WorldWideScience

Sample records for artemis promote homologous

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

    Science.gov (United States)

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

    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 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.

  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. Variable correction of Artemis deficiency by I-Sce1-meganuclease-assisted homologous recombination in murine hematopoietic stem cells.

    Science.gov (United States)

    Rivière, J; Hauer, J; Poirot, L; Brochet, J; Souque, P; Mollier, K; Gouble, A; Charneau, P; Fischer, A; Pâques, F; de Villartay, J-P; Cavazzana, M

    2014-05-01

    The correction of genetic mutations by homologous recombination is an attractive approach to gene therapy. We used the DNA double-strand breaks introduced by the site-specific endonuclease I-Sce1 as a means of increasing homologous recombination of an exogenous DNA template in murine hematopoietic stem cells (mHSCs). To develop this approach, we chose an Artemis knockout (Art(-/-)) mouse in which exon 12 of the Artemis gene had been replaced by an I-Sce1 recognition site. The I-Sce1 enzyme and the Artemis correction template were each delivered by a self-inactivating (SIN)-integrase-defective lentiviral vector (SIN-IDLV-CMV-ISce1 and SIN-IDLV-Art, respectively). Transduction of Art(-/-) mHSCs with the two vectors successfully reverted the Art(-/-) phenotype in 2 of our 10 experiments. Even though the potential for genotoxicity has yet to be evaluated, this new approach to gene editing appears to be promising. Improving the efficacy of this approach will require further technical work.

  4. Nucleosome resection at a double-strand break during Non-Homologous Ends Joining in mammalian cells - implications from repressive chromatin organization and the role of ARTEMIS

    Directory of Open Access Journals (Sweden)

    De Benedetti Arrigo

    2011-01-01

    Full Text Available Abstract Background The S. cerevisiae mating type switch model of double-strand break (DSB repair, utilizing the HO endonuclease, is one of the best studied systems for both Homologous Recombination Repair (HRR and direct ends-joining repair (Non-Homologous Ends Joining - NHEJ. We have recently transposed that system to a mammalian cell culture model taking advantage of an adenovirus expressing HO and an integrated genomic target. This made it possible to compare directly the mechanism of repair between yeast and mammalian cells for the same type of induced DSB. Studies of DSB repair have emphasized commonality of features, proteins and machineries between organisms, and differences when conservation is not found. Two proteins that stand out that differ between yeast and mammalian cells are DNA-PK, a protein kinase that is activated by the presence of DSBs, and Artemis, a nuclease whose activity is modulated by DNA-PK and ATM. In this report we describe how these two proteins may be involved in a specific pattern of ends-processing at the DSB, particularly in the context of heterochromatin. Findings We previously published that the repair of the HO-induced DSB was generally accurate and occurred by simple rejoining of the cohesive 3'-overhangs generated by HO. During continuous passage of those cells in the absence of puromycin selection, the locus appears to have become more heterochromatic and silenced by displaying several features. 1 The site had become less accessible to cleavage by the HO endonuclease; 2 the expression of the puro mRNA, which confers resistance to puromycin, had become reduced; 3 occupancy of nucleosomes at the site (ChIP for histone H3 was increased, an indicator for more condensed chromatin. After reselection of these cells by addition of puromycin, many of these features were reversed. However, even the reselected cells were not identical in the pattern of cleavage and repair as the cells when originally created

  5. 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...

  6. The ARTEMIS mission

    CERN Document Server

    Angelopoulos, Vassilis

    2014-01-01

    The ARTEMIS mission was initiated by skillfully moving the two outermost Earth-orbiting THEMIS spacecraft into lunar orbit to conduct unprecedented dual spacecraft observations of the lunar environment. ARTEMIS stands for Acceleration, Reconnection, Turbulence and Electrodynamics of the Moon's Interaction with the Sun. Indeed, this volume discusses initial findings related to the Moon’s magnetic and plasma environments and the electrical conductivity of the lunar interior. This work is aimed at researchers and graduate students in both heliophysics and planetary physics. Originally published in Space Science Reviews, Vol. 165/1-4, 2011.

  7. Artemis is required to improve the accuracy of repair of double-strand breaks with 5'-blocked termini generated from non-DSB-clustered lesions.

    Science.gov (United States)

    Malyarchuk, Svitlana; Castore, Reneau; Shi, Runhua; Harrison, Lynn

    2013-05-01

    Clustered DNA lesions are defined as ≥2 damage events within 20 bp. Oxidised bases, abasic (AP) sites, single-strand breaks and double-strand breaks (DSBs) exist in radiation-induced clusters, and these lesions are more difficult to repair and can be more mutagenic than single lesions. Understanding clustered lesion repair is therefore important for the design of complementary treatments to enhance radiotherapy. Non-DSB-clustered lesions consisting of opposing AP sites can be converted to DSBs by base excision repair, and non-homologous end-joining (NHEJ) plays a role in repairing these DSBs. Artemis is an endonuclease that removes blocking groups from DSB termini during NHEJ. Hence, we hypothesised that Artemis plays a role in the processing of DSBs or complex DSBs generated from non-DSB-clustered lesions. We examined the repair of clusters containing two or three lesions in wild-type (WT) or Artemis-deficient (ART(-/-)) mouse fibroblasts using a reporter plasmid. Each cluster contained two opposing tetrahydrofurans (an AP site analogue), which AP endonuclease can convert to a DSB with blocked 5' termini. Loss of Artemis did not decrease plasmid survival, but did result in more mutagenic repair with plasmids containing larger deletions. This increase in deletions did not occur with ClaI-linearised plasmid. Since Mre11 has been implicated in deletional NHEJ, we used small interfering RNA to reduce Mre11 in WT and ART(-/-) cells, but decreasing Mre11 did not change the size of deletions in the repair products. This work implicates Artemis in limiting the deletions introduced during repair of 5'-blocked termini DSBs generated from non-DSB-clustered lesions. Decreasing repair accuracy without decreasing repair capacity could result in mutated cells surviving irradiation. Inhibiting Artemis in normal cells could promote carcinogenesis, while in tumour cells enhanced mutagenic repair following irradiation could promote tumour recurrence.

  8. lac Up-promoter mutants with increased homology to the consensus promoter sequence.

    OpenAIRE

    Mandecki, W; Goldman, R A; Powell, B S; Caruthers, M H

    1985-01-01

    Four lac promoter mutants were constructed. The mutations increased the homology between the lac promoter and the consensus promoter sequences by introducing the consensus -10 and -35 regions and the consensus spacing of 17 residues between these two regions. The promoter mutants were cloned into a pBR322-derivatized vector upstream from the lacZ gene, and levels of beta-galactosidase were an indication of promoter activity. All mutants exhibited higher activity than did the wild-type promoter.

  9. 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.

  10. 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.

  11. COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining.

    Science.gov (United States)

    Lemmens, Bennie B L G; Johnson, Nicholas M; Tijsterman, Marcel

    2013-01-01

    Successful completion of meiosis requires the induction and faithful repair of DNA double-strand breaks (DSBs). DSBs can be repaired via homologous recombination (HR) or non-homologous end joining (NHEJ), yet only repair via HR can generate the interhomolog crossovers (COs) needed for meiotic chromosome segregation. Here we identify COM-1, the homolog of CtIP/Sae2/Ctp1, as a crucial regulator of DSB repair pathway choice during Caenorhabditis elegans gametogenesis. COM-1-deficient germ cells repair meiotic DSBs via the error-prone pathway NHEJ, resulting in a lack of COs, extensive chromosomal aggregation, and near-complete embryonic lethality. In contrast to its yeast counterparts, COM-1 is not required for Spo11 removal and initiation of meiotic DSB repair, but instead promotes meiotic recombination by counteracting the NHEJ complex Ku. In fact, animals defective for both COM-1 and Ku are viable and proficient in CO formation. Further genetic dissection revealed that COM-1 acts parallel to the nuclease EXO-1 to promote interhomolog HR at early pachytene stage of meiotic prophase and thereby safeguards timely CO formation. Both of these nucleases, however, are dispensable for RAD-51 recruitment at late pachytene stage, when homolog-independent repair pathways predominate, suggesting further redundancy and/or temporal regulation of DNA end resection during meiotic prophase. Collectively, our results uncover the potentially lethal properties of NHEJ during meiosis and identify a critical role for COM-1 in NHEJ inhibition and CO assurance in germ cells.

  12. An Artemis polymorphic variant reduces Artemis activity and confers cellular radiosensitivity

    NARCIS (Netherlands)

    Woodbine, Lisa; Grigoriadou, Sofia; Goodarzi, Aaron A.; Riballo, Enriqueta; Tape, Christopher; Oliver, Antony W.; van Zelm, Menno C.; Buckland, Matthew S.; Davies, E. Graham; Pearl, Laurence H.; Jeggo, Penny A.

    2010-01-01

    Artemis is required for V(D)J recombination and the repair of a subset of radiation-induced DNA double strand breaks (DSBs). Artemis-null patients display radiosensitivity (RS) and severe combined immunodeficiency (SCID), classified as RS-SCID. Strongly impacting hypomorphic Artemis mutations confer

  13. ARTEMIS orbit raising inflight experience with ion propulsion

    Science.gov (United States)

    Killinger, Rainer; Kukies, Ralf; Surauer, Michael; Tomasetto, Angeo; van Holtz, Leo

    2003-08-01

    To demonstrate and promote North/South station keeping (inclination control) using ion propulsion, ESA on July 12, 2001 onboard Ariane 510 launched its most advanced telecommunication satellite: ARTEMIS. Due to a launcher failure the satellite was injected into a useless too low elliptic orbit. The ARTEMIS mission was salvaged by an Alenia Spazio / Astrium / ESA team at Telespazio (Fucino) using in novel modes to operate the on-board chemical and ion propulsion systems provided by Astrium. Using the chemical propulsion_ system provided by Astrium GmbH - Lampoldshausen - the inital orbit, having an apogee of half the targeted altitude. was quickly upgraded to a safe circular parking orbit at 31000 km altitude. The Liquid Apogee Engine was fired in total 8 times to achieve apogee as well as perigee raising. The final orbit raising to geostationary altitude is being performed by means of the ion propulsion system (IPP) applied in a newly designed spacecraft attitude control mode. Alenia Spazio and Astrium, in close cooperation, quickly redesigned all control and data handling software modules affected since the original spacecraft configuration was designed for inclination control only and not to generate thrust with the ion engines in a direction tangential to the orbit. The flexibility of the IPP system consisting of 4 thruster assemblies, provided in its totality by Astrium including the 2 alignment mechanisms for precision thrust direction control, had proven invaluable. To demonstrate the technologies available in Europe and to enhanced reliability, Astrium implemented two different technologies: a Kaufmann type system (EITA) provided by Astrium Ltd. - Portsmouth; and a Radiofrequency Ion Thruster Assembly (RITA) provided by Astrium GmbH - Ottobrunn. Two ion engines of different technology were mounted side by side on one ITAM (Ion Thruster Alignment Mechanism) provided by Austrian Aerospace. Artemis, after EURECA launched on 31 July 1992 and retrieved on 1 July

  14. KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair.

    Directory of Open Access Journals (Sweden)

    Yi-Hui Lin

    Full Text Available Homologous recombination and non-homologous end joining are two major DNA double-strand-break repair pathways. While HR-mediated repair requires a homologous sequence as the guiding template to restore the damage site precisely, NHEJ-mediated repair ligates the DNA lesion directly and increases the risk of losing nucleotides. Therefore, how a cell regulates the balance between HR and NHEJ has become an important issue for maintaining genomic integrity over time. Here we report that SIRT1-dependent KAP1 deacetylation positively regulates NHEJ. We show that up-regulation of KAP1 attenuates HR efficiency while promoting NHEJ repair. Moreover, SIRT1-mediated KAP1 deacetylation further enhances the effect of NHEJ by stabilizing its interaction with 53BP1, which leads to increased 53BP1 focus formation in response to DNA damage. Taken together, our study suggests a SIRT1-KAP1 regulatory mechanism for HR-NHEJ repair pathway choice.

  15. 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.

  16. Chromosome movements promoted by the mitochondrial protein SPD-3 are required for homology search during Caenorhabditis elegans meiosis.

    Directory of Open Access Journals (Sweden)

    Leticia Labrador

    2013-05-01

    Full Text Available Pairing of homologous chromosomes during early meiosis is essential to prevent the formation of aneuploid gametes. Chromosome pairing includes a step of homology search followed by the stabilization of homolog interactions by the synaptonemal complex (SC. These events coincide with dramatic changes in nuclear organization and rapid chromosome movements that depend on cytoskeletal motors and are mediated by SUN-domain proteins on the nuclear envelope, but how chromosome mobility contributes to the pairing process remains poorly understood. We show that defects in the mitochondria-localizing protein SPD-3 cause a defect in homolog pairing without impairing nuclear reorganization or SC assembly, which results in promiscuous installation of the SC between non-homologous chromosomes. Preventing SC assembly in spd-3 mutants does not improve homolog pairing, demonstrating that SPD-3 is required for homology search at the start of meiosis. Pairing center regions localize to SUN-1 aggregates at meiosis onset in spd-3 mutants; and pairing-promoting proteins, including cytoskeletal motors and polo-like kinase 2, are normally recruited to the nuclear envelope. However, quantitative analysis of SUN-1 aggregate movement in spd-3 mutants demonstrates a clear reduction in mobility, although this defect is not as severe as that seen in sun-1(jf18 mutants, which also show a stronger pairing defect, suggesting a correlation between chromosome-end mobility and the efficiency of pairing. SUN-1 aggregate movement is also impaired following inhibition of mitochondrial respiration or dynein knockdown, suggesting that mitochondrial function is required for motor-driven SUN-1 movement. The reduced chromosome-end mobility of spd-3 mutants impairs coupling of SC assembly to homology recognition and causes a delay in meiotic progression mediated by HORMA-domain protein HTP-1. Our work reveals how chromosome mobility impacts the different early meiotic events that promote

  17. Homologous recombination promoted by reverse transcriptase during copying of two distinct RNA templates.

    Science.gov (United States)

    Negroni, M; Ricchetti, M; Nouvel, P; Buc, H

    1995-01-01

    Retroviruses are known to mutate at high rates. An important source of genetic variability is recombination taking place during reverse transcription of internal regions of the two genomic RNAs. We have designed an in vitro model system, involving genetic markers carried on two RNA templates, to allow a search for individual recombination events and to score their frequency of occurrence. We show that Moloney murine leukemia virus reverse transcriptase alone promotes homologous recombination efficiently. While RNA concentration has little effect on recombination frequency, there is a clear correlation between the amount of reverse transcriptase used in the assay and the extent of recombination observed. Under conditions mimicking the in vivo situation, a rate compatible with ex vivo estimates has been obtained. PMID:7542781

  18. LEDGF (p75) promotes DNA-end resection and homologous recombination

    DEFF Research Database (Denmark)

    Daugaard, Mads; Baude, Annika; Fugger, Kasper

    2012-01-01

    ) by the homologous recombination repair pathway. Depletion of LEDGF impairs the recruitment of C-terminal binding protein interacting protein (CtIP) to DNA DSBs and the subsequent CtIP-dependent DNA-end resection. LEDGF is constitutively associated with chromatin through its Pro-Trp-Trp-Pro (PWWP) domain that binds......Lens epithelium-derived growth factor p75 splice variant (LEDGF) is a chromatin-binding protein known for its antiapoptotic activity and ability to direct human immunodeficiency virus into active transcription units. Here we show that LEDGF promotes the repair of DNA double-strand breaks (DSBs...... preferentially to epigenetic methyl-lysine histone markers characteristic of active transcription units. LEDGF binds CtIP in a DNA damage-dependent manner, thereby enhancing its tethering to the active chromatin and facilitating its access to DNA DSBs. These data highlight the role of PWWP-domain proteins in DNA...

  19. ATPase activity tightly regulates RecA nucleofilaments to promote homologous recombination

    Science.gov (United States)

    Zhao, Bailin; Zhang, Dapeng; Li, Chengmin; Yuan, Zheng; Yu, Fangzhi; Zhong, Shangwei; Jiang, Guibin; Yang, Yun-Gui; Le, X Chris; Weinfeld, Michael; Zhu, Ping; Wang, Hailin

    2017-01-01

    Homologous recombination (HR), catalyzed in an evolutionarily conserved manner by active RecA/Rad51 nucleofilaments, maintains genomic integrity and promotes biological evolution and diversity. The structures of RecA/Rad51 nucleofilaments provide information critical for the entire HR process. By exploiting a unique capillary electrophoresis-laser-induced fluorescence polarization assay, we have discovered an active form of RecA nucleofilament, stimulated by ATP hydrolysis, that contains mainly unbound nucleotide sites. This finding was confirmed by a nuclease protection assay and electron microscopy (EM) imaging. We further found that these RecA-unsaturated filaments promote strand exchange in vitro and HR in vivo. RecA mutants (P67D and P67E), which only form RecA-unsaturated nucleofilaments, were able to mediate HR in vitro and in vivo, but mutants favoring the formation of the saturated nucleofilaments failed to support HR. We thus present a new model for RecA-mediated HR in which RecA utilizes its intrinsic DNA binding-dependent ATPase activity to remodel the nucleofilaments to a less saturated form and thereby promote HR. PMID:28101376

  20. 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.

  1. Genome-Wide Demethylation Promotes Triplet Repeat Instability Independently of Homologous Recombination

    Science.gov (United States)

    Dion, Vincent; Lin, Yunfu; Price, Brandee A.; Fyffe, Sharyl L.; Seluanov, Andrei; Gorbunova, Vera; Wilson, John H.

    2008-01-01

    Trinucleotide repeat instability is intrinsic to a family of human neurodegenerative diseases. The mechanism leading to repeat length variation is unclear. We previously showed that treatment with the demethylating agent 5-aza-2′-deoxycytidine (5-aza-CdR) dramatically increases triplet repeat instability in mammalian cells. Based on previous reports that demethylation increases homologous recombination (HR), and our own observations that HR destabilizes triplet repeats, we hypothesized that demethylation alters repeat stability by stimulating HR. Here, we test that hypothesis at the Aprt (adenosine phosphoribosyl transferase) locus in CHO cells, where CpG demethylation and HR have both been shown to increase CAG repeat instability. We find that the rate of HR at the Aprt locus is not altered by demethylation. The spectrum of recombinants, however, was shifted from the usual 6:1 ratio of conversions to crossovers to more equal proportions in 5-aza-CdR-treated cells. The subtle influences of demethylation on HR at the Aprt locus are not sufficient to account for its dramatic effects on repeat instability. We conclude that 5-aza-CdR promotes triplet repeat instability independently of HR. PMID:18083071

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

    Science.gov (United States)

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

    2011-10-01

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

  3. Identification of genes that promote or antagonize somatic homolog pairing using a high-throughput FISH-based screen.

    Directory of Open Access Journals (Sweden)

    Eric F Joyce

    Full Text Available The pairing of homologous chromosomes is a fundamental feature of the meiotic cell. In addition, a number of species exhibit homolog pairing in nonmeiotic, somatic cells as well, with evidence for its impact on both gene regulation and double-strand break (DSB repair. An extreme example of somatic pairing can be observed in Drosophila melanogaster, where homologous chromosomes remain aligned throughout most of development. However, our understanding of the mechanism of somatic homolog pairing remains unclear, as only a few genes have been implicated in this process. In this study, we introduce a novel high-throughput fluorescent in situ hybridization (FISH technology that enabled us to conduct a genome-wide RNAi screen for factors involved in the robust somatic pairing observed in Drosophila. We identified both candidate "pairing promoting genes" and candidate "anti-pairing genes," providing evidence that pairing is a dynamic process that can be both enhanced and antagonized. Many of the genes found to be important for promoting pairing are highly enriched for functions associated with mitotic cell division, suggesting a genetic framework for a long-standing link between chromosome dynamics during mitosis and nuclear organization during interphase. In contrast, several of the candidate anti-pairing genes have known interphase functions associated with S-phase progression, DNA replication, and chromatin compaction, including several components of the condensin II complex. In combination with a variety of secondary assays, these results provide insights into the mechanism and dynamics of somatic pairing.

  4. The eukaryotic Pso2/Snm1/Artemis proteins and their function as genomic and cellular caretakers

    Directory of Open Access Journals (Sweden)

    D. Bonatto

    2005-03-01

    Full Text Available DNA double-strand breaks (DSBs represent a major threat to the genomic stability of eukaryotic cells. DNA repair mechanisms such as non-homologous end joining (NHEJ are responsible for the maintenance of eukaryotic genomes. Dysfunction of one or more of the many protein complexes that function in NHEJ can lead to sensitivity to DNA damaging agents, apoptosis, genomic instability, and severe combined immunodeficiency. One protein, Pso2p, was shown to participate in the repair of DSBs induced by DNA inter-strand cross-linking (ICL agents such as cisplatin, nitrogen mustard or photo-activated bi-functional psoralens. The molecular function of Pso2p in DNA repair is unknown, but yeast and mammalian cell line mutants for PSO2 show the same cellular responses as strains with defects in NHEJ, e.g., sensitivity to ICLs and apoptosis. The Pso2p human homologue Artemis participates in V(DJ recombination. Mutations in Artemis induce a variety of immunological deficiencies, a predisposition to lymphomas, and an increase in chromosomal aberrations. In order to better understand the role of Pso2p in the repair of DSBs generated as repair intermediates of ICLs, an in silico approach was used to characterize the catalytic domain of Pso2p, which led to identification of novel Pso2p homologues in other organisms. Moreover, we found the catalytic core of Pso2p fused to different domains. In plants, a specific ATP-dependent DNA ligase I contains the catalytic core of Pso2p, constituting a new DNA ligase family, which was named LIG6. The possible functions of Pso2p/Artemis/Lig6p in NHEJ and V(DJ recombination and in other cellular metabolic reactions are discussed.

