homologous recombination (HR), and non-homologous end-joining (NHEJ) DNA-repair pathways in bovine embryos of different developmental potential. It also evaluated whether bovine embryos can respond to DNA double-strand breaks (DSBs) induced with ultraviolet irradiation by regulating expression of genes involved in HR and NHEJ repair pathways. Embryos with high, intermediate or low developmental competence were selected based on the cleavage time after in vitro insemination and were removed from in vitro culture before (36 h), during (72 h) and after (96 h) the expected period of embryonic genome activation. All studied genes were expressed before, during and after the genome activation period regardless the developmental competence of the embryos. Higher mRNA expression of 53BP1 and RAD52 was found before genome activation in embryos with low developmental competence. Expression of 53BP1, RAD51 and KU70 was downregulated at 72 h and upregulated at 168 h post-insemination in response to DSBs induced by ultraviolet irradiation. In conclusion, important genes controlling HR and NHEJ DNA-repair pathways are expressed in bovine embryos, however genes participating in these pathways are only regulated after the period of embryo genome activation in response to ultraviolet-induced DSBs.

  13. Homologous recombination and non-homologous end-joining repair pathways in bovine embryos with different developmental competence

    Energy Technology Data Exchange (ETDEWEB)

    Henrique Barreta, Marcos [Universidade Federal de Santa Catarina, Campus Universitario de Curitibanos, Curitibanos, SC (Brazil); Laboratorio de Biotecnologia e Reproducao Animal-BioRep, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Garziera Gasperin, Bernardo; Braga Rissi, Vitor; Cesaro, Matheus Pedrotti de [Laboratorio de Biotecnologia e Reproducao Animal-BioRep, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Ferreira, Rogerio [Centro de Educacao Superior do Oeste-Universidade do Estado de Santa Catarina, Chapeco, SC (Brazil); Oliveira, Joao Francisco de; Goncalves, Paulo Bayard Dias [Laboratorio de Biotecnologia e Reproducao Animal-BioRep, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Bordignon, Vilceu, E-mail: vilceu.bordignon@mcgill.ca [Department of Animal Science, McGill University, Ste-Anne-De-Bellevue, QC (Canada)

    2012-10-01

    This study investigated the expression of genes controlling homologous recombination (HR), and non-homologous end-joining (NHEJ) DNA-repair pathways in bovine embryos of different developmental potential. It also evaluated whether bovine embryos can respond to DNA double-strand breaks (DSBs) induced with ultraviolet irradiation by regulating expression of genes involved in HR and NHEJ repair pathways. Embryos with high, intermediate or low developmental competence were selected based on the cleavage time after in vitro insemination and were removed from in vitro culture before (36 h), during (72 h) and after (96 h) the expected period of embryonic genome activation. All studied genes were expressed before, during and after the genome activation period regardless the developmental competence of the embryos. Higher mRNA expression of 53BP1 and RAD52 was found before genome activation in embryos with low developmental competence. Expression of 53BP1, RAD51 and KU70 was downregulated at 72 h and upregulated at 168 h post-insemination in response to DSBs induced by ultraviolet irradiation. In conclusion, important genes controlling HR and NHEJ DNA-repair pathways are expressed in bovine embryos, however genes participating in these pathways are only regulated after the period of embryo genome activation in response to ultraviolet-induced DSBs.

  14. Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy.

    Science.gov (United States)

    Hengel, Sarah R; Spies, M Ashley; Spies, Maria

    2017-09-21

    To maintain stable genomes and to avoid cancer and aging, cells need to repair a multitude of deleterious DNA lesions, which arise constantly in every cell. Processes that support genome integrity in normal cells, however, allow cancer cells to develop resistance to radiation and DNA-damaging chemotherapeutics. Chemical inhibition of the key DNA repair proteins and pharmacologically induced synthetic lethality have become instrumental in both dissecting the complex DNA repair networks and as promising anticancer agents. The difficulty in capitalizing on synthetically lethal interactions in cancer cells is that many potential targets do not possess well-defined small-molecule binding determinates. In this review, we discuss several successful campaigns to identify and leverage small-molecule inhibitors of the DNA repair proteins, from PARP1, a paradigm case for clinically successful small-molecule inhibitors, to coveted new targets, such as RAD51 recombinase, RAD52 DNA repair protein, MRE11 nuclease, and WRN DNA helicase. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Pomegranate Intake Protects Against Genomic Instability Induced by Medical X-rays In Vivo in Mice.

    Science.gov (United States)

    Nallanthighal, Sameera; Shirode, Amit B; Judd, Julius A; Reliene, Ramune

    2016-01-01

    Ionizing radiation (IR) is a well-documented human carcinogen. The increased use of IR in medical procedures has doubled the annual radiation dose and may increase cancer risk. Genomic instability is an intermediate lesion in IR-induced cancer. We examined whether pomegranate extract (PE) suppresses genomic instability induced by x-rays. Mice were treated orally with PE and exposed to an x-ray dose of 2 Gy. PE intake suppressed x-ray-induced DNA double-strand breaks (DSBs) in peripheral blood and chromosomal damage in bone marrow. We hypothesized that PE-mediated protection against x-ray-induced damage may be due to the upregulation of DSB repair and antioxidant enzymes and/or increase in glutathione (GSH) levels. We found that expression of DSB repair genes was not altered (Nbs1 and Rad50) or was reduced (Mre11, DNA-PKcs, Ku80, Rad51, Rad52 and Brca2) in the liver of PE-treated mice. Likewise, mRNA levels of antioxidant enzymes were reduced (Gpx1, Cat, and Sod2) or were not altered (HO-1 and Sod1) as a function of PE treatment. In contrast, PE-treated mice with and without IR exposure displayed higher hepatic GSH concentrations than controls. Thus, ingestion of pomegranate polyphenols is associated with inhibition of x-ray-induced genomic instability and elevated GSH, which may reduce cancer risk.

  16. Enhancement of radiosensitivity in H1299 cancer cells by actin-associated protein cofilin

    International Nuclear Information System (INIS)

    Lee, Y.-J.; Sheu, T.-J.; Keng, Peter C.

    2005-01-01

    Cofilin is an actin-associated protein that belongs to the actin depolymerization factor/cofilin family and is important for regulation of actin dynamics. Cofilin can import actin monomers into the nucleus under certain stress conditions, however the biological effects of nuclear transport are unclear. In this study, we found that over-expression of cofilin led to increased radiation sensitivity in human non-small lung cancer H1299 cells. Cell survival as determined by colony forming assay showed that cells over-expressing cofilin were more sensitive to ionizing radiation (IR) than normal cells. To determine whether the DNA repair capacity was altered in cofilin over-expressing cells, comet assays were performed on irradiated cells. Repair of DNA damage caused by ionizing radiation was detected in cofilin over-expressing cells after 24 h of recovery. Consistent with this observation, the key components for repair of DNA double-strand breaks, including Rad51, Rad52, and Ku70/Ku80, were down-regulated in cofilin over-expressing cells after IR exposure. These findings suggest that cofilin can influence radiosensitivity by altering DNA repair capacity

  17. Two pathways of DNA double-strand break repair in G1 cells of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Glazunov, A.V.

    1988-01-01

    The G1 cells of the diploid yeast Saccharomyces cerevislae are known to be capable of a slow repair of DNA double-strand breaks (DSB) during holding the cells in a non-nutrient medium. In the present paper, it has been shown that S. cerevislae cells γ-irradiated in the G1 phase of cell cycle are capable of fast repair of DNA DSB; this process is completed within 30-40 min of holding the cells in water at 28 deg C. For this reason, the kinetics of DNA DSB repair during holding the cells in a non-nutrient medium are biphasic, i.e., the first, ''fast'' phase is completed within 30-40 min; wheras the second, ''slow'' one, within 48 h. Mutations rad51, rad52, rad54 and rad55 inhibit the fast repair of DNA DSB, whereas mutations rad50, rad53 and rad57 do not practically influence this process. It has been shown that the observed fast and slow repair of DNA DSB in the G1 diploid cells of S, cerevislae are separate pathways of DNA DSB repair in yeast

  18. TALEN-Induced Double-Strand Break Repair of CTG Trinucleotide Repeats

    Directory of Open Access Journals (Sweden)

    Valentine Mosbach

    2018-02-01

    Full Text Available Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for several neurodegenerative disorders, including myotonic dystrophy and Huntington’s disease. Because expansions trigger the disease, contracting repeat length could be a possible approach to gene therapy for these disorders. Here, we show that a TALEN-induced double-strand break was very efficient at contracting expanded CTG repeats in yeast. We show that RAD51, POL32, and DNL4 are dispensable for double-strand break repair within CTG repeats, the only required genes being RAD50, SAE2, and RAD52. Resection was totally abolished in the absence of RAD50 on both sides of the break, whereas it was reduced in a sae2Δ mutant on the side of the break containing the longest repeat tract, suggesting that secondary structures at double-strand break ends must be removed by the Mre11-Rad50 complex and Sae2. Following the TALEN double-strand break, single-strand annealing occurred between both sides of the repeat tract, leading to repeat contraction.

  19. From the Icy Satellites to Small Moons and Rings: Spectral Indicators by Cassini-VIMS Unveil Compositional Trends in the Saturnian System

    Science.gov (United States)

    Filacchione, G.; Capaccioni, F.; Ciarniello, M.; Nicholson, P. D.; Clark, R. N.; Cuzzi, J. N.; Buratti, B. B.; Cruikshank, D. P.; Brown, R. H.

    2017-01-01

    flat reflectance in the visible, making them remarkably different with respect to the other small moons. Moreover, we have observed that the two Tethys' lagrangian moons appear spectrally different, with Calypso characterized by more intense water ice bands than Telesto. Conversely, at visible wavelengths Polydeuces, Telesto and Methone are in absolute the more blue objects in the Saturn's system. The red slopes measured in the visible range on disk-integrated spectral data, showing varying degrees on all of the satellites, could be caused more by exogenic processes than by geologic and endogenic events which are operating on more localized scales. The principal exogenic processes active in the Saturn's system [11] which alter the satellites and rings surfaces are the E ring particles bombardment, the interaction with corotating plasma and energetic particles, the bombardment of exogenic dark material [12] and the water ice photolysis. A discussion about the correlations between these processes and the o bserved spectral classes is given. With the approaching of the Cassini "Gran Finale" orbits, VIMS will unveil with unprecedented spatial resolution the spectral properties of many small moons and rings. These data will be extremely valuable to improve our classification of the Saturn's satellites and rings.

  20. Males unveiling the different forms of conjugal violence Hombres develando las formas de la violencia conyugal Homens desvelando as formas da violência conjugal

    Directory of Open Access Journals (Sweden)

    Nadirlene Pereira Gomes

    2008-01-01

    Full Text Available OBJECTIVES: To identify the forms of unveiling violence from the discourse of a male group that perform violent acts against their partners. METHODS: Qualitative approach study. Seven males were interviewed and they beat their partners, residing in the outskirts of Salvador, BA. The subjects speeches were analyzed by means of content analysis. RESULTS: The study showed that the males interviewed experienced conjugal violence, which is revealed psychologically, sexually, morally and physically. CONCLUSION: The conjugal relationship is marked by an asymmetrical relation between males and females. When males feel they are being threatened, they use some means to control their partners, resorting to physical violence, inclusive. It is imperative to implement public policies that guarantee interventions with males and females, leading them to understand the social construction of gender identity.OBJETIVOS: Identificar las formas de develamiento de la violencia a partir del discurso de un grupo de hombres que practican actos violentos contra sus compañeras. MÉTODOS: Se trata de un estudio de abordaje cualitativo. Fueron entrevistados siete hombres que cometían actos violentos contra sus compañeras, residentes en la periferie de Salvador-BA. Las narrativas de los sujetos fueron analizadas por medio del análisis de contenido. RESULTADOS: El estudio mostró que los hombres entrevistados vivencian la violencia conyugal, la cual se devela bajo las formas psicológica, sexual, moral y física. CONCLUSIÓN: El relacionamiento conyugal está marcado por una relación asimétrica entre hombres y mujeres, de modo que, al sentir que su poder está siendo amenazado, el hombre utiliza algunos medios para controlar a sus compañeras, haciendo uso, inclusive, de la violencia física. Se hace necesaria la implementación de políticas públicas que garanticen intervenciones junto a hombres y mujeres que conduzcan a unos y otros a la comprensión de la construcci

  1. News Particle Physics: ATLAS unveils mural at CERN Prize: Corti Trust invites essay entries Astrophysics: CERN holds cosmic-ray conference Researchers in Residence: Lord Winston returns to school Music: ATLAS scientists record physics music Conference: Champagne flows at Reims event Competition: Students triumph at physics olympiad Teaching: Physics proves popular in Japanese schools Forthcoming Events

    Science.gov (United States)

    2011-01-01

    Particle Physics: ATLAS unveils mural at CERN Prize: Corti Trust invites essay entries Astrophysics: CERN holds cosmic-ray conference Researchers in Residence: Lord Winston returns to school Music: ATLAS scientists record physics music Conference: Champagne flows at Reims event Competition: Students triumph at physics olympiad Teaching: Physics proves popular in Japanese schools Forthcoming Events

  2. BRITE-Constellation high-precision time-dependent photometry of the early O-type supergiant ζ Puppis unveils the photospheric drivers of its small- and large-scale wind structures

    Science.gov (United States)

    Ramiaramanantsoa, Tahina; Moffat, Anthony F. J.; Harmon, Robert; Ignace, Richard; St-Louis, Nicole; Vanbeveren, Dany; Shenar, Tomer; Pablo, Herbert; Richardson, Noel D.; Howarth, Ian D.; Stevens, Ian R.; Piaulet, Caroline; St-Jean, Lucas; Eversberg, Thomas; Pigulski, Andrzej; Popowicz, Adam; Kuschnig, Rainer; Zocłońska, Elżbieta; Buysschaert, Bram; Handler, Gerald; Weiss, Werner W.; Wade, Gregg A.; Rucinski, Slavek M.; Zwintz, Konstanze; Luckas, Paul; Heathcote, Bernard; Cacella, Paulo; Powles, Jonathan; Locke, Malcolm; Bohlsen, Terry; Chené, André-Nicolas; Miszalski, Brent; Waldron, Wayne L.; Kotze, Marissa M.; Kotze, Enrico J.; Böhm, Torsten

    2018-02-01

    From 5.5 months of dual-band optical photometric monitoring at the 1 mmag level, BRITE-Constellation has revealed two simultaneous types of variability in the O4I(n)fp star ζ Puppis: one single periodic non-sinusoidal component superimposed on a stochastic component. The monoperiodic component is the 1.78-d signal previously detected by Coriolis/Solar Mass Ejection Imager, but this time along with a prominent first harmonic. The shape of this signal changes over time, a behaviour that is incompatible with stellar oscillations but consistent with rotational modulation arising from evolving bright surface inhomogeneities. By means of a constrained non-linear light-curve inversion algorithm, we mapped the locations of the bright surface spots and traced their evolution. Our simultaneous ground-based multisite spectroscopic monitoring of the star unveiled cyclical modulation of its He II λ4686 wind emission line with the 1.78-d rotation period, showing signatures of corotating interaction regions that turn out to be driven by the bright photospheric spots observed by BRITE. Traces of wind clumps are also observed in the He II λ4686 line and are correlated with the amplitudes of the stochastic component of the light variations probed by BRITE at the photosphere, suggesting that the BRITE observations additionally unveiled the photospheric drivers of wind clumps in ζ Pup and that the clumping phenomenon starts at the very base of the wind. The origins of both the bright surface inhomogeneities and the stochastic light variations remain unknown, but a subsurface convective zone might play an important role in the generation of these two types of photospheric variability.

  3. EL CUERPO DEL HÉROE: EL DESCUBRIMIENTO DEL BUSTO DE UN SOLDADO CAÍDO EN LA GUERRA DE MALVINAS / The Hero's Body: the Unveiling of the Bust of a Soldier Fallen in the Malvinas War

    Directory of Open Access Journals (Sweden)

    Laura Marina Panizo

    2013-07-01

    Full Text Available En este artículo veremos de qué manera el descubrimiento del busto del soldado caído en la Guerra de Malvinas, Elbio Aaujo, expresa un marco simbólico de interpretación de la muerte en la guerra de un grupo particular, y deviene para los familiares en un escenario de dramatización de la muerte que por la falta del cuerpo no pudo enfrentarse a través de sus formas habituales. Observaré al ritual desde el punto de vista de la performance, ya que nos permite ver de qué manera estamos refiriéndonos a experiencias vivenciadas en escenarios determinados, a través de los cuales es habitada la muerte de una persona, y significada de una manera particular. Así, veremos que a través del descubrimiento del busto, se sustituye la presencia del cuerpo ausente por otra materialidad y la puesta en escena actúa no sólo como un canal de comunicación a través del cual los deudos expresan al resto de la sociedad sus experiencias y los sentidos dados a la muerte en la guerra, sino que deviene también, para los familiares involucrados, en una práctica transformadora en cuanto a la reflexividad que propone sobre la condición social del muerto. Abstract In this paper we will show how the unveiling of the bust of Elbio Aaujo, a soldier fallen in the Malvinas War, expresses the symbolic framework for interpretation of death in battle of a particular group, at the same time becoming for his relatives the stage for dramatization of a death that could not be dealt with in the usual manner due to the lack of a body. We will deal with the ritual from the point of view of performance, since it allows us to see the ways experiences are lived in specific scenes, through which the death of a person is inhabited and signified in a particular way. Therefore, we will show that through the unveiling of the bust, the lack of the body is replaced by a different materiality and that the performance acts not only as a communication channel through which the bereaved

  4. Unveiling the pan-genome of the SXT/R391 family of ICEs: molecular characterisation of new variable regions of SXT/R391-like ICEs detected in Pseudoalteromonas sp. and Vibrio scophthalmi.

    Science.gov (United States)

    Rodríguez-Blanco, Arturo; Lemos, Manuel L; Osorio, Carlos R

    2016-08-01

    Integrating conjugative elements (ICEs) of the SXT/R391 family have been identified in fish-isolated bacterial strains collected from marine aquaculture environments of the northwestern Iberian Peninsula. Here we analysed the variable regions of two ICEs, one preliminarily characterised in a previous study (ICEVscSpa3) and one newly identified (ICEPspSpa1). Bacterial strains harboring these ICEs were phylogenetically assigned to Vibrio scophthalmi and Pseudoalteromonas sp., thus constituting the first evidence of SXT/R391-like ICEs in the genus Pseudoalteromonas to date. Variable DNA regions, which confer element-specific properties to ICEs of this family, were characterised. Interestingly, the two ICEs contained 29 genes not found in variable DNA insertions of previously described ICEs. Most notably, variable gene content for ICEVscSpa3 showed similarity to genes potentially involved in housekeeping functions of replication, nucleotide metabolism and transcription. For these genes, closest homologues were found clustered in the genome of Pseudomonas psychrotolerans L19, suggesting a transfer as a block to ICEVscSpa3. Genes encoding antibiotic resistance, restriction modification systems and toxin/antitoxin systems were absent from hotspots of ICEVscSpa3. In contrast, the variable gene content of ICEPspSpa1 included genes involved in restriction/modification functions in two different hotspots and genes related to ICE maintenance. The present study unveils a relatively large number of novel genes in SXT/R391-ICEs, and demonstrates the major role of ICE elements as contributors to horizontal gene transfer.

  5. ­Genomic data mining of the marine actinobacteria Streptomyces sp. H-KF8 unveils insights into multi-stress related genes and metabolic pathways involved in antimicrobial synthesis

    Directory of Open Access Journals (Sweden)

    Agustina Undabarrena

    2017-02-01

    Full Text Available Streptomyces sp. H-KF8 is an actinobacterial strain isolated from marine sediments of a Chilean Patagonian fjord. Morphological characterization together with antibacterial activity was assessed in various culture media, revealing a carbon-source dependent activity mainly against Gram-positive bacteria (S. aureus and L. monocytogenes. Genome mining of this antibacterial-producing bacterium revealed the presence of 26 biosynthetic gene clusters (BGCs for secondary metabolites, where among them, 81% have low similarities with known BGCs. In addition, a genomic search in Streptomyces sp. H-KF8 unveiled the presence of a wide variety of genetic determinants related to heavy metal resistance (49 genes, oxidative stress (69 genes and antibiotic resistance (97 genes. This study revealed that the marine-derived Streptomyces sp. H-KF8 bacterium has the capability to tolerate a diverse set of heavy metals such as copper, cobalt, mercury, chromate and nickel; as well as the highly toxic tellurite, a feature first time described for Streptomyces. In addition, Streptomyces sp. H-KF8 possesses a major resistance towards oxidative stress, in comparison to the soil reference strain Streptomyces violaceoruber A3(2. Moreover, Streptomyces sp. H-KF8 showed resistance to 88% of the antibiotics tested, indicating overall, a strong response to several abiotic stressors. The combination of these biological traits confirms the metabolic versatility of Streptomyces sp. H-KF8, a genetically well-prepared microorganism with the ability to confront the dynamics of the fjord-unique marine environment.

  6. A mechanism of gene amplification driven by small DNA fragments.

    Directory of Open Access Journals (Sweden)

    Kuntal Mukherjee

    Full Text Available DNA amplification is a molecular process that increases the copy number of a chromosomal tract and often causes elevated expression of the amplified gene(s. Although gene amplification is frequently observed in cancer and other degenerative disorders, the molecular mechanisms involved in the process of DNA copy number increase remain largely unknown. We hypothesized that small DNA fragments could be the trigger of DNA amplification events. Following our findings that small fragments of DNA in the form of DNA oligonucleotides can be highly recombinogenic, we have developed a system in the yeast Saccharomyces cerevisiae to capture events of chromosomal DNA amplification initiated by small DNA fragments. Here we demonstrate that small DNAs can amplify a chromosomal region, generating either tandem duplications or acentric extrachromosomal DNA circles. Small fragment-driven DNA amplification (SFDA occurs with a frequency that increases with the length of homology between the small DNAs and the target chromosomal regions. SFDA events are triggered even by small single-stranded molecules with as little as 20-nt homology with the genomic target. A double-strand break (DSB external to the chromosomal amplicon region stimulates the amplification event up to a factor of 20 and favors formation of extrachromosomal circles. SFDA is dependent on Rad52 and Rad59, partially dependent on Rad1, Rad10, and Pol32, and independent of Rad51, suggesting a single-strand annealing mechanism. Our results reveal a novel molecular model for gene amplification, in which small DNA fragments drive DNA amplification and define the boundaries of the amplicon region. As DNA fragments are frequently found both inside cells and in the extracellular environment, such as the serum of patients with cancer or other degenerative disorders, we propose that SFDA may be a common mechanism for DNA amplification in cancer cells, as well as a more general cause of DNA copy number variation

  7. Reconstitution of DNA strand exchange mediated by Rhp51 recombinase and two mediators.

    Directory of Open Access Journals (Sweden)

    Yumiko Kurokawa

    2008-04-01

    Full Text Available In the fission yeast Schizosaccharomyces pombe, genetic evidence suggests that two mediators, Rad22 (the S. pombe Rad52 homolog and the Swi5-Sfr1 complex, participate in a common pathway of Rhp51 (the S. pombe Rad51 homolog-mediated homologous recombination (HR and HR repair. Here, we have demonstrated an in vitro reconstitution of the central step of DNA strand exchange during HR. Our system consists entirely of homogeneously purified proteins, including Rhp51, the two mediators, and replication protein A (RPA, which reflects genetic requirements in vivo. Using this system, we present the first robust biochemical evidence that concerted action of the two mediators directs the loading of Rhp51 onto single-stranded DNA (ssDNA precoated with RPA. Dissection of the reaction reveals that Rad22 overcomes the inhibitory effect of RPA on Rhp51-Swi5-Sfr1-mediated strand exchange. In addition, Rad22 negates the requirement for a strict order of protein addition to the in vitro system. However, despite the presence of Rad22, Swi5-Sfr1 is still essential for strand exchange. Importantly, Rhp51, but neither Rad22 nor the Swi5-Sfr1 mediator, is the factor that displaces RPA from ssDNA. Swi5-Sfr1 stabilizes Rhp51-ssDNA filaments in an ATP-dependent manner, and this stabilization is correlated with activation of Rhp51 for the strand exchange reaction. Rad22 alone cannot activate the Rhp51 presynaptic filament. AMP-PNP, a nonhydrolyzable ATP analog, induces a similar stabilization of Rhp51, but this stabilization is independent of Swi5-Sfr1. However, hydrolysis of ATP is required for processive strand transfer, which results in the formation of a long heteroduplex. Our in vitro reconstitution system has revealed that the two mediators have indispensable, but distinct, roles for mediating Rhp51 loading onto RPA-precoated ssDNA.

  8. Unveiling the formation and evolution of comets

    Science.gov (United States)

    Lasue, J.; Levasseur-Regourd, A. C.; Botet, R.; Coradini, A.; Desanctis, M. C.; Kofman, W.

    2007-08-01

    Comet nuclei are considered as the most pristine bodies of the solar system and consequently their study sheds an important light on the processes occurring during the initial stages of the solar system formation. The analysis of the porosity and bulk density of such primordial bodies is especially important to understand their capacity to retain volatile components (organics and ices) present in the early solar nebula. Typical tensile strengths deduced for comet nuclei range from below 102N.m-2 from the Deep Impact mission [1] up to 104N.m-2 from the study of comet C/1999 S4 LINEAR breakup [2] and meteoroids [3]. A bulk density of about 350 kg/m3 has been obtained for 9P/Tempel 1 from the Deep Impact mission [4]. Moreover the properties of dust released from the comets strongly confirm such values. Instruments flying-by comet 1P/Halley had discovered the presence of organics, and pointed out the dust low albedo and extremely low density while analyses of Interplanetary Dust Particles collected in the stratosphere and remote spectroscopic observations have indicated that cometary dust consists of an un-equilibrated heterogeneous mixture of organic refractory materials and of amorphous and crystalline silicate minerals [5], as recently confirmed by Stardust [6]. Observations of the solar scattered light, together with elaborate simulations, give an estimation of the mass ratio between silicates and absorbing organics, the size distribution and the structure of the dust particles, suggesting that a fair amount consists in fluffy aggregates built up from submicronic grains [7,8], as recently confirmed by the analysis of dust craters and aerogel tracks on Stardust collector showing for some large particles (up to 100 μm) an extraordinary fluffy structure [9]. Simulations have been developed in our teams to describe the aspects of comet aggregation and evolution that have not been thoroughly explained yet. Particle aggregation simulations taking into account cohesive energy of the cometesimals and their probable re-accretion after collision events in the Kuiper Belt can be used to interpret the typical layered structure observed for comet 9P/Tempel 1 [10] and evaluate the tensile strengths inside the nucleus. Thermal evolution models of comet nuclei explain the current comet observations with the presence of primordial volatiles [11]. A quasi-3D approach (for non-spherically shaped comet nuclei) is used to interpret the current activity of comets in terms of initial characteristics, and to predict shape and internal stratification evolution of the nucleus. Tensile strength indications and activity predictions from such simulations will provide vital clues for the international Rosetta mission landing on the nucleus of comet 67P/Churyumov-Gerasimenko. During the Rosetta rendezvous, the CONSERT experiment will investigate the deep interior of the nucleus from measurements of the propagation delay of long wavelength radio waves [12]. The analysis and 3D reconstruction of the waves passing through the nucleus will put constraints on the materials constituting the comet and the inhomogeneities within the nucleus. While it is now established that nuclei have low densities and are significantly fragile, it will then be possible to better constrain their formation process and their evolution. [1] A'Hearn et al., Science 310, 258 (2005) [2] Samarasinha, Icarus 154, 540 (2001) [3] Trigo-Rodriguez and Llorca, Mon. Not. R. Astron. Soc. 372, 655 (2006) [4] A'Hearn and Combi, Icarus 187, 1 (2007) [5] Hanner and Bradley, In: Comets II, Festou, Keller, Weaver (eds), pp 555 (2004) [6] Brownlee et al., Science 314, 1711 (2006) [7] Lasue and Levasseur-Regourd, J. Quant. Spectros. Radiat. Transfer 100, 220-236 (2006) [8]Levasseur-Regourd et al., (2007), Planet Space Sci., doi:10.1016/j.pss.2006.11.014 in press. [9] Hörz et al., Science 314, 1716 (2006) [10] Belton et al., Icarus 187, 332 (2007) [11] DeSanctis et al., Astron. Astrophys. 444, 605 (2005) [12] Kofman et al., (2007), Space Sci. Rev., doi: 10.1007/s11214-006-9034-9 in press.

  9. Anaesthesia practice and reproductive outcomes: Facts unveiled

    Directory of Open Access Journals (Sweden)

    Amrutha Bindu Nagella

    2015-01-01

    Full Text Available Background and Aims: Anaesthetic practice is associated with a risk of chronic exposure to anaesthetic agents. With the advent of newer inhalational agents and changing anaesthetic practices, the risks for anaesthesiologists with regard to adverse reproductive outcomes is unknown. Hence, a nationwide online survey was conducted to study the anaesthetic practices prevalent in India and their association, if any, with poor reproductive outcomes. Methods: The online survey involved 9974 anaesthesiologists. A questionnaire soliciting information regarding anaesthetic practice techniques, reproductive outcomes and perinatal outcomes was designed. All the anaesthesiologists in the ISA National database were mailed a link to the above questionnaire. Results: Female anaesthesiologists and spouses of male anaesthesiologists had a higher incidence of first trimester spontaneous abortions than the general population. Female anaesthesiologists when compared with spouses of male anaesthesiologists faced more difficulty with conception (P = 0.015. Female anaesthesiologists who worked in the operating room (OR in their first trimester of gestation had a higher incidence of spontaneous abortions than those who did not work in the OR (P = 0.05. Longer hours of general anaesthesia conducted in the first trimester of pregnancy was associated with a higher risk of birth defects in their progeny (P = 0.05. Conclusion: Spontaneous abortions and birth defects were higher in female anaesthesiologists who worked in the OR in the first trimester of gestation. Both female anaesthesiologists and spouses of male anaesthesiologists had a greater risk for a first trimester miscarriage than the general population.

  10. The Quantum World Unveiled by Electron Waves

    International Nuclear Information System (INIS)

    Akira Tonomura

    1998-08-01

    This book emphasizes the experimental aspects of the author's own laboratory. Instead of merely presenting a dry collection of knowledge, the author unfolds to the readers his vivid experiences of enthusiasm, sheer pleasure, and yet frustrations in the course of his own research. In this way, the book aims to arouse the reader's curiosity in the strange behaviors of electrons in the microscopic world, which differ significantly from our common sense and daily experiences of the macroscopic world. The fields of physics explored in the book are quantum mechanics, superconductivity, electron microscopy, holography, magnetism, and unified theory - areas of the author's study using electron waves. A world-renowned expert in electron holography, the author promises the interested reader a fascinating ride through the quantum world of electron waves, accompanied by many colorful illustrations that delight the senses and captivate the imagination

  11. Unveiling the Sweet Conformations of Ketohexoses

    Science.gov (United States)

    Bermudez, C.; Pena, I.; Cabezas, C.; Daly, A. M.; Mata, S.; Alonso, J. L.

    2013-06-01

    The conformational behavior of ketohexoses D-Fructose, L-Sorbose, D-Tagatose and D-Psicose has been revealed from their rotational spectra. A broadband microwave spectrometer (CP-FTMW) has been used to rapidly acquire the rotational spectra in the 6 to 12 GHz frequency range. All observed species are stabilized by complicated intramolecular hydrogen-bonding networks. Structural motifs related to the sweetness of ketohexoses are revealed. G. G. Brown, B. C. Dian, K. O. Douglass, S. M. Geyer, S. T. Shipman, B. H. Pate, Rev. Sci. Instrum. 2008, 79, 053103. S. Mata, I. Peña, C. Cabezas, J. C. López, J. L. Alonso, J. Mol. Spectrosc. 2012, 280, 91.

  12. Unveiling China's impact on African environment

    International Nuclear Information System (INIS)

    Peh, Kelvin S.-H.; Eyal, Jonathan

    2010-01-01

    China's economic involvement in Africa has recently attracted unprecedented global attention. Chinese interest in the oil, gas and other natural resources on the continent entails - it is alleged - more harm than good for Africa's environment. Yet much of the discussion about China's role in Africa is conducted in the absence of the most basic information and raw data. We believe that despite all the obvious informational obstacles, the secrecy veil on the China's African involvement can be lifted. And this, in turn, could produce a more accurate picture of the real impact on the Africa's environment.

  13. How to unveil a T Tauri star

    International Nuclear Information System (INIS)

    Hartigan, P.; Hartmann, L.; Kenyon, S.; Hewett, R.; Stauffer, J.

    1989-01-01

    A method for separating the 'veiling' continuum often present in T Tauri stars from the underlying photospheric spectrum is described. Echelle observations from 5100 to 6800 A of the partially veiled T Tauri star BP Tau were analyzed to determine the shape of the veiling spectrum. The residuals of the fit indicate the deviation of the veiling spectrum from a simple continuum and identify the location and strength of any emission-line components. It is shown, by means of goodness-of-fit tests, that the spectrum of BP Tau can be decomposed into a normal stellar spectrum plus a smooth veiling continuum with only a few emission lines superposed. The continuum dominates the veiling spectrum in this spectral region; the veiling does not arise from numerous deep photospheric absorption lines that are filled in by weak emission. 36 refs

  14. Greenland unveils terms for offshore licenses

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that Greenland has spelled out terms for its first round of offshore licensing. The action off western Greenland could lead to the first oil and gas exploration there since an unsuccessful campaign in the 1970s. The Mineral Resources Administration (MRA) for Greenland pegged exploration license terms on 133 blocks, all south of the 66th parallel, at 10 years with options for 2 year extensions to a maximum of 6 more years. The license can cover as many as six blocks. In the first 3 year period companies will have only a seismic obligation of 1,588 km per six blocks. For the second 3 year period there will be a one well obligation and one well in each subsequent 2 year periods

  15. Unveiling the Higgs mechanism to students

    International Nuclear Information System (INIS)

    Organtini, Giovanni

    2012-01-01

    In this paper we outline a lecture given to undergraduate students to explain why physicists are so interested in the Higgs boson. The lecture was conceived for students not yet familiar with advanced physics and is suitable for those studying several other disciplines. The Higgs mechanism is introduced through semi-classical arguments mimicking basic field-theory concepts, assuming the validity of a symmetry principle in the expression of the energy of particles in a classical field. The lecture is divided into two parts. The first, suitable even for high-school students, shows how the mass of a particle results from a dynamical effect caused by interaction between a massless particle and a field (as in the Higgs mechanism). The audience for the second, much more technical part consists mainly of teachers and university students from disciplines other than physics. (paper)

  16. Unveiling the Mystical Lucban Pahiyas Festival

    Directory of Open Access Journals (Sweden)

    Rufina C. Rosaroso

    2015-11-01

    Full Text Available This is an ethnographic study which described the local knowledge of the Lucbanin on Pahiyas. The generation of information on the local knowledge as described by the Lucbanin unfolded the natives‘ meanings in celebrating Philippine festivities such as Pahiyas Festival. Further, their cultural practices and beliefs, handed down from generation to generation served as contributory factors in the acquisition of local knowledge on Pahiyas, revealing its priceless and transcendent beauty. Triangulation was used in the study to analyze and interpret field notes based on participant observations, interviews and document/s analyses. Theme analysis was conducted concurrently with data gathering. Coding was used to classify and identify emerging themes/categories which provided extensive analysis of the data. Results revealed that oral traditions played significant contributions in the acquisition of local knowledge of the Lucbanins in the preparations and celebration of Pahiyas Festival .Oral traditions coupled with direct and participants’ observations, formal and informal education as well as folklore served as mystical instruments in the preservation and promotion of Lucbanins’ cultural and spiritual values and beliefs, keeping Pahiyas Festival as a moving and dynamic legacy throughout the years. The role of oral traditions as rooted in Lucbanins’ local history is a symbol of a true and genuine Lucbanin, entirely different from other locals in the country.

