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Sample records for artemis promote homologous

  1. ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2

    OpenAIRE

    Beucher, Andrea; Birraux, Julie; Tchouandong, Leopoldine; Barton, Olivia; Shibata, Atsushi; Conrad, Sandro; Goodarzi, Aaron A.; KREMPLER, ANDREA; Jeggo, Penny; Lo¨brich, Markus

    2009-01-01

    Homologous recombination (HR) and non-homologous end joining (NHEJ) represent distinct pathways for repairing DNA double-strand breaks (DSBs). Previous work implicated Artemis and ATM in an NHEJ-dependent process, which repairs a defined subset of radiation-induced DSBs in G1-phase. Here, we show that in G2, as in G1, NHEJ represents the major DSB-repair pathway whereas HR is only essential for repair of ∼15% of X- or γ-ray-induced DSBs. In addition to requiring the known HR proteins, Brca2, ...

  2. DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.

    Directory of Open Access Journals (Sweden)

    Aya Kurosawa

    Full Text Available Nonhomologous end-joining (NHEJ and homologous recombination (HR are two major pathways for repairing DNA double-strand breaks (DSBs; however, their respective roles in human somatic cells remain to be elucidated. Here we show using a series of human gene-knockout cell lines that NHEJ repairs nearly all of the topoisomerase II- and low-dose radiation-induced DNA damage, while it negatively affects survival of cells harbouring replication-associated DSBs. Intriguingly, we find that loss of DNA ligase IV, a critical NHEJ ligase, and Artemis, an NHEJ factor with endonuclease activity, independently contribute to increased resistance to replication-associated DSBs. We also show that loss of Artemis alleviates hypersensitivity of DNA ligase IV-null cells to low-dose radiation- and topoisomerase II-induced DSBs. Finally, we demonstrate that Artemis-null human cells display increased gene-targeting efficiencies, particularly in the absence of DNA ligase IV. Collectively, these data suggest that DNA ligase IV and Artemis act cooperatively to promote NHEJ, thereby suppressing HR. Our results point to the possibility that HR can only operate on accidental DSBs when NHEJ is missing or abortive, and Artemis may be involved in pathway switching from incomplete NHEJ to HR.

  3. The nuclear protein Artemis promotes AMPK activation by stabilizing the LKB1–AMPK complex

    International Nuclear Information System (INIS)

    Highlights: ► The nuclear protein Artemis physically interacts with AMPKα2. ► Artemis co-localizes with AMPKα2 in the nucleus. ► Artemis promotes phosphorylation and activation of AMPK. ► The interaction between AMPKα2 and LKB1 is stabilized by Artemis. -- Abstract: AMP-activated protein kinase (AMPK) is a hetero-trimeric Ser/Thr kinase composed of a catalytic α subunit and regulatory β and γ subunits; it functions as an energy sensor that controls cellular energy homeostasis. In response to an increased cellular AMP/ATP ratio, AMPK is activated by phosphorylation at Thr172 in the α-subunit by upstream AMPK kinases (AMPKKs), including tumor suppressor liver kinase B1 (LKB1). To elucidate more precise molecular mechanisms of AMPK activation, we performed yeast two-hybrid screening and isolated the complementary DNA (cDNA) encoding the nuclear protein Artemis/DNA cross-link repair 1C (DCLRE1C) as an AMPKα2-binding protein. Artemis was found to co-immunoprecipitate with AMPKα2, and the co-localization of Artemis with AMPKα2 in the nucleus was confirmed by immunofluorescence staining in U2OS cells. Moreover, over-expression of Artemis enhanced the phosphorylation of AMPKα2 and the AMPK substrate acetyl-CoA carboxylase (ACC). Conversely, RNAi-mediated knockdown of Artemis reduced AMPK and ACC phosphorylation. In addition, Artemis markedly increased the physical association between AMPKα2 and LKB1. Taken together, these results suggest that Artemis functions as a positive regulator of AMPK signaling by stabilizing the LKB1–AMPK complex.

  4. The nuclear protein Artemis promotes AMPK activation by stabilizing the LKB1-AMPK complex

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Koji, E-mail: k_nakagawa@pharm.hokudai.ac.jp [Department of Pathophysiology and Therapeutics, Division of Pharmascience, Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Uehata, Yasuko; Natsuizaka, Mitsuteru; Kohara, Toshihisa; Darmanin, Stephanie [Department of Gastroenterology and Hematology, Graduate School of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Asaka, Masahiro [Department of Gastroenterology and Hematology, Graduate School of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Department of Cancer Preventive Medicine, Graduate School of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Takeda, Hiroshi [Department of Pathophysiology and Therapeutics, Division of Pharmascience, Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Department of Gastroenterology and Hematology, Graduate School of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Kobayashi, Masanobu [Department of Cancer Preventive Medicine, Graduate School of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); School of Nursing and Social Services, Health Sciences University of Hokkaido, Ishikari-Toubetsu, Hokkaido 061-0293 (Japan)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer The nuclear protein Artemis physically interacts with AMPK{alpha}2. Black-Right-Pointing-Pointer Artemis co-localizes with AMPK{alpha}2 in the nucleus. Black-Right-Pointing-Pointer Artemis promotes phosphorylation and activation of AMPK. Black-Right-Pointing-Pointer The interaction between AMPK{alpha}2 and LKB1 is stabilized by Artemis. -- Abstract: AMP-activated protein kinase (AMPK) is a hetero-trimeric Ser/Thr kinase composed of a catalytic {alpha} subunit and regulatory {beta} and {gamma} subunits; it functions as an energy sensor that controls cellular energy homeostasis. In response to an increased cellular AMP/ATP ratio, AMPK is activated by phosphorylation at Thr172 in the {alpha}-subunit by upstream AMPK kinases (AMPKKs), including tumor suppressor liver kinase B1 (LKB1). To elucidate more precise molecular mechanisms of AMPK activation, we performed yeast two-hybrid screening and isolated the complementary DNA (cDNA) encoding the nuclear protein Artemis/DNA cross-link repair 1C (DCLRE1C) as an AMPK{alpha}2-binding protein. Artemis was found to co-immunoprecipitate with AMPK{alpha}2, and the co-localization of Artemis with AMPK{alpha}2 in the nucleus was confirmed by immunofluorescence staining in U2OS cells. Moreover, over-expression of Artemis enhanced the phosphorylation of AMPK{alpha}2 and the AMPK substrate acetyl-CoA carboxylase (ACC). Conversely, RNAi-mediated knockdown of Artemis reduced AMPK and ACC phosphorylation. In addition, Artemis markedly increased the physical association between AMPK{alpha}2 and LKB1. Taken together, these results suggest that Artemis functions as a positive regulator of AMPK signaling by stabilizing the LKB1-AMPK complex.

  5. Lymphopoiesis in transgenic mice over-expressing Artemis.

    Science.gov (United States)

    Rivera-Munoz, P; Abramowski, V; Jacquot, S; André, P; Charrier, S; Lipson-Ruffert, K; Fischer, A; Galy, A; Cavazzana, M; de Villartay, J-P

    2016-02-01

    Artemis is a factor of the non-homologous end joining pathway involved in DNA double-strand break repair that has a critical role in V(D)J recombination. Mutations in DCLRE1C/ARTEMIS gene result in radiosensitive severe combined immunodeficiency in humans owing to a lack of mature T and B cells. Given the known drawbacks of allogeneic hematopoietic stem cell transplantation (HSCT), gene therapy appears as a promising alternative for these patients. However, the safety of an unregulated expression of Artemis has to be established. We developed a transgenic mouse model expressing human Artemis under the control of the strong CMV early enhancer/chicken beta actin promoter through knock-in at the ROSA26 locus to analyze this issue. Transgenic mice present a normal development, maturation and function of T and B cells with no signs of lymphopoietic malignancies for up to 15 months. These results suggest that the over-expression of Artemis in mice (up to 40 times) has no deleterious effects in early and mature lymphoid cells and support the safety of gene therapy as a possible curative treatment for Artemis-deficient patients. PMID:26361272

  6. Amarynthian Artemis

    OpenAIRE

    Fotini Koutsafti

    2008-01-01

    Fotini Koutsafti studied, inter alia, History and Archaeology in the Aristotle University of Thesaloniki, Philosophy in the Wurzburg University in Germany and later involved in literature, writing poems, prose and essays. She composed the poetry collection "Amarynthian Artemis" in 2007, a little before she passed away. Despite the fact that Intellectum Journal does not publish poetry, it was decided to make an exception in order to honour her memory and thus include the particular poem in the...

  7. Artemi Moiseev

    CERN Multimedia

    The ATLAS LAr community heard with great shock that Artemi Moiseev died on 18th August 2002 after a short, serious illness in hospital. His career as a physicist included outstanding contributions to several experiments using a wide variety of technologies. He was the leader of teams engaged in: the Mirabel bubble chamber working closely with the Saclay team, several spectrometer experiments at the 70 GeV accelerator at Serpukhov, in particular looking at Charm production, a proposal for a large LAr calorimeter project for the UNK, the R&D phase of the LHC heavily contributing to RD33. Right from the beginning of the ATLAS LAr activity he was one of the major carriers of the hadronic end-cap calorimeter project. His group in Protvino took over the construction and assembly of a major fraction of the hadronic calorimeter modules. This work is now close to completion. Artemi was also partly engaged in the cryostat area. Artemi contributed with a wide interest to the overall ongoing work of th...

  8. Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex

    Science.gov (United States)

    Chang, Howard H.Y.; Lieber, Michael R.

    2016-01-01

    Artemis is a vertebrate nuclease with both endo- and exonuclease activities that acts on a wide range of nucleic acid substrates. It is the main nuclease in the non-homologous DNA end-joining pathway (NHEJ). Not only is Artemis important for the repair of DNA double-strand breaks (DSBs) in NHEJ, it is essential in opening the DNA hairpin intermediates that are formed during V(D)J recombination. Thus, humans with Artemis deficiencies do not have T- or B-lymphocytes and are diagnosed with severe combined immunodeficiency (SCID). While Artemis is the only vertebrate nuclease capable of opening DNA hairpins, it has also been found to act on other DNA substrates that share common structural features. Here, we discuss the key structural features that all Artemis DNA substrates have in common, thus providing a basis for understanding how this structure-specific nuclease recognizes its DNA targets. PMID:27198222

  9. DNA Ligase IV and Artemis Act Cooperatively to Suppress Homologous Recombination in Human Cells: Implications for DNA Double-Strand Break Repair

    OpenAIRE

    Aya Kurosawa; Shinta Saito; Sairei So; Mitsumasa Hashimoto; Kuniyoshi Iwabuchi; Haruka Watabe; Noritaka Adachi

    2013-01-01

    Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are two major pathways for repairing DNA double-strand breaks (DSBs); however, their respective roles in human somatic cells remain to be elucidated. Here we show using a series of human gene-knockout cell lines that NHEJ repairs nearly all of the topoisomerase II- and low-dose radiation-induced DNA damage, while it negatively affects survival of cells harbouring replication-associated DSBs. Intriguingly, we find that loss of ...

  10. Functions and regulation of artemis. A goddess in the maintenance of genome integrity

    International Nuclear Information System (INIS)

    Artemis is a structure-specific endonuclease when associated with and phosphorylated by DNA-dependent protein kinase catalytic subunit. This structure-specific endonuclease is responsible for the resolution of hairpin coding ends in V(D)J recombination. In DNA double-strand break repair, Artemis is implicated in the end-processing step of the non-homologous end-joining (NHEJ) pathway. Recently, we have demonstrated that the involvement of Artemis in NHEJ depends on the type of DNA damage. Interestingly, recent evidence suggests that the end-processing activity is not the only function of Artemis. Indeed, Artemis is rapidly phosphorylated by ataxia telangiectasia mutated in response to DNA damage, and such phosphorylation of Artemis appears to be involved in the regulation of cell cycle checkpoints. These findings suggest that Artemis is a multifunctional protein participating in the maintenance of genome integrity at two distinct levels; one at the end processing step of NHEJ, and the other at the signaling pathway of cell cycle regulation. Therefore, understanding Artemis function may give us profound insights into the DNA repair network. In this review, we summarize the functions and regulation of Artemis. (author)

  11. A PHF8 homolog in C. elegans promotes DNA repair via homologous recombination.

    Directory of Open Access Journals (Sweden)

    Changrim Lee

    Full Text Available PHF8 is a JmjC domain-containing histone demethylase, defects in which are associated with X-linked mental retardation. In this study, we examined the roles of two PHF8 homologs, JMJD-1.1 and JMJD-1.2, in the model organism C. elegans in response to DNA damage. A deletion mutation in either of the genes led to hypersensitivity to interstrand DNA crosslinks (ICLs, while only mutation of jmjd-1.1 resulted in hypersensitivity to double-strand DNA breaks (DSBs. In response to ICLs, JMJD-1.1 did not affect the focus formation of FCD-2, a homolog of FANCD2, a key protein in the Fanconi anemia pathway. However, the dynamic behavior of RPA-1 and RAD-51 was affected by the mutation: the accumulations of both proteins at ICLs appeared normal, but their subsequent disappearance was retarded, suggesting that later steps of homologous recombination were defective. Similar changes in the dynamic behavior of RPA-1 and RAD-51 were seen in response to DSBs, supporting a role of JMJD-1.1 in homologous recombination. Such a role was also supported by our finding that the hypersensitivity of jmjd-1.1 worms to ICLs was rescued by knockdown of lig-4, a homolog of Ligase 4 active in nonhomologous end-joining. The hypersensitivity of jmjd-1.1 worms to ICLs was increased by rad-54 knockdown, suggesting that JMJD-1.1 acts in parallel with RAD-54 in modulating chromatin structure. Indeed, the level of histone H3 Lys9 tri-methylation, a marker of heterochromatin, was higher in jmjd-1.1 cells than in wild-type cells. We conclude that the histone demethylase JMJD-1.1 influences homologous recombination either by relaxing heterochromatin structure or by indirectly regulating the expression of multiple genes affecting DNA repair.

  12. Processing of 3'-Phosphoglycolate-Terminated DNA Double-StrandBreaks by Artemis Nuclease

    Energy Technology Data Exchange (ETDEWEB)

    Povrik, Lawrence F.; Zhou, Tong; Zhou, Ruizhe; Cowan, Morton J.; Yannone, Steven M.

    2005-10-01

    The Artemis nuclease is required for V(D)J recombination and for repair of an as yet undefined subset of radiation-induced DNA double-strand breaks. To assess the possibility that Artemis functions on oxidatively modified double-strand break termini, its activity toward model DNA substrates, bearing either 3{prime}-hydroxyl or 3{prime}-phosphoglycolate moieties, was examined. A 3{prime}-phosphoglycolate had little effect on Artemis-mediated trimming of long 3{prime} overhangs (>9 nucleotides), which were efficiently trimmed to 4-5 nucleotides. However, 3{prime}-phosphoglycolates on overhangs of 4-5 bases promoted selective Artemis-mediated trimming of a single 3{prime}-terminal nucleotide, while at least 2 nucleotides were trimmed from identical hydroxyl-terminated substrates. Artemis also efficiently removed a single nucleotide from a phosphoglycolate-terminated 3-base 3{prime} overhang, while leaving an analogous hydroxyl-terminated overhang largely intact. Such removal was dependent upon Ku, DNA-dependent protein kinase, and ATP. Together, these data suggest that Artemis-mediated cleavage of 3{prime} overhangs requires a minimum of 2 nucleotides, or a nucleotide plus a phosphoglycolate, 3{prime} to the cleavage site. Shorter 3{prime}-phosphoglycolate-terminated overhangs and blunt ends were also processed by Artemis, but much less efficiently. Consistent with the in vitro substrate specificity of Artemis, human cells lacking Artemis exhibited hypersensitivity to X-rays, bleomycin and neocarzinostatin, which all induce 3{prime}-phosphoglycolate-terminated double-strand breaks. Collectively, these results suggest that 3{prime}-phosphoglycolate termini and/or specific classes of DNA ends that arise from such blocked termini are relevant Artemis substrates in vivo.

  13. Czech Companies Involved in the ARTEMIS Programme

    Czech Academy of Sciences Publication Activity Database

    Kadlec, Jiří

    -, special issue (2013), s. 4-5. ISSN 1210-9592 R&D Projects: GA MŠk(CZ) LE13020 Keywords : ARTEMIS JU * embedded systems * european technology platforms * FP7 * ICT * microelectronics * ENIAC JU Subject RIV: AF - Documentation, Librarianship, Information Studies http://library.utia.cas.cz/separaty/2013/ZS/kadlec-czech companies involved in the artemis programme.pdf

  14. Differences in sensitivity to DNA-damaging agents between XRCC4- and artemis-deficient human cells

    International Nuclear Information System (INIS)

    Non-homologous end-joining (NHEJ) is the predominant pathway for the repair of DNA double-strand breaks (DSBs) in human cells. XRCC4 is indispensable to NHEJ and functions together with DNA ligase IV in the rejoining of broken DNA ends. Artemis is a nuclease required for trimming of some, but not all, types of broken DNA ends prior to rejoining by the DNA ligase IV/XRCC4 complex. To better understand the roles of these factors, we generated XRCC4- and Artemis-deficient cells from the human colon adenocarcinoma cell line HCT116 by gene targeting and examined their cellular responses to several DNA-damaging agents including X-rays. As anticipated, kinetic analyses of γ-H2AX foci and chromosomal aberrations after ionizing radiation (IR) demonstrated a serious incompetence of DSB repair in the XRCC4-deficient cells, and relatively moderate impairment in the Artemis-deficient cells. The XRCC4-deficient cells were highly sensitive to etoposide and 5-fluoro-2'-deoxyuridine as well as IR, and moderately sensitive to camptothecin, methyl methanesulfonate, cisplatin, mitomycin C, aphidicolin and hydroxyurea, compared to the parental HCT116 cells. The Artemis-deficient cells were not as sensitive as the XRCC4-deficient cells, except to cisplatin and mitomycin C. By contrast, the Artemis-deficient cells were significantly more resistant to hydroxyurea than the parental cells. These observations suggest that Artemis also functions in some DNA damage response pathways other than NHEJ in human cells. (author)

  15. SCID patients with ARTEMIS vs RAG deficiencies following HCT: increased risk of late toxicity in ARTEMIS-deficient SCID

    OpenAIRE

    Schuetz, Catharina; Neven, Benedicte; Dvorak, Christopher C.; Leroy, Sandrine; Ege, Markus J.; Pannicke, Ulrich; Schwarz, Klaus; Schulz, Ansgar S.; Hoenig, Manfred; Sparber-Sauer, Monika; Gatz, Susanne A.; Denzer, Christian; Blanche, Stephane; Moshous, Despina; Picard, Capucine

    2014-01-01

    No difference in survival, early toxicity, or occurrence of tumors between ARTEMIS and RAG-deficient SCID.ARTEMIS-deficient patients develop late toxicity following HCT: growth retardation, endocrinologic deficiencies, and dental abnormalities.

  16. Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans.

    Science.gov (United States)

    McClendon, T Brooke; Sullivan, Meghan R; Bernstein, Kara A; Yanowitz, Judith L

    2016-05-01

    Homologous recombination (HR) repairs cytotoxic DNA double-strand breaks (DSBs) with high fidelity. Deficiencies in HR result in genome instability. A key early step in HR is the search for and invasion of a homologous DNA template by a single-stranded RAD-51 nucleoprotein filament. The Shu complex, composed of a SWIM domain-containing protein and its interacting RAD51 paralogs, promotes HR by regulating RAD51 filament dynamics. Despite Shu complex orthologs throughout eukaryotes, our understanding of its function has been most extensively characterized in budding yeast. Evolutionary analysis of the SWIM domain identified Caenorhabditis elegans sws-1 as a putative homolog of the yeast Shu complex member Shu2. Using a CRISPR-induced nonsense allele of sws-1, we show that sws-1 promotes HR in mitotic and meiotic nuclei. sws-1 mutants exhibit sensitivity to DSB-inducing agents and fail to form mitotic RAD-51 foci following treatment with camptothecin. Phenotypic similarities between sws-1 and the two RAD-51 paralogs rfs-1 and rip-1 suggest that they function together. Indeed, we detect direct interaction between SWS-1 and RIP-1 by yeast two-hybrid assay that is mediated by the SWIM domain in SWS-1 and the Walker B motif in RIP-1 Furthermore, RIP-1 bridges an interaction between SWS-1 and RFS-1, suggesting that RIP-1 facilitates complex formation with SWS-1 and RFS-1 We propose that SWS-1, RIP-1, and RFS-1 compose a C. elegans Shu complex. Our work provides a new model for studying Shu complex disruption in the context of a multicellular organism that has important implications as to why mutations in the human RAD51 paralogs are associated with genome instability. PMID:26936927

  17. ARTEMIS: first naval staring IRST in service

    Science.gov (United States)

    Fontanella, Jean-Claude; Delacourt, Dominique; Klein, Yves

    2010-04-01

    Dealing with military and asymmetric threats represents a key issue for any military vessel in various environment. In order to support ship's self protection, Thales has designed a new generation of naval InfraRed Search and Track (IRST) called ARTEMIS. It has been selected to equip Future European Multi Roles Frigates (FREMM). ARTEMIS is a fully new passive staring IRST system capable of automatically detecting and tracking both air and surface targets simultaneously. It is able to detect and track maneuvering and stealthy new threats as well as surface asymmetric threats. The paper describes the novelties of the ARTEMIS staring architecture and some of its technologies. It describes also the advantages offered by this new concept of electro-optical surveillance with full static sensor heads compared to existing and future solutions, and its capabilities to comply with future integrated masts standards. The paper concludes by a presentation of the product for the French Navy.

  18. Characterization of the Promoter of a Homolog of Maize MADS-Box Gene m18

    Institute of Scientific and Technical Information of China (English)

    QIN Hui-juan; PAN Hong; FAN Xian-wei; WU Qiao; LI You-zhi

    2014-01-01

    Maize (Zea mays L.) is one of the world’s major food crops, and often suffers from tremendous yield loss caused by abiotic stresses. The MADS-box genes are known to play versatile roles in plants, controlling plant responses to multiple abiotic stresses. However, understanding of regulation of their expressions by the conventional loss-of-function approach is very dififcult. So far, regulation of MADS-box gene expression is little known. The best approach to retrieve expression regulation of this category of genes is to characterize expression of their promoters. In this study, the promoter of a homolog (GenBank accession no. EC864166) of maize MADS-box gene m18 was cloned by way of genome-walking PCR, named Pro66. Predicative analysis indicated that Pro66 contains more than one TATA box and multiple cis-acting environmental conditions-responsive elements (ECREs). Pro66 could drive expression of theβ-glucuronidase (GUS)-encoding gene in maize, and heterologous expression of GUS in red pepper stressed by water deifcit, salt, copper, iron deifciency, heat, cold, and grown under short and long photoperiods, echoing predicative ECREs. Conclusively, maize MADS-box gene m18 likely plays versatile functions in maize response to multiple abiotic stresses due to the promoter with multiple cis-acting elements. The complex arrangement of multiple cis-acting elements in the promoter features meticulously regulated expression of m18. The results give informative clues for heterologous utilisation of the promoters in monocot and dicot species. The copy of the ECREs and heterologous expression of the promoter in dicot species are also discussed.

  19. Lunabotics Mining: Evolution of ARTEMIS PRIME

    Science.gov (United States)

    Bertke, Sarah; Gries, Christine; Huff, Amanda; Logan, Brittany; Oliver, Kaitlin; Rigney, Erica; Tyree, Whitney; Young, Maegan

    2010-01-01

    This slide presentation reviews the development of Amassing Regolith with Topper Engineers eMploying Innovative Solutions (ARTEMIS) in a competition to develop robotic lunar mining capabilities. The goal of the competition was to design, build and operate a remotely controlled device that is capable of excavating, transporting and discharging lunar regolith simulant in a lunar environment over a 13 minute period.

  20. TDP1 promotes assembly of non-homologous end joining protein complexes on DNA.

    Science.gov (United States)

    Heo, Jinho; Li, Jing; Summerlin, Matthew; Hays, Annette; Katyal, Sachin; McKinnon, Peter J; Nitiss, Karin C; Nitiss, John L; Hanakahi, Leslyn A

    2015-06-01

    The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. In tumor cells, the ability to repair DSBs predicts response to radiation and many cytotoxic anti-cancer drugs. DSB repair pathways include homologous recombination and non-homologous end joining (NHEJ). NHEJ is a template-independent mechanism, yet many NHEJ repair products carry limited genetic changes, which suggests that NHEJ includes mechanisms to minimize error. Proteins required for mammalian NHEJ include Ku70/80, the DNA-dependent protein kinase (DNA-PKcs), XLF/Cernunnos and the XRCC4:DNA ligase IV complex. NHEJ also utilizes accessory proteins that include DNA polymerases, nucleases, and other end-processing factors. In yeast, mutations of tyrosyl-DNA phosphodiesterase (TDP1) reduced NHEJ fidelity. TDP1 plays an important role in repair of topoisomerase-mediated DNA damage and 3'-blocking DNA lesions, and mutation of the human TDP1 gene results in an inherited human neuropathy termed SCAN1. We found that human TDP1 stimulated DNA binding by XLF and physically interacted with XLF to form TDP1:XLF:DNA complexes. TDP1:XLF interactions preferentially stimulated TDP1 activity on dsDNA as compared to ssDNA. TDP1 also promoted DNA binding by Ku70/80 and stimulated DNA-PK activity. Because Ku70/80 and XLF are the first factors recruited to the DSB at the onset of NHEJ, our data suggest a role for TDP1 during the early stages of mammalian NHEJ. PMID:25841101

  1. APLF promotes the assembly and activity of non-homologous end joining protein complexes.

    Science.gov (United States)

    Grundy, Gabrielle J; Rulten, Stuart L; Zeng, Zhihong; Arribas-Bosacoma, Raquel; Iles, Natasha; Manley, Katie; Oliver, Antony; Caldecott, Keith W

    2013-01-01

    Non-homologous end joining (NHEJ) is critical for the maintenance of genetic integrity and DNA double-strand break (DSB) repair. NHEJ is regulated by a series of interactions between core components of the pathway, including Ku heterodimer, XLF/Cernunnos, and XRCC4/DNA Ligase 4 (Lig4). However, the mechanisms by which these proteins assemble into functional protein-DNA complexes are not fully understood. Here, we show that the von Willebrand (vWA) domain of Ku80 fulfills a critical role in this process by recruiting Aprataxin-and-PNK-Like Factor (APLF) into Ku-DNA complexes. APLF, in turn, functions as a scaffold protein and promotes the recruitment and/or retention of XRCC4-Lig4 and XLF, thereby assembling multi-protein Ku complexes capable of efficient DNA ligation in vitro and in cells. Disruption of the interactions between APLF and either Ku80 or XRCC4-Lig4 disrupts the assembly and activity of Ku complexes, and confers cellular hypersensitivity and reduced rates of chromosomal DSB repair in avian and human cells, respectively. Collectively, these data identify a role for the vWA domain of Ku80 and a molecular mechanism by which DNA ligase proficient complexes are assembled during NHEJ in mammalian cells, and reveal APLF to be a structural component of this critical DSB repair pathway. PMID:23178593

  2. Cults of Artemis in Ancient Greece

    OpenAIRE

    Rangos, Spyridon

    1996-01-01

    Artemis was a cruel and wild goddess. Her mythological apparatus was replete with blood and death. Her cults displayed awe-inspiring elements of primitivism. Together with Dionysus, to whom she is mythologically and ritually related, she presents a riddle for the student who tries to understand her place in the Greek pantheon. In accordance with the modern alertness to the dangers of oversimplification lurking behind sweeping general accounts, I have chosen six particular Artemisian cults in ...

  3. Coordinateendonucleolytic 5' and 3' trimming of terminally blocked blunt DNA double-strand break ends by Artemis nuclease and DNA-dependent protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Povirk, Lawrence; Yannone, Steven M.; Khan, Imran S.; Zhou, Rui-Zhe; Zhou, Tong; Valerie, Kristoffer; F., Lawrence

    2008-02-18

    Previous work showed that, in the presence of DNA-PK, Artemis slowly trims 3'-phosphoglycolate-terminated blunt ends. To examine the trimming reaction in more detail, long internally labeled DNA substrates were treated with Artemis. In the absence of DNA-PK, Artemis catalyzed extensive 5' {yields} 3' exonucleolytic resection of double-stranded DNA. This resection required a 5'-phosphate but did not require ATP, and was accompanied by endonucleolytic cleavage of the resulting 3' overhang. In the presence of DNA-PK, Artemis-mediated trimming was more limited, was ATP-dependent, and did not require a 5'-phosphate. For a blunt end with either a 3'-phosphoglycolate or 3'-hydroxyl terminus, endonucleolytic trimming of 2-4 nucleotides from the 3'-terminal strand was accompanied by trimming of 6 nucleotides from the 5'-terminal strand. The results suggest that autophosphorylated DNA-PK suppresses the exonuclease activity of Artemis toward blunt-ended DNA, and promotes slow and limited endonucleolytic trimming of the 5'-terminal strand, resulting in short 3' overhangs that are trimmed endonucleolytically. Thus, Artemis and DNA-PK can convert terminally blocked DNA ends of diverse geometry and chemical structure to a form suitable for polymerase mediated patching and ligation, with minimal loss of terminal sequence. Such processing could account for the very small deletions often found at DNA double-strand break repair sites.

  4. Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters.

    Science.gov (United States)

    Montiel, Daniel; Kang, Hahk-Soo; Chang, Fang-Yuan; Charlop-Powers, Zachary; Brady, Sean F

    2015-07-21

    Large-scale sequencing of prokaryotic (meta)genomic DNA suggests that most bacterial natural product gene clusters are not expressed under common laboratory culture conditions. Silent gene clusters represent a promising resource for natural product discovery and the development of a new generation of therapeutics. Unfortunately, the characterization of molecules encoded by these clusters is hampered owing to our inability to express these gene clusters in the laboratory. To address this bottleneck, we have developed a promoter-engineering platform to transcriptionally activate silent gene clusters in a model heterologous host. Our approach uses yeast homologous recombination, an auxotrophy complementation-based yeast selection system and sequence orthogonal promoter cassettes to exchange all native promoters in silent gene clusters with constitutively active promoters. As part of this platform, we constructed and validated a set of bidirectional promoter cassettes consisting of orthogonal promoter sequences, Streptomyces ribosome binding sites, and yeast selectable marker genes. Using these tools we demonstrate the ability to simultaneously insert multiple promoter cassettes into a gene cluster, thereby expediting the reengineering process. We apply this method to model active and silent gene clusters (rebeccamycin and tetarimycin) and to the silent, cryptic pseudogene-containing, environmental DNA-derived Lzr gene cluster. Complete promoter refactoring and targeted gene exchange in this "dead" cluster led to the discovery of potent indolotryptoline antiproliferative agents, lazarimides A and B. This potentially scalable and cost-effective promoter reengineering platform should streamline the discovery of natural products from silent natural product biosynthetic gene clusters. PMID:26150486

  5. Constitutive expression of human coagulating factor IX in HeLa cells by homologous recombination of the promoter

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Constitutive expression of hFIX protein in nonhepatocytes wasstudied. The gene targeting vector was constructed and transferred into HeLa cells. With the detection system of PCR, we demonstrated that the endogenous hFIX promoter was replaced with an hCMV promoter when targeted insertion of the constructor was directed by the sequence homology. The expression of hFIX in the modified HeLa cells, 11.2 ng/106 cell/24 h, strongly suggested that hFIX gene could be activated by a powerful promoter in nonhepatocytes. The results would make it possible to examine the feasibility of re-regulate gene expression by promoter replacement.

  6. The adiponectin receptor homologs in C. elegans promote energy utilization and homeostasis

    DEFF Research Database (Denmark)

    Svensson, Emma; Olsen, Louise Cathrine Braun; Mörck, Catarina;

    2011-01-01

    Adiponectin is an adipokine with insulin-sensitising actions in vertebrates. Its receptors, AdipoR1 and AdipoR2, are PAQR-type proteins with 7-transmembrane domains and topologies reversed that of GPCR's, i.e. their C-termini are extracellular. We identified three adiponectin receptor homologs in...

  7. Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs.

    Directory of Open Access Journals (Sweden)

    Zita Nagy

    2016-02-01

    Full Text Available DNA lesions are sensed by a network of proteins that trigger the DNA damage response (DDR, a signaling cascade that acts to delay cell cycle progression and initiate DNA repair. The Mediator of DNA damage Checkpoint protein 1 (MDC1 is essential for spreading of the DDR signaling on chromatin surrounding Double Strand Breaks (DSBs by acting as a scaffold for PI3K kinases and for ubiquitin ligases. MDC1 also plays a role both in Non-Homologous End Joining (NHEJ and Homologous Recombination (HR repair pathways. Here we identify two novel binding partners of MDC1, the poly (ADP-ribose Polymerases (PARPs TNKS1 and 2. We find that TNKSs are recruited to DNA lesions by MDC1 and regulate DNA end resection and BRCA1A complex stabilization at lesions leading to efficient DSB repair by HR and proper checkpoint activation.

  8. Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs.

    Science.gov (United States)

    Nagy, Zita; Kalousi, Alkmini; Furst, Audrey; Koch, Marc; Fischer, Benoit; Soutoglou, Evi

    2016-02-01

    DNA lesions are sensed by a network of proteins that trigger the DNA damage response (DDR), a signaling cascade that acts to delay cell cycle progression and initiate DNA repair. The Mediator of DNA damage Checkpoint protein 1 (MDC1) is essential for spreading of the DDR signaling on chromatin surrounding Double Strand Breaks (DSBs) by acting as a scaffold for PI3K kinases and for ubiquitin ligases. MDC1 also plays a role both in Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR) repair pathways. Here we identify two novel binding partners of MDC1, the poly (ADP-ribose) Polymerases (PARPs) TNKS1 and 2. We find that TNKSs are recruited to DNA lesions by MDC1 and regulate DNA end resection and BRCA1A complex stabilization at lesions leading to efficient DSB repair by HR and proper checkpoint activation. PMID:26845027

  9. Ubiquitylation of Rad51d Mediated by E3 Ligase Rnf138 Promotes the Homologous Recombination Repair Pathway

    Science.gov (United States)

    Han, Deqiang; Liang, Junbo; Lu, Yalan; Xu, Longchang; Miao, Shiying; Lu, Lin-Yu; Song, Wei; Wang, Linfang

    2016-01-01

    Ubiquitylation has an important role as a signal transducer that regulates protein function, subcellular localization, or stability during the DNA damage response. In this study, we show that Ring domain E3 ubiquitin ligases RNF138 is recruited to DNA damage site quickly. And the recruitment is mediated through its Zinc finger domains. We further confirm that RNF138 is phosphorylated by ATM at Ser124. However, the phosphorylation was dispensable for recruitment to the DNA damage site. Our findings also indicate that RAD51 assembly at DSB sites following irradiation is dramatically affected in RNF138-deficient cells. Hence, RNF138 is likely involved in regulating homologous recombination repair pathway. Consistently, efficiency of homologous recombination decreased observably in RNF138-depleted cells. In addition, RNF138-deficient cell is hypersensitive to DNA damage insults, such as IR and MMS. And the comet assay confirmed that RNF138 directly participated in DNA damage repair. Moreover, we find that RAD51D directly interacted with RNF138. And the recruitment of RAD51D to DNA damage site is delayed and unstable in RNF138-depleted cells. Taken together, these results suggest that RNF138 promotes the homologous recombination repair pathway. PMID:27195665

  10. Preparation to optical communication experiments with geostationary satellite ARTEMIS

    Science.gov (United States)

    Kuzkov, V. P.; Medveskij, M. M.; Yatskiv, D. Ya.; Nedashkovskij, V. N.; Suberlak, V. R.; Glushchenko, Yu. M.; Peretyatko, M. M.; Eremenko, N. A.

    2003-08-01

    We considered necessary conditions and performed expedient calculations for performing laser communication link experiments with geostationary satellite ARTEMIS (ESA). The scheme was proposed of performing these experiments by using two telescopes. The results of observation of the satellite are presented.

  11. EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair

    Science.gov (United States)

    Wu, Yuehan; Lee, Suk-Hee; Williamson, Elizabeth A.; Reinert, Brian L.; Cho, Ju Hwan; Xia, Fen; Jaiswal, Aruna Shanker; Srinivasan, Gayathri; Patel, Bhavita; Brantley, Alexis; Zhou, Daohong; Shao, Lijian; Pathak, Rupak; Hauer-Jensen, Martin; Singh, Sudha; Kong, Kimi; Wu, Xaiohua; Kim, Hyun-Suk; Beissbarth, Timothy; Gaedcke, Jochen; Burma, Sandeep; Nickoloff, Jac A.; Hromas, Robert A.

    2015-01-01

    Replication fork stalling and collapse is a major source of genome instability leading to neoplastic transformation or cell death. Such stressed replication forks can be conservatively repaired and restarted using homologous recombination (HR) or non-conservatively repaired using micro-homology mediated end joining (MMEJ). HR repair of stressed forks is initiated by 5’ end resection near the fork junction, which permits 3’ single strand invasion of a homologous template for fork restart. This 5’ end resection also prevents classical non-homologous end-joining (cNHEJ), a competing pathway for DNA double-strand break (DSB) repair. Unopposed NHEJ can cause genome instability during replication stress by abnormally fusing free double strand ends that occur as unstable replication fork repair intermediates. We show here that the previously uncharacterized Exonuclease/Endonuclease/Phosphatase Domain-1 (EEPD1) protein is required for initiating repair and restart of stalled forks. EEPD1 is recruited to stalled forks, enhances 5’ DNA end resection, and promotes restart of stalled forks. Interestingly, EEPD1 directs DSB repair away from cNHEJ, and also away from MMEJ, which requires limited end resection for initiation. EEPD1 is also required for proper ATR and CHK1 phosphorylation, and formation of gamma-H2AX, RAD51 and phospho-RPA32 foci. Consistent with a direct role in stalled replication fork cleavage, EEPD1 is a 5’ overhang nuclease in an obligate complex with the end resection nuclease Exo1 and BLM. EEPD1 depletion causes nuclear and cytogenetic defects, which are made worse by replication stress. Depleting 53BP1, which slows cNHEJ, fully rescues the nuclear and cytogenetic abnormalities seen with EEPD1 depletion. These data demonstrate that genome stability during replication stress is maintained by EEPD1, which initiates HR and inhibits cNHEJ and MMEJ. PMID:26684013

  12. Artemis JU and Eniac JU Projects with Czech Participation

    Czech Academy of Sciences Publication Activity Database

    Kadlec, Jiří; Nedvědová, K.

    -, special issue (2013), s. 6-9. ISSN 1210-9592 R&D Projects: GA MŠk(CZ) LE13020 Keywords : ARTEMIS JU * ENIAC JU * embedded systems * microelectronics * European Technology Platforms * FP7 * ICT Subject RIV: AF - Documentation, Librarianship, Information Studies http://library.utia.cas.cz/separaty/2013/ZS/kadlec-artemis ju and eniac ju projects with czech participation.pdf

  13. Efficient generation of double heterologous promoter controlled oncolytic adenovirus vectors by a single homologous recombination step in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Wildner Oliver

    2006-08-01

    Full Text Available Abstract Background Oncolytic adenoviruses are promising agents for the multimodal treatment of cancer. However, tumor-selectivity is crucial for their applicability in patients. Recent studies by several groups demonstrated that oncolytic adenoviruses with tumor-/tissue-specific expression of the E1 and E4 genes, which are pivotal for adenoviral replication, have a specificity profile that is superior to viruses that solely target the expression of E1 or E4 genes. Presently the E1 and E4 regions are modified in a time consuming sequential fashion. Results Based on the widely used adenoviral cloning system AdEasy we generated a novel transfer vector that allows efficient and rapid generation of conditionally replication-competent adenovirus type 5 based vectors with the viral E1 and E4 genes under the transcriptional control of heterologous promoters. For insertion of the promoters of interest our transfer vector has two unique multiple cloning sites. Additionally, our shuttle plasmid allows encoding of a transgene within the E1A transcription unit. The modifications, including E1 mutations, are introduced into the adenoviral genome by a single homologous recombination step in Escherichia coli. Subsequently infectious viruses are rescued from plasmids. As a proof-of-concept we generated two conditionally replication-competent adenoviruses Ad.Ki•COX and Ad.COX•Ki with the promoters of the Ki-67 protein and the cyclooxygenase-2 (COX-2 driving E1 and E4 and vice versa. Conclusion We demonstrated with our cloning system efficient generation of double heterologous promoter controlled oncolytic adenoviral vectors by a single homologous recombination step in bacteria. The generated viruses showed preferential replication in tumor cells and in a subcutaneous HT-29 colon cancer xenograft model the viruses demonstrated significant oncolytic activity comparable with dl327.

  14. Isolation and expression analysis of a LEAFY/FLORICAULA homolog and its promoter from London plane (Platanus acerifolia Willd.).

    Science.gov (United States)

    Lu, Shunjiao; Li, Zhineng; Zhang, Jiaqi; Yi, Shuangshuang; Liu, Lei; Bao, Manzhu; Liu, Guofeng

    2012-10-01

    The LEAFY/FLORICAULA (LFY/FLO) homologous genes are necessary for normal flower development in diverse angiosperm species. To understand the genetic and molecular mechanisms underlying floral initiation and development in Platanaceae, an early divergent eudicot family consisting of large monoecious trees, we isolated a homolog of LFY/FLO, PlacLFY, and its promoter from London plane (Platanus acerifolia). PlacLFY is 1,419 bp in length, with an ORF of 1,122 bp encoding a predicted polypeptide of 374 amino acids and 5'/3'-UTR of 54 and 213 bp, respectively. The putative PlacLFY protein showed a high degree of identity (56-84 %) with LFY/FLO homologs from other species, including two highly conserved regions, the N and C domains, and a less conserved amino-terminal proline-rich region. Real-time PCR analysis showed that PlacLFY was expressed mainly in male inflorescences from May of the first year to March of next year, with the highest expression level in December, and in female inflorescences from June to April of next year. PlacLFY mRNA was also detected strongly in subpetiolar buds of December from 4-year-old and adult trees, and slightly in stem of young seedling and young leaf of adult plant. Additionally, we cloned 1,138 bp promoter sequence of PlacLFY and we drove GUS expression in transgenic tobacco by the chimerical pPlacLFY::GUS construction. Histological GUS staining analysis indicated that PlacLFY promoter can drive GUS gene expression in shoot apex, stem, young leaf and petiole, flower stalk, petal tip, and young/semi-mature fruits of transgenic tobacco, which is almost identical to the expression pattern of PlacLFY in London plane. The results revealed that the PlacLFY gene isolated from London plane is expressed not only in reproductive organ but also in vegetative organs. Moreover, this expression pattern is consistent with the expression pattern in tobacco of a GUS reporter gene under the control of the potential promoter region of PlacLFY. PMID

  15. Identification of the MMS22L-TONSL complex that promotes homologous recombination

    DEFF Research Database (Denmark)

    Duro, Eris; Lundin, Cecilia; Ask, Katrine;

    2010-01-01

    Budding yeast Mms22 is required for homologous recombination (HR)-mediated repair of stalled or broken DNA replication forks. Here we identify a human Mms22-like protein (MMS22L) and an MMS22L-interacting protein, NF¿BIL2/TONSL. Depletion of MMS22L or TONSL from human cells causes a high level of...... double-strand breaks (DSBs) during DNA replication. Both proteins accumulate at stressed replication forks, and depletion of MMS22L or TONSL from cells causes hypersensitivity to agents that cause S phase-associated DSBs, such as topoisomerase (TOP) inhibitors. In this light, MMS22L and TONSL are...... stability when unscheduled DSBs occur in the vicinity of DNA replication forks....

  16. Geologic map of the Artemis Chasma quadrangle (V-48), Venus

    Science.gov (United States)

    Bannister, Roger A.; Hansen, Vicki L.

    2010-01-01

    Artemis, named for the Greek goddess of the hunt, represents an approximately 2,600 km diameter circular feature on Venus, and it may represent the largest circular structure in our solar system. Artemis, which lies between the rugged highlands of Aphrodite Terra to the north and relatively smooth lowlands to the south, includes an interior topographic high surrounded by the 2,100-km-diameter, 25- to 200-km-wide, 1- to 2-km-deep circular trough, called Artemis Chasma, and an outer rise that grades outward into the surrounding lowland. Although several other chasmata exist in the area and globally, other chasmata have generally linear trends that lack the distinctive circular pattern of Artemis Chasma. The enigmatic nature of Artemis has perplexed researchers since Artemis Chasma was first identified in Pioneer Venus data. Although Venus' surface abounds with circular to quasi-circular features at a variety of scales, including from smallest to largest diameter features: small shield edifices (>1 km), large volcanic edifices (100-1,000 km), impact craters (1-270 km), coronae (60-1,010 km), volcanic rises and crustal plateaus (~1,500-2,500 km), Artemis defies classification into any of these groups. Artemis dwarfs Venus' largest impact crater, Mead (~280 km diameter); Artemis also lacks the basin topography, multiple ring structures, and central peak expected for large impact basins. Topographically, Artemis resembles some Venusian coronae; however Artemis is an order of magnitude larger than the average corona (200 km) and about twice the size of Heng-O Corona (which is 1,010 km in diameter), the largest of Venusian coronae. In map view Artemis' size and shape resemble volcanic rises and crustal plateaus; however, both of these classes of features differ topographically from Artemis. Volcanic rises and crustal plateaus form broad domical regions, and steep-sided regions with flat tops, respectively; furthermore, neither rises nor plateaus include circular troughs

  17. Shu proteins promote the formation of homologous recombination intermediates that are processed by Sgs1-Rmi1-Top3

    DEFF Research Database (Denmark)

    Mankouri, Hocine W; Ngo, Hien-Ping; Hickson, Ian D

    2007-01-01

    CSM2, PSY3, SHU1, and SHU2 (collectively referred to as the SHU genes) were identified in Saccharomyces cerevisiae as four genes in the same epistasis group that suppress various sgs1 and top3 mutant phenotypes when mutated. Although the SHU genes have been implicated in homologous recombination...... formation of MMS-induced HRR intermediates (X-molecules) arising during replication in sgs1 cells, mutation of SHU genes attenuated the level of these structures. Similar findings were also observed in shu1 cells in which Rmi1 or Top3 function was impaired. We propose a model in which the Shu proteins act...... in HRR to promote the formation of HRR intermediates that are processed by the Sgs1-Rmi1-Top3 complex....

  18. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis).

    Science.gov (United States)

    Bi, Zhenghong; Li, Xiang; Huang, Huasun; Hua, Yuwei

    2016-01-01

    A homolog of MOTHER OF FT AND TFL1 (MFT) was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1)-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1) and FRUITFULL (FUL) were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS) assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA) due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species. PMID:26950112

  19. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis

    Directory of Open Access Journals (Sweden)

    Zhenghong Bi

    2016-03-01

    Full Text Available A homolog of MOTHER OF FT AND TFL1 (MFT was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT and TERMINAL FLOWER1 (TFL1-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1 and FRUITFULL (FUL were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species.

  20. The Fragaria vesca Homolog of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 Represses Flowering and Promotes Vegetative Growth[W

    Science.gov (United States)

    Mouhu, Katriina; Kurokura, Takeshi; Koskela, Elli A.; Albert, Victor A.; Elomaa, Paula; Hytönen, Timo

    2013-01-01

    In the annual long-day plant Arabidopsis thaliana, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) integrates endogenous and environmental signals to promote flowering. We analyzed the function and regulation of the SOC1 homolog (Fragaria vesca [Fv] SOC1) in the perennial short-day plant woodland strawberry (Fragaria vesca). We found that Fv SOC1 overexpression represses flower initiation under inductive short days, whereas its silencing causes continuous flowering in both short days and noninductive long days, similar to mutants in the floral repressor Fv TERMINAL FLOWER1 (Fv TFL1). Molecular analysis of these transgenic lines revealed that Fv SOC1 activates Fv TFL1 in the shoot apex, leading to the repression of flowering in strawberry. In parallel, Fv SOC1 regulates the differentiation of axillary buds to runners or axillary leaf rosettes, probably through the activation of gibberellin biosynthetic genes. We also demonstrated that Fv SOC1 is regulated by photoperiod and Fv FLOWERING LOCUS T1, suggesting that it plays a central role in the photoperiodic control of both generative and vegetative growth in strawberry. In conclusion, we propose that Fv SOC1 is a signaling hub that regulates yearly cycles of vegetative and generative development through separate genetic pathways. PMID:24038650

  1. The Fragaria vesca homolog of suppressor of overexpression of constans1 represses flowering and promotes vegetative growth.

    Science.gov (United States)

    Mouhu, Katriina; Kurokura, Takeshi; Koskela, Elli A; Albert, Victor A; Elomaa, Paula; Hytönen, Timo

    2013-09-01

    In the annual long-day plant Arabidopsis thaliana, suppressor of overexpression of constans1 (SOC1) integrates endogenous and environmental signals to promote flowering. We analyzed the function and regulation of the SOC1 homolog (Fragaria vesca [Fv] SOC1) in the perennial short-day plant woodland strawberry (Fragaria vesca). We found that Fv SOC1 overexpression represses flower initiation under inductive short days, whereas its silencing causes continuous flowering in both short days and noninductive long days, similar to mutants in the floral repressor Fv terminal flower1 (Fv TFL1). Molecular analysis of these transgenic lines revealed that Fv SOC1 activates Fv TFL1 in the shoot apex, leading to the repression of flowering in strawberry. In parallel, Fv SOC1 regulates the differentiation of axillary buds to runners or axillary leaf rosettes, probably through the activation of gibberellin biosynthetic genes. We also demonstrated that Fv SOC1 is regulated by photoperiod and Fv flowering locus T1, suggesting that it plays a central role in the photoperiodic control of both generative and vegetative growth in strawberry. In conclusion, we propose that Fv SOC1 is a signaling hub that regulates yearly cycles of vegetative and generative development through separate genetic pathways. PMID:24038650

  2. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities.

    Directory of Open Access Journals (Sweden)

    Janice B B Lam

    Full Text Available BACKGROUND: Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1 and thioredoxin reductase (TrxR1 were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1. CONCLUSION: Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K

  3. Defective DNA repair and increased genomic instability in Artemis-deficient murine cells.

    Science.gov (United States)

    Rooney, Sean; Alt, Frederick W; Lombard, David; Whitlow, Scott; Eckersdorff, Mark; Fleming, James; Fugmann, Sebastian; Ferguson, David O; Schatz, David G; Sekiguchi, JoAnn

    2003-03-01

    In developing lymphocytes, the recombination activating gene endonuclease cleaves DNA between V, D, or J coding and recombination signal (RS) sequences to form hairpin coding and blunt RS ends, which are fused to form coding and RS joins. Nonhomologous end joining (NHEJ) factors repair DNA double strand breaks including those induced during VDJ recombination. Human radiosensitive severe combined immunodeficiency results from lack of Artemis function, an NHEJ factor with in vitro endonuclease/exonuclease activities. We inactivated Artemis in murine embryonic stem (ES) cells by targeted mutation. Artemis deficiency results in impaired VDJ coding, but not RS, end joining. In addition, Artemis-deficient ES cells are sensitive to a radiomimetic drug, but less sensitive to ionizing radiation. VDJ coding joins from Artemis-deficient ES cells, which surprisingly are distinct from the highly deleted joins consistently obtained from DNA-dependent protein kinase catalytic subunit-deficient ES cells, frequently lack deletions and often display large junctional palindromes, consistent with a hairpin coding end opening defect. Strikingly, Artemis-deficient ES cells have increased chromosomal instability including telomeric fusions. Thus, Artemis appears to be required for a subset of NHEJ reactions that require end processing. Moreover, Artemis functions as a genomic caretaker, most notably in prevention of translocations and telomeric fusions. As Artemis deficiency is compatible with human life, Artemis may also suppress genomic instability in humans. PMID:12615897

  4. Interplay between Ku, Artemis, and the DNA-dependent protein kinase catalytic subunit at DNA ends.

    Science.gov (United States)

    Drouet, Jérôme; Frit, Philippe; Delteil, Christine; de Villartay, Jean-Pierre; Salles, Bernard; Calsou, Patrick

    2006-09-22

    Repair of DNA double strand breaks (DSB) by the nonhomologous end-joining pathway in mammals requires at least seven proteins involved in a simplified two-step process: (i) recognition and synapsis of the DNA ends dependent on the DNA-dependent protein kinase (DNA-PK) formed by the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs in association with Artemis; (ii) ligation dependent on the DNA ligase IV.XRCC4.Cernunnos-XLF complex. The Artemis protein exhibits exonuclease and endonuclease activities that are believed to be involved in the processing of a subclass of DSB. Here, we have analyzed the interactions of Artemis and nonhomologous end-joining pathway proteins both in a context of human nuclear cell extracts and in cells. DSB-inducing agents specifically elicit the mobilization of Artemis to damaged chromatin together with DNA-PK and XRCC4/ligase IV proteins. DNA-PKcs is necessary for the loading of Artemis on damaged DNA and is the main kinase that phosphorylates Artemis in cells damaged with highly efficient DSB producers. Under kinase-preventive conditions, both in vitro and in cells, Ku-mediated assembly of DNA-PK on DNA ends is responsible for a dissociation of the DNA-PKcs. Artemis complex. Conversely, DNA-PKcs kinase activity prevents Artemis dissociation from the DNA-PK.DNA complex. Altogether, our data allow us to propose a model in which a DNA-PKcs-mediated phosphorylation is necessary both to activate Artemis endonuclease activity and to maintain its association with the DNA end site. This tight functional coupling between the activation of both DNA-PKcs and Artemis may avoid improper processing of DNA. PMID:16857680

  5. The readout system for the ArTeMis camera

    Science.gov (United States)

    Doumayrou, E.; Lortholary, M.; Dumaye, L.; Hamon, G.

    2014-07-01

    During ArTeMiS observations at the APEX telescope (Chajnantor, Chile), 5760 bolometric pixels from 20 arrays at 300mK, corresponding to 3 submillimeter focal planes at 450μm, 350μm and 200μm, have to be read out simultaneously at 40Hz. The read out system, made of electronics and software, is the full chain from the cryostat to the telescope. The readout electronics consists of cryogenic buffers at 4K (NABU), based on CMOS technology, and of warm electronic acquisition systems called BOLERO. The bolometric signal given by each pixel has to be amplified, sampled, converted, time stamped and formatted in data packets by the BOLERO electronics. The time stamping is obtained by the decoding of an IRIG-B signal given by APEX and is key to ensure the synchronization of the data with the telescope. Specifically developed for ArTeMiS, BOLERO is an assembly of analogue and digital FPGA boards connected directly on the top of the cryostat. Two detectors arrays (18*16 pixels), one NABU and one BOLERO interconnected by ribbon cables constitute the unit of the electronic architecture of ArTeMiS. In total, the 20 detectors for the tree focal planes are read by 10 BOLEROs. The software is working on a Linux operating system, it runs on 2 back-end computers (called BEAR) which are small and robust PCs with solid state disks. They gather the 10 BOLEROs data fluxes, and reconstruct the focal planes images. When the telescope scans the sky, the acquisitions are triggered thanks to a specific network protocol. This interface with APEX enables to synchronize the acquisition with the observations on sky: the time stamped data packets are sent during the scans to the APEX software that builds the observation FITS files. A graphical user interface enables the setting of the camera and the real time display of the focal plane images, which is essential in laboratory and commissioning phases. The software is a set of C++, Labview and Python, the qualities of which are respectively used

  6. The ARTEMIS European driving cycles for measuring car pollutant emissions

    OpenAIRE

    ANDRE, M

    2004-01-01

    In the past 10 years, various work has been undertaken to collect data on the actual driving of European cars and to derive representative real-world driving cycles. A compilation and synthesis of this work is provided in this paper. In the frame of the European research project: ARTEMIS, this work has been considered to derive a set of reference driving cycles. The main objectives were as follows:- to derive a common set of reference real-world driving cycles to be used in the frame of the A...

  7. The elicitor-inducible alfalfa isoflavone reductase promoter confers different patterns of developmental expression in homologous and heterologous transgenic plants.

    Science.gov (United States)

    Oommen, A; Dixon, R A; Paiva, N L

    1994-01-01

    In legumes, the synthesis of infection- and elicitor-inducible antimicrobial phytoalexins occurs via the isoflavonoid branch of the phenylpropanoid pathway. To study transcriptional regulation of isoflavonoid pathway-specific genes, we have isolated the gene encoding isoflavone reductase (IFR), which is the enzyme that catalyzes the penultimate step in the synthesis of the phytoalexin medicarpin in alfalfa. Chimeric gene fusions were constructed between 765- and 436-bp promoter fragments of the IFR gene and the beta-glucuronidase reporter gene and transferred to alfalfa and tobacco by Agrobacterium-mediated transformation. Both promoter fragments conferred elicitor-mediated expression in cell suspension cultures derived from transgenic plants of both species and fungal infection-mediated expression in leaves of transgenic alfalfa. Developmental expression directed by both promoter fragments in transgenic alfalfa was observed only in the root meristem, cortex, and nodules, which is consistent with the accumulation of endogenous IFR transcripts. However, in transgenic tobacco, expression from the 765-bp promoter was observed in vegetative tissues (root meristem and cortex, inner vascular tissue of stems and petioles, leaf tips, and stem peripheries adjacent to petioles) and in reproductive tissues (stigma, placenta, base of the ovary, receptacle, seed, tapetal layer, and pollen grains), whereas the 436-bp promoter was expressed only in fruits, seed, and pollen. These data indicate that infection/elicitor inducibility of the IFR promoter in both species and developmental expression in alfalfa are determined by sequences downstream of position -436, whereas sequences between -436 and -765 confer a complex pattern of strong ectopic developmental expression in the heterologous species that lacks the isoflavonoid pathway. PMID:7866024

  8. Adams-Based Rover Terramechanics and Mobility Simulator - ARTEMIS

    Science.gov (United States)

    Trease, Brian P.; Lindeman, Randel A.; Arvidson, Raymond E.; Bennett, Keith; VanDyke, Lauren P.; Zhou, Feng; Iagnemma, Karl; Senatore, Carmine

    2013-01-01

    The Mars Exploration Rovers (MERs), Spirit and Opportunity, far exceeded their original drive distance expectations and have traveled, at the time of this reporting, a combined 29 kilometers across the surface of Mars. The Rover Sequencing and Visualization Program (RSVP), the current program used to plan drives for MERs, is only a kinematic simulator of rover movement. Therefore, rover response to various terrains and soil types cannot be modeled. Although sandbox experiments attempt to model rover-terrain interaction, these experiments are time-intensive and costly, and they cannot be used within the tactical timeline of rover driving. Imaging techniques and hazard avoidance features on MER help to prevent the rover from traveling over dangerous terrains, but mobility issues have shown that these methods are not always sufficient. ARTEMIS, a dynamic modeling tool for MER, allows planned drives to be simulated before commands are sent to the rover. The deformable soils component of this model allows rover-terrain interactions to be simulated to determine if a particular drive path would take the rover over terrain that would induce hazardous levels of slip or sink. When used in the rover drive planning process, dynamic modeling reduces the likelihood of future mobility issues because high-risk areas could be identified before drive commands are sent to the rover, and drives planned over these areas could be rerouted. The ARTEMIS software consists of several components. These include a preprocessor, Digital Elevation Models (DEMs), Adams rover model, wheel and soil parameter files, MSC Adams GUI (commercial), MSC Adams dynamics solver (commercial), terramechanics subroutines (FORTRAN), a contact detection engine, a soil modification engine, and output DEMs of deformed soil. The preprocessor is used to define the terrain (from a DEM) and define the soil parameters for the terrain file. The Adams rover model is placed in this terrain. Wheel and soil parameter files

  9. 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.