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

    Science.gov (United States)

    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; Horn, Biljana N; de Villartay, Jean-Pierre; Cavazzana, Marina; Debatin, Klaus-Michael; Friedrich, Wilhelm; Fischer, Alain; Cowan, Morton J

    2014-01-09

    A subgroup of severe combined immunodeficiencies (SCID) is characterized by lack of T and B cells and is caused by defects in genes required for T- and B-cell receptor gene rearrangement. Several of these genes are also involved in nonhomologous end joining of DNA double-strand break repair, the largest subgroup consisting of patients with T(-)B(-)NK(+)SCID due to DCLRE1C/ARTEMIS defects. We postulated that in patients with ARTEMIS deficiency, early and late complications following hematopoietic cell transplantation might be more prominent compared with patients with T(-)B(-)NK(+)SCID caused by recombination activating gene 1/2 (RAG1/2) deficiencies. We analyzed 69 patients with ARTEMIS and 76 patients with RAG1/2 deficiencies who received transplants from either HLA-identical donors without conditioning or from HLA-nonidentical donors without or with conditioning. There was no difference in survival or in the incidence or severity of acute graft-versus-host disease regardless of exposure to alkylating agents. Secondary malignancies were not observed. Immune reconstitution was comparable in both groups, however, ARTEMIS-deficient patients had a significantly higher occurrence of infections in long-term follow-up. There is a highly significant association between poor growth in ARTEMIS deficiency and use of alkylating agents. Furthermore, abnormalities in dental development and endocrine late effects were associated with alkylation therapy in ARTEMIS deficiency.

  6. 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.

  7. 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.

  8. 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

  9. Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance.

    Science.gov (United States)

    Jagut, Marlène; Hamminger, Patricia; Woglar, Alexander; Millonigg, Sophia; Paulin, Luis; Mikl, Martin; Dello Stritto, Maria Rosaria; Tang, Lois; Habacher, Cornelia; Tam, Angela; Gallach, Miguel; von Haeseler, Arndt; Villeneuve, Anne M; Jantsch, Verena

    2016-03-01

    During the first meiotic division, crossovers (COs) between homologous chromosomes ensure their correct segregation. COs are produced by homologous recombination (HR)-mediated repair of programmed DNA double strand breaks (DSBs). As more DSBs are induced than COs, mechanisms are required to establish a regulated number of COs and to repair remaining intermediates as non-crossovers (NCOs). We show that the Caenorhabditis elegans RMI1 homolog-1 (RMH-1) functions during meiosis to promote both CO and NCO HR at appropriate chromosomal sites. RMH-1 accumulates at CO sites, dependent on known pro-CO factors, and acts to promote CO designation and enforce the CO outcome of HR-intermediate resolution. RMH-1 also localizes at NCO sites and functions in parallel with SMC-5 to antagonize excess HR-based connections between chromosomes. Moreover, RMH-1 also has a major role in channeling DSBs into an NCO HR outcome near the centers of chromosomes, thereby ensuring that COs form predominantly at off-center positions.

  10. Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance

    Science.gov (United States)

    Jagut, Marlène; Hamminger, Patricia; Woglar, Alexander; Millonigg, Sophia; Paulin, Luis; Mikl, Martin; Dello Stritto, Maria Rosaria; Tang, Lois; Habacher, Cornelia; Tam, Angela; Gallach, Miguel; von Haeseler, Arndt; Villeneuve, Anne M.; Jantsch, Verena

    2016-01-01

    During the first meiotic division, crossovers (COs) between homologous chromosomes ensure their correct segregation. COs are produced by homologous recombination (HR)-mediated repair of programmed DNA double strand breaks (DSBs). As more DSBs are induced than COs, mechanisms are required to establish a regulated number of COs and to repair remaining intermediates as non-crossovers (NCOs). We show that the Caenorhabditis elegans RMI1 homolog-1 (RMH-1) functions during meiosis to promote both CO and NCO HR at appropriate chromosomal sites. RMH-1 accumulates at CO sites, dependent on known pro-CO factors, and acts to promote CO designation and enforce the CO outcome of HR-intermediate resolution. RMH-1 also localizes at NCO sites and functions in parallel with SMC-5 to antagonize excess HR-based connections between chromosomes. Moreover, RMH-1 also has a major role in channeling DSBs into an NCO HR outcome near the centers of chromosomes, thereby ensuring that COs form predominantly at off-center positions. PMID:27011106

  11. 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...

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

    Science.gov (United States)

    Furst, Audrey; Koch, Marc; Fischer, Benoit; Soutoglou, Evi

    2016-01-01

    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

  13. 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.

  14. Right or left turn? RecA family protein filaments promote homologous recombination through clockwise axial rotation.

    Science.gov (United States)

    Wang, Ting-Fang; Chen, Li-Tzu; Wang, Andrew H-J

    2008-01-01

    The RecA family proteins mediate homologous recombination, a ubiquitous mechanism for repairing DNA double-strand breaks (DSBs) and stalled replication forks. Members of this family include bacterial RecA, archaeal RadA and Rad51, and eukaryotic Rad51 and Dmc1. These proteins bind to single-stranded DNA at a DSB site to form a presynaptic nucleoprotein filament, align this presynaptic filament with homologous sequences in another double-stranded DNA segment, promote DNA strand exchange and then dissociate. It was generally accepted that RecA family proteins function throughout their catalytic cycles as right-handed helical filaments with six protomers per helical turn. However, we recently reported that archaeal RadA proteins can also form an extended right-handed filament with three monomers per helical turn and a left-handed protein filament with four monomers per helical turn. Subsequent structural and functional analyses suggest that RecA family protein filaments, similar to the F1-ATPase rotary motor, perform ATP-dependent clockwise axial rotation during their catalytic cycles. This new hypothesis has opened a new avenue for understanding the molecular mechanism of RecA family proteins in homologous recombination.

  15. Earth Orbit Raise Design for the Artemis Mission

    Science.gov (United States)

    Wiffen, Gregory J.; Sweetser, Theodore H.

    2011-01-01

    The Artemis mission is an extension of the Themis mission. The Themis mission1 consisted of five identical spacecraft in varying sized Earth orbits designed to make simultaneous measurements of the Earth's electric and magnetic environment. Themis was designed to observe geomagnetic storms resulting from solar wind's interaction with the Earth's magnetosphere. Themis was meant to answer the age old question of why the Earth's aurora can change rapidly on a global scale. The Themis spacecraft are spin stabilized with 20 meter long electric field booms as well as several shorter magnetometer booms. The goal of the Artemis2 mission extension is to deliver the field and particle measuring capabilities of two of the Themis spacecraft to the vicinity of the Moon. The Artemis mission required transferring two Earth orbiting Themis spacecraft on to two different low energy trans-lunar trajectories ultimately ending in lunar orbit. This paper describes the processes that resulted in successful orbit raise designs for both spacecraft.

  16. Epigenetic silencing of BTB and CNC homology 2 and concerted promoter CpG methylation in gastric cancer.

    Science.gov (United States)

    Haam, Keeok; Kim, Hee-Jin; Lee, Kyung-Tae; Kim, Jeong-Hwan; Kim, Mirang; Kim, Seon-Young; Noh, Seung-Moo; Song, Kyu-Sang; Kim, Yong Sung

    2014-09-01

    BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription factor with a prominent role in B-cell development. Genetic polymorphisms within a single locus encoding BACH2 are associated with various autoimmune diseases and allergies. In this study, restriction landmark genomic scanning revealed methylation at a NotI site in a CpG island covering the BACH2 promoter in gastric cancer cell lines and primary gastric tumors. Increased methylation of the BACH2 promoter was observed in 52% (43/83) of primary gastric tumors, and BACH2 hypermethylation was significantly associated with decreased gene expression. Treatment with 5-aza-2'-deoxycytidine and/or trichostatin. A restored BACH2 expression in BACH2-silenced gastric cancer cell lines, and knockdown of BACH2 using short hairpin RNA (i.e. RNA interference) increased cell proliferation in gastric cancer cells. Clinicopathologic data showed that decreased BACH2 expression occurred significantly more frequently in intestinal-type (27/44, 61%) compared with diffuse-type (13/50, 26%) gastric cancers (P<0.001). Furthermore, BACH2 promoter methylation paralleled that of previously identified targets, such as LRRC3B, LIMS2, PRKD1 and POPDC3, in a given set of gastric tumors. We propose that concerted methylation in many promoters plays a role in accelerating gastric tumor formation and that methylated promoter loci may be targets for therapeutic treatment, such as the recently introduced technique of epigenetic editing.

  17. Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

    Science.gov (United States)

    Morozov, Giora I.; Zhao, Huaying; Mage, Michael G.; Boyd, Lisa F.; Jiang, Jiansheng; Dolan, Michael A.; Venna, Ramesh; Norcross, Michael A.; McMurtrey, Curtis P.; Hildebrand, William; Schuck, Peter; Natarajan, Kannan; Margulies, David H.

    2016-01-01

    Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8+ T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing. PMID:26869717

  18. 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

    in the nematode C. elegans, named paqr-1, paqr-2 and paqr-3. These are differently expressed in the intestine (the main fat-storing tissue), hypodermis, muscles, neurons and secretory tissues, from which they could exert systemic effects. Analysis of mutants revealed that paqr-1 and -2 are novel metabolic...... regulators in C. elegans and that they act redundantly but independently from paqr-3. paqr-2 is the most important of the three paqr genes: mutants grow poorly, fail to adapt to growth at low temperature, and have a very high fat content with an abnormal enrichment in long (C20) poly-unsaturated fatty acids...... when combined with the paqr-1 mutation. paqr-2 mutants are also synthetic lethal with mutations in nhr-49, sbp-1 and fat-6, which are C. elegans homologs of nuclear hormone receptors, SREBP and FAT-6 (a Δ9 desaturase), respectively. Like paqr-2, paqr-1 is also synthetic lethal with sbp-1. Mutations...

  19. ARTEMIS: Reinvigorating History and Theory in Art and Design Education

    Science.gov (United States)

    Janet, Jeff; Miles, Melissa

    2009-01-01

    ARTEMIS (Art Educational Multiplayer Interactive Space) is an online multi-user virtual environment that is designed around the objects, artefacts, philosophies, personalities and critical discourses of the histories and theories of art and design. Conceived as a means of reinvigorating art history and theory education in the digital age, ARTEMIS…

  20. Laser Experiments with ARTEMIS Satellite in Cloudy Conditions

    Science.gov (United States)

    Kuzkov, Volodymyr; Sodnik, Zoran; Kuzkov, Sergii; Caramia, Vincenzo

    2014-05-01

    In July 2001, the ARTEMIS satellite with laser communication terminal OPALE on board was launched. 1789 laser communications sessions were performed between ARTEMIS and SPOT-4 (PASTEL) from 01 April 2003 to 09 January 2008 with total duration of 378 hours. In addition ESA's Optical Ground Station (OGS) performed laser communication experiments with OPALE in various atmospheric conditions. Since the launch of ARTEMIS, the amount of information handled by geostationary telecommunication satellites has increased dramatically and so has the demand for data rate that needs to be transmitted from ground. With limited bandwidth allocations in the radio frequency bands interest has grown for laser communication feeder link technology. In this respect there is interest to compare the influence of atmosphere conditions in different atmospheric regions with respect to laser transmission. Two locations are being compared, namely ESA's OGS (located in an altitude of 2400 m above sea level) and the Main Astronomical Observatory of Ukraine (MAO) (located at an altitude of 190 m above sea level). In 2002 MAO started the development of a ground laser communication system for the AZT-2 telescope. The MAO developed compact laser communication system is called LACES (Laser Atmosphere and Communication Experiments with Satellites) [1] and the work was supported by the National Space Agency of Ukraine and by ESA. The beacon laser from OPALE was occasionally detected even in cloudy conditions and an anomalous atmospheric refraction at low elevation angles was observed. The main results of laser experiments with ARTEMIS through clouds are presented in the paper.

  1. Tousled kinase activator, gallic acid, promotes homologous recombinational repair and suppresses radiation cytotoxicity in salivary gland cells.

    Science.gov (United States)

    Timiri Shanmugam, Prakash Srinivasan; Nair, Renjith Parameshwaran; De Benedetti, Arrigo; Caldito, Gloria; Abreo, Fleurette; Sunavala-Dossabhoy, Gulshan

    2016-04-01

    Accidental or medical radiation exposure of the salivary glands can gravely impact oral health. Previous studies have shown the importance of Tousled-like kinase 1 (TLK1) and its alternate start variant TLK1B in cell survival against genotoxic stresses. Through a high-throughput library screening of natural compounds, the phenolic phytochemical, gallic acid (GA), was identified as a modulator of TLK1/1B. This small molecule possesses anti-oxidant and free radical scavenging properties, but in this study, we report that in vitro it promotes survival of human salivary acinar cells, NS-SV-AC, through repair of ionizing radiation damage. Irradiated cells treated with GA show improved clonogenic survival compared to untreated controls. And, analyses of DNA repair kinetics by alkaline single-cell gel electrophoresis and γ-H2AX foci immunofluorescence indicate rapid resolution of DNA breaks in drug-treated cells. Study of DR-GFP transgene repair indicates GA facilitates homologous recombinational repair to establish a functional GFP gene. In contrast, inactivation of TLK1 or its shRNA knockdown suppressed resolution of radiation-induced DNA tails in NS-SV-AC, and homology directed repair in DR-GFP cells. Consistent with our results in culture, animals treated with GA after exposure to fractionated radiation showed better preservation of salivary function compared to saline-treated animals. Our results suggest that GA-mediated transient modulation of TLK1 activity promotes DNA repair and suppresses radiation cytoxicity in salivary gland cells.

  2. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency

    Science.gov (United States)

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A.; Fliegauf, Manfred; Sayar, Esra H.; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S¸ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-01-01

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease—all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients. PMID:26476407

  3. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.

    Science.gov (United States)

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A; Fliegauf, Manfred; Sayar, Esra H; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S Ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-12-20

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients.

  4. 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

    2016-03-02

    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.

  5. 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.

  6. Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

    Science.gov (United States)

    Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

    2017-02-01

    Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of

  7. MHD models compared with Artemis observations at -60 Re

    Science.gov (United States)

    Gencturk Akay, Iklim; Sibeck, David; Angelopoulos, Vassilis; Kaymaz, Zerefsan; Kuznetsova, Maria

    2016-07-01

    The distant magnetotail has been one of the least studied magnetic regions of the Earth's magnetosphere compared to the other near Earth both dayside and nightside magnetospheric regions owing to the limited number of spacecraft observations. Since 2011, ARTEMIS spacecraft give an excellent opportunity to study the magnetotail at lunar distances in terms of data quality and parameter space. This also gives opportunities to improve the magnetotail models at -60 Re and encourages the modelling studies of the distant magnetotail. Using ARTEMIS data in distant magnetotail, we create magnetic field and plasma flow vector maps in different planes and separated with IMF orientation to understand the magnetotail dynamics at this distance. For this study, we use CCMC's Run-on-Request resources of the MHD models; specifically SWMF-BATS-R-US, OpenGGCM, and LFM and perform the similar analysis with the models. Our main purpose in this study is to measure the performance of the MHD models at -60 Re distant magnetotail by comparing the model results with Artemis observations. In the literature, such a comprehensive comparative study is lacking in the distant tail. Preliminary results show that in general all three models underestimate the magnetic field structure while overestimating the flow speed. In the cross-sectional view, LFM seems to produce the better agreement with the observations. A clear dipolar magnetic field structure is seen with dawn-dusk asymmetry in all models owing to slight positive IMF By but the effect was found to be exaggerated. All models show tailward flows at this distance of the magnetotail, most possibly owing to the magnetic reconnection at the near Earth tail distances. A detailed comparison of several tail characteristics from the models will be presented and discussions will be given with respect to the observations from Artemis at this distance.

  8. Laser experiments in light cloudiness with the geostationary satellite ARTEMIS

    Science.gov (United States)

    Kuzkov, V.; Kuzkov, S.; Sodnik, Z.

    2016-08-01

    The geostationary satellite ARTEMIS was launched in July 2001. The satellite is equipped with a laser communication terminal, which was used for the world's first inter-satellite laser communication link between ARTEMIS and the low earth orbit satellite SPOT-4. Ground-to-space laser communication experiments were also conducted under various atmospheric conditions involving ESA's optical ground station. With a rapidly increasing volume of information transferred by geostationary satellites, there is a rising demand for high-speed data links between ground stations and satellites. For ground-to-space laser communications there are a number of important design parameters that need to be addressed, among them, the influence of atmospheric turbulence in different atmospheric conditions and link geometries. The Main Astronomical Observatory of NAS of Ukraine developed a precise computer tracking system for its 0.7 m AZT-2 telescope and a compact laser communication package LACES (Laser Atmosphere and Communication experiments with Satellites) for laser communication experiments with geostationary satellites. The specially developed software allows computerized tracking of the satellites using their orbital data. A number of laser experiments between MAO and ARTEMIS were conducted in partial cloudiness with some amount of laser light observed through clouds. Such conditions caused high break-up (splitting) of images from the laser beacon of ARTEMIS. One possible explanation is Raman scattering of photons on molecules of a water vapor in the atmosphere. Raman scattering causes a shift in a wavelength of the photons.In addition, a different value for the refraction index appears in the direction of the meridian for the wavelength-shifted photons. This is similar to the anomalous atmospheric refraction that appears at low angular altitudes above the horizon. We have also estimated the atmospheric attenuation and the influence of atmospheric turbulence on observed results

  9. Rad18 and Rnf8 facilitate homologous recombination by two distinct mechanisms, promoting Rad51 focus formation and suppressing the toxic effect of nonhomologous end joining

    NARCIS (Netherlands)

    Kobayashi, S.; Kasaishi, Y.; Nakada, S.; Takagi, T.; Era, S.; Motegi, A.; Chiu, R. K.; Takeda, S.; Hirota, K.

    2015-01-01

    The E2 ubiquitin conjugating enzyme Ubc13 and the E3 ubiquitin ligases Rad18 and Rnf8 promote homologous recombination (HR)-mediated double-strand break (DSB) repair by enhancing polymerization of the Rad51 recombinase at.-ray-induced DSB sites. To analyze functional interactions between the three e

  10. 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.

  11. 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

  12. Laser Ground System for Communication Experiments with ARTEMIS

    Science.gov (United States)

    Kuzkov, Volodymyr; Volovyk, Dmytro; Kuzkov, Sergii; Sodnik, Zoran; Pukha, Sergii; Caramia, Vincenzo

    2012-10-01

    The ARTEMIS satellite with the OPALE laser communication terminal on-board was launched on 12 July, 2001. 1789 laser communications sessions were performed between ARTEMIS and SPOT-4 (PASTEL) from 01 April 2003 to 09 January 2008 with total duration of 378 hours. Regular laser communication experiments between ESA's Optical Ground Station (OGS - altitude 2400 m above see level) and ARTEMIS in various atmosphere conditions were also performed. The Japanese Space Agency (JAXA) launched the KIRARI (OICETS) satellite with laser communication terminal called LUCE. Laser communication links between KIRARI and ARTEMIS were successfully realized and international laser communications experiments from the KIRARI satellite were also successfully performed with optical ground stations located in the USA (JPL), Spain (ESA OGS), Germany (DLR), and Japan (NICT). The German Space Agency (DLR) performed laser communication links between two LEO satellites (TerraSAR-X and NFIRE), demonstrating data transfer rates of 5.6Gbit/s and performed laser communication experiments between the satellites and the ESA optical ground station. To reduce the influence of weather conditions on laser communication between satellites and ground stations, a network of optical stations situated in different atmosphere regions needs to be created. In 2002, the Main Astronomical Observatory (MAO) started the development of its own laser communication system to be placed into the Cassegrain focus of its 0.7m AZT-2 telescope (Fe = 10.5m), located in Kyiv 190 meters above sea level. The work was supported by the National Space Agency of Ukraine and by ESA ARTEMIS has an orbital position of 21.4° E and an orbital inclination of more than 9.75°. As a result we developed a precise tracking system for AZT-2 telescope (weighing more than 2 tons) using micro-step motors. Software was developed for computer control of the telescope to track the satellite's orbit and a tracking accuracy of 0.6 arcsec was achieved

  13. The Artemis workbench for system-level performance evaluation of embedded systems

    NARCIS (Netherlands)

    A.D. Pimentel

    2008-01-01

    In this paper, we present an overview of the Artemis workbench, which provides modelling and simulation methods and tools for efficient performance evaluation and exploration of heterogeneous embedded multimedia systems. More specifically, we describe the Artemis system-level modelling methodology,

  14. 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

  15. 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

  16. 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...

  17. 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

  18. Structural Basis of DNA Ligase IV-Artemis Interaction in Nonhomologous End-Joining

    Directory of Open Access Journals (Sweden)

    Pablo De Ioannes

    2012-12-01

    Full Text Available DNA ligase IV (LigIV and Artemis are central components of the nonhomologous end-joining (NHEJ machinery that is required for V(DJ recombination and the maintenance of genomic integrity in mammalian cells. We report here crystal structures of the LigIV DNA binding domain (DBD in both its apo form and in complex with a peptide derived from the Artemis C-terminal region. We show that LigIV interacts with Artemis through an extended hydrophobic surface. In particular, we find that the helix α2 in LigIV-DBD is longer than in other mammalian ligases and presents residues that specifically interact with the Artemis peptide, which adopts a partially helical conformation on binding. Mutations of key residues on the LigIV-DBD hydrophobic surface abolish the interaction. Together, our results provide structural insights into the specificity of the LigIV-Artemis interaction and how the enzymatic activities of the two proteins may be coordinated during NHEJ.

  19. 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.

  20. 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

  1. Magnetic reconnection associated fluctuations in the deep magnetotail: ARTEMIS results

    Directory of Open Access Journals (Sweden)

    Z. Vörös

    2011-11-01

    Full Text Available On the basis of ARTEMIS two-probe mission magnetic reconnection (MR outflow associated magnetic fluctuations and turbulence are analyzed on 19 February 2011. In the deep-tail, at distances between X = 45 – 51 RE, evidence for reconnection associated plasma sheet thinning was found, accompanied by heating of the plasma sheet. Correlated flow and field reversals and the large-scale Hall-effect signatures indicated the presence of the reconnection X-line. Within fast reconnection plasma outflows, magnetic fluctuations exhibit the same spectral scaling features and kinked spectra as magnetic fluctuations in the solar wind or in various parts of geospace. It was shown that the proton scale magnetic fluctuations are constrained by oblique firehose, proton cyclotron and mirror instability thresholds. For parallel plasma β|| > 1, where the thresholds converge, perpendicular magnetic fluctuations are enhanced. Magnetic compressibility decreases with the distance to the neutral sheet, however, near the instability thresholds it is comparable to the values obtained in the solar wind.