  17. Unveiling the Dynamics of the Universe

    Directory of Open Access Journals (Sweden)

    Pedro Avelino

    2016-07-01

    Full Text Available We explore the dynamics and evolution of the Universe at early and late times, focusing on both dark energy and extended gravity models and their astrophysical and cosmological consequences. Modified theories of gravity not only provide an alternative explanation for the recent expansion history of the universe, but they also offer a paradigm fundamentally distinct from the simplest dark energy models of cosmic acceleration. In this review, we perform a detailed theoretical and phenomenological analysis of different modified gravity models and investigate their consistency. We also consider the cosmological implications of well motivated physical models of the early universe with a particular emphasis on inflation and topological defects. Astrophysical and cosmological tests over a wide range of scales, from the solar system to the observable horizon, severely restrict the allowed models of the Universe. Here, we review several observational probes—including gravitational lensing, galaxy clusters, cosmic microwave background temperature and polarization, supernova and baryon acoustic oscillations measurements—and their relevance in constraining our cosmological description of the Universe.

  18. Unveiling the Microfoundations of Absorptive Capacity

    DEFF Research Database (Denmark)

    Distel, Andreas Philipp

    2017-01-01

    to absorptive capacity at the organizational level and that this relationship is mediated through a microlevel process. The findings reveal that knowledge workers’ cognitive process of perspective taking and their creative behavior are important microfoundations of absorptive capacity. Moreover, the results...... emphasize the critical role of key employees in explaining firm-level heterogeneity in building organizational capabilities....

  19. Unveiling information on opportunity costs in REDD

    DEFF Research Database (Denmark)

    Delacote, Philip; Palmer, Charles; Bakkegaard, Riyong Kim

    2014-01-01

    Improving information about individual opportunity costs of deforestation agents has the potential to increase the efficiency of REDD when it takes the form of a payment for environmental services scheme. However, objectives pursued in REDD projects may vary across policy makers. Within a theoret......Improving information about individual opportunity costs of deforestation agents has the potential to increase the efficiency of REDD when it takes the form of a payment for environmental services scheme. However, objectives pursued in REDD projects may vary across policy makers. Within...... objectives in REDD-affected communities, having full information makes no difference to overall welfare as rents remain with agents. The amount of deforestation avoided will at least be as high as under asymmetric information. These results are illustrated with data collected on opportunity costs in Amazonas...

  20. Biggest bets in the universe unveiled

    CERN Multimedia

    Jamieson, Valerie

    2004-01-01

    Betting on the greatest unsolved problems in the universe is no longer the preserve of academic superstars such as Stephen Hawking. From Thursday, anyone will be able to place bets on whether the biggest physics experiments in the world will come good before 2010

  1. Unveiling Music Structure Via PLSA Similarity Fusion

    DEFF Research Database (Denmark)

    Arenas-García, Jerónimo; Meng, Anders; Petersen, Kaare Brandt

    2007-01-01

    Nowadays there is an increasing interest in developing methods for building music recommendation systems. In order to get a satisfactory performance from such a system, one needs to incorporate as much information about songs similarity as possible; however, how to do so is not obvious. In this p......Nowadays there is an increasing interest in developing methods for building music recommendation systems. In order to get a satisfactory performance from such a system, one needs to incorporate as much information about songs similarity as possible; however, how to do so is not obvious...... observed similarities can be satisfactorily explained using the latent semantics. Additionally, this approach significantly simplifies the song retrieval phase, leading to a more practical system implementation. The suitability of the PLSA model for representing music structure is studied in a simplified...

  2. Ettore Majorana unveiled genius and endless mysteries

    CERN Document Server

    Esposito, Salvatore

    2017-01-01

    This biography sheds new light on the life and work of physicist Ettore Majorana (including unpublished contributions), as well as on his mysterious disappearance in March 1938. Majorana is held by many, including Nobel Laureate, Enrico Fermi, to have been a genius of the rank of Galilei and Newton. In this intriguing story, the author, himself a leading expert on the work of Majorana, supplements the existing literature with new insights, anecdotes and personal accounts of contemporaries of Majorana.

  3. Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline

    Science.gov (United States)

    Cabezas, C.; Cortijo, V.; Mata, S.; Lopez, J. C.; Alonso, J. L.

    2013-06-01

    Recent improvements in our LA-MB-FTMW instrumentation have allowed the characterization of eleven and eight conformers for the neurotransmitters adrenaline and noradrenaline respectively. The observation of this rich conformational behavior is in accordance with the recent observation of seven conformers for dopamine and in sharp contrast with the conformational reduction proposed for catecholamines. C. Cabezas, I. Peña, J. C. López, J. L. Alonso J. Phys. Chem. Lett. 2013, 4, 486. H. Mitsuda, M. Miyazaki, I. B. Nielsen, P. Carcabal,C. Dedonder, C. Jouvet, S. Ishiuchi, M. Fujii J. Phys. Chem. Lett. 2010, 1, 1130.

  4. Dubbing SAGA unveils new epigenetic crosstalk.

    Science.gov (United States)

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

    2008-02-01

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

  5. Molecular Determinants of Radio Resistance in Prostate Cancer

    Science.gov (United States)

    2005-08-01

    Pathway Gene Accession # Ratio H/N Ratio Hypoxia/Normoxla (Log,) NER ERCCt NM001983 1.3 BER APE,2 NM_014481 1.0 MMR PMS2 NM_000535 1.3 HR RAD51...cross-complementing group 1; APEX2, apurinic!apyrimidinic endonuclease/redox factor 2; PMS2 , postmeiotic segregation increased 2; RAD51, RAD51 homolog

  6. Desvelamento crítico da pessoa estomizada: em ação o programa de educação permanente em saúde Develamiento crítico de la persona ostomizada: programa de educación permanente en salud en acción Critical unveiling of people with stomas: the continuing health education program in action

    Directory of Open Access Journals (Sweden)

    Regina Ribeiro Cunha

    2012-01-01

    en la Atención a la persona ostomizada. CONCLUSIÓN: El develamiento propuesto constituyó una vivencia para que esas personas ostomizadas estén habilitadas para "leer el mundo" y, así, conozcan y caminen rumbo a la transformación de su realidad.OBJECTIVE: To present the critical unveiling of the Itinerary of Freirean Research in the care of people with stoma. METHODS: A qualitative study in health linked to the methodological framework of Freire, which includes obtaining and analysis of data in dialogical circles, comprising three dialectical moments, intertwined in an interdisciplinary manner: thematic research, coding and decoding, and critical unveiling. This occurred in the period between April 2009 and February 2010, with an irregular number of participants, in the auditorium of the President Vargas Specialized Reference Unit, in the city of Belém / PA (Brazil. RESULTS: Inadequate training of health professionals was one of the most relevant topics generated, and unveiled the necessity of implementing a program of continuing education on the care of people with stoma. CONCLUSION: The proposed unveiling constituted a life experience so that these people with stomas were enabled to "read the world" and thus know and walk towards the transformation of their reality.

  7. The Fanconi Anemia BRCA Pathway as a Predictor of Benefit from Bevacizumab in a Large Phase-3 Clinical Trial in Ovarian Cancer

    Science.gov (United States)

    2014-10-01

    FAM175A (3), PMS2 (2), and MLH1 (1). Consistent with their role as ovarian cancer susceptibility genes, BRIP1, RAD51C, and RAD51D were significantly...ATM (11), RAD51C (10), NBN (9), TP53 (6), BARD1 (4), MSH6 (4), FAM175A (3), PMS2 (2), and MLH1 (1). Consistent with their role as ovarian cancer

  8. Coincident resection at both ends of random, γ-induced double-strand breaks requires MRX (MRN, Sae2 (Ctp1, and Mre11-nuclease.

    Directory of Open Access Journals (Sweden)

    James W Westmoreland

    2013-03-01

    Full Text Available Resection is an early step in homology-directed recombinational repair (HDRR of DNA double-strand breaks (DSBs. Resection enables strand invasion as well as reannealing following DNA synthesis across a DSB to assure efficient HDRR. While resection of only one end could result in genome instability, it has not been feasible to address events at both ends of a DSB, or to distinguish 1- versus 2-end resections at random, radiation-induced "dirty" DSBs or even enzyme-induced "clean" DSBs. Previously, we quantitatively addressed resection and the role of Mre11/Rad50/Xrs2 complex (MRX at random DSBs in circular chromosomes within budding yeast based on reduced pulsed-field gel electrophoretic mobility ("PFGE-shift". Here, we extend PFGE analysis to a second dimension and demonstrate unique patterns associated with 0-, 1-, and 2-end resections at DSBs, providing opportunities to examine coincidence of resection. In G2-arrested WT, Δrad51 and Δrad52 cells deficient in late stages of HDRR, resection occurs at both ends of γ-DSBs. However, for radiation-induced and I-SceI-induced DSBs, 1-end resections predominate in MRX (MRN null mutants with or without Ku70. Surprisingly, Sae2 (Ctp1/CtIP and Mre11 nuclease-deficient mutants have similar responses, although there is less impact on repair. Thus, we provide direct molecular characterization of coincident resection at random, radiation-induced DSBs and show that rapid and coincident initiation of resection at γ-DSBs requires MRX, Sae2 protein, and Mre11 nuclease. Structural features of MRX complex are consistent with coincident resection being due to an ability to interact with both DSB ends to directly coordinate resection. Interestingly, coincident resection at clean I-SceI-induced breaks is much less dependent on Mre11 nuclease or Sae2, contrary to a strong dependence on MRX complex, suggesting different roles for these functions at "dirty" and clean DSB ends. These approaches apply to resection at

  9. ESA unveils Spanish antenna for unique space mission

    Science.gov (United States)

    2000-05-01

    The newly refurbished antenna, which is located at the Villafranca del Castillo Satellite Tracking Station site (VILSPA) near Madrid, has been selected as the prime communication link with the Cluster II spacecraft. The VIL-1 antenna will play a vital role in ESA's Cluster mission by monitoring and controlling the four spacecraft and by receiving the vast amounts of data that will be returned to Earth during two years of operations. Scheduled for launch in summer 2000, the Cluster quartet will complete the most detailed investigation ever made into the interaction between our pl0anet's magnetosphere - the region of space dominated by Earth's magnetic field - and the continuous stream of charged particles emitted by the Sun - the solar wind. This exciting venture is now well under way, following completion of the satellite assembly and test programme and two successful verification flights by the newly developed Soyuz-Fregat launch vehicle. The ESA Flight Acceptance Review Board has accordingly given the go-ahead for final launch preparations at the Baikonur Cosmodrome in Kazakhstan. VILSPA, ESA and Cluster II Built in 1975, after an international agreement between the European Space Agency and the Spanish government, VILSPA is part of the European Space Operations Centre (ESOC) Tracking Station Network (ESTRACK). In the last 25 years, VILSPA has supported many ESA and international satellite programmes, including the International Ultraviolet Explorer (IUE), EXOSAT and the Infrared Space Observatory (ISO). In addition to supporting the Cluster II mission, it has been designated as the Science Operations Centre for ESA's XMM Newton mission and for the Far-Infrared Space Telescope (FIRST), which is due to launch in 2007. There are now more than half a dozen large dish antennae installed at VILSPA. One of these is the VIL-1 antenna, a 15 metre diameter dish which operates in the S-band radio frequency (1.8 - 2.7 GHz). This antenna has been modernised recently in order to support the forthcoming Cluster II mission. As a result, VILSPA now has two fully upgraded 15 metre S-band antennae, which should enable the facility to enter the new millennium confident in its ability to support future space programmes. Modernisation of VIL-1 included the replacement of the 60 dish panels, the subreflector, the antenna equipment room and other parts of the main structure. One of the most significant modifications has been the replacement of the Servo and tracking systems, since the Cluster II satellites will move in a highly elliptical orbit and require high speed tracking. Into Orbit The Cluster II mission will be launched by two Soyuz rockets provided by the French-Russian Starsem consortium. After two engine burns by the Fregat upper stage, the spacecraft will separate and use their own propulsion systems to reach their final orbits. Travelling in close formation, the four Cluster spacecraft will swoop to within 19,000 km of the Earth's surface and then retreat to 119,000 km - almost one third of the way to the Moon. The four satellites will be visible for an average of about 10 hours per day from the VILSPA ground station. However, only one satellite at a time can be in communication with the ground, which reduces the available time each day to around two and a half hours per satellite. Further challenges arise from the need to send new instructions to the 11 scientific instruments on each spacecraft, and from the vast amount of data to be returned each day from the 44 experiments. Over two years of operations, this adds up to 580 Gigabytes (580,000,000,000 bytes!) of data - equivalent to 290 million pages of printed text. VILSPA will be just one link in the overall Cluster II communications network. The day-to-day operation of the four spacecraft will be handled by the Operations Control Centre at ESOC (Darmstadt, Germany). All of the Cluster II data exchange between VILSPA and ESOC will be handled by dedicated communication lines. European Teamwork. Industrial enterprises in almost all of the 14 ESA member states and the United States have provided hardware for Cluster II, and several Spanish companies have made important contributions to the project. SENER in Bilbao has designed and built the communication and experiment booms for the spacecraft, while Alcatel Espacio in Tres Cantos (Madrid) has provided on-board transponders and high power amplifiers for the spacecraft. Construction of the eight Cluster / Cluster II spacecraft has been a major undertaking for European industry. Built into each 550 kg satellite are six propellant tanks, two pressure tanks, eight thrusters, 80 metres of pipework, about 5 km of wiring, 380 connectors and more than 14,000 electrical contacts. All of the spacecraft have been assembled at the Friedrichshafen (Germany) plant of prime contractor Dornier Satellitensysteme, and then sent to IABG in Ottobrunn, near Munich, for intensive vibration, thermal, vacuum and magnetic testing. Various companies have also participated in the relocation and upgrading of the VIL-1 antenna hardware. MAN (Germany) was responsible for the dismantling of the Odenwald antenna and installation of the dish at VILSPA, while VITROCISET (Italy) handled the transfer of the antenna 'back-end' equipment, which included the computers to process the satellite telemetry and telecommunications signals. These companies were supported by Spanish contractors and local industry.

  10. Limited communication capacity unveils strategies for human interaction

    Science.gov (United States)

    Miritello, Giovanna; Lara, Rubén; Cebrian, Manuel; Moro, Esteban

    2013-06-01

    Connectivity is the key process that characterizes the structural and functional properties of social networks. However, the bursty activity of dyadic interactions may hinder the discrimination of inactive ties from large interevent times in active ones. We develop a principled method to detect tie de-activation and apply it to a large longitudinal, cross-sectional communication dataset (~19 months, ~20 million people). Contrary to the perception of ever-growing connectivity, we observe that individuals exhibit a finite communication capacity, which limits the number of ties they can maintain active in time. On average men display higher capacity than women, and this capacity decreases for both genders over their lifespan. Separating communication capacity from activity reveals a diverse range of tie activation strategies, from stable to exploratory. This allows us to draw novel relationships between individual strategies for human interaction and the evolution of social networks at global scale.

  11. Metabolomics to unveil and understand phenotypic diversity between pathogen populations.

    Directory of Open Access Journals (Sweden)

    Ruben t'Kindt

    Full Text Available Leishmaniasis is a debilitating disease caused by the parasite Leishmania. There is extensive clinical polymorphism, including variable responsiveness to treatment. We study Leishmania donovani parasites isolated from visceral leishmaniasis patients in Nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. Here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for L. donovani to characterize the global metabolic differences between antimonial-sensitive and antimonial-resistant L. donovani isolates. Clones of drug-sensitive and drug-resistant parasite isolates from clinical samples were cultured in vitro and harvested for metabolomics analysis. The relative abundance of 340 metabolites was determined by ZIC-HILIC chromatography coupled to LTQ-Orbitrap mass spectrometry. Our measurements cover approximately 20% of the predicted core metabolome of Leishmania and additionally detected a large number of lipids. Drug-sensitive and drug-resistant parasites showed distinct metabolic profiles, and unsupervised clustering and principal component analysis clearly distinguished the two phenotypes. For 100 metabolites, the detected intensity differed more than three-fold between the 2 phenotypes. Many of these were in specific areas of lipid metabolism, suggesting that the membrane composition of the drug-resistant parasites is extensively modified. Untargeted metabolomics has been applied on clinical Leishmania isolates to uncover major metabolic differences between drug-sensitive and drug-resistant isolates. The identified major differences provide novel insights into the mechanisms involved in resistance to antimonial drugs, and facilitate investigations using targeted approaches to unravel the key changes mediating drug resistance.

  12. Amazing structure of respirasome: unveiling the secrets of cell respiration.

    Science.gov (United States)

    Guo, Runyu; Gu, Jinke; Wu, Meng; Yang, Maojun

    2016-12-01

    Respirasome, a huge molecular machine that carries out cellular respiration, has gained growing attention since its discovery, because respiration is the most indispensable biological process in almost all living creatures. The concept of respirasome has renewed our understanding of the respiratory chain organization, and most recently, the structure of respirasome solved by Yang's group from Tsinghua University (Gu et al. Nature 237(7622):639-643, 2016) firstly presented the detailed interactions within this huge molecular machine, and provided important information for drug design and screening. However, the study of cellular respiration went through a long history. Here, we briefly showed the detoured history of respiratory chain investigation, and then described the amazing structure of respirasome.

  13. Unveiling Leadership–Employee Performance Links: Perspective of Young Employees

    Directory of Open Access Journals (Sweden)

    Tehmina Fiaz Qazi

    2014-12-01

    Full Text Available This paper presents the impact of leadership style practiced by managers on their subordinates’ job performance. Emotional Intelligence of the employees has been considered as a moderator to the leadership-performance relationship. Self-administered questionnaire survey was conducted from convenient sampled 100 young employees of telecom and banking sector. They were asked to respond about their perception regarding their manager’s leadership style, job performance and their perceived level of emotional intelligence. 77 out of 100 distributed questionnaires were received back completely filled that yield response rate of 77%. Current research concluded that the style of leadership exhibited by a manager is significantly associated with the subordinates’ job performance while emotional intelligence of employees has no moderating effect on this leadership- performance relationship

  14. Unveiling the Hidden Bat Diversity of a Neotropical Montane Forest.

    Directory of Open Access Journals (Sweden)

    Gloriana Chaverri

    Full Text Available Mountain environments, characterized by high levels of endemism, are at risk of experiencing significant biodiversity loss due to current trends in global warming. While many acknowledge their importance and vulnerability, these ecosystems still remain poorly studied, particularly for taxa that are difficult to sample such as bats. Aiming to estimate the amount of cryptic diversity among bats of a Neotropical montane cloud forest in Talamanca Range-south-east Central America-, we performed a 15-night sampling campaign, which resulted in 90 captured bats belonging to 8 species. We sequenced their mitochondrial cytochrome c oxidase subunit I (COI and screened their inter- and intraspecific genetic variation. Phylogenetic relations with conspecifics and closely related species from other geographic regions were established using Maximum Likelihood and Bayesian inference methods, as well as median-joining haplotype networks. Mitochondrial lineages highly divergent from hitherto characterized populations (> 9% COI dissimilarity were found in Myotis oxyotus and Hylonycteris underwoodi. Sturnira burtonlimi and M. keaysi also showed distinct mitochondrial structure with sibling species and/or populations. These results suggest that mountains in the region hold a high degree of endemicity potential that has previously been ignored in bats. They also warn of the high extinction risk montane bats may be facing due to climatic change, particularly in isolated mountain systems like Talamanca Range.

  15. Health Canada unveils plan to distribute marijuana for medical use.

    Science.gov (United States)

    Thaczuk, Derek

    2003-08-01

    Under pressure from the courts, Health Canada reluctantly comes up with a distribution plan to provide dried cannabis and seeds to patients using medical marijuana. The plan has been greeted with considerable criticism

  16. Unveiling the curtain of superposition: Recent gedanken and laboratory experiments

    Science.gov (United States)

    Cohen, E.; Elitzur, A. C.

    2017-08-01

    What is the true meaning of quantum superposition? Can a particle genuinely reside in several places simultaneously? These questions lie at the heart of this paper which presents an updated survey of some important stages in the evolution of the three-boxes paradox, as well as novel conclusions drawn from it. We begin with the original thought experiment of Aharonov and Vaidman, and proceed to its non-counterfactual version. The latter was recently realized by Okamoto and Takeuchi using a quantum router. We then outline a dynamic version of this experiment, where a particle is shown to “disappear” and “re-appear” during the time evolution of the system. This surprising prediction based on self-cancellation of weak values is directly related to our notion of Quantum Oblivion. Finally, we present the non-counterfactual version of this disappearing-reappearing experiment. Within the near future, this last version of the experiment is likely to be realized in the lab, proving the existence of exotic hitherto unknown forms of superposition. With the aid of Bell’s theorem, we prove the inherent nonlocality and nontemporality underlying such pre- and post-selected systems, rendering anomalous weak values ontologically real.

  17. Unveiling the top secrets with the Large Hadron Collider

    Science.gov (United States)

    Chierici, R.

    2013-12-01

    Top quark physics is one of the pillars of fundamental research in the field of high energy physics. It not only gives access to precision measurements for constraining the Standard Model of particles and interactions but also it represents a privileged domain for new physics searches. This contribution summarizes the main results in top quark physics obtained with the two general-purpose detectors ATLAS and CMS during the first two years of operations of the Large Hadron Collider (LHC) at CERN. It covers the 2010 and 2011 data taking periods, where the LHC ran at a centre-of-mass energy of 7 TeV.

  18. Unveiling the top secrets with the Large Hadron Collider

    International Nuclear Information System (INIS)

    Chierici, R

    2013-01-01

    Top quark physics is one of the pillars of fundamental research in the field of high energy physics. It not only gives access to precision measurements for constraining the Standard Model of particles and interactions but also it represents a privileged domain for new physics searches. This contribution summarizes the main results in top quark physics obtained with the two general-purpose detectors ATLAS and CMS during the first two years of operations of the Large Hadron Collider (LHC) at CERN. It covers the 2010 and 2011 data taking periods, where the LHC ran at a centre-of-mass energy of 7 TeV. (paper)

  19. Structural evolution of calcite at high temperatures: Phase V unveiled

    Science.gov (United States)

    Ishizawa, Nobuo; Setoguchi, Hayato; Yanagisawa, Kazumichi

    2013-01-01

    The calcite form of calcium carbonate CaCO3 undergoes a reversible phase transition between Rc and Rm at ~1240 K under a CO2 atmosphere of ~0.4 MPa. The joint probability density function obtained from the single-crystal X-ray diffraction data revealed that the oxygen triangles of the CO3 group in the high temperature form (Phase V) do not sit still at specified positions in the space group Rm, but migrate along the undulated circular orbital about carbon. The present study also shows how the room temperature form (Phase I) develops into Phase V through an intermediate form (Phase IV) in the temperature range between ~985 K and ~1240 K. PMID:24084871

  20. Unveiling the checkered fortunes of the Ottoman Empire

    OpenAIRE

    Dimitrova-Grajzl, Valentina

    2013-01-01

    The Ottoman Empire has been predominantly viewed as the ćSick Man of Europe.ć The question arises, however, how this perceived inefficiency can be reconciled with the long existence and prosperity of the Empire. I argue that the Ottoman system could have been efficient subject to constraints. More specifically, I explore the role of the technology of predation and the adherence to the law in determining relative changes in the social order and the power of the Sultan, which in turn led to the...

  1. Hidden symmetries of the Principal Chiral Model unveiled

    International Nuclear Information System (INIS)

    Devchand, C.; Schiff, J.

    1996-12-01

    By relating the two-dimensional U(N) Principal Chiral Model to a Simple linear system we obtain a free-field parametrization of solutions. Obvious symmetry transformations on the free-field data give symmetries of the model. In this way all known 'hidden symmetries' and Baecklund transformations, as well as a host of new symmetries, arise. (author). 21 refs

  2. Unveiling galaxies the role of images in astronomical discovery

    CERN Document Server

    Roy, Jean-René

    2017-01-01

    Galaxies are known as the building blocks of the universe, but arriving at this understanding has been a thousand-year odyssey. This journey is told through the lens of the evolving use of images as investigative tools. Initial chapters explore how early insights developed in line with new methods of scientific imaging, particularly photography. The volume then explores the impact of optical, radio and x-ray imaging techniques. The final part of the story discusses the importance of atlases of galaxies; how astronomers organised images in ways that educated, promoted ideas and pushed for new knowledge. Images that created confusion as well as advanced knowledge are included to demonstrate the challenges faced by astronomers and the long road to understanding galaxies. By examining developments in imaging, this text places the study of galaxies in its broader historical context, contributing to both astronomy and the history of science.

  3. Gingival enlargement unveiling sarcoidosis: Report of a rare case

    Directory of Open Access Journals (Sweden)

    Sabeeha Abbas Kadiwala

    2013-01-01

    Full Text Available Sarcoidosis is classified as an acquired systemic granulomatous disease. Because of the fact that sarcoidosis affects multiple tissues and organs, it is characterized by many potential signs and symptoms, as well as by the presence of non-caseating granulomas in the organs involved. Although oral sarcoidosis is relatively rare, it may however, present in the oral cavity. This report presents a rare case of sarcoidosis with the initial presenting symptom as severe generalized gingival enlargement. The gingival enlargement was treated by gingivectomy. After histopathological examination of gingival biopsy and certain special investigations, a diagnosis of sarcoidosis was made.

  4. THE UNVEILING OF LIFE : LITURGY AND THE LURE OF KITSCH

    African Journals Online (AJOL)

    2010-09-01

    Sep 1, 2010 ... To reach an understanding of theological aesthetics proves to be an even more difficult task, given its ..... something. The performance (graceful effect) of the Gospel then .... revelations that lift us up and above the mundane.

  5. Challenging Google, Microsoft Unveils a Search Tool for Scholarly Articles

    Science.gov (United States)

    Carlson, Scott

    2006-01-01

    Microsoft has introduced a new search tool to help people find scholarly articles online. The service, which includes journal articles from prominent academic societies and publishers, puts Microsoft in direct competition with Google Scholar. The new free search tool, which should work on most Web browsers, is called Windows Live Academic Search…

  6. Multiple jaw cysts-unveiling the Gorlin-Goltz syndrome

    Directory of Open Access Journals (Sweden)

    S Manjima

    2015-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is a comparatively rare syndrome characterized by basal cell nevi, odontogenic keratocysts, and skeletal anomalies. Diagnosis is based on the major and minor clinical and radiographic criteria. Dentist plays a major role in the diagnosis of this disease due to the oral and maxillofacial manifestations of the syndrome. In some cases, jaw cysts are diagnosed by routine radiographs advised by the dentists. Odontogenic keratocysts in such syndromic patients will be multiple and extensive and in some cases results in cortical expansion and facial disfigurement. Thorough clinical examination and investigations prompt an early confirmation of the syndrome, which is very essential to avoid morbidity associated with the syndrome. Here, we report a case of multiple odontogenic cysts in a 16-year-old patient which later was diagnosed as a case of Gorlin Goltz syndrome.

  7. Multiple jaw cysts-unveiling the Gorlin-Goltz syndrome.

    Science.gov (United States)

    Manjima, S; Naik, Zameera; Keluskar, Vaishali; Bagewadi, Anjana

    2015-03-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is a comparatively rare syndrome characterized by basal cell nevi, odontogenic keratocysts, and skeletal anomalies. Diagnosis is based on the major and minor clinical and radiographic criteria. Dentist plays a major role in the diagnosis of this disease due to the oral and maxillofacial manifestations of the syndrome. In some cases, jaw cysts are diagnosed by routine radiographs advised by the dentists. Odontogenic keratocysts in such syndromic patients will be multiple and extensive and in some cases results in cortical expansion and facial disfigurement. Thorough clinical examination and investigations prompt an early confirmation of the syndrome, which is very essential to avoid morbidity associated with the syndrome. Here, we report a case of multiple odontogenic cysts in a 16-year-old patient which later was diagnosed as a case of Gorlin Goltz syndrome.

  8. Hopping in the Crowd to Unveil Network Topology

    Science.gov (United States)

    Asllani, Malbor; Carletti, Timoteo; Di Patti, Francesca; Fanelli, Duccio; Piazza, Francesco

    2018-04-01

    We introduce a nonlinear operator to model diffusion on a complex undirected network under crowded conditions. We show that the asymptotic distribution of diffusing agents is a nonlinear function of the nodes' degree and saturates to a constant value for sufficiently large connectivities, at variance with standard diffusion in the absence of excluded-volume effects. Building on this observation, we define and solve an inverse problem, aimed at reconstructing the a priori unknown connectivity distribution. The method gathers all the necessary information by repeating a limited number of independent measurements of the asymptotic density at a single node, which can be chosen randomly. The technique is successfully tested against both synthetic and real data and is also shown to estimate with great accuracy the total number of nodes.

  9. Transcription factor profiling unveils the oncogenes involved in the ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... responsible for the progression of different kinds of cancer. .... one cell type was hybridized to the c-DNA library of another cell type ..... why intravenous application of As2O3 in a 1 -10 uM .... tion by ascorbic acid (vitamin C).

  10. Affective Man-Machine Interface: Unveiling human emotions through biosignals

    NARCIS (Netherlands)

    van den Broek, Egon; Lisy, Viliam; Janssen, Joris H.; Westerink, Joyce H.D.M.; Schut, Marleen H.; Tuinenbreijer, Kees; Fred, A.; Filipe, J.; Gamboa, H.

    2010-01-01

    As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological processes, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and,

  11. Unveiling social awareness through literacy practices in an EFL class

    Directory of Open Access Journals (Sweden)

    Luzmel Alexánder Pérez

    2014-01-01

    Full Text Available This qualitative research study addresses issues of verbal and physical aggression among tenth grade students in a public school. Through a pedagogical intervention the participants worked collaboratively to reflect on social issues in their English language classes. Inquiry was a fundamental element in this study as it allowed students to explore, read, compare, and then reflect on issues that come from their own context and experiences (Giroux, 1988. Students’ reflections were collected through questionnaires, artifacts, and audio recorded interviews in order to gather information to reveal students’ social awareness of physical and verbal aggression in their school context.  The findings revealed that students see violence as a need to avoid their partners´ abuse. Students´ reflections showed that students considered that parents and teachers paid more attention to academic concerns, rather than personal growth. The study demonstrated that inquiry along with writing about social issues in English allowed students to develop rationality and sensitivity towards violent acts, furthermore, inquiry about their social problems encouraged students to work collaboratively, to reflect about their social conditions and to apply the use of the English language in contextualized situations.

  12. Europe Unveils 20-Year Plan for Brilliant Future in Astronomy

    Science.gov (United States)

    2008-11-01

    Astronomy is enjoying a golden age of fundamental, exciting discoveries. Europe is at the forefront, thanks to 50 years of progress in cooperation. To remain ahead over the next two to three decades, Europe must prioritise and coordinate the investment of its financial and human resources even more closely. The ASTRONET network, backed by the entire European scientific community, supported by the European Commission, and coordinated by the CNRS, today presents its Roadmap for a brilliant future for European astronomy. ESO's European Extremely Large Telescope is ranked as one of two top-priority large ground-based projects. Astronet and the E-ELT ESO PR Photo 43a/08 The E-ELT Europe is a leader in astronomy today, with the world's most successful optical observatory, ESO's Very Large Telescope, and cutting-edge facilities in radio astronomy and in space. In an unprecedented effort demonstrating the potential of European scientific cooperation, all of European astronomy is now joining forces to define the scientific challenges for the future and construct a common plan to address them in a cost-effective manner. In 2007, a top-level Science Vision was prepared to assess the most burning scientific questions over the next quarter century, ranging from dark energy to life on other planets. European astronomy now presents its Infrastructure Roadmap, a comprehensive 20-year plan to coordinate national and community investments to meet these challenges in a cost-effective manner. The Roadmap not only prioritises the necessary new frontline research facilities from radio telescopes to planetary probes, in space and on the ground, but also considers such key issues as existing facilities, human resources, ICT infrastructure, education and outreach, and cost -- of operations as well as construction. This bold new initiative -- ASTRONET -- was created by the major European funding agencies with support from the European Commission and is coordinated by the National Institute for Earth Sciences and Astronomy (INSU) of the CNRS. To build consensus on priorities in a very diverse community, the Science Vision and Roadmap were developed in an open process involving intensive interaction with the community through large open meetings and feedback via e-mail and the web. The result is a plan now backed by astronomers in 28 Member and Associated States of the EU, with over 500 million inhabitants. Over 60 selected experts from across Europe contributed to the construction of the ASTRONET Roadmap, ensuring that European astronomy has the tools to compete successfully in answering the challenges of the Science Vision. They identified and prioritised a set of new facilities to observe the Universe from radio waves to gamma rays, to open up new ways of probing the cosmos, such as gravitational waves, and to advance in the exploration of our Solar System. In the process, they considered all the elements needed by a successful scientific enterprise, from global-scale cooperation on the largest mega-project to the need for training and recruiting skilled young scientists and engineers. One of two top-priority large ground-based projects is ESO's European Extremely Large Telescope. Its 42-metre diameter mirror will make the E-ELT the largest optical/near-infrared telescope in the world -- "the biggest eye on the sky". The science to be done with the E-ELT is extremely exciting and includes studies of exoplanets and discs, galaxy formation and dark energy. ESO Director General Tim de Zeeuw says: "The top ranking of the E-ELT in the Roadmap is a strong endorsement from the European astronomical community. This flagship project will indisputably raise the European scientific, technological and industrial profile". Among other recommendations, the Roadmap considers how to maximise the future scientific impact of existing facilities in a cost-effective manner. It also identifies a need for better access to state-of-the art computing and laboratory facilities, and for a stronger involvement of European high-tech industry in the development of future facilities. Moreover, success depends critically upon an adequate supply of qualified scientists, and of engineers in fields ranging from IT to optics. Finally, the Roadmap proposes a series of measures to enhance the public understanding of astronomy as a means to boost recruitment in science and technology in schools and universities across Europe. Europe currently spends approximately €2 billion a year on astronomy in the broadest sense. Implementing the ASTRONET Roadmap will require a funding increase of around 20% -- less than €1 per year per European citizen. Global cooperation will be needed -- and is being planned -- for several of the largest projects.

  13. Mud banks of Kerala: Mystery yet to be unveiled!

    Digital Repository Service at National Institute of Oceanography (India)

    DineshKumar, P.K.

    -ships of those days could therefore anchor right in the sea, and remain as safely as in a pond. Devoid of waves, the ships were free from the thrust and pull normally experienced in the open sea. Consequently the big vessels remained in the sea...