  10. Lithium chloride protects retinal neurocytes from nutrient deprivation by promoting DNA non-homologous end-joining

    International Nuclear Information System (INIS)

    Lithium chloride is a therapeutic agent for treatment of bipolar affective disorders. Increasing numbers of studies have indicated that lithium has neuroprotective effects. However, the molecular mechanisms underlying the actions of lithium have not been fully elucidated. This study aimed to investigate whether lithium chloride produces neuroprotective function by improving DNA repair pathway in retinal neurocyte. In vitro, the primary cultured retinal neurocytes (85.7% are MAP-2 positive cells) were treated with lithium chloride, then cultured with serum-free media to simulate the nutrient deprived state resulting from ischemic insult. The neurite outgrowth of the cultured cells increased significantly in a dose-dependent manner when exposed to different levels of lithium chloride. Genomic DNA electrophoresis demonstrated greater DNA integrity of retinal neurocytes when treated with lithium chloride as compared to the control. Moreover, mRNA and protein levels of Ligase IV (involved in DNA non-homologous end-joining (NHEJ) pathway) in retinal neurocytes increased with lithium chloride. The end joining activity assay was performed to determine the role of lithium on NHEJ in the presence of extract from retinal neurocytes. The rejoining levels in retinal neurocytes treated with lithium were significantly increased as compared to the control. Furthermore, XRCC4, the Ligase IV partner, and the transcriptional factor, CREB and CTCF, were up-regulated in retinal cells after treating with 1.0 mM lithium chloride. Therefore, our data suggest that lithium chloride protects the retinal neural cells from nutrient deprivation in vitro, which may be similar to the mechanism of cell death in glaucoma. The improvement in DNA repair pathway involving in Ligase IV might have an important role in lithium neuroprotection. This study provides new insights into the neural protective mechanisms of lithium chloride.

  11. Directed homology

    DEFF Research Database (Denmark)

    Fahrenberg, Uli

    2004-01-01

    We introduce a new notion of directed homology for semicubical sets. We show that it respects directed homotopy and is functorial, and that it appears to enjoy some good algebraic properties. Our work has applications to higher-dimensional automata.......We introduce a new notion of directed homology for semicubical sets. We show that it respects directed homotopy and is functorial, and that it appears to enjoy some good algebraic properties. Our work has applications to higher-dimensional automata....

  12. ARTEMiS (Automated Robotic Terrestrial Exoplanet Microlensing Search) - A possible expert-system based cooperative effort to hunt for planets of Earth mass and below

    CERN Document Server

    Dominik, M; Allan, A; Rattenbury, N J; Tsapras, Y; Snodgrass, C; Bode, M F; Burgdorf, M J; Fraser, S N; Kerins, E; Mottram, C J; Steele, I A; Street, R A; Wheatley, P J; Wyrzykowski, L

    2008-01-01

    (abridged) The technique of gravitational microlensing is currently unique in its ability to provide a sample of terrestrial exoplanets around both Galactic disk and bulge stars, allowing to measure their abundance and determine their distribution with respect to mass and orbital separation. In order to achieve these goals in reasonable time, a well-coordinated effort involving a network of either 2m or 4 x 1m telescopes at each site is required. It could lead to the first detection of an Earth-mass planet outside the Solar system, and even planets less massive than Earth could be discovered. From April 2008, ARTEMiS (Automated Robotic Terrestrial Exoplanet Microlensing Search) is planned to provide a platform for a three-step strategy of survey, follow-up, and anomaly monitoring. As an expert system embedded in eSTAR (e-Science Telescopes for Astronomical Research), ARTEMiS will give advice on the optimal targets to be observed at any given time, and will also alert on deviations from ordinary microlensing l...

  13. Conceptual design of D-3He FRC reactor 'ARTEMIS'

    International Nuclear Information System (INIS)

    A comprehensive design study of the D-3He fueled field-reversed configuration (FRC) reactor 'ARTEMIS' is carried out for the purpose of proving its attractive characteristics and clarifying the critical issues for a commercial fusion reactor. The FRC burning plasma is stabilized and sustained in a steady equilibrium by means of a preferential trapping of D-3He fusion-produced energetic protons. A novel direct energy converter for 15MeV protons is also presented. On the bases of a consistent scenario of the fusion plasma production and simple engineering, a compact and simple reactor concept is presented. The design of the D-3He FRC power plant definitely offers the most attractive prospect for energy development. It is environmentally acceptable in view of radio-activity and fuel resources; and the estimated cost of electricity is low compared to a light water reactor. Critical issues concerning physics or engineering for the development of the D-3He FRC reactor are clarified. (author)

  14. Achaete-scute complex homolog-1 promotes DNA repair in the lung carcinogenesis through matrix metalloproteinase-7 and O(6-methylguanine-DNA methyltransferase.

    Directory of Open Access Journals (Sweden)

    Xiao-Yang Wang

    Full Text Available Lung cancer is the leading cause of cancer-related deaths in the world. Achaete-scute complex homolog-1 (Ascl1 is a member of the basic helix-loop-helix (bHLH transcription factor family that has multiple functions in the normal and neoplastic lung such as the regulation of neuroendocrine differentiation, prevention of apoptosis and promotion of tumor-initiating cells. We now show that Ascl1 directly regulates matrix metalloproteinase-7 (MMP-7 and O(6-methylguanine-DNA methyltransferase (MGMT. Loss- and gain-of-function experiments in human bronchial epithelial and lung carcinoma cell lines revealed that Ascl1, MMP-7 and MGMT are able to protect cells from the tobacco-specific nitrosamine NNK-induced DNA damage and the alkylating agent cisplatin-induced apoptosis. We also examined the role of Ascl1 in NNK-induced lung tumorigenesis in vivo. Using transgenic mice which constitutively expressed human Ascl1 in airway lining cells, we found that there was a delay in lung tumorigenesis. We conclude that Ascl1 potentially enhances DNA repair through activation of MMP-7 and MGMT which may impact lung carcinogenesis and chemoresistance. The study has uncovered a novel and unexpected function of Ascl1 which will contribute to better understanding of lung carcinogenesis and the broad implications of transcription factors in tobacco-related carcinogenesis.

  15. RSC Facilitates Rad59-Dependent Homologous Recombination between Sister Chromatids by Promoting Cohesin Loading at DNA Double-Strand Breaks ▿

    OpenAIRE

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

    2011-01-01

    Homologous recombination repairs DNA double-strand breaks by searching for, invading, and copying information from a homologous template, typically the homologous chromosome or sister chromatid. Tight wrapping of DNA around histone octamers, however, impedes access of repair proteins to DNA damage. To facilitate DNA repair, modifications of histones and energy-dependent remodeling of chromatin are required, but the precise mechanisms by which chromatin modification and remodeling enzymes cont...

  16. Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency

    NARCIS (Netherlands)

    K. Felgentreff (Kerstin); Y.N. Lee (Yu Nee); F. Frugoni (Francesco); L. Du (Likun); M. van der Burg (Mirjam); S. Giliani; I. Tezcan (Ilhan); I. Reisli (Ismail); E. Mejstříková (Ester); J.P. de Villartay; B.P. Sleckman (Barry P.); J. Manis (John); L.D. Notarangelo (Luigi Daniele)

    2015-01-01

    textabstractBackground The endonuclease ARTEMIS, which is encoded by the DCLRE1C gene, is a component of the nonhomologous end-joining pathway and participates in hairpin opening during the V(D)J recombination process and repair of a subset of DNA double-strand breaks. Patients with ARTEMIS deficien

  17. ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells

    Directory of Open Access Journals (Sweden)

    Tompkins Kathleen

    2010-10-01

    Full Text Available Abstract Background Unrepaired DNA double-stranded breaks (DSBs cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability. NHEJ defects lead to severe combined immunodeficiency (SCID and lymphoid cancer predisposition in both mice and humans. While NHEJ has been thoroughly investigated in lymphocytes, the importance of NHEJ in other cell types, especially with regard to tumor suppression, is less well documented. We previously reported evidence that the NHEJ pathway functions to suppress a range of nonlymphoid tumor types, including various classes of sarcomas, by unknown mechanisms. Results Here we investigate roles for the NHEJ factor ARTEMIS in multipotent mesenchymal stem/progenitor cells (MSCs, as putative sarcomagenic cells of origin. We demonstrate a key role for ARTEMIS in sarcoma suppression in a sensitized mouse tumor model. In this context, we found that ARTEMIS deficiency led to chromosomal damage but, paradoxically, enhanced resistance and proliferative potential in primary MSCs subjected to various stresses. Gene expression analysis revealed abnormally regulated stress response, cell proliferation, and signal transduction pathways in ARTEMIS-defective MSCs. Finally, we identified candidate regulatory genes that may, in part, mediate a stress-resistant, hyperproliferative phenotype in preneoplastic ARTEMIS-deficient MSCs. Conclusions Our discoveries suggest that Art prevents genome damage and restrains proliferation in MSCs exposed to various stress stimuli. We propose that deficiency leads to a preneoplastic state in primary MSCs and is associated with aberrant proliferative control and cellular stress

  18. Nuclear factor-κB-dependent microRNA-130a upregulation promotes cervical cancer cell growth by targeting phosphatase and tensin homolog.

    Science.gov (United States)

    Feng, Yeqian; Zhou, Shenghua; Li, Guiyuan; Hu, Chunhong; Zou, Wen; Zhang, Haixia; Sun, Lili

    2016-05-15

    Nuclear factor-κB (NF-κB) may activate a series of gene transcription control cellular signaling pathways whose products are components in a wide range of biological processes. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Using human cervical cancer cell lines, we explored whether NF-κB regulates the expression of microRNA-130a (miR-130a) through binding elements in the miR-130a promoter region. We found that miR-130a accelerates cervical cancer cell proliferation by targeting the phosphatase and tensin homolog on chromosome 10 (PTEN). Further, NF-κB activates both HeLa and CaSki cell growth by upregulating miR-130a. In addition, by targeting PTEN 3' untranslated region, miR-130a might increase cell growth and initiate protein kinase B (AKT) pathway activation. Lastly, PTEN protein was upregulated in response to NF-κB overexpression and downregulated in response to NF-κB inhibition. Compared to total AKT protein level, p-AKT was downregulated by NF-κB overexpression while upregulated by NF-κB inhibition, indicating PTEN pathway activated and affected by NF-κB. Taken together, our findings shed new light on the NF-κB/miR-130a/PTEN pathway in cervical cancer and add new insight regarding the carcinogenesis of cervical cancer. PMID:27040383

  19. MsDpo4—a DinB Homolog from Mycobacterium smegmatis—Is an Error-Prone DNA Polymerase That Can Promote G:T and T:G Mismatches

    Directory of Open Access Journals (Sweden)

    Amit Sharma

    2012-01-01

    Full Text Available Error-prone DNA synthesis in prokaryotes imparts plasticity to the genome to allow for evolution in unfavorable environmental conditions, and this phenomenon is termed adaptive mutagenesis. At a molecular level, adaptive mutagenesis is mediated by upregulating the expression of specialized error-prone DNA polymerases that generally belong to the Y-family, such as the polypeptide product of the dinB gene in case of E. coli. However, unlike E. coli, it has been seen that expression of the homologs of dinB in Mycobacterium tuberculosis are not upregulated under conditions of stress. These studies suggest that DinB homologs in Mycobacteria might not be able to promote mismatches and participate in adaptive mutagenesis. We show that a representative homolog from Mycobacterium smegmatis (MsDpo4 can carry out template-dependent nucleotide incorporation and therefore is a DNA polymerase. In addition, it is seen that MsDpo4 is also capable of misincorporation with a significant ability to promote G:T and T:G mismatches. The frequency of misincorporation for these two mismatches is similar to that exhibited by archaeal and prokaryotic homologs. Overall, our data show that MsDpo4 has the capacity to facilitate transition mutations and can potentially impart plasticity to the genome.

  20. Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription termination and DNA repair.

    Science.gov (United States)

    Morales, Julio C; Richard, Patricia; Rommel, Amy; Fattah, Farjana J; Motea, Edward A; Patidar, Praveen L; Xiao, Ling; Leskov, Konstantin; Wu, Shwu-Yuan; Hittelman, Walter N; Chiang, Cheng-Ming; Manley, James L; Boothman, David A

    2014-04-01

    Functions of Kub5-Hera (In Greek Mythology Hera controlled Artemis) (K-H), the human homolog of the yeast transcription termination factor Rtt103, remain undefined. Here, we show that K-H has functions in both transcription termination and DNA double-strand break (DSB) repair. K-H forms distinct protein complexes with factors that repair DSBs (e.g. Ku70, Ku86, Artemis) and terminate transcription (e.g. RNA polymerase II). K-H loss resulted in increased basal R-loop levels, DSBs, activated DNA-damage responses and enhanced genomic instability. Significantly lowered Artemis protein levels were detected in K-H knockdown cells, which were restored with specific K-H cDNA re-expression. K-H deficient cells were hypersensitive to cytotoxic agents that induce DSBs, unable to reseal complex DSB ends, and showed significantly delayed γ-H2AX and 53BP1 repair-related foci regression. Artemis re-expression in K-H-deficient cells restored DNA-repair function and resistance to DSB-inducing agents. However, R loops persisted consistent with dual roles of K-H in transcription termination and DSB repair. PMID:24589584

  1. Electronic components and systems in Europe. The future impact of ENIAC and ARTEMIS

    NARCIS (Netherlands)

    Leijten, A.J.M.; Prem, E.; Heide, M.J.L. de; Butter, M.; Marek, M.; Irran, J.

    2012-01-01

    This study investigates the opportunities to improve the effectiveness and impact of European industry driven public-private collaboration research and innovation initiatives in the field of electronic components and systems: ENIAC (nano-electronics) and Artemis (embedded systems) JTIs and the possi

  2. Artemis 123: Development of a whole-head infant MEG system

    Directory of Open Access Journals (Sweden)

    Timothy PL Roberts

    2014-03-01

    Full Text Available Background: A major motivation in designing the new infant and child magnetoencephalography (MEG system described in this manuscript is the premise that electrophysiological signatures (resting activity and evoked responses may serve as biomarkers of neurodevelopmental disorders, with neuronal abnormalities in conditions such as autism spectrum disorder potentially detectable early in development. Whole-head MEG systems are generally optimized/sized for adults. Since magnetic field produced by neuronal currents decreases as a function of distance^2 and infants and young children have smaller head sizes, whole-head adult MEG systems do not provide optimal signal-to-noise in younger individuals. This spurred development of a whole-head infant and young child MEG system – Artemis 123. Methods: In addition to describing the instrument design, the focus of this manuscript is use of Artemis 123 to obtain auditory evoked and resting-state neuromagnetic data in young children. Data were collected from a 14-month female, an 18-month female, and a 48-month male. Phantom data are also provided to show localization accuracy. Results: Artemis 123 auditory data showed generalizability and reproducibility, with auditory responses observed in all participants. The auditory MEG measures were found to be manipulable, exhibiting sensitivity to tone frequency. Furthermore, there appeared to be a predictable sensitivity of evoked components to development, with latencies decreasing with age. Resting-state showed characteristic oscillatory activity. Finally, phantom data showed that dipole sources could be localized with an errorConclusions: Artemis 123 allows efficient recording of whole-head MEG in infants four years and younger. Future work will examine the feasibility of obtaining somatosensory and visual recordings in similar-age children as well as obtaining recordings from younger infants. Thus, Artemis 123 offers the promise of detecting earlier diagnostic

  3. Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast

    DEFF Research Database (Denmark)

    Moss, Jennifer; Tinline-Purvis, Helen; Walker, Carol A;

    2010-01-01

    Nucleotide synthesis is a universal response to DNA damage, but how this response facilitates DNA repair and cell survival is unclear. Here we establish a role for DNA damage-induced nucleotide synthesis in homologous recombination (HR) repair in fission yeast. Using a genetic screen, we found th...

  4. ARTEMiS (Automated Robotic Terrestrial Exoplanet Microlensing Search): A possible expert-system based cooperative effort to hunt for planets of Earth mass and below

    Science.gov (United States)

    Dominik, M.; Horne, K.; Allan, A.; Rattenbury, N. J.; Tsapras, Y.; Snodgrass, C.; Bode, M. F.; Burgdorf, M. J.; Fraser, S. N.; Kerins, E.; Mottram, C. J.; Steele, I. A.; Street, R. A.; Wheatley, P. J.; Wyrzykowski, Ł.

    2008-03-01

    The technique of gravitational microlensing is currently unique in its ability to provide a sample of terrestrial exoplanets around both Galactic disk and bulge stars, allowing to measure their abundance and determine their distribution with respect to mass and orbital separation. Thus, valuable information for testing models of planet formation and orbital migration is gathered, constituting an important piece in the puzzle for the existence of life forms throughout the Universe. In order to achieve these goals in reasonable time, a well-coordinated effort involving a network of either 2m or 4×1m telescopes at each site is required. It could lead to the first detection of an Earth-mass planet outside the Solar system, and even planets less massive than Earth could be discovered. From April 2008, ARTEMiS (Automated Robotic Terrestrial Exoplanet Microlensing Search) is planned to provide a platform for a three-step strategy of survey, follow-up, and anomaly monitoring. As an expert system embedded in eSTAR (e-Science Telescopes for Astronomical Research), ARTEMiS will give advice for follow-up based on a priority algorithm that selects targets to be observed in order to maximize the expected number of planet detections, and will also alert on deviations from ordinary microlensing light curves by means of the SIGNALMEN anomaly detector. While the use of the VOEvent (Virtual Observatory Event) protocol allows a direct interaction with the telescopes that are part of the HTN (Heterogeneous Telescope Networks) consortium, additional interfaces provide means of communication with all existing microlensing campaigns that rely on human observers. The success of discovering a planet by microlensing critically depends on the availability of a telescope in a suitable location at the right time, which can mean within 10 min. To encourage follow-up observations, microlensing campaigns are therefore releasing photometric data in real time. On ongoing planetary anomalies, world

  5. Validation of Artemis Mobility Simulations for the Spirit, Opportunity, and Curiosity Mars Rovers

    Science.gov (United States)

    Stein, N.; Arvidson, R. E.; Heverly, M.; Lindemann, R.; Trease, B.; Iagnemma, K.; Senatore, C.

    2013-12-01

    Artemis is a framework for modeling the dynamical motions of rovers over realistic planetary terrains that include topography generated from orbital or rover-based data and interactions of driven wheels with deformable soils with compaction resistance due to wheel sinkage into soils (Bekker-Wong-Reece model) or with hard-surface contacts dominated by static and dynamic coefficients of friction (contact model). Artemis is being used to simulate flight-based drives for the Mars Exploration Rovers (Spirit, Opportunity) and Mars Science Laboratory (Curiosity). Critical to realistic simulations is validation of the models by comparison and registration to single-wheel tests in the laboratory using spare flight wheels and testing of rover drives on various surfaces on Earth. In this abstract we report results from modeling test rover drives on deformable soil and hard surfaces. First, a MER test rover was driven over a tilted hard-surfaced plane covered with high friction paint, with separate runs with tilts ranging from 0 to 20 degrees. The Artemis contact model with static and dynamic coefficients of friction of 0.780 and 0.580 reproduced the runs in a manner in which the tests and models were shown to be statistically indistinguishable. Second, the MSL Test Rover was driven over bedrock plates with slopes ranging from 0 to 30 degrees, and Artemis successfully modeled these runs with static and dynamic coefficients of friction of 0.577 and 0.450, respectively. The MSL Test Rover simulations yielded low, linearly increasing slip between 0% and 15% on slopes ranging from 0 to 20 deg, increasing nonlinearly to nearly 100% on the 30 degree slope. Third, both the MER and MSL Test Rovers were deployed to the Dumont Dunes in the Mojave Desert to do side-by-side runs up dune slopes with tilts ranging from 0 to 15 degrees. Test runs and Artemis (Bekker-Wong-Reece model) results are comparable in terms of wheel sinkages and slippage values. Uphill drives led to non

  6. Integrated Toolset for WSN Application Planning, Development, Commissioning and Maintenance: The WSN-DPCM ARTEMIS-JU Project

    Science.gov (United States)

    Antonopoulos, Christos; Asimogloy, Katerina; Chiti, Sarah; D’Onofrio, Luca; Gianfranceschi, Simone; He, Danping; Iodice, Antonio; Koubias, Stavros; Koulamas, Christos; Lavagno, Luciano; Lazarescu, Mihai T.; Mujica, Gabriel; Papadopoulos, George; Portilla, Jorge; Redondo, Luis; Riccio, Daniele; Riesgo, Teresa; Rodriguez, Daniel; Ruello, Giuseppe; Samoladas, Vasilis; Stoyanova, Tsenka; Touliatos, Gerasimos; Valvo, Angela; Vlahoy, Georgia

    2016-01-01

    In this article we present the main results obtained in the ARTEMIS-JU WSN-DPCM project between October 2011 and September 2015. The first objective of the project was the development of an integrated toolset for Wireless sensor networks (WSN) application planning, development, commissioning and maintenance, which aims to support application domain experts, with limited WSN expertise, to efficiently develop WSN applications from planning to lifetime maintenance. The toolset is made of three main tools: one for planning, one for application development and simulation (which can include hardware nodes), and one for network commissioning and lifetime maintenance. The tools are integrated in a single platform which promotes software reuse by automatically selecting suitable library components for application synthesis and the abstraction of the underlying architecture through the use of a middleware layer. The second objective of the project was to test the effectiveness of the toolset for the development of two case studies in different domains, one for detecting the occupancy state of parking lots and one for monitoring air concentration of harmful gasses near an industrial site. PMID:27271622

  7. Integrated Toolset for WSN Application Planning, Development, Commissioning and Maintenance: The WSN-DPCM ARTEMIS-JU Project.

    Science.gov (United States)

    Antonopoulos, Christos; Asimogloy, Katerina; Chiti, Sarah; D'Onofrio, Luca; Gianfranceschi, Simone; He, Danping; Iodice, Antonio; Koubias, Stavros; Koulamas, Christos; Lavagno, Luciano; Lazarescu, Mihai T; Mujica, Gabriel; Papadopoulos, George; Portilla, Jorge; Redondo, Luis; Riccio, Daniele; Riesgo, Teresa; Rodriguez, Daniel; Ruello, Giuseppe; Samoladas, Vasilis; Stoyanova, Tsenka; Touliatos, Gerasimos; Valvo, Angela; Vlahoy, Georgia

    2016-01-01

    In this article we present the main results obtained in the ARTEMIS-JU WSN-DPCM project between October 2011 and September 2015. The first objective of the project was the development of an integrated toolset for Wireless sensor networks (WSN) application planning, development, commissioning and maintenance, which aims to support application domain experts, with limited WSN expertise, to efficiently develop WSN applications from planning to lifetime maintenance. The toolset is made of three main tools: one for planning, one for application development and simulation (which can include hardware nodes), and one for network commissioning and lifetime maintenance. The tools are integrated in a single platform which promotes software reuse by automatically selecting suitable library components for application synthesis and the abstraction of the underlying architecture through the use of a middleware layer. The second objective of the project was to test the effectiveness of the toolset for the development of two case studies in different domains, one for detecting the occupancy state of parking lots and one for monitoring air concentration of harmful gasses near an industrial site. PMID:27271622

  8. Direct measurements of laser light aberration from the ARTEMIS geostationary satellite through thin clouds

    OpenAIRE

    Kuzkov, Volodymyr; Kuzkov, Sergii; Sodnik, Zoran

    2015-01-01

    A precise ground based telescope system was developed for laser communication experiments with the geostationary satellite ARTEMIS of ESA. Precise tracking of the satellite was realized by using time resolved coordinates of the satellite. During the experiments, the time propagation of laser signal from the satellite and the point-ahead angle for the laser beam were calculated. Some laser experiments though thin clouds were performed. A splitting of some images of the laser beam from the sate...

  9. Defective DNA Repair and Increased Genomic Instability in Artemis-deficient Murine Cells

    OpenAIRE

    Rooney, Sean; Alt, Frederick W.; Lombard, David; Whitlow, Scott; Eckersdorff, Mark; Fleming, James; Fugmann, Sebastian; Ferguson, David O.; Schatz, David G.; Sekiguchi, JoAnn

    2003-01-01

    In developing lymphocytes, the recombination activating gene endonuclease cleaves DNA between V, D, or J coding and recombination signal (RS) sequences to form hairpin coding and blunt RS ends, which are fused to form coding and RS joins. Nonhomologous end joining (NHEJ) factors repair DNA double strand breaks including those induced during VDJ recombination. Human radiosensitive severe combined immunodeficiency results from lack of Artemis function, an NHEJ factor with in vitro endonuclease/...

  10. Atmospheric influence on a laser beam observed on the OICETS – ARTEMIS communication demonstration link

    Directory of Open Access Journals (Sweden)

    A. Löscher

    2010-05-01

    Full Text Available In 2006 bi-directional optical inter-satellite communication experiments have been conducted between the Japan Aerospace Exploration Agency (JAXA Optical Inter-orbit Communications Engineering Test Satellite (OICETS and the European Space Agency (ESA multi purpose telecommunications and technology demonstration satellite (Advanced Relay and Technology MISsion ARTEMIS. On 5 April 2006 an experiment was successfully carried out maintaining the inter-satellite link during OICETS's setting behind the Earth limb until the signal was lost. This setup resembles an occultation observation where the influence of Earth's atmosphere is evident in the power fluctuations recorded at ARTEMIS's (and OICETS's receiver. These fluctuations are not existing or at a low level at a link path above the atmosphere and steadily increase as OICETS sets behind the horizon until the tracking of the signal is lost. This specific experiment was performed only once since atmospheric science was not the goal of this demonstration. Nevertheless this kind of data, if available more frequently in future, can help to study atmospheric turbulence and validate respective models. The data presented here had been recorded at ARTEMIS.

  11. Atmospheric influence on a laser beam observed on the OICETS – ARTEMIS communication demonstration link

    Directory of Open Access Journals (Sweden)

    A. Löscher

    2010-09-01

    Full Text Available In 2006 bi-directional optical inter-satellite communication experiments were conducted between the Japan Aerospace Exploration Agency (JAXA Optical Inter-orbit Communications Engineering Test Satellite (OICETS and the European Space Agency (ESA multi-purpose telecommunications and technology demonstration satellite (Advanced Relay and Technology MISsion ARTEMIS. On 5 April 2006, an experiment was successfully carried out by maintaining the inter-satellite link during OICETS's setting behind the Earth limb until the signal was lost. This setup resembles an occultation observation where the influence of Earth's atmosphere is evident in the power fluctuations recorded at ARTEMIS's (and OICETS's receiver. These fluctuations do not exist or are at a low level at a link path above the atmosphere and steadily increase as OICETS sets behind the horizon until the tracking of the signal is lost. This specific experiment was performed only once since atmospheric science was not the goal of this demonstration. Nevertheless, this kind of data, if available more frequently in future, can help to study atmospheric turbulence and validate models. The data present here were recorded at ARTEMIS.

  12. Homology, Analogy, and Ethology.

    Science.gov (United States)

    Beer, Colin G.

    1984-01-01

    Because the main criterion of structural homology (the principle of connections) does not exist for behavioral homology, the utility of the ethological concept of homology has been questioned. The confidence with which behavioral homologies can be claimed varies inversely with taxonomic distance. Thus, conjectures about long-range phylogenetic…

  13. Optical design for the 450, 350, and 200 µm ArTeMiS camera

    Science.gov (United States)

    Dubreuil, Didier; Martignac, Jérôme; Toussaint, Jean Christian; Visticot, François; Delisle, Cyrille; Gallais, Pascal; Le Pennec, Jean; Lerch, Thierry; André, Philippe; Lortholary, Michel; Maffei, Bruno; Haynes, Vic; Hurtado, Norma; Pisano, Giampaolo; Revéret, Vincent; Rodriguez, Louis; Talvard, Michel

    2014-07-01

    ArTeMiS is a submillimeter camera planned to work simultaneously at 450 μm, 350 μm and 200 μm by use of 3 focal planes of, respectively, 8, 8 and 4 bolometric arrays, each one made of 16 x18 pixels. In July 2013, with a preliminary setting reduced to 4 modules and to the 350 μm band, ArTeMiS was installed successfully at the Cassegrain focus of APEX, a 12 m antenna located on the Chajnantor plateau, Chile. After the summary of the scientific requirements, we describe the main lines of the ArTeMiS nominal optical design with its rationale and performances. This optical design is highly constrained by the room allocation available in the Cassegrain cabin. It is an all-reflective design including a retractable pick off mirror, a warm Fore Optics to image the focal plane of the telescope inside the cryostat, and the cold optics. The large size of the field of view at the focal plane of the telescope, 72 mm x 134 mm for the 350 μm and 450 μm beams, leads to the use of biconical toroidal mirrors. In this way, the nominal image quality obtained on the bolometric arrays is only just diffraction limited at some corners of the field of view. To keep a final PSF as much uniform as possible across the field of view, we have used the technic of manufacturing by diamond turning to machine the mirrors. This approach, while providing high accuracy on the shape of the mirrors, made easier the control of the two sub units, the Fore Optics and the cold optics, in the visible domain and at room temperature. Moreover, the use of the similar material (Aluminium alloy 6061) for the optical bench and the mirrors with their mount ensures a homothetic shrinking during the cooling down. The alignment protocol, drew up at the early step of the study, is also presented. It required the implementation of two additional mechanisms inside the cryostat to check the optical axis of the cold optics, in the real conditions of operation of ArTeMiS. In this way, it was possible to pre-align the

  14. NRAGE is involved in homologous recombination repair to resist the DNA-damaging chemotherapy and composes a ternary complex with RNF8-BARD1 to promote cell survival in squamous esophageal tumorigenesis.

    Science.gov (United States)

    Yang, Q; Pan, Q; Li, C; Xu, Y; Wen, C; Sun, F

    2016-08-01

    NRAGE, a neurotrophin receptor-interacting melanoma antigen-encoding gene homolog, is significantly increased in the nucleus of radioresistant esophageal tumor cell lines and is highly upregulated to promote cell proliferation in esophageal carcinomas (ECs). However, whether the overexpressed NRAGE promotes cell growth by participating in DNA-damage response (DDR) is still unclear. Here we show that NRAGE is required for efficient double-strand breaks (DSBs) repair via homologous recombination repair (HRR) and downregulation of NRAGE greatly sensitizes EC cells to DNA-damaging agents both in vitro and in vivo. Moreover, NRAGE not only regulates the stability of DDR factors, RNF8 and BARD1, in a ubiquitin-proteolytic pathway, but also chaperons the interaction between BARD1 and RNF8 via their RING domains to form a novel ternary complex. Additionally, the expression of NRAGE is closely correlated with RNF8 and BARD1 in esophageal tumor tissues. In summary, our findings reveal a novel function of NRAGE that will help to guide personalized esophageal cancer treatments by targeting NRAGE to increase cell sensitivity to DNA-damaging therapeutics in the long run. PMID:27035619

  15. Promotion

    OpenAIRE

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed.

  16. Intersection homology Betti numbers

    CERN Document Server

    Durfee, A H

    1993-01-01

    A generalization of the formula of Fine and Rao for the ranks of the intersection homology groups of a complex algebraic variety is given. The proof uses geometric properties of intersection homology and mixed Hodge theory.

  17. Use of Fuzzycones for Sun-Only Attitude Determination: THEMIS Becomes ARTEMIS

    Science.gov (United States)

    Hashmall, Joseph A.; Felikson, Denis; Sedlak, Joseph E.

    2009-01-01

    In order for two THEMIS probes to successfully transition to ARTEMIS it will be necessary to determine attitudes with moderate accuracy using Sun sensor data only. To accomplish this requirement, an implementation of the Fuzzycones maximum likelihood algorithm was developed. The effect of different measurement uncertainty models on Fuzzycones attitude accuracy was investigated and a bin-transition technique was introduced to improve attitude accuracy using data with uniform error distributions. The algorithm was tested with THEMIS data and in simulations. The analysis results show that the attitude requirements can be met using Fuzzycones and data containing two bin-transitions.

  18. Not All SCID Pigs Are Created Equally: Two Independent Mutations in the Artemis Gene Cause SCID in Pigs.

    Science.gov (United States)

    Waide, Emily H; Dekkers, Jack C M; Ross, Jason W; Rowland, Raymond R R; Wyatt, Carol R; Ewen, Catherine L; Evans, Alyssa B; Thekkoot, Dinesh M; Boddicker, Nicholas J; Serão, Nick V L; Ellinwood, N Matthew; Tuggle, Christopher K

    2015-10-01

    Mutations in >30 genes are known to result in impairment of the adaptive immune system, causing a group of disorders collectively known as SCID. SCID disorders are split into groups based on their presence and/or functionality of B, T, and NK cells. Piglets from a line of Yorkshire pigs at Iowa State University were shown to be affected by T(-)B(-)NK(+) SCID, representing, to our knowledge, the first example of naturally occurring SCID in pigs. In this study, we present evidence for two spontaneous mutations as the molecular basis for this SCID phenotype. Flow cytometry analysis of thymocytes showed an increased frequency of immature T cells in SCID pigs. Fibroblasts from these pigs were more sensitive to ionizing radiation than non-SCID piglets, eliminating the RAG1 and RAG2 genes. Genetic and molecular analyses showed that two mutations were present in the Artemis gene, which in the homozygous or compound heterozygous state cause the immunodeficient phenotype. Rescue of SCID fibroblast radiosensitivity by human Artemis protein demonstrated that the identified Artemis mutations are the direct cause of this cellular phenotype. The work presented in the present study reveals two mutations in the Artemis gene that cause T(-)B(-)NK(+) SCID in pigs. The SCID pig can be an important biomedical model, but these mutations would be undesirable in commercial pig populations. The identified mutations and associated genetic tests can be used to address both of these issues. PMID:26320255

  19. The ArT\\'eMiS wide-field submillimeter camera: preliminary on-sky performances at 350 microns

    CERN Document Server

    Reveret, Vincent; Pennec, Jean Le; Talvard, Michel; Agnèse, Patrick; Arnaud, Agnès; Clerc, Laurent; de Breuck, Carlos; Cigna, Jean-Charles; Delisle, Cyrille; Doumayrou, Eric; Duband, Lionel; Dubreuil, Didier; Dumaye, Luc; Ercolani, Eric; Gallais, Pascal; Groult, Elodie; Jourdan, Thierry; Leriche, Bernadette; Maffei, Bruno; Lortholary, Michel; Martignac, Jérôme; Rabaud, Wilfried; Relland, Johan; Rodriguez, Louis; Vandeneynde, Aurélie; Visticot, François

    2014-01-01

    ArTeMiS is a wide-field submillimeter camera operating at three wavelengths simultaneously (200, 350 and 450 microns). A preliminary version of the instrument equipped with the 350 microns focal plane, has been successfully installed and tested on APEX telescope in Chile during the 2013 and 2014 austral winters. This instrument is developed by CEA (Saclay and Grenoble, France), IAS (France) and University of Manchester (UK) in collaboration with ESO. We introduce the mechanical and optical design, as well as the cryogenics and electronics of the ArTeMiS camera. ArTeMiS detectors are similar to the ones developed for the Herschel PACS photometer but they are adapted to the high optical load encountered at APEX site. Ultimately, ArTeMiS will contain 4 sub-arrays at 200 microns and 2x8 sub-arrays at 350 and 450 microns. We show preliminary lab measurements like the responsivity of the instrument to hot and cold loads illumination and NEP calculation. Details on the on-sky commissioning runs made in 2013 and 2014...

  20. Repeatability and interobserver reproducibility of Artemis-2 high-frequency ultrasound in determination of human corneal thickness

    Directory of Open Access Journals (Sweden)

    Ogbuehi KC

    2012-05-01

    Full Text Available Kelechi C Ogbuehi, Uchechukwu L OsuagwuOutpatient Clinic, Department of Optometry, King Saud University, Riyadh, Kingdom of Saudi ArabiaBackground: The purpose of this study was to assess the repeatability and limits of agreement of corneal thickness values measured by a high-frequency ultrasound (Artemis-2, hand-held ultrasound pachymeter (DGH-500 and a specular microscope (SP-3000P.Methods: Central corneal thickness (CCT was analyzed in this prospective randomized study that included 32 patients (18 men and 14 women aged 21–24 years. Measurements were obtained in two sessions, one week apart, by two examiners with three devices in a randomized order. Nine measurements were taken (three with each device on one randomly selected eye of each patient in each measurement session. The coefficient of repeatability and interobserver reproducibility for the values of each method were calculated. The limits of agreement between techniques were also evaluated.Results: There were no significant differences in CCT values between sessions for each of the three devices (P > 0.05. The repeatability coefficients for the Artemis-2 (±8 µm/±9 µm were superior to those of the SP-3000P (±9 µm/±11 µm and DGH 500 (±12 µm/±12 µm in session 1/session 2 respectively, while the interobserver reproducibility index (differences between session 1 and session 2 was superior for the SP-3000P (±17 µm with respect to DHG-500 (±29 µm and the Artemis-2 (±31 µm. In session 1 and session 2, the limits of agreement between the techniques were 35 µm to -31 µm and 34 to -20 µm, respectively, for DGH-500 versus Artemis-2, 73 µm to 3 µm and 60 µm to 9 µm for Artemis-2 versus SP-3000P, and 58 µm to 22 µm and 72 µm to 10 µm for DGH-500 versus SP-3000P comparisons. The DGH-500 and Artemis-2 gave similar values (P > 0.05 in both sessions, but both (Artemis-2 and DGH-500 values were significantly greater than that of the SP-3000P (P < 0.05 in both sessions

  1. Lectures on functor homology

    CERN Document Server

    Touzé, Antoine

    2015-01-01

    This book features a series of lectures that explores three different fields in which functor homology (short for homological algebra in functor categories) has recently played a significant role. For each of these applications, the functor viewpoint provides both essential insights and new methods for tackling difficult mathematical problems. In the lectures by Aurélien Djament, polynomial functors appear as coefficients in the homology of infinite families of classical groups, e.g. general linear groups or symplectic groups, and their stabilization. Djament’s theorem states that this stable homology can be computed using only the homology with trivial coefficients and the manageable functor homology. The series includes an intriguing development of Scorichenko’s unpublished results. The lectures by Wilberd van der Kallen lead to the solution of the general cohomological finite generation problem, extending Hilbert’s fourteenth problem and its solution to the context of cohomology. The focus here is o...

  2. Lectures on knot homology

    CERN Document Server

    Nawata, Satoshi

    2015-01-01

    We provide various formulations of knot homology that are predicted by string dualities. In addition, we also explain the rich algebraic structure of knot homology which can be understood in terms of geometric representation theory in these formulations. These notes are based on lectures in the workshop "Physics and Mathematics of Link Homology" at Centre de Recherches Math\\'ematiques, Universit\\'e de Montr\\'eal.

  3. Homological stabilizer codes

    International Nuclear Information System (INIS)

    In this paper we define homological stabilizer codes on qubits which encompass codes such as Kitaev’s toric code and the topological color codes. These codes are defined solely by the graphs they reside on. This feature allows us to use properties of topological graph theory to determine the graphs which are suitable as homological stabilizer codes. We then show that all toric codes are equivalent to homological stabilizer codes on 4-valent graphs. We show that the topological color codes and toric codes correspond to two distinct classes of graphs. We define the notion of label set equivalencies and show that under a small set of constraints the only homological stabilizer codes without local logical operators are equivalent to Kitaev’s toric code or to the topological color codes. - Highlights: ► We show that Kitaev’s toric codes are equivalent to homological stabilizer codes on 4-valent graphs. ► We show that toric codes and color codes correspond to homological stabilizer codes on distinct graphs. ► We find and classify all 2D homological stabilizer codes. ► We find optimal codes among the homological stabilizer codes.

  4. Direct measurements of laser light aberration from the ARTEMIS geostationary satellite through thin clouds

    CERN Document Server

    Kuzkov, Volodymyr; Sodnik, Zoran

    2015-01-01

    A precise ground based telescope system was developed for laser communication experiments with the geostationary satellite ARTEMIS of ESA. Precise tracking of the satellite was realized by using time resolved coordinates of the satellite. During the experiments, the time propagation of laser signal from the satellite and the point-ahead angle for the laser beam were calculated. Some laser experiments though thin clouds were performed. A splitting of some images of the laser beam from the satellite along declination and right ascension coordinates of telescope could be observed through thin clouds. The splitting along the declination coordinate may be interpreted as refraction in the atmosphere. The splitting along the right ascension coordinate is equivalent to the calculated point-ahead angle for the satellite. We find out that a small part of laser beam was observed ahead of the velocity vector in the point where the satellite would be after the laser light from the satellite reaches the telescope. These re...

  5. Sutures and contact homology I

    OpenAIRE

    Colin, Vincent; Ghiggini, Paolo; Honda, Ko; Hutchings, Michael

    2010-01-01

    We define a relative version of contact homology for contact manifolds with convex boundary, and prove basic properties of this relative contact homology. Similar considerations also hold for embedded contact homology.

  6. Understanding temporal and spatial variability of the lunar helium atmosphere using simultaneous observations from LRO, LADEE, and ARTEMIS

    Science.gov (United States)

    Hurley, Dana M.; Cook, Jason C.; Benna, Mehdi; Halekas, Jasper S.; Feldman, Paul D.; Retherford, Kurt D.; Hodges, R. Richard; Grava, Cesare; Mahaffy, Paul; Gladstone, G. Randall; Greathouse, Thomas; Kaufmann, David E.; Elphic, Richard C.; Stern, S. Alan

    2016-07-01

    Simultaneous measurements of helium in the exosphere of the Moon are made from the Lunar Reconnaissance Orbiter (LRO) Lyman Alpha Mapping Project (LAMP) and the Lunar Atmosphere and Dust Environment Explorer (LADEE) Neutral Mass Spectrometer (NMS) through the entire 5-month span of the LADEE mission. In addition, the ARTEMIS mission monitored the solar wind alpha particle flux to the Moon. Modeling the lunar helium exosphere, we relate the LAMP polar observations to the LADEE equatorial observations. Further, using the ARTEMIS alpha flux in the Monte Carlo model reproduces the temporal variations in helium density. Comparing the LAMP data to the LADEE data shows excellent agreement. Comparing those with the ARTEMIS data reveals that the solar wind alpha flux is the primary driver to variability in the helium exosphere throughout the LADEE mission. Using a decay time for exospheric helium of 5 days, we determine that the solar wind contributes 64 ± 5% of the helium to the lunar exosphere. The remaining 36 ± 5% is presumed to come from outgassing of radiogenic helium from the interior of the Moon. Furthermore, the model reproduces the measurements if 63 ± 6% of the incident alpha particles are converted to thermalized helium atoms through the interaction between the alphas and the lunar surface. However, these values are dependent on both inferred source rates from LAMP and LADEE observations and on the assumed time constant of the exospheric decay rate.

  7. Braid Floer homology

    Science.gov (United States)

    van den Berg, J. B.; Ghrist, R.; Vandervorst, R. C.; Wójcik, W.

    2015-09-01

    Area-preserving diffeomorphisms of a 2-disc can be regarded as time-1 maps of (non-autonomous) Hamiltonian flows on R / Z ×D2. The periodic flow-lines define braid (conjugacy) classes, up to full twists. We examine the dynamics relative to such braid classes and define a new invariant for such classes, the BRAID FLOER HOMOLOGY. This refinement of Floer homology, originally used for the Arnol'd Conjecture, yields a Morse-type forcing theory for periodic points of area-preserving diffeomorphisms of the 2-disc based on braiding. Contributions of this paper include (1) a monotonicity lemma for the behavior of the nonlinear Cauchy-Riemann equations with respect to algebraic lengths of braids; (2) establishment of the topological invariance of the resulting braid Floer homology; (3) a shift theorem describing the effect of twisting braids in terms of shifting the braid Floer homology; (4) computation of examples; and (5) a forcing theorem for the dynamics of Hamiltonian disc maps based on braid Floer homology.

  8. Gorenstein homological dimensions

    DEFF Research Database (Denmark)

    Holm, Henrik Granau

    2004-01-01

    In basic homological algebra, the projective, injective and 2at dimensions of modules play an important and fundamental role. In this paper, the closely related Gorenstein projective, Gorenstein injective and Gorenstein 2at dimensions are studied. There is a variety of nice results about Gorenstein...... dimensions over special commutative noetherian rings; very often local Cohen–Macaulay rings with a dualizing module. These results are done by Avramov, Christensen, Enochs, Foxby, Jenda, Martsinkovsky and Xu among others. The aim of this paper is to generalize these results, and to give homological...

  9. Introduction to sutured Floer homology

    OpenAIRE

    Altman, Irida

    2013-01-01

    This article is a standalone introduction to sutured Floer homology for graduate students in geometry and topology. It is divided into three parts. The first part is an introductory level exposition of Lagrangian Floer homology. The second part is a construction of Heegaard Floer homology as a special, and slightly modified, case of Lagrangian Floer homology. The third part covers the background on sutured manifolds, the definition of sutured Floer homology, as well as a discussion of its mos...

  10. Limits on Fast Radio Bursts at 145 MHz with ARTEMIS, a real-time software backend

    CERN Document Server

    Karastergiou, A; Armour, W; Williams, C; Mort, B; Dulwich, F; Salvini, S; Magro, A; Roberts, S; Serylak, M; Doo, A; Bilous, A V; Breton, R P; Falcke, H; Griessmeier, J -M; Hessels, J W T; Keane, E F; Kondratiev, V I; Kramer, M; van Leeuwen, J; Noutsos, A; Oslowski, S; Sobey, C; Stappers, B W; Weltevrede, P

    2015-01-01

    Fast Radio Bursts (FRBs), are millisecond radio signals that exhibit dispersion larger than what the Galactic electron density can account for. We have conducted a 1446 hour survey for Fast Radio Bursts (FRBs) at 145~MHz, covering a total of 4193 sq. deg on the sky. We used the UK station of the LOFAR radio telescope -- the Rawlings Array -- , accompanied for a majority of the time by the LOFAR station at Nan\\c{c}ay, observing the same fields at the same frequency. Our real-time search backend, ARTEMIS, utilizes graphics processing units to search for pulses with dispersion measures up to 320 cm$^{-3}$ pc. Previous derived FRB rates from surveys around 1.4~GHz, and favoured FRB interpretations, motivated this survey, despite all previous detections occurring at higher dispersion measures. We detected no new FRBs above a signal-to-noise threshold of 10, leading to the most stringent upper limit yet on the FRB event rate at these frequencies: 29 sky$^{-1}$ day$^{-1}$ for 5~ms-duration pulses above 62~Jy. The no...

  11. Pseudocycles and Integral Homology

    OpenAIRE

    Zinger, Aleksey

    2006-01-01

    We describe a natural isomorphism between the set of equivalence classes of pseudocycles and the integral homology groups of a smooth manifold. Our arguments generalize to settings well-suited for applications in enumerative algebraic geometry and for construction of the virtual fundamental class in the Gromov-Witten theory.

  12. Homology cylinders and sutured manifolds for homologically fibered knots

    OpenAIRE

    Goda, Hiroshi; Sakasai, Takuya

    2008-01-01

    Sutured manifolds defined by Gabai are useful in the geometrical study of knots and 3-dimensional manifolds. On the other hand, homology cylinders are in an important position in the recent theory of homology cobordisms of surfaces and finite-type invariants. We study a relationship between them by focusing on sutured manifolds associated with a special class of knots which we call {\\it homologically fibered knots}. Then we use invariants of homology cylinders to give applications to...

  13. Development and verification of a high performance multi-group SP3 transport capability in the ARTEMIS core simulator

    International Nuclear Information System (INIS)

    For satisfaction of future global customer needs, dedicated efforts are being coordinated internationally and pursued continuously at AREVA NP. The currently ongoing CONVERGENCE project is committed to the development of the ARCADIAR next generation core simulation software package. ARCADIAR will be put to global use by all AREVA NP business regions, for the entire spectrum of core design processes, licensing computations and safety studies. As part of the currently ongoing trend towards more sophisticated neutronics methodologies, an SP3 nodal transport concept has been developed for ARTEMIS which is the steady-state and transient core simulation part of ARCADIAR. For enabling a high computational performance, the SPN calculations are accelerated by applying multi-level coarse mesh re-balancing. In the current implementation, SP3 is about 1.4 times as expensive computationally as SP1 (diffusion). The developed SP3 solution concept is foreseen as the future computational workhorse for many-group 3D pin-by-pin full core computations by ARCADIAR. With the entire numerical workload being highly parallelizable through domain decomposition techniques, associated CPU-time requirements that adhere to the efficiency needs in the nuclear industry can be expected to become feasible in the near future. The accuracy enhancement obtainable by using SP3 instead of SP1 has been verified by a detailed comparison of ARTEMIS 16-group pin-by-pin SPN results with KAERI's DeCart reference results for the 2D pin-by-pin Purdue UO2/MOX benchmark. This article presents the accuracy enhancement verification and quantifies the achieved ARTEMIS-SP3 computational performance for a number of 2D and 3D multi-group and multi-box (up to pin-by-pin) core computations. (authors)

  14. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Darroudi, Firouz [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands)]. E-mail: F.Darroudi@LUMC.NL; Wiegant, Wouter [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Meijers, Matty [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Friedl, Anna A. [Radiobiological Institute, University of Munich, Munich (Germany); Institute of Radiobiology, GSF National Research Center for Environment and Health, Neuherberg (Germany); Burg, Mirjam van der [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Fomina, Janna [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Dongen, Jacques J.M. van [Department of Immunology, Erasmus Medical Centre, Rotterdam (Netherlands); Gent, Dik C. van [Department of Cell Biology and Genetics, Erasmus Medical Centre, Rotterdam (Netherlands); Zdzienicka, Malgorzata Z. [Department of Toxicogenetics, Leiden University Medical Centre, Einthovenweg 20, 2300RC Leiden (Netherlands); Department of Molecular Cell Genetics, Collegium Medicum, N. Corpernicus University, Bydgoszcz (Poland)

    2007-02-03

    We analyzed the phenotype of cells derived from SCID patients with different mutations in the Artemis gene. Using clonogenic survival assay an increased sensitivity was found to X-rays (2-3-fold) and bleomycin (2-fold), as well as to etoposide, camptothecin and methylmethane sulphonate (up to 1.5-fold). In contrast, we did not find increased sensitivity to cross-linking agents mitomycin C and cis-platinum. The kinetics of DSB repair assessed by pulsed-field gel electrophoresis and {gamma}H2AX foci formation after ionizing irradiation, indicate that 15-20% of DSB are not repaired in Artemis-deficient cells. In order to get a better understanding of the repair defect in Artemis-deficient cells, we studied chromosomal damage at different stages of the cell cycle. In contrast to AT cells, Artemis-deficient cells appear to have a normal G{sub 1}/S-block that resulted in a similar frequency of dicentrics and translocations, however, frequency of acentrics fragments was found to be 2-4-fold higher compared to normal fibroblasts. Irradiation in G{sub 2} resulted in a higher frequency of chromatid-type aberrations (1.5-3-fold) than in normal cells, indicating that a fraction of DSB requires Artemis for proper repair. Our data are consistent with a function of Artemis protein in processing of a subset of complex DSB, without G{sub 1} cell cycle checkpoint defects. This type of DSB can be induced in high proportion and persist through S-phase and in part might be responsible for the formation of chromatid-type exchanges in G{sub 1}-irradiated Artemis-deficient cells. Among different human radiosensitive fibroblasts studied for endogenous (in untreated samples) as well as X-ray-induced DNA damage, the ranking order on the basis of higher incidence of spontaneously occurring chromosomal alterations and induced ones was: ligase 4 {>=} AT > Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when

  15. The FAO/NASA/NLR Artemis system - An integrated concept for environmental monitoring by satellite in support of food/feed security and desert locust surveillance

    Science.gov (United States)

    Hielkema, J. U.; Howard, J. A.; Tucker, C. J.; Van Ingen Schenau, H. A.

    1987-01-01

    The African real time environmental monitoring using imaging satellites (Artemis) system, which should monitor precipitation and vegetation conditions on a continental scale, is presented. The hardware and software characteristics of the system are illustrated and the Artemis databases are outlined. Plans for the system include the use of hourly digital Meteosat data and daily NOAA/AVHRR data to study environmental conditions. Planned mapping activities include monthly rainfall anomaly maps, normalized difference vegetation index maps for ten day and monthly periods with a spatial resolution of 7.6 km, ten day crop/rangeland moisture availability maps, and desert locust potential breeding activity factor maps for a plague prevention program.

  16. Preparing and measuring ultra-small radiocarbon samples with the ARTEMIS AMS facility in Saclay, France

    Energy Technology Data Exchange (ETDEWEB)

    Delque-Kolic, E., E-mail: emmanuelle.delque-kolic@cea.fr [LMC14, CEA Saclay, Batiment 450 Porte 4E, 91191 Gif sur Yvette (France); Comby-Zerbino, C.; Ferkane, S.; Moreau, C.; Dumoulin, J.P.; Caffy, I.; Souprayen, C.; Quiles, A.; Bavay, D.; Hain, S.; Setti, V. [LMC14, CEA Saclay, Batiment 450 Porte 4E, 91191 Gif sur Yvette (France)

    2013-01-15

    The ARTEMIS facility in Saclay France measures, on average, 4500 samples a year for French organizations working in an array of fields, including environmental sciences, archeology and hydrology. In response to an increasing demand for the isolation of specific soil compounds and organic water fractions, we were motivated to evaluate our ability to reduce microgram samples using our standard graphitization lines and to measure the graphite thus obtained with our 3MV NEC Pelletron AMS. Our reduction facility consists of two fully automated graphitization lines. Each line has 12 reduction reactors with a reduction volume of 18 ml for the first line and 12 ml for the second. Under routine conditions, we determined that we could reduce the samples down to 10 {mu}g of carbon, even if the graphitization yield is consequently affected by the lower sample mass. Our results when testing different Fe/C ratios suggest that an amount of 1.5 mg of Fe powder was ideal (instead of lower amounts of catalyst) to prevent the sample from deteriorating too quickly under the Cs+ beam, and to facilitate pressing procedures. Several sets of microsamples produced from HOxI standard, international references and backgrounds were measured. When measuring {sup 14}C-free wood charcoal and HOxI samples we determined that our modern and dead blanks, due to the various preparation steps, were of 1.1 {+-} 0.8 and 0.2 {+-} 0.1 {mu}g, respectively. The results presented here were obtained for IAEA-C1, {sup 14}C-free wood, IAEA-C6, IAEA-C2 and FIRI C.

  17. Persistent Homology of Filtered Covers

    CERN Document Server

    Fraser, Maia

    2012-01-01

    We prove an extension to the simplicial Nerve Lemma which establishes isomorphism of persistent homology groups, in the case where the covering spaces are filtered. While persistent homology is now widely used in topological data analysis, the usual Nerve Lemma does not provide isomorphism of persistent homology groups. Our argument involves some homological algebra: the key point being that although the maps produced in the standard proof of the Nerve Lemma do not commute as maps of chain complexes, the maps they induce on homology do.

  18. Equivariant elliptic homology

    International Nuclear Information System (INIS)

    In a previous paper we studied the modular properties of indices of elliptic operators on twisted loop spaces of manifolds with finite group actions. This motivates the introduction of the universal twisted elliptic genus. This genus can be interpreted as a ring homomorphism from the equivariant bordism ring MU*G to a ring Ell*G. It is shown that the functor X→Ell*G=MU*G(X)xMU*GEll*G defines an equivariant homology theory, and that the associated cohomology theory satisfies a conjecture of Atiyah and Segal about generalized Lefchetz formulas. (author). 24 refs

  19. Intersection homology Kunneth theorems

    OpenAIRE

    Friedman, Greg

    2008-01-01

    Cohen, Goresky and Ji showed that there is a Kunneth theorem relating the intersection homology groups $I^{\\bar p}H_*(X\\times Y)$ to $I^{\\bar p}H_*(X)$ and $I^{\\bar p}H_*(Y)$, provided that the perversity $\\bar p$ satisfies rather strict conditions. We consider biperversities and prove that there is a K\\"unneth theorem relating $I^{\\bar p,\\bar q}H_*(X\\times Y)$ to $I^{\\bar p}H_*(X)$ and $I^{\\bar q}H_*(Y)$ for all choices of $\\bar p$ and $\\bar q$. Furthermore, we prove that the Kunneth theorem...

  20. High resolution observations with Artemis-IV and the NRH. I. Type IV associated narrow-band bursts

    CERN Document Server

    Bouratzis, C; Alissandrakis, C E; Preka-Papadema, P; Moussas, X; Caroubalos, C; Tsitsipis, P; Kontogeorgos, A

    2016-01-01

    Narrow band bursts appear on dynamic spectra from microwave to decametric frequencies as fine structures with very small duration and bandwidth. They are thought to mark small scale magnetic reconnection. We analyzed 27 metric type-IV events with narrow band bursts observed by the ARTEMIS-IV radiospectrograph in 30/6/1999-1/8/2010. We examined the morphological characteristics of isolated narrow-band bursts and groups or chains of spikes. The events were recorded with the SAO (10 ms cadence) receiver of ARTEMIS-IV in the 270-450 MHz range. We measured the duration, spectral width, and frequency drift of ~12000 individual narrow-band bursts, groups, and chains. Spike sources were imaged with the NRH for the event of 21 April 2003. The mean duration of individual bursts at fixed frequency was ~100 ms, while the instantaneous relative bandwidth was ~2%. Some bursts had measurable frequency drift, positive or negative. Often spikes appeared in chains, which were closely spaced in time (column chains) or in freque...

  1. Lunar exospheric helium observations of LRO/LAMP coordinated with ARTEMIS

    Science.gov (United States)

    Grava, C.; Retherford, K. D.; Hurley, D. M.; Feldman, P. D.; Gladstone, G. R.; Greathouse, T. K.; Cook, J. C.; Stern, S. A.; Pryor, W. R.; Halekas, J. S.; Kaufmann, D. E.

    2016-07-01

    We present results from Lunar Reconnaissance Orbiter's (LRO) UV spectrograph LAMP (Lyman-Alpha Mapping Project) campaign to study the lunar atmosphere. Several off-nadir maneuvers (lateral rolls) were performed to search for resonantly scattering species, increasing the illuminated line-of-sight (and hence the signal from atoms resonantly scattering the solar photons) compared to previously reported LAMP's "twilight observations" (Cook, J.C., Stern, S.A. [2014]. Icarus 236, 48-55). Helium was the only element distinguishable on a daily basis, and we present latitudinal profiles of its line-of-sight column density in December 2013. We compared the helium line-of-sight column densities with solar wind alpha particle fluxes measured from the ARTEMIS (Acceleration, Reconnection, Turbulence, & Electrodynamics of Moon's Interaction with the Sun) twin spacecraft. Our data show a correlation with the solar wind alpha particle flux, confirming that the solar wind is the main source of the lunar helium. We also support the finding by Benna et al. (Benna, M. et al. [2015]. Geophys. Res. Lett. 42, 3723-3729) and Hurley et al. (Hurley, D.M. et al. [2015]. Icarus, this issue), that a non-zero contribution from endogenic helium, coming from radioactive decay of 232Th and 238U, is present. Moreover, our results suggest that not all of the incident alpha particles are converted to thermalized helium, allowing for a non-negligible fraction to escape as suprathermal helium or simply backscattered from the lunar surface. We compare LAMP-derived helium surface density with the one recorded by the mass spectrometer LACE (Lunar Atmospheric Composition Experiment) deployed on the lunar surface during the Apollo 17 mission, finding good agreement between the two measurements. The LRO/LAMP roll observations presented here are in agreement with the most recent lunar exospheric helium model (Hurley, D.M. et al. [2015]. Icarus, this issue) around mid- to high-latitudes (50-70°) regardless of

  2. 2-categories and cyclic homology

    OpenAIRE

    Slevin, Paul

    2016-01-01

    The topic of this thesis is the application of distributive laws between comonads to the theory of cyclic homology. Explicitly, our main aims are: 1) To study how the cyclic homology of associative algebras and of Hopf algebras in the original sense of Connes and Moscovici arises from a distributive law, and to clarify the role of different notions of bimonad in this generalisation. 2) To extend the procedure of twisting the cyclic homology of a unital associative algebra to any duplicial obj...