  2. Dynamic Hybrid Simulation of the Lunar Wake During ARTEMIS Crossing

    Science.gov (United States)

    Wiehle, S.; Plaschke, F.; Angelopoulos, V.; Auster, H.; Glassmeier, K.; Kriegel, H.; Motschmann, U. M.; Mueller, J.

    2010-12-01

    The interaction of the highly dynamic solar wind with the Moon is simulated with the A.I.K.E.F. (Adaptive Ion Kinetic Electron Fluid) code for the ARTEMIS P1 flyby on February 13, 2010. The A.I.K.E.F. hybrid plasma simulation code is the improved version of the Braunschweig code. It is able to automatically increase simulation grid resolution in areas of interest during runtime, which greatly increases resolution as well as performance. As the Moon has no intrinsic magnetic field and no ionosphere, the solar wind particles are absorbed at its surface, resulting in the formation of the lunar wake at the nightside. The solar wind magnetic field is basically convected through the Moon and the wake is slowly filled up with solar wind particles. However, this interaction is strongly influenced by the highly dynamic solar wind during the flyby. This is considered by a dynamic variation of the upstream conditions in the simulation using OMNI solar wind measurement data. By this method, a very good agreement between simulation and observations is achieved. The simulations show that the stationary structure of the lunar wake constitutes a tableau vivant in space representing the well-known Friedrichs diagram for MHD waves.

  3. Conceptual design of the D- sup 3 He reactor artemis

    Energy Technology Data Exchange (ETDEWEB)

    Momoto, H.; Tomita, Y. (National Inst. for Fusion Science, Nagoya (JP)); Ishida, A. (Niigata Univ. (Japan)); Miley, G.H. (Illinois Univ., Urbana, IL (United States)); Kohzaki, Y. (Inst. for Future Technology, Tokyo (JP)); Ohi, S. (Osaka Univ., Suita (Japan)); Ohnishi, M. (Kyoto Univ. (Japan)); Sato, H. (Himeji Inst. of Tech., Hyogo (Japan)); Steinhauer, L.C. (STI Optronics, Inc., Bellevue, WA (US)); Tuszewski, M. (Los Alamos National Lab., NM (United States))

    1992-07-01

    In this paper, a comprehensive design study of the D-{sup 3}He-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 preferential trapping of D-{sup 3}He fusion-produced energetic protons. A novel direct energy converter for 15-MeV protons is also presented. On the basis of consistent fusion plasma production and simple engineering, a compact and simple reactor concept is presented. The D-{sup 3}He FRC power plant offers a most attractive prospect for energy development. It is environmentally acceptable in terms of radioactivity and fuel resources, and the estimated cost of electricity is low compared with a light water reactor. Critical physics and engineering issues in the development of the D-{sup 3}He FRC reactor are clarified.

  4. 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....

  5. 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

  6. The Adventures of Artemis and the Llama: A Case for Imaginary Histories in Art Education

    Science.gov (United States)

    Vallance, Elizabeth

    2004-01-01

    Artemis is a late Hellenistic Greek marble sculpture of the huntress, running in a flowing garment, now lacking arms, legs, and head, and about three-quarters life-sized. The llama is a remarkable hollow male figure of smooth thin gold, and about two inches tall, and was made by the Inca before the Spanish conquest in 1532. This narrative is just…

  7. 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.

  8. 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

  9. 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.

  10. First Results from ARTEMIS, a New Two-Spacecraft Lunar Mission: Counter-Streaming Plasma Populations in the Lunar Wake

    Science.gov (United States)

    Halekas, J. S.; Angelopoulos, V.; Sibeck, D. G.; Khurana, K. K.; Russell, C. T.; Delory, G. T.; Farrell, W. M.; McFadden, J. P.; Bonnell, J. W.; Larson, D.; Ergun, R. E.; Plaschke, F.; Glassmeier, K. H.

    2011-12-01

    We present observations from the first passage through the lunar plasma wake by one of two spacecraft comprising ARTEMIS (Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun), a new lunar mission that re-tasks two of five probes from the THEMIS magnetospheric mission. On Feb 13, 2010, ARTEMIS probe P1 passed through the wake at ˜3.5 lunar radii downstream from the Moon, in a region between those explored by Wind and the Lunar Prospector, Kaguya, Chandrayaan, and Chang'E missions. ARTEMIS observed interpenetrating proton, alpha particle, and electron populations refilling the wake along magnetic field lines from both flanks. The characteristics of these distributions match expectations from self-similar models of plasma expansion into vacuum, with an asymmetric character likely driven by a combination of a tilted interplanetary magnetic field and an anisotropic incident solar wind electron population. On this flyby, ARTEMIS provided unprecedented measurements of the interpenetrating beams of both electrons and ions naturally produced by the filtration and acceleration effects of electric fields set up during the refilling process. ARTEMIS also measured electrostatic oscillations closely correlated with counter-streaming electron beams in the wake, as previously hypothesized but never before directly measured. These observations demonstrate the capability of the comprehensively instrumented ARTEMIS spacecraft and the potential for new lunar science from this unique two spacecraft constellation.

  11. First Results from ARTEMIS, A New Two-Spacecraft Lunar Mission: Counter-Streaming Plasma Populations in the Lunar Wake

    Science.gov (United States)

    Halekas, J. S.; Angelopoulos, V.; Sibeck, D. G.; Khurana, K. K.; Russell, C. T.; Delory, G. T.; Farrell, W. M.; McFadden, J. P.; Bonnell, J. W.; Larson, D.; Ergun, R. E.; Plaschke, F.; Glassmeier, K. H.

    2014-01-01

    We present observations from the first passage through the lunar plasma wake by one of two spacecraft comprising ARTEMIS (Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun), a new lunar mission that re-tasks two of five probes from the THEMIS magnetospheric mission. On Feb 13, 2010, ARTEMIS probe P1 passed through the wake at approximately 3.5 lunar radii downstream from the Moon, in a region between those explored by Wind and the Lunar Prospector, Kaguya, Chandrayaan, and Chang'E missions. ARTEMIS observed interpenetrating proton, alpha particle, and electron populations refilling the wake along magnetic field lines from both flanks. The characteristics of these distributions match expectations from self-similar models of plasma expansion into vacuum, with an asymmetric character likely driven by a combination of a tilted interplanetary magnetic field and an anisotropic incident solar wind electron population. On this flyby, ARTEMIS provided unprecedented measurements of the interpenetrating beams of both electrons and ions naturally produced by the filtration and acceleration effects of electric fields set up during the refilling process. ARTEMIS also measured electrostatic oscillations closely correlated with counter-streaming electron beams in the wake, as previously hypothesized but never before directly measured. These observations demonstrate the capability of the comprehensively instrumented ARTEMIS spacecraft and the potential for new lunar science from this unique two spacecraft constellation.

  12. Carbamoylcholine homologs

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Frølund, Bente; Bräuner-Osborne, Hans;

    2003-01-01

    -methylcarbamoylcholine and N,N-dimethylcarbamoylcholine (DMCC), which predominantly display nicotinic activity. In this study, 12 homologous analogs of DMCC and its corresponding tertiary amine, N,N-dimethylcarbamoyl-N,N-dimethylaminoethanol, were synthesized and their binding affinities to native mAChR and nAChR sites....... Furthermore, the compounds are tertiary amines, implying some advantages in terms of bioavailability pertinent to future in vivo pharmacological studies. Finally, observations made in the study hold promising perspectives for future development of ligands selective for specific nAChR subtypes....

  13. Mapping the Plasma Structure of the Central Magnetotail Using Artemis Observations

    Science.gov (United States)

    Gencturk Akay, Iklim; Sibeck, David; Angelopoulos, Vassilis; Kaymaz, Zerefsan

    2016-07-01

    Since 2011, ARTEMIS spacecraft 1 and 2 take observations from the dayside solar wind, nightside magnetopause and the magnetotail interior while they orbit around the Earth, as well as the Moon. With the state-of-the-art instruments, ARTEMIS probes perform the first systematic, two-point observations of the mid-to-distant tail and allow us to determine how the tail dynamics work and controlled at lunar distances, around -60 Re. In this study, we use magnetic field and plasma parameters of ARTEMIS probes to investigate the physical and dynamical processes that determine the structure of the tail and its variations in response to the changes in IMF and solar wind. We use approximately 2 years data from the ARTEMIS spacecraft to create the vector maps of the plasma flow. After several coordinate transformations, vector maps were constructed on different planes, xy-, xz-, and yz, in aberrated solar wind corrected GSM (aSWGSM) coordinates, and a relatively good orbital coverage of the central magnetotail was obtained. Flow vectors in YZ-plane are generally toward the center of the plasma sheet; being southward/northward in the northern/southern hemisphere. Vector maps of the flow in xy- and xz-planes show that the dominant flow is tailward. The percentage of tailward flows is about 62%-72% percentages and the speed of the flow ranges from a few tens of a km/sec to over 400km/sec. Vector maps were separated with respect to the IMF orientation. Magnetic field patterns complimentary to the flow patterns were also performed and revealed the expected distorted dipolar field topology at -60 Re. We discuss our findings from the magnetotail dynamics point of view and comparisons will be made with those obtained from earlier spacecraft missions.

  14. 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

    2016-06-02

    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.

  15. Analysis of the preliminary optical links between ARTEMIS and the Optical Ground Station

    Science.gov (United States)

    Reyes Garcia-Talavera, Marcos; Chueca, Sergio; Alonso, Angel; Viera, Teodora; Sodnik, Zoran

    2002-12-01

    In the frame of the SILEX project, the European Space Agency (ESA) has put into orbit two Laser Communication Terminals, to establish an experimental free space optical communication link between a GEO satellite (ARTEMIS) and a LEO satellite (SPOT IV), to relay earth observation data. In order to perform In Orbit Testing (IOT) of these, and other, optical communications systems, ESA and the Instituto de Astrofisica de Canarias (IAC) reached an agreement for building the Optical Ground Station (OGS), in the Teide Observatory of the IAC. With ARTEMIS placed in a circular parking orbit at about 31000 kilometres, its optical payload has been preliminary tested with the OGS. First results and analysis are presented on the space-to-ground bi-directional link, including pointing acquisition and tracking performance, Bit-Error Rate (BER) and transmitted beam divergence effects related with atmospheric models and predictions. Future plans include deeper optical bi-directional communication tests of OGS, not only with ARTEMIS but also with OSCAR-40 (downlink) and SMART-1 (up-link) satellites, in order to do a full characterisation of the performances of laser beam propagation through atmospheric turbulence and a comparison with theoretical predictions.

  16. 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.

  17. 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

  18. 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...

  19. Homology and causes.

    Science.gov (United States)

    Van Valen, L M

    1982-09-01

    Homology is resemblance caused by a continuity of information. In biology it is a unified developmental phenomenon. Homologies among and within individuals intergrade in several ways, so historical homology cannot be separated sharply from repetitive homology. Nevertheless, the consequences of historical and repetitive homologies can be mutually contradictory. A detailed discussion of the rise and fall of the "premolar-analogy" theory of homologies of mammalian molar-tooth cusps exemplifies such a contradiction. All other hypotheses of historical homology which are based on repetitive homology, such as the foliar theory of the flower considered phyletically, are suspect.

  20. Direct Measurements of Laser Communication Point-Ahead Angles from the ARTEMIS Geostationary Satellite Through Clouds

    Science.gov (United States)

    Kuzkov, V.; Sodnik, Z.; Kuzkov, S.

    2017-01-01

    Laser experiments with ARTEMIS geostationary satellite have been performed in partly cloudy weather using the developed system for the telescope. It has been found that the part of the laser beam is observed simultaneously at the points in direction of the velocity vector where the satellite would arrive at when the laser light reaches the telescope. These results agree with the theory of relativity for light aberration in transition from fixed to moving coordinate system.Observation results open the way for research and development of systems to compensate atmospheric turbulence in laser communications between ground stations and satellites through the atmosphere.

  1. A Study on the Artemis Fowl Series in the Context of Publishing Success

    OpenAIRE

    Lindve, Katarina

    2007-01-01

    A close reading of a series of books by Eoin Colfer that enjoyed universal success showed a change in the language between the books especially with respect to minor linguistic features such as choice of location and abstract vs. concrete language. The books are about the boy Artemis Fowl, and were presumably conceived as children’s books. My original thesis was that the writer could not be sure of the success of the first book, but would definitely be aware of a worldwide audience for at lea...

  2. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene

    Science.gov (United States)

    We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor c...

  3. 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...

  4. 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

  5. Replacement of Homologous Mouse DNA Sequence With Pathogenic 6-Base Human CREB1 Promoter Sequence Creates Murine Model of Major Depressive Disorder

    OpenAIRE

    Zubenko, George S.; Hughes, Hugh B.

    2011-01-01

    Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Families with Recurrent, Early-Onset MDD (RE-MDD), a severe, familial form of MDD, have provided an important resource for identifying and characterizing genetic variants that confer susceptibility to MDD and related disorders. Previous studies identified a rare, highly penetrant A(-115)G transition within the human CREB1 promoter that reduced promoter activity in vitro and was associated with depressive disorders in ...

  6. Anterior segment biometry using ultrasound biomicroscopy and the Artemis-2 very high frequency ultrasound scanner

    Directory of Open Access Journals (Sweden)

    Al-Farhan HM

    2013-01-01

    Full Text Available Haya M Al-Farhan, Reem N AlMutairiKing Saud University, College of Applied Medical Sciences, Department of Optometry and Vision Sciences, Riyadh, Kingdom of Saudi ArabiaPurpose: To compare the precision of anterior chamber angle (ACA and anterior chamber depth (ACD measurements taken with ultrasound biomicroscopy (UBM and the Artemis-2 Very High Frequency Ultrasound Scanner (VHFUS in normal subjects.Design: Prospective study.Methods: We randomly selected one eye from each of 59 normal subjects in this study. Two subjects dropped out of the study; the associated data were excluded from analysis. ACA and ACD measurements were obtained using the VHFUS and the UBM. The results were compared statistically using repeated-measures analysis of variance for the intraobserver repeatability, unpaired t-test, and limits of agreement.Results: The average ACA values for the UBM and the VHFUS (±standard deviation were 41.83° ± 5.03° and 33.36° ± 6.03°, respectively. The average ACD values were 2.96 ± 0.34 mm and 2.87 ± 0.31 mm. The intraobserver repeatability analysis of variance P-values for ACA and ACD measurements using UBM were 0.10 and 0.68, respectively; for the Artemis-2 VHFUS, the respective values were 0.68 and 0.09. The difference in ACA measurements was statistically significant (t = 8.41; P < 0.0001, while the difference in ACD values was not (t = 1.51; P < 0.13. The mean ACA difference was 8.50° ± 2.50°, and the limits of agreement were +13.30° to −3.60°. The mean ACD difference was 0.09 ± 0.27 mm, and the limits of agreement ranged from 0.61 mm to −0.43 mm. The mean difference percentage of ACD was 3.1% for both instruments.Conclusion: In case of the ACD, both instruments can be used interchangeably; however, with the ACA instruments, they cannot be used interchangeably.Keywords: anterior chamber angle, anterior chamber depth, Artemis-2 VHF scanner, ultrasound biomicroscope, normal eyes

  7. Combinatorial Floer Homology

    CERN Document Server

    de Silva, Vin; Salamon, Dietmar

    2012-01-01

    We define combinatorial Floer homology of a transverse pair of noncontractibe nonisotopic embedded loops in an oriented 2-manifold without boundary, prove that it is invariant under isotopy, and prove that it is isomorphic to the original Lagrangian Floer homology.

  8. 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...

  9. Tail reconnection region versus auroral activity inferred from conjugate ARTEMIS plasma sheet flow and auroral observations

    Science.gov (United States)

    Nishimura, Y.; Lyons, L. R.; Xing, X.; Angelopoulos, V.; Donovan, E. F.; Mende, S. B.; Bonnell, J. W.; Auster, U.

    2013-09-01

    sheet flow bursts have been suggested to correspond to different types of auroral activity, such as poleward boundary intensifications (PBIs), ensuing auroral streamers, and substorms. The flow-aurora association leads to the important question of identifying the magnetotail source region for the flow bursts and how this region depends on magnetic activity. The present study uses the ARTEMIS spacecraft coordinated with conjugate ground-based auroral imager observations to identify flow bursts beyond 45 RE downtail and corresponding auroral forms. We find that quiet-time flows are directed dominantly earthward with a one-to-one correspondence with PBIs. Flow bursts during the substorm recovery phase and during steady magnetospheric convection (SMC) periods are also directed earthward, and these flows are associated with a series of PBIs/streamers lasting for tens of minutes with similar durations to that of the series of earthward flows. Presubstorm onset flows are also earthward and associated with PBIs/streamers. The earthward flows during those magnetic conditions suggest that the flow bursts, which lead to PBIs and streamers, originate from further downtail of ARTEMIS, possibly from the distant-tail neutral line (DNL) or tailward-retreated near-Earth neutral line (NENL) rather than from the nominal NENL location in the midtail. We find that tailward flows are limited primarily to the substorm expansion phase. They continue throughout the period of auroral poleward expansion, indicating that the expansion-phase flows originate from the NENL and that NENL activity is closely related to the auroral expansion of the substorm expansion phase.

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

    Science.gov (United States)

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

    2016-11-01

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

  11. Robotics and telemanipulation technologies for endoscopic surgery. A review of the ARTEMIS project. Advanced Robotic Telemanipulator for Minimally Invasive Surgery.

    Science.gov (United States)

    Schurr, M O; Buess, G; Neisius, B; Voges, U

    2000-04-01

    In endoscopic surgery, the ability to guide the instrument is significantly decreased compared with open surgery. Rigid laparoscopic instruments offer only four of the six degrees of freedom required for the free handling of objects in space. Robotics technology can be used to restore full mobility of the endoscopic instrument. Therefore, we designed a master-slave manipulator system (ARTEMIS) for laparoscopic surgery as a prototype. The system consists of two robotic arms holding two steerable laparoscopic instruments. These two work units are controlled from a console equipped with two master arms operated by the surgeon. The systems and its components were evaluated experimentally. Laparoscopic manipulations were feasible with the ARTEMIS system. The placement of ligatures and sutures and the handling of catheters were possible in phantom models. The surgical practicability of the system was demonstrated in animal experiments. We conclude that robotic manipulators are feasible for experimental endoscopic surgery. Their clinical application requires further technical development.

  12. 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.

  13. 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...

  14. 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.

  15. PRL-1 protein promotes ERK1/2 and RhoA protein activation through a non-canonical interaction with the Src homology 3 domain of p115 Rho GTPase-activating protein.

    Science.gov (United States)

    Bai, Yunpeng; Luo, Yong; Liu, Sijiu; Zhang, Lujuan; Shen, Kui; Dong, Yuanshu; Walls, Chad D; Quilliam, Lawrence A; Wells, Clark D; Cao, Youjia; Zhang, Zhong-Yin

    2011-12-09

    Phosphatases of the regenerating liver (PRL) play oncogenic roles in cancer development and metastasis. Although previous studies indicate that PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways, the mechanism by which it activates these signaling events remains unclear. We have identified a PRL-1-binding peptide (Peptide 1) that shares high sequence identity with a conserved motif in the Src homology 3 (SH3) domain of p115 Rho GTPase-activating protein (GAP). p115 RhoGAP directly binds PRL-1 in vitro and in cells via its SH3 domain. Structural analyses of the PRL-1·Peptide 1 complex revealed a novel protein-protein interaction whereby a sequence motif within the PxxP ligand-binding site of the p115 RhoGAP SH3 domain occupies a folded groove within PRL-1. This prevents the canonical interaction between the SH3 domain of p115 RhoGAP and MEKK1 and results in activation of ERK1/2. Furthermore, PRL-1 binding activates RhoA signaling by inhibiting the catalytic activity of p115 RhoGAP. The results demonstrate that PRL-1 binding to p115 RhoGAP provides a coordinated mechanism underlying ERK1/2 and RhoA activation.

  16. In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma☆,☆☆

    Science.gov (United States)

    AlHilli, Mariam M.; Becker, Marc A.; Weroha, S. John; Flatten, Karen S.; Hurley, Rachel M.; Harrell, Maria I.; Oberg, Ann L.; Maurer, Matt J.; Hawthorne, Kieran M.; Hou, Xiaonan; Harrington, Sean C.; McKinstry, Sarah; Meng, X. Wei; Wilcoxen, Keith M.; Kalli, Kimberly R.; Swisher, Elizabeth M.; Kaufmann, Scott H.; Haluska, Paul

    2017-01-01

    Objective Poly(ADP-ribose) polymerase (PARP) inhibitors have yielded encouraging responses in high-grade serous ovarian carcinomas (HGSOCs), but the optimal treatment setting remains unknown. We assessed the effect of niraparib on HGSOC patient-derived xenograft (PDX) models as well as the relationship between certain markers of homologous recombination (HR) status, including BRCA1/2 mutations and formation of RAD51 foci after DNA damage, and response of these PDXs to niraparib in vivo. Methods Massively parallel sequencing was performed on HGSOCs to identify mutations contributing to HR deficiency. HR pathway integrity was assessed using fluorescence microscopy-based RAD51 focus formation assays. Effects of niraparib (MK-4827) on treatment-naïve PDX tumor growth as monotherapy, in combination with carboplatin/paclitaxel, and as maintenance therapy were assessed by transabdominal ultrasound. Niraparib responses were correlated with changes in levels of poly(ADP-ribose), PARP1, and repair proteins by western blotting. Results Five PDX models were evaluated in vivo. Tumor regressions were induced by single-agent niraparib in one of two PDX models with deleterious BRCA2 mutations and in a PDX with RAD51C promoter methylation. Diminished formation of RAD51 foci failed to predict response, but Artemis loss was associated with resistance. Niraparib generally failed to enhance responses to carboplatin/paclitaxel chemotherapy, but maintenance niraparib therapy delayed progression in a BRCA2-deficient PDX. Conclusions Mutations in HR genes are neither necessary nor sufficient to predict response to niraparib. Assessment of repair status through multiple complementary assays is needed to guide PARP inhibitor therapy, design future clinical trials and identify ovarian cancer patients most likely to benefit from PARP inhibition. PMID:27614696

  17. HOMOLOGY RIGIDITY OF GRASSMANNIANS

    Institute of Scientific and Technical Information of China (English)

    Li Fang; Duan Haibao

    2009-01-01

    Applying the theory of GrSbner basis to the Schubert presentation for the cohomology of Grassmannians [2], we extend the homology rigidity results known for the classical Grassmaniaas to the exceptional cases.