  14. Unveiling the Biometric Potential of Finger-Based ECG Signals

    Science.gov (United States)

    Lourenço, André; Silva, Hugo; Fred, Ana

    2011-01-01

    The ECG signal has been shown to contain relevant information for human identification. Even though results validate the potential of these signals, data acquisition methods and apparatus explored so far compromise user acceptability, requiring the acquisition of ECG at the chest. In this paper, we propose a finger-based ECG biometric system, that uses signals collected at the fingers, through a minimally intrusive 1-lead ECG setup recurring to Ag/AgCl electrodes without gel as interface with the skin. The collected signal is significantly more noisy than the ECG acquired at the chest, motivating the application of feature extraction and signal processing techniques to the problem. Time domain ECG signal processing is performed, which comprises the usual steps of filtering, peak detection, heartbeat waveform segmentation, and amplitude normalization, plus an additional step of time normalization. Through a simple minimum distance criterion between the test patterns and the enrollment database, results have revealed this to be a promising technique for biometric applications. PMID:21837235

  15. [Evolutionary process unveiled by the maximum genetic diversity hypothesis].

    Science.gov (United States)

    Huang, Yi-Min; Xia, Meng-Ying; Huang, Shi

    2013-05-01

    As two major popular theories to explain evolutionary facts, the neutral theory and Neo-Darwinism, despite their proven virtues in certain areas, still fail to offer comprehensive explanations to such fundamental evolutionary phenomena as the genetic equidistance result, abundant overlap sites, increase in complexity over time, incomplete understanding of genetic diversity, and inconsistencies with fossil and archaeological records. Maximum genetic diversity hypothesis (MGD), however, constructs a more complete evolutionary genetics theory that incorporates all of the proven virtues of existing theories and adds to them the novel concept of a maximum or optimum limit on genetic distance or diversity. It has yet to meet a contradiction and explained for the first time the half-century old Genetic Equidistance phenomenon as well as most other major evolutionary facts. It provides practical and quantitative ways of studying complexity. Molecular interpretation using MGD-based methods reveal novel insights on the origins of humans and other primates that are consistent with fossil evidence and common sense, and reestablished the important role of China in the evolution of humans. MGD theory has also uncovered an important genetic mechanism in the construction of complex traits and the pathogenesis of complex diseases. We here made a series of sequence comparisons among yeasts, fishes and primates to illustrate the concept of limit on genetic distance. The idea of limit or optimum is in line with the yin-yang paradigm in the traditional Chinese view of the universal creative law in nature.

  16. Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

    Directory of Open Access Journals (Sweden)

    Andrés B Lantos

    2016-04-01

    Full Text Available Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form.

  17. UNVEILING THE UNIVERSALITY OF I-LOVE-Q RELATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Sham, Y.-H.; Lin, L.-M.; Leung, P. T. [Department of Physics and Institute of Theoretical Physics, The Chinese University of Hong Kong, Hong Kong SAR (China); Chan, T. K., E-mail: yhsham@phy.cuhk.edu.hk, E-mail: chantsangkeung@gmail.com, E-mail: lmlin@phy.cuhk.edu.hk, E-mail: ptleung@phy.cuhk.edu.hk [Present address: Department of Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. (United States)

    2015-01-10

    The recent discovery of the universal I-Love-Q relations connecting the moment of inertia, tidal deformability, and the spin-induced quadrupole moment of compact stars is intriguing and totally unexpected. In this paper, we provide numerical evidence showing that the universality can be attributed to the incompressible limit of the I-Love-Q relations. The fact that modern equations of state are stiff, with an effective adiabatic index larger than about two, above the nuclear density range is the key to establishing the universality for neutron stars and quark stars with typical compactness from about 0.1 to 0.3. On the other hand, the I-Love-Q relations of low-mass neutron stars near the minimum mass limit depend more sensitively on the underlying equation of state because these stars are composed mainly of softer matter at low densities. However, the I-Love-Q relations for low-mass quark stars can still be represented accurately by the incompressible limit. We also study the I-Love relation connecting the moment of inertia and tidal deformability analytically in Newtonian gravity and show why the I-Love-Q relation is weakly dependent on the underlying equation of state and can be attributed to its incompressible limit.

  18. Unveiling the Low Surface Brightness Stellar Peripheries of Galaxies

    Science.gov (United States)

    Ferguson, Annette M. N.

    2018-01-01

    The low surface brightness peripheral regions of galaxies contain a gold mine of information about how minor mergers and accretions have influenced their evolution over cosmic time. Enormous stellar envelopes and copious amounts of faint tidal debris are natural outcomes of the hierarchical assembly process and the search for and study of these features, albeit highly challenging, offers the potential for unrivalled insight into the mechanisms of galaxy growth. Over the last two decades, there has been burgeoning interest in probing galaxy outskirts using resolved stellar populations. Wide-field surveys have uncovered vast tidal debris features and new populations of very remote globular clusters, while deep Hubble Space Telescope photometry has provided exquisite star formation histories back to the earliest epochs. I will highlight some recent results from studies within and beyond the Local Group and conclude by briefly discussing the great potential of future facilities, such as JWST, Euclid, LSST and WFIRST, for major breakthroughs in low surface brightness galaxy periphery science.

  19. German lab unveils plan to build physicists' next collider

    CERN Multimedia

    Abott, A

    2001-01-01

    An international team of physicists are to propose the construction of a major collider. 'TESLA' - the 'Tera electron volt Energy Superconducting Linear Accelerator' will be a linear electron-positron collider based on superconducting resonators. It will be based at DESY and cost around three billion US dollars (2 pages).

  20. Plant Physiology: Unveiling the Dark Side of Phloem Translocation.

    Science.gov (United States)

    Truernit, Elisabeth

    2017-05-08

    Sugars and other macromolecules arrive in heterotrophic plant tissues through the phloem, a long-distance transport system. Owing to a recent study, we now have a better understanding of how these molecules exit the phloem at their final destinations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The unveiling of life: Liturgy and the lure of kitsch

    Directory of Open Access Journals (Sweden)

    Johan Cilliers

    2010-11-01

    Full Text Available This article probes the classic definition of religious aesthetics as related to the notions of beauty, goodness and truth. The phenomenon of kitsch, understood as simulation (or inversion of beauty, goodness and truth, is taken cognisance of, especially in the light of contributions by Milan Kundera, Umberto Eco and Jean Baudrillard. The article briefly reflects on the liturgical consequences when kitsch manifests itself as simulated ‘beauty’, ‘goodness’ and ‘truth’ and concludes with some considerations regarding the characteristics of kitsch.

  2. Unveiling the mystery of visual information processing in human brain.

    Science.gov (United States)

    Diamant, Emanuel

    2008-08-15

    It is generally accepted that human vision is an extremely powerful information processing system that facilitates our interaction with the surrounding world. However, despite extended and extensive research efforts, which encompass many exploration fields, the underlying fundamentals and operational principles of visual information processing in human brain remain unknown. We still are unable to figure out where and how along the path from eyes to the cortex the sensory input perceived by the retina is converted into a meaningful object representation, which can be consciously manipulated by the brain. Studying the vast literature considering the various aspects of brain information processing, I was surprised to learn that the respected scholarly discussion is totally indifferent to the basic keynote question: "What is information?" in general or "What is visual information?" in particular. In the old days, it was assumed that any scientific research approach has first to define its basic departure points. Why was it overlooked in brain information processing research remains a conundrum. In this paper, I am trying to find a remedy for this bizarre situation. I propose an uncommon definition of "information", which can be derived from Kolmogorov's Complexity Theory and Chaitin's notion of Algorithmic Information. Embracing this new definition leads to an inevitable revision of traditional dogmas that shape the state of the art of brain information processing research. I hope this revision would better serve the challenging goal of human visual information processing modeling.

  3. Unveiling the unicorn: a leader's guide to ACO preparation.

    Science.gov (United States)

    Aslin, Paul

    2011-01-01

    The great uncertainty surrounding healthcare reform provides little incentive for action. However, as healthcare leaders wait for final rules and clarity about accountable care organizations (ACOs), inaction is the inappropriate response. Several central themes emerge from research about beginning the ACO process. Leaders should be able to understand and articulate ACO concepts. They should champion embracing cultural change while partnering with physicians. Inventory of skills and capabilities should take place to understand any deficiencies required to implement an ACO. Finally, a plan should be formed by asking strategic questions on each platform needed to ensure performance and strategic goals are at the forefront of decisions regarding structure and function of an ACO. It takes a visionary leader to accept these challenges.

  4. UNVEILING THE DUST NUCLEATION ZONE OF IRC+10216 WITH ALMA

    International Nuclear Information System (INIS)

    Cernicharo, J.; Daniel, F.; Goicoechea, J. R.; Castro-Carrizo, A.; Guélin, M.; Agundez, M.; Marcelino, N.; Joblin, C.

    2013-01-01

    We report the detection in IRC+10216 of lines of HNC J = 3 – 2 pertaining to nine excited vibrational states with energies up to ∼5300 K. The spectrum, observed with ALMA, also shows a surprising large number of narrow, unidentified lines that arise in the vicinity of the star. The HNC data are interpreted through a 1D-spherical non-local radiative transfer model, coupled to a chemical model that includes chemistry at thermochemical equilibrium for the innermost regions and reaction kinetics for the external envelope. Although unresolved by the current early ALMA data, the radius inferred for the emitting region is ∼0.''06 (i.e., ≅ 3 stellar radii), similar to the size of the dusty clumps reported by IR studies of the innermost region (r < 0.''3). The derived abundance of HNC relative to H 2 is 10 –8 < χ(HNC) <10 –6 , and drops quickly where the gas density decreases and the gas chemistry is dominated by reaction kinetics. Merging HNC data with that of molecular species present throughout the inner envelope, such as vibrationally excited HCN, SiS, CS, or SiO, should allow us to characterize the physical and chemical conditions in the dust formation zone

  5. Unveiling Hidden Social Design: New Roles for Sociologists

    Directory of Open Access Journals (Sweden)

    Popov Lubomir

    2017-06-01

    Full Text Available This paper will help foster a more favourable attitude to professional involvement in social design projects and highlight new areas of professional opportunity for sociologists. To overcome the psychological barriers to design engagement and to foster motivation for social design, the authors discuss a case of social design decision making by non-sociologists. The methodology is informed by Activity Theory and Design Theory, and the approach adopted is based on analyzing current best practices, departing from conventional and customary practices. The authors discuss the Fun Palace, which was an innovative architectural project in the 1960s Great Britain, conceived with a fundamental social aim of providing life-long education and professional retooling to working class people in a relaxed and entertaining environment. The paper highlights the sociological nature of decision making in the planning phase of the project as well as the need for sociological knowledge and skills. The explication of the social design activities in the Fun Palace project can inspire sociological practitioners with ideas about entering into various industries and, in particular, in the design of social organizations and buildings.

  6. Unveiling adaptation using high-resolution lineage tracking

    Science.gov (United States)

    Blundell, Jamie; Levy, Sasha; Fisher, Daniel; Petrov, Dmitri; Sherlock, Gavin

    2013-03-01

    Human diseases such as cancer and microbial infections are adaptive processes inside the human body with enormous population sizes: between 106 -1012 cells. In spite of this our understanding of adaptation in large populations is limited. The key problem is the difficulty in identifying anything more than a handful of rare, large-effect beneficial mutations. The development and use of molecular barcodes allows us to uniquely tag hundreds of thousands of cells and enable us to track tens of thousands of adaptive mutations in large yeast populations. We use this system to test some of the key theories on which our understanding of adaptation in large populations is based. We (i) measure the fitness distribution in an evolving population at different times, (ii) identify when an appreciable fraction of clones in the population have at most a single adaptive mutation and isolate a large number of clones with independent single adaptive mutations, and (iii) use this clone collection to determine the distribution of fitness effects of single beneficial mutations.

  7. Unveiling the Universality of I-Love-Q Relations

    Science.gov (United States)

    Sham, Y.-H.; Chan, T. K.; Lin, L.-M.; Leung, P. T.

    2015-01-01

    The recent discovery of the universal I-Love-Q relations connecting the moment of inertia, tidal deformability, and the spin-induced quadrupole moment of compact stars is intriguing and totally unexpected. In this paper, we provide numerical evidence showing that the universality can be attributed to the incompressible limit of the I-Love-Q relations. The fact that modern equations of state are stiff, with an effective adiabatic index larger than about two, above the nuclear density range is the key to establishing the universality for neutron stars and quark stars with typical compactness from about 0.1 to 0.3. On the other hand, the I-Love-Q relations of low-mass neutron stars near the minimum mass limit depend more sensitively on the underlying equation of state because these stars are composed mainly of softer matter at low densities. However, the I-Love-Q relations for low-mass quark stars can still be represented accurately by the incompressible limit. We also study the I-Love relation connecting the moment of inertia and tidal deformability analytically in Newtonian gravity and show why the I-Love-Q relation is weakly dependent on the underlying equation of state and can be attributed to its incompressible limit.

  8. NASA Unveils First Images From Chandra X-Ray Observatory

    Science.gov (United States)

    1999-08-01

    Extraordinary first images from NASA's Chandra X-ray Observatory trace the aftermath of a gigantic stellar explosion in such stunning detail that scientists can see evidence of what may be a neutron star or black hole near the center. Another image shows a powerful X-ray jet blasting 200,000 light years into intergalactic space from a distant quasar. Released today, both images confirm that NASA's newest Great Observatory is in excellent health and its instruments and optics are performing up to expectations. Chandra, the world's largest and most sensitive X-ray telescope, is still in its orbital check-out and calibration phase. "When I saw the first image, I knew that the dream had been realized," said Dr. Martin Weisskopf, Chandra Project Scientist, NASA's Marshall Space Flight Center, Huntsville, AL. "This observatory is ready to take its place in the history of spectacular scientific achievements." "We were astounded by these images," said Harvey Tananbaum, Director of the Smithsonian Astrophysical Observatory's Chandra X- ray Center, Cambridge, MA. "We see the collision of the debris from the exploded star with the matter around it, we see shock waves rushing into interstellar space at millions of miles per hour, and, as a real bonus, we see for the first time a tantalizing bright point near the center of the remnant that could possibly be a collapsed star associated with the outburst." Chandra's PKS 0637-752 PKS 0637-752 After the telescope's sunshade door was opened last week, one of the first images taken was of the 320-year-old supernova remnant Cassiopeia A, which astronomers believe was produced by the explosion of a massive star. Material blasted into space from the explosion crashed into surrounding material at 10 million miles per hour. This collision caused violent shock waves, like massive sonic booms, creating a vast 50-million degree bubble of X-ray emitting gas. Heavy elements in the hot gas produce X-rays of specific energies. Chandra's ability to precisely measure these X-rays tells how much of each element is present. With this information, astronomers can investigate how the elements necessary for life are created and spread throughout the galaxy by exploding stars. "Chandra will help to confirm one of the most fascinating theories of modern science -- that we came from the stars," said Professor Robert Kirshner of Harvard University. "Its ability to make X-ray images of comparable quality to optical images will have an impact on virtually every area of astronomy." Chandra also imaged a distant and very luminous quasar -- a single star-like object -- sporting a powerful X-ray jet blasting into space. The quasar radiates with the power of 10 trillion suns, energy which scientists believe comes from a supermassive black hole at its center. Chandra's image, combined with radio telescope observations, should provide insight into the process by which supermassive black holes can produce such cosmic jets. "Chandra has allowed NASA to seize the opportunity to put the U.S. back in the lead of observational X-ray astronomy," said Dr. Edward Weiler, Associate Administrator of Space Science, NASA Headquarters, Washington, DC. "History teaches us that whenever you develop a telescope 10 times better than what came before, you will revolutionize astronomy. Chandra is poised to do just that." The Chandra X-ray observatory was named in honor of the late Nobel laureate Subrahmanyan Chandrasekhar. NASA's Marshall Space Flight Center manages the Chandra program. TRW, Inc., Redondo Beach, CA, is the prime contractor for the spacecraft. The Smithsonian's Chandra X-ray Center controls science and flight operations from Cambridge, MA. Press: Fact Sheet The first Chandra images will be posted to the Internet at: http://chandra.nasa.gov and http://chandra.harvard.edu NASA press releases and other information are available automatically by sending an Internet electronic mail message to domo@hq.nasa.gov. In the body of the message (not the subject line) users should type the words "subscribe press-release" (no quotes). The system will reply with a confirmation via E-mail of each subscription. A second automatic message will include additional information on the service. NASA releases also are available via CompuServe using the command GO NASA. To unsubscribe from this mailing list, address an E-mail message to domo@hq.nasa.gov, leave the subject blank, and type only "unsubscribe press-release" (no quotes) in the body of the message.

  9. Pregnancy pragmatics unveiled: on bodies, bellies, and power in Cameroon

    NARCIS (Netherlands)

    van der Sijpt, E.

    2014-01-01

    Over the last few decades, anthropologists interested in reproduction have increasingly focused on the relationship between women’s (limited) reproductive agency and (bio)political forces such as patriarchy, medicine, the state, and the global political economy. In their quest for understanding

  10. Affective Man-Machine Interface: Unveiling Human Emotions through Biosignals

    Science.gov (United States)

    van den Broek, Egon L.; Lisý, Viliam; Janssen, Joris H.; Westerink, Joyce H. D. M.; Schut, Marleen H.; Tuinenbreijer, Kees

    As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological proce-sses, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and, as such, can serve as an advanced man-machine interface (MMI) for empathic consumer products. However, such a MMI requires the correct classification of biosignals to emotion classes. This chapter starts with an introduction on biosignals for emotion detection. Next, a state-of-the-art review is presented on automatic emotion classification. Moreover, guidelines are presented for affective MMI. Subsequently, a research is presented that explores the use of EDA and three facial EMG signals to determine neutral, positive, negative, and mixed emotions, using recordings of 21 people. A range of techniques is tested, which resulted in a generic framework for automated emotion classification with up to 61.31% correct classification of the four emotion classes, without the need of personal profiles. Among various other directives for future research, the results emphasize the need for parallel processing of multiple biosignals.

  11. Unveiling Quasiperiodicity through Nonlinear Wave Mixing in Periodic Media

    International Nuclear Information System (INIS)

    Bahabad, Alon; Arie, Ady; Voloch, Noa; Bruner, Ariel; Eger, David

    2007-01-01

    Quasiperiodicity is the concept of order without translation symmetry. The discovery of quasiperiodic order in natural materials transformed the way scientists examine and define ordered structure. We show and verify experimentally that quasiperiodicity can be observed by scattering processes from a periodic structure, provided the interaction area is of finite width. This is made through a momentum conservation condition, physically realizing a geometrical method used to model quasiperiodic structures by projecting a periodic structure of a higher dimension

  12. Unveiling Spatial Epidemiology of HIV with Mobile Phone Data

    Science.gov (United States)

    Brdar, Sanja; Gavrić, Katarina; Ćulibrk, Dubravko; Crnojević, Vladimir

    2016-01-01

    An increasing amount of geo-referenced mobile phone data enables the identification of behavioral patterns, habits and movements of people. With this data, we can extract the knowledge potentially useful for many applications including the one tackled in this study - understanding spatial variation of epidemics. We explored the datasets collected by a cell phone service provider and linked them to spatial HIV prevalence rates estimated from publicly available surveys. For that purpose, 224 features were extracted from mobility and connectivity traces and related to the level of HIV epidemic in 50 Ivory Coast departments. By means of regression models, we evaluated predictive ability of extracted features. Several models predicted HIV prevalence that are highly correlated (>0.7) with actual values. Through contribution analysis we identified key elements that correlate with the rate of infections and could serve as a proxy for epidemic monitoring. Our findings indicate that night connectivity and activity, spatial area covered by users and overall migrations are strongly linked to HIV. By visualizing the communication and mobility flows, we strived to explain the spatial structure of epidemics. We discovered that strong ties and hubs in communication and mobility align with HIV hot spots.

  13. Inclusive Financial System Reforms in Uganda: Unveiling Ambiguity

    OpenAIRE

    Ayoki, Milton

    2014-01-01

    This paper examines the financial system reforms in the context of financial sector deepening, and strategy for financial sector development and inclusion in Uganda. Results suggest that the indicators of financial sector development are largely as they were in 1996 and that the actual gains from financial inclusion strategies are small. Evidence suggests a weak link between financial deepening and financial usage by firms and households. It finds the acclaimed success (by policy makers and s...

  14. Magnetic seismology of interstellar gas clouds: Unveiling a hidden dimension.

    Science.gov (United States)

    Tritsis, Aris; Tassis, Konstantinos

    2018-05-11

    Stars and planets are formed inside dense interstellar molecular clouds by processes imprinted on the three-dimensional (3D) morphology of the clouds. Determining the 3D structure of interstellar clouds remains challenging because of projection effects and difficulties measuring the extent of the clouds along the line of sight. We report the detection of normal vibrational modes in the isolated interstellar cloud Musca, allowing determination of the 3D physical dimensions of the cloud. We found that Musca is vibrating globally, with the characteristic modes of a sheet viewed edge on, not the characteristics of a filament as previously supposed. We reconstructed the physical properties of Musca through 3D magnetohydrodynamic simulations, reproducing the observed normal modes and confirming a sheetlike morphology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  15. Stressed lungs: unveiling the role of circulating stress ...

    Science.gov (United States)

    Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction with lung lining components causing local oxidative changes, which then leads to cell damage and recruitment of inflammatory cells. It is postulated that the spillover of reactive intermediates and pro-inflammatory molecules from lung to systemic circulation mediates extra-pulmonary effects. However, recent work from our laboratory supports an alternative hypothesis that circulating stress hormones, such as epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects. We have shown in rats and humans that ozone increases the levels of circulating stress hormones through activation of the hypothalamus- pituitary-adrenal (HPA) axis before any measurable effects are observed in the lung. The surgical removal of adrenals diminishes circulating stress hormones and at the same time, the pulmonary effects of ozone suggesting a significant contribution of these hormones in ozone-induced lung injury and inflammation. While ozone effects in the lung have been extensively studied, the contribution of central nervous system -mediated hormonal stress response has not been examined. In order to understand the signaling pathways that might be involved in ozone-induced lun

  16. Unveiling Hidden Dynamics of Hippo Signalling: A Systems Analysis

    Directory of Open Access Journals (Sweden)

    Sung-Young Shin

    2016-08-01

    Full Text Available The Hippo signalling pathway has recently emerged as an important regulator of cell apoptosis and proliferation with significant implications in human diseases. In mammals, the pathway contains the core kinases MST1/2, which phosphorylate and activate LATS1/2 kinases. The pro-apoptotic function of the MST/LATS signalling axis was previously linked to the Akt and ERK MAPK pathways, demonstrating that the Hippo pathway does not act alone but crosstalks with other signalling pathways to coordinate network dynamics and cellular outcomes. These crosstalks were characterised by a multitude of complex regulatory mechanisms involving competitive protein-protein interactions and phosphorylation mediated feedback loops. However, how these different mechanisms interplay in different cellular contexts to drive the context-specific network dynamics of Hippo-ERK signalling remains elusive. Using mathematical modelling and computational analysis, we uncovered that the Hippo-ERK network can generate highly diverse dynamical profiles that can be clustered into distinct dose-response patterns. For each pattern, we offered mechanistic explanation that defines when and how the observed phenomenon can arise. We demonstrated that Akt displays opposing, dose-dependent functions towards ERK, which are mediated by the balance between the Raf-1/MST2 protein interaction module and the LATS1 mediated feedback regulation. Moreover, Ras displays a multi-functional role and drives biphasic responses of both MST2 and ERK activities; which are critically governed by the competitive protein interaction between MST2 and Raf-1. Our study represents the first in-depth and systematic analysis of the Hippo-ERK network dynamics and provides a concrete foundation for future studies.

  17. Unveiling the Domain Conflict – FOSS vs. IPR

    Directory of Open Access Journals (Sweden)

    Dr. Anurika Vaish

    2007-04-01

    Full Text Available In the present times the most talked about issues in the knowledge driven economic system are Free and Open Source Software (FOSS and Intellectual Property Right (IPR, both of which exist at poles apart. The question that prevails that is about the relevance of the either and that of the dominance of each one. The paper tries to probe into issues of general and specific relevance of FOSS and IPR as suppliers of certain set of utility and benefit to the user. It will also check the validity of the claim of FOSS and it licensing procedure comparing it with the user ship obligations of IPR protected products and services. The premise to the paper is that both FOSS and IPR have to exist and compliment each other ensuring a strong presence of resources in the public and private domain. The paper would certainly work on the area to validate the existence of conflict between the FOSS and IPR, or it is a mere false caution raised by groups pursuing either cause. Finally the paper would propose to demarcate the areas of dominance of FOSS and IPR and prove the utility at the socio-economic front.

  18. Unveiling the evolutionary phase of B[e] supergiants

    Czech Academy of Sciences Publication Activity Database

    Muratore, M.F.; Kraus, Michaela; Liermann, A.; Schnurr, O.; Cidale, L.S.; Arias, M.L.

    2010-01-01

    Roč. 53, - (2010), s. 123-126 E-ISSN 1669-9521 Institutional research plan: CEZ:AV0Z10030501 Keywords : B[e] supergiants * K-band spectra Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

  19. Unveiling consumer's privacy paradox behaviour in an economic exchange.

    Science.gov (United States)

    Motiwalla, Luvai F; Li, Xiao-Bai

    2016-01-01

    Privacy paradox is of great interest to IS researchers and firms gathering personal information. It has been studied from social, behavioural, and economic perspectives independently. However, prior research has not examined the degrees of influence these perspectives contribute to the privacy paradox problem. We combine both economic and behavioural perspectives in our study of the privacy paradox with a price valuation of personal information through an economic experiment combined with a behavioural study on privacy paradox. Our goal is to reveal more insights on the privacy paradox through economic valuation on personal information. Results indicate that general privacy concerns or individual disclosure concerns do not have a significant influence on the price valuation of personal information. Instead, prior disclosure behaviour in specific scenario, like with healthcare providers or social networks, is a better indicator of consumer price valuations.

  20. Unveiling Mycoplasma hyopneumoniae Promoters: Sequence Definition and Genomic Distribution

    Science.gov (United States)

    Weber, Shana de Souto; Sant'Anna, Fernando Hayashi; Schrank, Irene Silveira

    2012-01-01

    Several Mycoplasma species have had their genome completely sequenced, including four strains of the swine pathogen Mycoplasma hyopneumoniae. Nevertheless, little is known about the nucleotide sequences that control transcriptional initiation in these microorganisms. Therefore, with the objective of investigating the promoter sequences of M. hyopneumoniae, 23 transcriptional start sites (TSSs) of distinct genes were mapped. A pattern that resembles the σ70 promoter −10 element was found upstream of the TSSs. However, no −35 element was distinguished. Instead, an AT-rich periodic signal was identified. About half of the experimentally defined promoters contained the motif 5′-TRTGn-3′, which was identical to the −16 element usually found in Gram-positive bacteria. The defined promoters were utilized to build position-specific scoring matrices in order to scan putative promoters upstream of all coding sequences (CDSs) in the M. hyopneumoniae genome. Two hundred and one signals were found associated with 169 CDSs. Most of these sequences were located within 100 nucleotides of the start codons. This study has shown that the number of promoter-like sequences in the M. hyopneumoniae genome is more frequent than expected by chance, indicating that most of the sequences detected are probably biologically functional. PMID:22334569

  1. Unveiling the secrets of the universe Cern's openlab projects

    CERN Multimedia

    Garvey, Kelsey

    2009-01-01

    "Upon the 20th anniversary ot the birth of the World Wide Web, the European Union has declared 2009 the European Year of Creativity and Innovation. Cern, and specifically its openlab secor, has already begun to fulfil public expectations of this year of discovery" (2 pages)

  2. Alpha centauri unveiling the secrets of our nearest stellar neighbor

    CERN Document Server

    Beech, Martin

    2015-01-01

    As our closest stellar companion and composed of two Sun-like stars and a third small dwarf star, Alpha Centauri is an ideal testing ground of astrophysical models and has played a central role in the history and development of modern astronomy—from the first guesses at stellar distances to understanding how our own star, the Sun, might have evolved. It is also the host of the nearest known exoplanet, an ultra-hot, Earth-like planet recently discovered. Just 4.4 light years away Alpha Centauri is also the most obvious target for humanity’s first directed interstellar space probe. Such a mission could reveal the small-scale structure of a new planetary system and also represent the first step in what must surely be humanity’s greatest future adventure—exploration of the Milky Way Galaxy itself. For all of its closeness, α Centauri continues to tantalize astronomers with many unresolved mysteries, such as how did it form, how many planets does it contain and where are they, and how might we view its ex...

  3. Unveiling the biometric potential of finger-based ECG signals.

    Science.gov (United States)

    Lourenço, André; Silva, Hugo; Fred, Ana

    2011-01-01

    The ECG signal has been shown to contain relevant information for human identification. Even though results validate the potential of these signals, data acquisition methods and apparatus explored so far compromise user acceptability, requiring the acquisition of ECG at the chest. In this paper, we propose a finger-based ECG biometric system, that uses signals collected at the fingers, through a minimally intrusive 1-lead ECG setup recurring to Ag/AgCl electrodes without gel as interface with the skin. The collected signal is significantly more noisy than the ECG acquired at the chest, motivating the application of feature extraction and signal processing techniques to the problem. Time domain ECG signal processing is performed, which comprises the usual steps of filtering, peak detection, heartbeat waveform segmentation, and amplitude normalization, plus an additional step of time normalization. Through a simple minimum distance criterion between the test patterns and the enrollment database, results have revealed this to be a promising technique for biometric applications.

  4. [Cell-derived microparticles unveil their fibrinolytic and proteolytic function].

    Science.gov (United States)

    Doeuvre, Loïc; Angles-Cano, Eduardo

    2009-01-01

    Cell-derived microparticles (MP) are membrane microvesicles, 0.1-1 microm in size, shed by cells following activation or during apoptosis in a variety of pathological conditions. MPs released by blood cells or by vascular endothelial cells display molecular signatures that allow their identification and functional characterization. In addition, they provide tissue factor (TF) and a procoagulant phospholipid surface. Therefore, at present, the most strongly established applied research on MPs is their procoagulant activity as a determinant of thrombotic risk in various clinical conditions. Previous studies have indicated that MPs derived from malignant cells express matrix metalloproteinases, urokinase and its receptor (uPA/uPAR) that, in the presence of plasminogen, may act in concert to degrade extracellular matrix proteins. Recently, it was shown that MPs from TNFa-stimulated endothelial cells served as a surface for interaction with plasminogen and its conversion into plasmin by the uPA/uPAR system expressed at their surface. This capacity of MPs to promote plasmin generation confers them a new profibrinolytic and proteolytic function that may be of relevance in fibrinolysis, cell migration, angiogenesis, dissemination of malignant cells, cell detachment and apoptosis.

  5. Unveiling the Role of Galactic Rotation on Star Formation

    Science.gov (United States)

    Utreras, José; Becerra, Fernando; Escala, Andrés

    2016-12-01

    We study the star formation process at galactic scales and the role of rotation through numerical simulations of spiral and starburst galaxies using the adaptive mesh refinement code Enzo. We focus on the study of three integrated star formation laws found in the literature: the Kennicutt-Schmidt (KS) and Silk-Elmegreen (SE) laws, and the dimensionally homogeneous equation proposed by Escala {{{Σ }}}{SFR}\\propto \\sqrt{G/L}{{{Σ }}}{gas}1.5. We show that using the last we take into account the effects of the integration along the line of sight and find a unique regime of star formation for both types of galaxies, suppressing the observed bi-modality of the KS law. We find that the efficiencies displayed by our simulations are anti-correlated with the angular velocity of the disk Ω for the three laws studied in this work. Finally, we show that the dimensionless efficiency of star formation is well represented by an exponentially decreasing function of -1.9{{Ω }}{t}{ff}{ini}, where {t}{ff}{ini} is the initial free-fall time. This leads to a unique galactic star formation relation which reduces the scatter of the bi-modal KS, SE, and Escala relations by 43%, 43%, and 35%, respectively.

  6. Unveiling the Formation Pathway of Single Crystalline Porous Silicon Nanowires

    Science.gov (United States)

    Zhong, Xing; Qu, Yongquan; Lin, Yung-Chen; Liao, Lei; Duan, Xiangfeng

    2011-01-01

    Porous silicon nanowire is emerging as an interesting material system due to its unique combination of structural, chemical, electronic, and optical properties. To fully understand their formation mechanism is of great importance for controlling the fundamental physical properties and enabling potential applications. Here we present a systematic study to elucidate the mechanism responsible for the formation of porous silicon nanowires in a two-step silver-assisted electroless chemical etching method. It is shown that silicon nanowire arrays with various porosities can be prepared by varying multiple experimental parameters such as the resistivity of the starting silicon wafer, the concentration of oxidant (H2O2) and the amount of silver catalyst. Our study shows a consistent trend that the porosity increases with the increasing wafer conductivity (dopant concentration) and oxidant (H2O2) concentration. We further demonstrate that silver ions, formed by the oxidation of silver, can diffuse upwards and re-nucleate on the sidewalls of nanowires to initiate new etching pathways to produce porous structure. The elucidation of this fundamental formation mechanism opens a rational pathway to the production of wafer-scale single crystalline porous silicon nanowires with tunable surface areas ranging from 370 m2·g−1 to 30 m2·g−1, and can enable exciting opportunities in catalysis, energy harvesting, conversion, storage, as well as biomedical imaging and therapy. PMID:21244020

  7. Unveiling the edge of time black holes, white holes, wormholes

    CERN Document Server

    Gribbin, John

    1992-01-01

    Acclaimed science writer John Gribbin recounts dramatic stories that have led scientists to believe black holes and their more mysterious kin are not only real, but might actually provide a passage to other universes and travel through time.

  8. Unveiling CO2 heterogeneous freezing plumes during champagne cork popping.

    Science.gov (United States)

    Liger-Belair, Gérard; Cordier, Daniel; Honvault, Jacques; Cilindre, Clara

    2017-09-14

    Cork popping from clear transparent bottles of champagne stored at different temperatures (namely, 6, 12, and 20 °C) was filmed through high-speed video imaging in the visible light spectrum. During the cork popping process, a plume mainly composed of gaseous CO 2 with traces of water vapour freely expands out of the bottleneck through ambient air. Most interestingly, for the bottles stored at 20 °C, the characteristic grey-white cloud of fog classically observed above the bottlenecks of champagne stored at lower temperatures simply disappeared. It is replaced by a more evanescent plume, surprisingly blue, starting from the bottleneck. We suggest that heterogeneous freezing of CO 2 occurs on ice water clusters homogeneously nucleated in the bottlenecks, depending on the saturation ratio experienced by gas-phase CO 2 after adiabatic expansion (indeed highly bottle temperature dependent). Moreover, and as observed for the bottles stored at 20 °C, we show that the freezing of only a small portion of all the available CO 2 is able to pump the energy released through adiabatic expansion, thus completely inhibiting the condensation of water vapour found in air packages adjacent to the gas volume gushing out of the bottleneck.

  9. UNVEILING THE RESTRICTED AND EXTENDED POSSIBILITIES OF DISTRIBUTED LEADERSHIP

    OpenAIRE

    Irene Dieronitou

    2014-01-01

    The scope of this paper is to critically examine the opportunities as well as the fragmentations of the distributed leadership discourse and practices. In other words, this paper is both an argument for as well as a critique of the variety of forms of distributed leadership. Focusing mainly on Spillane’s et al form of distributed leadership and Fullan’s ‘System thinkers in action’, this paper has come to locate perspectives to distributed leadership on a spectrum, varying from ‘ex...