  3. Matrix Factorizations and Kauffman Homology

    CERN Document Server

    Gukov, S; Gukov, Sergei; Walcher, Johannes

    2005-01-01

    The topological string interpretation of homological knot invariants has led to several insights into the structure of the theory in the case of sl(N). We study possible extensions of the matrix factorization approach to knot homology for other Lie groups and representations. In particular, we introduce a new triply graded theory categorifying the Kauffman polynomial, test it, and predict the Kauffman homology for several simple knots.

  4. The Geometry of Homological Triangles

    CERN Document Server

    Smarandache, Florentin

    2012-01-01

    This book is addressed to students, professors and researchers of geometry, who will find herein many interesting and original results. The originality of the book The Geometry of Homological Triangles consists in using the homology of triangles as a "filter" through which remarkable notions and theorems from the geometry of the triangle are unitarily passed. Our research is structured in seven chapters, the first four are dedicated to the homology of the triangles, while the last ones to their applications.

  5. Homology of L_{\\infty}-Algebras and Cyclic Homology

    OpenAIRE

    Khalkhali, Masoud

    1998-01-01

    A classical result of Loday-Quillen and Tsygan states that the Lie algebra homology of the algebra of stable matrices over an associative algebra is isomorphic, as a Hopf algebra, to the exterior algebra of the cyclic homology of the algebra. In this paper we develop the necessary tools needed to extend extend this result to the category of L_{\\infty} algebras.

  6. Real-world driving cycles for measuring cars pollutant emissions – Part A: The ARTEMIS European driving cycles

    OpenAIRE

    ANDRE Michel

    2009-01-01

    Dans le cadre du projet de recherche Européen ARTEMIS, une compilation et une synthèse des travaux antérieurs sur les cycles de conduite ont été effectuées en vue de construire un ensemble de cycles de conduite de référence. L'utilisation de ces cycles dans le cadre des nombreuses campagnes de mesure des émissions de polluants des voitures particulières, permettra ainsi d'assurer la compatibilité et l'intégration des données d'émissions dans les systèmes d'inventaires Européens. Pour la const...

  7. Structure and composition of the distant lunar exosphere: Constraints from ARTEMIS observations of ion acceleration in time-varying fields

    Science.gov (United States)

    Halekas, J. S.; Poppe, A. R.; Farrell, W. M.; McFadden, J. P.

    2016-06-01

    By analyzing the trajectories of ionized constituents of the lunar exosphere in time-varying electromagnetic fields, we can place constraints on the composition, structure, and dynamics of the lunar exosphere. Heavy ions travel slower than light ions in the same fields, so by observing the lag between field rotations and the response of ions from the lunar exosphere, we can place constraints on the composition of the ions. Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) provides an ideal platform to utilize such an analysis, since its two-probe vantage allows precise timing of the propagation of field discontinuities in the solar wind, and its sensitive plasma instruments can detect the ion response. We demonstrate the utility of this technique by using fully time-dependent charged particle tracing to analyze several minutes of ion observations taken by the two ARTEMIS probes ~3000-5000 km above the dusk terminator on 25 January 2014. The observations from this time period allow us to reach several interesting conclusions. The ion production at altitudes of a few hundred kilometers above the sunlit surface of the Moon has an unexpectedly significant contribution from species with masses of 40 amu or greater. The inferred distribution of the neutral source population has a large scale height, suggesting that micrometeorite impact vaporization and/or sputtering play an important role in the production of neutrals from the surface. Our observations also suggest an asymmetry in ion production, consistent with either a compositional variation in neutral vapor production or a local reduction in solar wind sputtering in magnetic regions of the surface.

  8. K-Kolmogorov homology groups

    International Nuclear Information System (INIS)

    In the present work we use the idea of the K-groups to define the K-Kolmogorov homology groups, and their induced homomorphisms and boundary operators for the case of a pair of discrete coefficient groups, where K denotes a locally-finite simplicial complex. Moreover, we prove that our homology construction is exact. (author)

  9. Relative Homological Algebra Volume 1

    CERN Document Server

    2011-01-01

    This is the second revised edition of an introduction to contemporary relative homological algebra. It supplies important material essential to understand topics in algebra, algebraic geometry and algebraic topology. Each section comes with exercises providing practice problems for students as well as additional important results for specialists. The book is also suitable for an introductory course in commutative and ordinary homological algebra.

  10. A screen for Listeria monocytogenes hemolytic activity mutants reveals HPF, a homolog of Hibernation Promoting Factor, which is essential for ribosomal hibernation and important for competitive fitness in vitro and in vivo.

    OpenAIRE

    Kline, Benjamin Craft

    2012-01-01

    Listeria monocytogenes is an opportunistic, potentially deadly, foodborne pathogen of humans and other vertebrates. Resistance to stressful conditions such as low pH, high salt, and refrigeration temperatures makes L. monocytogenes ideally suited to thrive on food sources, promoting transmission. A set of conserved virulence factors promotes establishment of infection once L. monocytogenes enters the host. In this work, we sought to better understand both the pathogenesis and the biology of L...

  11. Mod two homology and cohomology

    CERN Document Server

    Hausmann, Jean-Claude

    2014-01-01

    Cohomology and homology modulo 2 helps the reader grasp more readily the basics of a major tool in algebraic topology. Compared to a more general approach to (co)homology this refreshing approach has many pedagogical advantages: It leads more quickly to the essentials of the subject, An absence of signs and orientation considerations simplifies the theory, Computations and advanced applications can be presented at an earlier stage, Simple geometrical interpretations of (co)chains. Mod 2 (co)homology was developed in the first quarter of the twentieth century as an alternative to integral homology, before both became particular cases of (co)homology with arbitrary coefficients. The first chapters of this book may serve as a basis for a graduate-level introductory course to (co)homology. Simplicial and singular mod 2 (co)homology are introduced, with their products and Steenrod squares, as well as equivariant cohomology. Classical applications include Brouwer's fixed point theorem, Poincaré duality, Borsuk-Ula...

  12. Preparation of uniformly labeled NMR samples in Escherichia coli under the tight control of the araBAD promoter: expression of an archaeal homolog of the RNase P Rpp29 protein.

    Science.gov (United States)

    Boomershine, William P; Raj, M L Stephen; Gopalan, Venkat; Foster, Mark P

    2003-04-01

    We report the first use of the tightly regulated araBAD promoter for generating uniformly labeled samples for NMR. The araBAD promoter provides a distinct advantage over that of the most commonly used protein overexpression systems in bacteria (e.g., in pET vectors: T7lac), in that it provides much tighter control over basal expression. However, use of araBAD-regulated expression for preparation of uniformly labeled protein samples for NMR is complicated by the fact that glucose (the most commonly used carbon source in defined minimal media) indirectly represses transcription, and thus, cannot be used. After experimenting with alternative media, we found that uniformly labeled NMR samples can be prepared using the highly regulated arabinose-inducible promoter and that suitable yields can be obtained in defined minimal media containing glycerol, not glucose, as the carbon source. PMID:12699688

  13. Fivebranes and 3-manifold homology

    CERN Document Server

    Gukov, Sergei; Vafa, Cumrun

    2016-01-01

    Motivated by physical constructions of homological knot invariants, we study their analogs for closed 3-manifolds. We show that fivebrane compactifications provide a universal description of various old and new homological invariants of 3-manifolds. In terms of 3d/3d correspondence, such invariants are given by the Q-cohomology of the Hilbert space of partially topologically twisted 3d N=2 theory T[M_3] on a Riemann surface with defects. We demonstrate this by concrete and explicit calculations in the case of monopole/Heegaard Floer homology and a 3-manifold analog of Khovanov-Rozansky link homology. The latter gives a categorification of Chern-Simons partition function. Some of the new key elements include the explicit form of the S-transform and a novel connection between categorification and a previously mysterious role of Eichler integrals in Chern-Simons theory.

  14. On the signatures of magnetic islands and multiple X-lines in the solar wind as observed by ARTEMIS and WIND

    International Nuclear Information System (INIS)

    We report the first observation consistent with a magnetic reconnection generated magnetic island at a solar wind current sheet that was observed on 10 June 2012 by the two ARTEMIS satellites and the upstream WIND satellite. The evidence consists of a core magnetic field within the island which is formed by enhanced Hall magnetic fields across a solar wind reconnection exhaust. The core field at ARTEMIS displays a local dip coincident with a peak plasma density enhancement and a locally slower exhaust speed which differentiates it from a regular solar wind exhaust crossing. Further indirect evidence of magnetic island formation is presented in the form of a tripolar Hall magnetic field, which is supported by an observed electron velocity shear, and plasma density depletion regions which are in general agreement with multiple reconnection X-line signatures at the same current sheet on the basis of predicted signatures of magnetic islands as generated by a kinetic reconnection simulation for solar wind-like conditions. The combined ARTEMIS and WIND observations of tripolar Hall magnetic fields across the same exhaust and Grad–Shrafranov reconstructions of the magnetic field suggest that an elongated magnetic island was encountered which displayed a 4RE normal width and a 43RE extent along the exhaust between two neighboring X-lines. (paper)

  15. Object-oriented persistent homology

    Science.gov (United States)

    Wang, Bao; Wei, Guo-Wei

    2016-01-01

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  16. High resolution observations with Artemis-IV and the NRH. I. Type IV associated narrow-band bursts

    Science.gov (United States)

    Bouratzis, C.; Hillaris, A.; Alissandrakis, C. E.; Preka-Papadema, P.; Moussas, X.; Caroubalos, C.; Tsitsipis, P.; Kontogeorgos, A.

    2016-02-01

    Context. Narrow-band bursts appear on dynamic spectra from microwave to decametric frequencies as fine structures with very small duration and bandwidth. They are believed to be manifestations of small scale energy release through magnetic reconnection. Aims: We analyzed 27 metric type IV events with embedded narrow-band bursts, which were observed by the ARTEMIS-IV radio spectrograph from 30 June 1999 to 1 August 2010. We examined the morphological characteristics of isolated narrow-band structures (mostly spikes) and groups or chains of structures. Methods: The events were recorded with the SAO high resolution (10 ms cadence) receiver of ARTEMIS-IV in the 270-450 MHz range. We measured the duration, spectral width, and frequency drift of ~12 000 individual narrow-band bursts, groups, and chains. Spike sources were imaged with the Nançay radioheliograph (NRH) for the event of 21 April 2003. Results: The mean duration of individual bursts at fixed frequency was ~100 ms, while the instantaneous relative bandwidth was ~2%. Some bursts had measurable frequency drift, either positive or negative. Quite often spikes appeared in chains, which were closely spaced in time (column chains) or in frequency (row chains). Column chains had frequency drifts similar to type-IIId bursts, while most of the row chains exhibited negative frequently drifts with a rate close to that of fiber bursts. From the analysis of NRH data, we found that spikes were superimposed on a larger, slowly varying, background component. They were polarized in the same sense as the background source, with a slightly higher degree of polarization of ~65%, and their size was about 60% of their size in total intensity. Conclusions: The duration and bandwidth distributions did not show any clear separation in groups. Some chains tended to assume the form of zebra, lace stripes, fiber bursts, or bursts of the type-III family, suggesting that such bursts might be resolved in spikes when viewed with high

  17. Localization theorems in topological Hochschild homology and topological cyclic homology

    CERN Document Server

    Blumberg, Andrew J

    2008-01-01

    We construct localization cofiber sequences for the topological Hochschild homology (THH) and topological cyclic homology (TC) of spectral categories. Using a ``global'' construction of the THH and TC of a scheme in terms of the perfect complexes in a spectrally enriched version of the category of unbounded complexes, the sequences specialize to localization cofiber sequences associated to the inclusion of an open subscheme. These are the targets of the cyclotomic trace from the localization sequence of Thomason-Trobaugh in K-theory. We also deduce a version of Thomason's blow-up formula for THH and TC.

  18. The clinical impact of deficiency in DNA non-homologous end-joining.

    Science.gov (United States)

    Woodbine, Lisa; Gennery, Andrew R; Jeggo, Penny A

    2014-04-01

    DNA non-homologous end-joining (NHEJ) is the major DNA double strand break (DSB) repair pathway in mammalian cells. Defects in NHEJ proteins confer marked radiosensitivity in cell lines and mice models, since radiation potently induces DSBs. The process of V(D)J recombination functions during the development of the immune response, and involves the introduction and rejoining of programmed DSBs to generate an array of diverse T and B cells. NHEJ rejoins these programmed DSBs. Consequently, NHEJ deficiency confers (severe) combined immunodeficiency - (S)CID - due to a failure to carry out V(D)J recombination efficiently. NHEJ also functions in class switch recombination, another step enhancing T and B cell diversity. Prompted by these findings, a search for radiosensitivity amongst (S)CID patients revealed a radiosensitive sub-class, defined as RS-SCID. Mutations in NHEJ genes, defining human syndromes deficient in DNA ligase IV (LIG4 Syndrome), XLF-Cernunnos, Artemis or DNA-PKcs, have been identified in such patients. Mutations in XRCC4 or Ku70,80 in patients have not been identified. RS-SCID patients frequently display additional characteristics including microcephaly, dysmorphic facial features and growth delay. Here, we overview the clinical spectrum of RS-SCID patients and discuss our current understanding of the underlying biology. PMID:24629483

  19. Reprint of "The clinical impact of deficiency in DNA non-homologous end-joining".

    Science.gov (United States)

    Woodbine, Lisa; Gennery, Andrew R; Jeggo, Penny A

    2014-05-01

    DNA non-homologous end-joining (NHEJ) is the major DNA double strand break (DSB) repair pathway in mammalian cells. Defects in NHEJ proteins confer marked radiosensitivity in cell lines and mice models, since radiation potently induces DSBs. The process of V(D)J recombination functions during the development of the immune response, and involves the introduction and rejoining of programmed DSBs to generate an array of diverse T and B cells. NHEJ rejoins these programmed DSBs. Consequently, NHEJ deficiency confers (severe) combined immunodeficiency - (S)CID - due to a failure to carry out V(D)J recombination efficiently. NHEJ also functions in class switch recombination, another step enhancing T and B cell diversity. Prompted by these findings, a search for radiosensitivity amongst (S)CID patients revealed a radiosensitive sub-class, defined as RS-SCID. Mutations in NHEJ genes, defining human syndromes deficient in DNA ligase IV (LIG4 Syndrome), XLF-Cernunnos, Artemis or DNA-PKcs, have been identified in such patients. Mutations in XRCC4 or Ku70,80 in patients have not been identified. RS-SCID patients frequently display additional characteristics including microcephaly, dysmorphic facial features and growth delay. Here, we overview the clinical spectrum of RS-SCID patients and discuss our current understanding of the underlying biology. PMID:24780557

  20. Grid diagrams and Khovanov homology

    DEFF Research Database (Denmark)

    Droz, Jean-Marie; Wagner, Emmanuel

    2009-01-01

    We explain how to compute the Jones polynomial of a link from one of its grid diagrams and we observe a connection between Bigelow’s homological definition of the Jones polynomial and Kauffman’s definition of the Jones polynomial. Consequently, we prove that the Maslov grading on the Seidel...

  1. Local contact homology and applications

    CERN Document Server

    Hryniewicz, Umberto

    2012-01-01

    We introduce a local version of contact homology for an isolated periodic orbit $\\gamma$ of the Reeb flow and prove that its rank is uniformly bounded for isolated iterations. Several applications are obtained, including a generalization of Gromoll-Meyer's theorem on the existence of infinitely many simple periodic orbits, resonance relations and conditions for the existence of non-hyperbolic periodic orbits.

  2. Which way up? Recognition of homologous DNA segments in parallel and antiparallel alignment

    CERN Document Server

    Lee, Dominic J; Albrecht, Tim; Kornyshev, Alexei A

    2014-01-01

    Homologous gene shuffling between DNA promotes genetic diversity and is an important pathway for DNA repair. For this to occur, homologous genes need to find and recognize each other. However, despite its central role in homologous recombination, the mechanism of homology recognition is still an unsolved puzzle. While specific proteins are known to play a role at later stages of recombination, an initial coarse grained recognition step has been proposed. This relies on the sequence dependence of the DNA structural parameters, such as twist and rise, mediated by intermolecular interactions, in particular electrostatic ones. In this proposed mechanism, sequences having the same base pair text, or are homologous, have lower interaction energy than those sequences with uncorrelated base pair texts; the difference termed the recognition energy. Here, we probe how the recognition energy changes when one DNA fragment slides past another, and consider, for the first time, homologous sequences in antiparallel alignmen...

  3. Development and verification of a high performance multi-group SP{sub 3} transport capability in the ARTEMIS core simulator

    Energy Technology Data Exchange (ETDEWEB)

    Van Geemert, Rene [AREVA, AREVA NP, Erlangen (Germany)

    2008-07-01

    For satisfaction of future global customer needs, dedicated efforts are being coordinated internationally and pursued continuously at AREVA NP. The currently ongoing CONVERGENCE project is committed to the development of the ARCADIA{sup R} next generation core simulation software package. ARCADIA{sup R} will be put to global use by all AREVA NP business regions, for the entire spectrum of core design processes, licensing computations and safety studies. As part of the currently ongoing trend towards more sophisticated neutronics methodologies, an SP{sub 3} nodal transport concept has been developed for ARTEMIS which is the steady-state and transient core simulation part of ARCADIA{sup R}. For enabling a high computational performance, the SP{sub N} calculations are accelerated by applying multi-level coarse mesh re-balancing. In the current implementation, SP{sub 3} is about 1.4 times as expensive computationally as SP{sub 1} (diffusion). The developed SP{sub 3} solution concept is foreseen as the future computational workhorse for many-group 3D pin-by-pin full core computations by ARCADIA{sup R}. With the entire numerical workload being highly parallelizable through domain decomposition techniques, associated CPU-time requirements that adhere to the efficiency needs in the nuclear industry can be expected to become feasible in the near future. The accuracy enhancement obtainable by using SP{sub 3} instead of SP{sub 1} has been verified by a detailed comparison of ARTEMIS 16-group pin-by-pin SP{sub N} results with KAERI's DeCart reference results for the 2D pin-by-pin Purdue UO{sub 2}/MOX benchmark. This article presents the accuracy enhancement verification and quantifies the achieved ARTEMIS-SP{sub 3} computational performance for a number of 2D and 3D multi-group and multi-box (up to pin-by-pin) core computations. (authors)

  4. Search for antimatter in 1012 eV cosmic rays using Artemis method and interpretation of the cosmic rays spectrum

    International Nuclear Information System (INIS)

    This thesis is divided into three parts. The first part is a review of the present knowledge of the antimatter and of the cosmic rays. Theoretical and experimental aspects are presented. It is demonstrated that a measurement of the antimatter abundance in TeV cosmic rays is of fundamental interest, and would establish the symmetric or asymmetric nature of the Universe. The second part is dedicated to the method of antimatter research through the Earth Moon ion spectrometer (ARTEMIS). The account is given of the winter 1996-97 41-nights observation campaign undertaken at the Whipple Observatory in Arizona (USA). A 109 photomultiplier camera is operated on the 40 meter telescope to detect by Cherenkov imaging the cosmic ray initiated showers. We describe the performance of an optical filter used to reduce the noise. The development and the utilization of a simulation program are described. The main work is the analysis of the data: data characterization, understanding of the apparatus, understanding of the noise and its influence, calibration, search for signals by different methods. Subtle systematic effects are uncovered. The simulations establish that the amount of data is insufficient to reveal a shadow effect in the cosmic ray flux. The conclusion of this work is that the experimental setup was not suitable, and we propose important improvements of the method based on a bigger focal plane that would allow to reach a one percent sensitivity on the antimatter content of the cosmic rays. In the third part of the thesis, an interpretation of the total cosmic ray spectrum is proposed and discussed. (author)

  5. Persistent Homology of Collaboration Networks

    Directory of Open Access Journals (Sweden)

    C. J. Carstens

    2013-01-01

    Full Text Available Over the past few decades, network science has introduced several statistical measures to determine the topological structure of large networks. Initially, the focus was on binary networks, where edges are either present or not. Thus, many of the earlier measures can only be applied to binary networks and not to weighted networks. More recently, it has been shown that weighted networks have a rich structure, and several generalized measures have been introduced. We use persistent homology, a recent technique from computational topology, to analyse four weighted collaboration networks. We include the first and second Betti numbers for the first time for this type of analysis. We show that persistent homology corresponds to tangible features of the networks. Furthermore, we use it to distinguish the collaboration networks from similar random networks.

  6. Homologous Recombination as a Replication Fork Escort: Fork-Protection and Recovery

    Directory of Open Access Journals (Sweden)

    Audrey Costes

    2012-12-01

    Full Text Available Homologous recombination is a universal mechanism that allows DNA repair and ensures the efficiency of DNA replication. The substrate initiating the process of homologous recombination is a single-stranded DNA that promotes a strand exchange reaction resulting in a genetic exchange that promotes genetic diversity and DNA repair. The molecular mechanisms by which homologous recombination repairs a double-strand break have been extensively studied and are now well characterized. However, the mechanisms by which homologous recombination contribute to DNA replication in eukaryotes remains poorly understood. Studies in bacteria have identified multiple roles for the machinery of homologous recombination at replication forks. Here, we review our understanding of the molecular pathways involving the homologous recombination machinery to support the robustness of DNA replication. In addition to its role in fork-recovery and in rebuilding a functional replication fork apparatus, homologous recombination may also act as a fork-protection mechanism. We discuss that some of the fork-escort functions of homologous recombination might be achieved by loading of the recombination machinery at inactivated forks without a need for a strand exchange step; as well as the consequence of such a model for the stability of eukaryotic genomes.

  7. The Homological Nature of Entropy

    Directory of Open Access Journals (Sweden)

    Pierre Baudot

    2015-05-01

    Full Text Available We propose that entropy is a universal co-homological class in a theory associated to a family of observable quantities and a family of probability distributions. Three cases are presented: (1 classical probabilities and random variables; (2 quantum probabilities and observable operators; (3 dynamic probabilities and observation trees. This gives rise to a new kind of topology for information processes, that accounts for the main information functions: entropy, mutual-informations at all orders, and Kullback–Leibler divergence and generalizes them in several ways. The article is divided into two parts, that can be read independently. In the first part, the introduction, we provide an overview of the results, some open questions, future results and lines of research, and discuss briefly the application to complex data. In the second part we give the complete definitions and proofs of the theorems A, C and E in the introduction, which show why entropy is the first homological invariant of a structure of information in four contexts: static classical or quantum probability, dynamics of classical or quantum strategies of observation of a finite system.

  8. Snapshots of Earth's magnetosphere and the near-Earth solar wind from the THEMIS and ARTEMIS missions during the Juno flyby on 09 October 2013 (Invited)

    Science.gov (United States)

    Turner, D. L.; Angelopoulos, V.; Runov, A.; Gabrielse, C.

    2013-12-01

    On 09 October 2013, NASA's Juno spacecraft is scheduled to make a near-Earth flyby for a gravity-assist maneuver to help it on its journey to explore the gas giant, Jupiter. Taking advantage of such a unique opportunity, here we will examine and present glimpses of Earth's magnetosphere and the near-Earth solar wind from NASA's THEMIS and ARTEMIS missions. During the Juno flyby, the three THEMIS spacecraft will travel through the inner magnetosphere and out into the near-Earth plasma sheet to an ~11.4 Earth radii (RE) apogee at ~21:30 magnetic local time. In lunar orbit, the two ARTEMIS spacecraft will be in the solar wind at ~60 RE off the dayside-dusk flank of the system. ARTEMIS data will be used to observe solar wind plasma and the interplanetary magnetic field, which will be useful for better comprehension of the data taken within the magnetosphere and to compare with Juno observations on its approach and escape trajectories during the flyby. THEMIS data, which will be the primary focus of this presentation, will be used to examine the state of the magnetosphere itself. We will highlight conditions in the inner magnetosphere, including the outer electron radiation belt, over the course of the flyby. Furthermore, taking advantage of the THEMIS orbits going into the pre-midnight plasma sheet, we will also report on conditions within the plasma sheet and any observations of energetic particle injections during the flyby, which will be of particular interest for multipoint comparisons of the injection signatures with NASA's Van Allen Probes, NOAA's GOES, and, of course, Juno. Energetic particle injections play a critical role in the evolution of Earth's ring current and the outer electron radiation belt by injecting the source particles that generate various plasma waves and the seed particles for both of those stably-trapped energetic particle populations. If we are lucky enough to observe any injections during the flyby, the additional point of observation from

  9. Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining.

    Science.gov (United States)

    Mahaney, Brandi L; Meek, Katheryn; Lees-Miller, Susan P

    2009-02-01

    DNA DSBs (double-strand breaks) are considered the most cytotoxic type of DNA lesion. They can be introduced by external sources such as IR (ionizing radiation), by chemotherapeutic drugs such as topoisomerase poisons and by normal biological processes such as V(D)J recombination. If left unrepaired, DSBs can cause cell death. If misrepaired, DSBs may lead to chromosomal translocations and genomic instability. One of the major pathways for the repair of IR-induced DSBs in mammalian cells is NHEJ (non-homologous end-joining). The main proteins required for NHEJ in mammalian cells are the Ku heterodimer (Ku70/80 heterodimer), DNA-PKcs [the catalytic subunit of DNA-PK (DNA-dependent protein kinase)], Artemis, XRCC4 (X-ray-complementing Chinese hamster gene 4), DNA ligase IV and XLF (XRCC4-like factor; also called Cernunnos). Additional proteins, including DNA polymerases mu and lambda, PNK (polynucleotide kinase) and WRN (Werner's Syndrome helicase), may also play a role. In the present review, we will discuss our current understanding of the mechanism of NHEJ in mammalian cells and discuss the roles of DNA-PKcs and DNA-PK-mediated phosphorylation in NHEJ. PMID:19133841

  10. Ancient and recent adaptive evolution of primate non-homologous end joining genes.

    Directory of Open Access Journals (Sweden)

    Ann Demogines

    2010-10-01

    Full Text Available In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little sequence change over time. Here, we report that while critical domains of these proteins are conserved as expected, the sequence of NHEJ proteins has also been shaped by recurrent positive selection, leading to rapid sequence evolution in other protein domains. In order to characterize the molecular evolution of the human NHEJ pathway, we generated large simian primate sequence datasets for NHEJ genes. Codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLλ, and CtIP. Analysis of human polymorphism data using the composite of multiple signals (CMS test revealed that XRCC4 has also been subjected to positive selection in modern humans. Crystal structures are available for XRCC4, Nbs1, and Polλ; and residues under positive selection fall exclusively on the surfaces of these proteins. Despite the positive selection of such residues, biochemical experiments with variants of one positively selected site in Nbs1 confirm that functions necessary for DNA repair and checkpoint signaling have been conserved. However, many viruses interact with the proteins of the NHEJ pathway as part of their infectious lifecycle. We propose that an ongoing evolutionary arms race between viruses and NHEJ genes may be driving the surprisingly rapid evolution of these critical genes.

  11. Homology in Electromagnetic Boundary Value Problems

    Directory of Open Access Journals (Sweden)

    Matti Pellikka

    2010-01-01

    Full Text Available We discuss how homology computation can be exploited in computational electromagnetism. We represent various cellular mesh reduction techniques, which enable the computation of generators of homology spaces in an acceptable time. Furthermore, we show how the generators can be used for setting up and analysis of an electromagnetic boundary value problem. The aim is to provide a rationale for homology computation in electromagnetic modeling software.

  12. Link homology and equivariant gauge theory

    OpenAIRE

    Poudel, Prayat; Saveliev, Nikolai

    2015-01-01

    The singular instanton Floer homology was defined by Kronheimer and Mrowka in connection with their proof that the Khovanov homology is an unknot detector. We study this theory for knots and two-component links using equivariant gauge theory on their double branched covers. We show that the special generator in the singular instanton Floer homology of a knot is graded by the knot signature mod 4, thereby providing a purely topological way of fixing the absolute grading in the theory. Our appr...

  13. Including Biological Literature Improves Homology Search

    OpenAIRE

    Chang, Jeffrey T.; Raychaudhuri, Soumya; Altman, Russ B

    2001-01-01

    Annotating the tremendous amount of sequence information being generated requires accurate automated methods for recognizing homology. Although sequence similarity is only one of many indicators of evolutionary homology, it is often the only one used. Here we find that supplementing sequence similarity with information from biomedical literature is successful in increasing the accuracy of homology search results. We modified the PSI-BLAST algorithm to use literature similarity in each iterati...

  14. Deoxyribonucleic Acid Homology Among Lactic Streptococci

    OpenAIRE

    Jarvis, Audrey W.; Jarvis, Brion D. W.

    1981-01-01

    A comparison was made by deoxyribonucleic acid homology of 45 strains of lactic streptococci, using two strains of Streptococcus cremoris and three strains of Streptococcus lactis as reference strains. All S. cremoris strains were grouped together by deoxyribonucleic acid homology. S. lactis strains formed a second group, except that three strains of S. lactis showed a high degree of homology with S. cremoris strains. The three Streptococcus diacetylactis strains could not be differentiated f...

  15. Homologous Recombination in Negative Sense RNA Viruses

    OpenAIRE

    Michael Worobey; Guan-Zhu Han

    2011-01-01

    Recombination is an important process that influences biological evolution at many different levels. More and more homologous recombination events have been reported among negative sense RNA viruses recently. While sporadic authentic examples indicate that homologous recombination does occur, recombination seems to be generally rare or even absent in most negative sense RNA viruses, and most of the homologous recombination events reported in the literature were likely generated artificially d...

  16. Účast ČR ve společných technologických iniciativách ARTEMIS a ENIAC

    Czech Academy of Sciences Publication Activity Database

    Kadlec, Jiří

    Praha : Ústav informatiky AV ČR, v.v.i, 2011 - (Klímová, H.; Kuželová, D.; Šíma, J.; Wiedermann, J.; Žák, S.), s. 95-113 ISBN 978-80-87136-11-9. [Hovory s informatiky 2011. Praha (CZ), 25.10.2011] R&D Projects: GA MŠk(CZ) OK08002 Institutional research plan: CEZ:AV0Z10750506 Keywords : joint technology initiative * embedded systems * microelectronics * FP7 Subject RIV: IN - Informatics, Computer Science http://library.utia.cas.cz/separaty/2011/ZS/kadlec-participation of the czech republic in artemis and eniac joint technology initiatives.pdf

  17. The molecular evolution of PL10 homologs

    Directory of Open Access Journals (Sweden)

    Chang Ti-Cheng

    2010-05-01

    Full Text Available Abstract Background PL10 homologs exist in a wide range of eukaryotes from yeast, plants to animals. They share a DEAD motif and belong to the DEAD-box polypeptide 3 (DDX3 subfamily with a major role in RNA metabolism. The lineage-specific expression patterns and various genomic structures and locations of PL10 homologs indicate these homologs have an interesting evolutionary history. Results Phylogenetic analyses revealed that, in addition to the sex chromosome-linked PL10 homologs, DDX3X and DDX3Y, a single autosomal PL10 putative homologous sequence is present in each genome of the studied non-rodent eutheria. These autosomal homologous sequences originated from the retroposition of DDX3X but were pseudogenized during the evolution. In rodents, besides Ddx3x and Ddx3y, we found not only Pl10 but another autosomal homologous region, both of which also originated from the Ddx3x retroposition. These retropositions occurred after the divergence of eutheria and opossum. In contrast, an additional X putative homologous sequence was detected in primates and originated from the transposition of DDX3Y. The evolution of PL10 homologs was under positive selection and the elevated Ka/Ks ratios were observed in the eutherian lineages for DDX3Y but not PL10 and DDX3X, suggesting relaxed selective constraints on DDX3Y. Contrary to the highly conserved domains, several sites with relaxed selective constraints flanking the domains in the mammalian PL10 homologs may play roles in enhancing the gene function in a lineage-specific manner. Conclusion The eutherian DDX3X/DDX3Y in the X/Y-added region originated from the translocation of the ancient PL10 ortholog on the ancestral autosome, whereas the eutherian PL10 was retroposed from DDX3X. In addition to the functional PL10/DDX3X/DDX3Y, conserved homologous regions on the autosomes and X chromosome are present. The autosomal homologs were also derived from DDX3X, whereas the additional X-homologs were derived

  18. Homotopic Chain Maps Have Equal s-Homology and d-Homology

    Directory of Open Access Journals (Sweden)

    M. Z. Kazemi-Baneh

    2016-01-01

    Full Text Available The homotopy of chain maps on preabelian categories is investigated and the equality of standard homologies and d-homologies of homotopic chain maps is established. As a special case, if X and Y are the same homotopy type, then their nth d-homology R-modules are isomorphic, and if X is a contractible space, then its nth d-homology R-modules for n≠0 are trivial.

  19. Invariants and structures of the homology cobordism group of homology cylinders

    OpenAIRE

    Song, Minkyoung

    2015-01-01

    The homology cobordism group of homology cylinders is a generalization of the mapping class group and the string link concordance group. We study this group and its filtrations by subgroups by developing new homomorphisms. First, we define extended Milnor invariants by combining the ideas of Milnor's link invariants and Johnson homomorphisms. They give rise to a descending filtration of the homology cobordism group of homology cylinders. We show that each successive quotient of the filtration...

  20. Buoyancy instability of homologous implosions

    Science.gov (United States)

    Johnson, Bryan

    2015-11-01

    Hot spot turbulence is a potential contributor to yield degradation in inertial confinement fusion (ICF) capsules, although its origin, if present, remains unclear. In this work, a perturbation analysis is performed of an analytical homologous solution that mimics the hot spot and surrounding cold fuel during the late stages of an ICF implosion. It is shown that the flow is governed by the Schwarzschild criterion for buoyant stability, and that during stagnation, short wavelength entropy and vorticity fluctuations amplify by a factor exp (π |N0 | ts) , where N0 is the buoyancy frequency at stagnation and ts is the stagnation time scale. This amplification factor is exponentially sensitive to mean flow gradients and varies from 103-107 for realistic gradients. Comparisons are made with a Lagrangian hydrodynamics code, and it is found that a numerical resolution of ~ 30 zones per wavelength is required to capture the evolution of vorticity accurately. This translates to an angular resolution of ~(12 / l) ∘ , or ~ 0 .1° to resolve the fastest growing modes (Legendre mode l > 100).

  1. Buoyancy instability of homologous implosions

    CERN Document Server

    Johnson, Bryan M

    2015-01-01

    I consider the hydrodynamic stability of imploding gases as a model for inertial confinement fusion capsules, sonoluminescent bubbles and the gravitational collapse of astrophysical gases. For oblate modes under a homologous flow, a monatomic gas is governed by the Schwarzschild criterion for buoyant stability. Under buoyantly unstable conditions, fluctuations experience power-law growth in time, with a growth rate that depends upon mean flow gradients and is independent of mode number. If the flow accelerates throughout the implosion, oblate modes amplify by a factor (2C)^(|N0| ti)$, where C is the convergence ratio of the implosion, N0 is the initial buoyancy frequency and ti is the implosion time scale. If, instead, the implosion consists of a coasting phase followed by stagnation, oblate modes amplify by a factor exp(pi |N0| ts), where N0 is the buoyancy frequency at stagnation and ts is the stagnation time scale. Even under stable conditions, vorticity fluctuations grow due to the conservation of angular...

  2. Stability of p53 homologs.

    Directory of Open Access Journals (Sweden)

    Tobias Brandt

    Full Text Available Most proteins have not evolved for maximal thermal stability. Some are only marginally stable, as for example, the DNA-binding domains of p53 and its homologs, whose kinetic and thermodynamic stabilities are strongly correlated. Here, we applied high-throughput methods using a real-time PCR thermocycler to study the stability of several full-length orthologs and paralogs of the p53 family of transcription factors, which have diverse functions, ranging from tumour suppression to control of developmental processes. From isothermal denaturation fluorimetry and differential scanning fluorimetry, we found that full-length proteins showed the same correlation between kinetic and thermodynamic stability as their isolated DNA-binding domains. The stabilities of the full-length p53 orthologs were marginal and correlated with the temperature of their organism, paralleling the stability of the isolated DNA-binding domains. Additionally, the paralogs p63 and p73 were significantly more stable and long-lived than p53. The short half-life of p53 orthologs and the greater persistence of the paralogs may be biologically relevant.

  3. Products and relations in symplectic Floer homology

    OpenAIRE

    Betz, Marty; Rade, Johan

    1995-01-01

    We give a construction of a version of the Gromov-Witten classes, Q: H_*(J) -> HF_*(M) otimes ... otimes HF^*(M), within the context of symplectic Floer (co)homology. In particular, this gives a functorial approach to products and relations in symplectic Floer (co)homology.

  4. On the computation of torus link homology

    OpenAIRE

    Elias, Ben; Hogancamp, Matthew

    2016-01-01

    We introduce a new method for computing triply graded link homology, which is particularly well-adapted to torus links. Our main application is to the (n,n)-torus links, for which we give an exact answer for all n. In several cases, our computations verify conjectures of Gorsky et al relating homology of torus links with Hilbert schemes.

  5. MIF proteins are not glutathione transferase homologs.

    OpenAIRE

    Pearson, W R

    1994-01-01

    Although macrophage migration inhibitory factor (MIF) proteins conjugate glutathione, sequence analysis does not support their homology to other glutathione transferases. Glutathione transferases are not detected with MIF proteins in searches of protein sequence databases, and MIF proteins do not share significant sequence similarity with glutathione transferases. Homology cannot be demonstrated by multiple sequence alignment or evolutionary tree construction; such methods assume that the pro...

  6. Matroid Filtrations and Computational Persistent Homology

    OpenAIRE

    Henselman, Gregory; Ghrist, Robert

    2016-01-01

    This technical report introduces a novel approach to efficient computation in homological algebra over fields, with particular emphasis on computing the persistent homology of a filtered topological cell complex. The algorithms here presented rely on a novel relationship between discrete Morse theory, matroid theory, and classical matrix factorizations. We provide background, detail the algorithms, and benchmark the software implementation in the Eirene package.

  7. Equivariant symplectic homology of Anosov contact structures

    CERN Document Server

    Macarini, Leonardo

    2011-01-01

    We show that the differential in positive equivariant symplectic homology or linearized contact homology vanishes for non-degenerate Reeb flows with a continuous invariant Lagrangian subbundle (e.g. Anosov Reeb flows). Several applications are given, including obstructions to the existence of these flows and abundance of periodic orbits for contact forms representing an Anosov contact structure.

  8. Výsledky třetí výzvy programu společných technologických iniciativ ARTEMIS JU a ENIAC JU

    Czech Academy of Sciences Publication Activity Database

    Kadlec, Jiří; Bystřická, J.

    2011-01-01

    Roč. 2011, č. 2 (2011), s. 18-19. ISSN 1214-7982 R&D Projects: GA MŠk(CZ) OK08002 Institutional research plan: CEZ:AV0Z10750506 Keywords : JTI * FP7 * embedded systems * microelectronics Subject RIV: AF - Documentation, Librarianship, Information Studies http://library.utia.cas.cz/separaty/2011/ZS/kadlec-3rd call results of joint technology inititives artemis and eniac .pdf

  9. Threading homology through algebra selected patterns

    CERN Document Server

    Boffi, Giandomenico

    2006-01-01

    Aimed at graduate students and researchers in mathematics, this book takes homological themes, such as Koszul complexes and their generalizations, and shows how these can be used to clarify certain problems in selected parts of algebra, as well as their success in solving a number of them. - ;Threading Homology through Algebra takes homological themes (Koszul complexes and their variations, resolutions in general) and shows how these affect the perception of certain problems in selected parts of algebra, as well as their success in solving a number of them. The text deals with regular local ri

  10. Superconformal field theories and cyclic homology

    CERN Document Server

    Eager, Richard

    2015-01-01

    One of the predictions of the AdS/CFT correspondence is the matching of protected operators between a superconformal field theory and its holographic dual. We review the spectrum of protected operators in quiver gauge theories that flow to superconformal field theories at low energies. The spectrum is determined by the cyclic homology of an algebra associated to the quiver gauge theory. Identifying the spectrum of operators with cyclic homology allows us to apply the Hochschild-Kostant-Rosenberg theorem to relate the cyclic homology groups to deRham cohomology groups. The map from cyclic homology to deRham cohomology can be viewed as a mathematical avatar of the passage from open to closed strings under the AdS/CFT correspondence.

  11. Exceptional cosmetic surgeries on homology spheres

    OpenAIRE

    Ravelomanana, Huygens C.

    2016-01-01

    We investigate the cosmetic surgery conjecture for hyperbolic knots in integer homology spheres, focusing on exceptional surgeries. We give some restrictions on the slopes of exceptional truly cosmetic surgeries according to the type of surgery.

  12. Cylindrical contact homology and topological entropy

    OpenAIRE

    Alves, Marcelo R. R.

    2014-01-01

    We establish a relation between the growth of the cylindrical contact homology of a contact manifold and the topological entropy of Reeb flows on this manifold. We show that if a contact manifold $(M,\\xi)$ admits a hypertight contact form $\\lambda_0$ for which the cylindrical contact homology has exponential homotopical growth rate, then the Reeb flow of every contact form on $(M,\\xi)$ has positive topological entropy. Using this result, we provide numerous new examples of contact 3-manifolds...

  13. Dualities in Persistent (Co)Homology

    Energy Technology Data Exchange (ETDEWEB)

    de Silva, Vin; Morozov, Dmitriy; Vejdemo-Johansson, Mikael

    2011-09-16

    We consider sequences of absolute and relative homology and cohomology groups that arise naturally for a filtered cell complex. We establishalgebraic relationships between their persistence modules, and show that they contain equivalent information. We explain how one can use the existingalgorithm for persistent homology to process any of the four modules, and relate it to a recently introduced persistent cohomology algorithm. Wepresent experimental evidence for the practical efficiency of the latter algorithm.

  14. On the hodological criterion for homology

    Science.gov (United States)

    Faunes, Macarena; Francisco Botelho, João; Ahumada Galleguillos, Patricio; Mpodozis, Jorge

    2015-01-01

    Owen's pre-evolutionary definition of a homolog as “the same organ in different animals under every variety of form and function” and its redefinition after Darwin as “the same trait in different lineages due to common ancestry” entail the same heuristic problem: how to establish “sameness.”Although different criteria for homology often conflict, there is currently a generalized acceptance of gene expression as the best criterion. This gene-centered view of homology results from a reductionist and preformationist concept of living beings. Here, we adopt an alternative organismic-epigenetic viewpoint, and conceive living beings as systems whose identity is given by the dynamic interactions between their components at their multiple levels of composition. We posit that there cannot be an absolute homology criterion, and instead, homology should be inferred from comparisons at the levels and developmental stages where the delimitation of the compared trait lies. In this line, we argue that neural connectivity, i.e., the hodological criterion, should prevail in the determination of homologies between brain supra-cellular structures, such as the vertebrate pallium. PMID:26157357

  15. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation

    DEFF Research Database (Denmark)

    Lombard, David B; Alt, Frederick W; Cheng, Hwei-Ling;

    2007-01-01

    Homologs of the Saccharomyces cerevisiae Sir2 protein, sirtuins, promote longevity in many organisms. Studies of the sirtuin SIRT3 have so far been limited to cell culture systems. Here, we investigate the localization and function of SIRT3 in vivo. We show that endogenous mouse SIRT3 is a soluble...

  16. Investigating homology between proteins using energetic profiles.

    Directory of Open Access Journals (Sweden)

    James O Wrabl

    2010-03-01

    Full Text Available Accumulated experimental observations demonstrate that protein stability is often preserved upon conservative point mutation. In contrast, less is known about the effects of large sequence or structure changes on the stability of a particular fold. Almost completely unknown is the degree to which stability of different regions of a protein is generally preserved throughout evolution. In this work, these questions are addressed through thermodynamic analysis of a large representative sample of protein fold space based on remote, yet accepted, homology. More than 3,000 proteins were computationally analyzed using the structural-thermodynamic algorithm COREX/BEST. Estimated position-specific stability (i.e., local Gibbs free energy of folding and its component enthalpy and entropy were quantitatively compared between all proteins in the sample according to all-vs.-all pairwise structural alignment. It was discovered that the local stabilities of homologous pairs were significantly more correlated than those of non-homologous pairs, indicating that local stability was indeed generally conserved throughout evolution. However, the position-specific enthalpy and entropy underlying stability were less correlated, suggesting that the overall regional stability of a protein was more important than the thermodynamic mechanism utilized to achieve that stability. Finally, two different types of statistically exceptional evolutionary structure-thermodynamic relationships were noted. First, many homologous proteins contained regions of similar thermodynamics despite localized structure change, suggesting a thermodynamic mechanism enabling evolutionary fold change. Second, some homologous proteins with extremely similar structures nonetheless exhibited different local stabilities, a phenomenon previously observed experimentally in this laboratory. These two observations, in conjunction with the principal conclusion that homologous proteins generally conserved

  17. Fine Structure of Metric Type-IV Radio Bursts Observed with the ARTEMIS-IV Radio Spectrograph: Association with Flares and Coronal Mass Ejections

    CERN Document Server

    Bouratzis, C; Alissandrakis, C E; Preka-Papadema, P; Moussas, X; Caroubalos, C; Tsitsipis, P; Kontogeorgos, A

    2014-01-01

    Fine structures embedded in type-IV burst continua may be used as diagnostics of the magnetic field restructuring and the corresponding energy release associated with the low corona development of flare/CME events. A catalog of 36 type-IV bursts observed with the SAO receiver of the ARTEMIS-IV solar radio-spectrograph in the 450--270 MHz range at high cadence (0.01 sec) was compiled; the fine structures were classified into five basic classes with two or more sub-classes each. The time of fine structure emission was compared with the injection of energetic electrons as evidenced by HXR and microwave emission, the SXR light-curves and the CME onset time. Our results indicate a very good temporal association between energy release episodes and pulsations, spikes, narrow-band bursts of the type-III family and zebra bursts. Of the remaining categories, the featureless broadband continuum starts near the time of the first energy release, between the CME onset and the SXR peak, but extends for several tens of minut...

  18. On the hodological criterion for homology

    Directory of Open Access Journals (Sweden)

    Macarena eFaunes

    2015-06-01

    Full Text Available Owen’s pre-evolutionary definition of a homologue as the same organ in different animals under every variety of form and function and its redefinition after Darwin as the same trait in different lineages due to common ancestry entail the same heuristic problem: how to establish sameness. Although different criteria for homology often conflict, there is currently a generalized acceptance of gene expression as the best criterion. This gene-centered view of homology results from a reductionist and preformationist concept of living beings. Here, we adopt an alternative organismic-epigenetic viewpoint, and conceive living beings as systems whose identity is given by the dynamic interactions between their components at their multiple levels of composition. We posit that there cannot be an absolute homology criterion, and instead, homology should be inferred from comparisons at the levels and developmental stages where the delimitation of the compared trait lies. In this line, we argue that neural connectivity, i.e., the hodological criterion, should prevail in the determination of homologies between brain supra-cellular structures, such as the vertebrate pallium.

  19. A pumilio homolog in Polycelis sp.

    Science.gov (United States)

    Yuwen, Yanqing; Dong, Zimei; Si, Xiaohui; Chen, Guangwen

    2014-02-01

    Pumilio proteins (PUMs), members of the pumilio/fem-3 mRNA-binding factor (PUF) family, are eukaryote-specific RNA-binding proteins. We isolated a 2,048-basepair cDNA fragment of a pumilio homolog from the planarian flatworm Polycelis sp. This pumilio protein (PyPUM) contains a conserved pumilio homology domain (PUM-HD) consisting of eight repeats and two flanking half repeats. PyPUM shows high similarity to Dugesia japonica pumilio (DjPUM) from another planarian D. japonica, and their PUM-HD also shows high similarity to each other. Furthermore, our data showed that there is a flatworm-specific spacer between repeats 7 and 8. Phylogenetic analysis showed that PyPUM has a closer relationship to other PUM homologs from flatworms. These results provide a foundation for future functional studies of pumilio gene in Polycelis sp. PMID:24292205

  20. Homological stability for oriented configuration spaces

    CERN Document Server

    Palmer, Martin

    2011-01-01

    We prove homological stability for sequences of "oriented configuration spaces" as the number of points in the configuration goes to infinity. These are spaces of configurations of n points in a connected manifold M of dimension at least 2 which 'admits a boundary', with labels in a path-connected space X, and with an orientation: an ordering of the points up to even permutations. They are double covers of the corresponding unordered configuration spaces, where the points do not have this orientation. To prove our result we adapt methods from a paper of Randal-Williams, which proves homological stability in the unordered case. Interestingly the oriented configuration spaces stabilise more slowly than the unordered ones: the stability slope we obtain is one-third, compared to one-half in the unordered case (these are the best possible slopes in their respective cases). This result can also be interpreted as homological stability for unordered configuration spaces with certain twisted coefficients.

  1. Irradiated homologous costal cartilage for augmentation rhinoplasty

    International Nuclear Information System (INIS)

    Although the ideal reconstructive material for augmentation rhinoplasty continues to challenge plastic surgeons, there exists no report in the literature that confines the use of irradiated homologous costal cartilage, first reported by Dingman and Grabb in 1961, to dorsal nasal augmentation. The purpose of this paper is to present a retrospective analysis of the author's experience using irradiated homologous costal cartilage in augmentation rhinoplasty. Twenty-seven dorsal nasal augmentations were performed in 24 patients between 16 and 49 years of age with a follow-up ranging from 1 to 27 months. Good-to-excellent results were achieved in 83.3% (20 of 24). Poor results requiring revision were found in 16.7% (4 of 24). Complication rates included 7.4% infection (2 of 27) and 14.8% warping (4 of 27). The resorption rate was zero. These results compare favorably with other forms of nasal augmentation. Advantages and disadvantages of irradiated homologous costal cartilage are discussed

  2. A Pyrococcus homolog of the leucine-responsive regulatory protein, LrpA, inhibits transcription by abrogating RNA polymerase recruitment

    OpenAIRE

    Dahlke, Isabell; Thomm, Michael

    2002-01-01

    The genomes of Archaea harbor homologs of the global bacterial regulator leucine-responsive regulatory protein (Lrp). Archaeal Lrp homologs are helix–turn–helix DNA-binding proteins that specifically repress the transcription of their own genes in vitro. Here, we analyze the interaction of Pyrococcus LrpA with components of the archaeal transcriptional machinery at the lrpA promoter. DNA–protein complexes can be isolated by electrophoretic mobility shift assays that contain both LrpA and the ...

  3. Flare build-up study: Homologous flares group - Interim report

    Science.gov (United States)

    Woodgate, B. E.

    1982-01-01

    When homologous flares are broadly defined as having footpoint structures in common, it is found that a majority of flares fall into homologous sets. Filament eruptions and mass ejection in members of an homologous flare set show that maintainance of the magnetic structure is not a necessary condition for homology.

  4. Homological and homotopical Dehn functions are different

    CERN Document Server

    Abrams, Aaron; Dani, Pallavi; Young, Robert

    2012-01-01

    The homological and homotopical Dehn functions are different ways of measuring the difficulty of filling a closed curve inside a group or a space. The homological Dehn function measures fillings of cycles by chains, while the homotopical Dehn function measures fillings of curves by disks. Since the two definitions involve different sorts of boundaries and fillings, there is no a priori relationship between the two functions, but prior to this work there were no known examples of finitely-presented groups for which the two functions differ. This paper gives the first such examples, constructed by amalgamating a free-by-cyclic group with several Bestvina-Brady groups.

  5. Relative K-homology and normal operators

    DEFF Research Database (Denmark)

    Manuilov, Vladimir; Thomsen, Klaus

    2009-01-01

    -term exact sequence which generalizes the excision six-term exact sequence in the first variable of KK-theory. Subsequently we investigate the relative K-homology which arises from the group of relative extensions by specializing to abelian $C^*$-algebras. It turns out that this relative K-homology carries...... substantial information also in the operator theoretic setting from which the BDF theory was developed and we conclude the paper by extracting some of this information on approximation of normal operators....

  6. Sutured Floer homology distinguishes between Seifert surfaces

    CERN Document Server

    Altman, Irida

    2010-01-01

    In this note we exhibit the first example of a knot in the three-sphere with a pair of minimal genus Seifert surfaces that can be distinguished using the sutured Floer homology of their complementary manifolds together with the Spin^c-grading. This answers a question of Juh\\'asz. More precisely, we show that the Euler characteristic of the sutured Floer homology of the complementary manifolds distinguishes between the two surfaces, and we exhibit an infinite family of knots with pairs of Seifert surfaces that can be distinguished in such a way.

  7. Sheaves on Graphs and Their Homological Invariants

    OpenAIRE

    Friedman, Joel

    2011-01-01

    We introduce a notion of a sheaf of vector spaces on a graph, and develop the foundations of homology theories for such sheaves. One sheaf invariant, its "maximum excess," has a number of remarkable properties. It has a simple definition, with no reference to homology theory, that resembles graph expansion. Yet it is a "limit" of Betti numbers, and hence has a short/long exact sequence theory and resembles the $L^2$ Betti numbers of Atiyah. Also, the maximum excess is defined via a supermodul...

  8. New mesogenic homologous series of -methylcinnamates

    Indian Academy of Sciences (India)

    R A Vora; A K Prajapati

    2001-04-01

    Compounds of a new smectogenic homologous series of -methylcinnamates were prepared by condensing different 4--alkoxybenzoyl chloride with methoxyethyl trans-4-hydroxy- -methylcinnamate. In this series, the first six members are non-mesogenic. -Heptyloxy derivative exhibits monotropic smectic A phase whereas rest of the members exhibit enantiotropic smectic A mesophase. The compounds are characterized by combination of elemental analysis and spectroscopic techniques. Enthalpies of few homologues are measured by DSC techniques. Fluorescent properties are also observed. The thermal stabilities of the present series are compared with those of other structurally related mesogenic homologous series.

  9. Relative Derived Equivalences and Relative Homological Dimensions

    Institute of Scientific and Technical Information of China (English)

    Sheng Yong PAN

    2016-01-01

    Let A be a small abelian category. For a closed subbifunctor F of Ext1A (−,−), Buan has generalized the construction of Verdier’s quotient category to get a relative derived category, where he localized with respect to F-acyclic complexes. In this paper, the homological properties of relative derived categories are discussed, and the relation with derived categories is given. For Artin algebras, using relative derived categories, we give a relative version on derived equivalences induced by F-tilting complexes. We discuss the relationships between relative homological dimensions and relative derived equivalences.

  10. Homology and cohomology of Rees semigroup algebras

    DEFF Research Database (Denmark)

    Grønbæk, Niels; Gourdeau, Frédéric; White, Michael C.

    2011-01-01

    Let S by a Rees semigroup, and let 1¹(S) be its convolution semigroup algebra. Using Morita equivalence we show that bounded Hochschild homology and cohomology of l¹(S) is isomorphic to those of the underlying discrete group algebra.......Let S by a Rees semigroup, and let 1¹(S) be its convolution semigroup algebra. Using Morita equivalence we show that bounded Hochschild homology and cohomology of l¹(S) is isomorphic to those of the underlying discrete group algebra....

  11. Contact homology of good toric contact manifolds

    CERN Document Server

    Abreu, Miguel

    2010-01-01

    In this paper we show that any good toric contact manifold has well defined cylindrical contact homology and describe how it can be combinatorially computed from the associated moment cone. As an application we compute the cylindrical contact homology of a particularly nice family of examples that appear in the work of Gauntlett-Martelli-Sparks-Waldram on Sasaki-Einstein metrics. We show in particular that these give rise to a new infinite family of non-equivalent contact structures on $S^2 \\times S^{3}$ in the unique homotopy class of almost contact structures with vanishing first Chern class.

  12. Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination

    OpenAIRE

    Taylor, Martin R.G.; Špírek, Mário; Chaurasiya, Kathy R.; Ward, Jordan D.; Carzaniga, Raffaella; Yu, Xiong; Egelman, Edward H.; Collinson, Lucy M.; Rueda, David; Krejci, Lumir; Boulton, Simon J.

    2015-01-01

    Summary Repair of DNA double strand breaks by homologous recombination (HR) is initiated by Rad51 filament nucleation on single-stranded DNA (ssDNA), which catalyzes strand exchange with homologous duplex DNA. BRCA2 and the Rad51 paralogs are tumor suppressors and critical mediators of Rad51. To gain insight into Rad51 paralog function, we investigated a heterodimeric Rad51 paralog complex, RFS-1/RIP-1, and uncovered the molecular basis by which Rad51 paralogs promote HR. Unlike BRCA2, which ...

  13. Betti numbers and stability for configuration spaces via factorization homology

    OpenAIRE

    Knudsen, Ben

    2014-01-01

    Using factorization homology, we realize the rational homology of the unordered configuration spaces of an arbitrary manifold $M$, possibly with boundary, as the homology of a Lie algebra constructed from the compactly supported cohomology of $M$. By locating the homology of each configuration space within the Chevalley-Eilenberg complex of this Lie algebra, we extend theorems of B\\"{o}digheimer-Cohen-Taylor and F\\'{e}lix-Thomas and give a new, combinatorial proof of the homological stability...

  14. Homological Perturbation Theory and Mirror Symmetry

    Institute of Scientific and Technical Information of China (English)

    Jian ZHOU

    2003-01-01

    We explain how deformation theories of geometric objects such as complex structures,Poisson structures and holomorphic bundle structures lead to differential Gerstenhaber or Poisson al-gebras. We use homological perturbation theory to construct A∞ algebra structures on the cohomology,and their canonically defined deformations. Such constructions are used to formulate a version of A∞algebraic mirror symmetry.

  15. Cell biology of homologous recombination in yeast

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine Valerie; Rothstein, Rodney; Lisby, Michael

    2011-01-01

    Homologous recombination is an important pathway for error-free repair of DNA lesions, such as single- and double-strand breaks, and for rescue of collapsed replication forks. Here, we describe protocols for live cell imaging of single-lesion recombination events in the yeast Saccharomyces...

  16. Planar open books and Floer homology

    OpenAIRE

    Ozsvath, Peter; Stipsicz, Andras I.; Szabo, Zoltan

    2005-01-01

    Giroux has described a correspondence between open book decompositions on a 3--manifold and contact structures. In this paper we use Heegaard Floer homology to give restrictions on contact structures which correspond to open book decompositions with planar pages, generalizing a recent result of Etnyre.

  17. Homological aperiodic tilings of 3-dimensional geometries

    CERN Document Server

    Nowak, Piotr W

    2012-01-01

    We construct the first aperiodic tiles for two amenable 3-dimensional Lie groups: Sol and the Heisenberg group. Our construction relies on the use of higher-dimensional uniformly finite homology. In particular, we settle completely the existence of aperiodic tiles for all of the non-compact geometries of 3-manifolds appearing in the geometrization conjecture.

  18. (Co)homology of Spectral Categories

    OpenAIRE

    Campbell, Jonathan A.

    2015-01-01

    In this article we develop the cotangent complex and (co)homology theories for spectral categories. Along the way, we reproduce standard model structures on spectral categories. As applications, we show that the invariants to descend to stable $\\infty$-categories and we prove a stabilization result for spectral categories.

  19. Einstein Metrics on Rational Homology Spheres

    OpenAIRE

    Boyer, Charles P.; Galicki, Krzysztof

    2003-01-01

    We prove the existence of Sasakian-Einstein metrics on infinitely many rational homology spheres in all odd dimensions greater than 3. In dimension 5 we obain somewhat sharper results. There are examples where the number of effective parameters in the Einstein metric grows exponentially with dimension.