  18. Sutures and contact homology I

    CERN Document Server

    Colin, Vincent; 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.

  19. 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.

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

    Science.gov (United States)

    Darroudi, Firouz; Wiegant, Wouter; Meijers, Matty; Friedl, Anna A; van der Burg, Mirjam; Fomina, Janna; van Dongen, Jacques J M; van Gent, Dik C; Zdzienicka, Małgorzata Z

    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 gammaH2AX 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(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(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(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(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> or =AT>Artemis. This observation implicates that in human fibroblasts following exposure to ionizing radiation a lower risk might be created when cells are devoid of

  1. 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

  2. Plasma Characteristics and Transport in the Near-Lunar Magnetotail: Observations from THEMIS/ARTEMIS

    Science.gov (United States)

    Stubbs, T. J.; Wang, Y.; Merka, J.; Sibeck, D. G.; Angelopoulos, V.

    2015-12-01

    The region of the Earth's magnetosphere tailward of ~30 RE remains relatively unexplored. A better characterization of the processes taking place in the mid-to-distant magnetotail is critical to a more complete understanding of the coupling between the solar wind and the Earth's magnetosphere. Similarly, an assessment of the magnetotail plasma encountered by the Moon will be valuable for understanding how the lunar environment is modified during these traversals. The THEMIS/ARTEMIS missions have returned sufficient data from this region of the magnetotail for a large-scale statistical survey to be undertaken with the publicly available data from NASA/CDAWeb. In this study various plasma moments are organized by occurrence frequency and location in the magnetotail. Further sorting is done to identify different regions within the magnetotail, such as the tail lobes and plasma sheet, and the physical processes taking place, such as reconnection. Additional sorting of the ion data has been required in order to identify intervals in the tail lobe where the signal-to-noise is so low that moments are erroneously calculated from just background counts. Initial results indicate that previous studies of the mid-to-distant magnetotail that were limited to using electron moments from the ISEE-3 mission overestimated Alfven Mach numbers. Super-Alfvenic flows, such as those associated with reconnection, are very rare in this region of the magnetotail. This survey is the first step in constructing a comprehensive large-scale picture of the energization, distribution, and transport of plasma in the mid-to-distant magnetotail, as well as characterizing the properties of the plasma environments encountered by the Moon during magnetotail traversals.

  3. 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.

  4. R&D Effort at NSCL with the Off-line ECR Ion Source ARTEMIS-B%NSCL的离线ECR离子源ARTEMIS-B的研究与发展

    Institute of Scientific and Technical Information of China (English)

    G.Machicoane; M.Doleans; G.Humenik; F.Marti; P.Miller; M.Steiner; J.Stetson; X.Wu; P.Zavodszky

    2007-01-01

    This paper reviews recent experimental work done with the off line source ARTEMIS-B at the NSCL.This source was built during the year 2005 and provides opportunities for off line development that can benefit the Coupled Cyclotron Facility(CCF)operation while minimizing the time taken away from the nuclear experimental program.The Artemis-B setup includes many beam diagnostics and a detailed description of the emittance scanner(Allison)and emittance measurement method is presented.A first beam dynamics study indicates that the analysis magnet has strong field aberrations and that the beam size in the dipole must be small in order to avoid significant beam brightness degradation.A second study compares beam brightness for different focusing systems between the ECR ion source and the analyzing magnet.Two electrostatic devices:a quadrupole triplet and a double quadrupole doublet have been tested successively and compared to a magnetic focusing solenoid.The experimental results tend to indicate a better beam brightness at smaller emittance for the electrostatic devices,although emittances measured for each focusing element were for a large part dependant on the tuning procedure developed to minimize the effects of the analyzing magnet.

  5. Control of intramolecular interactions between the pleckstrin homology and Dbl homology domains of Vav and Sos1 regulates Rac binding.

    Science.gov (United States)

    Das, B; Shu, X; Day, G J; Han, J; Krishna, U M; Falck, J R; Broek, D

    2000-05-19

    Vav and Sos1 are Dbl family guanine nucleotide exchange factors, which activate Rho family GTPases in response to phosphatidylinositol 3-kinase products. A pleckstrin homology domain adjacent to the catalytic Dbl homology domain via an unknown mechanism mediates the effects of phosphoinositides on guanine nucleotide exchange activity. Here we tested the possibility that phosphatidylinositol 3-kinase substrates and products control an interaction between the pleckstrin homology domain and the Dbl homology domain, thereby explaining the inhibitory effects of phosphatidylinositol 3-kinase substrates and stimulatory effects of the products. Binding studies using isolated fragments of Vav and Sos indicate phosphatidylinositol 3-kinase substrate promotes the binding of the pleckstrin homology domain to the Dbl homology domain and blocks Rac binding to the DH domain, whereas phosphatidylinositol 3-kinase products disrupt the Dbl homology/pleckstrin homology interactions and permit Rac binding. Additionally, Lck phosphorylation of Vav, a known activating event, reduces the affinities between the Vav Dbl homology and pleckstrin homology domains and permits Rac binding. We also show Vav activation in cells, as monitored by phosphorylation of Vav, Vav association with phosphatidylinositol 3,4,5-trisphosphate, and Vav guanine nucleotide exchange activity, is blocked by the phosphatidylinositol 3-kinase inhibitor wortmannin. These results suggest the molecular mechanisms for activation of Vav and Sos1 require disruption of inhibitory intramolecular interactions involving the pleckstrin homology and Dbl homology domains.

  6. 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...

  7. Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients.

    Science.gov (United States)

    Lagresle-Peyrou, Chantal; Benjelloun, Fatine; Hue, Christophe; Andre-Schmutz, Isabelle; Bonhomme, Delphine; Forveille, Monique; Beldjord, Kheira; Hacein-Bey-Abina, Salima; De Villartay, Jean-Pierre; Charneau, Pierre; Durandy, Anne; Fischer, Alain; Cavazzana-Calvo, Marina

    2008-02-01

    Severe combined immunodeficiency (SCID) caused by mutation of the recombination-activating gene 1 (RAG1) or Artemis gene lead to the absence of B- and T-cell differentiation. The only curative treatment is allogeneic bone marrow (BM) transplantation, which displays a high survival rate when an HLA compatible donor is available but has a poorer prognosis when the donor is partially compatible. Consequently, gene therapy may be a promising alternative strategy for these diseases. Here, we report that lentiviral gene-corrected BM CD34(+) cells (isolated from Artemis- or RAG1-deficient patients) sustain human B-cell differentiation following injection into non-obese diabetic/SCID (NOD-SCID) mice previously infused with anti-interleukin-2 receptor beta chain monoclonal antibody. In most of the mice BM, engrafted with Artemis-transduced cells, human B-cell differentiation occurred until the mature stage. The B cells were functional as human immunoglobulin M (IgM) was present in the serum. Following injection with RAG1-transduced cells, human engraftment occurred in vivo but B-cell differentiation until the mature stage was less frequent. However, when it occurred, it was always associated with human IgM production. This overall approach represents a useful tool for evaluating gene transfer efficiency in human SCID forms affecting B-cell development (such as Artemis deficiency) and for testing new vectors for improving in vivo RAG1 complementation.

  8. Structure of the catalytic region of DNA ligase IV in complex with an Artemis fragment sheds light on double-strand break repair.

    Science.gov (United States)

    Ochi, Takashi; Gu, Xiaolong; Blundell, Tom L

    2013-04-02

    Nonhomologous end joining (NHEJ) is central to the repair of double-stranded DNA breaks throughout the cell cycle and plays roles in the development of the immune system. Although three-dimensional structures of most components of NHEJ have been defined, those of the catalytic region of DNA ligase IV (LigIV), a specialized DNA ligase known to work in NHEJ, and of Artemis have remained unresolved. Here, we report the crystal structure at 2.4 Å resolution of the catalytic region of LigIV (residues 1-609) in complex with an Artemis peptide. We describe interactions of the DNA-binding domain of LigIV with the continuous epitope of Artemis, which, together, form a three-helix bundle. A kink in the first helix of LigIV introduced by a conserved VPF motif gives rise to a hydrophobic pocket, which accommodates a conserved tryptophan from Artemis. We provide structural insights into features of LigIV among human DNA ligases.

  9. 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...

  10. 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 Gorenste...

  11. On the shape of the Geomagnetic Tail at Lunar distances: Preliminary Resuts from Artemis Observations

    Science.gov (United States)

    Gencturk Akay, Iklim; Kaymaz, Zerefsan; Sibeck, David G.

    2013-04-01

    Geomagnetic tail is one of the least investigated regions of the magnetosphere behind the Earth owing to the limited number of spacecraft and observations. It is the region where the geomagnetic dipole field lines of the Earth are organized by the solar wind stretching. The characteristics of the geomagnetic tail and its response to IMF were studied by the missions, ISEE-3, IMP-8, Wind, Geotail, visited geomagnetic tail at different distances. The structure of the geomagnetic tail is controlled by the IMF orientation and its own internal dynamics. Geomagnetic tail has different regions where the plasma and magnetic field characteristics are largely depend on the IMF orientation. These characteristics show differences at different tail distances. For example it is determined that the tail twists as result of the reconnection with IMF By and this twist is higher as one move away from the Earth toward the distant tail. Like a windsock, it is expected that the IMF control will increase toward the distant tail. Twisting also displaces the north and south lobes on the dawn and dusk sides. Tail length and the shape are also different for different IMF orientations. Flattening of the geomagnetic tail cross-section occurs during the strong IMF Bys. It becomes an ellipse in the yz plane as the IMF By stress causes the tail to be flattened on the top and bottom. Models estimate that the geomagnetic tail length can be 165 Re while Pioneer spacecraft detected geomagnetic tail as long as 100 Re. These findings are based on the very limited data from brief geomagnetic tail encounters of the spacecraft. Since August 2011, with the repositioning of the two of THEMIS spacecraft pair, ARTEMIS is giving a new opportunity to study the geomagnetic tail at the lunar distances, 60 Re. Using these observations, we will investigate the geomagnetic field shape and its IMF dependence at 60 Re. Based on the magnetopause locations at 60 Re, we will study the shape of the tail on the xy

  12. 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

  13. Algebra V homological algebra

    CERN Document Server

    Shafarevich, I

    1994-01-01

    This book, the first printing of which was published as volume 38 of the Encyclopaedia of Mathematical Sciences, presents a modern approach to homological algebra, based on the systematic use of the terminology and ideas of derived categories and derived functors. The book contains applications of homological algebra to the theory of sheaves on topological spaces, to Hodge theory, and to the theory of modules over rings of algebraic differential operators (algebraic D-modules). The authors Gelfand and Manin explain all the main ideas of the theory of derived categories. Both authors are well-known researchers and the second, Manin, is famous for his work in algebraic geometry and mathematical physics. The book is an excellent reference for graduate students and researchers in mathematics and also for physicists who use methods from algebraic geometry and algebraic topology.

  14. Rabinowitz Floer homology: A survey

    CERN Document Server

    Albers, Peter

    2010-01-01

    Rabinowitz Floer homology is the semi-infinite dimensional Morse homology associated to the Rabinowitz action functional used in the pioneering work of Rabinowitz. Gradient flow lines are solutions of a vortex-like equation. In this survey article we describe the construction of Rabinowitz Floer homology and its applications to symplectic and contact topology, global Hamiltonian perturbations and the study of magnetic fields.

  15. First Lunar Wake Passage of ARTEMIS: Discrimination of Wake Effects and Solar Wind Fluctuations by 3D Hybrid Simulations

    Science.gov (United States)

    Wiehle, S.; Plaschke, F.; Motschmann, U.; Glassmeier, K. H.; Auster, H. U.; Angelopoulos, V.; Mueller, J.; Kriegel, H.; Georgescu, E.; Halekas, J.; Sibeck, D. G.; McFadden, J. P.

    2011-01-01

    The spacecraft P1 of the new ARTEMIS (Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun) mission passed the lunar wake for the first time on February 13, 2010. We present magnetic field and plasma data of this event and results of 3D hybrid simulations. As the solar wind magnetic field was highly dynamic during the passage, a simulation with stationary solar wind input cannot distinguish whether distortions were caused by these solar wind variations or by the lunar wake; therefore, a dynamic real-time simulation of the flyby has been performed. The input values of this simulation are taken from NASA OMNI data and adapted to the P1 data, resulting in a good agreement between simulation and measurements. Combined with the stationary simulation showing non-transient lunar wake structures, a separation of solar wind and wake effects is achieved. An anisotropy in the magnitude of the plasma bulk flow velocity caused by a non-vanishing magnetic field component parallel to the solar wind flow and perturbations created by counterstreaming ions in the lunar wake are observed in data and simulations. The simulations help to interpret the data granting us the opportunity to examine the entire lunar plasma environment and, thus, extending the possibilities of measurements alone: A comparison of a simulation cross section to theoretical predictions of MHD wave propagation shows that all three basic MHD modes are present in the lunar wake and that their expansion governs the lunar wake refilling process.

  16. Homology theory on algebraic varieties

    CERN Document Server

    Wallace, Andrew H

    1958-01-01

    Homology Theory on Algebraic Varieties, Volume 6 deals with the principles of homology theory in algebraic geometry and includes the main theorems first formulated by Lefschetz, one of which is interpreted in terms of relative homology and another concerns the Poincaré formula. The actual details of the proofs of these theorems are introduced by geometrical descriptions, sometimes aided with diagrams. This book is comprised of eight chapters and begins with a discussion on linear sections of an algebraic variety, with emphasis on the fibring of a variety defined over the complex numbers. The n

  17. Compositional Homology and Creative Thinking

    Directory of Open Access Journals (Sweden)

    Salvatore Tedesco

    2015-05-01

    Full Text Available The concept of homology is the most solid theoretical basis elaborated by the morphological thinking during its history. The enucleation of some general criteria for the interpretation of homology is today a fundamental tool for life sciences, and for restoring their own opening to the question of qualitative innovation that arose so powerfully in the original Darwinian project. The aim of this paper is to verify the possible uses of the concept of compositional homology in order to provide of an adequate understanding of the dynamics of creative thinking.

  18. 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.

  19. Regulation of Homologous Recombination by SUMOylation

    DEFF Research Database (Denmark)

    Pinela da Silva, Sonia Cristina

    Double-strand breaks (DSBs) are one of the most deleterious types of DNA lesions challenging genome integrity. The DNA damage response (DDR) promotes fast and effective detection and repair of the damaged DNA, leading to cell cycle arrest through checkpoint activation and the recruitment of repair...... factors such as the homologous recombination (HR) machinery. HR constitutes the main DSB repair pathway in Saccharomyces cerevisiae and despite being largely considered an error-free process and essential for genome stability, uncontrolled recombination can lead to loss of heterozygosity, translocations....... 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 protein...

  20. Ion density and temperature profiles along (XGSM) and across (ZGSM) the magnetotail as observed by THEMIS, Geotail, and ARTEMIS

    Science.gov (United States)

    Artemyev, A. V.; Angelopoulos, V.; Hietala, H.; Runov, A.; Shinohara, I.

    2017-02-01

    Characteristics of the two-dimensional configuration of the magnetotail current sheet are important for modeling magnetotail motion/evolution and charged particle energization. Because of the magnetotail current sheet's dynamical nature, however, simultaneous plasma and magnetic field measurements at different radial distances are required to reveal this configuration. Simultaneous observations of the magnetotail current sheet from Time History of Events and Macroscale Interactions during Substorms (THEMIS) D (around 10RE downtail), Geotail (around 30RE downtail), and Acceleration, Reconnection, Turbulence and Electrodynamics of the Moons Interaction with the Sun (ARTEMIS) P1 (around 55RE downtail) are used to study distributions of plasma (ion) density and temperature along (Earth-Sun direction) and across (north-south direction) the magnetotail. Fourteen events (each including several current sheet crossings at different downtail distances) are studied. We demonstrate that the plasma temperature along and across the magnetotail varies more significantly than plasma density does. The temperature decrease from equatorial plane to current sheet boundaries is a major contributor to the cross-tail pressure balance. The Alfven velocity VA,B calculated at the current sheet boundaries increases significantly toward the Earth from 700 km/s at lunar orbit ˜55RE to 2200 km/s around ˜10RE downtail. The corresponding energy EA=mpVA,B2 (mp is the proton mass) is 4 times larger than the plasma temperature T0 in the magnetotail's equatorial plane, whereas the ratio EA/T0 is constant along the magnetotail. The plasma temperature T0 measured around lunar orbit in the magnetotail agrees well with the simultaneously measured energy of solar wind protons mpVSW2/2 (VSW is the solar wind speed).

  1. 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

  2. A Single-Strand Annealing Protein Clamps DNA to Detect and Secure Homology.

    OpenAIRE

    Marcel Ander; Sivaraman Subramaniam; Karim Fahmy; Francis Stewart, A.; Erik Schäffer

    2015-01-01

    Repair of DNA breaks by single-strand annealing (SSA) is a major mechanism for the maintenance of genomic integrity. SSA is promoted by proteins (single-strand-annealing proteins [SSAPs]), such as eukaryotic RAD52 and λ phage Redβ. These proteins use a short single-stranded region to find sequence identity and initiate homologous recombination. However, it is unclear how SSAPs detect homology and catalyze annealing. Using single-molecule experiments, we provide evidence that homology is recog...

  3. Single chain fragment variable antibodies developed by using as target the 3rd fibronectin type III homologous repeat fragment of human neural cell adhesion molecule L1 promote cell migration and neuritogenesis.

    Science.gov (United States)

    Tang, Dan-Yang; Yu, Yang; Zhao, Xuan-Jun; Schachner, Melitta; Zhao, Wei-Jiang

    2015-01-15

    L1CAM plays important roles during ontogeny, including promotion of neuronal cell migration and neuritogenesis, and stimulation of axonal outgrowth, fasciculation and myelination. These functions are at least partially exerted through a 16-mer amino acid sequence in the third fibronectin type III-like repeat of L1, which associates with several interaction partners, including integrins, other adhesion molecules and growth factor receptors. Here, using the Tomlinson I library for phage display, we obtained two single-chain variable fragment antibodies (scFvs) against this peptide sequence of human L1, hereafter called H3 peptide. Both scFvs recognize the H3 peptide and the extracellular domain of L1, as tested by enzyme-linked immunosorbent assay (ELISA), Western blot analysis and immunofluorescence staining of L1 expresssing cells. Furthermore, both scFvs reduce U-87 MG cell adhesion to fibronectin, while stimulating cell migration. Application of scFvs to human neuroblastoma SK-N-SH cells promote process outgrowth. Similar to triggering of endogenous L1 functions at the cell surface, both scFvs activate the signal transducers Erk and Src in these cells. Our results indicate that scFvs against a functionally pivotal domain in L1 trigger its regeneration-beneficial functions in vitro, encouraging thoughts on therapy of neurodegenerative diseases in the hope to ameliorate human nervous system diseases.

  4. Homology of locally semialgebraic spaces

    CERN Document Server

    Delfs, Hans

    1991-01-01

    Locally semialgebraic spaces serve as an appropriate framework for studying the topological properties of varieties and semialgebraic sets over a real closed field. This book contributes to the fundamental theory of semialgebraic topology and falls into two main parts. The first dealswith sheaves and their cohomology on spaces which locally look like a constructible subset of a real spectrum. Topics like families of support, homotopy, acyclic sheaves, base-change theorems and cohomological dimension are considered. In the second part a homology theory for locally complete locally semialgebraic spaces over a real closed field is developed, the semialgebraic analogue of classical Bore-Moore-homology. Topics include fundamental classes of manifolds and varieties, Poincare duality, extensions of the base field and a comparison with the classical theory. Applying semialgebraic Borel-Moore-homology, a semialgebraic ("topological") approach to intersection theory on varieties over an algebraically closed field of ch...

  5. Homology group on manifolds and their foldings

    Directory of Open Access Journals (Sweden)

    M. Abu-Saleem

    2010-03-01

    Full Text Available In this paper, we introduce the definition of the induced unfolding on the homology group. Some types of conditional foldings restricted on the elements of the homology groups are deduced. The effect of retraction on the homology group of a manifold is dicussed. The unfolding of variation curvature of manifolds on their homology group are represented. The relations between homology group of the manifold and its folding are deduced.

  6. Homological Type of Geometric Transitions

    CERN Document Server

    Rossi, Michele

    2010-01-01

    The present paper gives an account and quantifies the change in topology induced by small and type II geometric transitions, by introducing the notion of the \\emph{homological type} of a geometric transition. The obtained results agree with, and go further than, most results and estimates, given to date by several authors, both in mathematical and physical literature.

  7. Homological stability of diffeomorphism groups

    DEFF Research Database (Denmark)

    Berglund, Alexander; Madsen, Ib Henning

    2013-01-01

    In this paper we prove a stability theorem for block diffeomorphisms of 2d -dimensional manifolds that are connected sums of S d ×S d . Combining this with a recent theorem of S. Galatius and O. Randal-Williams and Morlet’s lemma of disjunction, we determine the homology of the classifying space ...

  8. 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–Smith...

  9. The Neural Cell Adhesion Molecule (NCAM) Promotes Clustering and Activation of EphA3 Receptors in GABAergic Interneurons to Induce Ras Homolog Gene Family, Member A (RhoA)/Rho-associated protein kinase (ROCK)-mediated Growth Cone Collapse.