  10. UNVEILING THE UNIVERSALITY OF I-LOVE-Q RELATIONS

    International Nuclear Information System (INIS)

    Sham, Y.-H.; Lin, L.-M.; Leung, P. T.; Chan, T. K.

    2015-01-01

    The recent discovery of the universal I-Love-Q relations connecting the moment of inertia, tidal deformability, and the spin-induced quadrupole moment of compact stars is intriguing and totally unexpected. In this paper, we provide numerical evidence showing that the universality can be attributed to the incompressible limit of the I-Love-Q relations. The fact that modern equations of state are stiff, with an effective adiabatic index larger than about two, above the nuclear density range is the key to establishing the universality for neutron stars and quark stars with typical compactness from about 0.1 to 0.3. On the other hand, the I-Love-Q relations of low-mass neutron stars near the minimum mass limit depend more sensitively on the underlying equation of state because these stars are composed mainly of softer matter at low densities. However, the I-Love-Q relations for low-mass quark stars can still be represented accurately by the incompressible limit. We also study the I-Love relation connecting the moment of inertia and tidal deformability analytically in Newtonian gravity and show why the I-Love-Q relation is weakly dependent on the underlying equation of state and can be attributed to its incompressible limit

  11. UNVEILING THE DUST NUCLEATION ZONE OF IRC+10216 WITH ALMA

    Energy Technology Data Exchange (ETDEWEB)

    Cernicharo, J.; Daniel, F.; Goicoechea, J. R. [Departamento de Astrofísica, Centro de Astrobiología, CSIC-INTA, Ctra. de Torrejón a Ajalvir km 4, E-28850 Madrid (Spain); Castro-Carrizo, A.; Guélin, M. [Institut de Radioastronomie Millimétrique, 300 rue de la Piscine, F-38406, Saint Martin dHères (France); Agundez, M. [Univ. Bordeaux, LAB, UMR 5804, F-33270, Floirac (France); Marcelino, N. [NRAO, 520 Edgemont Road, Charlottesville, VA 22902 (United States); Joblin, C. [Université de Toulouse, UPS-OMP, IRAP, Toulouse (France)

    2013-12-01

    We report the detection in IRC+10216 of lines of HNC J = 3 – 2 pertaining to nine excited vibrational states with energies up to ∼5300 K. The spectrum, observed with ALMA, also shows a surprising large number of narrow, unidentified lines that arise in the vicinity of the star. The HNC data are interpreted through a 1D-spherical non-local radiative transfer model, coupled to a chemical model that includes chemistry at thermochemical equilibrium for the innermost regions and reaction kinetics for the external envelope. Although unresolved by the current early ALMA data, the radius inferred for the emitting region is ∼0.''06 (i.e., ≅ 3 stellar radii), similar to the size of the dusty clumps reported by IR studies of the innermost region (r < 0.''3). The derived abundance of HNC relative to H{sub 2} is 10{sup –8} < χ(HNC) <10{sup –6}, and drops quickly where the gas density decreases and the gas chemistry is dominated by reaction kinetics. Merging HNC data with that of molecular species present throughout the inner envelope, such as vibrationally excited HCN, SiS, CS, or SiO, should allow us to characterize the physical and chemical conditions in the dust formation zone.

  12. Homologous recombination contributes to the repair of DNA double-strand breaks induced by high-energy iron ions

    Energy Technology Data Exchange (ETDEWEB)

    Zafar, Faria; Seidler, Sara B.; Kronenberg, Amy; Schild, David; Wiese, Claudia

    2010-06-29

    To test the contribution of homologous recombinational repair (HRR) in repairing DNA damaged sites induced by high-energy iron ions, we used: (1) HRR-deficient rodent cells carrying a deletion in the RAD51D gene and (2) syngeneic human cells impaired for HRR by RAD51D or RAD51 knockdown using RNA interference. We show that in response to iron ions, HRR contributes to cell survival in rodent cells, and that HRR-deficiency abrogates RAD51 foci formation. Complementation of the HRR defect by human RAD51D rescues both enhanced cytotoxicity and RAD51 foci formation. For human cells irradiated with iron ions, cell survival is decreased, and, in p53 mutant cells, the levels of mutagenesis are increased when HRR is impaired. Human cells synchronized in S phase exhibit more pronounced resistance to iron ions as compared with cells in G1 phase, and this increase in radioresistance is diminished by RAD51 knockdown. These results implicate a role for RAD51-mediated DNA repair (i.e. HRR) in removing a fraction of clustered lesions induced by charged particle irradiation. Our results are the first to directly show the requirement for an intact HRR pathway in human cells in ensuring DNA repair and cell survival in response to high-energy high LET radiation.

  13. Homologous recombination contributes to the repair of DNA double-strand breaks induced by high-energy iron ions

    International Nuclear Information System (INIS)

    Zafar, Faria; Seidler, Sara B.; Kronenberg, Amy; Schild, David; Wiese, Claudia

    2010-01-01

    To test the contribution of homologous recombinational repair (HRR) in repairing DNA damaged sites induced by high-energy iron ions, we used: (1) HRR-deficient rodent cells carrying a deletion in the RAD51D gene and (2) syngeneic human cells impaired for HRR by RAD51D or RAD51 knockdown using RNA interference. We show that in response to iron ions, HRR contributes to cell survival in rodent cells, and that HRR-deficiency abrogates RAD51 foci formation. Complementation of the HRR defect by human RAD51D rescues both enhanced cytotoxicity and RAD51 foci formation. For human cells irradiated with iron ions, cell survival is decreased, and, in p53 mutant cells, the levels of mutagenesis are increased when HRR is impaired. Human cells synchronized in S phase exhibit more pronounced resistance to iron ions as compared with cells in G1 phase, and this increase in radioresistance is diminished by RAD51 knockdown. These results implicate a role for RAD51-mediated DNA repair (i.e. HRR) in removing a fraction of clustered lesions induced by charged particle irradiation. Our results are the first to directly show the requirement for an intact HRR pathway in human cells in ensuring DNA repair and cell survival in response to high-energy high LET radiation.

  14. Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination.

    NARCIS (Netherlands)

    J. Essers (Jeroen); R.W. Hendriks (Rudi); S.M.A. Swagemakers (Sigrid); C. Troelstra (Christine); J. de Wit (Jan); D. Bootsma (Dirk); J.H.J. Hoeijmakers (Jan); R. Kanaar (Roland)

    1997-01-01

    textabstractDouble-strand DNA break (DSB) repair by homologous recombination occurs through the RAD52 pathway in Saccharomyces cerevisiae. Its biological importance is underscored by the conservation of many RAD52 pathway genes, including RAD54, from fungi to humans. We have analyzed the phenotype

  15. Characterizing the Hypermutated Subtype of Advanced Prostate Cancer as a Predictive Biomarker for Precision Medicine

    Science.gov (United States)

    2016-10-01

    instability, MSI, MLH1, MSH2, MSH6, PMS2 , metastasis, precision medicine 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...hypermutation, hyper-mutation, microsatellite instability, MSI, MLH1, MSH2, MSH6, PMS2 , metastasis, precision medicine Colin Pritchard MD, PhD 2015-2016 Year 2...BRCC3 BRIP1 CHEK1 CHEK2 FAM175A MLH1 MRE11A MSH2 MSH6 NBN PALB2 PMS2 PRSS1 PTEN RAD50 RAD51B RAD51C RAD51D RBBP8 TP53 TP53BP1 XRCC2 Additional

  16. Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells.

    Science.gov (United States)

    Browning, Cynthia L; Qin, Qin; Kelly, Deborah F; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria; Wise, John Pierce

    2016-09-01

    Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. X-ray Absorption Spectroscopy Unveils the Formation of Gold Nanoparticles in Corn X-ray Absorption Spectroscopy Unveils the Formation of Gold Nanoparticles in Corn

    Directory of Open Access Journals (Sweden)

    Gustavo Cruz-Jiménez

    2012-02-01

    Full Text Available En este estudio se determinó, mediante espectroscopía de absorción de rayos-X, la posible biotransformación de oro en maíz (variedad Golden que se germinó y creció en KAuCl4. Adicionalmente se investigó el efecto de la tiourea y el tiocianato de amonio en la absorción de oro por la planta de maíz. Los resultados indicaron que concentraciones menores a 160 mg Au/L, no afectaron la germinación o el crecimiento de las plántulas. Tanto la tiourea como el tiocianato de amonio incrementaron 6 veces el contenido de oro en las raíces, mientras que la tiourea provocó un incremento de 10 veces la concentración de oro en tallos con respecto a los tratamientos sin este compuesto. El 91% del oro en el maíz se encontró como Au(0 y el resto como Au(III. Los análisis de estructura fi na revelaron que el oro se encontraba con un número de coordinación de 9,5 aproximadamente a 2,86 Å, indicando una esfera de coordinación incompleta, lo cual implica la presencia de una nano-fase. Usando la ecuación de Borowski se determinó que las nanopartículas tenían un tamaño promedio de 10,36 nm.In this study, X-ray absorption spectroscopy was used to determine the possible gold biotransformation by Zea mays (corn var. Golden, germinated and grown in a medium spikedwith KAuCl4. In addition, the gold uptake capacity of corn assisted by thiourea and ammoniumthiocyanate was investigated. Results showed that up to 160 mg/L, gold did no treduce corn seed germination or plant growth. Both thiourea and ammonium thiocyanateresulted in a 6-fold increase of gold concentration in roots and thiourea promoted a 10-fold increase of gold concentration in shoots. X-ray absorption near edge structure studies demonstrated that approximately 91% of the gold present in plant samples was Au(0. Theremaining 9% was present as Au(III. In addition, extended X-ray absorption fi ne structureresults showed that in corn roots, the gold coordination number was around 9,5 neighboringgold atoms at approximately 2,86 Å, indicating an incomplete fi rst coordination shell,which imply the presence of a nano-phase. The results demonstrated that Z. mays was ableto produce gold nanoparticles with a size of 10,36 nm.

  18. Clinical application of multigene panels: challenges of next generation counseling and cancer risk management

    Directory of Open Access Journals (Sweden)

    Thomas Paul Slavin

    2015-09-01

    Full Text Available Background: Multigene panels can be a cost- and time-effective alternative to sequentially testing multiple genes, especially with a mixed family cancer phenotype. However, moving beyond our single-gene testing paradigm has unveiled many new challenges to the clinician. The purpose of this article is to familiarize the reader with some of the challenges, as well as potential opportunities, of expanded hereditary cancer panel testing. Methods: We include results from 348 commercial multigene panel tests ordered from January 1, 2014, through October 1, 2014, by clinicians associated with the City of Hope’s Clinical Cancer Genetics Community of Practice. We also discuss specific challenging cases that arose during this period involving abnormalities in the genes: CDH1, TP53, PMS2, PALB2, CHEK2, NBN, and RAD51C. Results: If historically high risk genes only were included in the panels (BRCA1, BRCA2, MSH6, PMS2, TP53, APC, CDH1, the results would have been positive only 6.2% of the time, instead of 17%. Results returned with variants of uncertain significance (VUS 42% of the time. Conclusion: These figures and cases stress the importance of adequate pretest counseling in anticipation of higher percentages of positive, VUS, unexpected, and ambiguous test results. Test result ambiguity can be limited by the use of phenotype specific panels; if found, multiple resources (the literature, reference laboratory, colleagues, national experts, and research efforts can be accessed to better clarify counseling and management for the patient and family. For pathogenic variants in low and moderate risk genes, empiric risk modeling based on the patient’s personal and family history of cancer may supersede gene-specific risk. Commercial laboratory and patient contributions to public databases and research efforts will be needed to better classify variants and reduce clinical ambiguity of multigene panels.

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

    Science.gov (United States)

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

    2015-01-01

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

  20. Enhancing Targeted Genomic DNA Editing in Chicken Cells Using the CRISPR/Cas9 System

    Science.gov (United States)

    Wang, Ling; Yang, Likai; Guo, Yijie; Du, Weili; Yin, Yajun; Zhang, Tao; Lu, Hongzhao

    2017-01-01

    The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system. In addition, the combined effect of CRISPR nuclease and yRad52 dramatically increased the efficiency of the targeted substitution in the myostatin gene using 50-mer oligodeoxynucleotides (ssODN) as the donor DNA, resulting in a 36.7% editing efficiency after puromycin selection. Furthermore, based on the effect of yRad52, the frequency of exogenous gene integration in the chicken genome was more than 3-fold higher than that without yRad52. Collectively, these results suggest that ssODN is an ideal donor DNA for targeted substitution and that CRISPR/Cas9 combined with yRad52 significantly enhances chicken genome editing. These findings could be extensively applied in other organisms. PMID:28068387

  1. On the mobility of carbon-supported platinum nanoparticles towards unveiling cathode degradation in water electrolysis

    Science.gov (United States)

    Paciok, Paul; Schalenbach, Maximilian; Carmo, Marcelo; Stolten, Detlef

    2017-10-01

    This study investigates the influence of the hydrogen evolution reaction (HER) overpotential on the mobility of carbon-supported platinum particles. The migration of the platinum over the carbon support was analyzed by means of identical location transmission electron microscopy (IL-TEM). While at potentials of 0.1 and 0 V vs. reversible hydrogen electrode (RHE), no changes to the Pt/C material were observed. With a decrease of the overpotential to -0.1 V vs. RHE, an increase in the quantity of migrating platinum particles took place. At -0.2 V vs. RHE, a further rise in the particle migration was observed. The effect of the overpotential on the migration was explained by a higher hydrogen generation rate, the formation of a hydrogen monolayer on the platinum and the resulting changes of the platinum support distance. The mechanisms revealed in this study could describe a relevant source of degradation of PEM water electrolyzers.

  2. Shame veiled and unveiled: the shame affect and its re-emergence in the clinical setting.

    Science.gov (United States)

    Mann, Mali

    2010-09-01

    The paper examines the psychoanalytic theory of shame and the importance of developmental aspects of the shame affect. In a clinical setting, the discovery of the shame affect, stemming from unconscious and early traumatic situations, is an important and useful approach in helping the patient access painful memories and defenses against them. The defenses disguise the underlying shame affect; furthermore, vision is being bound up with the searing painful affect of shame. The anticipatory dread of scornful gaze of another person, similar to objective self-awareness can cause mortification. Fear of mortification and being exposed emerges in the clinical setting. Through the recognition of enactments in the transference and countertransference interchange, the analyst helps the patient working through them. Several case vignettes demonstrate these important concepts. Finally, the author discusses how shame in certain situations can be a powerful, positive motivator for human interactions.

  3. Social network architecture of human immune cells unveiled by quantitative proteomics.

    Science.gov (United States)

    Rieckmann, Jan C; Geiger, Roger; Hornburg, Daniel; Wolf, Tobias; Kveler, Ksenya; Jarrossay, David; Sallusto, Federica; Shen-Orr, Shai S; Lanzavecchia, Antonio; Mann, Matthias; Meissner, Felix

    2017-05-01

    The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not yet been established. We applied high-resolution mass-spectrometry-based proteomics to characterize 28 primary human hematopoietic cell populations in steady and activated states at a depth of >10,000 proteins in total. Protein copy numbers revealed a specialization of immune cells for ligand and receptor expression, thereby connecting distinct immune functions. By integrating total and secreted proteomes, we discovered fundamental intercellular communication structures and previously unknown connections between cell types. Our publicly accessible (http://www.immprot.org/) proteomic resource provides a framework for the orchestration of cellular interplay and a reference for altered communication associated with pathology.

  4. Si-BEARING MOLECULES TOWARD IRC+10216: ALMA UNVEILS THE MOLECULAR ENVELOPE OF CWLeo

    International Nuclear Information System (INIS)

    Prieto, L. Velilla; Cernicharo, J.; Quintana-Lacaci, G.; Agúndez, M.; Castro-Carrizo, A.; Guélin, M.; Fonfría, J. P.; Marcelino, N.; Zúñiga, J.; Requena, A.; Bastida, A.; Lique, F.

    2015-01-01

    We report the detection of SiS rotational lines in high-vibrational states as well as SiO and SiC 2 lines in their ground vibrational state toward IRC+10216 during the Atacama Large Millimeter Array Cycle 0. The spatial distribution of these molecules shows compact emission for SiS and a more extended emission for SiO and SiC 2 and also proves the existence of an increase in the SiC 2 emission at the outer shells of the circumstellar envelope (CSE). We analyze the excitation conditions of the vibrationally excited SiS using the population diagram technique, and we use a large velocity gradient model to compare with the observations. We found moderate discrepancies between the observations and the models that could be explained if SiS lines detected are optically thick. Additionally, the line profiles of the detected rotational lines in the high-energy vibrational states show a decreasing linewidth with increasing energy levels. This may be evidence that these lines could be excited only in the inner shells, i.e., the densest and hottest, of the CSE of IRC+10216

  5. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

    Directory of Open Access Journals (Sweden)

    Diego M Presman

    2014-03-01

    Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

  6. The effective theory of quintessence: the w < −1 side unveiled

    International Nuclear Information System (INIS)

    Creminelli, Paolo; Vernizzi, Filippo; D'Amico, Guido; Noreña, Jorge

    2009-01-01

    We study generic single-field dark energy models, by a parametrization of the most general theory of their perturbations around a given background, including higher derivative terms. In appropriate limits this approach reproduces standard quintessence, k-essence and ghost condensation. We find no general pathology associated to an equation of state w Q Q = −1. Stability requires that the w Q Q Q ) vs. speed of sound squared

  7. Unveiling common responses of Medicago truncatula to appropriate and inappropriate rust species

    Science.gov (United States)

    Vaz Patto, Maria Carlota; Rubiales, Diego

    2014-01-01

    Little is known about the nature of effective defense mechanisms in legumes to pathogens of remotely related plant species. Some rust species are among pathogens with broad host range causing dramatic losses in various crop plants. To understand and compare the different host and nonhost resistance (NHR) responses of legume species against rusts, we characterized the reaction of the model legume Medicago truncatula to one appropriate (Uromyces striatus) and two inappropriate (U. viciae-fabae and U. lupinicolus) rusts. We found that similar pre and post-haustorial mechanisms of resistance appear to be operative in M. truncatula against appropriate and inappropriate rust fungus. The appropriate U. striatus germinated better on M. truncatula accessions then the inappropriate U. viciae-fabae and U. lupinicolus, but once germinated, germ tubes of the three rusts had a similar level of success in finding stomata and forming an appressoria over a stoma. However, responses to different inappropriate rust species also showed some specificity, suggesting a combination of non-specific and specific responses underlying this legume NHR to rust fungi. Further genetic and expression analysis studies will contribute to the development of the necessary molecular tools to use the present information on host and NHR mechanisms to breed for broad-spectrum resistance to rust in legume species. PMID:25426128

  8. Signatures of the Galactic bar on stellar kinematics unveiled by APOGEE

    Science.gov (United States)

    Palicio, Pedro A.; Martinez-Valpuesta, Inma; Prieto, Carlos Allende; Vecchia, Claudio Dalla; Zamora, Olga; Zasowski, Gail; Fernandez-Trincado, J. G.; Masters, Karen L.; García-Hernández, D. A.; Roman-Lopes, Alexandre

    2018-05-01

    Bars are common galactic structures in the local universe that play an important role in the secular evolution of galaxies, including the Milky Way. In particular, the velocity distribution of individual stars in our galaxy is useful to shed light on stellar dynamics, and provides information complementary to that inferred from the integrated light of external galaxies. However, since a wide variety of models reproduce the distribution of velocity and the velocity dispersion observed in the Milky Way, we look for signatures of the bar on higher-order moments of the line-of-sight velocity (V_los) distribution. We make use of two different numerical simulations -one that has developed a bar and one that remains nearly axisymmetric- to compare them with observations in the latest APOGEE data release (SDSS DR14). This comparison reveals three interesting structures that support the notion that the Milky Way is a barred galaxy. A high skewness region found at positive longitudes constrains the orientation angle of the bar, and is incompatible with the orientation of the bar at ℓ = 0° proposed in previous studies. We also analyse the V_los distributions in three regions, and introduce the Hellinger distance to quantify the differences among them. Our results show a strong non-Gaussian distribution both in the data and in the barred model, confirming the qualitative conclusions drawn from the velocity maps. In contrast to earlier work, we conclude it is possible to infer the presence of the bar from the kurtosis distribution.

  9. IRAS 16547–4247: A NEW CANDIDATE OF A PROTOCLUSTER UNVEILED WITH ALMA

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Aya E. [College of Science, Ibaraki University, 2-1-1 Bunkyo, Mito 310-8512 (Japan); Saigo, Kazuya; Chibueze, James O.; Sanhueza, Patricio [National Astronomical Observatory of Japan 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Takakuwa, Shigehisa [Academia Sinica Institute of Astronomy and Astrophysics, PO Box 23-141, Taipei 10617, Taiwan (China); Garay, Guido, E-mail: ahiguchi@mx.ibaraki.ac.jp [Departamento de Astronomía, Universidad de Chile, Camino El Observatorio 1515, Las Condes, Santiago (Chile)

    2015-01-10

    We present the results of continuum and {sup 12}CO(3-2) and CH{sub 3}OH(7-6) line observations of IRAS 16547–4247 made with the Atacama Large Millimeter/submillimeter Array (ALMA) at an angular resolution of ∼0.''5. The {sup 12}CO(3-2) emission shows two high-velocity outflows whose driving sources are located within the dust continuum peak. The alignment of these outflows does not coincide with that of the wide-angle, large-scale, bipolar outflow detected with the Atacama Pathfinder Experiment in previous studies. The CH{sub 3}OH(7-6) line emission traces an hourglass structure associated with the cavity walls created by the outflow lobes. Taking into account our results together with the position of the H{sub 2}O and class I CH{sub 3}OH maser clusters, we discuss two possible scenarios that can explain the hourglass structure observed in IRAS 16547–4247: (1) precession of a biconical jet, (2) multiple, or at least two, driving sources powering intersecting outflows. Combining the available evidence, namely, the presence of two cross-aligned bipolar outflows and two different H{sub 2}O maser groups, we suggest that IRAS 16547–4247 represents an early formation phase of a protocluster.

  10. C14-Crash. The C14-method and dendrochronology, unveiling the illusion. 2. rev. ed.

    International Nuclear Information System (INIS)

    Bloess, C.; Niemitz, H.U.

    2000-01-01

    In this second edition of the book, which was published almost three years after the first edition, the authors reiterate and substantiate their doubts as to the basic theories underlying the radiocarbon dating method and the applicability of dendrochronology. (orig/CB) [de

  11. Unveiling the importance of being a preferred customer in order to develop innovations with suppliers

    NARCIS (Netherlands)

    Schiele, Holger

    2010-01-01

    Purpose of the paper and literature addressed: The purpose of this research is to understand why early supplier integration in new product development repeatedly fails and how to select the right suppliers to avoid supplier obstructionism. We review the literature on early supplier integration.

  12. Unveiling and Characterizing Early Bilateral Interactions between Biofilm and the Mouse Innate Immune System

    Directory of Open Access Journals (Sweden)

    Christiane Forestier

    2017-11-01

    Full Text Available A very substantial progress has been made in our understanding of infectious diseases caused by invasive bacteria. Under their planktonic forms, bacteria transiently reside in the otherwise sterile mammal body tissues, as the physiological inflammation insures both their clearance and repair of any tissue damage. Yet, the bacteria prone to experience planktonic to biofilm developmental transition still need to be studied. Of note, sessile bacteria not only persist but also concur preventing the effectors and regulators of the physiological inflammation to operate. Thus, it is urgent to design biologically sound experimental approaches aimed to extract, at the earliest stage, immune signatures of mono-bacteria planktonic to biofilm developmental transition in vivo and ex vivo. Indeed, the transition is often the first event to which succeeds the “chronicization” process whereby classical bacteria-targeting therapies are no more efficacious. An in vivo model of micro-injection of Staphylococcus aureus planktonic or biofilm cells in the ear pinna dermis of laboratory transgenic mice with fluorescent immune cells is proposed. It allows visualizing, in real time, the range of the early interactions between the S. aureus and myeloid cell subsets- the resident macrophages and dendritic cells, the recruited neutrophil granulocytes/polymorphonuclear neutrophils, monocytes otherwise known to differentiate as macrophages or dendritic cells. One main objective is to extract contrasting immune signatures of the modulation of the physiological inflammation with respect to the two bacterial lifestyles.

  13. Novel Fluorescent Microemulsion: Probing Properties, Investigating Mechanism, and Unveiling Potential Application.

    Science.gov (United States)

    Hou, Mengna; Dang, Leping; Liu, Tiankuo; Guo, Yun; Wang, Zhanzhong

    2017-08-09

    Nanoscale microemulsions have been utilized as delivery carriers for nutraceuticals and active biological drugs. Herein, we designed and synthesized a novel oil in water (O/W) fluorescent microemulsion based on isoamyl acetate, polyoxyethylene castor oil EL (CrEL), and water. The microemulsion emitted bright blue fluorescence, thus exhibiting its potential for active drug detection with label-free strategy. The microemulsion exhibited excitation-dependent emission and distinct red shift with longer excitation wavelengths. Lifetime and quantum yield of fluorescent microemulsion were 2.831 ns and 5.0%, respectively. An excellent fluorescent stability of the microemulsion was confirmed by altering pH, ionic strength, temperature, and time. Moreover, we proposed a probable mechanism of fluorochromic phenomenon, in connection with the aromatic ring structure of polyoxyethylene ether substituent in CrEL. Based on our findings, we concluded that this new fluorescent microemulsion is a promising drug carrier that can facilitate active drug detection with a label-free strategy. Although further research is required to understand the exact mechanism behind its fluorescence property, this work provided valuable guidance to develop new biosensors based on fluorescent microemulsion.

  14. Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS

    OpenAIRE

    Panda, Pritam Kumar; Rane, Riya; Ravichandran, Rahul; Singh, Shrinkhla; Panchal, Hetalkumar

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a hormonal imbalance in women, which causes problems during menstrual cycle and in pregnancy that sometimes results in fatality. Though the genetics of PCOS is not fully understood, early diagnosis and treatment can prevent long-term effects. In this study, we have studied the proteins involved in PCOS and the structural aspects of the proteins that are taken into consideration using computational tools. The proteins involved are modeled using Modeller 9v14...

  15. A mass-spring model unveils the morphogenesis of phototrophic Diatoma biofilms

    NARCIS (Netherlands)

    Celler, K.; Hödl, I.; Simone, A.; Battin, T.J.; Picioreanu, C.

    2014-01-01

    Diatoms often dominate planktonic communities in the ocean and phototrophic biofilms in streams and rivers, greatly contributing to global biogeochemical fluxes. In pelagic ecosystems, these microscopic algae can form chain-like microcolonies, which seem advantageous for nutrient uptake and protect

  16. Different Evolutionary History for Basque Diaspora Populations in USA and Argentina Unveiled by Mitochondrial DNA Analysis.

    Science.gov (United States)

    Baeta, Miriam; Núñez, Carolina; Cardoso, Sergio; Palencia-Madrid, Leire; Piñeiro-Hermida, Sergio; Arriba-Barredo, Miren; Villanueva-Millán, María Jesús; M de Pancorbo, Marian

    2015-01-01

    The Basque Diaspora in Western USA and Argentina represents two populations which have maintained strong Basque cultural and social roots in a completely different geographic context. Hence, they provide an exceptional opportunity to study the maternal genetic legacy from the ancestral Basque population and assess the degree of genetic introgression from the host populations in two of the largest Basque communities outside the Basque Country. For this purpose, we analyzed the complete mitochondrial DNA control region of Basque descendants living in Western USA (n = 175) and in Argentina (n = 194). The Diaspora populations studied here displayed a genetic diversity in their European maternal input which was similar to that of the Basque source populations, indicating that not important founder effects would have occurred. Actually, the genetic legacy of the Basque population still prevailed in their present-day maternal pools, by means of a haplogroup distribution similar to the source population characterized by the presence of autochthonous Basque lineages, such as U5b1f1a and J1c5c1. However, introgression of non-Basque lineages, mostly Native American, has been observed in the Diaspora populations, particularly in Argentina, where the quick assimilation of the newcomers would have favored a wider admixture with host populations. In contrast, a longer isolation of the Diaspora groups in USA, because of language and cultural differences, would have limited the introgression of local lineages. This study reveals important differences in the maternal evolutionary histories of these Basque Diaspora populations, which have to be taken into consideration in forensic and medical genetic studies.

  17. Unveiling the First Black Holes With JWST:Multi-wavelength Spectral Predictions

    Science.gov (United States)

    Natarajan, Priyamvada; Pacucci, Fabio; Ferrara, Andrea; Agarwal, Bhaskar; Ricarte, Angelo; Zackrisson, Erik; Cappelluti, Nico

    2017-04-01

    Growing supermassive black holes (˜ {10}9 {M}⊙ ) that power luminous z> 6 quasars from light seeds—the remnants of the first stars—within a Gyr of the Big Bang poses a timing challenge. The formation of massive black hole seeds via direct collapse with initial masses ˜ {10}4{--}{10}5 {M}⊙ alleviates this problem. Viable direct-collapse black hole formation sites, the satellite halos of star-forming galaxies, merge and acquire stars to produce a new, transient class of high-redshift objects, obese black hole galaxies (OBGs). The accretion luminosity outshines that of the stars in OBGs. We predict the multi-wavelength energy output of OBGs and growing Pop III remnants at z = 9 for standard and slim disk accretion, as well as high and low metallicities of the associated stellar population. We derive robust selection criteria for OBGs—a pre-selection to eliminate blue sources, followed by color-color cuts ([{F}090W-{F}220W]> 0;-0.3sift out OBGs from other bright, high- and low-redshift contaminants in the infrared. OBGs with predicted {M}{AB}< 25 are unambiguously detectable by the Mid-Infrared Instrument (MIRI), on the upcoming James Webb Space Telescope (JWST). For parameters explored here, growing Pop III remnants with predicted {M}{AB}< 30 will likely be undetectable by JWST. We demonstrate that JWST has the power to discriminate between initial seeding mechanisms.

  18. Novel epigenetic changes unveiled by monozygotic twins discordant for smoking habits.

    Science.gov (United States)

    Allione, Alessandra; Marcon, Francesca; Fiorito, Giovanni; Guarrera, Simonetta; Siniscalchi, Ester; Zijno, Andrea; Crebelli, Riccardo; Matullo, Giuseppe

    2015-01-01

    Exposure to cigarette smoking affects the epigenome and could increase the risk of developing diseases such as cancer and cardiovascular disorders. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to disease etiology. Previous studies are not completely concordant in the identification of differentially methylated regions in the DNA of smokers. We performed an epigenome-wide DNA methylation study in a group of monozygotic (MZ) twins discordant for smoking habits to determine the effect of smoking on DNA methylation. As MZ twins are considered genetically identical, this model allowed us to identify smoking-related DNA methylation changes independent from genetic components. We investigated the whole blood genome-wide DNA methylation profiles in 20 MZ twin pairs discordant for smoking habits by using the Illumina HumanMethylation450 BeadChip. We identified 22 CpG sites that were differentially methylated between smoker and non-smoker MZ twins by intra-pair analysis. We confirmed eight loci already described by other groups, located in AHRR, F2RL3, MYOG1 genes, at 2q37.1 and 6p21.33 regions, and also identified several new loci. Moreover, pathway analysis showed an enrichment of genes involved in GTPase regulatory activity. Our study confirmed the evidence of smoking-related DNA methylation changes, emphasizing that well-designed MZ twin models can aid the discovery of novel DNA methylation signals, even in a limited sample population.

  19. Unveiling the Secrets of Metallicity and Massive Star Formation Using DLAs Along Gamma-Ray Bursts

    Science.gov (United States)

    Cucchiara, A.; Fumagalli, M.; Rafelski, M.; Kocevski, D.; Prochaska, J. X.; Cooke, R. J.; Becker, G. D.

    2015-01-01

    We present the largest, publicly available, sample of Damped Lyman-alpha systems (DLAs) along Swift discovered Gamma-ray Bursts (GRB) line of sights in order to investigate the environmental properties of long GRB hosts in the z = 1.8 - 6 redshift range. Compared with the most recent quasar DLAs sample (QSO-DLA), our analysis shows that GRB-DLAs probe a more metal enriched environment at z approximately greater than 3, up to [X/H] approximately -0.5. In the z = 2 - 3 redshift range, despite the large number of lower limits, there are hints that the two populations may be more similar (only at 90% significance level) than at higher redshifts. Also, at high-z, the GRB-DLA average metallicity seems to decline at a shallower rate than the QSO-DLAs: GRB-DLA hosts may be polluted with metals at least as far as approximately 2 kpc from the GRB explosion site, probably due to previous star-formation episodes and/or supernovae explosions. This shallow metallicity trend, extended now up to z approximately 5, confirms previous results that GRB hosts are star-forming and have, on average, higher metallicity than the general QSO-DLA population. Finally, our host metallicity measurements are broadly consistent with the predictions derived from the hypothesis of two channels of GRB progenitors, one of which is mildly affected by a metallicity bias, although more data are needed to constrain the models at z approximately greater than 4.

  20. Environmental Chemical Assessment in Clinical Practice: Unveiling the Elephant in the Room

    Directory of Open Access Journals (Sweden)

    Nicole Bijlsma

    2016-02-01

    Full Text Available A growing body of evidence suggests chemicals present in air, water, soil, food, building materials and household products are toxicants that contribute to the many chronic diseases typically seen in routine medical practice. Yet, despite calls from numerous organisations to provide clinicians with more training and awareness in environmental health, there are multiple barriers to the clinical assessment of toxic environmental exposures. Recent developments in the fields of systems biology, innovative breakthroughs in biomedical research encompassing the “-omics” fields, and advances in mobile sensing, peer-to-peer networks and big data, provide tools that future clinicians can use to assess environmental chemical exposures in their patients. There is also a need for concerted action at all levels, including actions by individual patients, clinicians, medical educators, regulators, government and non-government organisations, corporations and the wider civil society, to understand the “exposome” and minimise the extent of toxic exposures on current and future generations. Clinical environmental chemical risk assessment may provide a bridge between multiple disciplines that uses new technologies to herald in a new era in personalised medicine that unites clinicians, patients and civil society in the quest to understand and master the links between the environment and human health.

  1. Wheat syntenome unveils new evidences of contrasted evolutionary plasticity between paleo- and neoduplicated subgenomes

    Czech Academy of Sciences Publication Activity Database

    Pont, C.; Murat, F.; Bidet, Y.; Doležel, Jaroslav; Fahima, T.; Budak, H.; Feuillet, C.; Salse, J.

    2013-01-01

    Roč. 76, č. 6 (2013), s. 1030-1044 ISSN 0960-7412 Institutional research plan: CEZ:AV0Z50380511 Keywords : paleogenomics * dominance * partitioning Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.815, year: 2013

  2. Reptile Toll-like receptor 5 unveils adaptive evolution of bacterial flagellin recognition

    NARCIS (Netherlands)

    Voogdt, Carlos G.P.; Bouwman, Lieneke I.; Kik, Marja J.L.; Wagenaar, Jaap A.; Putten, Van Jos P.M.