  20. Homological stability for unordered configuration spaces

    CERN Document Server

    Randal-Williams, Oscar

    2011-01-01

    This paper consists of two related parts. In the first part we give a self-contained proof of homological stability for the spaces C_n(M;X) of configurations of n unordered points in a connected open manifold M with labels in a path-connected space X, with the best possible integral stability range of 2* \\leq n. Along the way we give a new proof of the high connectivity of the complex of injective words. If the manifold has dimension at least three, we show that in rational homology the stability range may be improved to * \\leq n. In the second part we study to what extent the homology of the spaces C_n(M) can be considered stable when M is a closed manifold. In this case there are no stabilisation maps, but one may still ask if the dimensions of the homology groups over some field stabilise with n. We prove that this is true when M is odd-dimensional, or when the field is F_2 or Q. It is known to be false in the remaining cases.

  1. Homological stability for configuration spaces of manifolds

    CERN Document Server

    Church, Thomas

    2011-01-01

    Let C_n(M) be the configuration space of n distinct ordered points in M. We prove that if M is any connected orientable manifold (closed or open), the homology groups H_i(C_n(M); Q) are representation stable in the sense of [Church-Farb]. Applying this to the trivial representation, we obtain as a corollary that the unordered configuration space B_n(M) satisfies classical homological stability: for each i, H_i(B_n(M); Q) is isomorphic to H_i(B_{n+1}(M); Q) for n > i. This improves on results of McDuff, Segal, and others for open manifolds. Applied to closed manifolds, this provides natural examples where rational homological stability holds even though integral homological stability fails. To prove the main theorem, we introduce the notion of monotonicity for a sequence of S_n--representations, which is of independent interest. Sequences that are both monotone and uniformly representation stable form an abelian category. Monotonicity provides a new mechanism for proving representation stability using spectral...

  2. Khovanov-Rozansky homology and Directed Cycles

    OpenAIRE

    Wu, Hao

    2015-01-01

    We determine the cycle packing number of a directed graph using elementary projective algebraic geometry. Our idea is rooted in the Khovanov-Rozansky theory. In fact, using the Khovanov-Rozansky homology of a graph, we also obtain algebraic methods of detecting directed and undirected cycles containing a particular vertex or edge.

  3. The homology systole of hyperbolic Riemann surfaces

    OpenAIRE

    Parlier, Hugo

    2010-01-01

    The main goal of this note is to show that the study of closed hyperbolic surfaces with maximum length systole is in fact the study of surfaces with maximum length homological systole. The same result is shown to be true for once-punctured surfaces, and is shown to fail for surfaces with a large number of cusps.

  4. Involvement of the Artemis Protein in the Relative Biological Efficiency Observed With the 76-MeV Proton Beam Used at the Institut Curie Proton Therapy Center in Orsay

    Energy Technology Data Exchange (ETDEWEB)

    Calugaru, Valentin [Institut Curie Centre de Protonthérapie d' Orsay, Centre Universitaire, Orsay (France); Institut Curie, Centre Universitaire, Orsay (France); INSERM U612, Centre Universitaire, Orsay (France); Nauraye, Catherine [Institut Curie Centre de Protonthérapie d' Orsay, Centre Universitaire, Orsay (France); Cordelières, Fabrice P. [Institut Curie, Centre Universitaire, Orsay (France); Biard, Denis [Centre d' Etude Atomique, Direction des Sciences du Vivant, Institut des Maladies Emergentes et des Thérapies Innovantes, Service d' Etude des Prions et des Infections Atypiques, Fontenay-aux-Roses (France); De Marzi, Ludovic [Institut Curie Centre de Protonthérapie d' Orsay, Centre Universitaire, Orsay (France); Hall, Janet; Favaudon, Vincent [Institut Curie, Centre Universitaire, Orsay (France); INSERM U612, Centre Universitaire, Orsay (France); Mégnin-Chanet, Frédérique, E-mail: frederique.megnin@inserm.fr [Institut Curie, Centre Universitaire, Orsay (France); INSERM U612, Centre Universitaire, Orsay (France)

    2014-09-01

    Purpose: Previously we showed that the relative biological efficiency for induced cell killing by the 76-MeV beam used at the Institut Curie Proton Therapy Center in Orsay increased with depth throughout the spread-out Bragg peak (SOBP). To investigate the repair pathways underlying this increase, we used an isogenic human cell model in which individual DNA repair proteins have been depleted, and techniques dedicated to precise measurements of radiation-induced DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). Methods and Materials: The 3-Gy surviving fractions of HeLa cells individually depleted of Ogg1, XRCC1, and PARP1 (the base excision repair/SSB repair pathway) or of ATM, DNA-PKcs, XRCC4, and Artemis (nonhomologous end-joining pathway) were determined at the 3 positions previously defined in the SOBP. Quantification of incident SSBs and DSBs by the alkaline elution technique and 3-dimensional (3D) immunofluorescence of γ-H2AX foci, respectively, was performed in SQ20 B cells. Results: We showed that the amount of SSBs and DSBs depends directly on the particle fluence and that the increase in relative biological efficiency observed in the distal part of the SOBP is due to a subset of lesions generated under these conditions, leading to cell death via a pathway in which the Artemis protein plays a central role. Conclusions: Because therapies like proton or carbon beams are now being used to treat cancer, it is even more important to dissect the mechanisms implicated in the repair of the lesions generated by these particles. Additionally, alteration of the expression or activity of the Artemis protein could be a novel therapeutic tool before high linear energy transfer irradiation treatment.

  5. Involvement of the Artemis Protein in the Relative Biological Efficiency Observed With the 76-MeV Proton Beam Used at the Institut Curie Proton Therapy Center in Orsay

    International Nuclear Information System (INIS)

    Purpose: Previously we showed that the relative biological efficiency for induced cell killing by the 76-MeV beam used at the Institut Curie Proton Therapy Center in Orsay increased with depth throughout the spread-out Bragg peak (SOBP). To investigate the repair pathways underlying this increase, we used an isogenic human cell model in which individual DNA repair proteins have been depleted, and techniques dedicated to precise measurements of radiation-induced DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). Methods and Materials: The 3-Gy surviving fractions of HeLa cells individually depleted of Ogg1, XRCC1, and PARP1 (the base excision repair/SSB repair pathway) or of ATM, DNA-PKcs, XRCC4, and Artemis (nonhomologous end-joining pathway) were determined at the 3 positions previously defined in the SOBP. Quantification of incident SSBs and DSBs by the alkaline elution technique and 3-dimensional (3D) immunofluorescence of γ-H2AX foci, respectively, was performed in SQ20 B cells. Results: We showed that the amount of SSBs and DSBs depends directly on the particle fluence and that the increase in relative biological efficiency observed in the distal part of the SOBP is due to a subset of lesions generated under these conditions, leading to cell death via a pathway in which the Artemis protein plays a central role. Conclusions: Because therapies like proton or carbon beams are now being used to treat cancer, it is even more important to dissect the mechanisms implicated in the repair of the lesions generated by these particles. Additionally, alteration of the expression or activity of the Artemis protein could be a novel therapeutic tool before high linear energy transfer irradiation treatment

  6. Parametric representation of centrifugal pump homologous curves

    Energy Technology Data Exchange (ETDEWEB)

    Veloso, Marcelo A.; Mattos, Joao R.L. de, E-mail: velosom@cdtn.br, E-mail: jrmattos@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2015-07-01

    Essential for any mathematical model designed to simulate flow transient events caused by pump operations is the pump performance data. The performance of a centrifugal pump is characterized by four basic quantities: the rotational speed, the volumetric flow rate, the dynamic head, and the hydraulic torque. The curves showing the relationships between these four variables are called the pump characteristic curves. The characteristic curves are empirically developed by the pump manufacturer and uniquely describe head and torque as functions of volumetric flow rate and rotation speed. Because of comprising a large amount of points, this configuration is not suitable for computational purposes. However, it can be converted to a simpler form by the development of the homologous curves, in which dynamic head and hydraulic torque ratios are expressed as functions of volumetric flow and rotation speed ratios. The numerical use of the complete set of homologous curves requires specification of sixteen partial curves, being eight for the dynamic head and eight for the hydraulic torque. As a consequence, the handling of homologous curves is still somewhat complicated. In solving flow transient problems that require the pump characteristic data for all the operation zones, the parametric form appears as the simplest way to deal with the homologous curves. In this approach, the complete characteristics of a pump can be described by only two closed curves, one for the dynamic head and other for the hydraulic torque, both in function of a single angular coordinate defined adequately in terms of the quotient between volumetric flow ratio and rotation speed ratio. The usefulness and advantages of this alternative method are demonstrated through a practical example in which the homologous curves for a pump of the type used in the main coolant loops of a pressurized water reactor (PWR) are transformed to the parametric form. (author)

  7. A rationally designed peptide enhances homologous recombination in vitro and resistance to DNA damaging agents in vivo

    OpenAIRE

    Chen, Li-Tzu; Wang, Andrew H.-J.

    2010-01-01

    The RecA family of proteins is essential in homologous recombination, a critical step in DNA repair. Here, we report that a rationally-designed small peptide based on the crystal structure of Escherichia coli RecA–DNA complex can promote homologous recombination through the enhancement of both RecA-mediated strand assimilation and three-strand exchange activity. Among 17 peptides tested, peptide #3 with the amino acid sequence of IRFLTARRR has the most potent activity in promoting the RecA-me...

  8. Homological algebra in strongly non-Abelian settings

    CERN Document Server

    Grandis, Marco

    2013-01-01

    We propose here a study of 'semiexact' and 'homological' categories as a basis for a generalised homological algebra. Our aim is to extend the homological notions to deeply non-abelian situations, where satellites and spectral sequences can still be studied.This is a sequel of a book on 'Homological Algebra, The interplay of homology with distributive lattices and orthodox semigroups', published by the same Editor, but can be read independently of the latter.The previous book develops homological algebra in p-exact categories, i.e. exact categories in the sense of Puppe and Mitchell - a modera

  9. An efficient method of constructing homologous recom binant baculovirus with PCR-amplified fragments

    Institute of Scientific and Technical Information of China (English)

    HOU; Songwang; (侯松旺); CHEN; Xinwen; (陈新文); WANG; Hanzhong; (王汉中); HU; Zhihong; (胡志红)

    2003-01-01

    This paper describes a rapid method of constructing homologous recombinant baculovirus in E. coli with PCR-amplified fragments. By using this method, the traditional steps of constructing transfer vector are omitted. The method is based on phage λ red system which can promote the recombination between the homologous fragments with the length above 36 bp. Taking HaSNPV as an example, this paper describes the rapid recombination process by using chloramphenicol resistance gene (CmR) to replace orf135 in HaSNPV genome. A pair of primers with length of 60 bp was synthesized, in which 40 bp was homologous to the each end sequence of orf135, and the rest 20 bp was homologous to the each end sequence of CmR. By using these primers, a linear fragment containing the complete CmR gene between 40 bp of homologous arms of orf135 was generated by PCR with the plasmid pKD3 which contains CmR as the template. By transforming the linear fragment into the E. coli containing the bacterial artificial chromosome of HaSNPV and with the help of a plasmid expressing λ recombinase, the recombinants on which the homologue replacement had taken place were selected by chloramphenicol resistance. This method greatly shortens the process of constructing recombinant baculovirus since the process was performed in E. coli and does not need to construct transfer vectors. It can be further used for gene replacement and gene deletion of other large viral genomes.

  10. Homological Pisot Substitutions and Exact Regularity

    CERN Document Server

    Barge, Marcy; Jones, Leslie; Sadun, Lorenzo

    2010-01-01

    We consider one-dimensional substitution tiling spaces where the dilatation (stretching factor) is a degree d Pisot number, and where the first rational Cech cohomology is d-dimensional. We construct examples of such "homological Pisot" substitutions that do not have pure discrete spectra. These examples are not unimodular, and we conjecture that the coincidence rank must always divide a power of the norm of the dilatation. To support this conjecture, we show that homological Pisot substitutions exhibit an Exact Regularity Property (ERP), in which the number of occurrences of a patch for a return length is governed strictly by the length. The ERP puts strong constraints on the measure of any cylinder set in the corresponding tiling space.

  11. Homological mirror symmetry and tropical geometry

    CERN Document Server

    Catanese, Fabrizio; Kontsevich, Maxim; Pantev, Tony; Soibelman, Yan; Zharkov, Ilia

    2014-01-01

    The relationship between Tropical Geometry and Mirror Symmetry goes back to the work of Kontsevich and Y. Soibelman (2000), who applied methods of non-archimedean geometry (in particular, tropical curves) to Homological Mirror Symmetry. In combination with the subsequent work of Mikhalkin on the “tropical” approach to Gromov-Witten theory, and the work of Gross and Siebert, Tropical Geometry has now become a powerful tool. Homological Mirror Symmetry is the area of mathematics concentrated around several categorical equivalences connecting symplectic and holomorphic (or algebraic) geometry. The central ideas first appeared in the work of Maxim Kontsevich (1993). Roughly speaking, the subject can be approached in two ways: either one uses Lagrangian torus fibrations of Calabi-Yau manifolds (the so-called Strominger-Yau-Zaslow picture, further developed by Kontsevich and Soibelman) or one uses Lefschetz fibrations of symplectic manifolds (suggested by Kontsevich and further developed by Seidel). Tropical Ge...

  12. Homologous Pairing between Long DNA Double Helices

    Science.gov (United States)

    Mazur, Alexey K.

    2016-04-01

    Molecular recognition between two double stranded (ds) DNA with homologous sequences may not seem compatible with the B-DNA structure because the sequence information is hidden when it is used for joining the two strands. Nevertheless, it has to be invoked to account for various biological data. Using quantum chemistry, molecular mechanics, and hints from recent genetics experiments, I show here that direct recognition between homologous dsDNA is possible through the formation of short quadruplexes due to direct complementary hydrogen bonding of major-groove surfaces in parallel alignment. The constraints imposed by the predicted structures of the recognition units determine the mechanism of complexation between long dsDNA. This mechanism and concomitant predictions agree with the available experimental data and shed light upon the sequence effects and the possible involvement of topoisomerase II in the recognition.

  13. Homological stability for unordered configuration spaces

    DEFF Research Database (Denmark)

    Randal-Williams, Oscar

    2013-01-01

    This paper consists of two related parts. In the first part we give a self-contained proof of homological stability for the spaces C_n(M;X) of configurations of n unordered points in a connected open manifold M with labels in a path-connected space X, with the best possible integral stability range...... of the spaces C_n(M) can be considered stable when M is a closed manifold. In this case there are no stabilisation maps, but one may still ask if the dimensions of the homology groups over some field stabilise with n. We prove that this is true when M is odd-dimensional, or when the field is F_2 or Q...

  14. Hochschild homology, lax codescent, and duplicial structure

    OpenAIRE

    Garner, Richard; Lack, Stephen; Slevin, Paul

    2015-01-01

    We study the duplicial objects of Dwyer and Kan, which generalize the cyclic objects of Connes. We describe duplicial objects in terms of the decalage comonads, and we give a conceptual account of the construction of duplicial objects due to Bohm and Stefan. This is done in terms of a 2-categorical generalization of Hochschild homology. We also study duplicial structure on nerves of categories, bicategories, and monoidal categories.

  15. Nash equilibria via duality and homological selection

    Indian Academy of Sciences (India)

    Arnab Basu; Samik Basu; Mahan MJ

    2014-11-01

    Given a multifunction from to the -fold symmetric product Sym$_{k}(X)$, we use the Dold–Thom theorem to establish a homological selection theorem. This is used to establish existence of Nash equilibria. Cost functions in problems concerning the existence of Nash equilibria are traditionally multilinear in the mixed strategies. The main aim of this paper is to relax the hypothesis of multilinearity. We use basic intersection theory, Poincaré duality in addition to the Dold–Thom theorem.

  16. Recombineering Homologous Recombination Constructs in Drosophila

    OpenAIRE

    Carreira-Rosario, Arnaldo; Scoggin, Shane; Shalaby, Nevine A.; Williams, Nathan David; Hiesinger, P. Robin; Buszczak, Michael

    2013-01-01

    The continued development of techniques for fast, large-scale manipulation of endogenous gene loci will broaden the use of Drosophila melanogaster as a genetic model organism for human-disease related research. Recent years have seen technical advancements like homologous recombination and recombineering. However, generating unequivocal null mutations or tagging endogenous proteins remains a substantial effort for most genes. Here, we describe and demonstrate techniques for using recombineeri...

  17. On the definition of homological critical value

    OpenAIRE

    Govc, Dejan

    2013-01-01

    We point out that there is a problem with the definition of homological critical value (as defined in the widely cited paper \\cite{stability} by Cohen-Steiner, Edelsbrunner and Harer). Under that definition, the critical value lemma of \\cite{stability} in fact fails. We provide several counterexamples and a definition (due to Bubenik and Scott \\cite{categorification}) we feel should be preferred and under which the critical value lemma does indeed hold. One of the counterexamples we have foun...

  18. Persistent Homology and Partial Similarity of Shapes

    OpenAIRE

    Di Fabio, Barbara; Landi, Claudia

    2011-01-01

    The ability to perform shape retrieval based not only on full similarity, but also partial similarity is a key property for any content-based search engine. We prove that persistence diagrams can reveal a partial similarity between two shapes by showing a common subset of points. This can be explained using the Mayer-Vietoris formulas that we develop for ordinary, relative and extended persistent homology. An experiment outlines the potential of persistence diagrams as shape descriptors in re...

  19. Irradiated homologous costal cartilage for augmentation rhinoplasty

    Energy Technology Data Exchange (ETDEWEB)

    Lefkovits, G. (Lenox Hill Hospital, New York, NY (USA))

    1990-10-01

    Although the ideal reconstructive material for augmentation rhinoplasty continues to challenge plastic surgeons, there exists no report in the literature that confines the use of irradiated homologous costal cartilage, first reported by Dingman and Grabb in 1961, to dorsal nasal augmentation. The purpose of this paper is to present a retrospective analysis of the author's experience using irradiated homologous costal cartilage in augmentation rhinoplasty. Twenty-seven dorsal nasal augmentations were performed in 24 patients between 16 and 49 years of age with a follow-up ranging from 1 to 27 months. Good-to-excellent results were achieved in 83.3% (20 of 24). Poor results requiring revision were found in 16.7% (4 of 24). Complication rates included 7.4% infection (2 of 27) and 14.8% warping (4 of 27). The resorption rate was zero. These results compare favorably with other forms of nasal augmentation. Advantages and disadvantages of irradiated homologous costal cartilage are discussed.

  20. Note on homological modeling of the electric circuits

    International Nuclear Information System (INIS)

    Based on a simple example, it is explained how the homological analysis may be used for modeling of the electric circuits. The homological branch, mesh and nodal analyses are presented. Geometrical interpretations are given.

  1. Characterizing filaments in regions of high-mass star formation: High-resolution submilimeter imaging of the massive star-forming complex NGC 6334 with ArT\\'eMiS

    CERN Document Server

    André, Ph; Könyves, V; Arzoumanian, D; Tigé, J; Gallais, P; Roussel, H; Pennec, J Le; Rodriguez, L; Doumayrou, E; Dubreuil, D; Lortholary, M; Martignac, J; Talvard, M; Delisle, C; Visticot, F; Dumaye, L; De Breuck, C; Shimajiri, Y; Motte, F; Bontemps, S; Hennemann, M; Zavagno, A; Russeil, D; Schneider, N; Palmeirim, P; Peretto, N; Hill, T; Minier, V; Roy, A; Rygl, K L J

    2016-01-01

    Herschel observations of nearby molecular clouds suggest that interstellar filaments and prestellar cores represent two fundamental steps in the star formation process. The observations support a picture of low-mass star formation according to which ~ 0.1 pc-wide filaments form first in the cold interstellar medium, probably as a result of large-scale compression of interstellar matter by supersonic turbulent flows, and then prestellar cores arise from gravitational fragmentation of the densest filaments. Whether this scenario also applies to regions of high-mass star formation is an open question, in part because Herschel data cannot resolve the inner width of filaments in the nearest regions of massive star formation. We used the bolometer camera ArTeMiS on the APEX telescope to map the central part of the NGC6334 complex at a factor of > 3 higher resolution than Herschel at 350 microns. Combining ArTeMiS data with Herschel data allowed us to study the structure of the main filament of the complex with a re...

  2. Computing Small 1-Homological Models for Commutative Differential Graded Algebras

    OpenAIRE

    Alvarez, Victor; Armario, Jose Andres; Frau, Maria Dolores; Gonzalez-Diaz, Rocio; Jimenez, Maria Jose; Real, Pedro; Silva, Beatriz

    2001-01-01

    We use homological perturbation machinery specific for the algebra category [P. Real. Homological Perturbation Theory and Associativity. Homology, Homotopy and Applications vol. 2, n. 5 (2000) 51-88] to give an algorithm for computing the differential structure of a small 1--homological model for commutative differential graded algebras (briefly, CDGAs). The complexity of the procedure is studied and a computer package in Mathematica is described for determining such models.

  3. Tocopherol and tocotrienol homologs in parenteral lipid emulsions

    OpenAIRE

    Xu, Zhidong; Harvey, Kevin A.; Pavlina, Thomas M; Zaloga, Gary P.; Siddiqui, Rafat A.

    2014-01-01

    Parenteral lipid emulsions, which are made of oils from plant and fish sources, contain different types of tocopherols and tocotrienols (vitamin E homologs). The amount and types of vitamin E homologs in various lipid emulsions vary considerably and are not completely known. The objective of this analysis was to develop a quantitative method to determine levels of all vitamin E homologs in various lipid emulsions. An HPLC system was used to measure vitamin E homologs using a Pinnacle DB Silic...

  4. Equivariant geometric K-homology for compact Lie group actions

    CERN Document Server

    Baum, Paul; Schick, Thomas

    2009-01-01

    Let G be a compact Lie-group, X a compact G-CW-complex. We define equivariant geometric K-homology groups K^G_*(X), using an obvious equivariant version of the (M,E,f)-picture of Baum-Douglas for K-homology. We define explicit natural transformations to and from equivariant K-homology defined via KK-theory (the "official" equivariant K-homology groups) and show that these are isomorphism.

  5. PUF-8, a Pumilio Homolog, Inhibits the Proliferative Fate in the Caenorhabditis elegans Germline

    OpenAIRE

    Racher, Hilary; Hansen, Dave

    2012-01-01

    Stem cell populations are maintained by keeping a balance between self-renewal (proliferation) and differentiation of dividing stem cells. Within the Caenorhabditis elegans germline, the key regulator maintaining this balance is the canonical Notch signaling pathway, with GLP-1/Notch activity promoting the proliferative fate. We identified the Pumilio homolog, PUF-8, as an inhibitor of the proliferative fate of stem cells in the C. elegans germline. puf-8(0) strongly enhances overproliferatio...

  6. Duality and products in algebraic (co)homology theories

    OpenAIRE

    Kowalzig, N.; Kraehmer, U.

    2008-01-01

    The origin and interplay of products and dualities in algebraic (co)homology theories is ascribed to a ×A-Hopf algebra structure on the relevant universal enveloping algebra. This provides a unified treatment for example of results by Van den Bergh about Hochschild (co)homology and by Huebschmann about Lie–Rinehart (co)homology.

  7. Experimental investigation of interface conditions between oxidic melt and ablating concrete during MCCI by means of simulating material experiments: the Artemis program

    International Nuclear Information System (INIS)

    Full text of publication follows: In the frame work of R and D on Severe Accidents in PWR plants, an estimation by codes of time of basemat melt-through by Corium is required. For this, the heat flux distribution along the cavity wall must be properly modelled. Hence the knowledge of the heat transfer coefficient as well as the temperature at the interface between the melt and the solid become key issues. Phase diagram of the melt and composition governs the interface temperature which controls, at least partly, the thickness of the Corium crust formed on the molten concrete. Crust behaviour (time evolution of thickness, mechanical interaction with gas) implies a release mode of molten concrete in Corium which in turn alters the melt composition. Clearly, the molten corium-concrete interaction (MCCI) phenomenon is the result of a strong coupling between physico-chemistry and thermohydraulics. The main goal of the first test series of the Artemis program is to make a link between the interface temperature and the physico-chemistry of the melt (phase diagram) through tests conducted with simulating materials and to provide an insight on the existence, the behaviour and the composition of the crust. This test series considers 1D MCCI using a non eutectic LiCl-BaCl2 mixture poured at 1000 deg. C in a cylindrical test section (internal diameter 0.3 m) to interact with the 0.35 m deep basemat made of the same salt mixture at the eutectic composition. This 'concrete' was especially manufactured with sintered granulates to allow gas flow from the bottom (argon), then simulating gas released by concrete in the reactor case. Constant power is applied in the pool with an helical coil and 1D MCCI is ensured by counterbalancing heat losses by controlled heating at the lateral walls and at the top of the test section. Concrete ablation is followed from the output of 45 0.5 mm diameter thermocouples. An instrumented rod periodically investigates the temperature and the position

  8. Excluded volume effect enhances the homology pairing of model chromosomes

    CERN Document Server

    Takamiya, Kazunori; Isami, Shuhei; Nishimori, Hiraku; Awazu, Akinori

    2015-01-01

    To investigate the structural dynamics of the homology pairing of polymers, we mod- eled the scenario of homologous chromosome pairings during meiosis in Schizosaccharomyces pombe, one of the simplest model organisms of eukaryotes. We consider a simple model consist- ing of pairs of homologous polymers with the same structures that are confined in a cylindrical container, which represents the local parts of chromosomes contained in an elongated nucleus of S. pombe. Brownian dynamics simulations of this model showed that the excluded volume effects among non-homological chromosomes and the transitional dynamics of nuclear shape serve to enhance the pairing of homologous chromosomes.

  9. Exponential growth of colored HOMFLY-PT homology

    CERN Document Server

    Wedrich, Paul

    2016-01-01

    We define reduced colored sl(N) link homologies and use deformation spectral sequences to characterize their dependence on color and rank. We then define reduced colored HOMFLY-PT homologies and prove that they arise as large N limits of sl(N) homologies. Together, these results allow proofs of many aspects of the physically conjectured structure of the family of type A link homologies. In particular, we verify a conjecture of Gorsky, Gukov and Sto\\v{s}i\\'c about the growth of colored HOMFLY-PT homologies.

  10. Hochschild homology and microlocal Euler classes

    CERN Document Server

    Kashiwara, Masaki

    2012-01-01

    We define the notion of a Hochschild kernel on a manifold M. Roughly speaking, it is a sheaf on M x M for which the formalism of Hochschild homology applies. We associate a microlocal Euler class to such a kernel, a cohomology class with values in the relative dualizing complex of the cotangent bundle over M and we prove that this class is functorial with respect to the composition of kernels. This generalizes, unifies and simplifies various results of (relative) index theorems for constructible sheaves, D-modules and elliptic pairs.

  11. Periodic cyclic homology of affine Hecke algebras

    CERN Document Server

    Solleveld, Maarten

    2009-01-01

    This is the author's PhD-thesis, which was written in 2006. The version posted here is identical to the printed one. Instead of an abstract, the short list of contents: Preface 5 1 Introduction 9 2 K-theory and cyclic type homology theories 13 3 Affine Hecke algebras 61 4 Reductive p-adic groups 103 5 Parameter deformations in affine Hecke algebras 129 6 Examples and calculations 169 A Crossed products 223 Bibliography 227 Index 237 Samenvatting 245 Curriculum vitae 253

  12. L^2-homology for compact quantum groups

    OpenAIRE

    Kyed, David

    2006-01-01

    A notion of L^2-homology for compact quantum groups is introduced, generalizing the classical notion for countable, discrete groups. If the compact quantum group in question has tracial Haar state, it is possible to define its L^2-Betti numbers and Novikov-Shubin invariants/capacities. It is proved that these L^2-Betti numbers vanish for the Gelfand dual of a compact Lie group and that the zeroth Novikov-Shubin invariant equals the dimension of the underlying Lie group. Finally, we relate our...

  13. Homology of lipoprotein lipase to pancreatic lipase.

    OpenAIRE

    Ben-Avram, C M; Ben-Zeev, O; Lee, T.D. (Taunia D.); Haaga, K; Shively, J. E.; Goers, J; Pedersen, M.E; Reeve, J R; Schotz, M C

    1986-01-01

    Bovine milk lipoprotein lipase was subjected to amino acid sequence analysis. The first 19 amino-terminal residues were Asp-Arg-Ile-Thr-Gly-Gly-Lys-Asp-Phe-Arg-Asp-Ile-Glu-Ser-Lys-Phe-Ala-Leu- Arg. In addition, reversed-phase high-performance liquid chromatography of a tryptic digest of reduced and alkylated lipase resolved a number of peptides, five of which contained cysteine. Sequence analysis of the tryptic peptides revealed in most instances a close homology to porcine pancreatic lipase....

  14. Hochschild Homology and Cohomology of Klein Surfaces

    Directory of Open Access Journals (Sweden)

    Frédéric Butin

    2008-09-01

    Full Text Available Within the framework of deformation quantization, a first step towards the study of star-products is the calculation of Hochschild cohomology. The aim of this article is precisely to determine the Hochschild homology and cohomology in two cases of algebraic varieties. On the one hand, we consider singular curves of the plane; here we recover, in a different way, a result proved by Fronsdal and make it more precise. On the other hand, we are interested in Klein surfaces. The use of a complex suggested by Kontsevich and the help of Groebner bases allow us to solve the problem.

  15. Detailed assessment of homology detection using different substitution matrices

    Institute of Scientific and Technical Information of China (English)

    LI Jing; WANG Wei

    2006-01-01

    Homology detection plays a key role in bioinformatics, whereas substitution matrix is one of the most important components in homology detection. Thus, besides the improvement of alignment algorithms, another effective way to enhance the accuracy of homology detection is to use proper substitution matrices or even construct new matrices.A study on the features of various matrices and on the comparison of the performances between different matrices in homology detection enable us to choose the most proper or optimal matrix for some specific applications. In this paper, by taking BLOSUM matrices as an example, some detailed features of matrices in homology detection are studied by calculating the distributions of numbers of recognized proteins over different sequence identities and sequence lengths. Our results clearly showed that different matrices have different preferences and abilities to the recognition of remote homologous proteins. Furthermore, detailed features of the various matrices can be used to improve the accuracy of homology detection.

  16. The Homology Groups of a Partial Trace Monoid Action

    CERN Document Server

    Husainov, Ahmet A

    2011-01-01

    The aim of this paper is to investigate the homology groups of mathematical models of concurrency. We study the Baues-Wirsching homology groups of a small category associated with a partial monoid action on a set. We prove that these groups can be reduced to the Leech homology groups of the monoid. For a trace monoid with an action on a set, we will build a cubical complex of free Abelian groups with homology groups isomorphic to the integral homology groups of the action category. It allows us to solve the problem posed by the author in 2004 of the constructing an algorithm for computing homology groups of the CE nets. We describe the algorithm and give examples of calculating the homology groups.

  17. Transfers for ramified covering maps in homology and cohomology

    Directory of Open Access Journals (Sweden)

    Marcelo A. Aguilar

    2006-08-01

    Full Text Available Making use of a modified version, due to McCord, of the Dold-Thom construction of ordinary homology, we give a simple topological definition of a transfer for ramified covering maps in homology with arbitrary coefficients. The transfer is induced by a suitable map between topological groups. We also define a new cohomology transfer which is dual to the homology transfer. This duality allows us to show that our homology transfer coincides with the one given by L. Smith. With our definition of the homology transfer we can give simpler proofs of the properties of the known transfer and of some new ones. Our transfers can also be defined in Karoubi's approach to homology and cohomology. Furthermore, we show that one can define mixed transfers from other homology or cohomology theories to the ordinary ones.

  18. A homological study of Green polynomials

    CERN Document Server

    Kato, Syu

    2011-01-01

    We interpret the orthogonality relation of Kostka polynomials arising from complex reflection groups (c.f. [Shoji, Invent. Math. 74 (1983), J. Algebra 245 (2001)] and [Lusztig, Adv. Math. 61 (1986)]) in terms of homological algebra. This leads us to the notion of Kostka system, which can be seen as a categorical counter-part of Kostka polynomials. Then, we show that every generalized Springer correspondence (in good characteristic) (c.f. [Lusztig, Invent. Math. 75 (1984)]) gives rise to a Kostka system. This enables us to see the top-term generation property of the homology of generalized Springer fibers, and the transition formula of Kostka polynomials between two generalized Springer correspondences of type $\\mathsf{BC}$. The latter enhances one of the main results from [Ciubotaru-Kato-K, Invent. Math., to appear] to its graded version. In the appendix, we present a purely algebraic proof that a Kostka system exists for type $\\mathsf{A}$, and therefore one can skip geometric sections \\S 3--5 to see the key ...

  19. SANSparallel: interactive homology search against Uniprot.

    Science.gov (United States)

    Somervuo, Panu; Holm, Liisa

    2015-07-01

    Proteins evolve by mutations and natural selection. The network of sequence similarities is a rich source for mining homologous relationships that inform on protein structure and function. There are many servers available to browse the network of homology relationships but one has to wait up to a minute for results. The SANSparallel webserver provides protein sequence database searches with immediate response and professional alignment visualization by third-party software. The output is a list, pairwise alignment or stacked alignment of sequence-similar proteins from Uniprot, UniRef90/50, Swissprot or Protein Data Bank. The stacked alignments are viewed in Jalview or as sequence logos. The database search uses the suffix array neighborhood search (SANS) method, which has been re-implemented as a client-server, improved and parallelized. The method is extremely fast and as sensitive as BLAST above 50% sequence identity. Benchmarks show that the method is highly competitive compared to previously published fast database search programs: UBLAST, DIAMOND, LAST, LAMBDA, RAPSEARCH2 and BLAT. The web server can be accessed interactively or programmatically at http://ekhidna2.biocenter.helsinki.fi/cgi-bin/sans/sans.cgi. It can be used to make protein functional annotation pipelines more efficient, and it is useful in interactive exploration of the detailed evidence supporting the annotation of particular proteins of interest. PMID:25855811

  20. Sheaves on Graphs and Their Homological Invariants

    CERN Document Server

    Friedman, Joel

    2011-01-01

    We introduce a notion of a sheaf of vector spaces on a graph, and develop the foundations of homology theories for such sheaves. One sheaf invariant, its "maximum excess," has a number of remarkable properties. It has a simple definition, with no reference to homology theory, that resembles graph expansion. Yet it is a "limit" of Betti numbers, and hence has a short/long exact sequence theory and resembles the $L^2$ Betti numbers of Atiyah. Also, the maximum excess is defined via a supermodular function, which gives the maximum excess much stronger properties than one has of a typical Betti number. The maximum excess gives a simple interpretation of an important graph invariant, which will be used to study the Hanna Neumann Conjecture in a future paper. Our sheaf theory can be viewed as a vast generalization of algebraic graph theory: each sheaf has invariants associated to it---such as Betti numbers and Laplacian matrices---that generalize those in classical graph theory.

  1. Role of a Fur homolog in iron metabolism in Nitrosomonas europaea

    Directory of Open Access Journals (Sweden)

    Bottomley Peter J

    2011-02-01

    Full Text Available Abstract Background In response to environmental iron concentrations, many bacteria coordinately regulate transcription of genes involved in iron acquisition via the ferric uptake regulation (Fur system. The genome of Nitrosomonas europaea, an ammonia-oxidizing bacterium, carries three genes (NE0616, NE0730 and NE1722 encoding proteins belonging to Fur family. Results Of the three N. europaea fur homologs, only the Fur homolog encoded by gene NE0616 complemented the Escherichia coli H1780 fur mutant. A N. europaea fur:kanP mutant strain was created by insertion of kanamycin-resistance cassette in the promoter region of NE0616 fur homolog. The total cellular iron contents of the fur:kanP mutant strain increased by 1.5-fold compared to wild type when grown in Fe-replete media. Relative to the wild type, the fur:kanP mutant exhibited increased sensitivity to iron at or above 500 μM concentrations. Unlike the wild type, the fur:kanP mutant was capable of utilizing iron-bound ferrioxamine without any lag phase and showed over expression of several outer membrane TonB-dependent receptor proteins irrespective of Fe availability. Conclusions Our studies have clearly indicated a role in Fe regulation by the Fur protein encoded by N. europaea NE0616 gene. Additional studies are required to fully delineate role of this fur homolog.

  2. Chatter detection in turning using persistent homology

    Science.gov (United States)

    Khasawneh, Firas A.; Munch, Elizabeth

    2016-03-01

    This paper describes a new approach for ascertaining the stability of stochastic dynamical systems in their parameter space by examining their time series using topological data analysis (TDA). We illustrate the approach using a nonlinear delayed model that describes the tool oscillations due to self-excited vibrations in turning. Each time series is generated using the Euler-Maruyama method and a corresponding point cloud is obtained using the Takens embedding. The point cloud can then be analyzed using a tool from TDA known as persistent homology. The results of this study show that the described approach can be used for analyzing datasets of delay dynamical systems generated both from numerical simulation and experimental data. The contributions of this paper include presenting for the first time a topological approach for investigating the stability of a class of nonlinear stochastic delay equations, and introducing a new application of TDA to machining processes.

  3. Towards Stratification Learning through Homology Inference

    CERN Document Server

    Bendich, Paul; Wang, Bei

    2010-01-01

    A topological approach to stratification learning is developed for point cloud data drawn from a stratified space. Given such data, our objective is to infer which points belong to the same strata. First we define a multi-scale notion of a stratified space, giving a stratification for each radius level. We then use methods derived from kernel and cokernel persistent homology to cluster the data points into different strata, and we prove a result which guarantees the correctness of our clustering, given certain topological conditions; some geometric intuition for these topological conditions is also provided. Our correctness result is then given a probabilistic flavor: we give bounds on the minimum number of sample points required to infer, with probability, which points belong to the same strata. Finally, we give an explicit algorithm for the clustering, prove its correctness, and apply it to some simulated data.

  4. CIRCULAR RIBBON FLARES AND HOMOLOGOUS JETS

    International Nuclear Information System (INIS)

    Solar flare emissions in the chromosphere often appear as elongated ribbons on both sides of the magnetic polarity inversion line (PIL), which has been regarded as evidence of a typical configuration of magnetic reconnection. However, flares having a circular ribbon have rarely been reported, although it is expected in the fan-spine magnetic topology involving reconnection at a three-dimensional (3D) coronal null point. We present five circular ribbon flares with associated surges, using high-resolution and high-cadence Hα blue wing observations obtained from the recently digitized films of Big Bear Solar Observatory. In all the events, a central parasitic magnetic field is encompassed by the opposite polarity, forming a circular PIL traced by filament material. Consequently, a flare kernel at the center is surrounded by a circular flare ribbon. The four homologous jet-related flares on 1991 March 17 and 18 are of particular interest, as (1) the circular ribbons brighten sequentially, with cospatial surges, rather than simultaneously, (2) the central flare kernels show an intriguing 'round-trip' motion and become elongated, and (3) remote brightenings occur at a region with the same magnetic polarity as the central parasitic field and are co-temporal with a separate phase of flare emissions. In another flare on 1991 February 25, the circular flare emission and surge activity occur successively, and the event could be associated with magnetic flux cancellation across the circular PIL. We discuss the implications of these observations combining circular flare ribbons, homologous jets, and remote brightenings for understanding the dynamics of 3D magnetic restructuring.

  5. A roadmap for the computation of persistent homology

    CERN Document Server

    Otter, Nina; Tillmann, Ulrike; Grindrod, Peter; Harrington, Heather A

    2015-01-01

    Persistent homology is a method used in topological data analysis to study qualitative features of data, which is robust to perturbations, dimension independent and provides statistical summaries of the outputs. Despite recent progress, the computation of persistent homology for large data sets remains an open problem. We investigate the challenges of computing persistent homology and navigate through the different algorithms and data structures. Specifically, we evaluate the (currently available) open source implementations of persistent homology computations on a wide range of synthetic and real-world data sets, and indicate which algorithms and implementations are best suited to these data. We provide guidelines for the computation of persistent homology, make our own implementations used in this study available, and put forward measures to quantify the challenges of the computation of persistent homology.

  6. Impact of homologous and non-homologous recombination in the genomic evolution of Escherichia coli

    Directory of Open Access Journals (Sweden)

    Didelot Xavier

    2012-06-01

    Full Text Available Abstract Background Escherichia coli is an important species of bacteria that can live as a harmless inhabitant of the guts of many animals, as a pathogen causing life-threatening conditions or freely in the non-host environment. This diversity of lifestyles has made it a particular focus of interest for studies of genetic variation, mainly with the aim to understand how a commensal can become a deadly pathogen. Many whole genomes of E. coli have been fully sequenced in the past few years, which offer helpful data to help understand how this important species evolved. Results We compared 27 whole genomes encompassing four phylogroups of Escherichia coli (A, B1, B2 and E. From the core-genome we established the clonal relationships between the isolates as well as the role played by homologous recombination during their evolution from a common ancestor. We found strong evidence for sexual isolation between three lineages (A+B1, B2, E, which could be explained by the ecological structuring of E. coli and may represent on-going speciation. We identified three hotspots of homologous recombination, one of which had not been previously described and contains the aroC gene, involved in the essential shikimate metabolic pathway. We also described the role played by non-homologous recombination in the pan-genome, and showed that this process was highly heterogeneous. Our analyses revealed in particular that the genomes of three enterohaemorrhagic (EHEC strains within phylogroup B1 have converged from originally separate backgrounds as a result of both homologous and non-homologous recombination. Conclusions Recombination is an important force shaping the genomic evolution and diversification of E. coli, both by replacing fragments of genes with an homologous sequence and also by introducing new genes. In this study, several non-random patterns of these events were identified which correlated with important changes in the lifestyle of the bacteria, and

  7. Variants of equivariant Seiberg-Witten Floer homology

    OpenAIRE

    Marcolli, M.; Wang, B-L

    2005-01-01

    For a rational homology 3-sphere Y with a Spin c structure s, we show that simple algebraic manipulations of our construction of equivariant Seiberg-Witten Floer homology in lead to a collection of variants, which are all topological invariants. We establish a long exact sequence relating them and we show that they satisfy a duality under orientation reversal. We explain their relation to the equivariant Seiberg-Witten Floer (co)homologies introduced in [loc. cit.]. We conjecture the equivale...

  8. A local homology theory for linearly compact modules

    International Nuclear Information System (INIS)

    We introduce a local homology theory for linearly modules which is in some sense dual to the local cohomology theory of A. Grothendieck. Some basic properties of local homology modules are shown such as: the vanishing and non-vanishing, the noetherianness of local homology modules. By using duality, we extend some well-known results in theory of local cohomology of A. Grothendieck. (author)

  9. Euler Integration of Gaussian Random Fields and Persistent Homology

    CERN Document Server

    Bobrowski, Omer

    2010-01-01

    In this paper we extend the notion of the Euler characteristic to persistent homology and give the relationship between the Euler integral of a function and the Euler characteristic of the function's persistent homology. We then proceed to compute the expected Euler integral of a Gaussian random field using the Gaussian kinematic formula and obtain a simple closed form expression. This results in the first computation of a quantitative descriptor for the persistent homology of a Gaussian random field.

  10. Transcription patterns of genes encoding four metallothionein homologs in Daphnia pulex exposed to copper and cadmium are time- and homolog-dependent

    Energy Technology Data Exchange (ETDEWEB)

    Asselman, Jana, E-mail: jana.asselman@ugent.be [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, Ghent (Belgium); Shaw, Joseph R.; Glaholt, Stephen P. [The School of Public and Environmental Affairs, Indiana University, Bloomington, IN (United States); Colbourne, John K. [School of Biosciences, The University of Birmingham, Birmingham (United Kingdom); De Schamphelaere, Karel A.C. [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, Ghent (Belgium)

    2013-10-15

    Highlights: •Transcription patterns of 4 metallothionein isoforms in Daphnia pulex. •Under cadmium and copper stress these patterns are time-dependent. •Under cadmium and copper stress these patterns are homolog-dependent. •The results stress the complex regulation of metallothioneins. -- Abstract: Metallothioneins are proteins that play an essential role in metal homeostasis and detoxification in nearly all organisms studied to date. Yet discrepancies between outcomes of chronic and acute exposure experiments hamper the understanding of the regulatory mechanisms of their isoforms following metal exposure. Here, we investigated transcriptional differences among four identified homologs (mt1–mt4) in Daphnia pulex exposed across time to copper and cadmium relative to a control. Transcriptional upregulation of mt1 and mt3 was detected on day four following exposure to cadmium, whereas that of mt2 and mt4 was detected on day two and day eight following exposure to copper. These results confirm temporal and metal-specific differences in the transcriptional induction of genes encoding metallothionein homologs upon metal exposure which should be considered in ecotoxicological monitoring programs of metal-contaminated water bodies. Indeed, the mRNA expression patterns observed here illustrate the complex regulatory system associated with metallothioneins, as these patterns are not only dependent on the metal, but also on exposure time and the homolog studied. Further phylogenetic analysis and analysis of regulatory elements in upstream promoter regions revealed a high degree of similarity between metallothionein genes of Daphnia pulex and Daphnia magna, a species belonging to the same genus. These findings, combined with a limited amount of available expression data for D. magna metallothionein genes, tentatively suggest a potential generalization of the metallothionein response system between these Daphnia species.

  11. Homologous recombination: from model organisms to human disease

    NARCIS (Netherlands)

    M. Modesti (Mauro); R. Kanaar (Roland)

    2001-01-01

    textabstractRecent experiments show that properly controlled recombination between homologous DNA molecules is essential for the maintenance of genome stability and for the prevention of tumorigenesis.

  12. On the geography and botany of knot Floer homology

    OpenAIRE

    Hedden, Matthew; Watson, Liam

    2014-01-01

    This note explores two questions: (1) Which bigraded groups arise as the knot Floer homology of a knot in the three-sphere? (2) Given a knot, how many distinct knots share its Floer homology? Regarding the first, we show there exist bigraded groups satisfying all previously known constraints of knot Floer homology which do not arise as the invariant of a knot. This leads to a new constraint for knots admitting lens space surgeries, as well as a proof that the rank of knot Floer homology detec...

  13. Gene prediction by pattern recognition and homology search

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Y.; Uberbacher, E.C.

    1996-05-01

    This paper presents an algorithm for combining pattern recognition-based exon prediction and database homology search in gene model construction. The goal is to use homologous genes or partial genes existing in the database as reference models while constructing (multiple) gene models from exon candidates predicted by pattern recognition methods. A unified framework for gene modeling is used for genes ranging from situations with strong homology to no homology in the database. To maximally use the homology information available, the algorithm applies homology on three levels: (1) exon candidate evaluation, (2) gene-segment construction with a reference model, and (3) (complete) gene modeling. Preliminary testing has been done on the algorithm. Test results show that (a) perfect gene modeling can be expected when the initial exon predictions are reasonably good and a strong homology exists in the database; (b) homology (not necessarily strong) in general helps improve the accuracy of gene modeling; (c) multiple gene modeling becomes feasible when homology exists in the database for the involved genes.

  14. Homology cylinders and the acyclic closure of a free group

    OpenAIRE

    Sakasai, Takuya

    2005-01-01

    We give a Dehn-Nielsen type theorem for the homology cobordism group of homology cylinders by considering its action on the acyclic closure, which was defined by Levine, of a free group. Then we construct an additive invariant of those homology cylinders which act on the acyclic closure trivially. We also describe some tools to study the automorphism group of the acyclic closure of a free group generalizing those for the automorphism group of a free group or the homology cobordism group of ho...

  15. The σ enigma: bacterial σ factors, archaeal TFB and eukaryotic TFIIB are homologs.

    Science.gov (United States)

    Burton, Samuel P; Burton, Zachary F

    2014-01-01

    Structural comparisons of initiating RNA polymerase complexes and structure-based amino acid sequence alignments of general transcription initiation factors (eukaryotic TFIIB, archaeal TFB and bacterial σ factors) show that these proteins are homologs. TFIIB and TFB each have two-five-helix cyclin-like repeats (CLRs) that include a C-terminal helix-turn-helix (HTH) motif (CLR/HTH domains). Four homologous HTH motifs are present in bacterial σ factors that are relics of CLR/HTH domains. Sequence similarities clarify models for σ factor and TFB/TFIIB evolution and function and suggest models for promoter evolution. Commitment to alternate modes for transcription initiation appears to be a major driver of the divergence of bacteria and archaea. PMID:25483602

  16. Chromosome sites play dual roles to establish homologous synapsisduring meiosis in C. elegans

    Energy Technology Data Exchange (ETDEWEB)

    MacQueen, Amy J.; Phillips, Carolyn M.; Bhalla, Needhi; Weiser,Pinky; Villeneuve, Anne M.; Dernburg, Abby F.

    2005-06-05

    required for accurate segregation of homologous chromosomesduring meiosisin C. elegans. We find that these sites play two distinctroles that contribute to proper segregation. Chromosomes lacking PCsusually fail to synapse and also lack a synapsis-independentstabilization activity. The presence of a PC on justone copy of achromosome pair promotes synapsis but does not supportsynapsis-independent pairing stabilization, indicating that thesefunctions are separable. Once initiated, synapsis is highly processive,even between non homologous chromosomes of disparate lengths, elucidatinghow translocations suppress meiotic recombination in C. elegans. Thesefindings suggest a multistep pathway for chromosome synapsis in which PCsimpart selectivity and efficiency through a kinetic proofreadingmechanism. We speculate that concentration of these activities at oneregion per chromosome may have co-evolved with the loss of a pointcentromere to safeguard karyotype stability.

  17. Homologous recombination deficiency and ovarian cancer.

    Science.gov (United States)

    Ledermann, Jonathan A; Drew, Yvette; Kristeleit, Rebecca S

    2016-06-01

    The discovery that PARP inhibitors block an essential pathway of DNA repair in cells harbouring a BRCA mutation has opened up a new therapeutic avenue for high-grade ovarian cancers. BRCA1 and BRCA2 proteins are essential for high-fidelity repair of double-strand breaks of DNA through the homologous recombination repair (HRR) pathway. Deficiency in HRR (HRD) is a target for PARP inhibitors. The first PARP inhibitor, olaparib, has now been licensed for BRCA-mutated ovarian cancers. While mutated BRCA genes are individually most commonly associated with HRD other essential HRR proteins may be mutated or functionally deficient potentially widening the therapeutic opportunities for PARP inhibitors. HRD is the first phenotypically defined predictive marker for therapy with PARP inhibitors in ovarian cancer. Several different PARP inhibitors are being trialled in ovarian cancer and this class of drugs has been shown to be a new selective therapy for high-grade ovarian cancer. Around 20% of high-grade serous ovarian cancers harbour germline or somatic BRCA mutations and testing for BRCA mutations should be incorporated into routine clinical practice. The expanded use of PARP inhibitors in HRD deficient (non-BRCA mutant) tumours using a signature of HRD in clinical practice requires validation. PMID:27065456

  18. Circular Ribbon Flares and Homologous Jets

    CERN Document Server

    Wang, Haimin

    2012-01-01

    Solar flare emissions in the chromosphere often appear as elongated ribbons on both sides of the magnetic polarity inversion line (PIL), and this has been regarded as evidence of a typical configuration of magnetic reconnection. However, flares having a closed circular ribbon have rarely been reported, although it is expected in the fan--spine magnetic topology involving reconnection at a three-dimensional (3D) coronal null point. We present five circular ribbon flares with associated surges, using high-resolution and high-cadence \\ha blue wing observations obtained from the recently digitized films of Big Bear Solar Observatory (BBSO). In all the events, a central parasitic magnetic field is encompassed by the opposite magnetic polarity, forming a circular PIL that is also traced by filament material. Consequently, a flare kernel at the center is surrounded by a circular flare ribbon. The four homologous jet-related flares on 1991 March 17 and 18 are of particular interest, as (1) the circular ribbons bright...

  19. An adelic resolution for homology sheaves

    Energy Technology Data Exchange (ETDEWEB)

    Gorchinskii, S O [Steklov Mathematical Institute, Russian Academy of Sciences, Moscow (Russian Federation)

    2008-12-31

    We propose a generalization of the ordinary idele group by constructing certain adelic complexes for sheaves of K-groups on schemes. Such complexes are defined for any abelian sheaf on a scheme. We focus on the case when the sheaf is associated with the presheaf of a homology theory with certain natural axioms satisfied, in particular, by K-theory. In this case it is proved that the adelic complex provides a flabby resolution for this sheaf on smooth varieties over an infinite perfect field and that the natural morphism to the Gersten complex is a quasi-isomorphism. The main advantage of the new adelic resolution is that it is contravariant and multiplicative. In particular, this enables us to reprove that the intersection in Chow groups coincides (up to a sign) with the natural product in the corresponding K-cohomology groups. Also, we show that the Weil pairing can be expressed as a Massey triple product in K-cohomology groups with certain indices.

  20. Cylindrical contact homology of subcritical Stein-fillable contact manifolds

    OpenAIRE

    Yau, Mei-Lin

    2004-01-01

    We use contact handle decompositions and a stabilization process to compute the cylindrical contact homology of a subcritical Stein-fillable contact manifold with vanishing first Chern class, and show that it is completely determined by the homology of a subcritical Stein-filling of the contact manifold.

  1. CBH1 homologs and varian CBH1 cellulase

    Science.gov (United States)

    Goedegebuur, Frits; Gualfetti, Peter; Mitchinson, Colin; Neefe, Paulien

    2014-07-01

    Disclosed are a number of homologs and variants of Hypocrea jecorina Cel7A (formerly Trichoderma reesei cellobiohydrolase I or CBH1), nucleic acids encoding the same and methods for producing the same. The homologs and variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted and/or deleted.

  2. A configuration space for equivariant connective K-homology

    CERN Document Server

    Velasquez, Mario

    2012-01-01

    Following ideas of Graeme Segal we construct a configuration space that represents equivariant connective K-homology for group actions of finite groups and furthermore we describe explicitly the complex homology of this configuration space as a Hopf algebra. As a consequence of this work we obtain models of representing spaces for equivariant K-theory.

  3. The weight filtration for real algebraic varieties II: Classical homology

    OpenAIRE

    Mccrory, Clint; Parusinski, Adam

    2012-01-01

    We associate to each real algebraic variety a filtered chain complex, the weight complex, which is well-defined up to filtered quasi-isomorphism, and which induces on classical (compactly supported) homology with Z/2 coefficients an analog of the weight filtration for complex algebraic varieties. This complements our previous definition of the weight filtration of Borel-Moore homology.

  4. A spectrum-level Hodge filtration on topological Hochschild homology

    OpenAIRE

    Glasman, Saul

    2014-01-01

    We define a functorial spectrum-level filtration on the topological Hochschild homology of any commutative ring spectrum $R$, and more generally the factorization homology $R \\otimes X$ for any space $X$, echoing algebraic constructions of Loday and Pirashvili. We investigate the properties of this filtration and show that it breaks THH up into common eigenspectra of the Adams operations.

  5. The tedious task of finding homologous noncoding RNA genes

    DEFF Research Database (Denmark)

    Menzel, Karl Peter; Gorodkin, Jan; Stadler, Peter F

    2009-01-01

    : BLAST still works better or equally good as other methods unless extensive expert knowledge on the RNA family is included. However, when good curated data are available the recent development yields further improvements in finding remote homologs. Homology search beyond the reach of BLAST hence is not...

  6. Cycles in the chamber homology of GL(3)

    OpenAIRE

    Aubert, Anne-Marie; Hasan, Samir; Plymen, Roger

    2004-01-01

    Let F be a nonarchimedean local field and let GL(N) = GL(N,F). We prove the existence of parahoric types for GL(N). We construct representative cycles in all the homology classes of the chamber homology of GL(3).

  7. CBH1 homologs and variant CBH1 cellulases

    Energy Technology Data Exchange (ETDEWEB)

    Goedegebuur, Frits (Rozenlaan, NL); Gualfetti, Peter (San Francisco, CA); Mitchinson, Colin (Half Moon Bay, CA); Neefe, Paulien (Zoetermeer, NL)

    2011-05-31

    Disclosed are a number of homologs and variants of Hypocrea jecorina Cel7A (formerly Trichoderma reesei cellobiohydrolase I or CBH1), nucleic acids encoding the same and methods for producing the same. The homologs and variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted and/or deleted.

  8. Flare build-up study - Homologous flares group. I

    Science.gov (United States)

    Martres, M.-J.; Mein, N.; Mouradian, Z.; Rayrole, J.; Schmieder, B.; Simon, G.; Soru-Escaut, I.; Woodgate, B. E.

    1984-01-01

    Solar Maximum Mission observations have been used to study the origin and amount of energy, mechanism of storage and release, and conditions for the occurrence of solar flares, and some results of these studies as they pertain to homologous flares are briefly discussed. It was found that every set of flares produced 'rafales' of homologous flares, i.e., two, three, four, or more flares separated in time by an hour or less. No great changes in macroscopic photospheric patterns were observed during these flaring periods. A quantitative brightness parameter of the relation between homologous flares is defined. Scale changes detected in the dynamic spectrum of flare sites are in good agreement with a theoretical suggestion by Sturrock. Statistical results for different homologous flare active regions show the existence in homologous flaring areas of a 'pivot' of previous filaments interpreted as a signature of an anomaly in the solar rotation.

  9. Synaptonemal complex components persist at centromeres and are required for homologous centromere pairing in mouse spermatocytes.

    Directory of Open Access Journals (Sweden)

    C Gaston Bisig

    2012-06-01

    Full Text Available Recent studies in simple model organisms have shown that centromere pairing is important for ensuring high-fidelity meiotic chromosome segregation. However, this process and the mechanisms regulating it in higher eukaryotes are unknown. Here we present the first detailed study of meiotic centromere pairing in mouse spermatogenesis and link it with key events of the G2/metaphase I transition. In mouse we observed no evidence of the persistent coupling of centromeres that has been observed in several model organisms. We do however find that telomeres associate in non-homologous pairs or small groups in B type spermatogonia and pre-leptotene spermatocytes, and this association is disrupted by deletion of the synaptonemal complex component SYCP3. Intriguingly, we found that, in mid prophase, chromosome synapsis is not initiated at centromeres, and centromeric regions are the last to pair in the zygotene-pachytene transition. In late prophase, we first identified the proteins that reside at paired centromeres. We found that components of the central and lateral element and transverse filaments of the synaptonemal complex are retained at paired centromeres after disassembly of the synaptonemal complex along diplotene chromosome arms. The absence of SYCP1 prevents centromere pairing in knockout mouse spermatocytes. The localization dynamics of SYCP1 and SYCP3 suggest that they play different roles in promoting homologous centromere pairing. SYCP1 remains only at paired centromeres coincident with the time at which some kinetochore proteins begin loading at centromeres, consistent with a role in assembly of meiosis-specific kinetochores. After removal of SYCP1 from centromeres, SYCP3 then accumulates at paired centromeres where it may promote bi-orientation of homologous centromeres. We propose that, in addition to their roles as synaptonemal complex components, SYCP1 and SYCP3 act at the centromeres to promote the establishment and/or maintenance of

  10. Homologous series of induced early mutants in indican rice. Pt.1. The production of homologous series of early mutants

    International Nuclear Information System (INIS)

    The percentage of homologous series of early mutants induced from the same Indican rice variety were almost the same (1.37%∼1.64%) in 1983∼1993, but the ones from the different eco-typical varieties were different. The early variety was 0.73%, the mid variety was 1.51%, and the late variety was 1.97%. The percentage of homologous series of early mutants from the varieties with the same pedigree and relationship were similar, but the one from the cog nation were lower than those from distant varieties. There are basic laws and characters in the homologous series of early mutants: 1. The inhibited phenotype is the basic of the homologous series of early mutants; 2. The production of the homologous series of early mutants is closely related with the growing period of the parent; 3. The parallel mutation of the stem and leaves are simultaneously happened with the variation of early or late maturing; 4. The occurrence of the homologous series of early mutants is in a state of imbalance. According to the law of parallel variability, the production of homologous series of early mutants can be predicted as long as the parents' classification of plant, pedigree and ecological type are identified. Therefore, the early breeding can be guided by the law of homologous series of early mutants

  11. Peridinialean dinoflagellate plate patterns, labels and homologies

    Science.gov (United States)

    Edwards, L.E.