    Science.gov (United States)

    Sullivan, Chelsea S; Kümper, Maike; Temple, Brenda S; Maness, Patricia F

    2016-12-16

    Establishment of a proper balance of excitatory and inhibitory connectivity is achieved during development of cortical networks and adjusted through synaptic plasticity. The neural cell adhesion molecule (NCAM) and the receptor tyrosine kinase EphA3 regulate the perisomatic synapse density of inhibitory GABAergic interneurons in the mouse frontal cortex through ephrin-A5-induced growth cone collapse. In this study, it was demonstrated that binding of NCAM and EphA3 occurred between the NCAM Ig2 domain and EphA3 cysteine-rich domain (CRD). The binding interface was further refined through molecular modeling and mutagenesis and shown to be comprised of complementary charged residues in the NCAM Ig2 domain (Arg-156 and Lys-162) and the EphA3 CRD (Glu-248 and Glu-264). Ephrin-A5 induced co-clustering of surface-bound NCAM and EphA3 in GABAergic cortical interneurons in culture. Receptor clustering was impaired by a charge reversal mutation that disrupted NCAM/EphA3 association, emphasizing the importance of the NCAM/EphA3 binding interface for cluster formation. NCAM enhanced ephrin-A5-induced EphA3 autophosphorylation and activation of RhoA GTPase, indicating a role for NCAM in activating EphA3 signaling through clustering. NCAM-mediated clustering of EphA3 was essential for ephrin-A5-induced growth cone collapse in cortical GABAergic interneurons, and RhoA and a principal effector, Rho-associated protein kinase, mediated the collapse response. This study delineates a mechanism in which NCAM promotes ephrin-A5-dependent clustering of EphA3 through interaction of the NCAM Ig2 domain and the EphA3 CRD, stimulating EphA3 autophosphorylation and RhoA signaling necessary for growth cone repulsion in GABAergic interneurons in vitro, which may extend to remodeling of axonal terminals of interneurons in vivo.

  10. 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...

  11. The minimum amount of homology required for homologous recombination in mammalian cells.

    OpenAIRE

    Rubnitz, J; Subramani, S

    1984-01-01

    Although DNA sequence homology is believed to be a prerequisite for homologous recombination events in procaryotes and eucaryotes, no systematic study has been done on the minimum amount of homology required for homologous recombination in mammalian cells. We have used simian virus 40-pBR322 hybrid plasmids constructed in vitro as substrates to quantitate intramolecular homologous recombination in cultured monkey cells. Excision of wild-type simian virus 40 DNA by homologous recombination was...

  12. Sutured Floer homology and hypergraphs

    CERN Document Server

    Juhász, András; Rasmussen, Jacob

    2011-01-01

    By applying Seifert's algorithm to a special alternating diagram of a link L, one obtains a Seifert surface F of L. We show that the support of the sutured Floer homology of the sutured manifold complementary to F is affine isomorphic to the set of lattice points given as hypertrees in a certain hypergraph that is naturally associated to the diagram. This implies that the Floer groups in question are supported in a set of Spin^c structures that are the integer lattice points of a convex polytope. This property has an immediate extension to Seifert surfaces arising from homogeneous link diagrams (including all alternating and positive diagrams). In another direction, together with work in progress of the second author and others, our correspondence suggests a method for computing the "top" coefficients of the HOMFLY polynomial of a special alternating link from the sutured Floer homology of a Seifert surface complement for a certain dual link.

  13. Minimax Rates for Homology Inference

    CERN Document Server

    Balakrishnan, Sivaraman; Sheehy, Don; Singh, Aarti; Wasserman, Larry

    2011-01-01

    Often, high dimensional data lie close to a low-dimensional submanifold and it is of interest to understand the geometry of these submanifolds. The homology groups of a manifold are important topological invariants that provide an algebraic summary of the manifold. These groups contain rich topological information, for instance, about the connected components, holes, tunnels and sometimes the dimension of the manifold. In this paper, we consider the statistical problem of estimating the homology of a manifold from noisy samples under several different noise models. We derive upper and lower bounds on the minimax risk for this problem. Our upper bounds are based on estimators which are constructed from a union of balls of appropriate radius around carefully selected points. In each case we establish complementary lower bounds using Le Cam's lemma.

  14. Homologous recombination in Leishmania enriettii.

    OpenAIRE

    1991-01-01

    We have used derivatives of the recently developed stable transfection vector pALT-Neo to formally demonstrate that Leishmania enriettii contains the enzymatic machinery necessary for homologous recombination. This observation has implications for gene regulation, gene amplification, genetic diversity, and the maintenance of tandemly repeated gene families in the Leishmania genome as well as in closely related organisms, including Trypanosoma brucei. Two plasmids containing nonoverlapping del...

  15. Homologous recombination in Leishmania enriettii.

    Science.gov (United States)

    Tobin, J F; Laban, A; Wirth, D F

    1991-02-01

    We have used derivatives of the recently developed stable transfection vector pALT-Neo to formally demonstrate that Leishmania enriettii contains the enzymatic machinery necessary for homologous recombination. This observation has implications for gene regulation, gene amplification, genetic diversity, and the maintenance of tandemly repeated gene families in the Leishmania genome as well as in closely related organisms, including Trypanosoma brucei. Two plasmids containing nonoverlapping deletions of the chloramphenicol acetyltransferase (CAT) gene, as well as the neomycin-resistance gene, were cotransfected into L. enriettii. Analysis of the DNA from these cells by Southern blotting and plasmid rescue revealed that a full-length or doubly deleted CAT gene could be reconstructed by homologous crossing-over and/or gene conversion between the two deletion plasmids. Additionally, parasites cotransfected with pALT-Neo and pALT-CAT-S, a plasmid containing two copies of the chimeric alpha-tubulin-CAT gene, resulted in G418-resistant parasites expressing high levels of CAT activity. The structure of the DNA within these cells, as shown by Southern blot analysis and the polymerase chain reaction, is that which would be expected from a homologous exchange event occurring between the two plasmids.

  16. Deep homology: a view from systematics.

    Science.gov (United States)

    Scotland, Robert W

    2010-05-01

    Over the past decade, it has been discovered that disparate aspects of morphology - often of distantly related groups of organisms - are regulated by the same genetic regulatory mechanisms. Those discoveries provide a new perspective on morphological evolutionary change. A conceptual framework for exploring these research findings is termed 'deep homology'. A comparative framework for morphological relations of homology is provided that distinguishes analogy, homoplasy, plesiomorphy and synapomorphy. Four examples - three from plants and one from animals - demonstrate that homologous developmental mechanisms can regulate a range of morphological relations including analogy, homoplasy and examples of uncertain homology. Deep homology is part of a much wider range of phenomena in which biological (genes, regulatory mechanisms, morphological traits) and phylogenetic levels of homology can both be disassociated. Therefore, to understand homology, precise, comparative, independent statements of both biological and phylogenetic levels of homology are necessary.

  17. Homology requirements for recombination in Escherichia coli.

    OpenAIRE

    Watt, V M; Ingles, C J; Urdea, M S; Rutter, W J

    1985-01-01

    The DNA sequence homology required for recombination in Escherichia coli has been determined by measuring the recombination frequency between insulin DNA in a miniplasmid pi VX and a homologous sequence in a bacteriophage lambda vector. A minimum of approximately equal to 20 base pairs in a completely homologous segment is required for significant recombination. There is an exponential increase in the frequency of recombination when the length of homologous DNA is increased from 20 base pairs...

  18. 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.

  19. Virtual Khovanov homology using cobordisms

    DEFF Research Database (Denmark)

    Tubbenhauer, Daniel

    2014-01-01

    We give a geometric interpretation of the Khovanov complex for virtual links. Geometric interpretation means that we use a cobordism structure like D. Bar-Natan, but we allow non orientable cobordisms. Like D. Bar-Natans geometric complex our construction should work for virtual tangles too....... This geometric complex allows, in contrast to the geometric version of V. Turaev and P. Turner, a direct extension of the classical Khovanov complex (h=t=0) and of the variant of Lee (h=0,t=1). Furthermore we give a classification of all unoriented TQFTs which can be used to define virtual link homologies...

  20. Weak homology of elliptical galaxies

    CERN Document Server

    Bertin, G; Principe, M D

    2002-01-01

    We start by studying a small set of objects characterized by photometric profiles that have been pointed out to deviate significantly from the standard R^{1/4} law. For these objects we confirm that a generic R^{1/n} law, with n a free parameter, can provide superior fits (the best-fit value of n can be lower than 2.5 or higher than 10), better than those that can be obtained by a pure R^{1/4} law, by an R^{1/4}+exponential model, and by other dynamically justified self--consistent models. Therefore, strictly speaking, elliptical galaxies should not be considered homologous dynamical systems. Still, a case for "weak homology", useful for the interpretation of the Fundamental Plane of elliptical galaxies, could be made if the best-fit parameter n, as often reported, correlates with galaxy luminosity L, provided the underlying dynamical structure also follows a systematic trend with luminosity. We demonstrate that this statement may be true even in the presence of significant scatter in the correlation n(L). Pr...

  1. 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.

  2. Khovanov homology of links and graphs

    Science.gov (United States)

    Stosic, Marko

    2006-05-01

    In this thesis we work with Khovanov homology of links and its generalizations, as well as with the homology of graphs. Khovanov homology of links consists of graded chain complexes which are link invariants, up to chain homotopy, with graded Euler characteristic equal to the Jones polynomial of the link. Hence, it can be regarded as the "categorification" of the Jones polynomial. We prove that the first homology group of positive braid knots is trivial. Futhermore, we prove that non-alternating torus knots are homologically thick. In addition, we show that we can decrease the number of full twists of torus knots without changing low-degree homology and consequently that there exists stable homology for torus knots. We also prove most of the above properties for Khovanov-Rozansky homology. Concerning graph homology, we categorify the dichromatic (and consequently Tutte) polynomial for graphs, by categorifying an infinite set of its one-variable specializations. We categorify explicitly the one-variable specialization that is an analog of the Jones polynomial of an alternating link corresponding to the initial graph. Also, we categorify explicitly the whole two-variable dichromatic polynomial of graphs by using Koszul complexes. textbf{Key-words:} Khovanov homology, Jones polynomial, link, torus knot, graph, dichromatic polynomial

  3. Equivariant ordinary homology and cohomology

    CERN Document Server

    Costenoble, Steven R

    2016-01-01

    Filling a gap in the literature, this book takes the reader to the frontiers of equivariant topology, the study of objects with specified symmetries. The discussion is motivated by reference to a list of instructive “toy” examples and calculations in what is a relatively unexplored field. The authors also provide a reading path for the first-time reader less interested in working through sophisticated machinery but still desiring a rigorous understanding of the main concepts. The subject’s classical counterparts, ordinary homology and cohomology, dating back to the work of Henri Poincaré in topology, are calculational and theoretical tools which are important in many parts of mathematics and theoretical physics, particularly in the study of manifolds. Similarly powerful tools have been lacking, however, in the context of equivariant topology. Aimed at advanced graduate students and researchers in algebraic topology and related fields, the book assumes knowledge of basic algebraic topology and group act...

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. Why do bacteria engage in homologous recombination?

    NARCIS (Netherlands)

    Vos, M.

    2009-01-01

    Microbiologists have long recognized that the uptake and incorporation of homologous DNA from outside the cell is a common feature of bacteria, with important implications for their evolution. However, the exact reasons why bacteria engage in homologous recombination remain elusive. This Opinion art

  9. DNA Sequence Alignment during Homologous Recombination.

    Science.gov (United States)

    Greene, Eric C

    2016-05-27

    Homologous recombination allows for the regulated exchange of genetic information between two different DNA molecules of identical or nearly identical sequence composition, and is a major pathway for the repair of double-stranded DNA breaks. A key facet of homologous recombination is the ability of recombination proteins to perfectly align the damaged DNA with homologous sequence located elsewhere in the genome. This reaction is referred to as the homology search and is akin to the target searches conducted by many different DNA-binding proteins. Here I briefly highlight early investigations into the homology search mechanism, and then describe more recent research. Based on these studies, I summarize a model that includes a combination of intersegmental transfer, short-distance one-dimensional sliding, and length-specific microhomology recognition to efficiently align DNA sequences during the homology search. I also suggest some future directions to help further our understanding of the homology search. Where appropriate, I direct the reader to other recent reviews describing various issues related to homologous recombination.

  10. Hidden torsion, 3-manifolds, and homology cobordism

    CERN Document Server

    Cha, Jae Choon

    2011-01-01

    This paper continues our exploration of homology cobordism of 3-manifolds using our recent results on Cheeger-Gromov rho-invariants associated to amenable representations. We introduce a new type of torsion in 3-manifold groups we call hidden torsion, and an algebraic approximation we call local hidden torsion. We construct infinitely many hyperbolic 3-manifolds which have local hidden torsion in the transfinite lower central subgroup. By realizing Cheeger-Gromov invariants over amenable groups, we show that our hyperbolic 3-manifolds are not pairwise homology cobordant, yet remain indistinguishable by any prior known homology cobordism invariants.

  11. 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

  12. 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.

  13. The homologous recombination system of Ustilago maydis.

    Science.gov (United States)

    Holloman, William K; Schirawski, Jan; Holliday, Robin

    2008-08-01

    Homologous recombination is a high fidelity, template-dependent process that is used in repair of damaged DNA, recovery of broken replication forks, and disjunction of homologous chromosomes in meiosis. Much of what is known about recombination genes and mechanisms comes from studies on baker's yeast. Ustilago maydis, a basidiomycete fungus, is distant evolutionarily from baker's yeast and so offers the possibility of gaining insight into recombination from an alternative perspective. Here we have surveyed the genome of U. maydis to determine the composition of its homologous recombination system. Compared to baker's yeast, there are fundamental differences in the function as well as in the repertoire of dedicated components. These include the use of a BRCA2 homolog and its modifier Dss1 rather than Rad52 as a mediator of Rad51, the presence of only a single Rad51 paralog, and the absence of Dmc1 and auxiliary meiotic proteins.

  14. 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.

  15. The homologous recombination system of Ustilago maydis

    OpenAIRE

    Holloman, William K.; Schirawski, Jan; Holliday, Robin

    2008-01-01

    Homologous recombination is a high fidelity, template-dependent process that is used in repair of damaged DNA, recovery of broken replication forks, and disjunction of homologous chromosomes in meiosis. Much of what is known about recombination genes and mechanisms comes from studies on baker's yeast. Ustilago maydis, a basidiomycete fungus, is distant evolutionarily from baker's yeast and so offers the possibility of gaining insight into recombination from an alternative perspective. Here we...

  16. Homolog pairing and segregation in Drosophila meiosis.

    Science.gov (United States)

    McKee, B D

    2009-01-01

    Pairing of homologous chromosomes is fundamental to their reliable segregation during meiosis I and thus underlies sexual reproduction. In most eukaryotes homolog pairing is confined to prophase of meiosis I and is accompanied by frequent exchanges, known as crossovers, between homologous chromatids. Crossovers give rise to chiasmata, stable interhomolog connectors that are required for bipolar orientation (orientation to opposite poles) of homologs during meiosis I. Drosophila is unique among model eukaryotes in exhibiting regular homolog pairing in mitotic as well as meiotic cells. I review the results of recent molecular studies of pairing in both mitosis and meiosis in Drosophila. These studies show that homolog pairing is continuous between pre-meiotic mitosis and meiosis but that pairing frequencies and patterns are altered during the mitotic-meiotic transition. They also show that, with the exception of X-Y pairing in male meiosis, which is mediated specifically by the 240-bp rDNA spacer repeats, chromosome pairing is not restricted to specific sites in either mitosis or meiosis. Instead, virtually all chromosome regions, both heterochromatic and euchromatic, exhibit autonomous pairing capacity. Mutations that reduce the frequencies of both mitotic and meiotic pairing have been recently described, but no mutations that abolish pairing completely have been discovered, and the genetic control of pairing in Drosophila remains to be elucidated.

  17. 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

  18. A Khovanov Type Link Homology with Geometric Interpretation

    Institute of Scientific and Technical Information of China (English)

    Mei Li ZHANG; Feng Chun LEI

    2016-01-01

    We study a Khovanov type homology close to the original Khovanov homology theory from Frobenius system. The homology is an invariant for oriented links up to isotopy by applying a tautological functor on the geometric complex. The homology has also geometric descriptions by introducing the genus generating operations. We prove that Jones Polynomial is equal to a suitable Euler characteristic of the homology groups. As an application, we compute the homology groups of (2, k)-torus knots for every k∈N.

  19. 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

  20. 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...

  1. Hyper(co)homology for exact left covariant functors and a homology theory for topological spaces

    Science.gov (United States)

    Sklyarenko, E. G.

    1995-06-01

    Contents Introduction §1. Strong cohomology of dual complexes §2. Hyperhomology §3. Examples §4. Typical limit relations for Steenrod-Sitnikov homology §5. The strong homology of topological spaces §6. On the special position held by singular theory Bibliography

  2. [DNA homologous recombination repair in mammalian cells].

    Science.gov (United States)

    Popławski, Tomasz; Błasiak, Janusz

    2006-01-01

    DNA double-strand breaks (DSBs) are the most serious DNA damage. Due to a great variety of factors causing DSBs, the efficacy of their repair is crucial for the cell's functioning and prevents DNA fragmentation, chromosomal translocation and deletion. In mammalian cells DSBs can be repaired by non-homologous end joining (NHEJ), homologous recombination (HRR) and single strand annealing (SSA). HRR can be divided into the first and second phase. The first phase is initiated by sensor proteins belonging to the MRN complex, that activate the ATM protein which target HRR proteins to obtain the second response phase--repair. HRR is precise because it utilizes a non-damaged homologous DNA fragment as a template. The key players of HRR in mammalian cells are MRN, RPA, Rad51 and its paralogs, Rad52 and Rad54.

  3. Crystal structure of an archaeal actin homolog.

    Science.gov (United States)

    Roeben, Annette; Kofler, Christine; Nagy, István; Nickell, Stephan; Hartl, F Ulrich; Bracher, Andreas

    2006-04-21

    Prokaryotic homologs of the eukaryotic structural protein actin, such as MreB and ParM, have been implicated in determination of bacterial cell shape, and in the segregation of genomic and plasmid DNA. In contrast to these bacterial actin homologs, little is known about the archaeal counterparts. As a first step, we expressed a predicted actin homolog of the thermophilic archaeon Thermoplasma acidophilum, Ta0583, and determined its crystal structure at 2.1A resolution. Ta0583 is expressed as a soluble protein in T.acidophilum and is an active ATPase at physiological temperature. In vitro, Ta0583 forms sheets with spacings resembling the crystal lattice, indicating an inherent propensity to form filamentous structures. The fold of Ta0583 contains the core structure of actin and clearly belongs to the actin/Hsp70 superfamily of ATPases. Ta0583 is approximately equidistant from actin and MreB on the structural level, and combines features from both eubacterial actin homologs, MreB and ParM. The structure of Ta0583 co-crystallized with ADP indicates that the nucleotide binds at the interface between the subdomains of Ta0583 in a manner similar to that of actin. However, the conformation of the nucleotide observed in complex with Ta0583 clearly differs from that in complex with actin, but closely resembles the conformation of ParM-bound nucleotide. On the basis of sequence and structural homology, we suggest that Ta0583 derives from a ParM-like actin homolog that was once encoded by a plasmid and was transferred into a common ancestor of Thermoplasma and Ferroplasma. Intriguingly, both genera are characterized by the lack of a cell wall, and therefore Ta0583 could have a function in cellular organization.

  4. 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.

  5. 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.

  6. 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.

  7. 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....

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

    OpenAIRE

    Taylor, MRG; Špírek, M; Chaurasiya, KR; Ward, JD; Carzaniga, R.; Yu, X; Egelman, EH; Collinson, LM; Rueda, D.; Krejci, L; Boulton, SJ

    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 ...

  9. 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...

  10. Persistent Homology for Random Fields and Complexes

    CERN Document Server

    Adler, Robert J; Borman, Matthew S; Subag, Eliran; Weinberger, Shmuel

    2010-01-01

    We discuss and review recent developments in the area of applied algebraic topology, such as persistent homology and barcodes. In particular, we discuss how these are related to understanding more about manifold learning from random point cloud data, the algebraic structure of simplicial complexes determined by random vertices, and, in most detail, the algebraic topology of the excursion sets of random fields.

  11. 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...

  12. Gorenstein Homological Dimensions and Change of Rings

    Institute of Scientific and Technical Information of China (English)

    Xiaoyan YANG

    2012-01-01

    In this paper,we shall be concerned with what happens of Gorenstein homological dimensions when certain modifications are made to a ring. The five structural operations addressed later are the formation of excellent extensions,localizations,Morita equivalences,polynomial extensions and power series extensions.

  13. Persistent homology in graph power filtrations.

    Science.gov (United States)

    Parks, Allen D; Marchette, David J

    2016-10-01

    The persistence of homological features in simplicial complex representations of big datasets in R (n) resulting from Vietoris-Rips or Čech filtrations is commonly used to probe the topological structure of such datasets. In this paper, the notion of homological persistence in simplicial complexes obtained from power filtrations of graphs is introduced. Specifically, the rth complex, r ≥ 1, in such a power filtration is the clique complex of the rth power G(r) of a simple graph G. Because the graph distance in G is the relevant proximity parameter, unlike a Euclidean filtration of a dataset where regional scale differences can be an issue, persistence in power filtrations provides a scale-free insight into the topology of G. It is shown that for a power filtration of G, the girth of G defines an r range over which the homology of the complexes in the filtration are guaranteed to persist in all dimensions. The role of chordal graphs as trivial homology delimiters in power filtrations is also discussed and the related notions of 'persistent triviality', 'transient noise' and 'persistent periodicity' in power filtrations are introduced.

  14. Khovanov homology for virtual tangles and applications

    DEFF Research Database (Denmark)

    Tubbenhauer, Daniel

    We extend the cobordism based categorification of the virtual Jones polynomial to virtual tangles. This extension is combinatorial and has semi-local properties. We use the semi-local property to prove an applications, i.e. we give a discussion of Lee's degeneration of virtual homology....

  15. 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.