    2016-01-01

    Toll-like receptors (TLR) are ancient innate immune receptors crucial for immune homeostasis and protection against infection. TLRs are present in mammals, birds, amphibians and fish but have not been functionally characterized in reptiles despite the central position of this animal class in

  3. Reptile Toll-like receptor 5 unveils adaptive evolution of bacterial flagellin recognition

    NARCIS (Netherlands)

    Voogdt, Carlos G P|info:eu-repo/dai/nl/413535169; Bouwman, Lieneke I|info:eu-repo/dai/nl/341590797; Kik, Marja J L|info:eu-repo/dai/nl/080432565; Wagenaar, Jaap A|info:eu-repo/dai/nl/126613354; van Putten, Jos P M|info:eu-repo/dai/nl/069916527

    2016-01-01

    Toll-like receptors (TLR) are ancient innate immune receptors crucial for immune homeostasis and protection against infection. TLRs are present in mammals, birds, amphibians and fish but have not been functionally characterized in reptiles despite the central position of this animal class in

  4. Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal.

    Science.gov (United States)

    Baranska, Anna; Shawket, Alaa; Jouve, Mabel; Baratin, Myriam; Malosse, Camille; Voluzan, Odessa; Vu Manh, Thien-Phong; Fiore, Frédéric; Bajénoff, Marc; Benaroch, Philippe; Dalod, Marc; Malissen, Marie; Henri, Sandrine; Malissen, Bernard

    2018-04-02

    Here we describe a new mouse model that exploits the pattern of expression of the high-affinity IgG receptor (CD64) and allows diphtheria toxin (DT)-mediated ablation of tissue-resident macrophages and monocyte-derived cells. We found that the myeloid cells of the ear skin dermis are dominated by DT-sensitive, melanin-laden cells that have been missed in previous studies and correspond to macrophages that have ingested melanosomes from neighboring melanocytes. Those cells have been referred to as melanophages in humans. We also identified melanophages in melanocytic melanoma. Benefiting of our knowledge on melanophage dynamics, we determined the identity, origin, and dynamics of the skin myeloid cells that capture and retain tattoo pigment particles. We showed that they are exclusively made of dermal macrophages. Using the possibility to delete them, we further demonstrated that tattoo pigment particles can undergo successive cycles of capture-release-recapture without any tattoo vanishing. Therefore, congruent with dermal macrophage dynamics, long-term tattoo persistence likely relies on macrophage renewal rather than on macrophage longevity. © 2018 Baranska et al.

  5. Unveiling the climate memory of an Arctic polythermal glacier: a combined radar and thermomechanical modeling approach

    Science.gov (United States)

    Delcourt, C.; Van Liefferinge, B.; Pattyn, F.; Nolan, M.

    2011-12-01

    Based on borehole temperature measurements and radio-echo sounding surveys on McCall Glacier, Alaska (USA) we were able to identify and map the Cold Transition Surface (CTS) marking the limit between cold and warm ice of a polythermal glacier. In the accumulation area, the ice column is observed to be warm throughout, while in the ablation area, the amount of cold ice at the top of the ice column increases downstream, hence lowering the CTS. High englacial temperatures in the accumulation are explained by the latent heat release due to percolating meltwater and precipitation, hence warming the ice column. With increasing atmospheric temperatures and increasing ablation rates, reduction of the perennial snowpack results in surface runoff and ice cooling. Using a transient thermomechanically-coupled higher-order glacier model, the timing of the cooling was determined from which past equilibrium-line altitudes (ELA) were constructed, which are in accord with ELAs measured since the 1950s (IGY). The paper therefore shows that (i) mapping of the CTS allows reconstructing the recent climate history of polythermal glaciers, and (ii) with a warming climate, McCall Glacier tends to cool down in a counterintuitive way.

  6. Unveiling Undercover Cropland Inside Forests Using Landscape Variables: A Supplement to Remote Sensing Image Classification.

    Science.gov (United States)

    Ayanu, Yohannes; Conrad, Christopher; Jentsch, Anke; Koellner, Thomas

    2015-01-01

    The worldwide demand for food has been increasing due to the rapidly growing global population, and agricultural lands have increased in extent to produce more food crops. The pattern of cropland varies among different regions depending on the traditional knowledge of farmers and availability of uncultivated land. Satellite images can be used to map cropland in open areas but have limitations for detecting undergrowth inside forests. Classification results are often biased and need to be supplemented with field observations. Undercover cropland inside forests in the Bale Mountains of Ethiopia was assessed using field observed percentage cover of land use/land cover classes, and topographic and location parameters. The most influential factors were identified using Boosted Regression Trees and used to map undercover cropland area. Elevation, slope, easterly aspect, distance to settlements, and distance to national park were found to be the most influential factors determining undercover cropland area. When there is very high demand for growing food crops, constrained under restricted rights for clearing forest, cultivation could take place within forests as an undercover. Further research on the impact of undercover cropland on ecosystem services and challenges in sustainable management is thus essential.

  7. Multi-source self-calibration: Unveiling the microJy population of compact radio sources

    NARCIS (Netherlands)

    Radcliffe, J. F.; Garrett, M. A.; Beswick, R. J.; Muxlow, T. W. B.; Barthel, P. D.; Deller, A. T.; Middelberg, E.

    2016-01-01

    Context. Very long baseline interferometry (VLBI) data are extremely sensitive to the phase stability of the VLBI array. This is especially important when we reach μJy rms sensitivities. Calibration using standard phase-referencing techniques is often used to improve the phase stability of VLBI

  8. The Run-up to Volcanic Eruption Unveiled by Forensic Petrology and Geophysical Observations

    Science.gov (United States)

    Rasmussen, D. J.; Plank, T. A.; Roman, D. C.

    2017-12-01

    Volcanoes often warn of impending eruptions. However, one of the greatest challenges in volcano research is translating precursory geophysical signals into physical magmatic processes. Petrology offers powerful tools to study eruption run-up that benefit from direct response to magmatic forcings. Developing these tools, and tying them to geophysical observations, will help us identify eruption triggers (e.g., magmatic recharge, gas build-up, tectonic events) and understand the significance of monitored signals of unrest. We present an overview of petrologic tools used for studying eruption run-up, highlighting results from our study of the 1999 eruption of Shishaldin volcano. Olivine crystals contain chemical gradients, the consequence of diffusion following magma mixing events, which is modeled to determine mixing timescales. Modeled timescales provide strong evidence for at least three mixing events, which were triggered by magmatic recharge. Petrologic barometers indicate these events occurred at very shallow depths (within the volcanic edifice). The first mixing event occurred nine months before eruption, which was signaled by a swarm of deep-long period earthquake. Minor recharge events followed over two months, which are indicated by a second deep-long period earthquake swarm and a change in the local stress orientation measured by shear-wave splitting. Following these events, the system was relatively quiet until a large mixing event occurred 45 days prior to eruption, which was heralded by a large earthquake (M5.2). Following this event, geophysical signals of unrest intensified and became continuous. The final mixing event, beginning roughly a week before eruption, represents the final perturbation to the system before eruption. Our findings point to a relatively long run-up, which was subtle at first and intensified several weeks before eruption. This study highlights the strong link between geophysical signals of volcanic unrest and magmatic events, and helps open the door for the application of forensic petrology to unmonitored eruptions.

  9. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

    Science.gov (United States)

    Santiago, Jose A; Potashkin, Judith A

    2013-01-01

    Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that increased expression of APP in blood may modulate the neurodegenerative phenotype in type 2 diabetes patients.

  10. Unveiling the truth: warnings reduce the repetition-based truth effect.

    Science.gov (United States)

    Nadarevic, Lena; Aßfalg, André

    2017-07-01

    Typically, people are more likely to consider a previously seen or heard statement as true compared to a novel statement. This repetition-based "truth effect" is thought to rely on fluency-truth attributions as the underlying cognitive mechanism. In two experiments, we tested the nature of the fluency-attribution mechanism by means of warning instructions, which informed participants about the truth effect and asked them to prevent it. In Experiment 1, we instructed warned participants to consider whether a statement had already been presented in the experiment to avoid the truth effect. However, warnings did not significantly reduce the truth effect. In Experiment 2, we introduced control questions and reminders to ensure that participants understood the warning instruction. This time, warning reduced, but did not eliminate the truth effect. Assuming that the truth effect relies on fluency-truth attributions, this finding suggests that warned participants could control their attributions but did not disregard fluency altogether when making truth judgments. Further, we found no evidence that participants overdiscount the influence of fluency on their truth judgments.

  11. Unveiling the Role of the Magnetic Field at the Smallest Scales of Star Formation

    Energy Technology Data Exchange (ETDEWEB)

    Hull, Charles L. H.; Mocz, Philip; Burkhart, Blakesley; Goodman, Alyssa A.; Hernquist, Lars [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Girart, Josep M. [Institut de Ciències de l’Espai (CSIC-IEEC), Campus UAB, Carrer de Can Magrans S/N, E-08193 Cerdanyola del Vallès, Catalonia (Spain); Cortés, Paulo C. [National Radio Astronomy Observatory, Charlottesville, VA 22903 (United States); Springel, Volker [Heidelberger Institut für Theoretische Studien, Schloss-Wolfsbrunnenweg 35, D-69118 Heidelberg (Germany); Li, Zhi-Yun [Department of Astronomy, University of Virginia, Charlottesville, VA 22903 (United States); Lai, Shih-Ping, E-mail: chat.hull@cfa.harvard.edu [Institute of Astronomy and Department of Physics, National Tsing Hua University, 101 Section 2 Kuang Fu Road, 30013 Hsinchu, Taiwan (China)

    2017-06-20

    We report Atacama Large Millimeter/submillimeter Array (ALMA) observations of polarized dust emission from the protostellar source Ser-emb 8 at a linear resolution of 140 au. Assuming models of dust-grain alignment hold, the observed polarization pattern gives a projected view of the magnetic field structure in this source. Contrary to expectations based on models of strongly magnetized star formation, the magnetic field in Ser-emb 8 does not exhibit an hourglass morphology. Combining the new ALMA data with previous observational studies, we can connect magnetic field structure from protostellar core (∼80,000 au) to disk (∼100 au) scales. We compare our observations with four magnetohydrodynamic gravo-turbulence simulations made with the AREPO code that have initial conditions ranging from super-Alfvénic (weakly magnetized) to sub-Alfvénic (strongly magnetized). These simulations achieve the spatial dynamic range necessary to resolve the collapse of protostars from the parsec scale of star-forming clouds down to the ∼100 au scale probed by ALMA. Only in the very strongly magnetized simulation do we see both the preservation of the field direction from cloud to disk scales and an hourglass-shaped field at <1000 au scales. We conduct an analysis of the relative orientation of the magnetic field and the density structure in both the Ser-emb 8 ALMA observations and the synthetic observations of the four AREPO simulations. We conclude that the Ser-emb 8 data are most similar to the weakly magnetized simulations, which exhibit random alignment, in contrast to the strongly magnetized simulation, where the magnetic field plays a role in shaping the density structure in the source. In the weak-field case, it is turbulence—not the magnetic field—that shapes the material that forms the protostar, highlighting the dominant role that turbulence can play across many orders of magnitude in spatial scale.

  12. Solution of Heliospheric Propagation: Unveiling the Local Interstellar Spectra of Cosmic-ray Species

    Energy Technology Data Exchange (ETDEWEB)

    Boschini, M. J.; Torre, S. Della; Gervasi, M.; Grandi, D.; Vacca, G. La; Pensotti, S.; Rancoita, P. G.; Rozza, D.; Tacconi, M. [INFN, Milano-Bicocca, Milano (Italy); Jóhannesson, G. [Science Institute, University of Iceland, Dunhaga 3, IS-107 Reykjavik (Iceland); Kachelriess, M. [Institutt for fysikk, NTNU, NO-7491 Trondheim (Norway); Masi, N.; Quadrani, L. [INFN, Bologna (Italy); Moskalenko, I. V.; Orlando, E.; Porter, T. A. [Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305 (United States); Ostapchenko, S. S. [Frankfurt Institute of Advanced Studies, Frankfurt (Germany)

    2017-05-10

    Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with the data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range.

  13. USING MAGNETIC MOMENTS TO UNVEIL THE NUCLEAR STRUCTURE OF LOW-SPIN NUCLEAR STATES

    Directory of Open Access Journals (Sweden)

    Diego A. Torres

    2011-07-01

    Full Text Available The experimental study of magnetic moments for nuclear states near the ground state, I ≤ 2, provides a powerful tool to test nuclear structure models. Traditionally, the use of Coulomb excitation reactions has been used to study low spin states, mostly I = 2. The use of alternative reaction channels, such as α transfer, for the production of radioactive species that, otherwise, will be only produced in future radioactive beam facilities has proved to be an alternative to measure not only excited states with I > 2, but to populate and study long-live radioactive nuclei. This contribution will present the experimental tools and challenges for the use of the transient field technique for the measurement of g factors in nuclear states with I ≤ 2, using Coulomb excitation and α-transfer reactions. Recent examples of experimental results near the N = 50 shell closure, and the experimental challenges for future implementations with radioactive beams, will be discussed.

  14. Massive gene losses in Asian cultivated rice unveiled by comparative genome analysis

    Directory of Open Access Journals (Sweden)

    Itoh Takeshi

    2010-02-01

    Full Text Available Abstract Background Rice is one of the most important food crops in the world. With increasing world demand for food crops, there is an urgent need to develop new cultivars that have enhanced performance with regard to yield, disease resistance, and so on. Wild rice is expected to provide useful genetic resources that could improve the present cultivated species. However, the quantity and quality of these unexplored resources remain unclear. Recent accumulation of the genomic information of both cultivated and wild rice species allows for their comparison at the molecular level. Here, we compared the genome sequence of Oryza sativa ssp. japonica with sets of bacterial artificial chromosome end sequences (BESs from two wild rice species, O. rufipogon and O. nivara, and an African rice species, O. glaberrima. Results We found that about four to five percent of the BESs of the two wild rice species and about seven percent of the African rice could not be mapped to the japonica genome, suggesting that a substantial number of genes have been lost in the japonica rice lineage; however, their close relatives still possess their counterpart genes. We estimated that during evolution, O. sativa has lost at least one thousand genes that are still preserved in the genomes of the other species. In addition, our BLASTX searches against the non-redundant protein sequence database showed that disease resistance-related proteins were significantly overrepresented in the close relative-specific genomic portions. In total, 235 unmapped BESs of the three relatives matched 83 non-redundant proteins that contained a disease resistance protein domain, most of which corresponded to an NBS-LRR domain. Conclusion We found that the O. sativa lineage appears to have recently experienced massive gene losses following divergence from its wild ancestor. Our results imply that the domestication process accelerated large-scale genomic deletions in the lineage of Asian cultivated rice and that the close relatives of cultivated rice have the potential to restore the lost traits.

  15. Observational Study Unveils the Extensive Presence of Hazardous Elements in Beached Plastics from Lake Geneva

    Directory of Open Access Journals (Sweden)

    Montserrat Filella

    2018-02-01

    Full Text Available Over 3,000 samples of plastic litter have been retrieved from 12 pebble beaches around the shores of Lake Geneva. The plastic stock consisted of identifiable objects of various size and color, including bottles, bottle tops, cotton buds, pens, toys, and straws, an heterogeneous assortment of fragments whose origin was either discernible or unknown, and pieces or blocks of expanded polymer (polystyrene or polyurethane foam. Analysis of 670 samples by portable x-ray fluorescence (XRF spectrometry revealed high concentrations of hazardous elements or compounds among many plastics. These included Cd, Hg, and Pb (with maximum concentrations of 6,760, 810, and 23,500 ppm, respectively as stabilizers in PVC-based materials and/or brightly-colored sulfide or chromate pigments in primary and secondary plastics, and Br (with a maximum concentration of 27,400 ppm as a proxy for brominated flame retardants (BFRs in both plastics and foams. The abundance of hazardous elements in beached plastics that have been restricted or banned reflect the age and residence time of the plastic stock in the lake, coupled with a relatively high length of shoreline to surface area of the system. The migratability of hazardous elements from the polymeric matrix is likely to determine their environmental impacts and is recommended as a future area of research.

  16. Non-invasive Prenatal Testing and the Unveiling of an Impaired Translation Process.

    Science.gov (United States)

    Murdoch, Blake; Ravitsky, Vardit; Ogbogu, Ubaka; Ali-Khan, Sarah; Bertier, Gabrielle; Birko, Stanislav; Bubela, Tania; De Beer, Jeremy; Dupras, Charles; Ellis, Meika; Granados Moreno, Palmira; Joly, Yann; Kamenova, Kalina; Master, Zubin; Marcon, Alessandro; Paulden, Mike; Rousseau, François; Caulfield, Timothy

    2017-01-01

    Non-invasive prenatal testing (NIPT) is an exciting technology with the potential to provide a variety of clinical benefits, including a reduction in miscarriages, via a decline in invasive testing. However, there is also concern that the economic and near-future clinical benefits of NIPT have been overstated and the potential limitations and harms underplayed. NIPT, therefore, presents an opportunity to explore the ways in which a range of social pressures and policies can influence the translation, implementation, and use of a health care innovation. NIPT is often framed as a potential first tier screen that should be offered to all pregnant women, despite concerns over cost-effectiveness. Multiple forces have contributed to a problematic translational environment in Canada, creating pressure towards first tier implementation. Governments have contributed to commercialization pressure by framing the publicly funded research sector as a potential engine of economic growth. Members of industry have an incentive to frame clinical value as beneficial to the broadest possible cohort in order to maximize market size. Many studies of NIPT were directly funded and performed by private industry in laboratories lacking strong independent oversight. Physicians' fear of potential liability for failing to recommend NIPT may further drive widespread uptake. Broad social endorsement, when combined with these translation pressures, could result in the "routinization" of NIPT, thereby adversely affecting women's reproductive autonomy. Policymakers should demand robust independent evidence of clinical and public health utility relevant to their respective jurisdictions before making decisions regarding public funding for NIPT. Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

  17. Unveiling the secrets of geology, from the Earth to your daily life

    Science.gov (United States)

    Delfini, Claudia

    2015-04-01

    How should we share geological information? How can we start involving the public at large in topics that apparently are so far away from them? What kind of information would be interesting to disseminate to attract the attention of the people? "Geology at the table - cooking without borders" and "Minerals in your life", edited by EuroGeoSurveys, the Geological Surveys of Europe, are two publications that have showed how it is possible to reach thousands of people around Europe only following a few simple rules. A good scientific communicator must first understand its audience, their knowledge and beliefs, in order to adopt an attractive approach to their communication strategy. A good communicator has to adopt a simplified blend of the crucial information without depleting the content of the main message. One must avoid the danger of losing the audience's interest by keeping with simple language and information that is easy to understand and accessible to all. When it comes to the field of geology, communication efforts would ideally engage the audience and develop their interest, showing how their daily life is linked and conditioned to the geological phenomena. "Geology at the table - cooking without borders" and "Minerals in your life" are two examples of how geology, a topic unknown to many people, is part of our life. Leafing through the pages of these books it is possible to understand how important geology is for the existence of our society and its crucial role in the complex world we live in. In "Geology at the table - cooking without borders" twenty-eight European Geological Surveys have shown how their own national dishes contain references to our past, to the present, and to the future, which can easily be analysed and explained through geology. This cookbook offers a little taste of geology through wonderful recipes from all around Europe. While "Minerals in your life" is an educational book that combines a hilarious comic strip storyline with an extensive description of minerals, along with stunning images. The book explains that most, if not all objects around us, contain crucial minerals. Through one adventurous day of the cartoon protagonist, Norman, it is possible find out the minerals used in very common objects of our everyday life, from paper to shampoo, or from a bike to a television. Fifty-one top expert geologists contributed to describe the fascinating qualities of each mineral, for a total of thirty minerals. Whatever curiosities you may have about minerals, "Minerals in your life" satisfies them with an approach that it is as scientifically precise as entertaining. In following these basic principles geologists will be able to effectively communicate to the entire world that geology is a science that will contribute to the building of a better world of tomorrow.

  18. Unveiling the Role of CNTs on the Phase Formation of 1D Ferroelectrics

    KAUST Repository

    Mahajan, Amit; Reaney, I. M.; Da Costa, Pedro M. F. J.; Kingon, Angus I.; Kó nya, Zoltá n; Kukovecz, Akos; Vilarinho, P. M.

    2015-01-01

    nature of MWCNT/PZT synthesised at 500 ºC for 1 h was proved. Although further work is required to prove the concept of 3D capacitor arrays, our result suggests that it is feasible to utilise MWCNTs as templates/electrodes for the formation of 1D PZT nano

  19. Unveiling the Structural Origin of the High Carrier Mobility of a Molecular Monolayer on Boron Nitride

    OpenAIRE

    Xu, Rui; He, Daowei; Zhang, Yuhan; Wu, Bing; Liu, Fengyuan; Meng, Lan; Liu, Jun-Fang; Wu, Qisheng; Shi, Yi; Wang, Jinlan; Nie, Jia-Cai; Wang, Xinran; He, Lin

    2014-01-01

    Very recently, it was demonstrated that the carrier mobility of a molecular monolayer dioctylbenzothienobenzothiophene (C8-BTBT) on boron nitride can reach 10 cm2/Vs, the highest among the previously reported monolayer molecular field-effect transistors. Here we show that the high-quality single crystal of the C8-BTBT monolayer may be the key origin of the record-high carrier mobility. We discover that the C8-BTBT molecules prefer layer-by-layer growth on both hexagonal boron nitride and grap...

  20. Signal Sensing and Transduction by Histidine Kinases as Unveiled through Studies on a Temperature Sensor.

    Science.gov (United States)

    Abriata, Luciano A; Albanesi, Daniela; Dal Peraro, Matteo; de Mendoza, Diego

    2017-06-20

    Histidine kinases (HK) are the sensory proteins of two-component systems, responsible for a large fraction of bacterial responses to stimuli and environmental changes. Prototypical HKs are membrane-bound proteins that phosphorylate cognate response regulator proteins in the cytoplasm upon signal detection in the membrane or periplasm. HKs stand as potential drug targets but also constitute fascinating systems for studying proteins at work, specifically regarding the chemistry and mechanics of signal detection, transduction through the membrane, and regulation of catalytic outputs. In this Account, we focus on Bacillus subtilis DesK, a membrane-bound HK part of a two-component system that maintains appropriate membrane fluidity at low growth temperatures. Unlike most HKs, DesK has no extracytoplasmic signal-sensing domains; instead, sensing is carried out by 10 transmembrane helices (coming from two protomers) arranged in an unknown structure. The fifth transmembrane helix from each protomer connects, without any of the intermediate domains found in other HKs, into the dimerization and histidine phosphotransfer (DHp) domain located in the cytoplasm, which is followed by the ATP-binding domains (ABD). Throughout the years, genetic, biochemical, structural, and computational studies on wild-type, mutant, and truncated versions of DesK allowed us to dissect several aspects of DesK's functioning, pushing forward a more general understanding of its own structure/function relationships as well as those of other HKs. We have shown that the sensing mechanism is rooted in temperature-dependent membrane properties, most likely a combination of thickness, fluidity, and water permeability, and we have proposed possible mechanisms by which DesK senses these properties and transduces the signals. X-ray structures and computational models have revealed structural features of TM and cytoplasmic regions in DesK's kinase- and phosphatase-competent states. Biochemical and genetic experiments and molecular simulations further showed that reversible formation of a two-helix coiled coil in the fifth TM segment and the N-terminus of the cytoplasmic domain is essential for the sensing and signal transduction mechanisms. Together with other structural and functional works, the emerging picture suggests that diverse HKs possess distinct sensing and transduction mechanisms but share as rather general features (i) a symmetric phosphatase state and an asymmetric kinase state and (ii) similar functional outputs on the conserved DHp and ABD domains, achieved through different mechanisms that depend on the nature of the initial signal. We here advance (iii) an important role for TM prolines in transducing the initial signals to the cytoplasmic coiled coils, based on simulations of DesK's TM helices and our previous work on a related HK, PhoQ. Lastly, evidence for DesK, PhoQ, BvgS, and DctB HKs shows that (iv) overall catalytic output is tuned by a delicate balance between hydration potentials, coiled coil stability, and exposure of hydrophobic surface patches at their cytoplasmic coiled coils and at the N-terminal and C-terminal sides of their TM helices. This balance is so delicate that small perturbations, either physiological signals or induced by mutations, lead to large remodeling of the underlying conformational landscape achieving clear-cut changes in catalytic output, mirroring the required response speed of these systems for proper biological function.

  1. UNVEILING THE σ-DISCREPANCY IN INFRARED-LUMINOUS MERGERS. I. DUST AND DYNAMICS

    International Nuclear Information System (INIS)

    Rothberg, Barry; Fischer, Jacqueline

    2010-01-01

    Mergers in the local universe present a unique opportunity for studying the transformations of galaxies in detail. Presented here are recent results, based on multi-wavelength, high-resolution imaging and medium resolution spectroscopy, which demonstrate how star formation and the presence of red supergiants and/or asymptotic giant branch stars have led to a serious underestimation of the dynamical masses of infrared-bright galaxies. The dominance of a nuclear disk of young stars in the near-infrared bands, where dust obscuration does not block their signatures, can severely bias the global properties measured in a galaxy, including mass. This explains why past studies of gas-rich luminous infrared galaxies (LIRGs) and ultraluminous infrared galaxies, which have measured dynamical masses using the 1.62 or 2.29 μm CO band heads, have found that these galaxies are forming m m* ellipticals. Moreover, merger remnants, including LIRGs, are placed on the I-band fundamental plane for the first time and appear to be virtually indistinguishable from elliptical galaxies.

  2. Geophysical survey of two rural sites in Mallorca (Balearic Islands, Spain): Unveiling Roman villae

    Science.gov (United States)

    Mas Florit, Catalina; Cau Ontiveros, Miguel Ángel; Goossens, Lise; Meyer, Cornelius; Sala, Roger; Ortiz, Helena

    2018-03-01

    Two rural sites on the island of Mallorca (Balearic Islands, Spain) have been investigated with geophysical methods. A previous archaeological field survey provided surface ceramics that allowed for a first classification of the sites as possible Roman rural settlements, possibly villae. The objective of the investigation was to work towards the identification of architectural remains to better understand the true nature of the sites. Using the 7-probe fluxgate gradiometer array LEA MAX, magnetic measurements were executed on a large area on each site. GPR measurements were subsequently carried out to examine selected areas of interest in detail by means of the IDS GPR system based on the Fast-Wave module. The investigated areas demonstrated excellent surface conditions with a negligible number of sources of disturbance, permitting a detailed interpretation of the geophysical data. The results helped to reveal the presence of architectural remains beneath the soil at both sites.

  3. Unveiling the Galaxy Population at 1.3 < z < 4: the HUDF05 NICMOS Parallel Fields

    Science.gov (United States)

    Petty, Sara M.; deMello, Duilia F.; Wiklind, Tomy; Gardner, Jonathan P.; Mountain, Matt

    2010-01-01

    Using the Hubble Ultra Deep Field Near Infrared Camera and Multi-Object Spectrometer (HUDF-NICMOS) UDF05 parallel fields, we cross-matched 301 out of 630 galaxies with the ACS filters V606 and z850, NICMOS filters J110 and H160, and Spitzer IRAC filters at 3.6, 4.5, 5.8 , and 8.0 (mu)m. We modeled the spectral energy distributions (SEDs) to estimate: photometric redshifts, dust extinction, stellar mass, bolometric luminosity, starburst age and metallicity. To validate the photometric redshifts, comparisons with 16 spectroscopic redshifts give 75% within Delta or approx. 1.3. Based on the robustness of the photometric redshifts, we analyze a subsample of the 301 galaxies at 1.3 < or = z < or = 2 (35 objects) and 3 < or = z < or = 4 (31 objects) and determine that L(BoI) and the star formation rate increase significantly from z approx. 1.5 to 4. The Balmer decrement is indicative of more evolved galaxies, and at high redshifts, they serve as records of some of the first galaxies. Therefore, the galaxies in this sample are great candidates for future surveys with the James Webb Space Telescope and Atacama Large Millimeter Array.

  4. Unveiling the nature of the γ-ray emitting active galactic nucleus PKS 0521-36

    International Nuclear Information System (INIS)

    D'Ammando, F.; Istituto Nazionale di Astrofisica; Orienti, M.; Tavecchio, F.; Ghisellini, G.

    2015-01-01

    PKS 0521-36 is an active galactic nucleus (AGN) with uncertain classification. Here, we investigate the properties of this source from radio to γ-rays. The broad emission lines in the optical and ultraviolet bands and steep radio spectrum indicate a possible classification as an intermediate object between broad-line radio galaxies (BLRG) and steep spectrum radio quasars (SSRQ). On pc-scales PKS 0521-36 shows a knotty structure similar to misaligned AGN. The core dominance and the γ-ray properties are similar to those estimated for other SSRQ and BLRG detected in γ-rays, suggesting an intermediate viewing angle with respect to the observer. In this context the flaring activity detected from this source by Fermi-Large Area Telescope between 2010 June and 2012 February is very intriguing. We discuss the γ-ray emission of this source in the framework of the structured jet scenario, comparing the spectral energy distribution (SED) of the flaring state in 2010 June with that of a low state. We present three alternative models corresponding to three different choices of the viewing angles θv = 6°, 15°, and 20°. We obtain a good fit for the first two cases, but the SED obtained with θv = 15° if observed at a small angle does not resemble that of a typical blazar since the synchrotron emission should dominate by a large factor (~100) the inverse Compton component. This suggests that a viewing angle between 6° and 15° is preferred, with the rapid variability observed during γ-ray flares favouring a smaller angle. However, we cannot rule out that PKS 0521-36 is the misaligned counterpart of a synchrotron-dominated blazar.

  5. CUVE - Cubesat UV Experiment: Unveil Venus' UV Absorber with Cubesat UV Mapping Spectrometer

    Science.gov (United States)

    Cottini, V.; Aslam, S.; D'Aversa, E.; Glaze, L.; Gorius, N.; Hewagama, T.; Ignatiev, N.; Piccioni, G.

    2017-09-01

    Our Venus mission concept Cubesat UV Experiment (CUVE) is one of ten proposals selected for funding by the NASA PSDS3 Program - Planetary Science Deep Space SmallSat Studies. CUVE concept is to insert a CubeSat spacecraft into a Venusian orbit and perform remote sensing of the UV spectral region using a high spectral resolution point spectrometer to resolve UV molecular bands, observe nightglow, and characterize the unidentified main UV absorber. The UV spectrometer is complemented by an imaging UV camera with multiple bands in the UV absorber main band range for contextual imaging. CUVE Science Objectives are: the nature of the "Unknown" UV-absorber; the abundances and distributions of SO2 and SO at and above Venus's cloud tops and their correlation with the UV absorber; the atmospheric dynamics at the cloud tops, structure of upper clouds and wind measurements from cloud-tracking; the nightglow emissions: NO, CO, O2. This mission will therefore be an excellent platform to study Venus' cloud top atmospheric properties where the UV absorption drives the planet's energy balance. CUVE would complement past, current and future Venus missions with conventional spacecraft, and address critical science questions cost effectively.

  6. Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear.

    Science.gov (United States)

    Lindqvist, Charlotte; Schuster, Stephan C; Sun, Yazhou; Talbot, Sandra L; Qi, Ji; Ratan, Aakrosh; Tomsho, Lynn P; Kasson, Lindsay; Zeyl, Eve; Aars, Jon; Miller, Webb; Ingólfsson, Olafur; Bachmann, Lutz; Wiig, Oystein

    2010-03-16

    The polar bear has become the flagship species in the climate-change discussion. However, little is known about how past climate impacted its evolution and persistence, given an extremely poor fossil record. Although it is undisputed from analyses of mitochondrial (mt) DNA that polar bears constitute a lineage within the genetic diversity of brown bears, timing estimates of their divergence have differed considerably. Using next-generation sequencing technology, we have generated a complete, high-quality mt genome from a stratigraphically validated 130,000- to 110,000-year-old polar bear jawbone. In addition, six mt genomes were generated of extant polar bears from Alaska and brown bears from the Admiralty and Baranof islands of the Alexander Archipelago of southeastern Alaska and Kodiak Island. We show that the phylogenetic position of the ancient polar bear lies almost directly at the branching point between polar bears and brown bears, elucidating a unique morphologically and molecularly documented fossil link between living mammal species. Molecular dating and stable isotope analyses also show that by very early in their evolutionary history, polar bears were already inhabitants of the Artic sea ice and had adapted very rapidly to their current and unique ecology at the top of the Arctic marine food chain. As such, polar bears provide an excellent example of evolutionary opportunism within a widespread mammalian lineage.

  7. Unveiling the transcriptional features associated with coccolithovirus infection of natural Emiliania huxleyi blooms.

    Science.gov (United States)

    Pagarete, António; Le Corguillé, Gildas; Tiwari, Bela; Ogata, Hiroyuki; de Vargas, Colomban; Wilson, William H; Allen, Michael J

    2011-12-01

    Lytic viruses have been implicated in the massive cellular lysis observed during algal blooms, through which they assume a prominent role in oceanic carbon and nutrient flows. Despite their impact on biogeochemical cycling, the transcriptional dynamics of these important oceanic events is still poorly understood. Here, we employ an oligonucleotide microarray to monitor host (Emiliania huxleyi) and virus (coccolithovirus) transcriptomic features during the course of E. huxleyi blooms induced in seawater-based mesocosm enclosures. Host bloom development and subsequent coccolithovirus infection was associated with a major shift in transcriptional profile. In addition to the expected metabolic requirements typically associated with viral infection (amino acid and nucleotide metabolism, as well as transcription- and replication-associated functions), the results strongly suggest that the manipulation of lipid metabolism plays a fundamental role during host-virus interaction. The results herein reveal the scale, so far massively underestimated, of the transcriptional domination that occurs during coccolithovirus infection in the natural environment. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  8. Unveil the complexity of the molecular machinery involved in erythrophagocytosis by macrophages

    OpenAIRE

    Santarino, Inês Barreira

    2017-01-01

    ABSTRACT: Erythrophagocytosis is a highly regulated process where sequential events ensure the proper internalization and clearance of red blood cells. However, details on these processes are scarce and not fully understood, making it difficult to modulate and possibly treat associated diseases, such as malaria and sickle-cell disease. After their development in the bone marrow, red blood cells have a life span of approximately 120 days. With time, the plasma membrane of red blood cells under...

  9. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity.

    Science.gov (United States)

    Pigeyre, Marie; Yazdi, Fereshteh T; Kaur, Yuvreet; Meyre, David

    2016-06-01

    In high-, middle- and low-income countries, the rising prevalence of obesity is the underlying cause of numerous health complications and increased mortality. Being a complex and heritable disorder, obesity results from the interplay between genetic susceptibility, epigenetics, metagenomics and the environment. Attempts at understanding the genetic basis of obesity have identified numerous genes associated with syndromic monogenic, non-syndromic monogenic, oligogenic and polygenic obesity. The genetics of leanness are also considered relevant as it mirrors some of obesity's aetiologies. In this report, we summarize ten genetically elucidated obesity syndromes, some of which are involved in ciliary functioning. We comprehensively review 11 monogenic obesity genes identified to date and their role in energy maintenance as part of the leptin-melanocortin pathway. With the emergence of genome-wide association studies over the last decade, 227 genetic variants involved in different biological pathways (central nervous system, food sensing and digestion, adipocyte differentiation, insulin signalling, lipid metabolism, muscle and liver biology, gut microbiota) have been associated with polygenic obesity. Advances in obligatory and facilitated epigenetic variation, and gene-environment interaction studies have partly accounted for the missing heritability of obesity and provided additional insight into its aetiology. The role of gut microbiota in obesity pathophysiology, as well as the 12 genes associated with lipodystrophies is discussed. Furthermore, in an attempt to improve future studies and merge the gap between research and clinical practice, we provide suggestions on how high-throughput '-omic' data can be integrated in order to get closer to the new age of personalized medicine. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  10. Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS.