    1990-01-01

    Tabulation patterns for peridinialean dinoflagellate thecae and cysts have been traditionally expressed using a plate labelling system described by C.A. Kofoid in the early 1900's. This system can obscure dinoflagellate plate homologies and has not always been strictly applied. The plate-labelling system presented here introduces new series labels but incorporates key features and ideas from the more recently proposed systems of G.L. Eaton and F.J.R. Taylor, as modified by W.R. Evitt. Plate-series recognition begins with the cingulum (C-series) and proceeds from the cingulum toward the apex for the three series of the epitheca/epicyst and proceeds from the cingulum toward the antapex for the two series of the hypotheca/hypocyst. The epithecal/epicystal model consists of eight plates that touch the anterior margin of the cingulum (E-series: plates E1-E7, ES), seven plates toward the apex that touch the E-series plates (M-series: R, M1-M6), and up to seven plates near the apex that do not touch E-series plates (D-series: Dp-Dv). The hypothecal/hypocystal model consists of eight plates that touch the posterior margin of the cingulum (H-series: H1-H6,HR,HS) and three plates toward the antapex (T1-T3). Epithecal/epicystal tabulation patterns come in both 8- and 7- models, corresponding to eight and seven plates, respectively, in the E-series. Hypothecal/hypocystal tabulation patterns also come in both 8- and 7-models, corresponding to eight and seven plates, respectively, in the H-series. By convention, the 7-model epitheca/epicyst has no plates E1 and M1; the 7-model hypotheca/hypocyst has no plate H6. Within an 8-model or 7-model, the system emphasizes plates that are presumed to be homologous by giving them identical labels. I introduce the adjectives "monothigmate", "dithigmate," and "trithigmate" to designate plates touching one, two, and three plates, respectively, of the adjacent series. The term "thigmation" applies to the analysis of plate contacts between

  12. Productive homologous and non-homologous recombination of hepatitis C virus in cell culture.

    Directory of Open Access Journals (Sweden)

    Troels K H Scheel

    2013-03-01

    Full Text Available Genetic recombination is an important mechanism for increasing diversity of RNA viruses, and constitutes a viral escape mechanism to host immune responses and to treatment with antiviral compounds. Although rare, epidemiologically important hepatitis C virus (HCV recombinants have been reported. In addition, recombination is an important regulatory mechanism of cytopathogenicity for the related pestiviruses. Here we describe recombination of HCV RNA in cell culture leading to production of infectious virus. Initially, hepatoma cells were co-transfected with a replicating JFH1ΔE1E2 genome (genotype 2a lacking functional envelope genes and strain J6 (2a, which has functional envelope genes but does not replicate in culture. After an initial decrease in the number of HCV positive cells, infection spread after 13-36 days. Sequencing of recovered viruses revealed non-homologous recombinants with J6 sequence from the 5' end to the NS2-NS3 region followed by JFH1 sequence from Core to the 3' end. These recombinants carried duplicated sequence of up to 2400 nucleotides. HCV replication was not required for recombination, as recombinants were observed in most experiments even when two replication incompetent genomes were co-transfected. Reverse genetic studies verified the viability of representative recombinants. After serial passage, subsequent recombination events reducing or eliminating the duplicated region were observed for some but not all recombinants. Furthermore, we found that inter-genotypic recombination could occur, but at a lower frequency than intra-genotypic recombination. Productive recombination of attenuated HCV genomes depended on expression of all HCV proteins and tolerated duplicated sequence. In general, no strong site specificity was observed. Non-homologous recombination was observed in most cases, while few homologous events were identified. A better understanding of HCV recombination could help identification of natural

  13. Homologous DNA strand exchange activity of the human mitochondrial DNA helicase TWINKLE.

    Science.gov (United States)

    Sen, Doyel; Patel, Gayatri; Patel, Smita S

    2016-05-19

    A crucial component of the human mitochondrial DNA replisome is the ring-shaped helicase TWINKLE-a phage T7-gene 4-like protein expressed in the nucleus and localized in the human mitochondria. Our previous studies showed that despite being a helicase, TWINKLE has unique DNA annealing activity. At the time, the implications of DNA annealing by TWINKLE were unclear. Herein, we report that TWINKLE uses DNA annealing function to actively catalyze strand-exchange reaction between the unwinding substrate and a homologous single-stranded DNA. Using various biochemical experiments, we demonstrate that the mechanism of strand-exchange involves active coupling of unwinding and annealing reactions by the TWINKLE. Unlike strand-annealing, the strand-exchange reaction requires nucleotide hydrolysis and greatly stimulated by short region of homology between the recombining DNA strands that promote joint molecule formation to initiate strand-exchange. Furthermore, we show that TWINKLE catalyzes branch migration by resolving homologous four-way junction DNA. These four DNA modifying activities of TWINKLE: strand-separation, strand-annealing, strand-exchange and branch migration suggest a dual role of TWINKLE in mitochondrial DNA maintenance. In addition to playing a major role in fork progression during leading strand DNA synthesis, we propose that TWINKLE is involved in recombinational repair of the human mitochondrial DNA. PMID:26887820

  14. The Arabidopsis MutS homolog AtMSH5 is required for normal meiosis

    Institute of Scientific and Technical Information of China (English)

    Xiaoduo Lu; Xiaolin Liu; Lizhe An; Wei Zhang; Jian Sun; Huijuan Pei; Hongyan Meng; Yunliu Fan; Chunyi Zhang

    2008-01-01

    MSH5,a member of the MutS homolog DNA mismatch repair protein family,has been shown to be required for proper homologous chromosome recombination in diverse organisms such as mouse,budding yeast and Caenorhabditis elegans.In this paper,we show that a mutant Arabidopsis plant carrying the putative disrupted AtMSH5 gene exhibits defects during meiotic division,producing a proportion of nonviable pollen grains and abnormal embryo sacs,and thereby leading to a decrease in fertility.AtMSH5 expression is confined to meiotic floral buds,which is consistent with a possible role during meiosis.Cytological analysis of male meiosis revealed the presence of numerous univalents from diplotene to metaphase I,which were associated with a great reduction in chiasma frequencies.The average number of residual chiasmata in the mutant is reduced to 2.54 per meiocyte,which accounts for~25% of the amount in the wild type.Here,quantitative cytogenetical analysis reveals that the residual chiasmata in Atmsh5 mutants are randomly distributed among meiocytes,suggesting that AtMSH5 has an essential role during interferencesensitive chiasma formation.Taken together,the evidence indicates that AtMSH5 promotes homologous recombination through facilitating chiasma formation during prophase I in Arabidopsis.

  15. Sequence, expression divergence, and complementation of homologous ALCATRAZ loci in Brassica napus.

    Science.gov (United States)

    Hua, Shuijin; Shamsi, Imran Haider; Guo, Yuan; Pak, Haksong; Chen, Mingxun; Shi, Congguang; Meng, Huabing; Jiang, Lixi

    2009-08-01

    The genomic era provides new perspectives in understanding polyploidy evolution, mostly on the genome-wide scale. In this paper, we show the sequence and expression divergence between the homologous ALCATRAZ (ALC) loci in Brassica napus, responsible for silique dehiscence. We cloned two homologous ALC loci, namely BnaC.ALC.a and BnaA.ALC.a in B. napus. Driven by the 35S promoter, both the loci complemented to the alc mutation of Arabidopsis thaliana, yet only the expression of BnaC.ALC.a was detectable in the siliques of B. napus. Sequence alignment indicated that BnaC.ALC.a and BolC.ALC.a, or BnaA.ALC.a and BraA.ALC.a, possess a high level of similarity. The understanding of the sequence and expression divergence among homologous loci of a gene is of due importance for an effective gene manipulation and TILLING (or ECOTILLING) analysis for the allelic DNA variation at a given locus. PMID:19504267

  16. Relative antidipsogenic potencies of six homologous natriuretic peptides in eels.

    Science.gov (United States)

    Miyanishi, Hiroshi; Nobata, Shigenori; Takei, Yoshio

    2011-10-01

    Atrial natriuretic peptide (ANP) exhibits a potent antidipsogenic effect in seawater (SW) eels to limit excess Na(+) uptake, thereby effectively promoting SW adaptation. Recently, cardiac ANP, BNP and VNP and brain CNP1, 3 and 4, have been identified in eels. We examined the antidipsogenic effect of all homologous NPs using conscious, cannulated eels in both FW and SW together with parameters that affect drinking. A dose-response study (0.01-1 nmol/kg) in SW eels showed the relative potency of the antidipsogenic effect was in the order ANP ≥ VNP > BNP = CNP3 > CNP1 ≥ CNP4, while the order was ANP = VNP = BNP > CNP3 = CNP1 = CNP4 for the vasodepressor effect. The minimum effective dose of ANP for the antidipsogenic effect is much lower than that in mammals. ANP, BNP and VNP at 0.3 nmol/kg decreased drinking, plasma Na(+) concentration and aortic pressure and increased hematocrit in SW eels. The cardiac NPs induced similar changes in drinking, aortic pressure and hematocrit in FW eels, but aside from BNP no change in plasma Na(+) concentration. CNPs had no effect on drinking, plasma Na(+) concentration and hematocrit but induced mild hypotension in both FW and SW eels, except for CNP3 that inhibited drinking in SW eels. These results show that ANP, BNP and VNP are potent antidipsogenic hormones in eels in spite of other regulatory factors working to induce drinking, and that CNPs are without effects on drinking except for the ancestor of the cardiac NPs, CNP3. PMID:21967218

  17. Regulation of Homologous Recombination by SUMOylation

    DEFF Research Database (Denmark)

    Pinela da Silva, Sonia Cristina

    , deletions, and genome rearrangements that can lead to cell death or cancer in humans. The post-translational modification by SUMO (small ubiquitinlike modifier) has proven to be an important regulator of HR and genome integrity, but the molecular mechanisms responsible for these roles are still unclear. In...... this study I present new insights for the role of SUMOylation in regulating HR by dissecting the role of SUMO in the interaction between the central HR-mediator protein Rad52 and its paralogue Rad59 and the outcome of recombination. This data provides evidence for the importance of SUMO in promoting...

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

    Science.gov (United States)

    Keyamura, Kenji; Arai, Kota; Hishida, Takashi

    2016-07-01

    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. PMID:27390022

  20. The dynamics of homologous pairing during mating type interconversion in budding yeast.

    Directory of Open Access Journals (Sweden)

    Peter L Houston

    2006-06-01

    Full Text Available Cells repair most double-strand breaks (DSBs that arise during replication or by environmental insults through homologous recombination, a high-fidelity process critical for maintenance of genomic integrity. However, neither the detailed mechanism of homologous recombination nor the specific roles of critical components of the recombination machinery-such as Bloom and Werner syndrome proteins-have been resolved. We have taken a novel approach to examining the mechanism of homologous recombination by tracking both a DSB and the template from which it is repaired during the repair process in individual yeast cells. The two loci were labeled with arrays of DNA binding sites and visualized in live cells expressing green fluorescent protein-DNA binding protein chimeras. Following induction of an endonuclease that introduces a DSB next to one of the marked loci, live cells were imaged repeatedly to determine the relative positions of the DSB and the template locus. We found a significant increase in persistent associations between donor and recipient loci following formation of the DSB, demonstrating DSB-induced pairing between donor and template. However, such associations were transient and occurred repeatedly in every cell, a result not predicted from previous studies on populations of cells. Moreover, these associations were absent in sgs1 or srs2 mutants, yeast homologs of the Bloom and Werner syndrome genes, but were enhanced in a rad54 mutant, whose protein product promotes efficient strand exchange in vitro. Our results indicate that a DSB makes multiple and reversible contacts with a template during the repair process, suggesting that repair could involve interactions with multiple templates, potentially creating novel combinations of sequences at the repair site. Our results further suggest that both Sgs1 and Srs2 are required for efficient completion of recombination and that Rad54 may serve to dissociate such interactions. Finally, these

  1. Metazoan promoters

    DEFF Research Database (Denmark)

    Lenhard, Boris; Sandelin, Albin Gustav; Carninci, Piero

    2012-01-01

    Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters ...

  2. Molecular cloning, DNA sequence analysis, and characterization of the Corynebacterium diphtheriae dtxR homolog from Brevibacterium lactofermentum.

    OpenAIRE

    Oguiza, J A; Tao, X; Marcos, A T; Martín, J F; Murphy, J R

    1995-01-01

    A homolog of the Corynebacterium diphtheriae dtxR gene was isolated from Brevibacterium lactofermentum. The product of the B. lactofermentum dtxR gene was immunoreactive with polyclonal anti-DtxR antibodies and functioned as an iron-activated repressor capable of regulating the expression of beta-galactosidase from a diphtheria tox promoter/operator transcriptional fusion in recombinant Escherichia coli. The extents of induction by increasing concentrations of the chelator 2,2'-dipyridyl were...

  3. Health Promotion

    DEFF Research Database (Denmark)

    Povlsen, Lene; Borup, I.

    2015-01-01

    In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986......, the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation...... - an associate professorship was established with a focus on health promotion. Nevertheless, the concept of health promotion had been integrated with or mentioned in courses run prior to the new post. Subsequently, a wide spectrum of courses in health promotion was introduced, such as Empowerment for Child...

  4. Applications of homological mirror symmetry to hypergeometric systems: duality conjectures

    OpenAIRE

    Borisov, Lev A.; Horja, R. Paul

    2013-01-01

    Homological mirror symmetry for crepant resolutions of Gorenstein toric singularities leads to a pair of conjectures on certain hypergeometric systems of PDEs. We explain these conjectures and verify them in some cases.

  5. Homologous prominence non-radial eruptions: A case study

    CERN Document Server

    Duchlev, P; Madjarska, M S; Dechev, M

    2016-01-01

    The present study provides important details on homologous eruptions of a solar prominence that occurred in active region NOAA 10904 on 2006 August 22. We report on the preeruptive phase of the homologous feature as well as the kinematics and the morphology of a forth from a series of prominence eruptions that is critical in defining the nature of the previous consecutive eruptions. The evolution of the overlying coronal field during homologous eruptions is discussed and a new observational criterion for homologous eruptions is provided. We find a distinctive sequence of three activation periods each of them containing preeruptive precursors such as a brightening and enlarging of the prominence body followed by small surge- like ejections from its southern end observed in the radio 17 GHz. We analyse a fourth eruption that clearly indicates a full reformation of the prominence after the third eruption. The fourth eruption although occurring 11 hrs later has an identical morphology, the same angle of propagati...

  6. Regulation of homologous recombination at telomeres in budding yeast

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine; Lisby, Michael

    2010-01-01

    Homologous recombination is suppressed at normal length telomere sequences. In contrast, telomere recombination is allowed when telomeres erode in the absence of telomerase activity or as a consequence of nucleolytic degradation or incomplete replication. Here, we review the mechanisms that...

  7. Generalized local homology and cohomology for linearly compact modules

    International Nuclear Information System (INIS)

    We study generalized local homology for linearly compact modules. By duality, we get some properties of generalized local cohomology modules and extend well-known properties of local cohomology of A. Grothendieck. (author)

  8. Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription.

    Science.gov (United States)

    Delerive, Philippe; Galardi, Cristin M; Bisi, John E; Nicodeme, Edwige; Goodwin, Bryan

    2004-10-01

    The orphan nuclear receptor liver receptor homolog-1 (LRH-1) has been reported to play a role in bile acid biosynthesis and reverse cholesterol transport. In this study, we examined the role of LRH-1 in the regulation of the apolipoprotein AI (APOAI) gene. Using RNA interference and adenovirus-mediated overexpression, we show that LRH-1 directly regulates APOAI gene transcription. Transient transfection experiments and EMSAs revealed that LRH-1 directly regulates APOAI transcription by binding to an LRH-1 response element located in the proximal APOAI promoter region. Chromatin immunoprecipitation experiments revealed that LRH-1 binds to the human APO AI promoter in vivo. Finally, we show that the transcriptional repressor SHP (small heterodimer partner) suppressed APOAI gene expression by inhibiting LRH-1 transcriptional activity. Taken together, our results demonstrate that LRH-1 is a novel regulator of APOAI transcription and underscore the role of this receptor in cholesterol homeostasis. PMID:15218078

  9. A definition of graph homology and graph K-theory of algebras

    OpenAIRE

    Movshev, M. V.

    1999-01-01

    We introduce and study elementary properties of graph homology of algebras. This new homology theory shares many features of cyclic and Hochschild homology. We also define a graph K-theory together with an analog of Chern character.

  10. Sketches of a platypus: persistent homology and its algebraic foundations

    OpenAIRE

    Vejdemo-Johansson, Mikael

    2012-01-01

    The subject of persistent homology has vitalized applications of algebraic topology to point cloud data and to application fields far outside the realm of pure mathematics. The area has seen several fundamentally important results that are rooted in choosing a particular algebraic foundational theory to describe persistent homology, and applying results from that theory to prove useful and important results. In this survey paper, we shall examine the various choices in use, and what they allo...

  11. The rational Khovanov homology of 3-strand pretzel links

    OpenAIRE

    Manion, Andrew

    2011-01-01

    The 3-strand pretzel knots and links are a well-studied source of examples in knot theory. However, while there have been computations of the Khovanov homology of some sub-families of 3-strand pretzel knots, no general formula has been given for all of them. We give a general formula for the unreduced Khovanov homology of all 3-strand pretzel links, over the rational numbers.

  12. Characterization of nonconservative homologous junctions in mammalian cells.

    OpenAIRE

    Desautels, L; Brouillette, S; Wallenburg, J; Belmaaza, A; Gusew, N; Trudel, P; Chartrand, P

    1990-01-01

    Homologous recombination in mammalian cells between extrachromosomal molecules, as well as between episomes and chromosomes, can be mediated by a nonconservative mechanism. It has been proposed that the key steps in this process are the generation (by double-strand cleavage) of overlapping homologous ends, the creation of complementary single-strand ends (either by strand-specific exonuclease degradation or by unwinding of the DNA helix), and finally the creation of heteroduplex DNA by the an...

  13. WeederH: an algorithm for finding conserved regulatory motifs and regions in homologous sequences

    Directory of Open Access Journals (Sweden)

    Pesole Graziano

    2007-02-01

    Full Text Available Abstract Background This work addresses the problem of detecting conserved transcription factor binding sites and in general regulatory regions through the analysis of sequences from homologous genes, an approach that is becoming more and more widely used given the ever increasing amount of genomic data available. Results We present an algorithm that identifies conserved transcription factor binding sites in a given sequence by comparing it to one or more homologs, adapting a framework we previously introduced for the discovery of sites in sequences from co-regulated genes. Differently from the most commonly used methods, the approach we present does not need or compute an alignment of the sequences investigated, nor resorts to descriptors of the binding specificity of known transcription factors. The main novel idea we introduce is a relative measure of conservation, assuming that true functional elements should present a higher level of conservation with respect to the rest of the sequence surrounding them. We present tests where we applied the algorithm to the identification of conserved annotated sites in homologous promoters, as well as in distal regions like enhancers. Conclusion Results of the tests show how the algorithm can provide fast and reliable predictions of conserved transcription factor binding sites regulating the transcription of a gene, with better performances than other available methods for the same task. We also show examples on how the algorithm can be successfully employed when promoter annotations of the genes investigated are missing, or when regulatory sites and regions are located far away from the genes.

  14. Achieving efficient protein expression in Trichoderma reesei by using strong constitutive promoters

    OpenAIRE

    Li Junxin; Wang Juan; Wang Shaowen; Xing Miao; Yu Shaowen; Liu Gang

    2012-01-01

    Abstract Backgrounds The fungus Trichoderma reesei is an important workhorse for expression of homologous or heterologous genes, and the inducible cbh1 promoter is generally used. However, constitutive expression is more preferable in some cases than inducible expression that leads to production of unwanted cellulase components. In this work, constitutive promoters of T. reesei were screened and successfully used for high level homologous expression of xylanase II. Results The transcriptional...

  15. Analysis of promoters in transgenic barley and wheat.

    Science.gov (United States)

    Furtado, Agnelo; Henry, Robert J; Pellegrineschi, Alessandro

    2009-04-01

    Advances in the genetic transformation of cereals have improved the prospects of using biotechnology for plant improvement, and a toolbox of promoters with defined specificities would be a valuable resource in controlling the expression of transgenes in desired tissues for both plant improvement and molecular farming. A number of promoters have been isolated from the important cereals (wheat, barley, rice and maize), and these promoters have been tested mostly in homologous cereal systems and, to a lesser extent, in heterologous cereal systems. The use of these promoters across the important cereals would add value to the utility of each promoter. In addition, promoters with less sequence homology, but with similar specificities, will be crucial in avoiding homology-based gene silencing when expressing more than one transgene in the same tissue. We have tested wheat and barley promoters in transgenic barley and wheat to determine whether their specificity is shared across these two species. The barley bifunctional alpha-amylase/subtilisin inhibitor (Isa) promoter, specific to the pericarp in barley, failed to show any activity in wheat, whereas the wheat early-maturing (Em) promoter showed similar activity in wheat and barley. The wheat high-molecular-weight glutenin (HMW-Glu) and barley D-hordein (D-Hor) and B-hordein (B-Hor) storage protein promoters maintained endosperm-specific expression of green fluorescent protein (GFP) in wheat and barley, respectively. Using gfp, we have demonstrated that the Isa and Em promoters can be used as strong promoters to direct transgenes in specific tissues of barley and wheat grain. Differential promoter activity across cereals expands and adds value to a promoter toolbox for utility in plant biotechnology. PMID:19175520

  16. Trypanosoma brucei translation initiation factor homolog EIF4E6 forms a tripartite cytosolic complex with EIF4G5 and a capping enzyme homolog.

    Science.gov (United States)

    Freire, Eden R; Malvezzi, Amaranta M; Vashisht, Ajay A; Zuberek, Joanna; Saada, Edwin A; Langousis, Gerasimos; Nascimento, Janaína D F; Moura, Danielle; Darzynkiewicz, Edward; Hill, Kent; de Melo Neto, Osvaldo P; Wohlschlegel, James A; Sturm, Nancy R; Campbell, David A

    2014-07-01

    Trypanosomes lack the transcriptional control characteristic of the majority of eukaryotes that is mediated by gene-specific promoters in a one-gene-one-promoter arrangement. Rather, their genomes are transcribed in large polycistrons with no obvious functional linkage. Posttranscriptional regulation of gene expression must thus play a larger role in these organisms. The eIF4E homolog TbEIF4E6 binds mRNA cap analogs in vitro and is part of a complex in vivo that may fulfill such a role. Knockdown of TbEIF4E6 tagged with protein A-tobacco etch virus protease cleavage site-protein C to approximately 15% of the normal expression level resulted in viable cells that displayed a set of phenotypes linked to detachment of the flagellum from the length of the cell body, if not outright flagellum loss. While these cells appeared and behaved as normal under stationary liquid culture conditions, standard centrifugation resulted in a marked increase in flagellar detachment. Furthermore, the ability of TbEIF4E6-depleted cells to engage in social motility was reduced. The TbEIF4E6 protein forms a cytosolic complex containing a triad of proteins, including the eIF4G homolog TbEIF4G5 and a hypothetical protein of 70.3 kDa, referred to as TbG5-IP. The TbG5-IP analysis revealed two domains with predicted secondary structures conserved in mRNA capping enzymes: nucleoside triphosphate hydrolase and guanylyltransferase. These complex members have the potential for RNA interaction, either via the 5' cap structure for TbEIF4E6 and TbG5-IP or through RNA-binding domains in TbEIF4G5. The associated proteins provide a signpost for future studies to determine how this complex affects capped RNA molecules. PMID:24839125

  17. Isolation and characterization of various homologous and heterologous promoters in schwaqnniomyces (debaryomyces) occidentalis

    Czech Academy of Sciences Publication Activity Database

    Dorosh, Andriy; Hašek, Jiří; Janatová, Ivana

    Smolenice, 2004, s. 71. [Annual Conference on Yeasts /32./. Smolenice (SK), 12.05.2004-14.05.2004] R&D Projects: GA MŠk LN00B030 Institutional research plan: CEZ:AV0Z5020903 Keywords : tdh3 * ade2 Subject RIV: EE - Microbiology, Virology

  18. Multiscale analysis of nonlinear systems using computational homology

    Energy Technology Data Exchange (ETDEWEB)

    Konstantin Mischaikow, Rutgers University/Georgia Institute of Technology, Michael Schatz, Georgia Institute of Technology, William Kalies, Florida Atlantic University, Thomas Wanner,George Mason University

    2010-05-19

    This is a collaborative project between the principal investigators. However, as is to be expected, different PIs have greater focus on different aspects of the project. This report lists these major directions of research which were pursued during the funding period: (1) Computational Homology in Fluids - For the computational homology effort in thermal convection, the focus of the work during the first two years of the funding period included: (1) A clear demonstration that homology can sensitively detect the presence or absence of an important flow symmetry, (2) An investigation of homology as a probe for flow dynamics, and (3) The construction of a new convection apparatus for probing the effects of large-aspect-ratio. (2) Computational Homology in Cardiac Dynamics - We have initiated an effort to test the use of homology in characterizing data from both laboratory experiments and numerical simulations of arrhythmia in the heart. Recently, the use of high speed, high sensitivity digital imaging in conjunction with voltage sensitive fluorescent dyes has enabled researchers to visualize electrical activity on the surface of cardiac tissue, both in vitro and in vivo. (3) Magnetohydrodynamics - A new research direction is to use computational homology to analyze results of large scale simulations of 2D turbulence in the presence of magnetic fields. Such simulations are relevant to the dynamics of black hole accretion disks. The complex flow patterns from simulations exhibit strong qualitative changes as a function of magnetic field strength. Efforts to characterize the pattern changes using Fourier methods and wavelet analysis have been unsuccessful. (4) Granular Flow - two experts in the area of granular media are studying 2D model experiments of earthquake dynamics where the stress fields can be measured; these stress fields from complex patterns of 'force chains' that may be amenable to analysis using computational homology. (5) Microstructure

  19. Multiscale analysis of nonlinear systems using computational homology

    Energy Technology Data Exchange (ETDEWEB)

    Konstantin Mischaikow; Michael Schatz; William Kalies; Thomas Wanner

    2010-05-24

    This is a collaborative project between the principal investigators. However, as is to be expected, different PIs have greater focus on different aspects of the project. This report lists these major directions of research which were pursued during the funding period: (1) Computational Homology in Fluids - For the computational homology effort in thermal convection, the focus of the work during the first two years of the funding period included: (1) A clear demonstration that homology can sensitively detect the presence or absence of an important flow symmetry, (2) An investigation of homology as a probe for flow dynamics, and (3) The construction of a new convection apparatus for probing the effects of large-aspect-ratio. (2) Computational Homology in Cardiac Dynamics - We have initiated an effort to test the use of homology in characterizing data from both laboratory experiments and numerical simulations of arrhythmia in the heart. Recently, the use of high speed, high sensitivity digital imaging in conjunction with voltage sensitive fluorescent dyes has enabled researchers to visualize electrical activity on the surface of cardiac tissue, both in vitro and in vivo. (3) Magnetohydrodynamics - A new research direction is to use computational homology to analyze results of large scale simulations of 2D turbulence in the presence of magnetic fields. Such simulations are relevant to the dynamics of black hole accretion disks. The complex flow patterns from simulations exhibit strong qualitative changes as a function of magnetic field strength. Efforts to characterize the pattern changes using Fourier methods and wavelet analysis have been unsuccessful. (4) Granular Flow - two experts in the area of granular media are studying 2D model experiments of earthquake dynamics where the stress fields can be measured; these stress fields from complex patterns of 'force chains' that may be amenable to analysis using computational homology. (5) Microstructure

  20. RPA homologs and ssDNA processing during meiotic recombination.

    Science.gov (United States)

    Ribeiro, Jonathan; Abby, Emilie; Livera, Gabriel; Martini, Emmanuelle

    2016-06-01

    Meiotic homologous recombination is a specialized process that involves homologous chromosome pairing and strand exchange to guarantee proper chromosome segregation and genetic diversity. The formation and repair of DNA double-strand breaks (DSBs) during meiotic recombination differs from those during mitotic recombination in that the homologous chromosome rather than the sister chromatid is the preferred repair template. The processing of single-stranded DNA (ssDNA) formed on intermediate recombination structures is central to driving the specific outcomes of DSB repair during meiosis. Replication protein A (RPA) is the main ssDNA-binding protein complex involved in DNA metabolism. However, the existence of RPA orthologs in plants and the recent discovery of meiosis specific with OB domains (MEIOB), a widely conserved meiosis-specific RPA1 paralog, strongly suggest that multiple RPA complexes evolved and specialized to subdivide their roles during DNA metabolism. Here we review ssDNA formation and maturation during mitotic and meiotic recombination underlying the meiotic specific features. We describe and discuss the existence and properties of MEIOB and multiple RPA subunits in plants and highlight how they can provide meiosis-specific fates to ssDNA processing during homologous recombination. Understanding the functions of these RPA homologs and how they interact with the canonical RPA subunits is of major interest in the fields of meiosis and DNA repair. PMID:26520106

  1. Homology modeling a fast tool for drug discovery: Current perspectives

    Directory of Open Access Journals (Sweden)

    V K Vyas

    2012-01-01

    Full Text Available Major goal of structural biology involve formation of protein-ligand complexes; in which the protein molecules act energetically in the course of binding. Therefore, perceptive of protein-ligand interaction will be very important for structure based drug design. Lack of knowledge of 3D structures has hindered efforts to understand the binding specificities of ligands with protein. With increasing in modeling software and the growing number of known protein structures, homology modeling is rapidly becoming the method of choice for obtaining 3D coordinates of proteins. Homology modeling is a representation of the similarity of environmental residues at topologically corresponding positions in the reference proteins. In the absence of experimental data, model building on the basis of a known 3D structure of a homologous protein is at present the only reliable method to obtain the structural information. Knowledge of the 3D structures of proteins provides invaluable insights into the molecular basis of their functions. The recent advances in homology modeling, particularly in detecting and aligning sequences with template structures, distant homologues, modeling of loops and side chains as well as detecting errors in a model contributed to consistent prediction of protein structure, which was not possible even several years ago. This review focused on the features and a role of homology modeling in predicting protein structure and described current developments in this field with victorious applications at the different stages of the drug design and discovery.

  2. Fold homology detection using sequence fragment composition profiles of proteins.

    Science.gov (United States)

    Solis, Armando D; Rackovsky, Shalom R

    2010-10-01

    The effectiveness of sequence alignment in detecting structural homology among protein sequences decreases markedly when pairwise sequence identity is low (the so-called "twilight zone" problem of sequence alignment). Alternative sequence comparison strategies able to detect structural kinship among highly divergent sequences are necessary to address this need. Among them are alignment-free methods, which use global sequence properties (such as amino acid composition) to identify structural homology in a rapid and straightforward way. We explore the viability of using tetramer sequence fragment composition profiles in finding structural relationships that lie undetected by traditional alignment. We establish a strategy to recast any given protein sequence into a tetramer sequence fragment composition profile, using a series of amino acid clustering steps that have been optimized for mutual information. Our method has the effect of compressing the set of 160,000 unique tetramers (if using the 20-letter amino acid alphabet) into a more tractable number of reduced tetramers (approximately 15-30), so that a meaningful tetramer composition profile can be constructed. We test remote homology detection at the topology and fold superfamily levels using a comprehensive set of fold homologs, culled from the CATH database that share low pairwise sequence similarity. Using the receiver-operating characteristic measure, we demonstrate potentially significant improvement in using information-optimized reduced tetramer composition, over methods relying only on the raw amino acid composition or on traditional sequence alignment, in homology detection at or below the "twilight zone". PMID:20635424

  3. Promoting Models

    Science.gov (United States)

    Li, Qin; Zhao, Yongxin; Wu, Xiaofeng; Liu, Si

    There can be multitudinous models specifying aspects of the same system. Each model has a bias towards one aspect. These models often override in specific aspects though they have different expressions. A specification written in one model can be refined by introducing additional information from other models. The paper proposes a concept of promoting models which is a methodology to obtain refinements with support from cooperating models. It refines a primary model by integrating the information from a secondary model. The promotion principle is not merely an academic point, but also a reliable and robust engineering technique which can be used to develop software and hardware systems. It can also check the consistency between two specifications from different models. A case of modeling a simple online shopping system with the cooperation of the guarded design model and CSP model illustrates the practicability of the promotion principle.

  4. Quantization of gauge fields, graph polynomials and graph homology

    International Nuclear Information System (INIS)

    We review quantization of gauge fields using algebraic properties of 3-regular graphs. We derive the Feynman integrand at n loops for a non-abelian gauge theory quantized in a covariant gauge from scalar integrands for connected 3-regular graphs, obtained from the two Symanzik polynomials. The transition to the full gauge theory amplitude is obtained by the use of a third, new, graph polynomial, the corolla polynomial. This implies effectively a covariant quantization without ghosts, where all the relevant signs of the ghost sector are incorporated in a double complex furnished by the corolla polynomial–we call it cycle homology–and by graph homology. -- Highlights: •We derive gauge theory Feynman from scalar field theory with 3-valent vertices. •We clarify the role of graph homology and cycle homology. •We use parametric renormalization and the new corolla polynomial

  5. Protein Remote Homology Detection Based on an Ensemble Learning Approach

    Science.gov (United States)

    Chen, Junjie; Liu, Bingquan; Huang, Dong

    2016-01-01

    Protein remote homology detection is one of the central problems in bioinformatics. Although some computational methods have been proposed, the problem is still far from being solved. In this paper, an ensemble classifier for protein remote homology detection, called SVM-Ensemble, was proposed with a weighted voting strategy. SVM-Ensemble combined three basic classifiers based on different feature spaces, including Kmer, ACC, and SC-PseAAC. These features consider the characteristics of proteins from various perspectives, incorporating both the sequence composition and the sequence-order information along the protein sequences. Experimental results on a widely used benchmark dataset showed that the proposed SVM-Ensemble can obviously improve the predictive performance for the protein remote homology detection. Moreover, it achieved the best performance and outperformed other state-of-the-art methods. PMID:27294123

  6. Using Persistent Homology to Describe Rayleigh-Bénard Convection

    Science.gov (United States)

    Tithof, Jeffrey; Suri, Balachandra; Xu, Mu; Kramar, Miroslav; Levanger, Rachel; Mischaikow, Konstantin; Paul, Mark; Schatz, Michael

    2015-11-01

    Complex spatial patterns that exhibit aperiodic dynamics commonly arise in a wide variety of systems in nature and technology. Describing, understanding, and predicting the behavior of such patterns is an open problem. We explore the use of persistent homology (a branch of algebraic topology) to characterize spatiotemporal dynamics in a canonical fluid mechanics problem, Rayleigh Bénard convection. Persistent homology provides a powerful mathematical formalism in which the topological characteristics of a pattern (e.g. the midplane temperature field) are encoded in a so-called persistence diagram. By applying a metric to measure the pairwise distances across multiple persistence diagrams, we can quantify the similarities between different states in a time series. Our results show that persistent homology yields new physical insights into the complex dynamics of large spatially extended systems that are driven far-from-equilibrium. This work is supported under NSF grant DMS-1125302.

  7. Induction of intrachromosomal homologous recombination in whole plants

    International Nuclear Information System (INIS)

    The influence of different factors on frequencies of intrachromosomal homologous recombination in whole Arabidopsis thaliana and tobacco plants was analyzed using a disrupted β-glucuronidase marker gene. Recombination frequencies were enhanced several fold by DNA damaging agents like UV-light or MMS (methyl methanesulfonate). Applying 3-methoxybenzamide (3-MB), an inhibitor of poly(ADP)ribose polymerase (PARP), an enzyme that is postulated to be involved in DNA repair, enhanced homologous recombination frequencies strongly. These findings indicate that homologous recombination is involved in DNA repair and can (at least partially) compensate for other DNA repair pathways. Indications that recombination in plants can be induced by environmental stress factors that are not likely to be involved in DNA metabolism were also found; Arabidopsis plants growing in a medium containing 0.1 M NaCl exhibited elevated recombination frequencies. The possible general effects of ‘environmental’ challenges on genome flexibility are discussed. (author)

  8. Homologous flares and the evolution of NOAA Active Region 2372

    International Nuclear Information System (INIS)

    A detailed record of the evolution of NOAA Active Region 2372 has been compiled by the FBS Homology Study Group. It was one of the most prolific flare-producing regions observed by SMM. The flares occurred in distinct stages which corresponded to particular evolutionary phases in the development of the active region magnetic field. By comparison with a similar but less productive active region, it is found that the activity seems to be related to the magnetic complexity of the region and the amount of shear in the field. Further, the soft X-ray emission in the quiescent active region is related to its flare rate. Within the broader definition of homology adopted, there was a degree of homology between the events within each stage of evolution of AR2372

  9. Quantization of gauge fields, graph polynomials and graph homology

    Energy Technology Data Exchange (ETDEWEB)

    Kreimer, Dirk, E-mail: kreimer@physik.hu-berlin.de [Humboldt University, 10099 Berlin (Germany); Sars, Matthias [Humboldt University, 10099 Berlin (Germany); Suijlekom, Walter D. van [Radboud University Nijmegen, 6525 AJ Nijmegen (Netherlands)

    2013-09-15

    We review quantization of gauge fields using algebraic properties of 3-regular graphs. We derive the Feynman integrand at n loops for a non-abelian gauge theory quantized in a covariant gauge from scalar integrands for connected 3-regular graphs, obtained from the two Symanzik polynomials. The transition to the full gauge theory amplitude is obtained by the use of a third, new, graph polynomial, the corolla polynomial. This implies effectively a covariant quantization without ghosts, where all the relevant signs of the ghost sector are incorporated in a double complex furnished by the corolla polynomial–we call it cycle homology–and by graph homology. -- Highlights: •We derive gauge theory Feynman from scalar field theory with 3-valent vertices. •We clarify the role of graph homology and cycle homology. •We use parametric renormalization and the new corolla polynomial.

  10. Homological ring epimorphisms and recollements from exact pairs. I

    CERN Document Server

    Chen, Hongxing

    2012-01-01

    Homological ring epimorphisms are often used in modern representation theory and algebraic $K$-theory. In this paper, we give some new characterizations of when a universal localization related to an `exact' pair of ring homomorphisms is homological. These characterizations are flexible and applicable to many cases, thus give rise to a wide variety of new recollements (of derived module categories) which have become of interest in and attracted increasing attentions towards to understanding invariants in algebra and geometry. As a consequence, we show that if $\\lambda: R\\ra S$ is an injective homological ring epimorphism between commutative rings $R$ and $S$, then the derived module category of the endomorphism ring of the $R$-module $S\\oplus S / R$ always admits a recollement of the derived module categories of $R$ and the tensor product $S\\otimes_R End_R(S/R)$. In particular, this result is applicable to localizations of integral domains by multiplicative sets in commutative rings.

  11. Data bank homology search algorithm with linear computation complexity.

    Science.gov (United States)

    Strelets, V B; Ptitsyn, A A; Milanesi, L; Lim, H A

    1994-06-01

    A new algorithm for data bank homology search is proposed. The principal advantages of the new algorithm are: (i) linear computation complexity; (ii) low memory requirements; and (iii) high sensitivity to the presence of local region homology. The algorithm first calculates indicative matrices of k-tuple 'realization' in the query sequence and then searches for an appropriate number of matching k-tuples within a narrow range in database sequences. It does not require k-tuple coordinates tabulation and in-memory placement for database sequences. The algorithm is implemented in a program for execution on PC-compatible computers and tested on PIR and GenBank databases with good results. A few modifications designed to improve the selectivity are also discussed. As an application example, the search for homology of the mouse homeotic protein HOX 3.1 is given. PMID:7922689

  12. Two Lectures on Gauge Theory and Khovanov Homology

    CERN Document Server

    Witten, Edward

    2016-01-01

    In the first of these two lectures, I use a comparison to symplectic Khovanov homology to motivate the idea that the Jones polynomial and Khovanov homology of knots can be defined by counting the solutions of certain elliptic partial differential equations in 4 or 5 dimensions. The second lecture is devoted to a description of the rather unusual boundary conditions by which these equations should be supplemented. An appendix describes some physical background. (Versions of these lectures have been presented at various institutions including the Simons Center at Stonybrook, the TSIMF conference center in Sanya, and also Columbia University and the University of Pennsylvania.)

  13. Khovanov-Rozansky Graph Homology and Composition Product

    DEFF Research Database (Denmark)

    Wagner, Emmanuel

    2008-01-01

    In analogy with a recursive formula for the HOMFLY-PT polynomial of links given by Jaeger, we give a recursive formula for the graph polynomial introduced by Kauffman and Vogel. We show how this formula extends to the Khovanov–Rozansky graph homology.......In analogy with a recursive formula for the HOMFLY-PT polynomial of links given by Jaeger, we give a recursive formula for the graph polynomial introduced by Kauffman and Vogel. We show how this formula extends to the Khovanov–Rozansky graph homology....

  14. K-homology and Fredholm operators I: Dirac Operators

    OpenAIRE

    Baum, Paul; van Erp, Erik

    2016-01-01

    This is an expository paper which gives a proof of the Atiyah-Singer index theorem for Dirac operators, presenting the theorem as a computation of the K-homology of a point. This paper and its follow up ("K-homology and index theory II: Elliptic Operators") was written to clear up basic points about index theory that are generally accepted as valid, but for which no proof has been published. Some of these points are needed for the solution of the Heisenberg-elliptic index problem in our paper...

  15. Calcineurin homologous protein: a multifunctional Ca2+-binding protein family

    OpenAIRE

    Di Sole, Francesca; Vadnagara, Komal; MOE, ORSON W.; Babich, Victor

    2012-01-01

    The calcineurin homologous protein (CHP) belongs to an evolutionarily conserved Ca2+-binding protein subfamily. The CHP subfamily is composed of CHP1, CHP2, and CHP3, which in vertebrates share significant homology at the protein level with each other and between other Ca2+-binding proteins. The CHP structure consists of two globular domains containing from one to four EF-hand structural motifs (calcium-binding regions composed of two helixes, E and F, joined by a loop), the myristoylation, a...

  16. RNA Structural Homology Search with a Succinct Stochastic Grammar Model

    Institute of Scientific and Technical Information of China (English)

    Ying-Lei Song; Ji-Zhen Zhao; Chun-Mei Liu; Kan Liu; Russell Malmberg; Li-Ming Cai

    2005-01-01

    An increasing number of structural homology search tools, mostly based on profile stochastic context-free grammars (SCFGs) have been recently developed for the non-coding RNA gene identification. SCFGs can include statistical biases that often occur in RNA sequences, necessary to profile specific RNA structures for structural homology search. In this paper, a succinct stochastic grammar model is introduced for RNA that has competitive search effectiveness. More importantly, the profiling model can be easily extended to include pseudoknots, structures that are beyond the capability of profile SCFGs. In addition, the model allows heuristics to be exploited, resulting in a significant speed-up for the CYK algorithm-based search.

  17. Computability of Homology for Compact Absolute Neighbourhood Retracts

    OpenAIRE

    Collins, Pieter; Contributed Papers

    2009-01-01

    In this note we discuss the information needed to compute the homology groups of a topological space. We argue that the natural class of spaces to consider are the compact absolute neighbourhood retracts, since for these spaces the homology groups are finite. We show that we need to specify both a function which defines a retraction from a neighbourhood of the space in the Hilbert cube to the space itself, and a sufficiently fine over-approximation of the set. However, neither the retraction ...

  18. Cohesin Is limiting for the suppression of DNA damage-induced recombination between homologous chromosomes.

    Directory of Open Access Journals (Sweden)

    Shay Covo

    2010-07-01

    Full Text Available Double-strand break (DSB repair through homologous recombination (HR is an evolutionarily conserved process that is generally error-free. The risk to genome stability posed by nonallelic recombination or loss-of-heterozygosity could be reduced by confining HR to sister chromatids, thereby preventing recombination between homologous chromosomes. Here we show that the sister chromatid cohesion complex (cohesin is a limiting factor in the control of DSB repair and genome stability and that it suppresses DNA damage-induced interactions between homologues. We developed a gene dosage system in tetraploid yeast to address limitations on various essential components in DSB repair and HR. Unlike RAD50 and RAD51, which play a direct role in HR, a 4-fold reduction in the number of essential MCD1 sister chromatid cohesion subunit genes affected survival of gamma-irradiated G(2/M cells. The decreased survival reflected a reduction in DSB repair. Importantly, HR between homologous chromosomes was strongly increased by ionizing radiation in G(2/M cells with a single copy of MCD1 or SMC3 even at radiation doses where survival was high and DSB repair was efficient. The increased recombination also extended to nonlethal doses of UV, which did not induce DSBs. The DNA damage-induced recombinants in G(2/M cells included crossovers. Thus, the cohesin complex has a dual role in protecting chromosome integrity: it promotes DSB repair and recombination between sister chromatids, and it suppresses damage-induced recombination between homologues. The effects of limited amounts of Mcd1and Smc3 indicate that small changes in cohesin levels may increase the risk of genome instability, which may lead to genetic diseases and cancer.

  19. A homology-based pipeline for global prediction of post-translational modification sites

    Science.gov (United States)

    Chen, Xiang; Shi, Shao-Ping; Xu, Hao-Dong; Suo, Sheng-Bao; Qiu, Jian-Ding

    2016-05-01

    The pathways of protein post-translational modifications (PTMs) have been shown to play particularly important roles for almost any biological process. Identification of PTM substrates along with information on the exact sites is fundamental for fully understanding or controlling biological processes. Alternative computational strategies would help to annotate PTMs in a high-throughput manner. Traditional algorithms are suited for identifying the common organisms and tissues that have a complete PTM atlas or extensive experimental data. While annotation of rare PTMs in most organisms is a clear challenge. In this work, to this end we have developed a novel homology-based pipeline named PTMProber that allows identification of potential modification sites for most of the proteomes lacking PTMs data. Cross-promotion E-value (CPE) as stringent benchmark has been used in our pipeline to evaluate homology to known modification sites. Independent-validation tests show that PTMProber achieves over 58.8% recall with high precision by CPE benchmark. Comparisons with other machine-learning tools show that PTMProber pipeline performs better on general predictions. In addition, we developed a web-based tool to integrate this pipeline at http://bioinfo.ncu.edu.cn/PTMProber/index.aspx. In addition to pre-constructed prediction models of PTM, the website provides an extensional functionality to allow users to customize models.

  20. Phenylbutyrate inhibits homologous recombination induced by camptothecin and methyl methanesulfonate

    DEFF Research Database (Denmark)

    Kaiser, Gitte Schalck; Germann, Susanne Manuela; Westergaard, Tine;

    2011-01-01

    Homologous recombination is accompanied by extensive changes to chromatin organization at the site of DNA damage. Some of these changes are mediated through acetylation/deacetylation of histones. Here, we show that recombinational repair of DNA damage induced by the anti-cancer drug camptothecin...

  1. Vanishing of the contact homology of overtwisted contact 3--manifolds

    OpenAIRE

    Yau, Mei-Lin

    2004-01-01

    We give a proof of, for the case of contact structures defined by global contact 1-forms, a Theorem stated by Eliashberg that for any overtwisted contact structure on a closed 3-manifold, its contact homology is 0. A different proof is also outlined in the appendix by Yakov Eliashberg.

  2. Multiresolution persistent homology for excessively large biomolecular datasets

    Science.gov (United States)

    Xia, Kelin; Zhao, Zhixiong; Wei, Guo-Wei

    2015-10-01

    Although persistent homology has emerged as a promising tool for the topological simplification of complex data, it is computationally intractable for large datasets. We introduce multiresolution persistent homology to handle excessively large datasets. We match the resolution with the scale of interest so as to represent large scale datasets with appropriate resolution. We utilize flexibility-rigidity index to access the topological connectivity of the data set and define a rigidity density for the filtration analysis. By appropriately tuning the resolution of the rigidity density, we are able to focus the topological lens on the scale of interest. The proposed multiresolution topological analysis is validated by a hexagonal fractal image which has three distinct scales. We further demonstrate the proposed method for extracting topological fingerprints from DNA molecules. In particular, the topological persistence of a virus capsid with 273 780 atoms is successfully analyzed which would otherwise be inaccessible to the normal point cloud method and unreliable by using coarse-grained multiscale persistent homology. The proposed method has also been successfully applied to the protein domain classification, which is the first time that persistent homology is used for practical protein domain analysis, to our knowledge. The proposed multiresolution topological method has potential applications in arbitrary data sets, such as social networks, biological networks, and graphs.

  3. K-homology and index theory on contact manifolds

    CERN Document Server

    Baum, Paul F

    2011-01-01

    Let X be a closed connected contact manifold. On X there is a naturally arising class of hypoelliptic (but not elliptic) operators which are Fredholm. In this paper we solve the index problem for this class of operators. The solution is achieved by combining Van Erp's earlier partial result with the Baum-Douglas isomorphism of analytic and geometric K-homology.

  4. Multiresolution persistent homology for excessively large biomolecular datasets

    International Nuclear Information System (INIS)

    Although persistent homology has emerged as a promising tool for the topological simplification of complex data, it is computationally intractable for large datasets. We introduce multiresolution persistent homology to handle excessively large datasets. We match the resolution with the scale of interest so as to represent large scale datasets with appropriate resolution. We utilize flexibility-rigidity index to access the topological connectivity of the data set and define a rigidity density for the filtration analysis. By appropriately tuning the resolution of the rigidity density, we are able to focus the topological lens on the scale of interest. The proposed multiresolution topological analysis is validated by a hexagonal fractal image which has three distinct scales. We further demonstrate the proposed method for extracting topological fingerprints from DNA molecules. In particular, the topological persistence of a virus capsid with 273 780 atoms is successfully analyzed which would otherwise be inaccessible to the normal point cloud method and unreliable by using coarse-grained multiscale persistent homology. The proposed method has also been successfully applied to the protein domain classification, which is the first time that persistent homology is used for practical protein domain analysis, to our knowledge. The proposed multiresolution topological method has potential applications in arbitrary data sets, such as social networks, biological networks, and graphs

  5. On the skein exact squence for knot Floer homology

    OpenAIRE

    Ozsvath, Peter; Szabo, Zoltan

    2007-01-01

    The aim of this paper is to study the skein exact sequence for knot Floer homology. We prove precise graded version of this sequence, and also one using $\\HFm$. Moreover, a complete argument is also given purely within the realm of grid diagrams.

  6. Real bundle gerbes, orientifolds and twisted KR-homology

    CERN Document Server

    Hekmati, Pedram; Szabo, Richard J; Vozzo, Raymond F

    2016-01-01

    We introduce a notion of Real bundle gerbes on manifolds equipped with an involution. We elucidate their relation to Jandl gerbes and prove that they are classified by their Real Dixmier-Douady class in Grothendieck's equivariant sheaf cohomology. We show that the Grothendieck group of Real bundle gerbe modules is isomorphic to twisted KR-theory for a torsion Real Dixmier-Douady class. Building on the Baum-Douglas model for K-homology and the orientifold construction in string theory, we introduce geometric cycles for twisted KR-homology groups using Real bundle gerbe modules. We prove that this defines a real-oriented generalised homology theory dual to twisted KR-theory for Real closed manifolds, and more generally for Real finite CW-complexes, for any Real Dixmier-Douady class. This is achieved by defining an explicit natural transformation to analytic twisted KR-homology and proving that it is an isomorphism. Our constructions give a new framework for the classification of orientifolds in string theory, p...

  7. Monitoring homologous recombination in rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Here we describe a system to assay homologous recombination during the complete life cycle of rice (Oryza sativa L.). Rice plants were transformed with two copies of non-functional GUS reporter overlap fragments as recombination substrate. Recombination was observed in all plant organs examined, from the seed stage until the flowering stage of somatic plant development. Embryogenic cells exhibited the highest recombination ability with an average of 3 x 10-5 recombination events per genome, which is about 10-fold of that observed in root cells, and two orders of that observed in leaf cells. Histological analysis revealed that recombination events occurred in diverse cell types, but preferentially in cells with small size. Examples of this included embryogenic cells in callus, phloem cells in the leaf vein, and cells located in the root apical meristem. Steady state RNA analysis revealed that the expression levels of rice Rad51 homologs are positively correlated with increased recombination rates in embryogenic calli, roots and anthers. Finally, radiation treatment of plantlets from distinct recombination lines increased the recombination frequency to different extents. These results showed that homologous recombination frequency can be effectively measured in rice using a transgene reporter assay. This system will facilitate the study of DNA damage signaling and homologous recombination in rice, a model monocot.

  8. Monitoring homologous recombination in rice (Oryza sativa L.)

    Energy Technology Data Exchange (ETDEWEB)

    Yang Zhuanying; Tang Li [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China); Li Meiru [South China Botanic Garden, Chinese Academy of Sciences, Guangzhou 510650 (China); Chen Lei; Xu Jie [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China); Wu Goujiang [South China Botanic Garden, Chinese Academy of Sciences, Guangzhou 510650 (China); Li Hongqing, E-mail: hqli@scnu.edu.cn [Guangdong Provincial Key Lab of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631 (China)

    2010-09-10

    Here we describe a system to assay homologous recombination during the complete life cycle of rice (Oryza sativa L.). Rice plants were transformed with two copies of non-functional GUS reporter overlap fragments as recombination substrate. Recombination was observed in all plant organs examined, from the seed stage until the flowering stage of somatic plant development. Embryogenic cells exhibited the highest recombination ability with an average of 3 x 10{sup -5} recombination events per genome, which is about 10-fold of that observed in root cells, and two orders of that observed in leaf cells. Histological analysis revealed that recombination events occurred in diverse cell types, but preferentially in cells with small size. Examples of this included embryogenic cells in callus, phloem cells in the leaf vein, and cells located in the root apical meristem. Steady state RNA analysis revealed that the expression levels of rice Rad51 homologs are positively correlated with increased recombination rates in embryogenic calli, roots and anthers. Finally, radiation treatment of plantlets from distinct recombination lines increased the recombination frequency to different extents. These results showed that homologous recombination frequency can be effectively measured in rice using a transgene reporter assay. This system will facilitate the study of DNA damage signaling and homologous recombination in rice, a model monocot.

  9. Topological Hochschild homology and the Bass trace conjecture

    DEFF Research Database (Denmark)

    Berrick, A. J.; Hesselholt, Lars

    2015-01-01

    We use the methods of topological Hochschild homology to shed new light on groups satisfying the Bass trace conjecture. Factorization of the Hattori–Stallings rank map through the Bökstedt–Hsiang–Madsen cyclotomic trace map leads to Linnell's restriction on such groups. As a new consequence of this...

  10. On the Homology of Congruence Subgroups and K3(Z)

    Science.gov (United States)

    Lee, Ronnie; Szczarba, R. H.

    1975-01-01

    Let Γ(n;p) be the congruence subgroup of SL(n;Z) of level p. We study the homology and cohomology of Γ(n;p) as modules over SL(n;Fp) and apply our results to obtain an upper bound for the order of K3(Z). PMID:16592224

  11. On rationality of logarithmic Q-homology planes - I

    International Nuclear Information System (INIS)

    Normal surfaces over the complex plane are considered that are logarithmic (i.e., all its singularities are of the quotient type) and of which all reduced homology groups with rational coefficients vanish. It is proved that all such planes are rational. 16 refs

  12. Annotating Simplices with a Homology Basis and Its Applications

    CERN Document Server

    Busaryev, Oleksiy; Chen, Chao; Dey, Tamal K; Wang, Yusu

    2011-01-01

    Let $K$ be a simplicial complex and $g$ the rank of its $p$-th homology group $H_p(K)$ defined with $Z_2$ coefficients. We show that we can compute a basis $H$ of $H_p(K)$ and annotate each $p$-simplex of $K$ with a binary vector of length $g$ with the following property: the annotations, summed over all $p$-simplices in any $p$-cycle $z$, provide the coordinate vector of the homology class $[z]$ in the basis $H$. The basis and the annotations for all simplices can be computed in $O(n^{\\omega})$ time, where $n$ is the size of $K$ and $\\omega<2.376$ is a quantity so that two $n\\times n$ matrices can be multiplied in $O(n^{\\omega})$ time. The pre-computation of annotations permits answering queries about the independence or the triviality of $p$-cycles efficiently. Using annotations of edges in 2-complexes, we derive better algorithms for computing optimal basis and optimal homologous cycles in 1-dimensional homology. Specifically, for computing an optimal basis of $H_1(K)$, we improve the time complexity kn...

  13. On the zeroth L^2-homology of a quantum group

    OpenAIRE

    Kyed, David

    2009-01-01

    We prove that the zeroth L^2-Betti number of a compact quantum group vanishes unless the underlying C*-algebra is finite dimensional and that the zeroth L^2-homology itself is non-trivial exactly when the quantum group is coamenable.

  14. Multiresolution persistent homology for excessively large biomolecular datasets

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Kelin; Zhao, Zhixiong [Department of Mathematics, Michigan State University, East Lansing, Michigan 48824 (United States); Wei, Guo-Wei, E-mail: wei@math.msu.edu [Department of Mathematics, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824 (United States)

    2015-10-07

    Although persistent homology has emerged as a promising tool for the topological simplification of complex data, it is computationally intractable for large datasets. We introduce multiresolution persistent homology to handle excessively large datasets. We match the resolution with the scale of interest so as to represent large scale datasets with appropriate resolution. We utilize flexibility-rigidity index to access the topological connectivity of the data set and define a rigidity density for the filtration analysis. By appropriately tuning the resolution of the rigidity density, we are able to focus the topological lens on the scale of interest. The proposed multiresolution topological analysis is validated by a hexagonal fractal image which has three distinct scales. We further demonstrate the proposed method for extracting topological fingerprints from DNA molecules. In particular, the topological persistence of a virus capsid with 273 780 atoms is successfully analyzed which would otherwise be inaccessible to the normal point cloud method and unreliable by using coarse-grained multiscale persistent homology. The proposed method has also been successfully applied to the protein domain classification, which is the first time that persistent homology is used for practical protein domain analysis, to our knowledge. The proposed multiresolution topological method has potential applications in arbitrary data sets, such as social networks, biological networks, and graphs.

  15. Actions of SL(n,Z) on homology spheres

    OpenAIRE

    Parwani, Kamlesh

    2005-01-01

    Any continuous action of SL(n,Z), where n > 2, on a r-dimensional mod 2 homology sphere factors through a finite group action if r < n - 1. In particular, any continuous action of SL(n+2,Z) on the n-dimensional sphere factors through a finite group action.