  16. Homology stability for the general linear group

    NARCIS (Netherlands)

    Maazen, Hendrik

    1979-01-01

    This thesis studies the homology stability problem for general linear groups over Euclidean rings and over subrings of the field of rational numbers. Affine linear groups, acting on affine space rather than linear space, are also considered. In order to get stability results one establishes that cer

  17. Measurement of recombination frequencies between two homologous DNA segments embedded in a YAC vector.

    Science.gov (United States)

    Yasui, H; Kurosawa, Y

    1993-07-15

    We measured the frequencies of recombination in a yeast host between two homologous segments of DNA that had been inserted with the same polarity in a yeast artificial chromosome (YAC) vector. Three kinds of YAC clones were constructed in which the gene encoding neomycin(Nm) resistance was sandwiched between two homologous segments of DNA, such as the IS3 elements of Escherichia coli or human Alu sequences. Frequencies of homologous recombination in yeast were measured in terms of loss of resistance to Nm. In the case of IS3 fragments, homologous recombination between them did occur at a relatively high frequency (5 x 10(-4). In contrast, recombination between two Alu sequences did not occur at a detectable level during a 30-day incubation. Thus, the frequency was less than 10(-5). These results indicate that the Alu sequences do not sufficiently promote the frequency of recombination between two homologous fragments in yeast as to induce rearrangements of DNA in a substantial fraction of YAC clones in libraries.

  18. Translated points and Rabinowitz Floer homology

    CERN Document Server

    Albers, Peter

    2011-01-01

    We prove that if a contact manifold admits an exact filling then every local contactomorphism isotopic to the identity admits a translated point in the interior of its support, in the sense of Sandon [San11b]. In addition we prove that if the Rabinowitz Floer homology of the filling is non-zero then every contactomorphism isotopic to the identity admits a translated point, and if the Rabinowitz Floer homology of the filling is infinite dimensional then every contactmorphism isotopic to the identity has either infinitely many translated points, or a translated point on a closed leaf. Moreover if the contact manifold has dimension greater than or equal to 3, the latter option generically doesn't happen. Finally, we prove that a generic contactomorphism on $\\mathbb{R}^{2n+1}$ has infinitely many geometrically distinct iterated translated points all of which lie in the interior of its support.

  19. 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...

  20. Relative K-homology and normal operators

    DEFF Research Database (Denmark)

    Manuilov, Vladimir; Thomsen, Klaus

    2009-01-01

    Let $A$ be a $C^*$-algebra, $J \\subset A$ a $C^*$-subalgebra, and let $B$ be a stable $C^*$-algebra. Under modest assumptions we organize invertible $C^*$-extensions of $A$ by $B$ that are trivial when restricted onto $J$ to become a group $\\mathrm{Ext}_J^{-1}(A,B)$, which can be computed by a six......-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....

  1. 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.

  2. Homology and phylogeny and their automated inference

    Science.gov (United States)

    Fuellen, Georg

    2008-06-01

    The analysis of the ever-increasing amount of biological and biomedical data can be pushed forward by comparing the data within and among species. For example, an integrative analysis of data from the genome sequencing projects for various species traces the evolution of the genomes and identifies conserved and innovative parts. Here, I review the foundations and advantages of this “historical” approach and evaluate recent attempts at automating such analyses. Biological data is comparable if a common origin exists (homology), as is the case for members of a gene family originating via duplication of an ancestral gene. If the family has relatives in other species, we can assume that the ancestral gene was present in the ancestral species from which all the other species evolved. In particular, describing the relationships among the duplicated biological sequences found in the various species is often possible by a phylogeny, which is more informative than homology statements. Detecting and elaborating on common origins may answer how certain biological sequences developed, and predict what sequences are in a particular species and what their function is. Such knowledge transfer from sequences in one species to the homologous sequences of the other is based on the principle of ‘my closest relative looks and behaves like I do’, often referred to as ‘guilt by association’. To enable knowledge transfer on a large scale, several automated ‘phylogenomics pipelines’ have been developed in recent years, and seven of these will be described and compared. Overall, the examples in this review demonstrate that homology and phylogeny analyses, done on a large (and automated) scale, can give insights into function in biology and biomedicine.

  3. Homological Methods in Equations of Mathematical Physics

    OpenAIRE

    Krasil'shchik, Joseph; Verbovetsky, Alexander

    1998-01-01

    These lecture notes are a systematic and self-contained exposition of the cohomological theories naturally related to partial differential equations: the Vinogradov C-spectral sequence and the C-cohomology, including the formulation in terms of the horizontal (characteristic) cohomology. Applications to computing invariants of differential equations are discussed. The lectures contain necessary introductory material on the geometric theory of differential equations and homological algebra.

  4. 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.

  5. Dental homologies in lamniform sharks (Chondrichthyes: Elasmobranchii).

    Science.gov (United States)

    Shimada, Kenshu

    2002-01-01

    The dentitions of lamniform sharks are said to exhibit a unique heterodonty called the "lamnoid tooth pattern." The presence of an inflated hollow "dental bulla" on each jaw cartilage allows the recognition of homologous teeth across most modern macrophagous lamniforms based on topographic correspondence through the "similarity test." In most macrophagous lamniforms, three tooth rows are supported by the upper dental bulla: two rows of large anterior teeth followed by a row of small intermediate teeth. The lower tooth row occluding between the two rows of upper anterior teeth is the first lower anterior tooth row. Like the first and second lower anterior tooth rows, the third lower tooth row is supported by the dental bulla and may be called the first lower intermediate tooth row. The lower intermediate tooth row occludes between the first and second upper lateral tooth rows situated distal to the upper dental bulla, and the rest of the upper and lower tooth rows, all called lateral tooth rows, occlude alternately. Tooth symmetry cannot be used to identify their dental homology. The presence of dental bullae can be regarded as a synapomorphy of Lamniformes and this character is more definable than the "lamnoid tooth pattern." The formation of the tooth pattern appears to be related to the evolution of dental bullae. This study constitutes the first demonstration of supraspecific tooth-to-tooth dental homologies in nonmammalian vertebrates.

  6. Note on homological modeling of the electric circuits

    OpenAIRE

    2014-01-01

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

  7. Deletion of a KU80 homolog enhances homologous recombination in the thermotolerant yeast Kluyveromyces marxianus.

    Science.gov (United States)

    Choo, Jin Ho; Han, Changpyo; Kim, Jae-Young; Kang, Hyun Ah

    2014-10-01

    Targeted gene replacement in the thermotolerant yeast Kluyveromyces marxianus KCTC 17555 has been hampered by its propensity to non-homologous end joining (NHEJ). To enhance homologous recombination (HR) by blocking NHEJ, we identified and disrupted the K. marxianus KU80 gene. The ku80 deletion mutant strain (Kmku80∆) of K. marxianus KCTC 17555 did not show apparent growth defects under several conditions with the exception of exposure to tunicamycin. The targeted disruption of the three model genes, KmLEU2, KmPDC1, and KmPDC5, was increased by 13-70 % in Kmku80∆, although the efficiency was greatly affected by the length of the homologous flanking fragments. In contrast, the double HR frequency was 0-13.7 % in the wild-type strain even with flanking fragments 1 kb long. Therefore, Kmku80∆ promises to be a useful recipient strain for targeted gene manipulation.

  8. PRIMO: An Interactive Homology Modeling Pipeline

    Science.gov (United States)

    Glenister, Michael

    2016-01-01

    The development of automated servers to predict the three-dimensional structure of proteins has seen much progress over the years. These servers make calculations simpler, but largely exclude users from the process. In this study, we present the PRotein Interactive MOdeling (PRIMO) pipeline for homology modeling of protein monomers. The pipeline eases the multi-step modeling process, and reduces the workload required by the user, while still allowing engagement from the user during every step. Default parameters are given for each step, which can either be modified or supplemented with additional external input. PRIMO has been designed for users of varying levels of experience with homology modeling. The pipeline incorporates a user-friendly interface that makes it easy to alter parameters used during modeling. During each stage of the modeling process, the site provides suggestions for novice users to improve the quality of their models. PRIMO provides functionality that allows users to also model ligands and ions in complex with their protein targets. Herein, we assess the accuracy of the fully automated capabilities of the server, including a comparative analysis of the available alignment programs, as well as of the refinement levels used during modeling. The tests presented here demonstrate the reliability of the PRIMO server when producing a large number of protein models. While PRIMO does focus on user involvement in the homology modeling process, the results indicate that in the presence of suitable templates, good quality models can be produced even without user intervention. This gives an idea of the base level accuracy of PRIMO, which users can improve upon by adjusting parameters in their modeling runs. The accuracy of PRIMO’s automated scripts is being continuously evaluated by the CAMEO (Continuous Automated Model EvaluatiOn) project. The PRIMO site is free for non-commercial use and can be accessed at https://primo.rubi.ru.ac.za/. PMID:27855192

  9. 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

  10. Identification of plant microRNA homologs.

    Science.gov (United States)

    Dezulian, Tobias; Remmert, Michael; Palatnik, Javier F; Weigel, Detlef; Huson, Daniel H

    2006-02-01

    MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that regulate gene and protein expression in plants and animals. MiRNAs have so far been identified mostly by specific cloning of small RNA molecules, complemented by computational methods. We present a computational identification approach that is able to identify candidate miRNA homologs in any set of sequences, given a query miRNA. The approach is based on a sequence similarity search step followed by a set of structural filters.

  11. Railway vehicle performance optimisation using virtual homologation

    Science.gov (United States)

    Magalhães, H.; Madeira, J. F. A.; Ambrósio, J.; Pombo, J.

    2016-09-01

    Unlike regular automotive vehicles, which are designed to travel in different types of roads, railway vehicles travel mostly in the same route during their life cycle. To accept the operation of a railway vehicle in a particular network, a homologation process is required according to local standard regulations. In Europe, the standards EN 14363 and UIC 518, which are used for railway vehicle acceptance, require on-track tests and/or numerical simulations. An important advantage of using virtual homologation is the reduction of the high costs associated with on-track tests by studying the railway vehicle performance in different operation conditions. This work proposes a methodology for the improvement of railway vehicle design with the objective of its operation in selected railway tracks by using optimisation. The analyses required for the vehicle improvement are performed under control of the optimisation method global and local optimisation using direct search. To quantify the performance of the vehicle, a new objective function is proposed, which includes: a Dynamic Performance Index, defined as a weighted sum of the indices obtained from the virtual homologation process; the non-compensated acceleration, which is related to the operational velocity; and a penalty associated with cases where the vehicle presents an unacceptable dynamic behaviour according to the standards. Thus, the optimisation process intends not only to improve the quality of the vehicle in terms of running safety and ride quality, but also to increase the vehicle availability via the reduction of the time for a journey while ensuring its operational acceptance under the standards. The design variables include the suspension characteristics and the operational velocity of the vehicle, which are allowed to vary in an acceptable range of variation. The results of the optimisation lead to a global minimum of the objective function in which the suspensions characteristics of the vehicle are

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

    Science.gov (United States)

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

    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.

  13. 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.

  14. 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.

  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. Histone deacetylase inhibitors selectively target homology dependent DNA repair defective cells and elevate non-homologous endjoining activity.

    Directory of Open Access Journals (Sweden)

    Stephanie Smith

    Full Text Available BACKGROUND: We have previously used the ATAD5-luciferase high-throughput screening assay to identify genotoxic compounds with potential chemotherapeutic capabilities. The successful identification of known genotoxic agents, including the histone deacetylase inhibitor (HDACi trichostatin A (TSA, confirmed the specificity of the screen since TSA has been widely studied for its ability to cause apoptosis in cancer cells. Because many cancers have acquired mutations in DNA damage checkpoints or repair pathways, we hypothesized that these cancers may be susceptible to treatments that target compensatory pathways. Here, we used a panel of isogenic chicken DT40 B lymphocyte mutant and human cell lines to investigate the ability of TSA to define selective pathways that promote HDACi toxicity. RESULTS: HDACi induced a DNA damage response and reduced viability in all repair deficient DT40 mutants although ATM-nulls were least affected. The most dramatic sensitivity was observed in mutants lacking the homology dependent repair (HDR factor BLM or the non-homologous end-joining (NHEJ and HDR factors, KU/RAD54, suggesting an involvement of either HDR or NHEJ in HDACi-induced cell death. To extend these findings, we measured the frequencies of HDR and NHEJ after HDACi treatment and monitored viability in human cell lines comparably deficient in HDR or NHEJ. Although no difference in HDR frequency was observed between HDACi treated and untreated cells, HDR-defective human cell lines were clearly more sensitive than wild type. Unexpectedly, cells treated with HDACis showed a significantly elevated NHEJ frequency. CONCLUSIONS: HDACi targeting drugs induced significant increases in NHEJ activity in human cell lines but did not alter HDR frequency. Moreover, HDR is required for cellular resistance to HDACi therapy; therefore, NHEJ does not appear to be a critical axis for HDACi resistance. Rather, HDACi compounds induced DNA damage, most likely double strand breaks

  17. Resonance for loop homology of spheres

    CERN Document Server

    Hingston, Nancy

    2011-01-01

    A Riemannian or Finsler metric on a compact manifold M gives rise to a length function on the free loop space \\Lambda M, whose critical points are the closed geodesics in the given metric. If X is a homology class on \\Lambda M, the minimax critical level cr(X) is a critical value. Let M be a sphere of dimension >2, and fix a metric g and a coefficient field G. We prove that the limit as deg(X) goes to infinity of cr(X)/deg(X) exists. We call this limit the "global mean frequency" of M. As a consequence we derive resonance statements for closed geodesics on spheres; in particular either all homology on \\Lambda M of sufficiently high degreee lies hanging on closed geodesics whose mean frequency (average index / length) equals the global mean frequency, or there is a sequence of infinitely many closed geodesics whose mean frequencies converge to the global mean frequency. The proof uses the Chas-Sullivan product and results of Goresky-Hingston [GH].

  18. Bacteriophage Nf DNA region controlling late transcription: structural and functional homology with bacteriophage phi 29.

    Science.gov (United States)

    Nuez, B; Salas, M

    1993-06-25

    The putative region for the control of late transcription of the Bacillus subtilis phage Nf has been identified by DNA sequence homology with the equivalent region of the evolutionary related phage phi 29. A similar arrangement of early and late promoters has been detected in the two phages, suggesting that viral transcription could be regulated in a similar way at late times of the infection. Transcription of late genes requires the presence of a viral early protein, gpF in phage Nf and p4 in phage phi 29, being the latter known to bind to a DNA region located upstream from the phage phi 29 late promoter. We have identified a DNA region located upstream from the putative late promoter of phage Nf that is probably involved in binding protein gpF. Furthermore, we show that the phage phi 29 protein p4 is able to bind to this region and activate transcription from the phage Nf putative late promoter. Sequence alignment has also revealed the existence of significant internal homology between the two early promoters contained in this region of each phage.

  19. The CORVET subunit Vps8 cooperates with the Rab5 homolog Vps21 to induce clustering of late endosomal compartments

    NARCIS (Netherlands)

    Markgraf, Daniel F; Ahnert, Franziska; Arlt, Henning; Mari, Muriel; Peplowska, Karolina; Epp, Nadine; Griffith, Janice; Reggiori, Fulvio; Ungermann, Christian

    2009-01-01

    Membrane tethering, the process of mediating the first contact between membranes destined for fusion, requires specialized multisubunit protein complexes and Rab GTPases. In the yeast endolysosomal system, the hexameric HOPS tethering complex cooperates with the Rab7 homolog Ypt7 to promote homotypi

  20. Should nucleotide sequence analyzing computer algorithms always extend homologies by extending homologies?

    Science.gov (United States)

    Burnett, L; Basten, A; Hensley, W J

    1986-01-10

    Most computer algorithms used for comparing or aligning nucleotide sequences rely on the premise that the best way to extend a homology between the two sequences is to select a match rather than a mismatch. We have tested this assumption and found that it is not always valid.

  1. A Single-Strand Annealing Protein Clamps DNA to Detect and Secure Homology.

    Directory of Open Access Journals (Sweden)

    Marcel Ander

    2015-08-01

    Full Text Available Repair of DNA breaks by single-strand annealing (SSA is a major mechanism for the maintenance of genomic integrity. SSA is promoted by proteins (single-strand-annealing proteins [SSAPs], such as eukaryotic RAD52 and λ phage Redβ. These proteins use a short single-stranded region to find sequence identity and initiate homologous recombination. However, it is unclear how SSAPs detect homology and catalyze annealing. Using single-molecule experiments, we provide evidence that homology is recognized by Redβ monomers that weakly hold single DNA strands together. Once annealing begins, dimerization of Redβ clamps the double-stranded region and nucleates nucleoprotein filament growth. In this manner, DNA clamping ensures and secures a successful detection for DNA sequence homology. The clamp is characterized by a structural change of Redβ and a remarkable stability against force up to 200 pN. Our findings not only present a detailed explanation for SSAP action but also identify the DNA clamp as a very stable, noncovalent, DNA-protein interaction.

  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. Homological mirror symmetry. New developments and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Kapustin, Anton [California Inst. of Tech., Pasadena, CA (United States); Kreuzer, Maximilian [Technische Univ., Vienna (Austria). Inst. fuer Theoretische Physik; Schlesinger, Karl-Georg (eds.) [Vienna Univ. (Austria). Inst. fuer Theoretische Physik

    2009-07-01

    Homological Mirror Symmetry, the study of dualities of certain quantum field theories in a mathematically rigorous form, has developed into a flourishing subject on its own over the past years. The present volume bridges a gap in the literature by providing a set of lectures and reviews that both introduce and representatively review the state-of-the art in the field from different perspectives. With contributions by K. Fukaya, M. Herbst, K. Hori, M. Huang, A. Kapustin, L. Katzarkov, A. Klemm, M. Kontsevich, D. Page, S. Quackenbush, E. Sharpe, P. Seidel, I. Smith and Y. Soibelman, this volume will be a reference on the topic for everyone starting to work or actively working on mathematical aspects of quantum field theory. (orig.)

  5. Role of discs large homolog 5

    Institute of Scientific and Technical Information of China (English)

    Frauke Friedrichs; Monika Stoll

    2006-01-01

    In 2004, an association of genetic variation in the discs large homolog 5 (DLG5) gene with inflammatory bowel disease (IBD) was described in two large European study samples[1]. The initial report of DLG5 as a novel IBD susceptibility gene sparked a multitude of studies investigating its effect on CD and IBD, respectively,leading to controversial findings and ongoing discussions concerning the validity of the initial association finding and its role in the aetiology of Crohn disease. This review aims to summarize the current state of knowledge and to place the reported findings in the context of current concepts of complex diseases. This includes aspects of statistical power, phenotype differences and genetic heterogeneity between different populations as well as gene-gene and gene-environment interactions.

  6. How homologous recombination maintains telomere integrity.

    Science.gov (United States)

    Tacconi, Eliana M C; Tarsounas, Madalena

    2015-06-01

    Telomeres protect the ends of linear chromosomes against loss of genetic information and inappropriate processing as damaged DNA and are therefore crucial to the maintenance of chromosome integrity. In addition to providing a pathway for genome-wide DNA repair, homologous recombination (HR) plays a key role in telomere replication and capping. Consistent with this, the genomic instability characteristic of HR-deficient cells and tumours is driven in part by telomere dysfunction. Here, we discuss the mechanisms by which HR modulates the response to intrinsic cellular challenges that arise during telomere replication, as well as its impact on the assembly of telomere protective structures. How normal and tumour cells differ in their ability to maintain telomeres is deeply relevant to the search for treatments that would selectively eliminate cells whose capacity for HR-mediated repair has been compromised.

  7. The Chromosomal Courtship Dance-homolog pairing in early meiosis.

    Science.gov (United States)

    Klutstein, Michael; Cooper, Julia Promisel

    2014-02-01

    The intermingling of genomes that characterizes sexual reproduction requires haploid gametes in which parental homologs have recombined. For this, homologs must pair during meiosis. In a crowded nucleus where sequence homology is obscured by the enormous scale and packaging of the genome, partner alignment is no small task. Here we review the early stages of this process. Chromosomes first establish an initial docking site, usually at telomeres or centromeres. The acquisition of chromosome-specific patterns of binding factors facilitates homolog recognition. Chromosomes are then tethered to the nuclear envelope (NE) and subjected to nuclear movements that 'shake off' inappropriate contacts while consolidating homolog associations. Thereafter, homolog connections are stabilized by building the synaptonemal complex or its equivalent and creating genetic crossovers. Recent perspectives on the roles of these stages will be discussed.

  8. 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

  9. Transcriptional regulation of fruit ripening by tomato FRUITFULL homologs and associated MADS box proteins.

    Science.gov (United States)

    Fujisawa, Masaki; Shima, Yoko; Nakagawa, Hiroyuki; Kitagawa, Mamiko; Kimbara, Junji; Nakano, Toshitsugu; Kasumi, Takafumi; Ito, Yasuhiro

    2014-01-01

    The tomato (Solanum lycopersicum) MADS box FRUITFULL homologs FUL1 and FUL2 act as key ripening regulators and interact with the master regulator MADS box protein RIPENING INHIBITOR (RIN). Here, we report the large-scale identification of direct targets of FUL1 and FUL2 by transcriptome analysis of FUL1/FUL2 suppressed fruits and chromatin immunoprecipitation coupled with microarray analysis (ChIP-chip) targeting tomato gene promoters. The ChIP-chip and transcriptome analysis identified FUL1/FUL2 target genes that contain at least one genomic region bound by FUL1 or FUL2 (regions that occur mainly in their promoters) and exhibit FUL1/FUL2-dependent expression during ripening. These analyses identified 860 direct FUL1 targets and 878 direct FUL2 targets; this set of genes includes both direct targets of RIN and nontargets of RIN. Functional classification of the FUL1/FUL2 targets revealed that these FUL homologs function in many biological processes via the regulation of ripening-related gene expression, both in cooperation with and independent of RIN. Our in vitro assay showed that the FUL homologs, RIN, and tomato AGAMOUS-LIKE1 form DNA binding complexes, suggesting that tetramer complexes of these MADS box proteins are mainly responsible for the regulation of ripening.