    Science.gov (United States)

    Panda, Pritam Kumar; Rane, Riya; Ravichandran, Rahul; Singh, Shrinkhla; Panchal, Hetalkumar

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a hormonal imbalance in women, which causes problems during menstrual cycle and in pregnancy that sometimes results in fatality. Though the genetics of PCOS is not fully understood, early diagnosis and treatment can prevent long-term effects. In this study, we have studied the proteins involved in PCOS and the structural aspects of the proteins that are taken into consideration using computational tools. The proteins involved are modeled using Modeller 9v14 and Ab-initio programs. All the 43 proteins responsible for PCOS were subjected to phylogenetic analysis to identify the relatedness of the proteins. Further, microarray data analysis of PCOS datasets was analyzed that was downloaded from GEO datasets to find the significant protein-coding genes responsible for PCOS, which is an addition to the reported protein-coding genes. Various statistical analyses were done using R programming to get an insight into the structural aspects of PCOS that can be used as drug targets to treat PCOS and other related reproductive diseases.

  11. ESO unveils an amazing, interactive, 360-degree panoramic view of the entire night sky

    Science.gov (United States)

    2009-09-01

    The first of three images of ESO's GigaGalaxy Zoom project - a new magnificent 800-million-pixel panorama of the entire sky as seen from ESO's observing sites in Chile - has just been released online. The project allows stargazers to explore and experience the Universe as it is seen with the unaided eye from the darkest and best viewing locations in the world. This 360-degree panoramic image, covering the entire celestial sphere, reveals the cosmic landscape that surrounds our tiny blue planet. This gorgeous starscape serves as the first of three extremely high-resolution images featured in the GigaGalaxy Zoom project, launched by ESO within the framework of the International Year of Astronomy 2009 (IYA2009). GigaGalaxy Zoom features a web tool that allows users to take a breathtaking dive into our Milky Way. With this tool users can learn more about many different and exciting objects in the image, such as multicoloured nebulae and exploding stars, just by clicking on them. In this way, the project seeks to link the sky we can all see with the deep, "hidden" cosmos that astronomers study on a daily basis. The wonderful quality of the images is a testament to the splendour of the night sky at ESO's sites in Chile, which are the most productive astronomical observatories in the world. The plane of our Milky Way Galaxy, which we see edge-on from our perspective on Earth, cuts a luminous swath across the image. The projection used in GigaGalaxy Zoom place the viewer in front of our Galaxy with the Galactic Plane running horizontally through the image - almost as if we were looking at the Milky Way from the outside. From this vantage point, the general components of our spiral galaxy come clearly into view, including its disc, marbled with both dark and glowing nebulae, which harbours bright, young stars, as well as the Galaxy's central bulge and its satellite galaxies. The painstaking production of this image came about as a collaboration between ESO, the renowned French writer and astrophotographer Serge Brunier and his fellow Frenchman Frédéric Tapissier. Brunier spent several weeks during the period between August 2008 and February 2009 capturing the sky, mostly from ESO observatories at La Silla and Paranal in Chile. In order to cover the full Milky Way, Brunier also made a week-long trip to La Palma, one of the Canary Islands, to photograph the northern skies [1]. Once the raw photographs were in hand, image processing by Tapissier and ESO experts helped to convey accurately the night sky as our eyes behold it [2]. The resulting image, now available on GigaGalaxy Zoom, is composed of almost 300 fields each individually captured by Brunier four times, adding up to nearly 1200 photos that encompass the entire night sky. "I wanted to show a sky that everyone can relate to - with its constellations, its thousands of stars, with names familiar since childhood, its myths shared by all civilisations since Homo became Sapiens," says Brunier. "The image was therefore made as man sees it, with a regular digital camera under the dark skies in the Atacama Desert and on La Palma." As photographing extended over several months, objects from the Solar System came and went through the star fields, with bright planets such as Venus and Jupiter. A brilliant, emerald-green comet also flew by, although spotting it among a background of tens of millions of stars will be difficult (but rewarding). Overall, the creators of the GigaGalaxy Zoom project hope that these tremendous efforts in bringing the night sky as observed under the best conditions on the planet to stargazers everywhere will inspire awe for the beautiful, immense Universe that we live in. "The vision of the IYA2009 is to help people rediscover their place in the Universe through the day- and night-time sky, and this is exactly what the GigaGalaxy Zoom project is all about," says project coordinator Henri Boffin. The second dramatic GigaGalaxy Zoom image will be revealed next week, on 21 September 2009. Notes [1] During his quest, Brunier used a Nikon D3 digital camera. The apparent motion of the sky caused by Earth's rotation was corrected for using a small, precise equatorial mount moving in the opposite direction, which made a whole circle in 23 hours 56 minutes around the Earth's axis of rotation. Each photo required a six-minute exposure, for a total exposure time of more than 120 hours. [2] The data processing, using software called Autopano Pro Giga, took great care in respecting the colours and "texture" of the Milky Way. Frédéric Tapissier needed about 340 computing hours on a powerful PC to complete the task. More information As part of the IYA2009, ESO is participating in several remarkable outreach activities, in line with its world-leading rank in the field of astronomy. ESO is hosting the IYA2009 Secretariat for the International Astronomical Union, which coordinates the Year globally. ESO is one of the Organisational Associates of IYA2009, and was also closely involved in the resolution submitted to the United Nations (UN) by Italy, which led to the UN's 62nd General Assembly proclaiming 2009 the International Year of Astronomy. In addition to a wide array of activities planned both at the local and international level, ESO is leading three of the twelve global Cornerstone Projects. ESO, the European Southern Observatory, is the foremost intergovernmental astronomy organisation in Europe and the world's most productive astronomical observatory. It is supported by 14 countries: Austria, Belgium, the Czech Republic, Denmark, France, Finland, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, Switzerland and the United Kingdom. ESO carries out an ambitious programme focused on the design, construction and operation of powerful ground-based observing facilities enabling astronomers to make important scientific discoveries. ESO also plays a leading role in promoting and organising cooperation in astronomical research. ESO operates three unique world-class observing sites in Chile: La Silla, Paranal and Chajnantor. At Paranal, ESO operates the Very Large Telescope, the world's most advanced visible-light astronomical observatory. ESO is the European partner of a revolutionary astronomical telescope ALMA, the largest astronomical project in existence. ESO is currently planning a 42-metre European Extremely Large optical/near-infrared Telescope, the E-ELT, which will become "the world's biggest eye on the sky". Serge Brunier is a French journalist, photographer and writer who specialises in popularising astronomy. He is a regular contributor to Science & Vie magazine, and to the France Info radio station. He has written numerous popular astronomy books, translated into over ten languages, and is a prize-winning photographer, who has captured images of solar eclipses from the most amazing places in the world. A life-long quest for the best skies in the world led him to Chile. This whole sky panorama was presented from 25 August till 13 September 2009 in the exhibition "Un ciel pour la planète" (A sky for the planet) in the Atrium of the Monte-Carlo Casino, Monaco. With a giant print of 12 times 6 metres, the exhibition was under the Patronage of The Prince Albert II of Monaco, and showed with images and videos the making of this unique ESO project.

  12. Comparative analyses of glycerotoxin expression unveil a novel structural organization of the bloodworm venom system.

    Science.gov (United States)

    Richter, Sandy; Helm, Conrad; Meunier, Frederic A; Hering, Lars; Campbell, Lahcen I; Drukewitz, Stephan H; Undheim, Eivind A B; Jenner, Ronald A; Schiavo, Giampietro; Bleidorn, Christoph

    2017-03-04

    We present the first molecular characterization of glycerotoxin (GLTx), a potent neurotoxin found in the venom of the bloodworm Glycera tridactyla (Glyceridae, Annelida). Within the animal kingdom, GLTx shows a unique mode of action as it can specifically up-regulate the activity of Ca v 2.2 channels (N-type) in a reversible manner. The lack of sequence information has so far hampered a detailed understanding of its mode of action. Our analyses reveal three ~3.8 kb GLTx full-length transcripts, show that GLTx represents a multigene family, and suggest it functions as a dimer. An integrative approach using transcriptomics, quantitative real-time PCR, in situ hybridization, and immunocytochemistry shows that GLTx is highly expressed exclusively in four pharyngeal lobes, a previously unrecognized part of the venom apparatus. Our results overturn a century old textbook view on the glycerid venom system, suggesting that it is anatomically and functionally much more complex than previously thought. The herein presented GLTx sequence information constitutes an important step towards the establishment of GLTx as a versatile tool to understand the mechanism of synaptic function, as well as the mode of action of this novel neurotoxin.

  13. Unveiling Flat Traffic on the Internet: An SSH Attack Case Study

    NARCIS (Netherlands)

    Jonker, Mattijs; Hofstede, R.J.; Sperotto, Anna; Pras, Aiko

    Many types of brute-force attacks are known to exhibit a characteristic ‘flat’ behavior at the network-level, meaning that connections belonging to an attack feature a similar number of packets and bytes, and duration. Flat traffic usually results from repeating similar application-layer actions,

  14. TU-CD-303-05: Unveiling Tumor Heterogeneity by Molecular Imaging

    International Nuclear Information System (INIS)

    Jeraj, R.

    2015-01-01

    Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of these advances in cancer biology research will give medical physicists a new perspective in daily clinical physics practice and in future radiation therapy technological development. Furthermore, academic medical physics should continue to be an integral part of the multidisciplinary cancer research community, harnessing our newly acquired understanding of radiation effects, and developing novel cost-effective treatment strategies to better combat cancer. Learning Objectives: Understand that localized radiation can lead to non-localized secondary effects such as radiation-induced immune response, bystander effect, and abscopal effect. Understand that the non-localized radiation effects may be harnessed to improve cancer treatment. Learn examples of physics participation in multidisciplinary research to advance cancer biology. Recognize the challenges and possibilities of physics applications in cancer research. Chang: NIH 5RC2CA148487-02 and 1U54CA151652-01 Graves: IDEA award (19IB-0106) from the California Breast Cancer Research Program (CBCRP), and by NIH P01 CA67166

  15. Unveiling the Effects of Citizen Journalism Practice on College Students' Social Capital

    Science.gov (United States)

    Nah, Seungahn; Namkoong, Kang; Van Stee, Stephanie K.; Record, Rachael A.

    2014-01-01

    This study examined the effects of citizen journalism practices on social capital concerning nonprofit and voluntary organizations (i.e., satisfaction, trust, and engagement). Through a quasi-experimental design, the analyses revealed that students in the treatment group, in which participants engaged in citizen journalism practice, had greater…

  16. Unveiled: Interrogating the Use of Applied Drama in Multiple and Specific Sites

    Science.gov (United States)

    Daboo, Jerri

    2007-01-01

    This article examines a view of site through postcolonial feminism to suggest that multiple and contradictory discourses of culture, location, gender and context are all vital in an understanding of a specific site when working with a community. These views are applied to a project undertaken with a group of Asian women in Britain exploring issues…

  17. Supersymmetry squarks, photinos, and the unveiling of the ultimate laws of nature

    CERN Document Server

    Kane, Gordon L

    2000-01-01

    The next breakthrough in physics, supersymmetry will unite the fundamental forces of nature and revolutionize our understanding of space and time. . For most of human history, man has been trying to discover just how the universe works. The Standard Model of particle physics, which describes the fundamental constituents and forces of nature, has proved a useful explanation, and recent theories attempting to unify these fundamental forces-such as string theory-have been wonderfully encouraging. Experimental proof, however, has always lagged behind theory. Now, thanks to powerful new tools and the dedication of a handful of pioneers at the frontiers of research, we are approaching the next great leap in understanding: supersymmetry. In this groundbreaking work, renowned physicist Gordon Kane takes us inside both the conceptual framework of supersymmetry and the giant particle accelerators-the atom smashers-where this fascinating discovery should occur. After giving us the basics of the Standard Model, Kane expl...

  18. Unveiling Research Agendas: a study of the influences on research problem selection among academic researchers

    Energy Technology Data Exchange (ETDEWEB)

    Bianco, M.; Sutz, J.

    2016-07-01

    Research problem selection is central to the dynamics of scientific knowledge production. Research agendas result from the selection of research problems and the formulation of individual and/or collective academic strategies to address them. But, why researchers study what they study? This paper presents incipient research focused on the way different factors influence the construction of academic research agendas. It takes a researcher-oriented approach relying on opinions and perspectives of a wide range of researchers in all fields of knowledge. The empirical work is carried out in Uruguay, a country in the periphery of mainstream science, whose academic community struggles in search of a balance between the requirements of the world community of scholars and the demands from different national stakeholders. The methodology and research results from this study may be relevant to other countries, at different peripheries. Further, understanding the interplay of influences that shape research agendas is an important tool for policy analysis and planning everywhere. (Author)

  19. Cardiac troponin and tropomyosin: structural and cellular perspectives to unveil the Hypertrophic Cardiomyopathy phenotype

    Directory of Open Access Journals (Sweden)

    Mayra de A. Marques

    2016-09-01

    Full Text Available Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1,400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the disease of the sarcomere. The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53, seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We highlight the importance of a better understanding of allosteric communications within these thin-filament proteins to decipher the HCM pathological state.

  20. Unveiling novel RecO distant orthologues involved in homologous recombination.

    Directory of Open Access Journals (Sweden)

    Stéphanie Marsin

    2008-08-01

    Full Text Available The generation of a RecA filament on single-stranded DNA is a critical step in homologous recombination. Two main pathways leading to the formation of the nucleofilament have been identified in bacteria, based on the protein complexes mediating RecA loading: RecBCD (AddAB and RecFOR. Many bacterial species seem to lack some of the components involved in these complexes. The current annotation of the Helicobacter pylori genome suggests that this highly diverse bacterial pathogen has a reduced set of recombination mediator proteins. While it is now clear that homologous recombination plays a critical role in generating H. pylori diversity by allowing genomic DNA rearrangements and integration through transformation of exogenous DNA into the chromosome, no complete mediator complex is deduced from the sequence of its genome. Here we show by bioinformatics analysis the presence of a RecO remote orthologue that allowed the identification of a new set of RecO proteins present in all bacterial species where a RecR but not RecO was previously identified. HpRecO shares less than 15% identity with previously characterized homologues. Genetic dissection of recombination pathways shows that this novel RecO and the remote RecB homologue present in H. pylori are functional in repair and in RecA-dependent intrachromosomal recombination, defining two initiation pathways with little overlap. We found, however, that neither RecOR nor RecB contributes to transformation, suggesting the presence of a third, specialized, RecA-dependent pathway responsible for the integration of transforming DNA into the chromosome of this naturally competent bacteria. These results provide insight into the mechanisms that this successful pathogen uses to generate genetic diversity and adapt to changing environments and new hosts.

  1. Synchronization unveils the organization of ecological networks with positive and negative interactions

    Science.gov (United States)

    Girón, Andrea; Saiz, Hugo; Bacelar, Flora S.; Andrade, Roberto F. S.; Gómez-Gardeñes, Jesús

    2016-06-01

    Network science has helped to understand the organization principles of the interactions among the constituents of large complex systems. However, recently, the high resolution of the data sets collected has allowed to capture the different types of interactions coexisting within the same system. A particularly important example is that of systems with positive and negative interactions, a usual feature appearing in social, neural, and ecological systems. The interplay of links of opposite sign presents natural difficulties for generalizing typical concepts and tools applied to unsigned networks and, moreover, poses some questions intrinsic to the signed nature of the network, such as how are negative interactions balanced by positive ones so to allow the coexistence and survival of competitors/foes within the same system? Here, we show that synchronization phenomenon is an ideal benchmark for uncovering such balance and, as a byproduct, to assess which nodes play a critical role in the overall organization of the system. We illustrate our findings with the analysis of synthetic and real ecological networks in which facilitation and competitive interactions coexist.

  2. An integrative taxonomy approach unveils unknown and threatened moth species in Amazonian rainforest fragments

    Czech Academy of Sciences Publication Activity Database

    Lamarre, Greg P. A.; Decaëns, T.; Rougerie, R.; Barbut, J.; Dewaard, J. R.; Hebert, P. D. N.; Herbin, D.; Laguerre, M.; Thiaucourt, P.; Martins, M. B.

    2016-01-01

    Roč. 9, č. 5 (2016), s. 475-479 ISSN 1752-458X EU Projects: European Commission(XE) 669609 - Diversity6continents Institutional support: RVO:60077344 Keywords : Amazonian forest * Belém center of endemism * centinelan extinction Subject RIV: EG - Zoology Impact factor: 1.840, year: 2016 http://onlinelibrary.wiley.com/doi/10.1111/icad.12187/full

  3. Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences.

    Science.gov (United States)

    Dantas-Torres, Filipe; Solano-Gallego, Laia; Baneth, Gad; Ribeiro, Vitor Marcio; de Paiva-Cavalcanti, Milena; Otranto, Domenico

    2012-12-01

    Canine leishmaniosis is a potentially life-threatening disease which is spreading geographically in the Old and New Worlds, where different diagnostic procedures, treatments, and control strategies are currently in place. This Opinion article outlines the similarities and differences between canine leishmaniosis in the Old and New Worlds, with emphasis on South America and Europe. Finally, it calls the attention of veterinary and public health authorities to standardize and improve practices for diagnosing, treating, and preventing the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Patient perspectives about bariatric surgery unveil experiences, education, satisfaction, and recommendations for improvement.

    Science.gov (United States)

    Groller, Karen D; Teel, Cynthia; Stegenga, Kristin H; El Chaar, Maher

    2018-02-17

    Following bariatric surgery, up to 35% of patients struggle with strict regimens and experience weight recidivism within 2 years [1-5]. Accredited weight management centers (WMC) must provide educational programs and support patients in lifestyle changes before and after surgery. Educational programs, however, may not be evidence-based or patient-centered and may vary in curriculum, approach, and educator type [6]. To obtain patient descriptions about the weight loss surgery (WLS) experience, including education, satisfaction, and recommendations for improvement. Participants were recruited from a university hospital-based WMC in Pennsylvania. This qualitative descriptive study used purposive sampling and inductive content analysis. A NEW ME-VERSION 2.0, encompassed themes from semistructured interviews with 11 participants (36% male). Theme 1: Programming and Tools, explained how individuals undergoing WLS found support through educational programming. Theme 2: Updates and Upgrades, identified issues surrounding quality of life and challenges before and after surgery. Theme 3: Lessons Learned and Future Considerations, identified satisfaction levels and recommendations for improving the WLS experience. Participants reported positive experiences, acknowledging educational programs and extensive WMC resources, yet also offered recommendations for improving educational programming. Patient narratives provided evidence about the WLS experience. Achievement of weight goals, adherence to rules, and improved health status contributed to perceptions of WLS success. Participants encouraged educators to identify expected outcomes of educational programming, monitor holistic transformations, foster peer support, and use technology in WMC programming. Results also validated the need for the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program's education requirement (standard 5.1). Future educational research could help develop best practices in WLS patient education and assess associations between education and clinical outcomes. Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  5. A characteristic oxygen abundance gradient in galaxy disks unveiled with CALIFA

    Czech Academy of Sciences Publication Activity Database

    Sanchez, S.F.; Rosales-Ortega, F.F.; Iglesias-Paramo, J.; Molla, M.; Barrera-Ballesteros, J.; Marino, R.A.; Pérez, E.; Sanchez-Blazquez, P.; Gonzalez Delgado, R.; Jungwiert, Bruno

    2014-01-01

    Roč. 563, March (2014), A49/1-A49/25 ISSN 0004-6361 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M100031241; Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M100031201 Program:M Institutional support: RVO:67985815 Keywords : HII regions * galaxies * ISM: abundances Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.378, year: 2014

  6. Unveiling clusters of RNA transcript pairs associated with markers of Alzheimer's disease progression.

    Directory of Open Access Journals (Sweden)

    Ahmed Shamsul Arefin

    Full Text Available BACKGROUND: One primary goal of transcriptomic studies is identifying gene expression patterns correlating with disease progression. This is usually achieved by considering transcripts that independently pass an arbitrary threshold (e.g. p<0.05. In diseases involving severe perturbations of multiple molecular systems, such as Alzheimer's disease (AD, this univariate approach often results in a large list of seemingly unrelated transcripts. We utilised a powerful multivariate clustering approach to identify clusters of RNA biomarkers strongly associated with markers of AD progression. We discuss the value of considering pairs of transcripts which, in contrast to individual transcripts, helps avoid natural human transcriptome variation that can overshadow disease-related changes. METHODOLOGY/PRINCIPAL FINDINGS: We re-analysed a dataset of hippocampal transcript levels in nine controls and 22 patients with varying degrees of AD. A large-scale clustering approach determined groups of transcript probe sets that correlate strongly with measures of AD progression, including both clinical and neuropathological measures and quantifiers of the characteristic transcriptome shift from control to severe AD. This enabled identification of restricted groups of highly correlated probe sets from an initial list of 1,372 previously published by our group. We repeated this analysis on an expanded dataset that included all pair-wise combinations of the 1,372 probe sets. As clustering of this massive dataset is unfeasible using standard computational tools, we adapted and re-implemented a clustering algorithm that uses external memory algorithmic approach. This identified various pairs that strongly correlated with markers of AD progression and highlighted important biological pathways potentially involved in AD pathogenesis. CONCLUSIONS/SIGNIFICANCE: Our analyses demonstrate that, although there exists a relatively large molecular signature of AD progression, only a small number of transcripts recurrently cluster with different markers of AD progression. Furthermore, considering the relationship between two transcripts can highlight important biological relationships that are missed when considering either transcript in isolation.

  7. Innovative method for optimizing Side-Scan Sonar mapping: The blind band unveiled

    Science.gov (United States)

    Pergent, Gérard; Monnier, Briac; Clabaut, Philippe; Gascon, Gilles; Pergent-Martini, Christine; Valette-Sansevin, Audrey

    2017-07-01

    Over the past few years, the mapping of Mediterranean marine habitats has become a priority for scientists, environment managers and stakeholders, in particular in order to comply with European directives (Water Framework Directive and Marine Strategy Framework Directive) and to implement legislation to ensure their conservation. Side-scan sonar (SSS) is recognised as one of the most effective tool for underwater mapping. However, interpretation of acoustic data (sonograms) requires extensive field calibration and the ground-truthing process remains essential. Several techniques are commonly used, with sampling methods involving grabs, scuba diving observations or Remotely Operated Vehicle (ROV) underwater video recordings. All these techniques are time consuming, expensive and only provide sporadic informations. In the present study, the possibility of coupling a camera with a SSS and acquiring underwater videos in a continuous way has been tested. During the 'PosidCorse' oceanographic survey carried out along the eastern coast of Corsica, optical and acoustic data were respectively obtained using a GoPro™ camera and a Klein 3000™ SSS. Thereby, five profiles were performed between 10 and 50 m depth, corresponding to more than 20 km of data acquisition. The vertical images recorded with the camera fixed under the SSS and positioned facing downwards provided photo mosaics of very good quality corresponding to the entire sonograms's blind band. From the photo mosaics, 94% of the different bottom types and main habitats have been identified; specific structures linked to hydrodynamics conditions, anthropic and biological activities have also been observed as well as the substrate on which the Posidonia oceanica meadow grows. The association between acoustic data and underwater videos has proved to be a non-destructive and cost-effective method for ground-truthing in marine habitats mapping. Nevertheless, in order to optimize the results over the next surveys, certain limitations will need to be remedied.

  8. Unveiling the Sources of Chromium in Pictorialist Photographs: Gum-Dichromate Process or Paper Sizing?

    DEFF Research Database (Denmark)

    Vila, Anna; Centeno, Silvia A; Kennedy, Nora W

    2015-01-01

    For this issue of Hand Papermaking devoted to paper sizing, we offer a review and extension of pertinent results obtained in our investigations of the gum-dichromate photographic process, commonly known as the gum-bichromate process.1 We have published three articles to date on our findings; this...

  9. 3C 273 with NuSTAR: Unveiling the Active Galactic Nucleus

    DEFF Research Database (Denmark)

    Madsen, Kristin K.; Fürst, Felix; Walton, Dominic J.

    2015-01-01

    We present results from a 244 ks NuSTAR observation of 3C 273 obtained during a cross-calibration campaign with the Chandra, INTEGRAL, Suzaku, Swift, and XMM-Newton observatories. We show that the spectrum, when fit with a power-law model using data from all observatories except INTEGRAL over the 1......-78 keV band, leaves significant residuals in the NuSTAR data between 30 and 78 keV. The NuSTAR 3-78 keV spectrum is well. described by an exponentially cutoff power law (Γ = 1.646± 0.006, Ecutoff = 202-34 +51 keV) with a weak reflection component from cold, dense material. There is also evidence......-energy power. law is consistent with the presence of a beamed jet, which begins to dominate over emission from the inner accretion flow at 30-40 keV. Modeling the jet locally (in the NuSTAR + INTEGRAL band) as a power. law, we find that the coronal component is fit by ΓAGN = 1.638 ± 0.045, Ecutoff = 47 ± 15 ke...

  10. Unveiling ν secrets with cosmological data: Neutrino masses and mass hierarchy

    Science.gov (United States)

    Vagnozzi, Sunny; Giusarma, Elena; Mena, Olga; Freese, Katherine; Gerbino, Martina; Ho, Shirley; Lattanzi, Massimiliano

    2017-12-01

    Using some of the latest cosmological data sets publicly available, we derive the strongest bounds in the literature on the sum of the three active neutrino masses, Mν, within the assumption of a background flat Λ CDM cosmology. In the most conservative scheme, combining Planck cosmic microwave background temperature anisotropies and baryon acoustic oscillations (BAO) data, as well as the up-to-date constraint on the optical depth to reionization (τ ), the tightest 95% confidence level upper bound we find is Mν0.06 eV from oscillations data would raise the quoted upper bounds by O (0.1 σ ) and would not affect our conclusions.

  11. What Do Diploma Theses Unveil about Academic Public Policy in the Czech Republic?

    Directory of Open Access Journals (Sweden)

    Mouralová Magdalena

    2015-12-01

    Full Text Available Although textbooks, conference papers, scientific journals and monographs deal with the research aspects of public policy, only little attention is paid to the way it is taught at universities. In this article we aim to explore academic public policy in the Czech Republic - specifically in terms of teaching outputs - using a unique method: an analysis of diploma theses. In the sample there were diploma theses defended within all the full-time Master’s study programmes having “public policy” in their names in the Czech Republic between 1995 and 2013. We conclude that there are two traditions of academic public policy in the Czech Republic, which enriches previous findings in the area and makes them more accurate. The research design and thoroughly described methodology invite other researchers to conduct international comparison of the features of academic public policy. The findings may also illustrate the trajectory made by the newly established discipline of public policy in the past twenty years in the Czech Republic, which may be of great interest to the newly formed international public policy community.

  12. Unveiling scientific communities about sustainability and innovation. A bibliometric journey around sustainable terms

    DEFF Research Database (Denmark)

    Franceschini, Simone; Faria, Lourenco; Jurowetzki, Roman

    2016-01-01

    Literature about the relationship between innovation and sustainability has skyrocketed in the last two decades and new terms have appeared. However, only very few bibliometric analyses have reviewed some of these terms (eco-innovation, environmental innovation, green innovation, and sustainable ...

  13. Participatory practices in heritage management in world heritage cities: unveiling the city representatives’ perceptions

    NARCIS (Netherlands)

    Rosetti, I.

    2018-01-01

    Community engagement is today a goal of heritage management. Participatory practices are generally advocated for matters of authenticity and ethics, but also for the economic, environmental, cultural and social, in short, sustainable development of local communities. However, criticisms and

  14. Temperature induced syllable breaking unveils nonlinearly interacting timescales in birdsong motor pathway.

    Directory of Open Access Journals (Sweden)

    Matías A Goldin

    Full Text Available The nature of telencephalic control over premotor and motor circuits is debated. Hypotheses range from complete usurping of downstream circuitry to highly interactive mechanisms of control. We show theoretically and experimentally, that telencephalic song motor control in canaries is consistent with a highly interactive strategy. As predicted from a theoretical model of respiratory control, mild cooling of a forebrain nucleus (HVC led to song stretching, but further cooling caused progressive restructuring of song, consistent with the hypothesis that respiratory gestures are subharmonic responses to a timescale present in the output of HVC. This interaction between a life-sustaining motor function (respiration and telencephalic song motor control suggests a more general mechanism of how nonlinear integration of evolutionarily new brain structures into existing circuitry gives rise to diverse, new behavior.

  15. Ectopic Bone Matrix Mineralization: Unveiling the Osteoinductive Nature of Crab Cuticle

    Science.gov (United States)

    Omokanwaye, Tiffany Suella

    Engineered nanomaterials are increasingly used in a variety of industrial processes and consumer products. Numerous studies have reported toxicity of different NPs during the last years. Thus, there are growing concerns about the potential impacts to the health and environment of engineered nanoparticles (NPs). However, some methodological problems complicate the interpretation of nanotoxicity studies. On the one hand, some NPs have shown to interfere with classical toxicity assays based on colorimetric or fluorescent measurements. On the other hand, most NPs tend to aggregate in media used in toxicity tests, which complicates the interpretation of the toxicity results. The first objective of this dissertation was to evaluate a novel impedance-based and label-free real time cell analyzer (RTCA) as a high throughput method for screening the cytotoxicity of nanoparticles and to validate the RTCA results using a conventional cytotoxicity test (MTT). Several inorganic NPs were tested for potential cytotoxicity to human bronchial epithelial cells (16HBE14o-). In general, there was a good correlation in cytotoxicity measurements between the two methods. Moreover, none of the NPs tested showed interference with the impedance measurements performed by the RTCA system. The results demonstrate the potential and validity of the impedance-based RTCA technique to rapidly screen for NP toxicity. The second objective of this dissertation was to assess the toxicity of different inorganic NPs to the eukaryotic cell model Saccharomyces cerevisiae, and to test the influence of NP aggregation state in their toxicity. Nanotoxicity was assessed by monitoring oxygen consumption in batch cultures and by analysis of cell membrane integrity. Mn2O3 NPs showed the highest inhibition of O2 consumption and cell membrane damage, while the other NPs caused low or no toxicity to the yeast. Most NPs showed high tendency to aggregate in the assay medium, so a non-toxic dispersant was used to improve NP stability. In contrast to aggregated CeO2 NPs, dispersed CeO 2 NPs showed toxicity to the yeast. However, dispersant supplementation decreased the inhibition caused by Mn2O3 NPs at low concentrations, which could indicate that dispersant association with the particles may have an impact on the interaction between the NPs and the cells. The proven toxicity of some NPs raises concerns about their environmental fate. Municipal and industrial wastewaters are considered primary sources of NPs to the environment. However, information on the behavior and impact of NPs on wastewater treatment processes is very limited. A third objective of this dissertation was to evaluate the fate and long-term effect of ZnO and CuO NPs during wastewater treatment in high-rate anaerobic bioreactors. Laboratory-scale upflow anaerobic sludge blanket (UASB) reactors were fed with synthetic wastewater containing NPs for extended periods of time (> 90 d). Extensive removal (62-82%) of ZnO and CuO NPs was observed during wastewater treatment in the UASB reactors. Scanning electron microscopy and chemical analysis confirmed that NPs were associated with the anaerobic sludge. While short-term exposure to low levels of ZnO and CuO NPs only caused minor inhibition to methanogenesis, extended exposure to NPs accumulated in the sludge bed led to a gradual and partial inhibitory response in the reactors. The inhibitory effect was also evident in the decline in the acetoclastic methanogenic activity of the biomass.

  16. Unveiling Collaborative Group Identities in Social Synthetic Environments from Interaction Data

    DEFF Research Database (Denmark)

    Grappiolo, Corrado

    used to simulate aspects of real-life, yet by maintaining a customisable level of control of the phenomena under investigation. Examples of social synthetic environments are theoretical games and cooperative computer games. The proposed framework is composed of two pipelined modules. The first one....... This dissertation successfully leverages on the hypothesis that it is possible to infer the existence of group structures by solely focusing on the ongoing interactions. The limitations of the approach and possible strategies to overcome them are also proposed....

  17. GEMINI/GeMS Observations Unveil the Structure of the Heavily Obscured Globular Cluster Liller 1.

    Science.gov (United States)

    Saracino, S.; Dalessandro, E.; Ferraro, F. R.; Lanzoni, B.; Geisler, D.; Mauro, F.; Villanova, S.; Moni Bidin, C.; Miocchi, P.; Massari, D.

    2015-06-01

    By exploiting the exceptional high-resolution capabilities of the near-IR camera GSAOI combined with the Gemini Multi-Conjugate Adaptive System at the GEMINI South Telescope, we investigated the structural and physical properties of the heavily obscured globular cluster Liller 1 in the Galactic bulge. We have obtained the deepest and most accurate color-magnitude diagram published so far for this cluster, reaching {{K}s}˜ 19 (below the main-sequence turnoff level). We used these data to redetermine the center of gravity of the system, finding that it is located about 2.″2 southeast from the literature value. We also built new star density and surface brightness profiles for the cluster and rederived its main structural and physical parameters (scale radii, concentration parameter, central mass density, total mass). We find that Liller 1 is significantly less concentrated (concentration parameter c=1.74) and less extended (tidal radius {{r}t}=298\\prime\\prime and core radius {{r}c}=5\\buildrel{\\prime\\prime}\\over{.} 39) than previously thought. By using these newly determined structural parameters, we estimated the mass of Liller 1 to be {{M}tot}=2.3+0.3-0.1× {{10}6} {{M}⊙ } ({{M}tot}=1.5+0.2-0.1× {{10}6} {{M}⊙ } for a Kroupa initial mass function), which is comparable to that of the most massive clusters in the Galaxy (ω Centari and Terzan 5). Also, Liller 1 has the second-highest collision rate (after Terzan 5) among all star clusters in the Galaxy, thus confirming that it is an ideal environment for the formation of collisional objects (such as millisecond pulsars). Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência, Tecnologia e Inovação (Brazil), and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina). Based on observations gathered with the ESO-VISTA telescope (program ID 179.B-2002).

  18. The Unexpectedly Bright Comet C-2012 F6 (Lemmon) Unveiled at Near-Infrared Wavelengths

    Science.gov (United States)

    Paganini, Lucas; Disanti, Michael A.; Mumma, Michael J.; Villanueva, Geronimo L.; Bonev, Boncho P.; Keane, Jacqueline V.; Gibb, Erika L.; Boehnhardt, Hermann; Meech, Karen J.