  16. Using intron position conservation for homology-based gene prediction.

    Science.gov (United States)

    Keilwagen, Jens; Wenk, Michael; Erickson, Jessica L; Schattat, Martin H; Grau, Jan; Hartung, Frank

    2016-05-19

    Annotation of protein-coding genes is very important in bioinformatics and biology and has a decisive influence on many downstream analyses. Homology-based gene prediction programs allow for transferring knowledge about protein-coding genes from an annotated organism to an organism of interest.Here, we present a homology-based gene prediction program called GeMoMa. GeMoMa utilizes the conservation of intron positions within genes to predict related genes in other organisms. We assess the performance of GeMoMa and compare it with state-of-the-art competitors on plant and animal genomes using an extended best reciprocal hit approach. We find that GeMoMa often makes more precise predictions than its competitors yielding a substantially increased number of correct transcripts. Subsequently, we exemplarily validate GeMoMa predictions using Sanger sequencing. Finally, we use RNA-seq data to compare the predictions of homology-based gene prediction programs, and find again that GeMoMa performs well.Hence, we conclude that exploiting intron position conservation improves homology-based gene prediction, and we make GeMoMa freely available as command-line tool and Galaxy integration. PMID:26893356

  17. Single-stranded heteroduplex intermediates in λ Red homologous recombination

    Directory of Open Access Journals (Sweden)

    Zhang Youming

    2010-07-01

    Full Text Available Abstract Background The Red proteins of lambda phage mediate probably the simplest and most efficient homologous recombination reactions yet described. However the mechanism of dsDNA recombination remains undefined. Results Here we show that the Red proteins can act via full length single stranded intermediates to establish single stranded heteroduplexes at the replication fork. We created asymmetrically digestible dsDNA substrates by exploiting the fact that Redα exonuclease activity requires a 5' phosphorylated end, or is blocked by phosphothioates. Using these substrates, we found that the most efficient configuration for dsDNA recombination occurred when the strand that can prime Okazaki-like synthesis contained both homology regions on the same ssDNA molecule. Furthermore, we show that Red recombination requires replication of the target molecule. Conclusions Hence we propose a new model for dsDNA recombination, termed 'beta' recombination, based on the formation of ssDNA heteroduplexes at the replication fork. Implications of the model were tested using (i an in situ assay for recombination, which showed that recombination generated mixed wild type and recombinant colonies; and (ii the predicted asymmetries of the homology arms, which showed that recombination is more sensitive to non-homologies attached to 5' than 3' ends. Whereas beta recombination can generate deletions in target BACs of at least 50 kb at about the same efficiency as small deletions, the converse event of insertion is very sensitive to increasing size. Insertions up to 3 kb are most efficiently achieved using beta recombination, however at greater sizes, an alternative Red-mediated mechanism(s appears to be equally efficient. These findings define a new intermediate in homologous recombination, which also has practical implications for recombineering with the Red proteins.

  18. PUF-8, a Pumilio homolog, inhibits the proliferative fate in the Caenorhabditis elegans germline.

    Science.gov (United States)

    Racher, Hilary; Hansen, Dave

    2012-10-01

    Stem cell populations are maintained by keeping a balance between self-renewal (proliferation) and differentiation of dividing stem cells. Within the Caenorhabditis elegans germline, the key regulator maintaining this balance is the canonical Notch signaling pathway, with GLP-1/Notch activity promoting the proliferative fate. We identified the Pumilio homolog, PUF-8, as an inhibitor of the proliferative fate of stem cells in the C. elegans germline. puf-8(0) strongly enhances overproliferation of glp-1(gf) mutants and partially suppresses underproliferation of a weak glp-1(lf) mutant. The germline tumor that is formed in a puf-8(0); glp-1(gf) double mutant is due to a failure of germ cells to enter meiotic prophase. puf-8 likely inhibits the proliferative fate through negatively regulating GLP-1/Notch signaling or by functioning parallel to it. PMID:23050230

  19. Transcriptional and post-translational regulation of mouse cation transport regulator homolog 1.

    Science.gov (United States)

    Oh-Hashi, Kentaro; Nomura, Yuki; Shimada, Kiyo; Koga, Hisashi; Hirata, Yoko; Kiuchi, Kazutoshi

    2013-08-01

    Recently, cation transport regulator homolog 1 (Chac1) has been identified as a novel pro-apoptotic factor in cells under endoplasmic reticulum (ER) stress. Of the three major ER stress sensors, it is suggested that ATF4 participates in the transcriptional regulation of Chac1 gene expression. The precise characterization of the Chac1 promoter, however, has not yet been elucidated. In this study, we detected the induction of Chac1 mRNA expression using DNA array analysis and RT-PCR of thapsigargin (Tg)-inducible genes in Neuro2a cells. Chac1 mRNA expression was also induced immediately following treatment with tunicamycin (Tm) and brefeldin A. Characterization of the mouse Chac1 promoter activity using a luciferase reporter assay revealed that the CREB/ATF element and amino acid response element in the mouse Chac1 promoter are functional and respond to Tm stimulation and ATF4 overexpression. Mutations in either element in the Chac1 promoter did not inhibit the responsiveness of this promoter to Tm and ATF4; however, mutations in both of these elements dramatically decreased the basal activity and response to ER stress stimuli. In addition to the transcriptional regulation, we found that Chac1 protein expression was only detected in the presence of MG132, a proteasome inhibitor, even though mouse Chac1 gene was transiently overexpressed in Neuro2a cells. Taken together, we are the first to demonstrate the transcriptional and post-translational regulation of Chac1 expression in a neuronal cell line. PMID:23615711

  20. Evidence for a Chk2-BRCA1-BRCA2 pathway in controlling homologous recombination

    International Nuclear Information System (INIS)

    The BRCA2 protein is thought to play a role as a supportive protein for the assembly of Rad51 filaments at the sites of DNA damage or stalled DNA replication, and thereby facilitates the process of homologous recombination (HR). We provide direct evidence that the interaction of BRCA2 and Rad51, via the BRC repeat motifs of BRCA2, is the key to its function in HR. Furthermore, the BRCA2's role to facilitate HR is dependent on a replicating DNA template, closely linking the process of HR to DNA replication. To date, no other role for BRCA2 has been elucidated in-vivo. BRCA1, by contrast, has a complex series of functions including a supportive role in HR, a possible role in non-homologous recombination (NHR), transcriptional co-activation and E3 ubiquitin ligase activity. The protein undergoes extensive post-translational modification, principally by phosphorylation, in both S-phase and in response to DNA damage. We show that ATM-dependent modifications of BRCA1 are important for S-phase and G2/M checkpoints, but have no direct impact on DNA repair. However, a chk2 dependent modification of BRCA1 at serine-988, appears critical for the promotion of Rad51-dependent HR and the inhibition of Mre11/Rad50/NBS1- dependent repair. Direct modification of chk2 kinase activity, by over-expression of a kinase-dead chk2, results in an identical phenotype as seen with the S988A mutation of BRCA1. Taken together, these results suggest that a chk2-BRCA1-BRCA2 dependent pathway promotes error-free HR, suppresses error-prone NHR and thereby maintains genomic stability

  1. Promoting industrialisation

    International Nuclear Information System (INIS)

    When the first nuclear power programme is decided upon, automatically the country has to initiate in parallel a programme to modify or add to its current industrial structure and resources. The extent of this new industrialisation depends upon many factors which both, the Government and the Industries have to consider. The Government has a vital role which includes the setting up of the background against which the industrial promotion should take place and in many cases may have also to play an active role all along this programme. Equally, the existing industries have an important role so as to achieve the most efficient participation in the nuclear programme. Invariably the industrial promotional programme will incur a certain degree of transfer of technology, the extent depending on the policies adopted. For this technology transfer to take place efficiently, both the donor and the receiver have to recognise each other's legitimate ambitions and fears. The transfer of technology is a process having a high human content and both donor and receiver have to take this into account. This can be further complicated when there is a difference in culture between them. Technology transfer is carried out within a contractual and organisational framework which will identify the donor (licensor) and the receiver (licensee). This framework may take various forms from a simple cooperative agreement, through a joint-venture organisation right to a standard contract between two separate entities. Each arrangement has its advantages and drawbacks and requires investment of different degrees. One of the keys to a successful industrial promotion is having it carried out in a timely fashion which will be parallel with the nuclear power programme. Experience in some countries has shown the problems when the industrialisation is out of phase with the programme whilst in other cases this industrialisation was at a level and scale unjustified. (author)

  2. Effects of polymerization and nucleotide identity on the conformational dynamics of the bacterial actin homolog MreB

    OpenAIRE

    Colavin, Alexandre; Hsin, Jen; Huang, Kerwyn Casey

    2014-01-01

    Cytoskeletal filaments drive many dynamic cellular processes, such as the regulation of shape by actin networks in eukaryotes and by the actin homolog MreB in rod-shaped bacteria. Here, we use all-atom molecular dynamics simulations to demonstrate close parallels between the conformational dynamics of actin and MreB, in which polymerization induces flattening of MreB subunits that restructures the ATP binding pocket to promote hydrolysis. We also find that ATP-bound MreB filaments are substan...

  3. The light organ symbiont Vibrio fischeri possesses a homolog of the Vibrio cholerae transmembrane transcriptional activator ToxR.

    OpenAIRE

    Reich, K A; Schoolnik, G K

    1994-01-01

    A cross-hybridizing DNA fragment to Vibrio cholerae toxR was cloned from the nonpathogenic light organ symbiont Vibrio fischeri, and three proteins homologous to V. cholerae ToxR, ToxS, and HtpG were deduced from its DNA sequence. V. fischeri ToxR was found to activate a V. cholerae ToxR-regulated promoter, and an antiserum raised against the amino-terminal domain of V. cholerae ToxR cross-reacts V. fischeri ToxR.

  4. The endless tale of non-homologous end-joining

    Institute of Scientific and Technical Information of China (English)

    Eric Weterings; David J Chen

    2008-01-01

    DNA double-strand breaks (DSBs) are introduced in cells by ionizing radiation and reactive oxygen species. In addi-tion, they are commonly generated during V(D)J recombination, an essential aspect of the developing immune system. Failure to effectively repair these DSBs can result in chromosome breakage, cell death, onset of cancer, and defects in the immune system of higher vertebrates. Fortunately, all mammalian cells possess two enzymatic pathways that mediate the repair of DSBs: homologous recombination and non-homologous end-joining (NHEJ). The NHEJ process utilizes enzymes that capture both ends of the broken DNA molecule, bring them together in a synaptic DNA-protein complex, and finally repair the DNA break. In this review, all the known enzymes that play a role in the NHEJ process are discussed and a working model for the co-operation of these enzymes during DSB repair is presented.

  5. Community-local homology of force chains in granular materials

    Science.gov (United States)

    Giusti, Chad; Owens, Eli; Daniels, Karen; Bassett, Danielle

    2015-03-01

    The development of robust quantitative measurements of the structure of force chains in granular materials remains an open problem. Recent work of Bassett, et. al. applies community detection algorithms to extract subnetworks of strongly interacting particles, and then computes geometric measures of these networks to characterize local branching. Separately, Kramar, et. al. apply persistent homology to extract robust global signatures of chains in terms of their Betti numbers. Here, we investigate a hybrid of these two approaches, computing low-dimensional persistent homology of the clique complexes of communities in force-chain graphs. Such invariants measure the tendency of core chain sections to branch while remaining insensitive to the presence of tightly-packed collections of particles, thus making them natural candidates for both local and global stability analysis.

  6. Phylogeny and Homologous Recombination in Japanese Encephalitis Viruses

    Institute of Scientific and Technical Information of China (English)

    Li Xiao-xue; Cong Ying-ying; Wang Xin; Ren Yu-dong; Ren Xiao-feng; Lu Ai-guo; Li Guang-xing

    2015-01-01

    Japanese encephalitis virus (JEV) is a significant causative agent of arthropod-borne encephalitis and what is less clear that the factors cause the virus wide spread. The objective was to confirm whether the homologous recombination imposed on JEV. The phylogenetic and homologous recombination analyses were performed based on 163 complete JEV genomes which were recently isolated. They were still separated into five genotypes (GI-GV) and the most of recently isolated JEVs were GI rather than GIII in Asian areas including mainland China. Two recombinant events were identified in JEV and the evidence of the recombination was observed between China and Japan isolates that partitioned into two distinct subclades, but still the same genotype (GIII). Our data further suggested that most of the nucleotides in JEV genome were under negative selection; however, changes within codon 2 316 (amino acid NS4b-44) showed an evidence of the positive selection.

  7. Optimization criteria and biological process enrichment in homologous multiprotein modules.

    Science.gov (United States)

    Hodgkinson, Luqman; Karp, Richard M

    2013-06-25

    Biological process enrichment is a widely used metric for evaluating the quality of multiprotein modules. In this study, we examine possible optimization criteria for detecting homologous multiprotein modules and quantify their effects on biological process enrichment. We find that modularity, linear density, and module size are the most important criteria considered, complementary to each other, and that graph theoretical attributes account for 36% of the variance in biological process enrichment. Variations in protein interaction similarity within module pairs have only minor effects on biological process enrichment. As random modules increase in size, both biological process enrichment and modularity tend to improve, although modularity does not show this upward trend in modules with size at most 50 proteins. To adjust for these trends, we recommend a size correction based on random sampling of modules when using biological process enrichment or other attributes to evaluate module boundaries. Characteristics of homologous multiprotein modules optimized for each of the optimization criteria are examined. PMID:23757502

  8. Homology and isomorphism: Bourdieu in conversation with New Institutionalism.

    Science.gov (United States)

    Wang, Yingyao

    2016-06-01

    Bourdieusian Field Theory (BFT) provided decisive inspiration for the early conceptual formulation of New Institutionalism (NI). This paper attempts to reinvigorate the stalled intellectual dialogue between NI and BFT by comparing NI's concept of isomorphism with BFT's notion of homology. I argue that Bourdieu's understanding of domination-oriented social action, transposable habitus, and a non-linear causality, embodied in his neglected concept of homology, provides an alternative theorization of field-level convergence to New Institutionalism's central idea of institutional isomorphism. To showcase how BFT can be useful for organizational research, I postulate a habitus-informed and field-conditioned theory of transference to enrich NI's spin-off thesis of 'diffusion'. I propose that while NI can benefit from BFT's potential of bringing social structure back into organizational research, BFT can enrich its social analysis by borrowing from NI's elaboration of the symbolic system of organizations. PMID:27218878

  9. Intermediaries in Bredon (Co)homology and Classifying Spaces

    CERN Document Server

    Dembegioti, Fotini; Talelli, Olympia

    2011-01-01

    For certain contractible G-CW-complexes and F a family of subgroups of G, we construct a spectral sequence converging to the F-Bredon cohomology of G with E1-terms given by the F-Bredon cohomology of the stabilizer subgroups. As applications, we obtain several corollaries concerning the cohomological and geometric dimensions of the classifying space for the family F. We also introduce a hierarchically defined class of groups which contains all countable elementary amenable groups and countable linear groups of characteristic zero, and show that if a group G is in this class, then G has finite F-Bredon (co)homological dimension if and only if G has jump F-Bredon (co)homology.

  10. Homological algebra of Novikov-Shubin invariants and Morse inequalities

    CERN Document Server

    Farber, M

    1996-01-01

    It is shown that the topological phenomenon "zero in the continuous spectrum", discovered by S.P.Novikov and M.A.Shubin, can be explained in terms of a homology theory on the category of finite polyhedra with values in certain abelian category. This approach implies homotopy invariance of the Novikov-Shubin invariants. Its main advantage is that it allows to use the standard homological techniques, such as spectral sequences, derived functors, universal coefficients etc., while studying the Novikov-Shubin invariants. It also leads to some new quantitative invariants, measuring the Novikov-Shubin phenomenon in a different way, which are used in order to strengthen the Morse type inequalities of Novikov and Shubin.

  11. Cosmetic Surgery in Integral Homology $L$-Spaces

    CERN Document Server

    Wu, Zhongtao

    2009-01-01

    Let $K$ be a non-trivial knot in $S^3$, and let $r$ and $r'$ be two distinct rational numbers of same sign, allowing $r$ to be infinite; we prove that there is no orientation-preserving homeomorphism between the manifolds $S^3_r(K)$ and $S^3_{r'}(K)$. We further generalize this uniqueness result to knots in arbitrary integral homology L-spaces.

  12. Quantifying Homologous Replacement of Loci between Haloarchaeal Species

    OpenAIRE

    Williams, David; Gogarten, J. Peter; Papke, R. Thane

    2012-01-01

    In vitro studies of the haloarchaeal genus Haloferax have demonstrated their ability to frequently exchange DNA between species, whereas rates of homologous recombination estimated from natural populations in the genus Halorubrum are high enough to maintain random association of alleles between five loci. To quantify the effects of gene transfer and recombination of commonly held (relaxed core) genes during the evolution of the class Halobacteria (haloarchaea), we reconstructed the history of...

  13. Characterization of a canine homolog of hepatitis C virus

    OpenAIRE

    Kapoor, Amit; Simmonds, Peter; Gerold, Gisa; Qaisar, Natasha; Jain, Komal; Henriquez, Jose A.; Firth, Cadhla; Hirschberg, David L.; Rice, Charles M.; Shields, Shelly; Lipkin, W. Ian

    2011-01-01

    An estimated 3% of the world's population is chronically infected with hepatitis C virus (HCV). Although HCV was discovered more than 20 y ago, its origin remains obscure largely because no closely related animal virus homolog has been identified; furthermore, efforts to understand HCV pathogenesis have been hampered by the absence of animal models other than chimpanzees for human disease. Here we report the identification in domestic dogs of a nonprimate hepacivirus. Comparative phylogenetic...

  14. Amifostine Metabolite WR-1065 Disrupts Homologous Recombination in Mammalian Cells

    OpenAIRE

    Dziegielewski, Jaroslaw; Goetz, Wilfried; Murley, Jeffrey S.; David J Grdina; Morgan, William F.; Janet E. Baulch

    2010-01-01

    Repair of DNA damage through homologous recombination (HR) pathways plays a crucial role in maintaining genome stability. However, overstimulation of HR pathways in response to genotoxic stress may abnormally elevate recombination frequencies, leading to increased mutation rates and delayed genomic instability. Radiation-induced genomic instability has been detected after exposure to both low- and high-linear energy transfer (LET) radiations, but the mechanisms responsible for initiating or p...

  15. Chimpanzee chromosome 13 is homologous to human chromosome 2p

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Similarities between human and chimpanzee chromosomes are shown by chromosome banding techniques and somatic cell hybridization techniques. Cell hybrids were obtained from the chimpanzee lymphocyte LE-7, and the Chinese hamster mutant cell, Gal-2. Experiments showed that the ACPL, MDHs, and Gal-Act genes could be assigned to chimpanzee chromosome 13, and since these genes have been assigned to human chromosme 2p, it is suggested that chimpanzee chromosome 13 is homologous to human chromosome 2p. (HLW)

  16. The many facets of homologous recombination at telomeres

    OpenAIRE

    Clémence Claussin; Michael Chang

    2015-01-01

    The ends of linear chromosomes are capped by nucleoprotein structures called telomeres. A dysfunctional telomere may resemble a DNA double-strand break (DSB), which is a severe form of DNA damage. The presence of one DSB is sufficient to drive cell cycle arrest and cell death. Therefore cells have evolved mechanisms to repair DSBs such as homologous recombination (HR). HR-mediated repair of telomeres can lead to genome instability, a hallmark of cancer cells, wh...

  17. Homology Modeling and Molecular Docking for the Science Curriculum

    OpenAIRE

    Owen M. McDougal; Comia, Nic; Sambasivarao, S.V.; Remm, Andrew; Mallory, Chris; Oxford, Julia Thom; Maupin, C. Mark; Andersen, Tim

    2013-01-01

    DockoMatic 2.0 is a powerful open source software program (downloadable from sourceforge.net) that simplifies the exploration of computational biochemistry. This manuscript describes a practical tutorial for use in the undergraduate curriculum that introduces students to macromolecular structure creation, ligand binding calculations, and visualization of docking results. A student procedure is provided that illustrates use of DockoMatic to create a homology model for the amino propeptide regi...

  18. GHOSTM: a GPU-accelerated homology search tool for metagenomics.

    Directory of Open Access Journals (Sweden)

    Shuji Suzuki

    Full Text Available BACKGROUND: A large number of sensitive homology searches are required for mapping DNA sequence fragments to known protein sequences in public and private databases during metagenomic analysis. BLAST is currently used for this purpose, but its calculation speed is insufficient, especially for analyzing the large quantities of sequence data obtained from a next-generation sequencer. However, faster search tools, such as BLAT, do not have sufficient search sensitivity for metagenomic analysis. Thus, a sensitive and efficient homology search tool is in high demand for this type of analysis. METHODOLOGY/PRINCIPAL FINDINGS: We developed a new, highly efficient homology search algorithm suitable for graphics processing unit (GPU calculations that was implemented as a GPU system that we called GHOSTM. The system first searches for candidate alignment positions for a sequence from the database using pre-calculated indexes and then calculates local alignments around the candidate positions before calculating alignment scores. We implemented both of these processes on GPUs. The system achieved calculation speeds that were 130 and 407 times faster than BLAST with 1 GPU and 4 GPUs, respectively. The system also showed higher search sensitivity and had a calculation speed that was 4 and 15 times faster than BLAT with 1 GPU and 4 GPUs. CONCLUSIONS: We developed a GPU-optimized algorithm to perform sensitive sequence homology searches and implemented the system as GHOSTM. Currently, sequencing technology continues to improve, and sequencers are increasingly producing larger and larger quantities of data. This explosion of sequence data makes computational analysis with contemporary tools more difficult. We developed GHOSTM, which is a cost-efficient tool, and offer this tool as a potential solution to this problem.

  19. Optimizing the design of oligonucleotides for homology directed gene targeting.

    Directory of Open Access Journals (Sweden)

    Judith Miné-Hattab

    Full Text Available BACKGROUND: Gene targeting depends on the ability of cells to use homologous recombination to integrate exogenous DNA into their own genome. A robust mechanistic model of homologous recombination is necessary to fully exploit gene targeting for therapeutic benefit. METHODOLOGY/PRINCIPAL FINDINGS: In this work, our recently developed numerical simulation model for homology search is employed to develop rules for the design of oligonucleotides used in gene targeting. A Metropolis Monte-Carlo algorithm is used to predict the pairing dynamics of an oligonucleotide with the target double-stranded DNA. The model calculates the base-alignment between a long, target double-stranded DNA and a probe nucleoprotein filament comprised of homologous recombination proteins (Rad51 or RecA polymerized on a single strand DNA. In this study, we considered different sizes of oligonucleotides containing 1 or 3 base heterologies with the target; different positions on the probe were tested to investigate the effect of the mismatch position on the pairing dynamics and stability. We show that the optimal design is a compromise between the mean time to reach a perfect alignment between the two molecules and the stability of the complex. CONCLUSION AND SIGNIFICANCE: A single heterology can be placed anywhere without significantly affecting the stability of the triplex. In the case of three consecutive heterologies, our modeling recommends using long oligonucleotides (at least 35 bases in which the heterologous sequences are positioned at an intermediate position. Oligonucleotides should not contain more than 10% consecutive heterologies to guarantee a stable pairing with the target dsDNA. Theoretical modeling cannot replace experiments, but we believe that our model can considerably accelerate optimization of oligonucleotides for gene therapy by predicting their pairing dynamics with the target dsDNA.

  20. A Smale Type Result and Applications to Contact Homology

    Directory of Open Access Journals (Sweden)

    Vittorio Martino

    2014-12-01

    Full Text Available In this note we will show that the injection of a suitable subspace of the space of Legendrian loops into the full loop space is an S1-equivariant homotopy equivalence. Moreover, since the smaller space is the space of variations of a given action functional, we will compute the relative Contact Homology of a family of tight contact forms on the three-dimensional torus.

  1. Topological Hochschild homology and the Bass trace conjecture

    OpenAIRE

    Berrick, A. J.; Hesselholt, Lars

    2013-01-01

    We use the methods of topological Hochschild homology to shed new light on the groups satisfying the Bass trace conjecture. We show that the factorization of the Hattori-Stallings rank map through the Bokstedt-Hsiang-Madsen cyclotomic trace map leads to Linnell's restriction on such groups. As a new consequence of this restriction, we show that the conjecture holds for any group G with the property that every subgroup that is isomorphic to the additive group of rational numbers has nontrivial...

  2. FastBLAST: homology relationships for millions of proteins.

    Directory of Open Access Journals (Sweden)

    Morgan N Price

    Full Text Available BACKGROUND: All-versus-all BLAST, which searches for homologous pairs of sequences in a database of proteins, is used to identify potential orthologs, to find new protein families, and to provide rapid access to these homology relationships. As DNA sequencing accelerates and data sets grow, all-versus-all BLAST has become computationally demanding. METHODOLOGY/PRINCIPAL FINDINGS: We present FastBLAST, a heuristic replacement for all-versus-all BLAST that relies on alignments of proteins to known families, obtained from tools such as PSI-BLAST and HMMer. FastBLAST avoids most of the work of all-versus-all BLAST by taking advantage of these alignments and by clustering similar sequences. FastBLAST runs in two stages: the first stage identifies additional families and aligns them, and the second stage quickly identifies the homologs of a query sequence, based on the alignments of the families, before generating pairwise alignments. On 6.53 million proteins from the non-redundant Genbank database ("NR", FastBLAST identifies new families 25 times faster than all-versus-all BLAST. Once the first stage is completed, FastBLAST identifies homologs for the average query in less than 5 seconds (8.6 times faster than BLAST and gives nearly identical results. For hits above 70 bits, FastBLAST identifies 98% of the top 3,250 hits per query. CONCLUSIONS/SIGNIFICANCE: FastBLAST enables research groups that do not have supercomputers to analyze large protein sequence data sets. FastBLAST is open source software and is available at http://microbesonline.org/fastblast.

  3. The homological content of the Jones representations at $q = -1$

    DEFF Research Database (Denmark)

    Egsgaard, Jens Kristian; Fuglede Jørgensen, Søren

    We generalize a discovery of Kasahara and show that the Jones representations of braid groups, when evaluated at $q = -1$, are related to the action on homology of a branched double cover of the underlying punctured disk. As an application, we prove for a large family of pseudo-Anosov mapping cla...... classes a conjecture put forward by Andersen, Masbaum, and Ueno by extending their original argument for the sphere with four marked points to our more general case....

  4. Identification of New Herpesvirus Gene Homologs in the Human Genome

    OpenAIRE

    Holzerlandt, Ria; Orengo, Christine; Kellam, Paul; Albà, M. Mar

    2002-01-01

    Viruses are intracellular parasites that use many cellular pathways during their replication. Large DNA viruses, such as herpesviruses, have captured a repertoire of cellular genes to block or mimic host immune responses, apoptosis regulation, and cell-cycle control mechanisms. We have conducted a systematic search for all homologs of herpesvirus proteins in the human genome using position-specific scoring matrices representing herpesvirus protein sequence domains, and pair-wise sequence comp...

  5. Persistent Homology Transform for Modeling Shapes and Surfaces

    OpenAIRE

    Turner, Katharine; Mukherjee, Sayan; Doug M Boyer

    2013-01-01

    In this paper we introduce a statistic, the persistent homology transform (PHT), to model surfaces in $\\mathbb{R}^3$ and shapes in $\\mathbb{R}^2$. This statistic is a collection of persistence diagrams - multiscale topological summaries used extensively in topological data analysis. We use the PHT to represent shapes and execute operations such as computing distances between shapes or classifying shapes. We prove the map from the space of simplicial complexes in $\\mathbb{R}^3$ into the space ...

  6. Exploitation of sulfonylurea resistance marker and non-homologous end joining mutants for functional analysis in Zymoseptoria tritici.

    Science.gov (United States)

    Sidhu, Y S; Cairns, T C; Chaudhari, Y K; Usher, J; Talbot, N J; Studholme, D J; Csukai, M; Haynes, K

    2015-06-01

    The lack of techniques for rapid assembly of gene deletion vectors, paucity of selectable marker genes available for genetic manipulation and low frequency of homologous recombination are major constraints in construction of gene deletion mutants in Zymoseptoria tritici. To address these issues, we have constructed ternary vectors for Agrobacterium tumefaciens mediated transformation of Z. tritici, which enable the single step assembly of multiple fragments via yeast recombinational cloning. The sulfonylurea resistance gene, which is a mutated allele of the Magnaporthe oryzae ILV2 gene, was established as a new dominant selectable marker for Z. tritici. To increase the frequency of homologous recombination, we have constructed Z. tritici strains deficient in the non-homologous end joining pathway of DNA double stranded break repair by inactivating the KU70 and KU80 genes. Targeted gene deletion frequency increased to more than 85% in both Z. tritici ku70 and ku80 null strains, compared to ⩽10% seen in the wild type parental strain IPO323. The in vitro growth and in planta pathogenicity of the Z. tritici ku70 and ku80 null strains were comparable to strain IPO323. Together these molecular tools add significantly to the platform available for genomic analysis through targeted gene deletion or promoter replacements and will facilitate large-scale functional characterization projects in Z. tritici. PMID:26092796

  7. Efficient chromosomal gene modification with CRISPR/cas9 and PCR-based homologous recombination donors in cultured Drosophila cells.

    Science.gov (United States)

    Böttcher, Romy; Hollmann, Manuel; Merk, Karin; Nitschko, Volker; Obermaier, Christina; Philippou-Massier, Julia; Wieland, Isabella; Gaul, Ulrike; Förstemann, Klaus

    2014-06-01

    The ability to edit the genome is essential for many state-of-the-art experimental paradigms. Since DNA breaks stimulate repair, they can be exploited to target site-specific integration. The clustered, regularly interspaced, short palindromic repeats (CRISPR)/cas9 system from Streptococcus pyogenes has been harnessed into an efficient and programmable nuclease for eukaryotic cells. We thus combined DNA cleavage by cas9, the generation of homologous recombination donors by polymerase chain reaction (PCR) and transient depletion of the non-homologous end joining factor lig4. Using cultured Drosophila melanogaster S2-cells and the phosphoglycerate kinase gene as a model, we reached targeted integration frequencies of up to 50% in drug-selected cell populations. Homology arms as short as 29 nt appended to the PCR primer resulted in detectable integration, slightly longer extensions are beneficial. We confirmed established rules for S. pyogenes cas9 sgRNA design and demonstrate that the complementarity region allows length variation and 5'-extensions. This enables generation of U6-promoter fusion templates by overlap-extension PCR with a standardized protocol. We present a series of PCR template vectors for C-terminal protein tagging and clonal Drosophila S2 cell lines with stable expression of a myc-tagged cas9 protein. The system can be used for epitope tagging or reporter gene knock-ins in an experimental setup that can in principle be fully automated. PMID:24748663

  8. TALEN-mediated homologous recombination in Daphnia magna.

    Science.gov (United States)

    Nakanishi, Takashi; Kato, Yasuhiko; Matsuura, Tomoaki; Watanabe, Hajime

    2015-01-01

    Transcription Activator-Like Effector Nucleases (TALENs) offer versatile tools to engineer endogenous genomic loci in various organisms. We established a homologous recombination (HR)-based knock-in using TALEN in the crustacean Daphnia magna, a model for ecological and toxicological genomics. We constructed TALENs and designed the 67 bp donor insert targeting a point deletion in the eyeless mutant that shows eye deformities. Co-injection of the TALEN mRNA with donor DNA into eggs led to the precise integration of the donor insert in the germ line, which recovered eye deformities in offspring. The frequency of HR events in the germ line was 2% by using both plasmid and single strand oligo DNA with 1.5 kb and 80 nt homology to the target. Deficiency of ligase 4 involved in non-homologous end joining repair did not increase the HR efficiency. Our data represent efficient HR-based knock-in by TALENs in D. magna, which is a promising tool to understand Daphnia gene functions. PMID:26674741

  9. Xenogeneic homologous genes, molecular evolution and cancer therapy

    Institute of Scientific and Technical Information of China (English)

    田聆; 魏于全

    2001-01-01

    Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.

  10. Quantifying homologous replacement of loci between haloarchaeal species.

    Science.gov (United States)

    Williams, David; Gogarten, J Peter; Papke, R Thane

    2012-01-01

    In vitro studies of the haloarchaeal genus Haloferax have demonstrated their ability to frequently exchange DNA between species, whereas rates of homologous recombination estimated from natural populations in the genus Halorubrum are high enough to maintain random association of alleles between five loci. To quantify the effects of gene transfer and recombination of commonly held (relaxed core) genes during the evolution of the class Halobacteria (haloarchaea), we reconstructed the history of 21 genomes representing all major groups. Using a novel algorithm and a concatenated ribosomal protein phylogeny as a reference, we created a directed horizontal genetic transfer (HGT) network of contemporary and ancestral genomes. Gene order analysis revealed that 90% of testable HGTs were by direct homologous replacement, rather than nonhomologous integration followed by a loss. Network analysis revealed an inverse log-linear relationship between HGT frequency and ribosomal protein evolutionary distance that is maintained across the deepest divergences in Halobacteria. We use this mathematical relationship to estimate the total transfers and amino acid substitutions delivered by HGTs in each genome, providing a measure of chimerism. For the relaxed core genes of each genome, we conservatively estimate that 11-20% of their evolution occurred in other haloarchaea. Our findings are unexpected, because the transfer and homologous recombination of relaxed core genes between members of the class Halobacteria disrupts the coevolution of genes; however, the generation of new combinations of divergent but functionally related genes may lead to adaptive phenotypes not available through cumulative mutations and recombination within a single population. PMID:23160063

  11. Membrane and Protein Interactions of the Pleckstrin Homology Domain Superfamily.

    Science.gov (United States)

    Lenoir, Marc; Kufareva, Irina; Abagyan, Ruben; Overduin, Michael

    2015-01-01

    The human genome encodes about 285 proteins that contain at least one annotated pleckstrin homology (PH) domain. As the first phosphoinositide binding module domain to be discovered, the PH domain recruits diverse protein architectures to cellular membranes. PH domains constitute one of the largest protein superfamilies, and have diverged to regulate many different signaling proteins and modules such as Dbl homology (DH) and Tec homology (TH) domains. The ligands of approximately 70 PH domains have been validated by binding assays and complexed structures, allowing meaningful extrapolation across the entire superfamily. Here the Membrane Optimal Docking Area (MODA) program is used at a genome-wide level to identify all membrane docking PH structures and map their lipid-binding determinants. In addition to the linear sequence motifs which are employed for phosphoinositide recognition, the three dimensional structural features that allow peripheral membrane domains to approach and insert into the bilayer are pinpointed and can be predicted ab initio. The analysis shows that conserved structural surfaces distinguish which PH domains associate with membrane from those that do not. Moreover, the results indicate that lipid-binding PH domains can be classified into different functional subgroups based on the type of membrane insertion elements they project towards the bilayer. PMID:26512702

  12. Accelerated homologous recombination and subsequent genome modification in Drosophila.

    Science.gov (United States)

    Baena-Lopez, Luis Alberto; Alexandre, Cyrille; Mitchell, Alice; Pasakarnis, Laurynas; Vincent, Jean-Paul

    2013-12-01

    Gene targeting by 'ends-out' homologous recombination enables the deletion of genomic sequences and concurrent introduction of exogenous DNA with base-pair precision without sequence constraint. In Drosophila, this powerful technique has remained laborious and hence seldom implemented. We describe a targeting vector and protocols that achieve this at high frequency and with very few false positives in Drosophila, either with a two-generation crossing scheme or by direct injection in embryos. The frequency of injection-mediated gene targeting can be further increased with CRISPR-induced double-strand breaks within the region to be deleted, thus making homologous recombination almost as easy as conventional transgenesis. Our targeting vector replaces genomic sequences with a multifunctional fragment comprising an easy-to-select genetic marker, a fluorescent reporter, as well as an attP site, which acts as a landing platform for reintegration vectors. These vectors allow the insertion of a variety of transcription reporters or cDNAs to express tagged or mutant isoforms at endogenous levels. In addition, they pave the way for difficult experiments such as tissue-specific allele switching and functional analysis in post-mitotic or polyploid cells. Therefore, our method retains the advantages of homologous recombination while capitalising on the mutagenic power of CRISPR. PMID:24154526

  13. Membrane and Protein Interactions of the Pleckstrin Homology Domain Superfamily

    Directory of Open Access Journals (Sweden)

    Marc Lenoir

    2015-10-01

    Full Text Available The human genome encodes about 285 proteins that contain at least one annotated pleckstrin homology (PH domain. As the first phosphoinositide binding module domain to be discovered, the PH domain recruits diverse protein architectures to cellular membranes. PH domains constitute one of the largest protein superfamilies, and have diverged to regulate many different signaling proteins and modules such as Dbl homology (DH and Tec homology (TH domains. The ligands of approximately 70 PH domains have been validated by binding assays and complexed structures, allowing meaningful extrapolation across the entire superfamily. Here the Membrane Optimal Docking Area (MODA program is used at a genome-wide level to identify all membrane docking PH structures and map their lipid-binding determinants. In addition to the linear sequence motifs which are employed for phosphoinositide recognition, the three dimensional structural features that allow peripheral membrane domains to approach and insert into the bilayer are pinpointed and can be predicted ab initio. The analysis shows that conserved structural surfaces distinguish which PH domains associate with membrane from those that do not. Moreover, the results indicate that lipid-binding PH domains can be classified into different functional subgroups based on the type of membrane insertion elements they project towards the bilayer.

  14. Homologous recombination in DNA repair and DNA damage tolerance

    Institute of Scientific and Technical Information of China (English)

    Xuan Li; Wolf-Dietrich Heyer

    2008-01-01

    Homologous recombination (HR) comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks (DSBs) and interstrand crosslinks (ICLs). In addition, recombination provides critical sup-port for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR: homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modaUties of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.

  15. Characterization and sequence analysis of the F2 promoter from corynephage BFK20

    International Nuclear Information System (INIS)

    F2 promoter from corynephage BFK20 was isolated and characterized. It was functional in Escherichia coli and Corynebacterium glutamicum. Cloning of the F2 promoter into the pJUP05 promoter probe vector caused an increase of the neomycin phosphotransferase II specific activity. According to the Northern blot hybridization the nptII gene was expressed from the cloned F2 promoter. The apparent transcription start point in E. coli and C. glutamicum was determined. The-35 region of F2 promoter showed high similarity to that of E. coli promoter consensus sequence, but its - 10 region was G+C rich and had no significant homology to that. (author)

  16. Identification of viruses and viroids by next-generation sequencing and homology-dependent and homology-independent algorithms.

    Science.gov (United States)

    Wu, Qingfa; Ding, Shou-Wei; Zhang, Yongjiang; Zhu, Shuifang

    2015-01-01

    A fast, accurate, and full indexing of viruses and viroids in a sample for the inspection and quarantine services and disease management is desirable but was unrealistic until recently. This article reviews the rapid and exciting recent progress in the use of next-generation sequencing (NGS) technologies for the identification of viruses and viroids in plants. A total of four viroids/viroid-like RNAs and 49 new plant RNA and DNA viruses from 18 known or unassigned virus families have been identified from plants since 2009. A comparison of enrichment strategies reveals that full indexing of RNA and DNA viruses as well as viroids in a plant sample at single-nucleotide resolution is made possible by one NGS run of total small RNAs, followed by data mining with homology-dependent and homology-independent computational algorithms. Major challenges in the application of NGS technologies to pathogen discovery are discussed. PMID:26047558

  17. New Proposal of Setal Homology in Schizomida and Revision of Surazomus (Hubbardiidae) from Ecuador

    OpenAIRE

    Osvaldo Villarreal Manzanilla; Gustavo Silva de Miranda; Alessandro Ponce de Leão Giupponi

    2016-01-01

    The homology of three somatic systems in Schizomida is studied yielding the following results: (1) proposal of homology and chaetotaxy of abdominal setae in Surazomus; (2) revision of the cheliceral chaetotaxy in Schizomida, with suggestion of new homology scheme between Hubbardiidae and Protoschizomidae, description of a new group of setae in Hubbardiinae (G7), and division of setae group 5 in two subgroups, G5A and G5B; (3) proposal of segmental homology between trimerous and tetramerous fe...

  18. Homology for higher-rank graphs and twisted C*-algebras

    OpenAIRE

    Kumjian, Alex; Pask, David; Sims, Aidan

    2011-01-01

    We introduce a homology theory for k-graphs and explore its fundamental properties. We establish connections with algebraic topology by showing that the homology of a k-graph coincides with the homology of its topological realisation as described by Kaliszewski et al. We exhibit combinatorial versions of a number of standard topological constructions, and show that they are compatible, from a homological point of view, with their topological counterparts. We show how to twist the C*-algebra o...

  19. Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew.

    OpenAIRE

    Freeman, R. M.; Plutzky, J; Neel, B G

    1992-01-01

    src homology 2 (SH2) domains direct binding to specific phosphotyrosyl proteins. Recently, SH2-containing protein-tyrosine-phosphatases (PTPs) were identified. Using degenerate oligonucleotides and the PCR, we have cloned a cDNA for an additional PTP, SH-PTP2, which contains two SH2 domains and is expressed ubiquitously. When expressed in Escherichia coli, SH-PTP2 displays tyrosine-specific phosphatase activity. Strong sequence similarity between SH-PTP2 and the Drosophila gene corkscrew (csw...

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

    Science.gov (United States)

    Keyamura, Kenji; Arai, Kota

    2016-01-01

    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. PMID:27390022

  1. Tomato Cf resistance proteins mediate recognition of cognate homologous effectors from fungi pathogenic on dicots and monocots.

    Science.gov (United States)

    Stergiopoulos, Ioannis; van den Burg, Harrold A; Okmen, Bilal; Beenen, Henriek G; van Liere, Sabine; Kema, Gert H J; de Wit, Pierre J G M

    2010-04-20

    Most fungal effectors characterized so far are species-specific and facilitate virulence on a particular host plant. During infection of its host tomato, Cladosporium fulvum secretes effectors that function as virulence factors in the absence of cognate Cf resistance proteins and induce effector-triggered immunity in their presence. Here we show that homologs of the C. fulvum Avr4 and Ecp2 effectors are present in other pathogenic fungi of the Dothideomycete class, including Mycosphaerella fijiensis, the causal agent of black Sigatoka disease of banana. We demonstrate that the Avr4 homolog of M. fijiensis is a functional ortholog of C. fulvum Avr4 that protects fungal cell walls against hydrolysis by plant chitinases through binding to chitin and, despite the low overall sequence homology, triggers a Cf-4-mediated hypersensitive response (HR) in tomato. Furthermore, three homologs of C. fulvum Ecp2 are found in M. fijiensis, one of which induces different levels of necrosis or HR in tomato lines that lack or contain a putative cognate Cf-Ecp2 protein, respectively. In contrast to Avr4, which acts as a defensive virulence factor, M. fijiensis Ecp2 likely promotes virulence by interacting with a putative host target causing host cell necrosis, whereas Cf-Ecp2 could possibly guard the virulence target of Ecp2 and trigger a Cf-Ecp2-mediated HR. Overall our data suggest that Avr4 and Ecp2 represent core effectors that are collectively recognized by single cognate Cf-proteins. Transfer of these Cf genes to plant species that are attacked by fungi containing these cognate core effectors provides unique ways for breeding disease-resistant crops. PMID:20368413

  2. Genetic selection and DNA sequences of 4.5S RNA homologs

    DEFF Research Database (Denmark)

    Brown, S; Thon, G; Tolentino, E

    1989-01-01

    A general strategy for cloning the functional homologs of an Escherichia coli gene was used to clone homologs of 4.5S RNA from other bacteria. The genes encoding these homologs were selected by their ability to complement a deletion of the gene for 4.5S RNA. DNA sequences of the regions encoding...

  3. Equidistribution of geodesics on homology classes and analogues for free groups

    DEFF Research Database (Denmark)

    Petridis, Y.N.; Risager, Morten

    2005-01-01

    We investigate how often geodesics have homology in a fixed set of the homology lattice of a compact Riemann surface. We prove that closed geodesics are equidistributed on a random set of homology classes and certain arithmetic sets. We explain the analogues for free groups, conjugacy classes and...... discrete logarithms, in particular, we investigate the density of conjugacy classes with relatively prime discrete logarithms....

  4. On mathematical arbitrariness of some papers on the potential homologous linear rule investigation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The history of homologous linear rule investigation is reviewed simply. The author puts forward a problem worth paying attention to in the recent potential homologous linear rule investigation, especially some mistakes made in these investigations on mathematical foundations. The author also exposes the mathematical arbitrariness of some papers on their potential homologous linear rule investigation.

  5. p21 controls patterning but not homologous recombination in RPE development.

    Science.gov (United States)

    Bishop, A J R; Kosaras, B; Hollander, M C; Fornace, A; Sidman, R L; Schiestl, R H

    2006-01-01

    p21/WAF1/CIP1/MDA6 is a key cell cycle regulator. Cell cycle regulation is an important part of development, differentiation, DNA repair and apoptosis. Following DNA damage, p53 dependent expression of p21 results in a rapid cell cycle arrest. p21 also appears to be important for the development of melanocytes, promoting their differentiation and melanogenesis. Here, we examine the effect of p21 deficiency on the development of another pigmented tissue, the retinal pigment epithelium. The murine mutation pink-eyed unstable (p(un)) spontaneously reverts to a wild-type allele by homologous recombination. In a retinal pigment epithelium cell this results in pigmentation, which can be observed in the adult eye. The clonal expansion of such cells during development has provided insight into the pattern of retinal pigment epithelium development. In contrast to previous results with Atm, p53 and Gadd45, p(un) reversion events in p21 deficient mice did not show any significant change. These results suggest that p21 does not play any role in maintaining overall genomic stability by regulating homologous recombination frequencies during development. However, the absence of p21 caused a distinct change in the positions of the reversion events within the retinal pigment epithelium. Those events that would normally arrest to produce single cell events continued to proliferate uncovering a cell cycle dysregulation phenotype. It is likely that p21 is involved in controlling the developmental pattern of the retinal pigment. We also found a C57BL/6J specific p21 dependent ocular defect in retinal folding, similar to those reported in the absence of p53. PMID:16202662

  6. OpaR, a Homolog of Vibrio harveyi LuxR, Controls Opacity of Vibrio parahaemolyticus

    Science.gov (United States)

    McCarter, Linda L.

    1998-01-01

    Vibrio parahaemolyticus is an organism well adapted to communal life on surfaces. When grown on a surface or in a viscous layer, the bacterium induces a large gene system and differentiates to swarmer cells capable of movement over and colonization of surfaces. V. parahaemolyticus displays additional phenotypic versatility manifested as variable colony morphology, switching between translucent and opaque colony types. Although not itself luminescent, V. parahaemolyticus produces autoinducer molecules capable of inducing luminescence in Vibrio harveyi. To examine the role of quorum signaling in the lifestyles of V. parahaemolyticus, the functional homolog of the gene encoding the V. harveyi autoinducer-controlled transcriptional regulatory protein LuxR was cloned. Sequence analysis of the clone predicted an open reading frame with a deduced product 96% identical to LuxR. Introduction of the clone carrying the luxR-like locus into V. parahaemolyticus dramatically affected colony morphology, converting a translucent strain to an opaque one. When the coding sequence for the luxR homolog was placed under the control of the Ptac promoter, conversion to the opaque phenotype became inducible by isopropyl-β-d-thiogalactopyranoside. Allelic disruption of the luxR-like gene on the chromosome of an opaque strain produced a translucent strain proficient in swarming ability. Primer extension mapping demonstrated opaR transcription in opaque but not translucent cell types. It is postulated that this gene, which has been named opaR, encodes a transcription factor controlling cell type. The underlying genetic basis for opaque-translucent variation may be the consequence of a genomic alteration detected in the opaR locus of opaque and translucent strains. PMID:9620967

  7. Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish

    International Nuclear Information System (INIS)

    Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors. - Highlights: • Zebra fish OGR1 and GPR4 homologs (zOGR1, zGPR4) are proton-sensing receptors. • The signaling pathways activated by zOGR1 and zGPR4 are different. • Histidine residues critical for sensing protons are conserved

  8. Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish

    Energy Technology Data Exchange (ETDEWEB)

    Mochimaru, Yuta [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan); Azuma, Morio [Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555 (Japan); Oshima, Natsuki; Ichijo, Yuta; Satou, Kazuhiro [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan); Matsuda, Kouhei [Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555 (Japan); Asaoka, Yoichi; Nishina, Hiroshi [Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510 (Japan); Nakakura, Takashi [Department of Anatomy, Graduate School of Medicine, Teikyo University, 2-11-1 Kaga Itabashi-Ku, Tokyo 173-8605 (Japan); Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tomura, Hideaki, E-mail: tomurah@meiji.ac.jp [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan)

    2015-02-20

    Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors. - Highlights: • Zebra fish OGR1 and GPR4 homologs (zOGR1, zGPR4) are proton-sensing receptors. • The signaling pathways activated by zOGR1 and zGPR4 are different. • Histidine residues critical for sensing protons are conserved.

  9. Building multiclass classifiers for remote homology detection and fold recognition

    Directory of Open Access Journals (Sweden)

    Karypis George

    2006-10-01

    Full Text Available Abstract Background Protein remote homology detection and fold recognition are central problems in computational biology. Supervised learning algorithms based on support vector machines are currently one of the most effective methods for solving these problems. These methods are primarily used to solve binary classification problems and they have not been extensively used to solve the more general multiclass remote homology prediction and fold recognition problems. Results We present a comprehensive evaluation of a number of methods for building SVM-based multiclass classification schemes in the context of the SCOP protein classification. These methods include schemes that directly build an SVM-based multiclass model, schemes that employ a second-level learning approach to combine the predictions generated by a set of binary SVM-based classifiers, and schemes that build and combine binary classifiers for various levels of the SCOP hierarchy beyond those defining the target classes. Conclusion Analyzing the performance achieved by the different approaches on four different datasets we show that most of the proposed multiclass SVM-based classification approaches are quite effective in solving the remote homology prediction and fold recognition problems and that the schemes that use predictions from binary models constructed for ancestral categories within the SCOP hierarchy tend to not only lead to lower error rates but also reduce the number of errors in which a superfamily is assigned to an entirely different fold and a fold is predicted as being from a different SCOP class. Our results also show that the limited size of the training data makes it hard to learn complex second-level models, and that models of moderate complexity lead to consistently better results.

  10. Construction of a novel kind of expression plasmid by homologous recombination in Saccharomyces cerevisiae

    Institute of Scientific and Technical Information of China (English)

    CHEN; Xiangling

    2005-01-01

    [1]Brunelli, J. P., Pall, M. L., A series of yeast vectors for expression of cDNAs and other DNA sequences, Yeast, 1993, 9: 1299―1308.[2]Sikorski, R. S., Hieter, P., A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae, Genetics, 1989, 122: 19―27.[3]Bonneaud, N., Ozier-Kalogerogoulos, O., Li, G. et al., A family of low and high copy replicative, integrative and single-stranded S. cerevisiae /E. coli shuttle vector, Yeast, 1991, 7: 609―615.[4]Huo, K. K., Yu, L. L., Chen, X. J., Li, Y. Y., A stable vector for high-level expression and secretion of human interferon alpha A in yeast, Science in China, Ser. B, 1993, 36(5): 557―567.[5]Zhou, Z. X., Yuan, H. Y., He, W. et al., Expression of the modified HBsAg gene SA-28 directed by a constitutive promoter, Journal of Fudan university (Natural Science), 2000, 39(3): 264―268.[6]Paques, F., Haber, J. E., Multiple pathways of recombination induces by double-strand breaks in Saccharomyces cerevisiae, Microbiology and Molecular Biology Reviews, 1999, 63(2): 349―404.[7]Martin, K., Damage-induced recombination in the yeast Saccharomyces cerevisiae, Mutation Research, 2000, 451: 91―105.[8]Alira, S., Tomoko, O., Homologous recombination and the roles of double-strand breaks, TIBS, 1995, 20: 387―391.[9]Patrick, S., Kelly, M. T., Stephen, V. K., Recombination factor of Saccharomyces cerevisiae, Mutation Research, 2000, 451: 257―275.[10]Manivasakam, P., Weber, S. C., McElver, J., Schiestl, R. H., Micro-homology mediated PCR targeting in Saccharomyces cerevisiae, Nucleic Acids Res., 1995, 23(14): 2799―2800.[11]Baudin, A., Lacroute, F., Cullin, C., A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae, Nucleic Acids Res., 1993, 21(14): 3329―3330.[12]Hua, S. B., Qiu, M., Chan, E., Zhu, L., Luo, Y., Minimum length of sequence homology required for in vivo cloning by homolo-gous recombination in yeast, Plasmid, 1997, 38

  11. The colocalization transition of homologous chromosomes at meiosis

    Science.gov (United States)

    Nicodemi, Mario; Panning, Barbara; Prisco, Antonella

    2008-06-01

    Meiosis is the specialized cell division required in sexual reproduction. During its early stages, in the mother cell nucleus, homologous chromosomes recognize each other and colocalize in a crucial step that remains one of the most mysterious of meiosis. Starting from recent discoveries on the system molecular components and interactions, we discuss a statistical mechanics model of chromosome early pairing. Binding molecules mediate long-distance interaction of special DNA recognition sequences and, if their concentration exceeds a critical threshold, they induce a spontaneous colocalization transition of chromosomes, otherwise independently diffusing.

  12. K-homology and Fredholm Operators II: Elliptic Operators

    OpenAIRE

    Baum, Paul; van Erp, Erik

    2016-01-01

    This is an expository paper which gives a proof of the Atiyah-Singer index theorem for elliptic operators. Specifcally, we compute the geometric K-cycle that corresponds to the analytic K-cycle determined by the operator. This paper and its companion ("K-homology and index theory II: Dirac Operators") was written to clear up basic points about index theory that are generally accepted as valid, but for which no proof has been published. Some of these points are needed for the solution of the H...

  13. Immunological response to the Brucella abortus GroEL homolog.

    OpenAIRE

    Lin, J.; Adams, L G; Ficht, T A

    1996-01-01

    Western blot (immunoblot) analysis of sera from cattle vaccinated with Brucella abortus S19 exhibit an elevated serologic response to Hsp62, the GroEL homolog (BaGroEL). Serologic screening of individual cows vaccinated with B. abortus S19 revealed no correlation between the immune response to BaGroEL and protection against a challenge with virulent organisms. The humoral immune response to BaGroEL was restricted to a region of the mature protein which mapped to amino acids 317 to 355 and may...

  14. Homological projective duality for linear systems with base locus

    OpenAIRE

    Carocci, Francesca; Turcinovic, Zak

    2015-01-01

    We show how blowing up varieties in base loci of linear systems gives a procedure for creating new homological projective duals from old. Starting with a HP dual pair $X,Y$ and smooth orthogonal linear sections $X_L,Y_L$, we prove that the blowup of $X$ in $X_L$ is naturally HP dual to $Y_L$. The result does not need $Y$ to exist as a variety, i.e. it may be "noncommutative". We extend the result to the case where the base locus $X_L$ is a multiple of a smooth variety and the universal hyperp...

  15. Length Formulas for the Homology of Generalized Koszul Complexes

    OpenAIRE

    Ichim, Bogdan; Vetter, Udo

    2005-01-01

    Let $M$ be a finite module over a noetherian ring $R$ with a free resolution of length 1. We consider the generalized Koszul complexes $\\mathcal{C}_{\\bar\\lambda}(t)$ associated with a map $\\bar\\lambda:M\\to\\mathcal{H}$ into a finite free $R$-module $\\mathcal{H}$ (see [IV], section 3), and investigate the homology of $\\mathcal{C}_{\\bar\\lambda}(t)$ in the special setup when $\\grade I_M=\\rank M=\\dim R$. ($I_M$ is the first non-vanishing Fitting ideal of $M$.) In this case the (interesting) homolo...

  16. Reducible Galois representations and the homology of GL(3,Z)

    CERN Document Server

    Ash, Avner

    2012-01-01

    We prove the following theorem: Let $\\bar\\F_p$ be an algebraic closure of a finite field of characteristic $p$. Let $\\rho$ be a continuous homomorphism from the absolute Galois group of $\\Q$ to $\\GL(3,\\bar\\F_p)$ which is isomorphic to a direct sum of a character and a two-dimensional odd irreducible representation. Under the condition that the conductor of $\\rho$ is squarefree, we prove that $\\rho$ is attached to a Hecke eigenclass in the homology of an arithmetic subgroup $\\Gamma$ of $\\GL(3,\\Z)$. In addition, we prove that the coefficient module needed is, in fact, predicted by a conjecture of Ash, Doud, Pollack, and Sinnott.

  17. Homology of the open moduli space of curves

    DEFF Research Database (Denmark)

    Madsen, Ib Henning

    2012-01-01

    This is a survey on the proof of a generalized version of the Mumford conjecture obtained in joint work with M. Weiss stating that a certain map between some classifying spaces which a priori have different natures induces an isomorphism at the level of integral homology. We also discuss our proo...... of the original Mumford conjecture stating that the stable rational cohomology of the moduli space of Riemann surfaces is a certain polynomial algebra generated by the Mumford–Morita–Miller cohomology classes of even degrees....

  18. Parallel Computation of Persistent Homology using the Blowup Complex

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Ryan [Stanford Univ., CA (United States); Morozov, Dmitriy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-04-27

    We describe a parallel algorithm that computes persistent homology, an algebraic descriptor of a filtered topological space. Our algorithm is distinguished by operating on a spatial decomposition of the domain, as opposed to a decomposition with respect to the filtration. We rely on a classical construction, called the Mayer--Vietoris blowup complex, to glue global topological information about a space from its disjoint subsets. We introduce an efficient algorithm to perform this gluing operation, which may be of independent interest, and describe how to process the domain hierarchically. We report on a set of experiments that help assess the strengths and identify the limitations of our method.

  19. Discovery of a Homolog of Siderophilin in a Plant

    Institute of Scientific and Technical Information of China (English)

    Yun-Biao FEI; Peng-Xiu CAO; Su-Qin GAO; Ling-Bo WEI; Bin WANG

    2005-01-01

    Members belonging to the siderophilin family are iron-binding and iron-transporting proteins,which includes transferrin and lactoferrin. They have only been found in animals previously. If siderophilin could be found in and isolated from a plant, its production and subsequent extensive application could be increased. The present study is the first to report the discovery of a homolog of siderophilin in a plant. In order to purify antifreeze proteins from Ammopiptanthus mongolicus (Maxim.) Cheng f., the authors processed the proteins from the leaves using techniques such as column chromatography using DEAE-Cellulose-52, gel filtration via Sephacryl S-100 HR medium, hydrophobic interaction chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mass spectroscopy was performed on the three proteins purified and the sequence of one of the proteins (containing 32 amino acids) was found to have 97%homology with the corresponding part of one type of human lactoferrin. Moreover, one of the two peptides belongs to an iron-binding domain. So, it is possible that siderophilin also exists in plants and plays a role as an antibacterial and antifungal, among other actions.