  10. Heteromorphic Sex Chromosomes: Navigating Meiosis without a Homologous Partner

    OpenAIRE

    Checchi, Paula M.; Engebrecht, JoAnne

    2011-01-01

    Accurate chromosome segregation during meiosis relies on homology between the maternal and paternal chromosomes. Yet by definition, sex chromosomes of the heterogametic sex lack a homologous partner. Recent studies in a number of systems have shed light on the unique meiotic behavior of heteromorphic sex chromosomes, and highlight both the commonalities and differences in divergent species. During meiotic prophase, the homology-dependent processes of pairing, synapsis, and recombination have ...

  11. RPA homologs and ssDNA processing during meiotic recombination

    OpenAIRE

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

    2015-01-01

    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 re...

  12. 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...... and their features, helping researchers who are investigating functional categories of promoters and their modes of regulation. Additional features of promoters that are being characterized include types of histone modifications, nucleosome positioning, RNA polymerase pausing and novel small RNAs. In this Review, we...... discuss recent findings relating to metazoan promoters and how these findings are leading to a revised picture of what a gene promoter is and how it works....

  13. [Homologous recombination among bacterial genomes: the measurement and identification].

    Science.gov (United States)

    Xianwei, Yang; Ruifu, Yang; Yujun, Cui

    2016-02-01

    Homologous recombination is one of important sources in shaping the bacterial population diversity, which disrupts the clonal relationship among different lineages through horizontal transferring of DNA-segments. As consequence of blurring the vertical inheritance signals, the homologous recombination raises difficulties in phylogenetic analysis and reconstruction of population structure. Here we discuss the impacts of homologous recombination in inferring phylogenetic relationship among bacterial isolates, and summarize the tools and models separately used in recombination measurement and identification. We also highlight the merits and drawbacks of various approaches, aiming to assist in the practical application for the analysis of homologous recombination in bacterial evolution research.

  14. 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.

  15. A chemical compound that stimulates the human homologous recombination protein RAD51.

    Science.gov (United States)

    Jayathilaka, Krishanthi; Sheridan, Sean D; Bold, Tyler D; Bochenska, Katarzyna; Logan, Hillary L; Weichselbaum, Ralph R; Bishop, Douglas K; Connell, Philip P

    2008-10-14

    RAD51 and other members of the RecA family of strand exchange proteins assemble on ssDNA to form presynaptic filaments, which carry out the central steps of homologous recombination. A microplate-based assay was developed for high-throughput measurement of hRAD51 filament formation on ssDNA. With this method, a 10,000 compound library was screened, leading to the identification of a small molecule (RS-1) that enhances hRAD51 binding in a wide range of biochemical conditions. Salt titration experiments showed that RS-1 can enhance filament stability. Ultrastructural analysis of filaments formed on ssDNA showed that RS-1 can increase both protein-DNA complex lengths and the pitch of helical filament turns. RS-1 stimulated hRAD51-mediated homologous strand assimilation (D-loop) activity by at least 5- to 11-fold, depending on the condition. This D-loop stimulation occurred even in the presence of Ca(2+) or adenylyl-imidodiphosphate, indicating that the mechanism of stimulation was distinct from that conferred by Ca(2+) and/or inhibition of ATPase. No D-loop activity was observed in the absence of a nucleotide triphosphate cofactor, indicating that the compound does not substitute for this requirement. These results indicate that RS-1 enhances the homologous recombination activity of hRAD51 by promoting the formation of active presynaptic filaments. Cell survival assays in normal neonatal human dermal fibroblasts demonstrated that RS-1 promotes a dose-dependent resistance to the cross-linking chemotherapeutic drug cisplatin. Given that RAD51-dependent recombination is a major determinant of cisplatin resistance, RS-1 seems to function in vivo to stimulate homologous recombination repair proficiency. RS-1 has many potential applications in both research and medical settings.

  16. Pleckstrin homology domains and the cytoskeleton.

    Science.gov (United States)

    Lemmon, Mark A; Ferguson, Kathryn M; Abrams, Charles S

    2002-02-20

    Pleckstrin homology (PH) domains are 100-120 amino acid protein modules best known for their ability to bind phosphoinositides. All possess an identical core beta-sandwich fold and display marked electrostatic sidedness. The binding site for phosphoinositides lies in the center of the positively charged face. In some cases this binding site is well defined, allowing highly specific and strong ligand binding. In several of these cases the PH domains specifically recognize 3-phosphorylated phosphoinositides, allowing them to drive membrane recruitment in response to phosphatidylinositol 3-kinase activation. Examples of these PH domain-containing proteins include certain Dbl family guanine nucleotide exchange factors, protein kinase B, PhdA, and pleckstrin-2. PH domain-mediated membrane recruitment of these proteins contributes to regulated actin assembly and cell polarization. Many other PH domain-containing cytoskeletal proteins, such as spectrin, have PH domains that bind weakly, and to all phosphoinositides. In these cases, the individual phosphoinositide interactions may not be sufficient for membrane association, but appear to require self-assembly of their host protein and/or cooperation with other anchoring motifs within the same molecule to drive membrane attachment.

  17. A cytohesin homolog in Dictyostelium amoebae.

    Directory of Open Access Journals (Sweden)

    Maria Christina Shina

    Full Text Available BACKGROUND: Dictyostelium, an amoeboid motile cell, harbors several paralogous Sec7 genes that encode members of three distinct subfamilies of the Sec7 superfamily of Guanine nucleotide exchange factors. Among them are proteins of the GBF/BIG family present in all eukaryotes. The third subfamily represented with three members in D. discoideum is the cytohesin family that has been thought to be metazoan specific. Cytohesins are characterized by a Sec7 PH tandem domain and have roles in cell adhesion and migration. PRINCIPAL FINDINGS: Dictyostelium SecG exhibits highest homologies to the cytohesins. It harbors at its amino terminus several ankyrin repeats that are followed by the Sec7 PH tandem domain. Mutants lacking SecG show reduced cell-substratum adhesion whereas cell-cell adhesion that is important for development is not affected. Accordingly, multicellular development proceeds normally in the mutant. During chemotaxis secG(- cells elongate and migrate in a directed fashion towards cAMP, however speed is moderately reduced. SIGNIFICANCE: The data indicate that SecG is a relevant factor for cell-substrate adhesion and reveal the basic function of a cytohesin in a lower eukaryote.

  18. Complete Cohomologies and Some Homological Invariants

    Institute of Scientific and Technical Information of China (English)

    Javad Asadollahi; Shokrollah Salarian

    2007-01-01

    There is a complete cohomology theory developed over a commutative noetherian ring in which injectives take the role of projectives in Vogel's construction of complete cohomology theory. We study the interaction between this complete cohomology, that is referred to as I-complete cohomology, and Vogel's one and give some sufficient conditions for their equivalence. Using I-complete functors, we assign a new homological invariant to any finitely generated module over an arbitrary commutative noetherian local ring,that would generalize Auslander's delta invariant. We generalize the results about the δ-invariant to arbitrary rings and give a sufficient condition for the vanishing of this new invariant. We also introduce an analogue of the notion of the index of a Gorenstein local ring, introduced by Auslander, for arbitrary local rings and study its behavior under flat extensions of local rings. Finally, we study the connection between the index and Loewy length of a local ring and generalize the main result of [11] to arbitrary rings.

  19. Precise genome editing by homologous recombination.

    Science.gov (United States)

    Hoshijima, K; Jurynec, M J; Grunwald, D J

    2016-01-01

    Simple and efficient methods are presented for creating precise modifications of the zebrafish genome. Edited alleles are generated by homologous recombination between the host genome and double-stranded DNA (dsDNA) donor molecules, stimulated by the induction of double-strand breaks at targeted loci in the host genome. Because several kilobase-long tracts of sequence can be exchanged, multiple genome modifications can be generated simultaneously at a single locus. Methods are described for creating: (1) alleles with simple sequence changes or in-frame additions, (2) knockin/knockout alleles that express a reporter protein from an endogenous locus, and (3) conditional alleles in which exons are flanked by recombinogenic loxP sites. Significantly, our approach to genome editing allows the incorporation of a linked reporter gene into the donor sequences so that successfully edited alleles can be identified by virtue of expression of the reporter. Factors affecting the efficiency of genome editing are discussed, including the finding that dsDNA products of I-SceI meganuclease enzyme digestion are particularly effective as donor molecules for gene-editing events. Reagents and procedures are described for accomplishing efficient genome editing in the zebrafish.

  20. Altering symplectic manifolds by homologous recombination

    CERN Document Server

    Abouzaid, Mohammed

    2010-01-01

    We use symplectic cohomology to study the non-uniqueness of symplectic structures on the smooth manifolds underlying affine varieties. Starting with a Lefschetz fibration on such a variety and a finite set of primes, the main new tool is a method, which we call homologous recombination, for constructing a Lefschetz fibration whose total space is smoothly equivalent to the original variety, but for which symplectic cohomology with coefficients in the given set of primes vanishes (there is also a simpler version that kills symplectic cohomology completely). Rather than relying on a geometric analysis of periodic orbits of a flow, the computation of symplectic cohomology depends on describing the Fukaya category associated to the new fibration. As a consequence we use a result of McLean to prove, for example, that an affine variety of real dimension greater than or equal to 4 supports infinitely many different (Wein)stein structures of finite type, and, assuming a mild cohomological condition, uncountably many d...

  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. Molecular Phylogenetics and the Perennial Problem of Homology.

    Science.gov (United States)

    Inkpen, S Andrew; Doolittle, W Ford

    2016-12-01

    The concept of homology has a long history, during much of which the issue has been how to reconcile similarity and common descent when these are not coextensive. Although thinking molecular phylogeneticists have learned not to say "percent homology," the problems are deeper than that and unresolved.

  3. 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...

  4. 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 contribute to regulating mitotic homologous recombination at telomeres and the role of these mechanisms in signalling short telomeres in the budding yeast Saccharomyces cerevisiae....

  5. [DNA homology in various strains of nitrogen-fixing bacteria].

    Science.gov (United States)

    Vardevanian, P O; Minasbekian, L A; Parsadanian, M A

    2000-01-01

    Melting temperature and GC content were evaluated for DNA of some nitrogen-fixing bacteria of Rhizobium leguminosarum and Onobrychis spp. (Adans). The degree of homology between strains of the same species was determined. A combination of thermal denaturing and molecular hybridization can serve as a rapid test for evaluating the genome homology of the organisms compared.

  6. DNA strand exchange and RecA homologs in meiosis.

    Science.gov (United States)

    Brown, M Scott; Bishop, Douglas K

    2014-12-04

    Homology search and DNA strand-exchange reactions are central to homologous recombination in meiosis. During meiosis, these processes are regulated such that the probability of choosing a homolog chromatid as recombination partner is enhanced relative to that of choosing a sister chromatid. This regulatory process occurs as homologous chromosomes pair in preparation for assembly of the synaptonemal complex. Two strand-exchange proteins, Rad51 and Dmc1, cooperate in regulated homology search and strand exchange in most organisms. Here, we summarize studies on the properties of these two proteins and their accessory factors. In addition, we review current models for the assembly of meiotic strand-exchange complexes and the possible mechanisms through which the interhomolog bias of recombination partner choice is achieved.

  7. Remarks on Khovanov Homology and the Potts Model

    CERN Document Server

    Kauffman, Louis H

    2009-01-01

    This paper is about Khovanov homology and its relationships with statistical mechanics models such as the Ising model and the Potts model. The paper gives a relatively self-contained introduction to Khovanov homology, and also to a reformulation of the Potts model in terms of a bracket state sum expansion on a knot diagram K(G) related to a planar graph G via the medial construction. We consider the original Khovanov homology and also the homology defined by Stosic via the dichromatic polynomial, and examine those values of the Potts model where the partition function can be expressed in terms of homological Euler characteristics. These points occur at imaginary temperature, and consequences of this phenomenon will be studied in subsequent work. This paper is dedicated to Oleg Viro on his 60-th birthday.

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

    DEFF Research Database (Denmark)

    Scheel, Troels K H; Galli, Andrea; Li, Yi-Ping

    2013-01-01

    . 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...

  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. Relative rates of homologous and nonhomologous recombination in transfected DNA.

    Science.gov (United States)

    Roth, D B; Wilson, J H

    1985-05-01

    Both homologous and nonhomologous recombination events occur at high efficiency in DNA molecules transfected into mammalian cells. Both types of recombination occur with similar overall efficiencies, as measured by an endpoint assay, but their relative rates are unknown. In this communication, we measure the relative rates of homologous and nonhomologous recombination in DNA transfected into monkey cells. This measurement is made by using a linear simian virus 40 genome that contains a 131-base-pair duplication at its termini. Once inside the cell, this molecule must circularize to initiate lytic infection. Circularization can occur either by direct, nonhomologous end-joining or by homologous recombination within the duplicated region. Although the products of the two recombination pathways are different, they are equally infectious. Since homologous and nonhomologous recombination processes are competing for the same substrate, the relative amounts of the products of each pathway should reflect the relative rates of homologous and nonhomologous recombination. Analysis of individual recombinant genomes from 164 plaques indicates that the rate of circularization by nonhomologous recombination is 2- to 3-fold higher than the rate of homologous recombination. The assay system described here may prove to be useful for testing procedures designed to influence the relative rates of homologous and nonhomologous recombination.

  11. Homologous recombination in bovine pestiviruses. Phylogenetic and statistic evidence.

    Science.gov (United States)

    Jones, Leandro Roberto; Weber, E Laura

    2004-12-01

    Bovine pestiviruses (Bovine Viral Diarrea Virus 1 (BVDV 1) and Bovine Viral Diarrea Virus 2 (BVDV 2)) belong to the genus Pestivirus (Flaviviridae), which is composed of positive stranded RNA viruses causing significant economic losses world-wide. We used phylogenetic and bootstrap analyses to systematically scan alignments of previously sequenced genomes in order to explore further the evolutionary mechanisms responsible for variation in the virus. Previously published data suggested that homologous crossover might be one of the mechanisms responsible for the genomic rearrangements observed in cytopathic (cp) strains of bovine pestiviruses. Nevertheless, homologous recombination involves not just homologous crossovers, but also replacement of a homologous region of the acceptor RNA. Furthermore, cytopathic strains represent dead paths in evolution, since they are isolated exclusively from the fatal cases of mucosal disease. Herein, we report evidence of homologous inter-genotype recombination in the genome of a non-cytopathic (ncp) strain of Bovine Viral Diarrea Virus 1, the type species of the genus Pestivirus. We also show that intra-genotype homologous recombination might be a common phenomenon in both species of Pestivirus. This evidence demonstrates that homologous recombination contribute to the diversification of bovine pestiviruses in nature. Implications for virus evolution, taxonomy and phylogenetics are discussed.

  12. 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.

  13. Cyclic structures in algebraic (co)homology theories

    CERN Document Server

    Kowalzig, Niels

    2010-01-01

    This note discusses the cyclic cohomology of a left Hopf algebroid ($\\times_A$-Hopf algebra) with coefficients in a right module-left comodule, defined using a straightforward generalisation of the original operators given by Connes and Moscovici for Hopf algebras. Lie-Rinehart homology is a special case of this theory. A generalisation of cyclic duality that makes sense for arbitrary para-cyclic objects yields a dual homology theory. The twisted cyclic homology of an associative algebra provides an example of this dual theory that uses coefficients that are not necessarily stable anti Yetter-Drinfel'd modules.

  14. Importing the homology concept from biology into developmental psychology.

    Science.gov (United States)

    Moore, David S

    2013-01-01

    To help introduce the idea of homology into developmental psychology, this article presents some of the concepts, distinctions, and guidelines biologists and philosophers of biology have devised to study homology. Some unresolved issues related to this idea are considered as well. Because homology reflects continuity across time, developmental scientists should find this concept to be useful in the study of psychological/behavioral development, just as biologists have found it essential in the study of the evolution and development of morphological and other characteristics.

  15. 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...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Saccharomyces cerevisiae Rad52 protein promotes homologous recombination by nucleating the Rad51 recombinase onto replication protein A-coated single-stranded DNA strands and also by directly annealing such strands. We show that the purified rad52-R70A mutant protein, with a compromised amino...... conversion intermediates reveals that rad52-R70A cells can mediate DNA strand invasion but are unable to complete the recombination event. These results provide evidence that DNA binding by the evolutionarily conserved amino terminus of Rad52 is needed for the capture of the second DNA end during homologous......-terminal DNA binding domain, is capable of Rad51 delivery to DNA but is deficient in DNA annealing. Results from chromatin immunoprecipitation experiments find that rad52-R70A associates with DNA double-strand breaks and promotes recruitment of Rad51 as efficiently as wild-type Rad52. Analysis of gene...

  17. Meiotic crossover control by concerted action of Rad51-Dmc1 in homolog template bias and robust homeostatic regulation.

    Directory of Open Access Journals (Sweden)

    Jessica P Lao

    Full Text Available During meiosis, repair of programmed DNA double-strand breaks (DSBs by recombination promotes pairing of homologous chromosomes and their connection by crossovers. Two DNA strand-exchange proteins, Rad51 and Dmc1, are required for meiotic recombination in many organisms. Studies in budding yeast imply that Rad51 acts to regulate Dmc1's strand exchange activity, while its own exchange activity is inhibited. However, in a dmc1 mutant, elimination of inhibitory factor, Hed1, activates Rad51's strand exchange activity and results in high levels of recombination without participation of Dmc1. Here we show that Rad51-mediated meiotic recombination is not subject to regulatory processes associated with high-fidelity chromosome segregation. These include homolog bias, a process that directs strand exchange between homologs rather than sister chromatids. Furthermore, activation of Rad51 does not effectively substitute for Dmc1's chromosome pairing activity, nor does it ensure formation of the obligate crossovers required for accurate homolog segregation. We further show that Dmc1's dominance in promoting strand exchange between homologs involves repression of Rad51's strand-exchange activity. This function of Dmc1 is independent of Hed1, but requires the meiotic kinase, Mek1. Hed1 makes a relatively minor contribution to homolog bias, but nonetheless this is important for normal morphogenesis of synaptonemal complexes and efficient crossing-over especially when DSB numbers are decreased. Super-resolution microscopy shows that Dmc1 also acts to organize discrete complexes of a Mek1 partner protein, Red1, into clusters along lateral elements of synaptonemal complexes; this activity may also contribute to homolog bias. Finally, we show that when interhomolog bias is defective, recombination is buffered by two feedback processes, one that increases the fraction of events that yields crossovers, and a second that we propose involves additional DSB formation

  18. 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

  19. Regulation of Rad51 promoter

    Science.gov (United States)

    Hine, Christopher M; Li, Hongjie; Xie, Li; Mao, Zhiyong; Seluanov, Andrei; Gorbunova, Vera

    2014-01-01

    The DNA double-strand break repair and homologous recombination protein Rad51 is overexpressed in the majority of human cancers. This correlates with therapy resistance and decreased patient survival. We previously showed that constructs containing Rad51 promoter fused to a reporter gene are, on average, 850-fold more active in cancer cells than in normal cells. It is not well understood what factors and sequences regulate the Rad51 promoter and cause its high activity in cancerous cells. Here we characterized regulatory regions and examined genetic requirements for oncogenic stimulation of the Rad51 promoter. We identified specific regions responsible for up- and downregulation of the Rad51 promoter in cancerous cells. Furthermore, we show that Rad51 expression is positively regulated by EGR1 transcription factor. We then modeled the malignant transformation process by expressing a set of oncoproteins in normal human fibroblasts. Expression of different combinations of SV40 large T antigen, oncogenic Ras and SV40 small T antigen resulted in step-wise increase in Rad51 promoter activity, with all the 3 oncoproteins together leading to a 47-fold increase in expression. Cumulatively, these results suggest that Rad51 promoter is regulated by multiple factors, and that its expression is gradually activated as cells progress toward malignancy. PMID:24781030

  20. Seiberg-Witten-Floer Homology and Gluing Formulae

    Institute of Scientific and Technical Information of China (English)

    Alan L. CAREY; Bai Ling WANG

    2003-01-01

    This paper gives a detailed construction of Seiberg-Witten-Floer homology for a closed oriented 3-manifold with a non-torsion Spinc structure. Gluing formulae for certain 4-dimensional manifolds splitting along an embedded 3-manifold are obtained.

  1. Recombination, Pairing, and Synapsis of Homologs during Meiosis.

    Science.gov (United States)

    Zickler, Denise; Kleckner, Nancy

    2015-05-18

    Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships.

  2. Homological Dimensions of the Extension Algebras of Monomial Algebras

    Institute of Scientific and Technical Information of China (English)

    Hong Bo SHI

    2015-01-01

    The main objective of this paper is to study the dimension trees and further the homo-logical dimensions of the extension algebras — dual and trivially twisted extensions — with a unified combinatorial approach using the two combinatorial algorithms — Topdown and Bottomup. We first present a more complete and clearer picture of a dimension tree, with which we are then able, on the one hand, to sharpen some results obtained before and furthermore reveal a few more hidden sub-tle homological phenomenons of or connections between the involved algebras; on the other hand, to provide two more effi cient combinatorial algorithms for computing dimension trees, and consequently the homological dimensions as an application. We believe that the more refined complete structural information on dimension trees will be useful to study other homological properties of this class of extension algebras.

  3. Spectral Invariants in Rabinowitz Floer homology and Global Hamiltonian perturbations

    CERN Document Server

    Albers, Peter

    2010-01-01

    Spectral invariant were introduced in Hamiltonian Floer homology by Viterbo, Oh, and Schwarz. We extend this concept to Rabinowitz Floer homology. As an application we derive new quantitative existence results for leaf-wise intersections. The importance of spectral invariants for the presented application is that spectral invariants allow us to derive existence of critical points of the Rabinowitz action functional even in degenerate situations where the functional is not Morse.

  4. Relative rates of homologous and nonhomologous recombination in transfected DNA.

    OpenAIRE

    Roth, D B; Wilson, J H

    1985-01-01

    Both homologous and nonhomologous recombination events occur at high efficiency in DNA molecules transfected into mammalian cells. Both types of recombination occur with similar overall efficiencies, as measured by an endpoint assay, but their relative rates are unknown. In this communication, we measure the relative rates of homologous and nonhomologous recombination in DNA transfected into monkey cells. This measurement is made by using a linear simian virus 40 genome that contains a 131-ba...