    2013-01-01

    We acquired near-infrared spectra of the Oort cloud comet C/2012 F6 (Lemmon) at three different heliocentric distances (R h) during the comet's 2013 perihelion passage, providing a comprehensive measure of the outgassing behavior of parent volatiles and cosmogonic indicators. Our observations were performed pre-perihelion at R h = 1.2 AU with CRIRES (on 2013 February 2 and 4), and post-perihelion at R h = 0.75 AU with CSHELL (on March 31 and April 1) and R h = 1.74 AU with NIRSPEC (on June 20). We detected 10 volatile species (H2O, OH* prompt emission, C2H6, CH3OH, H2CO, HCN, CO, CH4, NH3, and NH2), and obtained upper limits for two others (C2H2 and HDO). One-dimensional spatial profiles displayed different distributions for some volatiles, confirming either the existence of polar and apolar ices, or of chemically distinct active vents in the nucleus. The ortho-para ratio for water was 3.31 +/- 0.33 (weighted mean of CRIRES and NIRSPEC results), implying a spin temperature >37 K at the 95% confidence limit. Our (3s) upper limit for HDO corresponds to D/H comet C/2012 F6 as rather depleted in C2H6 and CH3OH, while HCN, CH4, and CO displayed abundances close to their median values found among comets. H2CO was the only volatile showing a relative enhancement. The relative paucity of C2H6 and CH3OH (with respect to H2O) suggests formation within warm regions of the nebula. However, the normal abundance of HCN and hypervolatiles CH4 and CO, and the enhancement of H2CO, may indicate a possible heterogeneous nucleus of comet C/2012 F6 (Lemmon), possibly as a result of radial mixing within the protoplanetary disk

  19. Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear

    Science.gov (United States)

    Lindqvist, Charlotte; Schuster, Stephan C.; Sun, Yazhou; Talbot, Sandra L.; Qi, Ji; Ratan, Aakrosh; Tomsho, Lynn P.; Kasson, Lindsay; Zeyl, Eve; Aars, Jon; Miller, Webb; Ingólfsson, Ólafur; Bachmann, Lutz; Wiig, Øystein

    2010-01-01

    The polar bear has become the flagship species in the climate-change discussion. However, little is known about how past climate impacted its evolution and persistence, given an extremely poor fossil record. Although it is undisputed from analyses of mitochondrial (mt) DNA that polar bears constitute a lineage within the genetic diversity of brown bears, timing estimates of their divergence have differed considerably. Using next-generation sequencing technology, we have generated a complete, high-quality mt genome from a stratigraphically validated 130,000- to 110,000-year-old polar bear jawbone. In addition, six mt genomes were generated of extant polar bears from Alaska and brown bears from the Admiralty and Baranof islands of the Alexander Archipelago of southeastern Alaska and Kodiak Island. We show that the phylogenetic position of the ancient polar bear lies almost directly at the branching point between polar bears and brown bears, elucidating a unique morphologically and molecularly documented fossil link between living mammal species. Molecular dating and stable isotope analyses also show that by very early in their evolutionary history, polar bears were already inhabitants of the Artic sea ice and had adapted very rapidly to their current and unique ecology at the top of the Arctic marine food chain. As such, polar bears provide an excellent example of evolutionary opportunism within a widespread mammalian lineage. PMID:20194737

  20. Traversing Urban Social Spaces: How Online Research Helps Unveil Offline Practice

    Science.gov (United States)

    Carroll, Julie-Anne; Foth, Marcus; Adkins, Barbara

    This article presents a discussion of methodological considerations in urban informatics research. As an exemplar, we examine a health communication research blog set up to produce insights into the choices made by residents of a master-planned development affecting their health and well-being. It served both as a repository for collection and a tool for the strategic selection and analysis of internet research data. We reflect on the nature of the online data contributed by an urban demographic about their physical activity practices within this particular neighbourhood. The blog provided a forum for detailed responses which allowed participants to reflect on their answers over a period of time, and write with the privacy and protection effects provided by the anonymity of contributions, coupled with the advantage of being able to view the contributions made by other residents. Opinions, stories and discussions were instigated by questions and photographs posted on the blog about residents' levels of engagement with the neighbourhood for staying active and healthy. Residents reported on the social and physical aspects of the new urban environment that either encouraged or inhibited them from leading active and healthy lifestyles. In this context the blog provided insights into the role of both the planning rhetoric associated with a new urban village and the meanings attached to the lifeworld of the residents in their health practices. A total of 214 contributions to the blog were made by the residents, with the analysis and findings highlighting implications for urban design and health promotion research and practice.

  1. Unveiling the high-activity origin of single-atom iron catalysts for oxygen reduction reaction.

    Science.gov (United States)

    Yang, Liu; Cheng, Daojian; Xu, Haoxiang; Zeng, Xiaofei; Wan, Xin; Shui, Jianglan; Xiang, Zhonghua; Cao, Dapeng

    2018-06-26

    It is still a grand challenge to develop a highly efficient nonprecious-metal electrocatalyst to replace the Pt-based catalysts for oxygen reduction reaction (ORR). Here, we propose a surfactant-assisted method to synthesize single-atom iron catalysts (SA-Fe/NG). The half-wave potential of SA-Fe/NG is only 30 mV less than 20% Pt/C in acidic medium, while it is 30 mV superior to 20% Pt/C in alkaline medium. Moreover, SA-Fe/NG shows extremely high stability with only 12 mV and 15 mV negative shifts after 5,000 cycles in acidic and alkaline media, respectively. Impressively, the SA-Fe/NG-based acidic proton exchange membrane fuel cell (PEMFC) exhibits a high power density of 823 mW cm -2 Combining experimental results and density-functional theory (DFT) calculations, we further reveal that the origin of high-ORR activity of SA-Fe/NG is from the Fe-pyrrolic-N species, because such molecular incorporation is the key, leading to the active site increase in an order of magnitude which successfully clarifies the bottleneck puzzle of why a small amount of iron in the SA-Fe catalysts can exhibit extremely superior ORR activity.

  2. Proteomics unveil corticoid-induced S100A11 shuttling in keratinocyte differentiation

    International Nuclear Information System (INIS)

    Dezitter, Xavier; Hammoudi, Fatma; Belverge, Nicolas; Deloulme, Jean-Christophe; Drobecq, Herve; Masselot, Bernadette; Formstecher, Pierre; Mendy, Denise; Idziorek, Thierry

    2007-01-01

    Unlike classical protein extraction techniques, proteomic mapping using a selective subcellular extraction kit revealed S100A11 as a new member of the S100 protein family modulated by glucocorticoids in keratinocytes. Glucocorticoids (GC)-induced S100A11 redistribution in the 'organelles and membranes' compartment. Microscopic examination indicated that glucocorticoids specifically routed cytoplasmic S100A11 toward perinuclear compartment. Calcium, a key component of skin terminal differentiation, directed S100A11 to the plasma membrane as previously reported. When calcium was added to glucocorticoids, minor change was observed at the proteomic level while confocal microscopy revealed a rapid and dramatic translocation of S100A11 toward plasma membrane. This effect was accompanied by strong nuclear condensation, loss of mitochondrial potential and DNA content, and increased high molecular weight S100A11 immunoreactivity, suggesting corticoids accelerate calcium-induced terminal differentiation. Finally, our results suggest GC-induced S100A11 relocalization could be a key step in both keratinocyte homeostasis and glucocorticoids side effects in human epidermis

  3. Fifteen Projects Unveiled to Green Local Communities, Create Jobs and Manage Stormwater Runoff

    Science.gov (United States)

    BALTIMORE - Today the U.S. Environmental Protection Agency (EPA) and the Chesapeake Bay Trust, in partnership with Maryland's Department of Natural Resources, announced $727,500 in grants to be awarded to 15 organizations through the Green Streets,

  4. Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear

    OpenAIRE

    Lindqvist, Charlotte; Schuster, Stephan C.; Sun, Yazhou; Talbot, Sandra L.; Qi, Ji; Ratan, Aakrosh; Tomsho, Lynn P.; Kasson, Lindsay; Zeyl, Eve; Aars, Jon; Miller, Webb; Ingólfsson, Ólafur; Bachmann, Lutz; Wiig, Øystein

    2010-01-01

    The polar bear has become the flagship species in the climate-change discussion. However, little is known about how past climate impacted its evolution and persistence, given an extremely poor fossil record. Although it is undisputed from analyses of mitochondrial (mt) DNA that polar bears constitute a lineage within the genetic diversity of brown bears, timing estimates of their divergence have differed considerably. Using next-generation sequencing technology, we have generated a complete, ...

  5. Protein-Glycan Quinary Interactions in Crowding Environment Unveiled by NMR Spectroscopy.

    Science.gov (United States)

    Diniz, Ana; Dias, Jorge S; Jiménez-Barbero, Jesús; Marcelo, Filipa; Cabrita, Eurico J

    2017-09-21

    Protein-glycan interactions as modulators for quinary structures in crowding environments were explored. The interaction between human galectin 3 (Gal-3) and distinct macromolecular crowders, such as bovine and human serum albumin (BSA and HSA), Ficoll 70 and PEG3350, was scrutinized. The molecular recognition event of the specific ligand, lactose, by Gal-3 in crowding conditions was evaluated. Gal-3 interactions were monitored by NMR analysing chemical shift perturbation (CSP) and line broadening of 1 H 15 N-HSQC signals. The intensity of the Gal-3 1 H 15 N-HSQC signals decreased in the presence of all crowders, due to the increase in the solution viscosity and to the formation of large protein complexes. When glycosylated containing samples of BSA and HSA were used, signal broadening was more severe than that observed in the presence of the more viscous solutions of PEG3350 and Ficoll 70. However, for the samples containing glycoproteins, the signal intensity of 1 H 15 N-HSQC recovered upon addition of lactose. We show that serum proteins interact with Gal-3, through their α2,3-linked sialylgalactose moieties exposed at their surfaces, competing with lactose for the same binding site. The quinary interaction between Gal-3 and serum glycoproteins, could help to co-localize Gal-3 at the cell surface, and may play a role in adhesion and signalling functions of this protein. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The Negative Sign and Exponential Expressions: Unveiling Students' Persistent Errors and Misconceptions

    Science.gov (United States)

    Cangelosi, Richard; Madrid, Silvia; Cooper, Sandra; Olson, Jo; Hartter, Beverly

    2013-01-01

    The purpose of this study was to determine whether or not certain errors made when simplifying exponential expressions persist as students progress through their mathematical studies. College students enrolled in college algebra, pre-calculus, and first- and second-semester calculus mathematics courses were asked to simplify exponential…

  7. ERP Response Unveils Effect of Second Language Manipulation on First Language Processing.

    Directory of Open Access Journals (Sweden)

    Elvira Khachatryan

    Full Text Available Lexical access in bilinguals has been considered either selective or non-selective and evidence exists in favor of both hypotheses. We conducted a linguistic experiment to assess whether a bilingual's language mode influences the processing of first language information. We recorded event related potentials during a semantic priming paradigm with a covert manipulation of the second language (L2 using two types of stimulus presentations (short and long. We observed a significant facilitation of word pairs related in L2 in the short version reflected by a decrease in N400 amplitude in response to target words related to the English meaning of an inter-lingual homograph (homograph-unrelated group. This was absent in the long version, as the N400 amplitude for this group was similar to the one for the control-unrelated group. We also interviewed the participants whether they were aware of the importance of L2 in the experiment. We conclude that subjects participating in the long and short versions were in different language modes: closer to monolingual mode for the long and closer to bilingual mode for the short version; and that awareness about covert manipulation of L2 can influence the language mode, which in its turn influences the processing of the first language.

  8. Unveiling the relationship between the transaction timing, spending and dropout behavior of customers

    NARCIS (Netherlands)

    Glady, N.; Lemmens, A.; Croux, C.

    The customer lifetime value combines into one construct the transaction timing, spending and dropout processes that characterize the purchase behavior of customers. Recently, the potential relationship between these processes, either at the individual customer level (i.e. intra-customer correlation)

  9. Unveiling the fungal mycobiota present throughout the cork stopper manufacturing process

    NARCIS (Netherlands)

    Barreto, M.C.; Houbraken, J.; Samson, R.A.; Brito, D.; Gadanho, M.; San Romão, M.V.

    2012-01-01

    A particular fungal population is present in the main stages of the manufacturing process of cork discs. Its diversity was studied using both dependent (isolation) and independent culture methods (denaturing gel gradient electrophoresis and cloning of the ITS1-5.8S-ITS2 region). The mycobiota in the

  10. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor

    DEFF Research Database (Denmark)

    Presman, Diego M; Ogara, M Florencia; Stortz, Martín

    2014-01-01

    Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR) transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation wi...

  11. Unveiling the diversification dynamics of Australasian predaceous diving beetles in the Cenozoic.

    Science.gov (United States)

    Toussaint, Emmanuel F A; Condamine, Fabien L; Hawlitschek, Oliver; Watts, Chris H; Porch, Nick; Hendrich, Lars; Balke, Michael

    2015-01-01

    During the Cenozoic, Australia experienced major climatic shifts that have had dramatic ecological consequences for the modern biota. Mesic tropical ecosystems were progressively restricted to the coasts and replaced by arid-adapted floral and faunal communities. Whilst the role of aridification has been investigated in a wide range of terrestrial lineages, the response of freshwater clades remains poorly investigated. To gain insights into the diversification processes underlying a freshwater radiation, we studied the evolutionary history of the Australasian predaceous diving beetles of the tribe Hydroporini (147 described species). We used an integrative approach including the latest methods in phylogenetics, divergence time estimation, ancestral character state reconstruction, and likelihood-based methods of diversification rate estimation. Phylogenies and dating analyses were reconstructed with molecular data from seven genes (mitochondrial and nuclear) for 117 species (plus 12 outgroups). Robust and well-resolved phylogenies indicate a late Oligocene origin of Australasian Hydroporini. Biogeographic analyses suggest an origin in the East Coast region of Australia, and a dynamic biogeographic scenario implying dispersal events. The group successfully colonized the tropical coastal regions carved by a rampant desertification, and also colonized groundwater ecosystems in Central Australia. Diversification rate analyses suggest that the ongoing aridification of Australia initiated in the Miocene contributed to a major wave of extinctions since the late Pliocene probably attributable to an increasing aridity, range contractions and seasonally disruptions resulting from Quaternary climatic changes. When comparing subterranean and epigean genera, our results show that contrasting mechanisms drove their diversification and therefore current diversity pattern. The Australasian Hydroporini radiation reflects a combination of processes that promoted both diversification, resulting from new ecological opportunities driven by initial aridification, and a subsequent loss of mesic adapted diversity due to increasing aridity. © The Author(s) 2014. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. A Bayesian inference approach to unveil supply curves in electricity markets

    DEFF Research Database (Denmark)

    Mitridati, Lesia Marie-Jeanne Mariane; Pinson, Pierre

    2017-01-01

    in the literature on modeling this uncertainty. In this study we introduce a Bayesian inference approach to reveal the aggregate supply curve in a day-ahead electricity market. The proposed algorithm relies on Markov Chain Monte Carlo and Sequential Monte Carlo methods. The major appeal of this approach......With increased competition in wholesale electricity markets, the need for new decision-making tools for strategic producers has arisen. Optimal bidding strategies have traditionally been modeled as stochastic profit maximization problems. However, for producers with non-negligible market power...

  13. The features of the Cosmic Web unveiled by the flip-flop field

    Science.gov (United States)

    Shandarin, Sergei F.; Medvedev, Mikhail V.

    2017-07-01

    Currently the dark matter environment is widely accepted as a framework for understanding of the observed structure in the universe. N-body simulations are indispensable for the analysis of the formation and evolution of the dark matter web. Two primary fields - density and velocity fields - are used in most of studies. Dark matter provides two additional fields that are unique for collisionless media only. They are the multistream field in Eulerian space and flip-flop field in Lagrangian space. The flip-flop field represents the number of sign reversals of an elementary volume of each collisionless fluid element. This field can be estimated by counting the sign reversals of the Jacobian at each particle at every time step of the simulation. The Jacobian is evaluated by numerical differentiation of the Lagrangian submanifold, I.e. the three-dimensional dark matter sheet in the six-dimensional space formed by three Lagrangian and three Eulerian coordinates. We present the results of the statistical study of the evolution of the flip-flop field from z = 50 to the present time z = 0. A number of statistical characteristics show that the pattern of the flip-flop field remains remarkably stable from z ≈ 30 to the present time. As a result the flip-flop field evaluated at z = 0 stores a wealth of information about the dynamical history of the dark matter web. In particular one of the most intriguing properties of the flip-flop is a unique capability to preserve the information about the merging history of haloes.

  14. TU-CD-303-05: Unveiling Tumor Heterogeneity by Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jeraj, R. [University of Wisconsin (United States)

    2015-06-15

    Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of these advances in cancer biology research will give medical physicists a new perspective in daily clinical physics practice and in future radiation therapy technological development. Furthermore, academic medical physics should continue to be an integral part of the multidisciplinary cancer research community, harnessing our newly acquired understanding of radiation effects, and developing novel cost-effective treatment strategies to better combat cancer. Learning Objectives: Understand that localized radiation can lead to non-localized secondary effects such as radiation-induced immune response, bystander effect, and abscopal effect. Understand that the non-localized radiation effects may be harnessed to improve cancer treatment. Learn examples of physics participation in multidisciplinary research to advance cancer biology. Recognize the challenges and possibilities of physics applications in cancer research. Chang: NIH 5RC2CA148487-02 and 1U54CA151652-01 Graves: IDEA award (19IB-0106) from the California Breast Cancer Research Program (CBCRP), and by NIH P01 CA67166.

  15. Unveiling the geography of historical patents in the United States from 1836 to 1975

    NARCIS (Netherlands)

    Petralia, Sergio; Balland, Pierre-Alexandre; Rigby, David L

    2016-01-01

    It is clear that technology is a key driver of economic growth. Much less clear is where new technologies are produced and how the geography of U.S. invention has changed over the last two hundred years. Patent data report the geography, history, and technological characteristics of invention.

  16. Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor

    OpenAIRE

    Wang,Guang-Yu; Li,Ling; Liu,Bo; Han,Xiao; Wang,Chunhua; Wang,Jiwen

    2018-01-01

    Guang-Yu Wang,1,* Ling Li,2,* Bo Liu,1 Xiao Han,1 Chun-Hua Wang,1 Ji-Wen Wang3 1Department of Neurosurgery, 2Department of Pediatrics, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, 3Department of Neurology, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Pudong New District, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to explore ...

  17. Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor

    OpenAIRE

    Wang G; Li L; Liu B; Han X; Wang CH; Wang JW

    2018-01-01

    Guang-Yu Wang,1,* Ling Li,2,* Bo Liu,1 Xiao Han,1 Chun-Hua Wang,1 Ji-Wen Wang3 1Department of Neurosurgery, 2Department of Pediatrics, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, 3Department of Neurology, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Pudong New District, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to explore significant gene...

  18. Unveiling HIV dynamics among transgender women: a respondent driven sampling study in Rio de Janeiro, Brazil

    Science.gov (United States)

    Grinsztejn, Beatriz; Jalil, Emilia Moreira; Monteiro, Laylla; Velasque, Luciane; Moreira, Ronaldo I.; Garcia, Ana Cristina F.; Castro, Cristiane V.; Krüger, Alícia; Luz, Paula M.; Liu, Albert Y.; Farland, Willi Mc; Buchbinder, Susan; Veloso, Valdilea G.; Wilson, Erin C.

    2017-01-01

    Background The burden of HIV in transgender women (transwomen) in Brazil remains unknown. We aimed to estimate HIV prevalence among transwomen, and identify the factors associated with newly diagnosed HIV infections. Methods “Transcender” was a respondent driven sampling study of transwomen in Rio de Janeiro, Brazil, conducted from August 2015 to January 2016. Twelve seeds were recruited from social movements and formative phase. Eligibility criteria were: self-identification as transwomen, being 18 years of age or older, living in Rio de Janeiro or metropolitan area, and having a valid peer recruitment coupon. Participants were categorized as HIV-negative, known HIV infected, or newly diagnosed as HIV infected. Predictors of newly diagnosed HIV infections were assessed by comparing the newly diagnosed with the HIV-negative. Population estimates were adjusted using the RDSII estimator. Findings In total, 345 eligible transwomen were enrolled. The study sample was young and diverse on gender identity. Population estimates of no prior HIV testing, HIV-infection and newly diagnosed as HIV-infected were 29·1%, 32·1% and 7·0%, respectively (based on n=60 with no prior testing, n=141 HIV-infected, n=40 newly diagnosed). Syphilis, rectal chlamydia and gonorrhea infection were diagnosed in 28·9%, 14·6%, and 13·5%, respectively. Newly diagnosed HIV infections were associated with black race (22·8; 95%CI 2·9–178·9), travesti (34·1; 95%CI 5·8–200·2) or transsexual woman (41·3; 95%CI 6·3–271·2) gender identity, history of sex work (30·7; 95%CI 3·5–267·3), and history of sniffing cocaine (4·4; 95%CI 1·4–14·1). Interpretation Our results suggest that transwomen bear the largest burden of HIV among any population at risk in Brazil. The high proportion of HIV diagnosis among young participants points to the need for tailored long-term health care and prevention services in order to curb the HIV epidemic and improve the quality-of-life of transwomen in Brazil. Funding This work was supported by Brazilian Research Council (470056/2014-2) and NIAID-NIH (UM1AI069496). PMID:28188030

  19. IC 3639 - A New Bona Fide Compton-Thick AGN Unveiled By NuSTAR

    Science.gov (United States)

    Boorman, Peter G.; Gandhi, P.; Alexander, D. M.; Annuar, A.; Ballantyne, D. R.; Bauer, F.; Boggs, S. E.; Brandt, W. N.; Brightman, M.; Christensen, F. E.; hide

    2016-01-01

    We analyze high-quality NuSTAR observations of the local (z = 0.011) Seyfert 2 active galactic nucleus (AGN) IC 3639, in conjunction with archival Suzaku and Chandra data. This provides the first broadband X-ray spectral analysis of the source, spanning nearly two decades in energy (0.5-30 keV). Previous X-ray observations of the source below 10 keV indicated strong reflection/obscuration on the basis of a pronounced iron fluorescence line at 6.4 keV. The hard X-ray energy coverage of NuSTAR, together with self-consistent toroidal reprocessing models, enables direct broadband constraints on the obscuring column density of the source. We find the source to be heavily Compton-thick (CTK) with an obscuring column in excess of 3.6 x 10(exp 24) cm(exp -2), unconstrained at the upper end. We further find an intrinsic 2-10 keV luminosity of log(sub 10) (L(sub 2-10 keV) [erg s(exp -1)])= 43.4(+0.6/-1.1) to 90% confidence, almost 400 times the observed flux, and consistent with various multiwavelength diagnostics. Such a high ratio of intrinsic to observed flux, in addition to an Fe-K(alpha) fluorescence line equivalent width exceeding 2 keV, is extreme among known bona fide CTK AGNs, which we suggest are both due to the high level of obscuration present around IC 3639. Our study demonstrates that broadband spectroscopic modeling with NuSTAR enables large corrections for obscuration to be carried out robustly and emphasizes the need for improved modeling of AGN tori showing intense iron fluorescence.

  20. IC 3639 - A new bona fide Compton thick AGN unveiled by NuSTAR

    DEFF Research Database (Denmark)

    Boorman, Peter G.; Gandhi, P.; Alexander, D.

    2016-01-01

    We analyse high-quality NuSTAR observations of the local (z = 0.011) Seyfert 2 active galactic nucleus (AGN) IC 3639, in conjunction with archival Suzaku and Chandra data. This provides the first broadband X-ray spectral analysis of the source, spanning nearly two decades in energy (0.5 -30 keV)....

  1. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

    Directory of Open Access Journals (Sweden)

    Jose A Santiago

    Full Text Available Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level.Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP, previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS and the Prognostic Biomarker Study (PROBE, revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients.These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that increased expression of APP in blood may modulate the neurodegenerative phenotype in type 2 diabetes patients.

  2. Integrative Network Analysis Unveils Convergent Molecular Pathways in Parkinson's Disease and Diabetes

    OpenAIRE

    Santiago, Jose A.; Potashkin, Judith A.

    2013-01-01

    Background Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. ...

  3. THE EXTENDED He IIλ4686-EMITTING REGION IN IZw 18 UNVEILED: CLUES FOR PECULIAR IONIZING SOURCES

    Energy Technology Data Exchange (ETDEWEB)

    Kehrig, C.; Vílchez, J. M.; Pérez-Montero, E.; Iglesias-Páramo, J.; Bayo, F. M. [Instituto de Astrofísica de Andalucía (CSIC), Glorieta de la Astronomía s/n, E-18008 Granada (Spain); Brinchmann, J. [Leiden Observatory, Leiden University, P.O. Box 9513, NL-2300 RA Leiden (Netherlands); Kunth, D.; Durret, F. [Institut d’Astrophysique de Paris, UMR 7095, CNRS and UPMC, 98 bis Bd Arago, F-75014 Paris (France)

    2015-03-10

    New integral field spectroscopy has been obtained for IZw 18, the nearby lowest-metallicity galaxy considered to be our best local analog of systems forming at high redshift (z). Here we report the spatially resolved spectral map of the nebular He ii λ4686 emission in IZw 18, from which we derived for the first time its total He ii-ionizing flux. Nebular He ii emission implies the existence of a hard radiation field. He ii-emitters are observed to be more frequent among high-z galaxies than for local objects. Therefore, investigating the He ii-ionizing source(s) in IZw 18 may reveal the ionization processes at high z. He ii emission in star-forming galaxies has been suggested to be mainly associated with Wolf–Rayet stars (WRs), but WRs cannot satisfactorily explain the He ii-ionization at all times, particularly at the lowest metallicities. Shocks from supernova remnants, or X-ray binaries, have been proposed as additional potential sources of He ii-ionizing photons. Our data indicate that conventional He ii-ionizing sources (WRs, shocks, X-ray binaries) are not sufficient to explain the observed nebular He iiλ4686 emission in IZw 18. We find that the He ii-ionizing radiation expected from models for either low-metallicity super-massive O stars or rotating metal-free stars could account for the He ii-ionization budget measured, while only the latter models could explain the highest values of He iiλ4686/Hβ observed. The presence of such peculiar stars in IZw 18 is suggestive and further investigation in this regard is needed. This letter highlights that some of the clues of the early universe can be found here in our cosmic backyard.

  4. China’s War by Other Means: Unveiling China’s Quest for Information Dominance

    Science.gov (United States)

    2017-06-09

    of the U.S. Persian Gulf War – delivering the message the “PLA’s capabilities during a crisis would deter any enemy.” In 1995, relations were...Chen, King C. “China’s War Against Vietnam, 1979: A Military Analysis.” Journal of East Asian Affairs 3, no. 1 (Spring/Summer 1983). Accessed May 8

  5. Genome-wide SNP data unveils the globalization of domesticated pigs.

    Science.gov (United States)

    Yang, Bin; Cui, Leilei; Perez-Enciso, Miguel; Traspov, Aleksei; Crooijmans, Richard P M A; Zinovieva, Natalia; Schook, Lawrence B; Archibald, Alan; Gatphayak, Kesinee; Knorr, Christophe; Triantafyllidis, Alex; Alexandri, Panoraia; Semiadi, Gono; Hanotte, Olivier; Dias, Deodália; Dovč, Peter; Uimari, Pekka; Iacolina, Laura; Scandura, Massimo; Groenen, Martien A M; Huang, Lusheng; Megens, Hendrik-Jan

    2017-09-21

    Pigs were domesticated independently in Eastern and Western Eurasia early during the agricultural revolution, and have since been transported and traded across the globe. Here, we present a worldwide survey on 60K genome-wide single nucleotide polymorphism (SNP) data for 2093 pigs, including 1839 domestic pigs representing 122 local and commercial breeds, 215 wild boars, and 39 out-group suids, from Asia, Europe, America, Oceania and Africa. The aim of this study was to infer global patterns in pig domestication and diversity related to demography, migration, and selection. A deep phylogeographic division reflects the dichotomy between early domestication centers. In the core Eastern and Western domestication regions, Chinese pigs show differentiation between breeds due to geographic isolation, whereas this is less pronounced in European pigs. The inferred European origin of pigs in the Americas, Africa, and Australia reflects European expansion during the sixteenth to nineteenth centuries. Human-mediated introgression, which is due, in particular, to importing Chinese pigs into the UK during the eighteenth and nineteenth centuries, played an important role in the formation of modern pig breeds. Inbreeding levels vary markedly between populations, from almost no runs of homozygosity (ROH) in a number of Asian wild boar populations, to up to 20% of the genome covered by ROH in a number of Southern European breeds. Commercial populations show moderate ROH statistics. For domesticated pigs and wild boars in Asia and Europe, we identified highly differentiated loci that include candidate genes related to muscle and body development, central nervous system, reproduction, and energy balance, which are putatively under artificial selection. Key events related to domestication, dispersal, and mixing of pigs from different regions are reflected in the 60K SNP data, including the globalization that has recently become full circle since Chinese pig breeders in the past decades started selecting Western breeds to improve local Chinese pigs. Furthermore, signatures of ongoing and past selection, acting at different times and on different genetic backgrounds, enhance our insight in the mechanism of domestication and selection. The global diversity statistics presented here highlight concerns for maintaining agrodiversity, but also provide a necessary framework for directing genetic conservation.

  6. Unveiling the role and life strategies of viruses from the surface to the dark ocean

    KAUST Repository

    Lara, Elena; Vaqué , Dolors; Sà , Elisabet Laia; Boras, Julia A.; Gomes, Ana; Borrull, Encarna; Dí ez-Vives, Cristina; Teira, Eva; Pernice, Massimo C.; Garcia, Francisca C.; Forn, Irene; Castillo, Yaiza M.; Peiró , Aida; Salazar, Guillem; Moran, Xose Anxelu G.; Massana, Ramon; Catalá , Teresa S.; Luna, Gian Marco; Agusti, Susana; Estrada, Marta; Gasol, Josep M M; Duarte, Carlos M.

    2017-01-01

    Viruses are a key component of marine ecosystems, but the assessment of their global role in regulating microbial communities and the flux of carbon is precluded by a paucity of data, particularly in the deep ocean. We assessed patterns in viral abundance and production and the role of viral lysis as a driver of prokaryote mortality, from surface to bathypelagic layers, across the tropical and subtropical oceans. Viral abundance showed significant differences between oceans in the epipelagic and mesopelagic, but not in the bathypelagic, and decreased with depth, with an average power-law scaling exponent of −1.03 km−1 from an average of 7.76 × 106 viruses ml−1 in the epipelagic to 0.62 × 106 viruses ml−1 in the bathypelagic layer with an average integrated (0 to 4000 m) viral stock of about 0.004 to 0.044 g C m−2, half of which is found below 775 m. Lysogenic viral production was higher than lytic viral production in surface waters, whereas the opposite was found in the bathypelagic, where prokaryotic mortality due to viruses was estimated to be 60 times higher than grazing. Free viruses had turnover times of 0.1 days in the bathypelagic, revealing that viruses in the bathypelagic are highly dynamic. On the basis of the rates of lysed prokaryotic cells, we estimated that viruses release 145 Gt C year−1 in the global tropical and subtropical oceans. The active viral processes reported here demonstrate the importance of viruses in the production of dissolved organic carbon in the dark ocean, a major pathway in carbon cycling.

  7. Marketing modest fashion or fashioning modesty? HijUp Unveiled at London Fashion Week

    OpenAIRE

    Wilson, Jonathan

    2016-01-01

    The Indonesians came, they saw and we learned more about their spicy blend of fashion and fun, in the streets of London. Here’s a slice of what’s going on in the emerging global Modest Fashion scene.

  8. Synchronization unveils the organization of ecological networks with positive and negative interactions.

    Science.gov (United States)

    Girón, Andrea; Saiz, Hugo; Bacelar, Flora S; Andrade, Roberto F S; Gómez-Gardeñes, Jesús

    2016-06-01

    Network science has helped to understand the organization principles of the interactions among the constituents of large complex systems. However, recently, the high resolution of the data sets collected has allowed to capture the different types of interactions coexisting within the same system. A particularly important example is that of systems with positive and negative interactions, a usual feature appearing in social, neural, and ecological systems. The interplay of links of opposite sign presents natural difficulties for generalizing typical concepts and tools applied to unsigned networks and, moreover, poses some questions intrinsic to the signed nature of the network, such as how are negative interactions balanced by positive ones so to allow the coexistence and survival of competitors/foes within the same system? Here, we show that synchronization phenomenon is an ideal benchmark for uncovering such balance and, as a byproduct, to assess which nodes play a critical role in the overall organization of the system. We illustrate our findings with the analysis of synthetic and real ecological networks in which facilitation and competitive interactions coexist.

  9. Rotation measure synthesis at the 2 m wavelength of the FAN region: unveiling screens and bubbles

    Science.gov (United States)

    Iacobelli, M.; Haverkorn, M.; Katgert, P.

    2013-01-01

    Context. Rotation measure synthesis of the Westerbork Synthesis Radio Telescope (WSRT) observations at λ ~ 2 m of the FAN region at l = 137°, b = +7° shows the morphology of structures in the ionized interstellar medium. Aims: We interpret the diffuse polarized synchrotron emission in terms of coherent structures in the interstellar medium and the properties of the interstellar magnetic field. Methods: We performed statistical analysis of the polarization data cube obtained through rotation measure synthesis. For the first time, cross-correlation is applied to identify and characterize polarized structures in Faraday depth space. Complementary information about the medium are derived from Hα emission, properties of nearby pulsars, and optical polarized starlight measurements. Results: We find an overall asymmetric Faraday dispersion function in a Faraday depth range of [-13, +5] rad m-2, which is peaked around -1 rad m-2. Three morphological patterns are recognized, showing structures on scales from degrees down to the beam size. The first structure is a nearby synchrotron emission component with low Faraday depth, filling the entire field of view. The second pattern is a circular polarization structure with enhanced (negative) Faraday depth, which has the same morphology as a low-emission region within the third component. This third component is interpreted as the background in which the circular structure is embedded. At low Faraday depth values, a low gradient across the imaged field is detected, almost aligned with the Galactic plane. Power spectra of polarized structures in Faraday depth space provide evidence of turbulence. Conclusions: A sign reversal in Faraday depth from the nearby component to the circular component indicates a reversal of the magnetic field component along the line of sight, from towards the observer and nearby to away from the observer at large distances. The distance to the nearby, extended component is estimated as ≲100 pc, which suggests that this structure corresponds to the Local Bubble wall. For the circular component, various physical interpretations are discussed. The most likely explanation is that the circular component seems to be the presence of a nearby (~200 pc away) relic Strömgren sphere, associated with an old unidentified white dwarf star and expanding in a low-density environment. Faraday rotation datacubes are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/549/A56

  10. Unveiling the nucleon tensor charge at Jefferson Lab: A study of the SoLID case

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Zhihong; Sato, Nobuo; Allada, Kalyan; Liu, Tianbo; Chen, Jian-Ping; Gao, Haiyan; Kang, Zhong-Bo; Prokudin, Alexei; Sun, Peng; Yuan, Feng

    2017-04-01

    © 2017 The Authors Future experiments at the Jefferson Lab 12 GeV upgrade, in particular, the Solenoidal Large Intensity Device (SoLID), aim at a very precise data set in the region where the partonic structure of the nucleon is dominated by the valence quarks. One of the main goals is to constrain the quark transversity distributions. We apply recent theoretical advances of the global QCD extraction of the transversity distributions to study the impact of future experimental data from the SoLID experiments. Especially, we develop a simple strategy based on the Hessian matrix analysis that allows one to estimate the uncertainties of the transversity quark distributions and their tensor charges extracted from SoLID data simulation. We find that the SoLID measurements with the proton and the effective neutron targets can improve the precision of the u- and d-quark transversity distributions up to one order of magnitude in the range 0.05 < x < 0.6.

  11. Unveiling the oxidative metabolism of Achatina fulica (Mollusca: Gastropoda) experimentally infected to Angiostrongylus cantonensis (Nematoda: Metastrongylidae).