  20. Using persistent homology and dynamical distances to analyze protein binding.

    Science.gov (United States)

    Kovacev-Nikolic, Violeta; Bubenik, Peter; Nikolić, Dragan; Heo, Giseon

    2016-03-01

    Persistent homology captures the evolution of topological features of a model as a parameter changes. The most commonly used summary statistics of persistent homology are the barcode and the persistence diagram. Another summary statistic, the persistence landscape, was recently introduced by Bubenik. It is a functional summary, so it is easy to calculate sample means and variances, and it is straightforward to construct various test statistics. Implementing a permutation test we detect conformational changes between closed and open forms of the maltose-binding protein, a large biomolecule consisting of 370 amino acid residues. Furthermore, persistence landscapes can be applied to machine learning methods. A hyperplane from a support vector machine shows the clear separation between the closed and open proteins conformations. Moreover, because our approach captures dynamical properties of the protein our results may help in identifying residues susceptible to ligand binding; we show that the majority of active site residues and allosteric pathway residues are located in the vicinity of the most persistent loop in the corresponding filtered Vietoris-Rips complex. This finding was not observed in the classical anisotropic network model. PMID:26812805

  1. Characterization of a canine homolog of hepatitis C virus.

    Science.gov (United States)

    Kapoor, Amit; Simmonds, Peter; Gerold, Gisa; Qaisar, Natasha; Jain, Komal; Henriquez, Jose A; Firth, Cadhla; Hirschberg, David L; Rice, Charles M; Shields, Shelly; Lipkin, W Ian

    2011-07-12

    An estimated 3% of the world's population is chronically infected with hepatitis C virus (HCV). Although HCV was discovered more than 20 y ago, its origin remains obscure largely because no closely related animal virus homolog has been identified; furthermore, efforts to understand HCV pathogenesis have been hampered by the absence of animal models other than chimpanzees for human disease. Here we report the identification in domestic dogs of a nonprimate hepacivirus. Comparative phylogenetic analysis of the canine hepacivirus (CHV) confirmed it to be the most genetically similar animal virus homolog of HCV. Bayesian Markov chains Monte Carlo and associated time to most recent common ancestor analyses suggest a mean recent divergence time of CHV and HCV clades within the past 500-1,000 y, well after the domestication of canines. The discovery of CHV may provide new insights into the origin and evolution of HCV and a tractable model system with which to probe the pathogenesis, prevention, and treatment of diseases caused by hepacivirus infection. PMID:21610165

  2. Gimeracil sensitizes cells to radiation via inhibition of homologous recombination

    International Nuclear Information System (INIS)

    Background and purpose: 5-Chloro-2,4-dihydroxypyridine (Gimeracil) is a component of an oral fluoropyrimidine derivative S-1. Gimeracil is originally added to S-1 to yield prolonged 5-FU concentrations in tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We found that Gimeracil by itself had the radiosensitizing effect. Methods and materials: We used various cell lines deficient in non-homologous end-joining (NHEJ) or homologous recombination (HR) as well as DLD-1 and HeLa in clonogenic assay. γ-H2AX focus formation and SCneo assay was performed to examine the effects of Gimeracil on DNA double strand break (DSB) repair mechanisms. Results: Results of γ-H2AX focus assay indicated that Gimeracil inhibited DNA DSB repair. It did not sensitize cells deficient in HR but sensitized those deficient in NHEJ. In SCneo assay, Gimeracil reduced the frequency of neo-positive clones. Additionally, it sensitized the cells in S-phase more than in G0/G1. Conclusions: Gimeracil inhibits HR. Because HR plays key roles in the repair of DSBH caused by radiotherapy, Gimeracil may enhance the efficacy of radiotherapy through the suppression of HR-mediated DNA repair pathways.

  3. Open-closed field theories, string topology, and Hochschild homology

    CERN Document Server

    Blumberg, Andrew J; Teleman, Constantin

    2009-01-01

    In this expository paper we discuss a project regarding the string topology of a manifold, that was inspired by recent work of Moore-Segal, Costello, and Hopkins and Lurie, on "open-closed topological conformal field theories". Given a closed, oriented manifold M, we describe the "string topology category" S_M, which is enriched over chain complexes over a fixed field k. The objects of S_M are connected, closed, oriented submanifolds N of M, and the complex of morphisms between N_1 and N_2 is a chain complex homotopy equivalent to the singular chains C_*(P_{N_1, N_2}), where C_*(P_{N_1, N_2}) is the space of paths in M that start in N_1 and end in N_2. The composition pairing in this category is a chain model for the open string topology operations of Sullivan and expanded upon by Harrelson, and Ramirez. We will describe a calculation yielding that the Hochschild homology of the category S_M is the homology of the free loop space, LM. Another part of the project is to calculate the Hochschild cohomology of th...

  4. Non-homologous end joining: advances and frontiers.

    Science.gov (United States)

    Yang, Kai; Guo, Rong; Xu, Dongyi

    2016-07-01

    DNA double-strand breaks (DSBs) are the most serious form of DNA damage. In human cells, non-homologous end joining (NHEJ) is the major pathway for the repair of DSBs. Different types of DSBs result in different subsets of NHEJ repair strategies. These variations in NHEJ repair strategies depend on numerous elements, such as the flexible recruitment of NHEJ-related proteins, the complexity of the DSB ends, and the spatial- and temporal-ordered formation of the multi-protein complex. On the one hand, current studies of DNA DSBs repair focus on the repair pathway choices between homologous recombination and classic or alternative NHEJ. On the other hand, increasing researches have also deepened the significance and dug into the cross-links between the NHEJ pathway and the area of genome organization and aging. Although remarkable progress has been made in elucidating the underlying principles during the past decades, the detailed mechanism of action in response to different types of DSBs remains largely unknown and needs further evaluation in the future study. PMID:27217473

  5. Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems

    Directory of Open Access Journals (Sweden)

    Michael A. Choma

    2011-05-01

    The physiology of the Drosophila melanogaster cardiovascular system remains poorly characterized compared with its vertebrate counterparts. Basic measures of physiological performance remain unknown. It also is unclear whether subtle physiological defects observed in the human cardiovascular system can be reproduced in D. melanogaster. Here we characterize the cardiovascular physiology of D. melanogaster in its pre-pupal stage by using high-speed dye angiography and optical coherence tomography. The heart has vigorous pulsatile contractions that drive intracardiac, aortic and extracellular-extravascular hemolymph flow. Several physiological measures, including weight-adjusted cardiac output, body-length-adjusted aortic velocities and intracardiac shear forces, are similar to those in the closed vertebrate cardiovascular systems, including that of humans. Extracellular-extravascular flow in the pre-pupal D. melanogaster circulation drives convection-limited fluid transport. To demonstrate homology in heart dysfunction, we showed that, at the pre-pupal stage, a troponin I mutant, held-up2 (hdp2, has impaired systolic and diastolic heart wall velocities. Impaired heart wall velocities occur in the context of a non-dilated phenotype with a mildly depressed fractional shortening. We additionally derive receiver operating characteristic curves showing that heart wall velocity is a potentially powerful discriminator of systolic heart dysfunction. Our results demonstrate physiological homology and support the use of D. melanogaster as an animal model of complex cardiovascular disease.

  6. On discrete symmetries and torsion homology in F-theory

    Science.gov (United States)

    Mayrhofer, Christoph; Palti, Eran; Till, Oskar; Weigand, Timo

    2015-06-01

    We study the relation between discrete gauge symmetries in F-theory compactifications and torsion homology on the associated Calabi-Yau manifold. Focusing on the simplest example of a symmetry, we show that there are two physically distinct ways that such a discrete gauge symmetry can arise. First, compactifications of M-Theory on Calabi-Yau threefolds which support a genus-one fibration with a bi-section are known to be dual to six-dimensional F-theory vacua with a gauge symmetry. We show that the resulting five-dimensional theories do not have a symmetry but that the latter emerges only in the F-theory decompactification limit. Accordingly the genus-one fibred Calabi-Yau manifolds do not exhibit torsion in homology. Associated to the bi-section fibration is a Jacobian fibration which does support a section. Compactifying on these related but distinct varieties does lead to a symmetry in five dimensions and, accordingly, we find explicitly an associated torsion cycle. We identify the expected particle and membrane system of the discrete symmetry in terms of wrapped M2 and M5 branes and present a field-theory description of the physics for both cases in terms of circle reductions of six-dimensional theories. Our results and methods generalise straightforwardly to larger discrete symmetries and to four-dimensional compactifications.

  7. Tpr homologs in Treponema paraluiscuniculi Cuniculi A strain.

    Science.gov (United States)

    Giacani, Lorenzo; Sun, Eileen S; Hevner, Karin; Molini, Barbara J; Van Voorhis, Wesley C; Lukehart, Sheila A; Centurion-Lara, Arturo

    2004-11-01

    Treponema paraluiscuniculi, the etiologic agent of rabbit venereal syphilis, is morphologically indistinguishable from Treponema pallidum subsp. pallidum (T. pallidum), the human syphilis treponeme, and induces similar immune responses and histopathologic changes in the infected host. Because of their high degree of relatedness, comparative studies are likely to identify genetic determinants that contribute to pathogenesis or virulence in human syphilis. The tpr (Treponema pallidum repeat) genes are believed to code for potential virulence factors. In this study, we identified 10 tpr homologs in Treponema paraluiscuniculi Cuniculi A strain and determined their sequence architecture. Half of this group of paralogous genes were predicted to be nonfunctional due to the presence of frameshifts and premature stop codons. Furthermore, the immune response against the T. paraluiscuniculi Tpr homologs in long-term-infected rabbits was studied by enzyme-linked immunosorbent assay and lymphocyte proliferation assay, showing that TprK is the only target of the antibody and T-cell responses during experimental infection and emphasizing the importance of this putative virulence factor in venereal treponematosis. PMID:15501788

  8. Patterning of inflorescences and flowers by the F-Box protein DOUBLE TOP and the LEAFY homolog ABERRANT LEAF AND FLOWER of petunia.

    Science.gov (United States)

    Souer, Erik; Rebocho, Alexandra B; Bliek, Mattijs; Kusters, Elske; de Bruin, Robert A M; Koes, Ronald

    2008-08-01

    Angiosperms display a wide variety of inflorescence architectures differing in the positions where flowers or branches arise. The expression of floral meristem identity (FMI) genes determines when and where flowers are formed. In Arabidopsis thaliana, this is regulated via transcription of LEAFY (LFY), which encodes a transcription factor that promotes FMI. We found that this is regulated in petunia (Petunia hybrida) via transcription of a distinct gene, DOUBLE TOP (DOT), a homolog of UNUSUAL FLORAL ORGANS (UFO) from Arabidopsis. Mutation of DOT or its tomato (Solanum lycopersicum) homolog ANANTHA abolishes FMI. Ubiquitous expression of DOT or UFO in petunia causes very early flowering and transforms the inflorescence into a solitary flower and leaves into petals. Ectopic expression of DOT or UFO together with LFY or its homolog ABERRANT LEAF AND FLOWER (ALF) in petunia seedlings activates genes required for identity or outgrowth of organ primordia. DOT interacts physically with ALF, suggesting that it activates ALF by a posttranslational mechanism. Our findings suggest a wider role than previously thought for DOT and UFO in the patterning of flowers and indicate that the different roles of LFY and UFO homologs in the spatiotemporal control of floral identity in distinct species result from their divergent expression patterns. PMID:18713949

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

    International Nuclear Information System (INIS)

    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.

  10. 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.

  11. New promoters for strain engineering of Penicillium chrysogenum.

    Science.gov (United States)

    Polli, Fabiola; Meijrink, Ben; Bovenberg, Roel A L; Driessen, Arnold J M

    2016-04-01

    Filamentous fungi such as Aspergillus and Penicillium are widely used as hosts for the industrial products such as proteins and secondary metabolites. Although filamentous fungi are versatile in recognizing transcriptional and translational elements present in genes from other filamentous fungal species, only few promoters have been applied and compared in performance so far in Penicillium chrysogenum. Therefore, a set of homologous and heterologous promoters were tested in a reporter system to obtain a set of potential different strengths. Through in vivo homologous recombination in Saccharomyces cerevisiae, twelve Aspergillus niger and P. chrysogenum promoter-reporter pathways were constructed that drive the expression of green fluorescent protein while concurrent expression of the red fluorescent protein was used as an internal standard and placed under control of the PcPAF promoter. The pathways were integrated into the genome of P. chrysogenum and tested using the BioLector system for fermentation. Reporter gene expression was monitored during growth and classified according to promoter strength and expression profile. A set of novel promoters was obtained that can be used to tune the expression of target genes in future strain engineering programs. PMID:26701309

  12. Lunar scout: A Project Artemis proposal

    Science.gov (United States)

    1992-01-01

    The results of a student project to design a lunar lander in the context of a specifically defined mission are presented. The Lunar Scout will be launched from Cape Canaveral, Florida onboard a Delta II launch vehicle. The Delta II will carry the lander and its payload to a 1367 km orbit. Once it reaches that altitude, a STAR 48A solid rocket motor will kick the spacecraft into a lunar trajectory. After burnout of the lunar insertion motor, it will be jettisoned from the spacecraft. The flight from the earth to the moon will take approximately 106.4 hours. During this time the battery, which was fully charged prior to launch, will provide all power to the spacecraft. Every hour, the spacecraft will use its sun sensors and star trackers to update its position, maintain some stabilization and relay it back to earth using the dipole antennas. At the start of its lunar trajectory, the spacecraft will fire one of its 1.5 N thrusters to spin in at a very small rate. The main reason for this is to prevent one side of the spacecraft from overheating in the sun. When the spacecraft nears the moon, it will orient itself for the main retro burn. At an altitude of 200 km, a 4400 N bipropellant liquid thruster will ignite to slow the spacecraft. During the burn, the radar altimeter will be turned on to guide the spacecraft. The main retro rocket will slow the lander to 10 m/s at an approximate altitude of 40 km above the moon. From there, the space craft will use four 4.5 N hydrazine vertical thrusters and 1.5 N horizontal thrusters to guide the spacecraft to a soft landing. Once on the ground, the lander will shutoff the radar and attitude control systems. After the debris from the impact has settled, the six solar panels will be deployed to begin recharging the batteries and to power up the payload. The feedhorn antenna will then rotate to fix itself on the earth. Once it moves, it will stay in that position for the spacecraft's lifetime. The payload will then be activated to begin the lunar mission.

  13. The graded Jacobi algebras and (co)homology

    International Nuclear Information System (INIS)

    Jacobi algebroids (i.e. 'Jacobi versions' of Lie algebroids) are studied in the context of graded Jacobi brackets on graded commutative algebras. This unifies various concepts of graded Lie structures in geometry and physics. A method of describing such structures by classical Lie algebroids via certain gauging (in the spirit of E Witten's gauging of the exterior derivative) is developed. One constructs a corresponding Cartan differential calculus (graded commutative one) in a natural manner. This, in turn, gives canonical generating operators for triangular Jacobi algebroids. One gets, in particular, the Lichnerowicz-Jacobi homology operators associated with classical Jacobi structures. Courant-Jacobi brackets are obtained in a similar way and used to define an abstract notion of a Courant-Jacobi algebroid and Dirac-Jacobi structure

  14. Homology Models of Melatonin Receptors: Challenges and Recent Advances

    Directory of Open Access Journals (Sweden)

    Silvia Rivara

    2013-04-01

    Full Text Available Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs, named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putative bioactive conformations of ligands. The receptor models will be described, and they will be discussed in light of the available information from mutagenesis experiments and ligand-based pharmacophore models. The ability of these ligand-receptor complexes to rationalize structure-activity relationships of known series of melatonergic compounds will be commented upon.

  15. Quota Complexes, Persistant Homology and the Goldbach Conjecture

    CERN Document Server

    Pakianathan, Jonathan

    2011-01-01

    In this paper we introduce the concept of a quota complex and study how the topology of these quota complexes changes as the quota is changed. This problem is a simple "linear" version of the general question in Morse Theory of how the topology of a space varies with a parameter. We give examples of natural and basic quota complexes where this problem codifies questions about the distribution of primes, squares and divisors in number theory and as an example provide natural topological formulations of the prime number theorem, the twin prime conjecture, Goldbach's conjecture, Lehmer's conjecture, the Riemann Hypothesis and the existance of odd perfect numbers among other things. We also consider random quota complexes associated to sequences of independent random variables and show that various formulas for expected topological quantities give L-series and Euler product analogs of interest. Keywords: Quota system, persistant homology, Goldbach conjecture, Riemann Hypothesis, random complexes.

  16. Homological interpretation of extensions and biextensions of 1-motives

    OpenAIRE

    Bertolin, Cristiana

    2008-01-01

    Let k be a separably closed field. Let K_i=[A_i \\to B_i] (for i=1,2,3) be three 1-motives defined over k. We define the geometrical notions of extension of K_1 by K_3 and of biextension of (K_1,K_2) by K_3. We then compute the homological interpretation of these new geometrical notions: namely, the group Biext^0(K_1,K_2;K_3) of automorphisms of any biextension of (K_1,K_2) by K_3 is canonically isomorphic to the cohomology group Ext^0(K_1 \\otimes K_2,K_3), and the group Biext^1(K_1,K_2;K_3) o...

  17. Future trypanosomatid phylogenies: refined homologies, supertrees and networks

    Directory of Open Access Journals (Sweden)

    Stothard JR

    2000-01-01

    Full Text Available There has been good progress in inferring the evolutionary relationships within trypanosomes from DNA data as until relatively recently, many relationships have remained rather speculative. Ongoing molecular studies have provided data that have adequately shown Trypanosoma to be monophyletic and, rather surprisingly, that there are sharply contrasting levels of genetic variation within and between the major trypanosomatid groups. There are still, however, areas of research that could benefit from further development and resolution that broadly fall upon three questions. Are the current statements of evolutionary homology within ribosomal small sub-unit genes in need of refinement? Can the published phylograms be expanded upon to form `supertrees' depicting further relationships? Does a bifurcating tree structure impose an untenable dogma upon trypanosomatid phylogeny where hybridisation or reticulate evolutionary steps have played a part? This article briefly addresses these three questions and, in so doing, hopes to stimulate further interest in the molecular evolution of the group.

  18. Optimised fine and coarse parallelism for sequence homology search.

    Science.gov (United States)

    Meng, Xiandong; Chaudhary, Vipin

    2006-01-01

    New biological experimental techniques are continuing to generate large amounts of data using DNA, RNA, human genome and protein sequences. The quantity and quality of data from these experiments makes analyses of their results very time-consuming, expensive and impractical. Searching on DNA and protein databases using sequence comparison algorithms has become one of the most powerful techniques to better understand the functionality of particular DNA, RNA, genome, or protein sequence. This paper presents a technique to effectively combine fine and coarse grain parallelism using general-purpose processors for sequence homology database searches. The results show that the classic Smith-Waterman sequence alignment algorithm achieves super linear performance with proper scheduling and multi-level parallel computing at no additional cost. PMID:18048183

  19. Homological finiteness properties of monoids, their ideals and maximal subgroups

    CERN Document Server

    Gray, Robert

    2010-01-01

    We consider the general question of how the homological finiteness property left-FPn holding in a monoid influences, and conversely depends on, the property holding in the substructures of that monoid. In particular we show that left-FPn is inherited by the maximal subgroups in a completely simple minimal ideal, in the case that the minimal ideal has finitely many left ideals. For completely simple semigroups we prove the converse, and as a corollary show that a completely simple semigroup is of type left- and right-FPn if and only if it has finitely many left and right ideals and all of its maximal subgroups are of type FPn. Also, given an ideal of a monoid, we show that if the ideal has a two-sided identity element then the containing monoid is of type left-FPn if and only if the ideal is of type left-FPn.

  20. Representation theory a homological algebra point of view

    CERN Document Server

    Zimmermann, Alexander

    2014-01-01

      Introducing the representation theory of groups and finite dimensional algebras, this book first studies basic non-commutative ring theory, covering the necessary background of elementary homological algebra and representations of groups to block theory. It further discusses vertices, defect groups, Green and Brauer correspondences and Clifford theory. Whenever possible the statements are presented in a general setting for more general algebras, such as symmetric finite dimensional algebras over a field. Then, abelian and derived categories are introduced in detail and are used to explain stable module categories, as well as derived categories and their main invariants and links between them. Group theoretical applications of these theories are given – such as the structure of blocks of cyclic defect groups – whenever appropriate. Overall, many methods from the representation theory of algebras are introduced. Representation Theory assumes only the most basic knowledge of linear algebra, groups, rings ...

  1. Development and characterization of a homologous radioimmunoassay for equine prolactin

    International Nuclear Information System (INIS)

    A specific and sensitive homologous radioimmunoassay has been developed for equine prolactin, suitable for measuring prolactin concentrations in serum of horses. The sensitivity of the assay ranged from 0.4 to 0.6 ng/ml and the intra- and inter-assay coefficients of variation averaged 6.9 and 15.4%, respectively, for five doses of hormone. Cross-reactivity with other mammalian and nonmammalian prolactins and growth hormones was less than 20 and 0.3%, respectively. Cross-reactivity with equine growth hormone was less than 0.07%. Equine serum and pituitary extracts showed parallel dilution-response curves with equine prolactin. The percentage recovery of exogenous equine prolactin in serum was 89%. Preliminary analysis of several physiological samples (stallions, pregnant, and nonpregnant mares) yielded values from 0.6 to 12.0 ng/ml

  2. Studies of Flerovium and Element 115 Homologs with Macrocyclic Extractants

    International Nuclear Information System (INIS)

    Study of the chemistry of the heaviest elements, Z >= 104, poses a unique challenge due to their low production cross-sections and short half-lives. Chemistry also must be studied on the one-atom-at-a-time scale, requiring automated, fast, and very efficient chemical schemes. Recent studies of the chemical behavior of copernicium (Cn, element 112) and flerovium (Fl, element 114) together with the discovery of isotopes of these elements with half-lives suitable for chemical studies have spurred a renewed interest in the development of rapid systems designed to study the chemical properties of elements with Z >= 114. This dissertation explores both extraction chromatography and solvent extraction as methods for development of a rapid chemical separation scheme for the homologs of flerovium (Pb, Sn, Hg) and element 115 (Bi, Sb), with the goal of developing a chemical scheme that, in the future, can be applied to on-line chemistry of both Fl and element 115. Carrier-free radionuclides, used in these studies, of the homologs of Fl and element 115 were obtained by proton activation of high-purity metal foils at the Lawrence Livermore National Laboratory (LLNL) Center for Accelerator Mass Spectrometry (CAMS): natIn(p,n)113Sn, natSn(p,n)124Sb, and Au(p,n)197m,gHg. The carrier-free activity was separated from the foils by novel separation schemes based on ion exchange and extraction chromatography techniques. Carrier-free Pb and Bi isotopes were obtained from development of a novel generator based on cation exchange chromatography using the 232U parent to generate 212Pb and 212Bi. Macrocyclic extractants, specifically crown ethers and their derivatives, were chosen for these studies; crown ethers show high selectivity for metal ions. Finally. a potential chemical system for Fl was established based on the Eichrom Pb resin, and insight to an improved system based on thiacrown ethers is presented.

  3. Internal and External Reconnection Series Homologous Solar Flares

    Science.gov (United States)

    Sterling, Alphonse C.; Moore, Ronald L.

    2001-01-01

    Using data from the extreme ultraviolet imaging telescope (EIT) on SOHO and the soft X-ray telescope (SXT) on Yohkoh, we examine a series of morphologically homologous solar flares occurring in National Oceanic and Atmospheric Administration (NOAA) active region 8210 over May 1-2, 1998. An emerging flux region (EFR) impacted against a sunspot to the west and next to a coronal hole to the east is the source of the repeated flaring. An SXT sigmoid parallels the EFR's neutral line at the site of the initial flaring in soft X rays. In EIT each flaring episode begins with the formation of a crinkle pattern external to the EFR. These EIT crinkles move out from, and then in toward, the EFR with velocities approx. 20 km/ s. A shrinking and expansion of the width of the coronal hole coincides with the crinkle activity, and generation and evolution of a postflare loop system begins near the time of crinkle formation. Using a schematic based on magnetograms of the region, we suggest that these observations are consistent with the standard reconnection-based model for solar eruptions but are modified by the presence of the additional magnetic fields of the sunspot and coronal hole. In the schematic, internal reconnection begins inside of the EFR-associated fields, unleashing a flare, postflare loops, and a coronal mass ejection (CME). External reconnection, first occurring between the escaping CME and the coronal hole field and second occurring between fields formed as a result of the first external reconnection, results in the EIT crinkles and changes in the coronal hole boundary. By the end of the second external reconnection, the initial setup is reinstated; thus the sequence can repeat, resulting in morphologically homologous eruptions. Our inferred magnetic topology is similar to that suggested in the "breakout model" of eruptions although we cannot determine if our eruptions are released primarily by the breakout mechanism (external reconnection) or, alternatively

  4. A rat homolog of the mouse deafness mutant jerker (je).

    Science.gov (United States)

    Truett, G E; Walker, J A; Brock, J W

    1996-05-01

    An autosomal recessive deafness mutant was discovered in our colony of Zucker (ZUC) rats. These mutants behave like shaker-waltzer deafness mutants, and their inner ear pathology classifies them among neuroepithelial degeneration type of deafness mutants. To determine whether this rat deafness mutation (-) defines a unique locus or one that has been previously described, we mapped its chromosomal location. F2 progeny of (Pbrc:ZUC x BN/Crl) A/a B/b H/h +/- F1 rats were scored for coat color and behavioral phenotypes. Segregation analysis indicated that the deafness locus might be loosely linked with B on rat Chromosome (Chr) 5 (RNO5). Therefore, 40 -/- rats were scored for BN and ZUC alleles at four additional loci, D5Mit11, D5Mit13, Oprd1, and Gnb1, known to map to RNO5 or its homolog, mouse Chr 4 (MMU4). Linkage analysis established the gene order (cM distance) as D5Mit11-(19.3)-B-(17.9)-D5Mit13-(19. 2)-Oprd1-(21.5) - (1.2) Gnb1, placing the deafness locus on distal RNO5. The position of the deafness locus on RNO5 is similar to that ofjerker (je) on MMU4; the phenotypes and patterns of inheritance of the deafness mutation and je are also similar. It seems likely that the mutation affects the rat homolog of je. The rat deafness locus should, therefore, be named jerker and assigned the gene symbol Je. PMID:8661723

  5. Dynamic evolution of rht-1 homologous regions in grass genomes.

    Directory of Open Access Journals (Sweden)

    Jing Wu

    Full Text Available Hexaploid bread wheat contains A, B, and D three subgenomes with its well-characterized ancestral genomes existed at diploid and tetraploid levels, making the wheat act as a good model species for studying evolutionary genomic dynamics. Here, we performed intra- and inter-species comparative analyses of wheat and related grass genomes to examine the dynamics of homologous regions surrounding Rht-1, a well-known "green revolution" gene. Our results showed that the divergence of the two A genomes in the Rht-1 region from the diploid and tetraploid species is greater than that from the tetraploid and hexaploid wheat. The divergence of D genome between diploid and hexaploid is lower than those of A genome, suggesting that D genome diverged latter than others. The divergence among the A, B and D subgenomes was larger than that among different ploidy levels for each subgenome which mainly resulted from genomic structural variation of insertions and, perhaps deletions, of the repetitive sequences. Meanwhile, the repetitive sequences caused genome expansion further after the divergence of the three subgenomes. However, several conserved non-coding sequences were identified to be shared among the three subgenomes of wheat, suggesting that they may have played an important role to maintain the homolog of three subgenomes. This is a pilot study on evolutionary dynamics across the wheat ploids, subgenomes and differently related grasses. Our results gained new insights into evolutionary dynamics of Rht-1 region at sequence level as well as the evolution of wheat during the plolyploidization process.

  6. A quality metric for homology modeling: the H-factor

    Directory of Open Access Journals (Sweden)

    di Luccio Eric

    2011-02-01

    Full Text Available Abstract Background The analysis of protein structures provides fundamental insight into most biochemical functions and consequently into the cause and possible treatment of diseases. As the structures of most known proteins cannot be solved experimentally for technical or sometimes simply for time constraints, in silico protein structure prediction is expected to step in and generate a more complete picture of the protein structure universe. Molecular modeling of protein structures is a fast growing field and tremendous works have been done since the publication of the very first model. The growth of modeling techniques and more specifically of those that rely on the existing experimental knowledge of protein structures is intimately linked to the developments of high resolution, experimental techniques such as NMR, X-ray crystallography and electron microscopy. This strong connection between experimental and in silico methods is however not devoid of criticisms and concerns among modelers as well as among experimentalists. Results In this paper, we focus on homology-modeling and more specifically, we review how it is perceived by the structural biology community and what can be done to impress on the experimentalists that it can be a valuable resource to them. We review the common practices and provide a set of guidelines for building better models. For that purpose, we introduce the H-factor, a new indicator for assessing the quality of homology models, mimicking the R-factor in X-ray crystallography. The methods for computing the H-factor is fully described and validated on a series of test cases. Conclusions We have developed a web service for computing the H-factor for models of a protein structure. This service is freely accessible at http://koehllab.genomecenter.ucdavis.edu/toolkit/h-factor.

  7. BLANNOTATOR: enhanced homology-based function prediction of bacterial proteins

    Directory of Open Access Journals (Sweden)

    Kankainen Matti

    2012-02-01

    Full Text Available Abstract Background Automated function prediction has played a central role in determining the biological functions of bacterial proteins. Typically, protein function annotation relies on homology, and function is inferred from other proteins with similar sequences. This approach has become popular in bacterial genomics because it is one of the few methods that is practical for large datasets and because it does not require additional functional genomics experiments. However, the existing solutions produce erroneous predictions in many cases, especially when query sequences have low levels of identity with the annotated source protein. This problem has created a pressing need for improvements in homology-based annotation. Results We present an automated method for the functional annotation of bacterial protein sequences. Based on sequence similarity searches, BLANNOTATOR accurately annotates query sequences with one-line summary descriptions of protein function. It groups sequences identified by BLAST into subsets according to their annotation and bases its prediction on a set of sequences with consistent functional information. We show the results of BLANNOTATOR's performance in sets of bacterial proteins with known functions. We simulated the annotation process for 3090 SWISS-PROT proteins using a database in its state preceding the functional characterisation of the query protein. For this dataset, our method outperformed the five others that we tested, and the improved performance was maintained even in the absence of highly related sequence hits. We further demonstrate the value of our tool by analysing the putative proteome of Lactobacillus crispatus strain ST1. Conclusions BLANNOTATOR is an accurate method for bacterial protein function prediction. It is practical for genome-scale data and does not require pre-existing sequence clustering; thus, this method suits the needs of bacterial genome and metagenome researchers. The method and a

  8. Cubical homology and the Leech dimension of free partially commutative monoids

    International Nuclear Information System (INIS)

    The paper is devoted to problems arising when applying homological algebra to computer science. It is proved that the Leech dimension of a free partially commutative monoid is equal to the least upper bound of the cardinalities of finite subsets of pairwise commuting generators of the monoid. For an arbitrary free partially commutative monoid M(E,I) in which every subset of pairwise commuting generators is finite and for any contravariant natural system F on M(E,I) we construct a semicubical set T(E,I) with a homological system F-bar on this set such that the Leech homology groups Hn(M(E,I),F) are isomorphic to the cubical homology groups H-n(T(E,I),F-bar). Complexes of Abelian groups are also constructed enabling one to obtain (under additional finiteness conditions) algorithms for computing the Leech homology groups and homology groups with coefficients in right M(E,I)-modules. Bibliography: 16 titles.

  9. Cubical homology and the Leech dimension of free partially commutative monoids

    Science.gov (United States)

    Khusainov, Akhmet A.

    2008-12-01

    The paper is devoted to problems arising when applying homological algebra to computer science. It is proved that the Leech dimension of a free partially commutative monoid is equal to the least upper bound of the cardinalities of finite subsets of pairwise commuting generators of the monoid. For an arbitrary free partially commutative monoid M(E,I) in which every subset of pairwise commuting generators is finite and for any contravariant natural system F on M(E,I) we construct a semicubical set T(E,I) with a homological system \\overline F on this set such that the Leech homology groups H_n(M(E,I),F) are isomorphic to the cubical homology groups H_n(T(E,I),\\overline F). Complexes of Abelian groups are also constructed enabling one to obtain (under additional finiteness conditions) algorithms for computing the Leech homology groups and homology groups with coefficients in right M(E,I)-modules. Bibliography: 16 titles.

  10. Possible quantum algorithm for the Lipshitz-Sarkar-Steenrod square for Khovanov homology

    Science.gov (United States)

    Ospina, Juan

    2013-05-01

    Recently the celebrated Khovanov Homology was introduced as a target for Topological Quantum Computation given that the Khovanov Homology provides a generalization of the Jones polynomal and then it is possible to think about of a generalization of the Aharonov.-Jones-Landau algorithm. Recently, Lipshitz and Sarkar introduced a space-level refinement of Khovanov homology. which is called Khovanov Homotopy. This refinement induces a Steenrod square operation Sq2 on Khovanov homology which they describe explicitly and then some computations of Sq2 were presented. Particularly, examples of links with identical integral Khovanov homology but with distinct Khovanov homotopy types were showed. In the presente work we will introduce possible quantum algorithms for the Lipshitz- Sarkar-Steenrod square for Khovanov Homolog and their possible simulations using computer algebra.

  11. Nanog reporter system in mouse embryonic stem cells based on highly efficient BAC homologous recombination

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Nanog is a novel transcription factor specifically expressed in mouse embryonic stem cells (mES cells). It has been reported that Nanog plays an essential role in maintaining multi-potency of ES cells. The expression of Nanog is very sensitive to ES cells differentiation, making Nanog one of the best markers to indicate the status of ES cells. In this study, we developed an efficient method to construct Nanog promoter driven EGFP reporter system based on the BAC homologous recombination. We further generated a Nanog-EGFP reporter mES cell line. This reporter mES cell line exhibited features similar to those of normal mES cells, and the EGFP reporter efficiently reflected the expression of Nanog, indicating the differentiation status of mES cells. We achieved a reliable experimental reporter system to research self-renewal and differentiation of mES cells. The system could facilitate research on culture system of mES cells and researches on the expression and regulation of Nanog and other related factors in mES cells.

  12. Enhancing xylanase production in the thermophilic fungus Myceliophthora thermophila by homologous overexpression of Mtxyr1.

    Science.gov (United States)

    Wang, Juan; Wu, Yaning; Gong, Yanfen; Yu, Shaowen; Liu, Gang

    2015-09-01

    The xylanase regulator 1 protein in Myceliophthora thermophila ATCC42464 (MtXyr1) is 60 % homologous with that of Trichoderma reesei. However, MtXyr1's regulatory role on cellulolytic and xylanolytic genes in M. thermophila is unknown. Herein, MtXyr1 was overexpressed under the control of the MtPpdc (pyruvate decarboxylase) promoter. Compared with the wild type, the extracellular xylanase activities of the transformant cultured in non-inducing and inducing media for 120 h were 25.19- and 9.04-fold higher, respectively. The Mtxyr1 mRNA level was 300-fold higher than in the wild type in corncob-containing medium. However, the filter paper activity and endoglucanase activities were unchanged in corncob-containing medium and glucose-containing medium. The different zymograms between the transformant and the wild type were analyzed and identified by mass spectrometry as three xylanases of the glycoside hydrolase (GH) family 11. Thus, overexpression of xyr1 resulted in enhanced xylanase activity in M. thermophila. Xylanase production could be improved by overexpressing Mtxyr1 in M. thermophila. PMID:26173497

  13. Binding energies of nucleobase complexes: Relevance to homology recognition of DNA

    Science.gov (United States)

    León, Sergio Cruz; Prentiss, Mara; Fyta, Maria

    2016-06-01

    The binding energies of complexes of DNA nucleobase pairs are evaluated using quantum mechanical calculations at the level of dispersion corrected density functional theory. We begin with Watson-Crick base pairs of singlets, duplets, and triplets and calculate their binding energies. At a second step, mismatches are incorporated into the Watson-Crick complexes in order to evaluate the variation in the binding energy with respect to the canonical Watson-Crick pairs. A linear variation of this binding energy with the degree of mismatching is observed. The binding energies for the duplets and triplets containing mismatches are further compared to the energies of the respective singlets in order to assess the degree of collectivity in these complexes. This study also suggests that mismatches do not considerably affect the energetics of canonical base pairs. Our work is highly relevant to the recognition process in DNA promoted through the RecA protein and suggests a clear distinction between recognition in singlets, and recognition in duplets or triplets. Our work assesses the importance of collectivity in the homology recognition of DNA.

  14. The transcriptional regulator LEUNIG_HOMOLOG regulates mucilage release from the Arabidopsis testa.

    Science.gov (United States)

    Walker, Murray; Tehseen, Muhammad; Doblin, Monika S; Pettolino, Filomena A; Wilson, Sarah M; Bacic, Antony; Golz, John F

    2011-05-01

    Exposure of the mature Arabidopsis (Arabidopsis thaliana) seed to water results in the rapid release of pectinaceous mucilage from the outer cells of the testa. Once released, mucilage completely envelops the seed in a gel-like capsule. The physical force required to rupture the outer cell wall of the testa comes from the swelling of the mucilage as it expands rapidly following hydration. In this study, we show that mutations in the transcriptional regulator LEUNIG_HOMOLOG (LUH) cause a mucilage extrusion defect due to altered mucilage swelling. Based on sugar linkage and immunomicroscopic analyses, we show that the structure of luh mucilage is altered, having both an increase in substituted rhamnogalacturonan I and in methyl-esterified homogalacturonan. Also correlated with the structural modification of luh mucilage is a significant decrease in MUCILAGE MODIFIED2 (MUM2; a β-galactosidase) expression in the luh seed coat, raising the possibility that reduced activity of this glycosidase is directly responsible for the luh mucilage defects. Consistent with this is the structural similarity between mum2 and luh mucilage as well as the observation that elevating MUM2 expression in luh mutants completely suppresses the mucilage extrusion defect. Suppression of the luh mutant phenotype was also observed when LEUNIG, a transcriptional corepressor closely related to LUH, was introduced in luh mutants under the control of the LUH promoter. Based on these data, we propose a new model for the regulation of pectin biosynthesis during plant growth and development. PMID:21402796

  15. Molecular characterization of interferon regulatory factor 2 (IRF-2) homolog in pearl oyster Pinctada fucata.

    Science.gov (United States)

    Huang, Xian-De; Liu, Wen-Guang; Wang, Qi; Zhao, Mi; Wu, Shan-Zeng; Guan, Yun-Yan; Shi, Yu; He, Mao-Xian

    2013-05-01

    Interferon regulatory factors (IRFs) control many facets of the innate and adaptive immune responses, regulate the development of the immune system itself and involve in reproduction and morphogenesis. In the present study, the IRF-2 homology gene, PfIRF-2 from pearl oyster Pinctada fucata was cloned and its genomic structure and promoter were analyzed. PfIRF-2 encodes a putative protein of 350 amino acids, and contains a highly conserved N-terminal DNA-binding domain and a variable C-terminal regulatory domain. Comparison and phylogenetic analysis revealed that PfIRF-2 shared a relatively higher identity with other mollusk but relatively lower identity with vertebrate IRF-2, and was clustered with IRF-1 subfamily composed of IRF-2 and IRF-1. Furthermore, gene expression analysis revealed that PfIRF-2 involved in the immune response to LPS and poly(I:C) stimulation. Immunofluorescence assay showed that the expressed PfIRF-2 was translocated into the nucleus and dual-luciferase reporter assays indicated that PfIRF-2 could involved and activate interferon signaling or NF-κB signal pathway in HEK293 cells. The study of PfIRF-2 may help better understand the innate immune in mollusk. PMID:23422814

  16. Amblyomma americanum salivary gland homolog of nSec1 is essential for saliva protein secretion

    International Nuclear Information System (INIS)

    Soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins assemble in tight core complexes which promote fusion of carrier vesicles with target compartments. Members of this class of proteins are expressed in all eukaryotic cells and distributed in distinct subcellular compartments. All vesicle transport mechanisms known to date have an essential requirement for a member of the Sec1 protein family, including the nSec1 in regulated exocytosis. A homolog of nSec1 was cloned and sequenced from the salivary glands of partially fed female ticks. Double-stranded RNA was used to specifically reduce the amount of nSec1 mRNA and protein in female adult tick salivary glands. This reduction was accompanied by a decrease in anticoagulant protein release by the glands and by abnormalities in feeding by dsRNA treated ticks. We report the efficacy of double-stranded RNA-mediated interference in 'knocking down' nSec1 both in vivo and in vitro in tick salivary glands and the applicability of this technique for studying the mechanism of exocytosis in tick salivary glands

  17. Isolation of a rice gene homologous to the human putative tumor suppressor gene QM

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    QM gene was originally isolated from human by Dowdy et al during a search for a wilms′ tumor suppressor gene. Researches of QM gene focused mainly on animals and yeasts, little was known about plant QM gene. For better understanding of QM gene in rice, a QM homologous fragment was used as a probe to screen rice (Oryza sativa subsp. indica c.v. Guanglu′ ai 4) genomic DNA library,and two clones were obtained. One of them, OSQM2, encoded a highly basic protein of 184 amino acids, the sequence was about 3.1 kb long with a very special promoter region compared with other known QM genes. Seven potential G boxes could be found between -690 and -230. G box, which contains a ACGT core motif, had been reported in many plants to act as a cis acting DNA element in the regulation of genes in a variety of environmental conditions, such as ABA regulated gene expression, red light, UV light, anaerobiosis, and wounding etc. Two closely linked DRE related motifs (dehydration responsive element) could also be found between -182 and 173, which had a CCGAC conserved sequence and had been identified in many cold and drought responsive genes in Arabidopsis. Six MYC recognition sequences with the conserved motif NCANNTGN were also presented, which might be essential for ABA and drought responsive expression of the plant genes.

  18. DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Yuxin Feng

    Full Text Available Estrogen receptor alpha (ERα, a ligand-dependent transcription factor, mediates the expression of its target genes by interacting with corepressors and coactivators. Since the first cloning of SRC1, more than 280 nuclear receptor cofactors have been identified, which orchestrate target gene transcription. Aberrant activity of ER or its accessory proteins results in a number of diseases including breast cancer. Here we identified SFR1, a protein involved in DNA homologous recombination, as a novel binding partner of ERα. Initially isolated in a yeast two-hybrid screen, the interaction of SFR1 and ERα was confirmed in vivo by immunoprecipitation and mammalian one-hybrid assays. SFR1 co-localized with ERα in the nucleus, potentiated ER's ligand-dependent and ligand-independent transcriptional activity, and occupied the ER binding sites of its target gene promoters. Knockdown of SFR1 diminished ER's transcriptional activity. Manipulating SFR1 expression by knockdown and overexpression revealed a role for SFR1 in ER-dependent and -independent cancer cell proliferation. SFR1 differs from SRC1 by the lack of an intrinsic activation function. Taken together, we propose that SFR1 is a novel transcriptional modulator for ERα and a potential target in breast cancer therapy.

  19. Protein disulfide isomerase homolog TrPDI2 contributing to cellobiohydrolase production in Trichoderma reesei.

    Science.gov (United States)

    Wang, Guokun; Lv, Pin; He, Ronglin; Wang, Haijun; Wang, Lixian; Zhang, Dongyuan; Chen, Shulin

    2015-09-01

    The majority of the cysteine residues in the secreted proteins form disulfide bonds via protein disulfide isomerase (PDI)-mediated catalysis, stabilizing the enzyme activity. The role of PDI in cellulase production is speculative, as well as the possibility of PDI as a target for improving enzyme production efficiency of Trichoderma reesei, a widely used producer of enzyme for the production of lignocellulose-based biofuels and biochemicals. Here, we report that a PDI homolog, TrPDI2 in T. reesei exhibited a 36.94% and an 11.81% similarity to Aspergillus niger TIGA and T. reesei PDI1, respectively. The capability of TrPDI2 to recover the activity of reduced and denatured RNase by promoting refolding verified its protein disulfide isomerase activity. The overexpression of Trpdi2 increased the secretion and the activity of CBH1 at the early stage of cellulase induction. In addition, both the expression level and redox state of TrPDI2 responded to cellulase induction in T. reesei, providing sustainable oxidative power to ensure cellobiohydrolase maturation and production. The results suggest that TrPDI2 may contribute to cellobiohydrolase secretion by enhancing the capability of disulfide bond formation, which is essential for protein folding and maturation. PMID:26138396

  20. Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining.

    Science.gov (United States)

    Xia, F; Taghian, D G; DeFrank, J S; Zeng, Z C; Willers, H; Iliakis, G; Powell, S N

    2001-07-17

    Carriers of BRCA2 germline mutations are at high risk to develop early-onset breast cancer. The underlying mechanisms of how BRCA2 inactivation predisposes to malignant transformation have not been established. Here, we provide direct functional evidence that human BRCA2 promotes homologous recombination (HR), which comprises one major pathway of DNA double-strand break repair. We found that up-regulated HR after transfection of wild-type (wt) BRCA2 into a human tumor line with mutant BRCA2 was linked to increased radioresistance. In addition, BRCA2-mediated enhancement of HR depended on the interaction with Rad51. In contrast to the tumor suppressor BRCA1, which is involved in multiple DNA repair pathways, BRCA2 status had no impact on the other principal double-strand break repair pathway, nonhomologous end joining. Thus, there exists a specific regulation of HR by BRCA2, which may function to maintain genomic integrity and suppress tumor development in proliferating cells. PMID:11447276

  1. DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha.

    Science.gov (United States)

    Feng, Yuxin; Singleton, David; Guo, Chun; Gardner, Amanda; Pakala, Suresh; Kumar, Rakesh; Jensen, Elwood; Zhang, Jinsong; Khan, Sohaib

    2013-01-01

    Estrogen receptor alpha (ERα), a ligand-dependent transcription factor, mediates the expression of its target genes by interacting with corepressors and coactivators. Since the first cloning of SRC1, more than 280 nuclear receptor cofactors have been identified, which orchestrate target gene transcription. Aberrant activity of ER or its accessory proteins results in a number of diseases including breast cancer. Here we identified SFR1, a protein involved in DNA homologous recombination, as a novel binding partner of ERα. Initially isolated in a yeast two-hybrid screen, the interaction of SFR1 and ERα was confirmed in vivo by immunoprecipitation and mammalian one-hybrid assays. SFR1 co-localized with ERα in the nucleus, potentiated ER's ligand-dependent and ligand-independent transcriptional activity, and occupied the ER binding sites of its target gene promoters. Knockdown of SFR1 diminished ER's transcriptional activity. Manipulating SFR1 expression by knockdown and overexpression revealed a role for SFR1 in ER-dependent and -independent cancer cell proliferation. SFR1 differs from SRC1 by the lack of an intrinsic activation function. Taken together, we propose that SFR1 is a novel transcriptional modulator for ERα and a potential target in breast cancer therapy. PMID:23874500

  2. Azotobacter vinelandii nifD- and nifE-encoded polypeptides share structural homology

    OpenAIRE

    Dean, Dennis R.; Brigle, Kevin E.

    1985-01-01

    The Azotobacter vinelandii nifE gene was isolated and its complete nucleotide sequence was determined. The amino acid sequences deduced from the A. vinelandii nifE and nifD gene sequences were compared and found to share striking primary sequence homology. This homology implies a functional and possibly an evolutionary relationship between these two gene products. The structural homology is discussed with regard to the potential FeMo cofactor binding properties of these polypeptides and the p...

  3. Genetic probing of homologous recombination and non-homologous end joining during meiotic prophase in irradiated mouse spermatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Emad A. [Department of Endocrinology and Metabolism, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Department of Zoology, Faculty of Science, Assiut University, 71516 Assiut (Egypt); Philippens, Marielle E.P.; Kal, Henk B. [Department of Radiotherapy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht (Netherlands); Rooij, Dirk G. de, E-mail: d.g.derooij@uu.nl [Department of Endocrinology and Metabolism, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam (Netherlands); Boer, Peter de [Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen (Netherlands)

    2010-06-01

    This study was designed to obtain a better insight into the relative contribution of homologous recombination (HR) and non-homologous end joining (NHEJ) to the repair of radiation-induced DNA double-strand breaks (DSBs) at first meiotic prophase. Early and late pachytene and early diplotene spermatocytes that had completed crossing over were sampled. We studied the kinetics of {gamma}-H2AX chromatin foci removal after irradiation of mice deficient for HR and mice deficient for NHEJ. Analyzing {gamma}-H2AX signals in unirradiated RAD54/RAD54B deficient spermatocytes indicated incomplete meiotic recombination repair due to the pronounced increase of {gamma}-H2AX foci in late prophase primary spermatocytes. In these mice, 8 h after irradiation, early pachytene spermatocytes showed a reduction of the numbers of {gamma}-H2AX foci by 52% compared to 82% in the wild type, the difference being significant. However, after crossing over (in late pachytene and early diplotene), no effect of RAD54/RAD54B deficiency on the reduction of irradiation-induced foci was observed. In NHEJ deficient SCID mice, repair kinetics in early spermatocytes were similar to those in wild type mice. However, 1 h after irradiation in late pachytene and early diplotene spermatocytes 1.7 times more foci were found than in wild type mice. This difference might be related to the absence of a DNA-PKcs dependent fast repair component in SCID mice. As subsequent repair is normal, HR likely is taking over. Taken together, the results obtained in RAD54/RAD54B deficient mice and in SCID mice indicate that DSB repair in early pachytene spermatocytes is mainly carried out through HR. In late spermatocytes (late pachytenes and early diplotenes) NHEJ is active. However, probably there is an interplay between these repair pathways and when in late spermatocytes the NHEJ pathway is compromised HR may take over.

  4. Chromosome Painting Reveals Asynaptic Full Alignment of Homologs and HIM-8–Dependent Remodeling of X Chromosome Territories during Caenorhabditis elegans Meiosis

    Science.gov (United States)

    Nabeshima, Kentaro; Mlynarczyk-Evans, Susanna; Villeneuve, Anne M.

    2011-01-01

    During early meiotic prophase, a nucleus-wide reorganization leads to sorting of chromosomes into homologous pairs and to establishing associations between homologous chromosomes along their entire lengths. Here, we investigate global features of chromosome organization during this process, using a chromosome painting method in whole-mount Caenorhabditis elegans gonads that enables visualization of whole chromosomes along their entire lengths in the context of preserved 3D nuclear architecture. First, we show that neither spatial proximity of premeiotic chromosome territories nor chromosome-specific timing is a major factor driving homolog pairing. Second, we show that synaptonemal complex-independent associations can support full lengthwise juxtaposition of homologous chromosomes. Third, we reveal a prominent elongation of chromosome territories during meiotic prophase that initiates prior to homolog association and alignment. Mutant analysis indicates that chromosome movement mediated by association of chromosome pairing centers (PCs) with mobile patches of the nuclear envelope (NE)–spanning SUN-1/ZYG-12 protein complexes is not the primary driver of territory elongation. Moreover, we identify new roles for the X chromosome PC (X-PC) and X-PC binding protein HIM-8 in promoting elongation of X chromosome territories, separable from their role(s) in mediating local stabilization of pairing and association of X chromosomes with mobile SUN-1/ZYG-12 patches. Further, we present evidence that HIM-8 functions both at and outside of PCs to mediate chromosome territory elongation. These and other data support a model in which synapsis-independent elongation of chromosome territories, driven by PC binding proteins, enables lengthwise juxtaposition of chromosomes, thereby facilitating assessment of their suitability as potential pairing partners. PMID:21876678

  5. Homologous series of induced early mutants in Indica rice. Pt.3: The relationship between the induction of homologous series of early mutants and its different pedigree

    International Nuclear Information System (INIS)

    The percentage of homologous series of early mutants (PHSEM) induced by irradiation was closely related to its pedigree. This study showed that PHSEM for varieties with the same pedigree were similar, and there were three different level of dominance (high, low and normal) in the homologous series induced from different pedigree. The PHSEM for varieties derived form distant-relative-parents were higher than that derived from close-relative-parents. There was the dominance pedigree for the induction of homologous series of early mutants. IR8(Peta x DGWG), IR127 (Cpslo x Sigadis) and IR24 (IR8 x IR127) were dominant pedigree, and varieties derived from them could be easily induced the homologous series of early mutants

  6. Molecular cloning and functional analysis of the FLOWERING LOCUS T (FT) homolog GhFT1 from Gossypium hirsutum

    Institute of Scientific and Technical Information of China (English)

    Danli Guo; Chao Li; Rui Dong; Xiaobo Li; Xiangwen Xiao; Xianzhong Huang

    2015-01-01

    FLOWERING LOCUS T (FT) encodes a member of the phosphatidylethanolamine-binding protein (PEBP) family that functions as the mobile floral signal, playing an important role in regulating the floral transition in angiosperms. We isolated an FT-homolog (GhFT1) from Gossypium hirsutum L. cultivar, Xinluzao 33 GhFT1 was predominantly expressed in stamens and sepals, and had a relatively higher expression level during the initiation stage of fiber development. GhFT1 mRNA displayed diurnal oscillations in both long-day and short-day condition, suggesting that the expression of this gene may be under the control of the circadian clock. Subcel ular analysis revealed that GhFT1 protein located in the cytoplasm and nucleus. Ectopic expression of GhFT1 in transgenic arabidopsis plants resulted in early flowering compared with wild-type plants. In addition, ectopic expression of GhFT1 in arabidopsis ft-10 mutants partial y rescued the extremely late flowering phenotype. Finally, several flowering related genes functioning downstream of AtFT were highly upregulated in the 35S::GhFT1 transgenic arabidopsis plants. In summary, GhFT1 is an FT-homologous gene in cotton that regulates flower transition similar to its orthologs in other plant species and thus it may be a candidate target for promoting early maturation in cotton breeding.

  7. TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions.

    Science.gov (United States)

    Rai, Rekha; Chen, Yong; Lei, Ming; Chang, Sandy

    2016-01-01

    Repressor/activator protein 1 (RAP1) is a highly conserved telomere-interacting protein. Yeast Rap1 protects telomeres from non-homologous end joining (NHEJ), plays important roles in telomere length control and is involved in transcriptional gene regulation. However, a role for mammalian RAP1 in telomere end protection remains controversial. Here we present evidence that mammalian RAP1 is essential to protect telomere from homology directed repair (HDR) of telomeres. RAP1 cooperates with the basic domain of TRF2 (TRF2(B)) to repress PARP1 and SLX4 localization to telomeres. Without RAP1 and TRF2(B), PARP1 and SLX4 HR factors promote rapid telomere resection, resulting in catastrophic telomere loss and the generation of telomere-free chromosome fusions in both mouse and human cells. The RAP1 Myb domain is required to repress both telomere loss and formation of telomere-free fusions. Our results highlight the importance of the RAP1-TRF2 heterodimer in protecting telomeres from inappropriate processing by the HDR pathway. PMID:26941064

  8. Introduction to 'Homology and convergence in nervous system evolution'.

    Science.gov (United States)

    Strausfeld, Nicholas J; Hirth, Frank

    2016-01-01

    The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso-ventral and anterior-posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the 'Cambrian explosion' arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss

  9. Studies of Flerovium and Element 115 Homologs with Macrocyclic Extractants

    Energy Technology Data Exchange (ETDEWEB)

    Despotopulos, John D. [Univ. of Nevada, Las Vegas, NV (United States)

    2015-03-12

    Study of the chemistry of the heaviest elements, Z ≥ 104, poses a unique challenge due to their low production cross-sections and short half-lives. Chemistry also must be studied on the one-atom-at-a-time scale, requiring automated, fast, and very efficient chemical schemes. Recent studies of the chemical behavior of copernicium (Cn, element 112) and flerovium (Fl, element 114) together with the discovery of isotopes of these elements with half-lives suitable for chemical studies have spurred a renewed interest in the development of rapid systems designed to study the chemical properties of elements with Z ≥ 114. This dissertation explores both extraction chromatography and solvent extraction as methods for development of a rapid chemical separation scheme for the homologs of flerovium (Pb, Sn, Hg) and element 115 (Bi, Sb), with the goal of developing a chemical scheme that, in the future, can be applied to on-line chemistry of both Fl and element 115. Carrier-free radionuclides, used in these studies, of the homologs of Fl and element 115 were obtained by proton activation of high-purity metal foils at the Lawrence Livermore National Laboratory (LLNL) Center for Accelerator Mass Spectrometry (CAMS): natIn(p,n)113Sn, natSn(p,n)124Sb, and Au(p,n)197m,gHg. The carrier-free activity was separated from the foils by novel separation schemes based on ion exchange and extraction chromatography techniques. Carrier-free Pb and Bi isotopes were obtained from development of a novel generator based on cation exchange chromatography using the 232U parent to generate 212Pb and 212Bi. Macrocyclic extractants, specifically crown ethers and their derivatives, were chosen for these studies; crown ethers show high selectivity for metal ions. Finally. a potential chemical system for Fl was established based on the Eichrom Pb resin, and insight to an improved system based on thiacrown ethers is

  10. Novel Synthetic Promoters from the Cestrum Yellow Leaf Curling Virus.

    Science.gov (United States)

    Sahoo, Dipak Kumar; Sarkar, Shayan; Maiti, Indu B; Dey, Nrisingha

    2016-01-01

    Constitutive promoters direct gene expression uniformly in most tissues and cells at all stages of plant growth and development; they confer steady levels of transgene expression in plant cells and hence their demand is high in plant biology. The gene silencing due to promoter homology can be avoided by either using diverse promoters isolated from different plant and viral genomes or by designing synthetic promoters. The aim of this chapter was to describe the basic protocols needed to develop and analyze novel, synthetic, nearly constitutive promoters from Cestrum yellow leaf curling virus (CmYLCV) through promoter/leader deletion and activating cis-sequence analysis. We also describe the methods to evaluate the strength of the promoters efficiently in various transient expression systems like agroinfiltration assay, gene-gun method, and assay in tobacco protoplasts. Besides, the detailed methods for developing transgenic plants (tobacco and Arabidopsis) for evaluation of the promoter using the GUS reporter gene are also described. The detailed procedure for electrophoretic mobility shift assay (EMSA) coupled with super-shift EMSA analysis are also described for showing the binding of tobacco transcription factor, TGA1a to cis-elements in the CmYLCV distal promoter region. PMID:27557764

  11. Failure of homologous synapsis and sex-specific reproduction problems

    Directory of Open Access Journals (Sweden)

    Hiroki eKurahashi

    2012-06-01

    Full Text Available The prophase of meiosis I ensures the correct segregation of chromosomes to each daughter cell. This includes the pairing, synapsis and recombination of homologous chromosomes. A subset of chromosomal abnormalities, including translocation and inversion, disturbs these processes, resulting in the failure to complete synapsis. This activates the meiotic pachytene checkpoint, and the gametes are fated to undergo cell cycle arrest and subsequent apoptosis. Spermatogenic cells appear to be more vulnerable to the pachytene checkpoint, and male carriers of chromosomal abnormalities are more susceptible to infertility. In contrast, oocytes tend to bypass the checkpoint and instead generate other problems, such as chromosome imbalance that often leads to recurrent pregnancy loss in female carriers. Recent advances in genetic manipulation technologies have increased our knowledge about the pachytene checkpoint and surveillance systems that detect chromosomal synapsis. This review focuses on the consequences of synapsis failure in humans and provides an overview of the mechanisms involved. We also discuss the sexual dimorphism of the involved pathways that leads to the differences in reproductive outcomes between males and females.

  12. Homologous radioimmunoassay for human epidermal growth factor (urogastrone)

    International Nuclear Information System (INIS)

    Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +- 3.0 and 52.0 +- 3.5 (mean +- SE) μg/total vol, or 29.7 +- 1.1 and 39.8 +- 1.7 μg/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +- 2.7 μg/g creatinine; P 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion

  13. Microbial antigenic variation mediated by homologous DNA recombination.

    Science.gov (United States)

    Vink, Cornelis; Rudenko, Gloria; Seifert, H Steven

    2012-09-01

    Pathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. One of the most widely used strategies of immune evasion is antigenic variation, in which immunogenic molecules expressed on the surface of a microorganism are continuously modified. As a consequence, the host is forced to constantly adapt its humoral immune response against this pathogen. An antigenic change thus provides the microorganism with an opportunity to persist and/or replicate within the host (population) for an extended period of time or to effectively infect a previously infected host. In most cases, antigenic variation is caused by genetic processes that lead to the modification of the amino acid sequence of a particular antigen or to alterations in the expression of biosynthesis genes that induce changes in the expression of a variant antigen. Here, we will review antigenic variation systems that rely on homologous DNA recombination and that are found in a wide range of cellular, human pathogens, including bacteria (such as Neisseria spp., Borrelia spp., Treponema pallidum, and Mycoplasma spp.), fungi (such as Pneumocystis carinii) and parasites (such as the African trypanosome Trypanosoma brucei). Specifically, the various DNA recombination-based antigenic variation systems will be discussed with a focus on the employed mechanisms of recombination, the DNA substrates, and the enzymatic machinery involved. PMID:22212019

  14. Sunspot Waves and Triggering of Homologous Active Region Jets

    CERN Document Server

    Chandra, Ramesh; Mulay, Sargam; Tripathi, Durgesh

    2014-01-01

    We present and discuss multi-wavelength observations of five homologous recurrent solar jets that occurred in active region NOAA 11133 on 11 December, 2010. These jets were well observed by the Solar Dynamic observatory (SDO) with high spatial and temporal resolution. The speed of the jets ranged between 86 and 267 km/s. A type III radio burst was observed in association with all the five jets. The investigation of the over all evolution of magnetic field in the source regions suggested that the flux was continuously emerging on longer term. However, all the jets but J5 were triggered during a local dip in the magnetic flux, suggesting the launch of the jets during localised submergence of magnetic flux. Additionally, using the PFSS modelling of the photospheric magnetic field, we found that all the jets were ejected in the direction of open field lines. We also traced sunspot oscillations from the sunspot interior to foot-point of jets and found presence of ~ 3 minute oscillations in all the SDO/AIA passband...

  15. Characterization of a Canine Homolog of Human Aichivirus▿

    Science.gov (United States)

    Kapoor, Amit; Simmonds, Peter; Dubovi, Edward J.; Qaisar, Natasha; Henriquez, Jose A.; Medina, Jan; Shields, Shelly; Lipkin, W. Ian

    2011-01-01

    Many of our fatal “civilization” infectious diseases have arisen from domesticated animals. Although picornaviruses infect most mammals, infection of a companion animal is not known. Here we describe the identification and genomic characterization of the first canine picornavirus. Canine kobuvirus (CKoV), identified in stool samples from dogs with diarrhea, has a genomic organization typical of a picornavirus and encodes a 2,469-amino-acid polyprotein flanked by 5′ and 3′ untranslated regions. Comparative phylogenetic analysis using various structural and nonstructural proteins of CKoV confirmed it as the animal virus homolog most closely related to human Aichivirus (AiV). Bayesian Markov chain Monte Carlo analysis suggests a mean recent divergence time of CKoV and AiV within the past 20 to 50 years, well after the domestication of canines. The discovery of CKoV provides new insights into the origin and evolution of AiV and the species specificity and pathogenesis of kobuviruses. PMID:21880761

  16. Characterization of a canine homolog of human Aichivirus.

    Science.gov (United States)

    Kapoor, Amit; Simmonds, Peter; Dubovi, Edward J; Qaisar, Natasha; Henriquez, Jose A; Medina, Jan; Shields, Shelly; Lipkin, W Ian

    2011-11-01

    Many of our fatal "civilization" infectious diseases have arisen from domesticated animals. Although picornaviruses infect most mammals, infection of a companion animal is not known. Here we describe the identification and genomic characterization of the first canine picornavirus. Canine kobuvirus (CKoV), identified in stool samples from dogs with diarrhea, has a genomic organization typical of a picornavirus and encodes a 2,469-amino-acid polyprotein flanked by 5' and 3' untranslated regions. Comparative phylogenetic analysis using various structural and nonstructural proteins of CKoV confirmed it as the animal virus homolog most closely related to human Aichivirus (AiV). Bayesian Markov chain Monte Carlo analysis suggests a mean recent divergence time of CKoV and AiV within the past 20 to 50 years, well after the domestication of canines. The discovery of CKoV provides new insights into the origin and evolution of AiV and the species specificity and pathogenesis of kobuviruses. PMID:21880761

  17. The many facets of homologous recombination at telomeres

    Directory of Open Access Journals (Sweden)

    Clémence Claussin

    2015-07-01

    Full Text Available The ends of linear chromosomes are capped by nucleoprotein structures called telomeres. A dysfunctional telomere may resemble a DNA double-strand break (DSB, which is a severe form of DNA damage. The presence of one DSB is sufficient to drive cell cycle arrest and cell death. Therefore cells have evolved mechanisms to repair DSBs such as homologous recombination (HR. HR-mediated repair of telomeres can lead to genome instability, a hallmark of cancer cells, which is why such repair is normally inhibited. However, some HR-mediated processes are required for proper telomere function. The need for some recombination activities at telomeres but not others necessitates careful and complex regulation, defects in which can lead to catastrophic consequences. Furthermore, some cell types can maintain telomeres via telomerase-independent, recombination-mediated mechanisms. In humans, these mechanisms are called alternative lengthening of telomeres (ALT and are used in a subset of human cancer cells. In this review, we summarize the different recombination activities occurring at telomeres and discuss how they are regulated. Much of the current knowledge is derived from work using yeast models, which is the focus of this review, but relevant studies in mammals are also included.

  18. Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuria.

    Science.gov (United States)

    Zalman, L S; Wood, L M; Frank, M M; Müller-Eberhard, H J

    1987-02-01

    The affected E of two patients with paroxysmal nocturnal hemoglobinuria (PNH) were enriched by lysing the unaffected, normal E with anti-human decay-accelerating factor (DAF) and guinea pig serum. The membranes of the unlysed, DAF-deficient cells (PNH-E) were dissolved and examined by SDS-PAGE and immunoblotting using an antiserum to homologous restriction factor (HRF). Whereas the 65 kD complement regulatory protein was readily detectable in the normal controls, it was completely lacking in both samples of PNH-E membranes. Functional studies likewise indicated the absence of HRF activity from PNH-E. When radiolabeled, isolated HRF protein was offered to PNH-E, it became firmly attached to the cell. Approximately 1,000 molecules of HRF per cell reduced the characteristic susceptibility of these cells to reactive lysis by C5b-9 to nearly normal levels. The results suggest that HRF, which is known to control the action of C8 and C9 on normal human E membranes, is deficient in PNH, as well as acetylcholinesterase and DAF. PMID:2434597

  19. Transcription-coupled homologous recombination after oxidative damage.

    Science.gov (United States)

    Wei, Leizhen; Levine, Arthur Samuel; Lan, Li

    2016-08-01

    Oxidative DNA damage induces genomic instability and may lead to mutagenesis and carcinogenesis. As severe blockades to RNA polymerase II (RNA POLII) during transcription, oxidative DNA damage and the associated DNA strand breaks have a profoundly deleterious impact on cell survival. To protect the integrity of coding regions, high fidelity DNA repair at a transcriptionally active site in non-dividing somatic cells, (i.e., terminally differentiated and quiescent/G0 cells) is necessary to maintain the sequence integrity of transcribed regions. Recent studies indicate that an RNA-templated, transcription-associated recombination mechanism is important to protect coding regions from DNA damage-induced genomic instability. Here, we describe the discovery that G1/G0 cells exhibit Cockayne syndrome (CS) B (CSB)-dependent assembly of homologous recombination (HR) factors at double strand break (DSB) sites within actively transcribed regions. This discovery is a challenge to the current dogma that HR occurs only in S/G2 cells where undamaged sister chromatids are available as donor templates. PMID:27233112

  20. Homology among tet determinants in conjugative elements of streptococci

    Energy Technology Data Exchange (ETDEWEB)

    Smith, M.D.; Hazum, S.; Guild, W.R.

    1981-10-01

    A mutation to tetracycline sensitivity in a resistant strain of Streptococcus pneumoniae was shown by several criteria to be due to a point mutation in the conjugative o(cat-tet) element found in the chromosomes of strains derived from BM6001, a clinical strain resistant to tetracycline and chloramphenicol. Strains carrying the mutation were transformed back to tetracycline resistance with the high efficiency of a point marker by donor deoxyribonucleic acids from its ancestral strain and from nine other clinical isolates of pneumococcus and by deoxyribonucleic acids from Group D Streptococcus faecalis and Group B Streptococcus agalactiae strains that also carry conjugative tet elements in their chromosomes. It was not transformed to resistance by tet plasmid deoxyribonucleic acids from either gram-negative or gram-positive species, except for one that carried transposon TN916, the conjugative tet element present in the chromosomes of some S. faecalis strains. The results showed that the tet determinants in conjugative elements of several streptococcal species share a high degree of deoxyribonucleic acid sequence homology and suggested that they differ from other tet genes.

  1. V-antigen homologs in pathogenic gram-negative bacteria.

    Science.gov (United States)

    Sawa, Teiji; Katoh, Hideya; Yasumoto, Hiroaki

    2014-05-01

    Gram-negative bacteria cause many types of infections in animals from fish and shrimps to humans. Bacteria use Type III secretion systems (TTSSs) to translocate their toxins directly into eukaryotic cells. The V-antigen is a multifunctional protein required for the TTSS in Yersinia and Pseudomonas aeruginosa. V-antigen vaccines and anti-V-antigen antisera confer protection against Yersinia or P. aeruginosa infections in animal models. The V-antigen forms a pentameric cap structure at the tip of the Type III secretory needle; this structure, which has evolved from the bacterial flagellar cap structure, is indispensable for toxin translocation. Various pathogenic gram-negative bacteria such as Photorhabdus luminescens, Vibrio spp., and Aeromonas spp. encode homologs of the V-antigen. Because the V-antigens of pathogenic gram-negative bacteria play a key role in toxin translocation, they are potential therapeutic targets for combatting bacterial virulence. In the USA and Europe, these vaccines and specific antibodies against V-antigens are in clinical trials investigating the treatment of Yersinia or P. aeruginosa infections. Pathogenic gram-negative bacteria are of great interest because of their ability to infect fish and shrimp farms, their potential for exploitation in biological terrorism attacks, and their ability to cause opportunistic infections in humans. Thus, elucidation of the roles of the V-antigen in the TTSS and mechanisms by which these functions can be blocked is critical to facilitating the development of improved anti-V-antigen strategies. PMID:24641673

  2. miRviewer: a multispecies microRNA homologous viewer

    Directory of Open Access Journals (Sweden)

    Kiezun Adam

    2012-02-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are short non-coding RNAs that regulate gene expression via binding to the 3' ends of mRNAs. MiRNAs have been associated with many cellular events ascertaining their central role in gene regulation. In order to better understand miRNAs of interest it is of utmost importance to learn about the genomic conservation of these genes. Findings The miRviewer web-server, presented here, encompasses all known miRNAs of currently fully annotated animal genomes in a visual 'birds-eye' view representation. miRviewer provides a graphical outlook of the current miRNA world together with sequence alignments and secondary structures of each miRNA. As a test case we experimentally examined the expression of several miRNAs in various animals. Conclusions miRviewer completes the homologous miRNA space with hundreds of unreported miRNAs and is available at: http://people.csail.mit.edu/akiezun/miRviewer

  3. Pharmacokinetics of the dimethylheptyl homolog of cannabidiol in dogs.

    Science.gov (United States)

    Samara, E; Bialer, M

    1988-01-01

    Cannabidiol (CBD) is one of the major nonpsychoactive cannabinoids produced by Cannabis sativa L. Recent studies have shown that a dimethylheptyl homolog (DMH) of CBD is more active as an anticonvulsant than is the naturally occurring CBD. In considering DMH as a potential antiepileptic agent, its pharmacokinetics was studied in dogs (N = 8) after both iv (20 mg) and oral (80 mg) administration. After iv administration, DMH was rapidly distributed. DMH has a mean terminal half-life of 2 hr, its plasma levels decline in a biphasic fashion, and its total body clearance is 8.3 liters/hr. This clearance value, after being normalized to blood clearance by the use of mathematical equations, was less than one half of the value of the hepatic blood flow and its extraction ratio (E) by the liver is 0.39, DMH was observed to have a mean volume of distribution of 10 liters (or 0.5 liters/kg). In four of the eight dogs studied, DMH could not be detected in the plasma after oral administration. In the other four, the oral bioavailability was 3, 21, 39, and 43%, respectively. After oral administration, DMH has a low and variable bioavailability, due to a liver first-pass effect and incomplete absorption from the gastrointestinal tract. In comparison with CBD, DMH has a shorter half-life and lower clearance and volume of distribution values, and its liver extraction ratio is about one half that of CBD. PMID:2907468

  4. Identification, localization, and sequencing of fetal bovine VASA homolog.

    Science.gov (United States)

    Bartholomew, Rachel A; Parks, John E

    2007-10-01

    The vasa gene, first described in Drosophila, is purported to be important in germ cell development. Vasa is present across several invertebrate and vertebrate taxa, including frogs, fish, chickens, and humans. Vasa, a DEAD (asparagine-glutamine-alanine-asparagine) box protein shown to function as an RNA helicase in vitro, has not been investigated previously in fetal stage cattle. Total RNA was extracted from bovine fetal gonads obtained at 35-55 days, 55-80 days, and 80-120 days of gestation to amplify a 296 bp reverse transcription polymerase chain reaction (RT-PCR) product using primers for human vasa. The complete coding sequence of bovine vasa was cloned with 5' and 3' random amplification of cDNA ends polymerase chain reaction (RACE-PCR) and subsequently identified as bovine vasa homolog (BVH). Northern blot analysis revealed that among the tissues examined (gonad, liver, heart, brain, and femur), the vasa gene was expressed in the gonad. This localization, the conserved pattern of gene expression, and the gene sequence suggests that BVH plays a role in bovine germ cell development as proposed for other mammalian species. PMID:17150314

  5. Glutamate receptor homologs in plants: Functions and Evolutionary Origins

    Directory of Open Access Journals (Sweden)

    Michelle Beth Price

    2012-10-01

    Full Text Available The plant glutamate receptors (GLRs are homologs of mammalian ionotropic glutamate receptors (iGluRs which were discovered more than 10 years ago, and are hypothesized to be potential amino acid sensors in plants. Although initial progress on this gene family has been hampered by gene redundancy and technical issues such as gene toxicity; genetic, pharmacological, and electrophysiological approaches are starting to uncover the functions of this protein family. In parallel, there has been tremendous progress in elucidating the structure of animal glutamate receptors (iGluRs, which in turn will help understanding of the molecular mechanisms of plant GLR functions.In this review, we will summarize recent progress on the plant GLRs. Emerging evidence implicates plant GLRs in various biological processes in and beyond N sensing, and implies that there is some overlap in the signaling mechanisms of amino acids between plants and animals. Phylogenteic analysis using glutamate receptors from metazoans, plants and bacteria showed that the plant GLRs are no more closely related to metazoan iGluRs as they are to bacterial glutamate receptors, indicating the separation of plant, eukaryotic, and bacterial GLRs might have happened as early on as the last universal common ancestor. Structural similarities and differences with animal iGluRs, and the implication thereof, are also discussed.

  6. On Discrete Symmetries and Torsion Homology in F-Theory

    CERN Document Server

    Mayrhofer, Christoph; Till, Oskar; Weigand, Timo

    2014-01-01

    We study the relation between discrete gauge symmetries in F-theory compactifications and torsion homology on the associated Calabi-Yau manifold. Focusing on the simplest example of a $\\mathbb Z_2$ symmetry, we show that there are two physically distinct ways that such a discrete gauge symmetry can arise. First, compactifications of M-Theory on Calabi-Yau threefolds which support a genus-one fibration with a bi-section are known to be dual to six-dimensional F-theory vacua with a $\\mathbb Z_2$ gauge symmetry. We show that the resulting five-dimensional theories do not have a $\\mathbb Z_2$ symmetry but that the latter emerges only in the F-theory decompactification limit. Accordingly the genus-one fibred Calabi-Yau manifolds do not exhibit discrete torsion. Associated to the bi-section fibration is a Jacobian fibration which does support a section. Compactifying on these related but distinct varieties does lead to a $\\mathbb Z_2$ symmetry in five dimensions and, accordingly, we find explicitly an associated di...

  7. [Non-homologous DNA end joining--new proteins, new functions, new mechanisms].

    Science.gov (United States)

    Popławski, Tomasz; Stoczyńska, Ewelina; Błasiak, Janusz

    2009-01-01

    Humans use primarily nonhomologous end joining (NHEJ) to repair DNA double strand breaks (DSBs), which are the most serious DNA damage, resulting in cell death if non-repaired or missrepaired. NHEJ directly joins together DNA ends resulted from DSBs. This pathway plays a key role in the development of vertebrate immune system through its involvement in the V(D)J recombination. Classical NHEJ in vertebrates involves a heterodimer of Ku proteins, the catalytic subunits of DNA-dependent protein kinase (DNA-PKCS), Artemis, Cernunnos-XLF and XRCC4/ligase DNA IV complex. This classical pathway may be assisted by DNA polymerases mu and lambda. Last 2 years brought new information on the mechanisms, proteins and functions of this DNA repair pathway. In 2006 Cernunnos-XLF was discovered, a protein playing a key role in NHEJ. Some alternative NHEJ pathways were also identified, lacking some of the main proteins of classical NHEJ, but involving other factors, including BRCA1, 53BP1, hPNK, WRN or MDC1. The results obtained so far suggest that not all key components and basic mechanisms of NHEJ have been identified. Future aspects of NHEJ research should include the determination of its role in cancer, aging, immune system development and basic nuclear metabolism. PMID:19514464

  8. On the homological dimensions of Leavitt path algebras with coefficients in commutative rings

    OpenAIRE

    Lopatkin, V.; Nam, T. G.

    2016-01-01

    In this paper, we give sharp bounds for the homological dimensions of the Leavitt path algebra $L_R(E)$ of a finite graph $E$ with coefficients in a commutative ring $R$, as well as establish a formula for calculating the homological dimensions of $L_R(E)$ when $R$ is a commutative unital algebra over a field.

  9. Assembly and sorting of homologous BAC contigs in allotetraploid cotton genomes

    Science.gov (United States)

    Upland cotton (G. hirsutum) is a diploidized allopolyploid species containing At and Dt sub-genomes that have partial homology. Assembly and sorting of homologous BAC contigs into their subgenomes and further to individual chromosomes are of both great interest and great challenge for genome-wide i...

  10. Nielsen theory, Floer homology and a generalisation of the Poincare-Birkhoff theorem

    OpenAIRE

    Fel'shtyn, Alexander

    2008-01-01

    The purpose of this mostly expository paper is to discuss a connection between Nielsen fixed point theory and symplectic Floer homology theory for symplectomorphisms of surface and a calculation of Seidel's symplectic Floer homology for different mapping classes. We also describe symplectic zeta functions and asympltotic symplectic invariant. A generalisation of the Poincare- Birkhoff fixed point theorem and Arnold conjecture is proposed.

  11. Density parameter estimation for finding clusters of homologous proteins-tracing actinobacterial pathogenicity lifestyles

    DEFF Research Database (Denmark)

    Röttger, Richard; Kalaghatgi, Prabhav; Sun, Peng;

    2013-01-01

    Homology detection is a long-standing challenge in computational biology. To tackle this problem, typically all-versus-all BLAST results are coupled with data partitioning approaches resulting in clusters of putative homologous proteins. One of the main problems, however, has been widely neglected...

  12. The good pants homology and a proof of the Ehrenpreis conjecture

    CERN Document Server

    Kahn, Jeremy

    2011-01-01

    We develop the notion of the good pants homology and show that it agrees with the standard homology on closed surfaces (the good pants are pairs of pants whose cuffs have the length nearly equal to some large number R). Combined with our previous work on the Surface Subgroup Theorem, this yields a proof of the Ehrenpreis conjecture.

  13. Twisted homological stability for extensions and automorphism groups of free nilpotent groups

    DEFF Research Database (Denmark)

    Szymik, Markus

    2014-01-01

    We prove twisted homological stability with polynomial coefficients for automorphism groups of free nilpotent groups of any given class. These groups interpolate between two extremes for which homological stability was known before, the general linear groups over the integers and the automorphism...

  14. A cohesin-based structural platform supporting homologous chromosome pairing in meiosis.

    Science.gov (United States)

    Ding, Da-Qiao; Haraguchi, Tokuko; Hiraoka, Yasushi

    2016-08-01

    The pairing and recombination of homologous chromosomes during the meiotic prophase is necessary for the accurate segregation of chromosomes in meiosis. However, the mechanism by which homologous chromosomes achieve this pairing has remained an open question. Meiotic cohesins have been shown to affect chromatin compaction; however, the impact of meiotic cohesins on homologous pairing and the fine structures of cohesion-based chromatin remain to be determined. A recent report using live-cell imaging and super-resolution microscopy demonstrated that the lack of meiotic cohesins alters the chromosome axis structures and impairs the pairing of homologous chromosomes. These results suggest that meiotic cohesin-based chromosome axis structures are crucial for the pairing of homologous chromosomes. PMID:26856595

  15. Mammalian X homolog acts as sex chromosome in lacertid lizards.

    Science.gov (United States)

    Rovatsos, M; Vukić, J; Kratochvíl, L

    2016-07-01

    Among amniotes, squamate reptiles are especially variable in their mechanisms of sex determination; however, based largely on cytogenetic data, some lineages possess highly evolutionary stable sex chromosomes. The still very limited knowledge of the genetic content of squamate sex chromosomes precludes a reliable reconstruction of the evolutionary history of sex determination in this group and consequently in all amniotes. Female heterogamety with a degenerated W chromosome typifies the lizards of the family Lacertidae, the widely distributed Old World clade including several hundreds of species. From the liver transcriptome of the lacertid Takydromus sexlineatus female, we selected candidates for Z-specific genes as the loci lacking single-nucleotide polymorphisms. We validated the candidate genes through the comparison of the copy numbers in the female and male genomes of T. sexlineatus and another lacertid species, Lacerta agilis, by quantitative PCR that also proved to be a reliable technique for the molecular sexing of the studied species. We suggest that this novel approach is effective for the detection of Z-specific and X-specific genes in lineages with degenerated W, respectively Y chromosomes. The analyzed gene content of the Z chromosome revealed that lacertid sex chromosomes are not homologous with those of other reptiles including birds, but instead the genes have orthologs in the X-conserved region shared by viviparous mammals. It is possible that this part of the vertebrate genome was independently co-opted for the function of sex chromosomes in viviparous mammals and lacertids because of its content of genes involved in gonad differentiation. PMID:26980341

  16. Ab initio Study of Naptho-Homologated DNA Bases

    Energy Technology Data Exchange (ETDEWEB)

    Sumpter, Bobby G [ORNL; Vazquez-Mayagoitia, Alvaro [ORNL; Huertas, Oscar [Universitat de Barcelona; Fuentes-Cabrera, Miguel A [ORNL; Orozco, Modesto [Institut de Recerca Biomedica, Parc Cientific de Barcelona, Barcelona, Spain; Luque, Javier [Universitat de Barcelona

    2008-01-01

    Naptho-homologated DNA bases have been recently used to build a new type of size expanded DNA known as yyDNA. We have used theoretical techniques to investigate the structure, tautomeric preferences, base-pairing ability, stacking interactions, and HOMO-LUMO gaps of the naptho-bases. The structure of these bases is found to be similar to that of the benzo-fused predecessors (y-bases) with respect to the planarity of the aromatic rings and amino groups. Tautomeric studies reveal that the canonical-like form of naptho-thymine (yyT) and naptho-adenine (yyA) are the most stable tautomers, leading to hydrogen-bonded dimers with the corresponding natural nucleobases that mimic the Watson-Crick pairing. However, the canonical-like species of naptho-guanine (yyG) and naptho-cytosine (yyC) are not the most stable tautomers, and the most favorable hydrogen-bonded dimers involve wobble-like pairings. The expanded size of the naphto-bases leads to stacking interactions notably larger than those found for the natural bases, and they should presumably play a dominant contribution in modulating the structure of yyDNA duplexes. Finally, the HOMO-LUMO gap of the naptho-bases is smaller than that of their benzo-base counterparts, indicating that size-expansion of DNA bases is an efficient way of reducing their HOMO-LUMO gap. These results are examined in light of the available experimental evidence reported for yyT and yyC.

  17. Genetic Manipulation of Homologous Recombination In Vivo Attenuates Intestinal Tumorigenesis.

    Science.gov (United States)

    McIlhatton, Michael A; Murnan, Kevin; Carson, Daniel; Boivin, Gregory P; Croce, Carlo M; Groden, Joanna

    2015-07-01

    Although disruption of DNA repair capacity is unquestionably associated with cancer susceptibility in humans and model organisms, it remains unclear if the inherent tumor phenotypes of DNA repair deficiency syndromes can be regulated by manipulating DNA repair pathways. Loss-of-function mutations in BLM, a member of the RecQ helicase family, cause Bloom's syndrome (BS), a rare, recessive genetic disorder that predisposes to many types of cancer. BLM functions in many aspects of DNA homeostasis, including the suppression of homologous recombination (HR) in somatic cells. We investigated whether BLM overexpression, in contrast with loss-of-function mutations, attenuated the intestinal tumor phenotypes of Apc(Min/+) and Apc(Min/+);Msh2(-/-) mice, animal models of familial adenomatous polyposis coli (FAP). We constructed a transgenic mouse line expressing human BLM (BLM-Tg) and crossed it onto both backgrounds. BLM-Tg decreased adenoma incidence in a dose-dependent manner in our Apc(Min/) (+) model of FAP, although levels of GIN were unaffected and concomitantly increased animal survival over 50%. It did not reduce intestinal tumorigenesis in Apc(Min/) (+);Msh2(-/-) mice. We used the pink-eyed unstable (p(un)) mouse model to demonstrate that increasing BLM dosage in vivo lowered endogenous levels of HR by 2-fold. Our data suggest that attenuation of the Min phenotype is achieved through a direct effect of BLM-Tg on the HR repair pathway. These findings demonstrate that HR can be manipulated in vivo to modulate tumor formation at the organismal level. Our data suggest that lowering HR frequencies may have positive therapeutic outcomes in the context of specific hereditary cancer predisposition syndromes, exemplified by FAP. PMID:25908507

  18. Promoting preschool reading

    OpenAIRE

    Istenič, Vesna

    2013-01-01

    The thesis titled Promoting preschool reading consists of a theoretiral and an empirical part. In the theoretical part I wrote about reading, the importance of reading, types of reading, about reading motivation, promoting reading motivation, internal and external motivation, influence of reading motivation on the child's reading activity, reading and familial literacy, the role of adults in promotion reading literacy, reading to a child and promoting reading in pre-school years, where I ...

  19. Sport Promotion Strategies

    OpenAIRE

    Alexandru Lucian MIHAI

    2013-01-01

    In sport marketing, the word promotion covers a range of interrelated activities. All of these activities are designed to attract attention, stimulate the interest and awareness of consumers, and of course, encourage them to purchase a sport product. Promotion is about communicating with and educating consumers. The purpose of a sport promotional strategy is to build brand loyalty and product credibility, develop image, and position the brand. A promotional strategy is similar to a marketing ...

  20. How Promotions Work

    OpenAIRE

    Robert C. Blattberg; Richard Briesch; Fox, Edward J.

    1995-01-01

    By synthesizing findings across the sales promotion literature, this article helps the reader understand how promotions work. We identify and explain empirical generalizations related to sales promotion; that is, effects that have been found consistently in multiple studies involving different researchers. We also identify issues which have generated conflicting findings in the research, as well as important sales promotion topics that have not yet been studied. This overview of the research ...

  1. Efficient generation of double heterologous promoter controlled oncolytic adenovirus vectors by a single homologous recombination step in Escherichia coli

    OpenAIRE

    Wildner Oliver; Hoffmann Dennis

    2006-01-01

    Abstract Background Oncolytic adenoviruses are promising agents for the multimodal treatment of cancer. However, tumor-selectivity is crucial for their applicability in patients. Recent studies by several groups demonstrated that oncolytic adenoviruses with tumor-/tissue-specific expression of the E1 and E4 genes, which are pivotal for adenoviral replication, have a specificity profile that is superior to viruses that solely target the expression of E1 or E4 genes. Presently the E1 and E4 reg...

  2. Constitutive expression of human coagulating factor IX in HeLa cells by homologous recombination of the promoter

    Institute of Scientific and Technical Information of China (English)

    YANG; Xiaoqing; (

    2001-01-01

    [1]Jiao Jiujiu, Grey hydrogeologic system analysis and time series model, Survey Science and Technology (in Chinese), 1987,(10): 39-43.[2]Li Shuwen, Wang Baolai, Xiao Guoqiang, A compound model of grey and periodic scrape and its application in groundwater prediction, Journal of Hebei Institute of Architectural Science & Technology (in Chinese), 1992, (3): 246-251.[3]Wang Qingyin, Li Shuwen, Grey distributed parameter model and groundwater analog, Journal of Hebei Institute of Architectural Science & Technology (in Chinese), 1992, (3): 66-70.[4]Guo Chunqing, Xia Riyuan, Liu Zhenglin, Gray Systematic Theory and Methodological Study of Krast Groundwater Resources Evaluation (in Chinese), Beijing: Geological Publishing House, 1993, 3-60.[5]Wang Qingyin, Liu Kaidi, The Mathematical Method of Grey Systematic Theory and Its Application (in Chinese), Chengdu: Publishing House of Southwestern China University of Communication, 1990, 23-27.[6]Wang Qingyin, Wu Heqing, The concept of grey number and its property, in Proceedings of NAFIPS98, USA, 1998,45-49.[7]Givoli, D., Doukhovni, I., Finite element programming approach for contact problems with geometrical nonlinearity, Computers and Structures, 1996, (8): 31-41.[8]Li Shuwen, Wang Zhiqiang, Wu Qiang, The superiority of storage-centered finite element method in solving seepage problem, Coal Geology and Exploration (in Chinese), 1999, (5): 46-49.

  3. The Drosophila BCL6 homolog Ken and Barbie promotes somatic stem cell self-renewal in the testis niche.

    Science.gov (United States)

    Issigonis, Melanie; Matunis, Erika

    2012-08-15

    Stem cells sustain tissue regeneration by their remarkable ability to replenish the stem cell pool and to generate differentiating progeny. Signals from local microenvironments, or niches, control stem cell behavior. In the Drosophila testis, a group of somatic support cells called the hub creates a stem cell niche by locally activating the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway in two adjacent types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs). Here, we find that ken and barbie (ken) is autonomously required for the self-renewal of CySCs but not GSCs. Furthermore, Ken misexpression in the CySC lineage induces the cell-autonomous self-renewal of somatic cells as well as the nonautonomous self-renewal of germ cells outside the niche. Thus, Ken, like Stat92E and its targets ZFH1 (Leatherman and Dinardo, 2008) and Chinmo (Flaherty et al., 2010), is necessary and sufficient for CySC renewal. However, ken is not a JAK-STAT target in the testis, but instead acts in parallel to Stat92E to ensure CySC self-renewal. Ken represses a subset of Stat92E targets in the embryo (Arbouzova et al., 2006) suggesting that Ken maintains CySCs by repressing differentiation factors. In support of this hypothesis, we find that the global JAK-STAT inhibitor Protein tyrosine phosphatase 61F (Ptp61F) is a JAK-STAT target in the testis that is repressed by Ken. Together, our work demonstrates that Ken has an important role in the inhibition of CySC differentiation. Studies of ken may inform our understanding of its vertebrate orthologue B-Cell Lymphoma 6 (BCL6) and how misregulation of this oncogene leads to human lymphomas. PMID:22580161

  4. The Drosophila BCL6 homolog ken and barbie promotes somatic stem cell self-renewal in the testis niche

    OpenAIRE

    Issigonis, Melanie; Matunis, Erika

    2012-01-01

    Stem cells sustain tissue regeneration by their remarkable ability to replenish the stem cell pool and to generate differentiating progeny. Signals from local microenvironments, or niches, control stem cell behavior. In the Drosophila testis, a group of somatic support cells called the hub creates a stem cell niche by locally activating the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway in two adjacent types of stem cells: germline stem cells (GSCs) and somat...

  5. What do health-promoting schools promote?

    DEFF Research Database (Denmark)

    Simovska, Venka

    2012-01-01

    -promotion interventions. Directly or indirectly the articles reiterate the idea that health promotion in schools needs to be linked with the core task of the school – education, and to the values inherent to education, such as inclusion, democracy, participation and influence, critical literacy and action competence......Purpose – The editorial aims to provide a brief overview of the individual contributions to the special issue, and a commentary positioning the contributions within research relating to the health-promoting schools initiative in Europe. Design/methodology/approach – The members of the Schools...... for Health in Europe Research Group were invited to submit their work addressing processes and outcomes in school health promotion to this special issue of Health Education. Additionally, an open call for papers was published on the Health Education web site. Following the traditional double blind peer...

  6. Developing a Promotional Video

    Science.gov (United States)

    Epley, Hannah K.

    2014-01-01

    There is a need for Extension professionals to show clientele the benefits of their program. This article shares how promotional videos are one way of reaching audiences online. An example is given on how a promotional video has been used and developed using iMovie software. Tips are offered for how professionals can create a promotional video and…

  7. Knock-in of large reporter genes in human cells via CRISPR/Cas9-induced homology-dependent and independent DNA repair.

    Science.gov (United States)

    He, Xiangjun; Tan, Chunlai; Wang, Feng; Wang, Yaofeng; Zhou, Rui; Cui, Dexuan; You, Wenxing; Zhao, Hui; Ren, Jianwei; Feng, Bo

    2016-05-19

    CRISPR/Cas9-induced site-specific DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. Extensive efforts have been made to knock-in exogenous DNA to a selected genomic locus in human cells; which, however, has focused on HDR-based strategies and was proven inefficient. Here, we report that NHEJ pathway mediates efficient rejoining of genome and plasmids following CRISPR/Cas9-induced DNA DSBs, and promotes high-efficiency DNA integration in various human cell types. With this homology-independent knock-in strategy, integration of a 4.6 kb promoterless ires-eGFP fragment into the GAPDH locus yielded up to 20% GFP+ cells in somatic LO2 cells, and 1.70% GFP+ cells in human embryonic stem cells (ESCs). Quantitative comparison further demonstrated that the NHEJ-based knock-in is more efficient than HDR-mediated gene targeting in all human cell types examined. These data support that CRISPR/Cas9-induced NHEJ provides a valuable new path for efficient genome editing in human ESCs and somatic cells. PMID:26850641

  8. Distribution of the phenotypic effects of random homologous recombination between two virus species.

    Directory of Open Access Journals (Sweden)

    Florence Vuillaume

    2011-05-01

    Full Text Available Recombination has an evident impact on virus evolution and emergence of new pathotypes, and has generated an immense literature. However, the distribution of phenotypic effects caused by genome-wide random homologous recombination has never been formally investigated. Previous data on the subject have promoted the implicit view that most viral recombinant genomes are likely to be deleterious or lethal if the nucleotide identity of parental sequences is below 90%. We decided to challenge this view by creating a bank of near-random recombinants between two viral species of the genus Begomovirus (Family Geminiviridae exhibiting 82% nucleotide identity, and by testing infectivity and in planta accumulation of recombinant clones randomly extracted from this bank. The bank was created by DNA-shuffling-a technology initially applied to the random shuffling of individual genes, and here implemented for the first time to shuffle full-length viral genomes. Together with our previously described system allowing the direct cloning of full-length infectious geminivirus genomes, it provided a unique opportunity to generate hundreds of "mosaic" virus genomes, directly testable for infectivity. A subset of 47 randomly chosen recombinants was sequenced, individually inoculated into tomato plants, and compared with the parental viruses. Surprisingly, our results showed that all recombinants were infectious and accumulated at levels comparable or intermediate to that of the parental clones. This indicates that, in our experimental system, despite the fact that the parental genomes differ by nearly 20%, lethal and/or large deleterious effects of recombination are very rare, in striking contrast to the common view that has emerged from previous studies published on other viruses.

  9. Retroviral vectors for homologous recombination provide efficient cloning and expression in mammalian cells.

    Science.gov (United States)

    Kobayashi, Eiji; Kishi, Hiroyuki; Ozawa, Tatsuhiko; Horii, Masae; Hamana, Hiroshi; Nagai, Terumi; Muraguchi, Atsushi

    2014-02-14

    Homologous recombination technologies enable high-throughput cloning and the seamless insertion of any DNA fragment into expression vectors. Additionally, retroviral vectors offer a fast and efficient method for transducing and expressing genes in mammalian cells, including lymphocytes. However, homologous recombination cannot be used to insert DNA fragments into retroviral vectors; retroviral vectors contain two homologous regions, the 5'- and 3'-long terminal repeats, between which homologous recombination occurs preferentially. In this study, we have modified a retroviral vector to enable the cloning of DNA fragments through homologous recombination. To this end, we inserted a bacterial selection marker in a region adjacent to the gene insertion site. We used the modified retroviral vector and homologous recombination to clone T-cell receptors (TCRs) from single Epstein Barr virus-specific human T cells in a high-throughput and comprehensive manner and to efficiently evaluate their function by transducing the TCRs into a murine T-cell line through retroviral infection. In conclusion, the modified retroviral vectors, in combination with the homologous recombination method, are powerful tools for the high-throughput cloning of cDNAs and their efficient functional analysis. PMID:24462869

  10. Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish.

    Science.gov (United States)

    Mochimaru, Yuta; Azuma, Morio; Oshima, Natsuki; Ichijo, Yuta; Satou, Kazuhiro; Matsuda, Kouhei; Asaoka, Yoichi; Nishina, Hiroshi; Nakakura, Takashi; Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu; Tomura, Hideaki

    2015-02-20

    Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors. PMID:25576873

  11. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress

    Science.gov (United States)

    Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S.

    2016-01-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  12. A Geometric Description of Equivariant K-Homology for Proper Actions

    CERN Document Server

    Baum, Paul; Schick, Thomas

    2009-01-01

    Let G be a discrete group and let X be a G-finite, proper G-CW-complex. We prove that Kasparov's equivariant K-homology groups KK^G(C_0(X),\\C) are isomorphic to the geometric equivariant K-homology groups of X that are obtained by making the geometric K-homology theory of Baum and Douglas equivariant in the natural way. This reconciles the original and current formulations of the Baum-Connes conjecture for discrete groups.

  13. Structure of the gene complementing uvr-402 in Streptococcus pneumoniae: homology with Escherichia coli uvrB and the homologous gene in Micrococcus luteus.

    OpenAIRE

    Sicard, N.; Oreglia, J; Estevenon, A M

    1992-01-01

    The repair ability for UV-induced damage observed for Streptococcus pneumoniae proceeds through a system similar to the Uvr-dependent system in Escherichia coli. The DNA sequence of a gene complementing uvr-402, a mutation conferring UV sensitivity, was determined. Alignments of the deduced amino acid sequence revealed an extensive sequence homology of 55% with the UvrB protein of E. coli and 59% with the UvrB-homologous protein of Micrococcus luteus. Nucleotide-binding site consensus was obs...

  14. Scaffold protein enigma homolog 1 overcomes the repression of myogenesis activation by inhibitor of DNA binding 2.

    Science.gov (United States)

    Nakatani, Miyuki; Ito, Jumpei; Koyama, Riko; Iijima, Masumi; Yoshimoto, Nobuo; Niimi, Tomoaki; Kuroda, Shun'ichi; Maturana, Andrés D

    2016-05-27

    Enigma Homolog 1 (ENH1) is a scaffold protein for signaling proteins and transcription factors. Previously, we reported that ENH1 overexpression promotes the differentiation of C2C12 myoblasts. However, the molecular mechanism underlying the role of ENH1 in the C2C12 cells differentiation remains elusive. ENH1 was shown to inhibit the proliferation of neuroblastoma cells by sequestering Inhibitor of DNA binding protein 2 (Id2) in the cytosol. Id2 is a repressor of basic Helix-Loop-Helix transcription factors activity and prevents myogenesis. Here, we found that ENH1 overcome the Id2 repression of C2C12 cells myogenic differentiation and that ENH1 overexpression promotes mice satellite cells activation, the first step toward myogenic differentiation. In addition, we show that ENH1 interacted with Id2 in C2C12 cells and mice satellite cells. Collectively, our results suggest that ENH1 plays an important role in the activation of myogenesis through the repression of Id2 activity. PMID:27114303

  15. On the Homology of Configuration Spaces Associated to Centers of Mass

    CERN Document Server

    Tamaki, Dai

    2010-01-01

    The aim of this paper is to make sample computations with the Salvetti complex of the "center of mass" arrangement introduced in [arXiv:math/0611732] by Cohen and Kamiyama. We compute the homology of the Salvetti complex of these arrangements with coefficients in the sign representation of symmetric groups on F_p in the case of four particles. We show, when p is an odd prime, the homology is isomorphic to the homology of the configuration space F(C,4) of distinct four points in the complex plane with the same coefficients. When p=2, we show the homology is different from that of F(C,4), hence obtain an alternative and more direct proof of a theorem of Cohen and Kamiyama in [arXiv:math/0611732].

  16. Analysis of genetic homology and genotyping in Carbapenems-resistant Klebsiella pneumonia

    Institute of Scientific and Technical Information of China (English)

    杨丽君

    2013-01-01

    Objective To investigate genotyping and homology of Carbapenems-resistant Klebsiella pneumonia isolated from clinical specimens.Methods A total of 175 clinical isolates of Carbapenemsresistant Klebsiella pneumoniae were isolated from clinical specimens from January 2011 to June 2012

  17. On Quillen homology and a homotopy completion tower for algebras over operads

    CERN Document Server

    Harper, John E

    2011-01-01

    We describe and study a (homotopy) completion tower for algebras and left modules over operads in symmetric spectra. We prove that a weak equivalence on topological Quillen homology induces a weak equivalence on homotopy completion, and that for $0$-connected algebras and modules over a $-1$-connected operad, the homotopy completion tower interpolates between topological Quillen homology and the identity functor. By an explicit calculation of its layers, we show that the homotopy completion tower is the precise analog---in the context of algebras and modules over operads---of the Goodwillie tower of the identity functor. As easy consequences of the strong convergence properties of the homotopy completion tower, we prove a Whitehead theorem and a Hurewicz theorem for topological Quillen homology. We also prove a relative Hurewicz theorem that provides conditions under which topological Quillen homology detects $n$-connected maps. We prove a finiteness theorem relating finiteness properties of topological Quill...

  18. Effect of hydroxyurea on the promoter occupancy profiles of tumor suppressor p53 and p73

    Directory of Open Access Journals (Sweden)

    Lu Xin

    2009-06-01

    Full Text Available Abstract Background The p53 tumor suppressor and its related protein, p73, share a homologous DNA binding domain, and mouse genetics studies have suggested that they have overlapping as well as distinct biological functions. Both p53 and p73 are activated by genotoxic stress to regulate an array of cellular responses. Previous studies have suggested that p53 and p73 independently activate the cellular apoptotic program in response to cytotoxic drugs. The goal of this study was to compare the promoter-binding activity of p53 and p73 at steady state and after genotoxic stress induced by hydroxyurea. Results We employed chromatin immunoprecipitation, the NimbleGen promoter arrays and a model-based algorithm for promoter arrays to identify promoter sequences enriched in anti-p53 or anti-p73 immunoprecipitates, either before or after treatment with hydroxyurea, which increased the expression of both p53 and p73 in the human colon cancer cell line HCT116-3(6. We calculated a model-based algorithm for promoter array score for each promoter and found a significant correlation between the promoter occupancy profiles of p53 and p73. We also found that after hydroxyurea treatment, the p53-bound promoters were still bound by p73, but p73 became associated with additional promoters that that did not bind p53. In particular, we showed that hydroxyurea induces the binding of p73 but not p53 to the promoter of MLH3, which encodes a mismatch repair protein, and causes an up-regulation of the MLH3 mRNA. Conclusion These results suggest that hydroxyurea exerts differential effects on the promoter-binding functions of p53 and p73 and illustrate the power of model-based algorithm for promoter array in the analyses of promoter occupancy profiles of highly homologous transcription factors.

  19. Homology equivalences inducing an epimorphism on the fundamental group and Quillen's plus construction

    OpenAIRE

    Rodriguez, Jose L.; Scevenels, Dirk

    2003-01-01

    Quillen's plus construction is a topological construction that kills the maximal perfect subgroup of the fundamental group of a space without changing the integral homology of the space. In this paper we show that there is a topological construction that, while leaving the integral homology of a space unaltered, kills even the intersection of the transfinite lower central series of its fundamental group. Moreover, we show that this is the maximal subgroup that can be factored out of the funda...

  20. Robust Remote Homology Detection by Feature Based Profile Hidden Markov Models

    OpenAIRE

    Plötz Thomas; Fink Gernot A.

    2005-01-01

    The detection of remote homologies is of major importance for molecular biology applications like drug discovery. The problem is still very challenging even for state-of-the-art probabilistic models of protein families, namely Profile HMMs. In order to improve remote homology detection we propose feature based semi-continuous Profile HMMs. Based on a richer sequence representation consisting of features which capture the biochemical properties of residues in their local context, family specif...

  1. The σ enigma: Bacterial σ factors, archaeal TFB and eukaryotic TFIIB are homologs

    OpenAIRE

    Burton, Samuel P; Burton, Zachary F.

    2014-01-01

    Structural comparisons of initiating RNA polymerase complexes and structure-based amino acid sequence alignments of general transcription initiation factors (eukaryotic TFIIB, archaeal TFB and bacterial σ factors) show that these proteins are homologs. TFIIB and TFB each have two-five-helix cyclin-like repeats (CLRs) that include a C-terminal helix-turn-helix (HTH) motif (CLR/HTH domains). Four homologous HTH motifs are present in bacterial σ factors that are relics of CLR/HTH domains. Sequen...

  2. ANTIGENIC RELATEDNESS OF SELECTED FLAVIVIRUSES: STUDY WITH HOMOLOGOUS AND HETEROLOGOUS IMMUNE MOUSE ASCITIC FLUIDS

    OpenAIRE

    S.S. Baba; Fagbami, A. H.; O. D. OLALEYE

    1998-01-01

    The antigenic relationship of 9 flaviviruses, Yellow fever (YF) , Wesselsbron (WSL) , Uganda S (UGS) , Potiskum (POT), West Nile (WN) , Banzi (BAN) , Zika (ZK) , Dengue type 1 (DEN-1) and Dengue type 2 (DEN-2), was assessed by cross-haemagglutination-inhibition (Cross-HI) and cross-complement fixation (Cross-CF) reactions between each of the viruses and their homologous immune mouse ascitic fluids. Titre ratios were calculated using the heterologous and homologous titres. Cross-CF reactions r...

  3. Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling

    OpenAIRE

    Oviedo, Néstor J.; Pearson, Bret J.; Levin, Michael; Sánchez Alvarado, Alejandro

    2008-01-01

    We have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stem cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1 and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting pheno...

  4. Hyperplasia of interstitial cells of cajal in sprouty homolog 4 deficient mice.

    Directory of Open Access Journals (Sweden)

    An Thys

    Full Text Available Gastrointestinal stromal tumors, which are thought to derive from interstitial cells of Cajal or their precursors, often harbor an oncogenic mutation of the KIT receptor tyrosine kinase. Sprouty homolog 4, a known negative regulator of ERK pathway, has been identified in the interstitial cells of Cajal in the KitK641E murine model of gastrointestinal stromal tumors. Sprouty homolog 4 was upregulated both at the mRNA and protein level in these cells, suggesting that Sprouty homolog 4 is downstream of oncogenic KIT activation and potentially engaged in the negative feedback loop of ERK activation in this model. Here, we used KitK641E heterozygous and Sprouty homolog 4 knock out animals to quantify interstitial cells of Cajal in situ, using quantitative immunofluorescence for the receptor tyrosine kinase Kit and for phosphodiesterase 3a (PDE3A. In the antrum of Sprouty homolog 4 knock out mice, hyperplasia of interstitial cells of Cajal was reminiscent of the KitK641E heterozygous mice antrum. Additionally, the density of interstitial cells of Cajal was higher in the colon of adult Sprouty homolog 4 knock out mice than in WT littermates, although hyperplasia seemed more severe in KitK641E heterozygous mice. Functional transit studies also show similarities between Sprouty homolog 4 knock out and KitK641E heterozygous mice, as the total transit time in 9 month old animals was significantly increased in both genotypes compared to WT littermates. We concluded that the lack of Sprouty homolog 4 expression leads to hyperplasia of the interstitial cells of Cajal and is functionally associated with a delayed transit time.

  5. Rounding corners of polygons and the embedded contact homology of T^3

    OpenAIRE

    Hutchings, Michael; Sullivan, Michael C

    2004-01-01

    The embedded contact homology (ECH) of a 3-manifold with a contact form is a variant of Eliashberg-Givental-Hofer's symplectic field theory, which counts certain embedded J-holomorphic curves in the symplectization. We show that the ECH of T^3 is computed by a combinatorial chain complex which is generated by labeled convex polygons in the plane with vertices at lattice points, and whose differential involves `rounding corners'. We compute the homology of this combinatorial chain complex. The...

  6. Drosophila homologs of transcriptional mediator complex subunits are required for adult cell and segment identity specification

    OpenAIRE

    Boube, Muriel; Faucher, Christian; Joulia, Laurent; Cribbs, David L.; Bourbon, Henri-Marc

    2000-01-01

    The origins of specificity in gene expression are a central concern in understanding developmental control. Mediator protein complexes regulate transcriptional initiation, acting as modular adaptors linking specific transcription factors to core RNA polymerase II. Here, we identified the Drosophila homologs of 23 human mediator genes and mutations of two, dTRAP240 and of dTRAP80 (the putative fly homolog of yeast SRB4). Clonal analysis indicates a general role for dTRAP80 necessary for cell v...

  7. Equidistribution of geodesics on homology classes and analogues for free groups

    DEFF Research Database (Denmark)

    Risager, Morten S.

    2008-01-01

    We investigate how often geodesics have homology in a fixed set of the homology lattice of a compact Riemann surface. We prove that closed geodesics are equidistributed on any set with asymptotic density with respect to a specific norm. We explain the analogues for free groups, conjugacy classes ...... and discrete logarithms, in particular, we investigate the density of conjugacy classes with relatively prime discrete logarithms....

  8. Optimal Cloning of PCR Fragments by Homologous Recombination in Escherichia coli

    OpenAIRE

    Jacobus, Ana Paula; Gross, Jeferson

    2015-01-01

    PCR fragments and linear vectors containing overlapping ends are easily assembled into a propagative plasmid by homologous recombination in Escherichia coli. Although this gap-repair cloning approach is straightforward, its existence is virtually unknown to most molecular biologists. To popularize this method, we tested critical parameters influencing the efficiency of PCR fragments cloning into PCR-amplified vectors by homologous recombination in the widely used E. coli strain DH5α. We found...

  9. Different functions for homologous serotonergic interneurons and serotonin in species-specific rhythmic behaviours

    OpenAIRE

    Newcomb, James M.; Katz, Paul S.

    2008-01-01

    Closely related species can exhibit different behaviours despite homologous neural substrates. The nudibranch molluscs Tritonia diomedea and Melibe leonina swim differently, yet their nervous systems contain homologous serotonergic neurons. In Tritonia, the dorsal swim interneurons (DSIs) are members of the swim central pattern generator (CPG) and their neurotransmitter serotonin is both necessary and sufficient to elicit a swim motor pattern. Here it is shown that the DSI homologues in Melib...

  10. DNA synaptase: an enzyme that fuses DNA molecules at a region of homology.

    OpenAIRE

    Potter, H; Dressler, D

    1980-01-01

    This paper describes an enzyme from Escherichia coli, and its purification to apparent homogeneity. The protein, which we call "DNA synaptase" and which may be representative of a class of enzymes, fuses double-stranded DNA molecules at a region of homology. In addition, the purified enzyme is able to catalyze the association of single-stranded DNA with homologous duplex DNA. The genome fusion reaction catalyzed by the purified enzyme occurs in the presence of Mg2+, spermidine, and 2-mercapto...

  11. Evolutionarily different alphoid repeat DNA on homologous chromosomes in human and chimpanzee.

    OpenAIRE

    Jørgensen, A L; Laursen, H B; Jones, C; Bak, A L

    1992-01-01

    Centromeric alphoid DNA in primates represents a class of evolving repeat DNA. In humans, chromosomes 13 and 21 share one subfamily of alphoid DNA while chromosomes 14 and 22 share another subfamily. We show that similar pairwise homogenizations occur in the chimpanzee (Pan troglodytes), where chromosomes 14 and 22, homologous to human chromosomes 13 and 21, share one partially homogenized alphoid DNA subfamily and chromosomes 15 and 23, homologous to human chromosomes 14 and 22, share anothe...

  12. Homology between the glycoproteins of vesicular stomatitis virus and rabies virus.

    OpenAIRE

    Rose, J. K.; Doolittle, R. F.; Anilionis, A; Curtis, P J; Wunner, W H

    1982-01-01

    We compared the predicted amino acid sequences of the vesicular stomatitis virus and rabies virus glycoproteins by using a computer program which provides an optimal alignment and a statistical significance for the match. Highly significant homology between these two proteins was detected, including identical positioning of one glycosylation site. A significant homology between the predicted amino acid sequences of vesicular stomatitis virus and influenza virus matrix proteins was also found.

  13. The Homology Relation between Molecules: a Revival of an Old Way for Classification of Molecules

    OpenAIRE

    Dobrowolski, Jan Cz.

    2009-01-01

    The homology (homolo) relation between molecules was introduced. This relation is a generalization of an old idea of series of homologous compounds. The homolo relation operates on a molecule by removing all the structural fragments that are identical with a certain selected fragment. As a result a multiset of fragments is produced. It was shown that the homolo relation is an equivalence relation in a set of molecules. Thus, by choosing various reference fragments, the molecules can be classi...

  14. Gene silencing and homology-dependent gene silencing in Arabidopsis: genetic modifiers and DNA methylation.

    OpenAIRE

    Furner, I J; Sheikh, M. A.; Collett, C E

    1998-01-01

    Transgenes inserted into the plant genome can become inactive (gene silencing) or result in silencing of homologous cellular genes [homology-dependent gene silencing (HDG silencing)]. In an earlier study we reported HDG silencing of chalcone synthase (CHS) in Arabidopsis. This study concerns genetic revertants of one of the CHS HDG-silencing transgenic homozygotes. Two monogenic recessive trans-acting mutations (hog1 and ddm1) that impair gene silencing and HDG silencing were identified. Thes...

  15. Functional Analysis of Three Sulfide:Quinone Oxidoreductase Homologs in Chlorobaculum tepidum▿ †

    OpenAIRE

    Chan, Leong-Keat; Morgan-Kiss, Rachael M; Hanson, Thomas E.

    2008-01-01

    Sulfide:quinone oxidoreductase (SQR) catalyzes sulfide oxidation during sulfide-dependent chemo- and phototrophic growth in bacteria. The green sulfur bacterium Chlorobaculum tepidum (formerly Chlorobium tepidum) can grow on sulfide as the sole electron donor and sulfur source. C. tepidum contains genes encoding three SQR homologs: CT0117, CT0876, and CT1087. This study examined which, if any, of the SQR homologs possess sulfide-dependent ubiquinone reduction activity and are required for gro...

  16. Predicting RNA secondary structure by the comparative approach: how to select the homologous sequences

    Directory of Open Access Journals (Sweden)

    Tahi Fariza

    2007-11-01

    Full Text Available Abstract Background The secondary structure of an RNA must be known before the relationship between its structure and function can be determined. One way to predict the secondary structure of an RNA is to identify covarying residues that maintain the pairings (Watson-Crick, Wobble and non-canonical pairings. This "comparative approach" consists of identifying mutations from homologous sequence alignments. The sequences must covary enough for compensatory mutations to be revealed, but comparison is difficult if they are too different. Thus the choice of homologous sequences is critical. While many possible combinations of homologous sequences may be used for prediction, only a few will give good structure predictions. This can be due to poor quality alignment in stems or to the variability of certain sequences. This problem of sequence selection is currently unsolved. Results This paper describes an algorithm, SSCA, which measures the suitability of sequences for the comparative approach. It is based on evolutionary models with structure constraints, particularly those on sequence variations and stem alignment. We propose three models, based on different constraints on sequence alignments. We show the results of the SSCA algorithm for predicting the secondary structure of several RNAs. SSCA enabled us to choose sets of homologous sequences that gave better predictions than arbitrarily chosen sets of homologous sequences. Conclusion SSCA is an algorithm for selecting combinations of RNA homologous sequences suitable for secondary structure predictions with the comparative approach.

  17. Evidence of protein-free homology recognition in magnetic bead force–extension experiments

    Science.gov (United States)

    (O’) Lee, D. J.; Danilowicz, C.; Rochester, C.; Prentiss, M.

    2016-01-01

    Earlier theoretical studies have proposed that the homology-dependent pairing of large tracts of dsDNA may be due to physical interactions between homologous regions. Such interactions could contribute to the sequence-dependent pairing of chromosome regions that may occur in the presence or the absence of double-strand breaks. Several experiments have indicated the recognition of homologous sequences in pure electrolytic solutions without proteins. Here, we report single-molecule force experiments with a designed 60 kb long dsDNA construct; one end attached to a solid surface and the other end to a magnetic bead. The 60 kb constructs contain two 10 kb long homologous tracts oriented head to head, so that their sequences match if the two tracts fold on each other. The distance between the bead and the surface is measured as a function of the force applied to the bead. At low forces, the construct molecules extend substantially less than normal, control dsDNA, indicating the existence of preferential interaction between the homologous regions. The force increase causes no abrupt but continuous unfolding of the paired homologous regions. Simple semi-phenomenological models of the unfolding mechanics are proposed, and their predictions are compared with the data. PMID:27493568

  18. Homology Priority Task Scheduling in μC/OS-Ⅱ Real-Time Kernel

    Institute of Scientific and Technical Information of China (English)

    WANG Xibo; ZHOU Benhai; YU Ge; LI Qian

    2007-01-01

    μC/OS- Ⅱ is an open source real-time kernel adopting priority preemptive schedule strategy. Aiming at the problem of μC/OS-Ⅱ failing to support homology priority tasks scheduling,an approach for solution is proposed. The basic idea is adding round-robin scheduling strategy in its original scheduler in order to schedule homology priority tasks through time slice roundrobin. Implementation approach is given in detail. Firstly, the Task Control Block (TCB) is extended. And then, a new priority index table is created, in which each index pointer points to a set of homology priority tasks. Eventually, on the basis of reconstructing μC/OS-Ⅱ real-time kernel, task scheduling module is rewritten.Otherwise, schedulability of homology task supported by modified kernel had been analyzed, and deadline formula of created homology tasks is given. By theoretical analysis and experiment verification, the modified kernel can support homology priority tasks scheduling, meanwhile, it also remains preemptive property of original μC/OS- Ⅱ.

  19. Possible universal quantum algorithms for generalized Khovanov homology and the Rasmussen's invariant

    Science.gov (United States)

    Vélez, Mario; Ospina, Juan

    2012-06-01

    Possible quantum algorithms for generalized Khovanov homology and the Rasmussen's invariant are proposed. Such algorithms are resulting from adaptations of the recently proposed Kauffman's algorithm for the standard Khovanov homology. The method that was applied consists in to write the relevant quantum invariant as the trace of a certain unitary operator and then to compute the trace using the Hadamard test. We apply such method to the quantum computation of the Jones polynomial, HOMFLY polynomial, Chromatic polynomial, Tutte polynomial and Bollobàs- Riordan polynomial. These polynomials are quantum topological invariants for knots, links, graphs and ribbon graphs respectively. The Jones polynomial is categorified by the standard Khovanov homology and the others polynomials are categorified by generalized Khovanov homologies, such as the Khovanov-Rozansky homology and the graph homologies. The algorithm for the Rasmussen's invariant is obtained using the gauge theory; and the recently introduced program of homotopyfication is linked with the super-symmetric quantum mechanics. It is claimed that a new program of analytification could be development from the homotopyfication using the celebrated Atiyah-Singer theorem and its super-symmetric interpretations. It is hoped that the super-symmetric quantum mechanics provides the hardware for the implementation of the proposed quantum algorithms.

  20. Successful event promotions

    OpenAIRE

    Vitikainen, Anna; Pakarinen, Siiri

    2015-01-01

    The field of event promotions is a growing industry. As it is still a new area of business, the information available is broad and not very detailed. Promotions are usually seen as a bigger field in advertising and specific information about event promotions is more difficult to find. Today marketing is shifting from basic, traditional advertising to digital marketing and telling the brands’ story by creating an unforgettable and positive experience. Companies are trying to come up with new w...