    Science.gov (United States)

    Tunholi-Alves, Vinícius Menezes; Tunholi, Victor Menezes; Garcia, Juberlan; Mota, Esther Maria; Castro, Rosane Nora; Pontes, Emerson Guedes; Pinheiro, Jairo

    2018-06-01

    For the first time, alterations in the oxidative metabolism of Achatina fulica experimentally infected with different parasite loads of Angiostrongylus cantonensis were determined. For this, the hemolymph activities of lactate dehydrogenase (LDH) and hexokinase and the glucose concentrations in the hemolymph, as well as the polysaccharide reserves in the digestive gland and cephalopedal mass, were assessed. Additionally, the contents of some carboxylic acids in the hemolymph of infected and uninfected snails were determined by high-performance liquid chromatography (HPLC), permitting a better understanding of the alterations related to the host's oxidative metabolism. As the main results, activation of oxidative pathways, such as the glycolytic pathway, was demonstrated in response to the increase in the activity of hexokinase. This tendency was confirmed by the decrease in the contents of glucose in the hemolymph of parasitized snails, indicating that the infection by A. cantonensis alters the host's metabolism, and that these changes are strongly influenced by the parasite load. This metabolic scenario was accompanied by activation of the anaerobic fermentative metabolism, indicated not only by an increase in the activity of (LDH), but also by a reduction of the content of pyruvic acid and accumulation of lactic acid in the hemolymph of parasitized snails. In this circumstance, maintenance of the host's redox balance occurs through activation of the fermentative pathways, and LDH plays a central role in this process. Together, the results indicate that A. cantonensis infection induces activation of the anaerobic metabolism of A. fulica, characterized not only by the accumulation of lactic acid, but also by a reduction in the pyruvic acid and oxalic acid contents in the hemolymph of the infected snails.

  12. Comparative fecal metagenomics unveils unique functional capacity of the swine gut

    Directory of Open Access Journals (Sweden)

    Martinson John

    2011-05-01

    Full Text Available Abstract Background Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health as well as to food and water safety due to the presence of human pathogens in pig feces. Nonetheless, limited information on the functional diversity of the swine gut microbiome is available. Results Analysis of 637, 722 pyrosequencing reads (130 megabases generated from Yorkshire pig fecal DNA extracts was performed to help better understand the microbial diversity and largely unknown functional capacity of the swine gut microbiome. Swine fecal metagenomic sequences were annotated using both MG-RAST and JGI IMG/M-ER pipelines. Taxonomic analysis of metagenomic reads indicated that swine fecal microbiomes were dominated by Firmicutes and Bacteroidetes phyla. At a finer phylogenetic resolution, Prevotella spp. dominated the swine fecal metagenome, while some genes associated with Treponema and Anareovibrio species were found to be exclusively within the pig fecal metagenomic sequences analyzed. Functional analysis revealed that carbohydrate metabolism was the most abundant SEED subsystem, representing 13% of the swine metagenome. Genes associated with stress, virulence, cell wall and cell capsule were also abundant. Virulence factors associated with antibiotic resistance genes with highest sequence homology to genes in Bacteroidetes, Clostridia, and Methanosarcina were numerous within the gene families unique to the swine fecal metagenomes. Other abundant proteins unique to the distal swine gut shared high sequence homology to putative carbohydrate membrane transporters. Conclusions The results from this metagenomic survey demonstrated the presence of genes associated with resistance to antibiotics and carbohydrate metabolism suggesting that the swine gut microbiome may be shaped by husbandry practices.

  13. Unveiling the equation of state of nuclear matter with binary neutron stars

    Energy Technology Data Exchange (ETDEWEB)

    Galeazzi, F.; Rezzolla, L. [Frankfurt Univ., Frankfurt am Main (Germany). Inst. for Theoretical Physics

    2016-11-01

    2015 marked the hundred anniversary of Albert Einstein's lecture at the Prussian Academy of Science in which he introduced, for the first time, the famous field equations which became the core of his theory of general relativity. This masterpiece of 20th century science has proven extremely solid in all its predictions from the precession of the perihelion of Mercury to the observation of gravitational lensing in distant galaxies, to the more mundane time-delay corrections required by the global positioning system. One last piece of the puzzle is although still missing and comprise the direct measurement of the gravitational wave (GW) radiation emitted by any accelerating mass. These ripples in the spacetime fabric are extremely weak even when produced in the most extreme of the conditions as the ones present during the mergers of two black holes or neutron stars. For this reason they have eluded experimental scientists for almost four decades. But things are about to change, last year a new array of advanced gravitational wave detectors, namely advanced LIGO and Virgo came online in late September and they are expected to observe up to 40 events per year involving the mergers of two compact objects. Despite the high sensitivity of this generation of ground base interferometers, it is still necessary to use accurate gravitational waveforms models to extract all the information from the signal produced by the detector. In this project we focus on the merger of two neutron stars which orbit together in a binary system. The nonlinear nature of the Einstein equations coupled with the complex microphysics behind neutron star matter requires the use of sophisticated codes which uses advanced numerical techniques to produce accurate results. By using the GW signals calculated in our numerical simulations we will be able to strongly link the properties of neutron star matter to a precise set of observable frequencies from the detector. This information, together with the electromagnetic counterparts of these events, will shed some light on the engine that powers short gamma ray bursts. The properties of matter at the ultra high densities and low temperatures reached inside neutron stars cannot be observed in a conventional laboratory on Earth and for this reason accurate GW astronomy is a unique opportunity to constraint the current knowledge of the equation of state that describes these regimes. But GWs are not the only observable that can be linked to the equation of state of neutron star matter, during the violent merger of two neutron stars large amount of neutron rich material is ejected leading to the creation of heavy elements. While undergoing radioactive decay, these elements emit in near-infrared and optical bands of the electromagnetic spectrum. The characteristics of these emissions are strongly affected by the composition, temperature and total mass of the dynamically ejected material and for this reason we have developed a series of cutting-edge methods to simulate in full general relativity the inspiral, merger and collapse including relativistic hydrodynamics, the use of nuclear finite-temperature equations of state and an approximate treatment of neutrino emission and absorption. Such simulations require the use of computational facilities such as the one at LRZ where we make use of thousands of CPUs every week for each of our simulations and producing several terabytes of data. This data are processed in situ at the LRZ facility and, for a more detailed analysis, transferred to our local cluster in Frankfurt am Main (LOEWE).

  14. Vulnerabilities in Yersinia pestis caf operon are unveiled by a Salmonella vector.

    Science.gov (United States)

    Cao, Ling; Lim, Timothy; Jun, SangMu; Thornburg, Theresa; Avci, Recep; Yang, Xinghong

    2012-01-01

    During infection, Yersinia pestis uses its F1 capsule to enhance survival and cause virulence to mammalian host. Since F1 is produced in large quantities and secreted into the host tissues, it also serves as a major immune target. To hold this detrimental effect under proper control, Y. pestis expresses the caf operon (encoding the F1 capsule) in a temperature-dependent manner. However, additional properties of the caf operon limit its expression. By overexpressing the caf operon in wild-type Salmonella enterica serovar Typhimurium under a potent promoter, virulence of Salmonella was greatly attenuated both in vitro and in vivo. In contrast, expression of the caf operon under the regulation of its native promoter exhibited negligible impairment of Salmonellae virulence. In-depth investigation revealed all individual genes in the caf operon attenuated Salmonella when overexpressed. The deleterious effects of caf operon and the caf individual genes were further confirmed when they were overexpressed in Y. pestis KIM6+. This study suggests that by using a weak inducible promoter, the detrimental effects of the caf operon are minimally manifested in Y. pestis. Thus, through tight regulation of the caf operon, Y. pestis precisely balances its capsular anti-phagocytic properties with the detrimental effects of caf during interaction with mammalian host.

  15. Trajectory Analysis Unveils Reelin's Role in the Directed Migration of Granule Cells in the Dentate Gyrus.

    Science.gov (United States)

    Wang, Shaobo; Brunne, Bianka; Zhao, Shanting; Chai, Xuejun; Li, Jiawei; Lau, Jeremie; Failla, Antonio Virgilio; Zobiak, Bernd; Sibbe, Mirjam; Westbrook, Gary L; Lutz, David; Frotscher, Michael

    2018-01-03

    Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer. In contrast, directed migration was not observed when Reelin was ubiquitously present in the medium of reeler slices. These results indicate that topographically administered Reelin controls the formation of a granule cell layer. SIGNIFICANCE STATEMENT Neuronal migration and the various factors controlling its onset, speed, directionality, and arrest are poorly understood. Slice cultures offer a unique model to study the migration of individual neurons in an almost natural environment. In the present study, we took advantage of the expression of proopiomelanocortin-EGFP by newly generated, migrating granule cells to analyze their migratory trajectories in hippocampal slice cultures from wild-type mice and mutants deficient in Reelin signaling. We show that the compartmentalized presence of Reelin is essential for the directionality, but not the actual migratory process or speed, of migrating granule cells leading to their characteristic lamination in the dentate gyrus. Copyright © 2018 the authors 0270-6474/18/380137-12$15.00/0.

  16. (Un)Becoming Tourist-Teachers: Unveiling White Racial Identity in Cross-Cultural Teaching Programmes

    Science.gov (United States)

    Enriquez-Gibson, Judith; Gibson, Ian

    2015-01-01

    The importance of cross-cultural experiences in teacher education has become more pressing than ever. The composition of schools across Australia is increasingly more diverse, therefore it is pertinent to examine and develop pre-service teachers' worldview and culturally sensitive dispositions critical for teaching in predominantly multicultural…

  17. Unveiled Sentiments: Gendered Islamophobia and Experiences of Veiling among Muslim Girls in a Canadian Islamic School

    Science.gov (United States)

    Zine, Jasmin

    2006-01-01

    The practice of veiling has made Muslim women subject to dual oppressions--racism and Islamophobia--in society at large and patriarchal oppression and sexism from within their communities. Based on a narrative analysis of the politics of veiling in schools and society, the voices of young Muslim women attending a Canadian Islamic school speak to…

  18. Unveiling the participation of avian kinin ornithokinin and its receptors in the chicken inflammatory response.

    Science.gov (United States)

    Guabiraba, Rodrigo; Garrido, Damien; Bailleul, Geoffrey; Trotereau, Angélina; Pinaud, Mélanie; Lalmanach, Anne-Christine; Chanteloup, Nathalie K; Schouler, Catherine

    2017-06-01

    Vasoactive peptides are key early mediators of inflammation released through activation of different enzymatic systems. The mammalian kinin-kallikrein (K-KLK) system produces bradykinin (BK) through proteolytic cleavage of a kininogen precursor by enzymes named kallikreins. BK acts through specific ubiquitous G-protein coupled receptors (B1R and B2R) to participate in physiological processes and inflammatory responses, such as activation of mononuclear phagocytes. In chickens, the BK-like nonapeptide ornithokinin (OK) has been shown to promote intracellular calcium increase in embryonic fibroblasts and to be vasodilatory in vivo. Also, one of its receptors (B2R) was already cloned. However, the participation of chicken K-KLK system components in the inflammatory response remains unknown and was therefore investigated. We first showed that B1R, B2R and kininogen 1 (KNG1) are expressed in unstimulated chicken tissues and macrophages. We next showed that chicken B1R and B2R are expressed at transcript and protein levels in chicken macrophages and are upregulated by E. coli LPS or avian pathogenic E. coli (APEC) infection. Interestingly, exogenous OK induced internalization and degradation of OK receptors protein, notably B2R. Also, OK induced intracellular calcium increase and potentiated zymosan-induced ROS production and Dextran-FITC endocytosis by chicken macrophages. Exogenous OK itself did not promote APEC killing and had no pro-inflammatory effect. However, when combined with LPS or APEC, OK upregulated cytokine/chemokine gene expression and NO production by chicken macrophages. This effect was not blocked by canonical non-peptide B1R or B2R receptor antagonists but was GPCR- and PI3K/Akt-dependent. In vivo, pulmonary colibacillosis led to upregulation of OK receptors expression in chicken lungs and liver. Also, colibacillosis led to significant upregulation of OK precursor KNG1 expression in liver and in cultured hepatocytes (LMH). We therefore provide hitherto unknown information on how OK and its receptors are involved in inflammation and infection in chickens. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Unveiling common responses of Medicago truncatula to appropriate and inappropriate rust species

    Directory of Open Access Journals (Sweden)

    Maria Carlota eVaz Patto

    2014-11-01

    Full Text Available Little is known about the nature of effective defense mechanisms in legumes to pathogens of remotely related plant species. Some rust species are among pathogens with broad host range causing dramatic losses in various crop plants. To understand and compare the different host and nonhost resistance responses of legume species against rusts, we characterized the reaction of the model legume Medicago truncatula to one appropriate (Uromyces striatus and two inappropriate (U. viciae-fabae and U. lupinicolus rusts. We found that similar pre and post-haustorial mechanisms of resistance appear to be operative in M. truncatula against appropriate and inappropriate rust fungus. The appropriate U. striatus germinated better on M. truncatula accessions then the inappropriate U. viciae-fabae and U. lupinicolus, but once germinated, germ tubes of the three rusts had a similar level of success in finding stomata and forming an appressoria over a stoma. However responses to different inappropriate rust species also showed some specificity, suggesting a combination of non specific and specific responses underlying this legume nonhost resistance to rust fungi. Further genetic and expression analysis studies will contribute to the development of the necessary molecular tools to use the present information on host and nonhost resistance mechanisms to breed for broad-spectrum resistance to rust in legume species.

  20. Reptile Toll-like receptor 5 unveils adaptive evolution of bacterial flagellin recognition.

    Science.gov (United States)

    Voogdt, Carlos G P; Bouwman, Lieneke I; Kik, Marja J L; Wagenaar, Jaap A; van Putten, Jos P M

    2016-01-07

    Toll-like receptors (TLR) are ancient innate immune receptors crucial for immune homeostasis and protection against infection. TLRs are present in mammals, birds, amphibians and fish but have not been functionally characterized in reptiles despite the central position of this animal class in vertebrate evolution. Here we report the cloning, characterization, and function of TLR5 of the reptile Anolis carolinensis (Green Anole lizard). The receptor (acTLR5) displays the typical TLR protein architecture with 22 extracellular leucine rich repeats flanked by a N- and C-terminal leucine rich repeat domain, a membrane-spanning region, and an intracellular TIR domain. The receptor is phylogenetically most similar to TLR5 of birds and most distant to fish TLR5. Transcript analysis revealed acTLR5 expression in multiple lizard tissues. Stimulation of acTLR5 with TLR ligands demonstrated unique responsiveness towards bacterial flagellin in both reptile and human cells. Comparison of acTLR5 and human TLR5 using purified flagellins revealed differential sensitivity to Pseudomonas but not Salmonella flagellin, indicating development of species-specific flagellin recognition during the divergent evolution of mammals and reptiles. Our discovery of reptile TLR5 fills the evolutionary gap regarding TLR conservation across vertebrates and provides novel insights in functional evolution of host-microbe interactions.

  1. Unveiling E-Bike Potential for Commuting Trips from GPS Traces

    Directory of Open Access Journals (Sweden)

    Angel J. Lopez

    2017-06-01

    Full Text Available Common goals of sustainable mobility approaches are to reduce the need for travel, to facilitate modal shifts, to decrease trip distances and to improve energy efficiency in the transportation systems. Among these issues, modal shift plays an important role for the adoption of vehicles with fewer or zero emissions. Nowadays, the electric bike (e-bike is becoming a valid alternative to cars in urban areas. However, to promote modal shift, a better understanding of the mobility behaviour of e-bike users is required. In this paper, we investigate the mobility habits of e-bikers using GPS data collected in Belgium from 2014 to 2015. By analysing more than 10,000 trips, we provide insights about e-bike trip features such as: distance, duration and speed. In addition, we offer a deep look into which routes are preferred by bike owners in terms of their physical characteristics and how weather influences e-bike usage. Results show that trips with higher travel distances are performed during working days and are correlated with higher average speeds. Usage patterns extracted from our data set also indicate that e-bikes are preferred for commuting (home-work and business (work related trips rather than for recreational trips.

  2. Unveiling the Mysteries of Mars with a Miniaturized Variable Pressure Scanning Electron Microscope (MVP-SEM)

    Science.gov (United States)

    Edmunson, J.; Gaskin, J. A.; Doloboff, I. J.; Jerman, G.

    2017-01-01

    Development of a miniaturized scanning electron microscope that will utilize the martian atmosphere to dissipate charge during analysis continues. This instrument is expected to be used on a future rover or lander to answer fundamental Mars science questions. To identify the most important questions, a survey was taken at the 47th Lunar and Planetary Science Conference (LPSC). From the gathered information initial topics were identified for a SEM on the martian surface. These priorities are identified and discussed below. Additionally, a concept of operations is provided with the goal of maximizing the science obtained with the minimum amount of communication with the instrument.

  3. Seasonal patterns in Arctic prasinophytes and inferred ecology of Bathycoccus unveiled in an Arctic winter metagenome.

    Science.gov (United States)

    Joli, Nathalie; Monier, Adam; Logares, Ramiro; Lovejoy, Connie

    2017-06-01

    Prasinophytes occur in all oceans but rarely dominate phytoplankton populations. In contrast, a single ecotype of the prasinophyte Micromonas is frequently the most abundant photosynthetic taxon reported in the Arctic from summer through autumn. However, seasonal dynamics of prasinophytes outside of this period are little known. To address this, we analyzed high-throughput V4 18S rRNA amplicon data collected from November to July in the Amundsen Gulf Region, Beaufort Sea, Arctic. Surprisingly during polar sunset in November and December, we found a high proportion of reads from both DNA and RNA belonging to another prasinophyte, Bathycoccus. We then analyzed a metagenome from a December sample and the resulting Bathycoccus metagenome assembled genome (MAG) covered ~90% of the Bathycoccus Ban7 reference genome. In contrast, only ~20% of a reference Micromonas genome was found in the metagenome. Our phylogenetic analysis of marker genes placed the Arctic Bathycoccus in the B1 coastal clade. In addition, substitution rates of 129 coding DNA sequences were ~1.6% divergent between the Arctic MAG and coastal Chilean upwelling MAGs and 17.3% between it and a South East Atlantic open ocean MAG in the B2 Clade. The metagenomic analysis also revealed a winter viral community highly skewed toward viruses targeting Micromonas, with a much lower diversity of viruses targeting Bathycoccus. Overall a combination of Micromonas being relatively less able to maintain activity under dark winter conditions and viral suppression of Micromonas may have contributed to the success of Bathycoccus in the Amundsen Gulf during winter.

  4. Food-Bridging: A New Network Construction to Unveil the Principles of Cooking

    Directory of Open Access Journals (Sweden)

    Tiago Simas

    2017-06-01

    Full Text Available In this manuscript, we propose, analyze, and discuss a possible new principle behind traditional cuisine: the Food-bridging hypothesis and its comparison with the food-pairing hypothesis using the same dataset and graphical models employed in the food-pairing study by Ahn et al. (2011. The Food-bridging hypothesis assumes that if two ingredients do not share a strong molecular or empirical affinity, they may become affine through a chain of pairwise affinities. That is, in a graphical model as employed by Ahn et al., a chain represents a path that joints the two ingredients, the shortest path represents the strongest pairwise chain of affinities between the two ingredients. Food-pairing and Food-bridging are different hypotheses that may describe possible mechanisms behind the recipes of traditional cuisines. Food-pairing intensifies flavor by mixing ingredients in a recipe with similar chemical compounds, and food-bridging smoothes contrast between ingredients. Both food-pairing and food-bridging are observed in traditional cuisines, as shown in this work. We observed four classes of cuisines according to food-pairing and food-bridging: (1 East Asian cuisines, at one extreme, tend to avoid food-pairing as well as food-bridging; and (4 Latin American cuisines, at the other extreme, follow both principles. For the two middle classes: (2 Southeastern Asian cuisines, avoid food-pairing and follow food-bridging; and (3 Western cuisines, follow food-pairing and avoid food-bridging.

  5. Unveiling of a cryptic Dicranomyia (Idiopyga from northern Finland using integrative approach (Diptera, Limoniidae

    Directory of Open Access Journals (Sweden)

    Jukka Salmela

    2014-12-01

    Full Text Available The subgenus Idiopyga Savchenko, 1987 is a northern hemisphere group of short-palped crane flies (Diptera, Limoniidae. In the current article we describe a new species, Dicranomyia (I. boreobaltica Salmela sp.n., and redescribe the male and female post-abdomen of a closely related species, D. (I. intricata Alexander. A standard DNA barcoding fragment of 5′ region of the cytochrome c oxidase I (COI gene of the new species is presented, whilst the K2P minimum distances between the new species and 10 other species of the subgenus were found to range from 5.1 to 15.7 % (mean 11.2 %. Phylogenetic analyses (parsimony and maximum likelihood based on COI sequences support the identity of the new species and its close relationship with D. (I. intricata and D. (I. esbeni (Nielsen. The new species is known from the northern Baltic area of Finland. The new species has been mostly collected from Baltic coastal meadows but an additional relict population is known from a calcareous rich fen that was estimated to have been at sea level circa 600-700 years ago. Dicranomyia (I. intricata (syn. D. suecica Nielsen is a Holarctic species, occurring in the north boreal and subarctic vegetation zones in Fennoscandia.

  6. Food marketing targeting children: unveiling the ethical perspectives in the discourse on self-regulation.

    Science.gov (United States)

    Silva, Dillian Adelaine Cesar da; Cunha, Antonio Carlos Rodrigues da; Cunha, Thiago Rocha da; Rosaneli, Caroline Filla

    2017-07-01

    When it comes to food marketing, children are one of the major targets. Regulatory actions can play a strategic role in health protection. The objective of this research was to characterize the ethical perspective in the discourse against state regulatory actions on food marketing directed at children, aiming to understand the context of the discourse's production and how it creates meaning. The methodology adopted was qualitative, with documentary analysis and use of concepts and procedures from Discourse Analysis. The work of Hans Jonas, specifically his Responsibility Principle, and Garrafa and Port's Intervention Bioethics oriented the analysis. The self-regulation discourse analysis showed an ethical perspective in which relations of consumption predominate over the children´s vulnerability. The rhetorical excess is constant, as well as the use of resources like naturalization, untruthfulness, ideological dissimulation and euphemism. An erasure of social conflicts takes place, and an ahistorical perspective is present. The discourse does not align with Jonas´ Responsibility Principle, nor those of Intervention Bioethics. Lastly, the ethical perspective of the discourse represents a double paradox, because it is a business discourse that hides its competitive roots and metamorphoses into an ethical one.

  7. Gas-rich galaxy pair unveiled in the lensed quasar 0957+561

    Science.gov (United States)

    Planesas; Martin-Pintado; Neri; Colina

    1999-12-24

    Molecular gas in the host galaxy of the lensed quasar 0957+561 (QSO 0957+561) at the redshift of 1.41 has been detected in the carbon monoxide (CO) line. This detection shows the extended nature of the molecular gas distribution in the host galaxy and the pronounced lensing effects due to the differentially magnified CO luminosity at different velocities. The estimated mass of molecular gas is about 4 x 10(9) solar masses, a molecular gas mass typical of a spiral galaxy like the Milky Way. A second, weaker component of CO is interpreted as arising from a close companion galaxy that is rich in molecular gas and has remained undetected so far. Its estimated molecular gas mass is 1.4 x 10(9) solar masses, and its velocity relative to the main galaxy is 660 kilometers per second. The ability to probe the molecular gas distribution and kinematics of galaxies associated with high-redshift lensed quasars can be used to improve the determination of the Hubble constant H(0).

  8. NEURON-GLIA INTERACTIONS IN PERIPHERAL VASOPRESSIN AND OXYTOCIN SYSTEMS UNVEILED IN TRANSGENIC RATS

    Czech Academy of Sciences Publication Activity Database

    Dayanithi, Govindan; Forostyak, Oksana; Forostyak, Serhiy; Arboleda Toro, David; Viero, C.; Strunin, Dmytro; Folková, Dagmar; Syková, Eva; Shibuya, I.; Ueta, Y.; Toescu, E.C.; Verkhratsky, Alexei

    2011-01-01

    Roč. 59, Supplement 1 (2011), S103-S103 ISSN 0894-1491. [European meeting on Glia l Cells in Health and Disease /10./. 13.09.2011-17.09.2011, Prague] Institutional research plan: CEZ:AV0Z50390703 Keywords : neuropeptides * nociception * lactation Subject RIV: FH - Neurology

  9. Unveiling the Role of CNTs on the Phase Formation of 1D Ferroelectrics

    KAUST Repository

    Mahajan, Amit

    2015-05-21

    Carbon nanotubes (CNTs) have the potential to act as templates or bottom electrodes for three dimension (3D) capacitor arrays, which utilise one dimension (1D) ferroelectric nanostructures to increase memory size and density. However, growing a ferroelectric on the surface of CNTs is non-trivial. Here, we demonstrate that multi-walled (MW) CNTs decrease the time and temperature for formation of lead zirconium titanate Pb(Zr1-xTix)O3 (PZT) by ~100 ºC commensurate with a decrease in activation energy from 68±15 kJ/mol to 27±2 kJ/mol. As a consequence, monophasic PZT was obtained at 575 ºC for MWCNTs/PZT whereas for pure PZT traces of pyrochlore were still present at 650 ºC, where PZT phase formed due to homogeneous nucleation. The piezoelectric nature of MWCNT/PZT synthesised at 500 ºC for 1 h was proved. Although further work is required to prove the concept of 3D capacitor arrays, our result suggests that it is feasible to utilise MWCNTs as templates/electrodes for the formation of 1D PZT nano ferroelectrics.

  10. UNVEILING THE EVOLUTIONARY SEQUENCE FROM INFALLING ENVELOPES TO KEPLERIAN DISKS AROUND LOW-MASS PROTOSTARS

    Energy Technology Data Exchange (ETDEWEB)

    Yen, Hsi-Wei [Institute of Astrophysics, National Taiwan University, Taipei 10617, Taiwan (China); Takakuwa, Shigehisa; Ohashi, Nagayoshi; Ho, Paul T. P., E-mail: hwyen@asiaa.sinica.edu.tw [Academia Sinica Institute of Astronomy and Astrophysics, P.O. Box 23-141, Taipei 10617, Taiwan (China)

    2013-07-20

    We performed Submillimeter Array observations in the C{sup 18}O (2-1) emission line toward six Class 0 and I protostars to study rotational motions of their surrounding envelopes and circumstellar material on 100-1000 AU scales. C{sup 18}O (2-1) emission with intensity peaks located at the protostellar positions is detected toward all six sources. The rotational velocities of the protostellar envelopes as a function of radius were measured from the position-velocity diagrams perpendicular to the outflow directions passing through the protostellar positions. Two Class 0 sources, B335 and NGC 1333 IRAS 4B, show no detectable rotational motion, while L1527 IRS (Class 0/I) and L1448-mm (Class 0) exhibit rotational motions with radial profiles of V{sub rot}{proportional_to}r {sup -1.0{+-}0.2} and {proportional_to}r {sup -1.0{+-}0.1}, respectively. The other Class I sources, TMC-1A and L1489 IRS, exhibit the fastest rotational motions among the sample, and their rotational motions have flatter radial profiles of V{sub rot}{proportional_to}r {sup -0.6{+-}0.1} and {proportional_to}r {sup -0.5{+-}0.1}, respectively. The rotational motions with the radial dependence of {approx}r {sup -1} can be interpreted as rotation with a conserved angular momentum in a dynamically infalling envelope, while those with the radial dependence of {approx}r {sup -0.5} can be interpreted as Keplerian rotation. These observational results demonstrate categorization of rotational motions from infalling envelopes to Keplerian-disk formation. Models of the inside-out collapse where the angular momentum is conserved are discussed and compared with our observational results.

  11. UNVEILING THE NEW GENERATION OF STARS IN NGC 604 WITH GEMINI-NIRI

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Cecilia; Bosch, Guillermo L. [Facultad de Ciencias Astronomicas y Geofisicas, Universidad Nacional de La Plata, Paseo de Bosque S/N (B1900FWA), La Plata (Argentina); Barba, Rodolfo H., E-mail: ceciliaf@fcaglp.unlp.edu.ar [Instituto de Ciencias Astronomicas, de la Tierra y del Espacio (ICATE-CONICET), Av. Espana Sur 1512 (J5402DSP), San Juan (Argentina)

    2012-02-15

    We present a near-infrared study focused on the detection and characterization of the youngest stellar component of the NGC 604 giant star-forming region in the Triangulum galaxy (M 33). By means of color-color diagrams derived from the photometry of JHK{sub s} images taken with the Gemini Near Infrared Imaging and Spectrometer (NIRI), we have found 68 candidate massive young stellar objects. The spatial distribution of these sources matches the areas where previous studies suggested that star formation might be taking place, and the high spatial resolution of our deep NIRI imaging allows us to pinpoint the star-forming knots. An analysis of the fraction of objects that show infrared excess suggests that the star formation is still active, supporting the presence of a second generation of stars being born, although the evidence for or against sequential star formation does not seem to be conclusive.

  12. Unveiling network-based functional features through integration of gene expression into protein networks.

    Science.gov (United States)

    Jalili, Mahdi; Gebhardt, Tom; Wolkenhauer, Olaf; Salehzadeh-Yazdi, Ali

    2018-06-01

    Decoding health and disease phenotypes is one of the fundamental objectives in biomedicine. Whereas high-throughput omics approaches are available, it is evident that any single omics approach might not be adequate to capture the complexity of phenotypes. Therefore, integrated multi-omics approaches have been used to unravel genotype-phenotype relationships such as global regulatory mechanisms and complex metabolic networks in different eukaryotic organisms. Some of the progress and challenges associated with integrated omics studies have been reviewed previously in comprehensive studies. In this work, we highlight and review the progress, challenges and advantages associated with emerging approaches, integrating gene expression and protein-protein interaction networks to unravel network-based functional features. This includes identifying disease related genes, gene prioritization, clustering protein interactions, developing the modules, extract active subnetworks and static protein complexes or dynamic/temporal protein complexes. We also discuss how these approaches contribute to our understanding of the biology of complex traits and diseases. This article is part of a Special Issue entitled: Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Sri Lankan livelihoods after the tsunami: searching for entrepreneurs, unveiling relations of power.

    Science.gov (United States)

    Kapadia, Kamal

    2015-01-01

    This paper analyses the performance of aid-funded livelihoods recovery efforts in Sri Lanka following the Indian Ocean tsunami of 26 December 2004, with special attention paid to the effects on the rural poor. It argues that successful livelihoods recovery was hampered by an excessive focus by aid agencies on entrepreneurs and entrepreneurship, and by the lack of a politically informed understanding of the economy. Based on ethnographic and survey-based research, the study demonstrates that the category of 'entrepreneur' is misleading for large parts of the economy. Indeed, the desire to build an entrepreneurial economy actually hampered successful livelihoods recovery in Sri Lanka and, in some cases, reinforced inequitable relations of power. The paper concludes that for livelihoods recovery programmes to be effective, they must be founded on an understanding of the relations of power that constitute the economy; these relations operate across scales, and are historically and geographically specific. © 2014 The Author(s). Disasters © Overseas Development Institute, 2014.

  14. Unveiling of a Trinuclear Cyclic Peroxidovanadate: A Potential Oxidant in Vanadium-Catalyzed Reactions

    Czech Academy of Sciences Publication Activity Database

    Krivosudský, Ondřej; Schwendt, P.; Gyepes, Robert

    2015-01-01

    Roč. 94, č. 13 (2015), s. 6306-6311 ISSN 0020-1669 Institutional support: RVO:61388955 Keywords : NUCLEAR-MAGNETIC-RESONANCE * NMR CHEMICAL-SHIFTS * CRYSTAL-STRUCTURE Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.820, year: 2015

  15. Gr and hp-1 tomato mutants unveil unprecedented interactions between arbuscular mycorrhizal symbiosis and fruit ripening.

    Science.gov (United States)

    Chialva, Matteo; Zouari, Inès; Salvioli, Alessandra; Novero, Mara; Vrebalov, Julia; Giovannoni, James J; Bonfante, Paola

    2016-07-01

    Systemic responses to an arbuscular mycorrhizal fungus reveal opposite phenological patterns in two tomato ripening mutants depending whether ethylene or light reception is involved. The availability of tomato ripening mutants has revealed many aspects of the genetics behind fleshy fruit ripening, plant hormones and light signal reception. Since previous analyses revealed that arbuscular mycorrhizal symbiosis influences tomato berry ripening, we wanted to test the hypothesis that an interplay might occur between root symbiosis and fruit ripening. With this aim, we screened seven tomato mutants affected in the ripening process for their responsiveness to the arbuscular mycorrhizal fungus Funneliformis mosseae. Following their phenological responses we selected two mutants for a deeper analysis: Green ripe (Gr), deficient in fruit ethylene perception and high-pigment-1 (hp-1), displaying enhanced light signal perception throughout the plant. We investigated the putative interactions between ripening processes, mycorrhizal establishment and systemic effects using biochemical and gene expression tools. Our experiments showed that both mutants, notwithstanding a normal mycorrhizal phenotype at root level, exhibit altered arbuscule functionality. Furthermore, in contrast to wild type, mycorrhization did not lead to a higher phosphate concentration in berries of both mutants. These results suggest that the mutations considered interfere with arbuscular mycorrhiza inducing systemic changes in plant phenology and fruits metabolism. We hypothesize a cross talk mechanism between AM and ripening processes that involves genes related to ethylene and light signaling.

  16. Comparative Fecal Metagenomics Unveils Unique Functional Capacity of the Swine Gut

    Science.gov (United States)

    Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health and to food and water safety due to the presence of human pathogens in pig feces. Limited information on the physiological...

  17. Terrorism in Newsweek: Unveiling the Connection between Language, Ideology, and Powe

    Directory of Open Access Journals (Sweden)

    Bambang Trisno Adi

    2016-08-01

    Full Text Available The study analyzes the discourse on terrorism in the Newsweek magazine and exposes how the notion of ideology and power contributes to the hegemonic representations of Muslims and Islam in the post 9/11 attacks on the World Trade Centre (WTC. Two Newsweek articles appeared on the 24th September 2001 were selected. The study employed Fairclough’s Critical Discourse Analysis (CDA; this is a five-stage analytical methodology that perceives language within a three-dimensional framework: text, discourse, and society. The representation of discourse on terrorism, as found in the analysis, supports a conception that media coverage is not merely the representation of facts but also that of ideas which has gone through various considerations incorporating the three key notions of text, discourse and society altogether. The elements within the textual level and discourse level were ideologically used to represent terrorism with regard to its actor, process, and goal, constituting a commonsense as to how it should be perceived. The study concluded that the representation of discourse on terrorism in Newsweek during the post 9/11 period was perceived from what Chomsky considers as the propagandistic approach

  18. Integrated bioinformatic analysis unveils significant genes and pathways in the pathogenesis of supratentorial primitive neuroectodermal tumor

    Directory of Open Access Journals (Sweden)

    Wang G

    2018-04-01

    Full Text Available Guang-Yu Wang,1,* Ling Li,2,* Bo Liu,1 Xiao Han,1 Chun-Hua Wang,1 Ji-Wen Wang3 1Department of Neurosurgery, 2Department of Pediatrics, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, 3Department of Neurology, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Pudong New District, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to explore significant genes and pathways involved in the pathogenesis of supratentorial primitive neuroectodermal tumor (sPNET. Materials and methods: Gene expression profile of GSE14295 was downloaded from publicly available Gene Expression Omnibus (GEO database. Differentially expressed genes (DEGs were screened out in primary sPNET samples compared with normal fetal and adult brain reference