  5. Pairs of periodic orbits with fixed homology difference

    DEFF Research Database (Denmark)

    Risager, Morten S.; Sharp, Richard

    2010-01-01

    We obtain an asymptotic formula for the number of pairs of closed orbits of a  weak-mixing transitive Anosov ¿ow whose homology classes have a ¿xed di¿erence.......We obtain an asymptotic formula for the number of pairs of closed orbits of a  weak-mixing transitive Anosov ¿ow whose homology classes have a ¿xed di¿erence....

  6. Continuation homomorphism in Rabinowitz Floer homology for symplectic deformations

    CERN Document Server

    Bae, Youngjin

    2010-01-01

    Will Merry computed Rabinowitz Floer homology above Mane's critical value in terms of loop space homology by establishing an Abbondandolo-Schwarz short exact sequence. The purpose of this article is to provide an alternative proof of Merry's result. We construct a continuation homomorphism for symplectic deformations which enables us to reduce the computation to the untwisted case. Our construction takes advantage of a special version of the isoperimetric inequality which above Mane's critical value holds true.

  7. Rational equivariant K-homology of low dimensional groups

    CERN Document Server

    Lafont, Jean-François; Sánchez-García, Rubén J

    2011-01-01

    We consider groups G which have a cocompact, 3-manifold model for the classifying space \\underline{E}G. We provide an algorithm for computing the rationalized equivariant K-homology of \\underline{E}G. Under the additional hypothesis that the quotient 3-orbifold \\underline{E}G/G is geometrizable, the rationalized K-homology groups coincide with the rationalized K-theory of the reduced C*-algebra of G. We illustrate our algorithm on some concrete examples.

  8. Metagenomic gene annotation by a homology-independent approach

    Energy Technology Data Exchange (ETDEWEB)

    Froula, Jeff; Zhang, Tao; Salmeen, Annette; Hess, Matthias; Kerfeld, Cheryl A.; Wang, Zhong; Du, Changbin

    2011-06-02

    Fully understanding the genetic potential of a microbial community requires functional annotation of all the genes it encodes. The recently developed deep metagenome sequencing approach has enabled rapid identification of millions of genes from a complex microbial community without cultivation. Current homology-based gene annotation fails to detect distantly-related or structural homologs. Furthermore, homology searches with millions of genes are very computational intensive. To overcome these limitations, we developed rhModeller, a homology-independent software pipeline to efficiently annotate genes from metagenomic sequencing projects. Using cellulases and carbonic anhydrases as two independent test cases, we demonstrated that rhModeller is much faster than HMMER but with comparable accuracy, at 94.5percent and 99.9percent accuracy, respectively. More importantly, rhModeller has the ability to detect novel proteins that do not share significant homology to any known protein families. As {approx}50percent of the 2 million genes derived from the cow rumen metagenome failed to be annotated based on sequence homology, we tested whether rhModeller could be used to annotate these genes. Preliminary results suggest that rhModeller is robust in the presence of missense and frameshift mutations, two common errors in metagenomic genes. Applying the pipeline to the cow rumen genes identified 4,990 novel cellulases candidates and 8,196 novel carbonic anhydrase candidates.In summary, we expect rhModeller to dramatically increase the speed and quality of metagnomic gene annotation.

  9. Mutation of the BRCA1 SQ-cluster results in aberrant mitosis, reduced homologous recombination, and a compensatory increase in non-homologous end joining.

    Science.gov (United States)

    Beckta, Jason M; Dever, Seth M; Gnawali, Nisha; Khalil, Ashraf; Sule, Amrita; Golding, Sarah E; Rosenberg, Elizabeth; Narayanan, Aarthi; Kehn-Hall, Kylene; Xu, Bo; Povirk, Lawrence F; Valerie, Kristoffer

    2015-09-29

    Mutations in the breast cancer susceptibility 1 (BRCA1) gene are catalysts for breast and ovarian cancers. Most mutations are associated with the BRCA1 N- and C-terminal domains linked to DNA double-strand break (DSB) repair. However, little is known about the role of the intervening serine-glutamine (SQ) - cluster in the DNA damage response beyond its importance in regulating cell cycle checkpoints. We show that serine-to-alanine alterations at critical residues within the SQ-cluster known to be phosphorylated by ATM and ATR result in reduced homologous recombination repair (HRR) and aberrant mitosis. While a S1387A BRCA1 mutant - previously shown to abrogate S-phase arrest in response to radiation - resulted in only a modest decrease in HRR, S1387A together with an additional alteration, S1423A (BRCA12P), reduced HRR to vector control levels and similar to a quadruple mutant also including S1457A and S1524A (BRCA14P). These effects appeared to be independent of PALB2. Furthermore, we found that BRCA14P promoted a prolonged and struggling HRR late in the cell cycle and shifted DSB repair from HRR to non-homologous end joining which, in the face of irreparable chromosomal damage, resulted in mitotic catastrophe. Altogether, SQ-cluster phosphorylation is critical for allowing adequate time for completing normal HRR prior to mitosis and preventing cells from entering G1 prematurely resulting in gross chromosomal aberrations.

  10. 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.

  11. Characterization of three loci for homologous gene targeting and transgene expression.

    Science.gov (United States)

    Eyquem, Justin; Poirot, Laurent; Galetto, Roman; Scharenberg, Andrew M; Smith, Julianne

    2013-08-01

    Integrative gene transfer is widely used for bioproduction, drug screening, and therapeutic applications but usual viral methods lead to random and multicopy insertions, contribute to unstable transgene expression and can disturb endogenous gene expression. Homologous targeting of an expression cassette using rare-cutting endonucleases is a potential solution; however the number of studied loci remains limited. Furthermore, the behavior and performance of various types of gene cassettes following gene targeting is poorly defined. Here we have evaluated three loci for gene targeting, including one locus compatible with the proposed Safe Harbor criteria for human translational applications. Using optimized conditions for homologous gene targeting, reporter genes under the control of different promoters were efficiently inserted at each locus in both sense and antisense orientations. Sustainable expression was achieved at all three loci without detectable disturbance of flanking gene expression. However, the promoter, the integration locus and the cassette orientation have a strong impact on transgene expression. Finally, single targeted integrations exhibited greatly improved transgene expression stability versus multicopy or random integration. Taken together, our data suggest a potential set of loci for site-specific transgene integration, suitable for a variety of biotechnological applications.

  12. Epididymis-specific lipocalin promoters

    Institute of Scientific and Technical Information of China (English)

    Kichiya Suzuki; Xiuping Yu; Pierre Chaurand; Yoshihiko Araki; Jean-Jacques Lareyre; Richard M. Caprioli; Marie-Claire Orgebin-Crist; Robert J. Matusik

    2007-01-01

    Our goal is to decipher which DNA sequences are required for tissue-specific expression of epididymal genes. At least 6 epididymis-specific lipocalin genes are known. These are differently regulated and regionalized in the epididymis.Lipocalin 5 (Lcn5 or mE-RABP) and Lipocalin 8 (Lcn8 or mEP17) are homologous genes belonging to the epididymis-specific lipocalin gene cluster. Both the 5 kb promoter fragment of the Lcn5 gene and the 5.3 kb promoter fragment of the Lcn8 gene can direct transgene expression in the epididymis (Lcn5 to the distal caput and Lcn8 to the initial segment), indicating that these promoter fragments contain important cis-regulatory element(s) for epididymisspecific gene expression. To define further the fragments regulating gene expression, the Lcn5 promoter was examined in transgenic mice and immortalized epididymal cell lines. After serial deletion, the 1.8 kb promoter fragment of the Lcn5 gene was sufficient for tissue-specific and region-specific gene expression in transgenic mice. Transient transfection analysis revealed that a transcription factor forkhead box A2 (Foxa2) interacts with androgen receptor and binds to the 100 bp fragment of the Lcn5 promoter between 1.2 kb and 1.3 kb and that Foxa2 expression inhibitsandrogen-dependent induction of the Lcn5 promoter activity. Immunohistochemistry indicated a restricted expression of Foxa2 in the epididymis where endogenous Lcn5 gene expression is suppressed and that the Foxa2 inhibition of the Lcn5 promoter is consistent with the lack of expression of Lcn5 in the corpus and cauda. Our approach provides a basic strategy for further analysis of the epididymal lipocalin gene regulation and flexible control of epididymal function.

  13. 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

  14. 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

  15. Primary homologies of the circumorbital bones of snakes.

    Science.gov (United States)

    Palci, Alessandro; Caldwell, Michael W

    2013-09-01

    Some snakes have two circumorbital ossifications that in the current literature are usually referred to as the postorbital and supraorbital. We review the arguments that have been proposed to justify this interpretation and provide counter-arguments that reject those conjectures of primary homology based on the observation of 32 species of lizards and 81 species of snakes (both extant and fossil). We present similarity arguments, both topological and structural, for reinterpretation of the primary homologies of the dorsal and posterior orbital ossifications of snakes. Applying the test of similarity, we conclude that the posterior orbital ossification of snakes is topologically consistent as the homolog of the lacertilian jugal, and that the dorsal orbital ossification present in some snakes (e.g., pythons, Loxocemus, and Calabaria) is the homolog of the lacertilian postfrontal. We therefore propose that the terms postorbital and supraorbital should be abandoned as reference language for the circumorbital bones of snakes, and be replaced with the terms jugal and postfrontal, respectively. The primary homology claim for the snake "postorbital" fails the test of similarity, while the term "supraorbital" is an unnecessary and inaccurate application of the concept of a neomorphic ossification, for an element that passes the test of similarity as a postfrontal. This reinterpretation of the circumorbital bones of snakes is bound to have important repercussions for future phylogenetic analyses and consequently for our understanding of the origin and evolution of snakes.

  16. PDBalert: automatic, recurrent remote homology tracking and protein structure prediction

    Directory of Open Access Journals (Sweden)

    Söding Johannes

    2008-11-01

    Full Text Available Abstract Background During the last years, methods for remote homology detection have grown more and more sensitive and reliable. Automatic structure prediction servers relying on these methods can generate useful 3D models even below 20% sequence identity between the protein of interest and the known structure (template. When no homologs can be found in the protein structure database (PDB, the user would need to rerun the same search at regular intervals in order to make timely use of a template once it becomes available. Results PDBalert is a web-based automatic system that sends an email alert as soon as a structure with homology to a protein in the user's watch list is released to the PDB database or appears among the sequences on hold. The mail contains links to the search results and to an automatically generated 3D homology model. The sequence search is performed with the same software as used by the very sensitive and reliable remote homology detection server HHpred, which is based on pairwise comparison of Hidden Markov models. Conclusion PDBalert will accelerate the information flow from the PDB database to all those who can profit from the newly released protein structures for predicting the 3D structure or function of their proteins of interest.

  17. 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.

  18. Heteromorphic sex chromosomes: navigating meiosis without a homologous partner.

    Science.gov (United States)

    Checchi, Paula M; Engebrecht, Joanne

    2011-09-01

    Accurate chromosome segregation during meiosis relies on homology between the maternal and paternal chromosomes. Yet by definition, sex chromosomes of the heterogametic sex lack a homologous partner. Recent studies in a number of systems have shed light on the unique meiotic behavior of heteromorphic sex chromosomes, and highlight both the commonalities and differences in divergent species. During meiotic prophase, the homology-dependent processes of pairing, synapsis, and recombination have been modified in many different ways to ensure segregation of heteromorphic sex chromosomes at the first meiotic division. Additionally, an almost universal feature of heteromorphic sex chromosomes during meiosis is transcriptional silencing, or meiotic sex chromosome inactivation, an essential process proposed to prevent expression of genes deleterious to meiosis in the heterogametic sex as well as to shield unpaired sex chromosomes from recognition by meiotic checkpoints. Comparative analyses of the meiotic behavior of sex chromosomes in nematodes, mammals, and birds reveal important conserved features as well as provide insight into sex chromosome evolution.

  19. Nasal pungency, odor, and eye irritation thresholds for homologous acetates.

    Science.gov (United States)

    Cometto-Muñiz, J E; Cain, W S

    1991-08-01

    We measured detection thresholds for nasal pungency (in anosmics), odor (in normosmics) and eye irritation employing a homologous series of acetates: methyl through octyl acetate, decyl and dodecyl acetate. All anosmics reliably detected the series up to heptyl acetate. Only the anosmics without smell since birth (congenital) reliably detected octyl acetate, and only one congenital anosmic detected decyl and dodecyl acetate. Anosmics who lost smell from head trauma proved to be selectively less sensitive. As expected, odor thresholds lay well below pungency thresholds. Eye irritation thresholds for selected acetates came close to nasal pungency thresholds. All three types of thresholds decreased logarithmically with carbon chain length, as previously seen with homologous alcohols and as seen in narcotic and toxic phenomena. Results imply that nasal pungency for these stimuli rests upon a physical, rather than chemical, interaction with susceptible mucosal structures. When expressed as thermodynamic activity, nasal pungency thresholds remain remarkably constant within and across the homologous series of acetates and alcohols.

  20. Differential forms on singular varieties and cyclic homology

    CERN Document Server

    Brasselet, J P; Brasselet, Jean-Paul; Legrand, André

    1996-01-01

    A classical result of A. Connes asserts that the Frechet algebra of smooth functions on a smooth compact manifold X provides, by a purely algebraic procedure, the de Rham cohomology of X. Namely the procedure uses Hochschild and cyclic homology of this algebra. In the situation of a Thom-Mather stratified variety, we construct a Frechet algebra of functions on the regular part and a module of poles along the singular part. We associate to these objects a complex of differential forms and an Hochschild complex, on the regular part, both with poles along the singular part. The de Rham cohomology of the first complex and the cylic homology of the second one are related to the intersection homology of the variety, the corresponding perversity is determined by the orders of poles.

  1. 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.

  2. Bacterial actin and tubulin homologs in cell growth and division.

    Science.gov (United States)

    Busiek, Kimberly K; Margolin, William

    2015-03-16

    In contrast to the elaborate cytoskeletal machines harbored by eukaryotic cells, such as mitotic spindles, cytoskeletal structures detectable by typical negative stain electron microscopy are generally absent from bacterial cells. As a result, for decades it was thought that bacteria lacked cytoskeletal machines. Revolutions in genomics and fluorescence microscopy have confirmed the existence not only of smaller-scale cytoskeletal structures in bacteria, but also of widespread functional homologs of eukaryotic cytoskeletal proteins. The presence of actin, tubulin, and intermediate filament homologs in these relatively simple cells suggests that primitive cytoskeletons first arose in bacteria. In bacteria such as Escherichia coli, homologs of tubulin and actin directly interact with each other and are crucial for coordinating cell growth and division. The function and direct interactions between these proteins will be the focus of this review.

  3. 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....

  4. 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.

  5. Ganea Term for Homology of Leibniz n-Algebras

    Institute of Scientific and Technical Information of China (English)

    J.M. Casas

    2005-01-01

    We extend the five-term exact sequence of homology with trivial coefficients of Leibniz n-algebras nH L1 ( K ) → nH L1 (L) → M → nH L0( K ) → nH L0( L ) → 0 associated to a central extension of Leibniz n-algebras 0 → M →K → L → 0 by means of a sixth term which is a generalization of the Ganea term for homology of Leibniz algebras. We use this sequence in order to analyze several questions related with the centre and central extensions of a Leibniz n-algebra.

  6. 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.

  7. Characterization and expression pattern of the novel MIA homolog TANGO.

    Science.gov (United States)

    Bosserhoff, A K; Moser, M; Buettner, R

    2004-07-01

    A novel human gene, TANGO, encoding a MIA ('melanoma inhibitory activity') homologous protein was identified by a gene bank search. TANGO, together with the homologous genes MIA, OTOR (FPD, MIAL) and MIA2 define a novel gene family sharing important structural features, significant homology at both the nucleotide and protein level, and similar genomic organization. The four members share 34-45% amino acid identity and 47-59% cDNA sequence identity. TANGO encodes a mature protein of 103 amino acids in addition to a hydrophobic secretory signal sequence. Sequence homology confirms the highly conserved SH3 structure present also in MIA, OTOR and MIA2. Thus, it appears that there are a number of extracellular proteins with SH3-fold like structures. Interestingly, in situ hybridization, RT-PCR and Northern Blots revealed very broad TANGO expression patterns in contrast to the highly restricted expression patterns previously determined for the other members of the MIA gene family. The only cells lacking TANGO expression are cells belonging to the hematopoetic system. High levels of TANGO expression were observed both during embryogenesis and in adult tissues.

  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. 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.

  10. O-minimal homotopy and generalized (co)homology

    CERN Document Server

    Piȩkosz, Artur

    2008-01-01

    This article gives a version of the homotopy theory (giving also generalized homology and cohomology theories), developed by H. Delfs and M. Knebusch in the semialgebraic case, extended to regular paracompact locally definable spaces and weakly definable spaces over a model R of an o-minimal theory T extending RCF, with some restrictions on T.

  11. Action of the cork twist on Floer homology

    CERN Document Server

    Akbulut, Selman

    2011-01-01

    We utilize the Ozsvath-Szabo contact invariant to detect the action of involutions on certain homology spheres that are surgeries on symmetric links, generalizing a previous result of Akbulut and Durusoy. Potentially this may be useful to detect different smooth structures on 4-manifolds by cork twisting operation.

  12. 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...

  13. Disruption of an ADE6 Homolog of Ustilago maydis

    Science.gov (United States)

    Ustilago maydis secretes iron-binding compounds during times of iron depletion. A putative homolog of the Sacharromyces cereviseae ADE6 and Escherichia coli purL genes was identified near a multigenic complex, which contains two genes sid1 and sid2 involved in a siderophore biosynthetic pathway. The...

  14. Homology and K-theory of the Bianchi groups

    CERN Document Server

    Rahm, Alexander D

    2011-01-01

    We reveal a correspondence between the homological torsion of the Bianchi groups and new geometric invariants, which are effectively computable thanks to their action on hyperbolic space. We use it to explicitly compute their integral group homology and equivariant K-homology. By the Baum/Connes conjecture, which holds for the Bianchi groups, we obtain the K-theory of their reduced C\\ast -algebras in terms of isomorphic images of the computed K-homology. We further find an application to Chen/Ruan orbifold cohomology. Nous mettons en \\'evidence une correspondance entre la torsion homologique des groupes de Bianchi et de nouveaux invariants g\\'eom\\'etriques, calculables gr\\^ace \\'a leur action sur l'espace hyperbolique. Nous l'utilisons pour calculer explicitement leur homologie de groupe \\'a coefficients entiers et leur K-homologie \\'equivariante. En cons\\'equence de la conjecture de Baum/Connes, qui est v\\'erifi\\'ee pour ces groupes, nous obtenons la K-th\\'eorie de leurs C\\ast-alg\\'ebres r\\'eduites en termes...

  15. Homology of classical groups and K-theory

    NARCIS (Netherlands)

    Mirzaii, B.

    2004-01-01

    The study of the homology groups of classical group over a ring R with coefficient A, where A is a commutative ring with trivial group action, seems important, notably because of their close relation to algebraic and Hermitian Ktheory and their appearance in the study of scissors congruence of polyh

  16. 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.

  17. 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.

  18. Identification and Characterization of FaFT1: A Homolog of FLOWERING LOCUS T from Strawberry

    Directory of Open Access Journals (Sweden)

    Hengjiu Lei

    2015-05-01

    Full Text Available FLOWERING LOCUS T(FT -like genes play crucial roles in flowering transition in several plant species. In this study, a homolog of FT, designated as FaFT1, was isolated and characterized from strawberry. The open reading frame of FaFT1 was 531 bp, encoding a protein of 176 amino acids. Phylogenetic and sequence analysis showed that the FaFT1 protein contained the conservation of Tyr84 and Gln139, as well as the highly conserved amino acid sequences LGRQTVYAPGWRQN and LYN and that it was a member of the FT-like genes of dicots. Subcellular localization analysis revealed that the FaFT1 protein mainly localized in the nuclei of the Arabidopsis protoplasts. FaFT1 was highly expressed in strawberry mature leaves and its expression level decreased under floral induction conditions. Additionally, FaFT1 expression exhibited diurnal circadian rhythm both under SD and LD conditions. Over expression of FaFT1 in wild-type Arabidopsis caused early flowering. Taken together, these results indicate that FaFT1 is a putative FT homolog in strawberry, acting as a floral promoter in Arabidopsis.

  19. Molecular characterization and homologous overexpression of [FeFe]-hydrogenase in Clostridium tyrobutyricum JM1

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Ji Hye [Biosciences Center, National Renewable Energy Laboratory, 1617 Cole Blvd, Golden, CO 80401-3393 (United States); Jeon, Che Ok [Department of Life Science, Chung-Ang University, Seoul 156-756 (Korea); Lee, Seung Yoon [K-water Research Institute, Korea Water Resources Corporation, 462-1, Jeonmin-dong, Yuseong-gu, Daejon 305-703 (Korea); Lee, Dae Sung [Department of Environmental Engineering, Kyungpook National University, 1370 Sankyuk-dong, Buk-gu, Daegu 702-701 (Korea); Park, Jong Moon [Department of Chemical Engineering, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk 790-784 (Korea)

    2010-02-15

    The H{sub 2}-evoving [FeFe]-hydrogenase in Clostridium tyrobutyricum JM1 was isolated to elucidate molecular characterization and modular structure of the hydrogenase. Then, homologous overexpression of the hydrogenase gene was for the first time performed to enhance hydrogen production. The hydA open reading frame (ORF) was 1734-bp, encodes 577 amino acids with a predicted molecular mass of 63,970 Da, and presents 80% and 75% identity at the amino acid level with the [FeFe]-hydrogenase genes of Clostridium kluyveri DSM 555 and Clostridium acetobutylicum ATCC 824, respectively. One histidine residue and 19 cysteine residues, known to fasten one [2Fe-2S] cluster, three [4Fe-4S] clusters and one H-cluster, were conserved in hydA of C. tyrobutyricum. A 2327-bp DNA region containing the ORF and the putative promoter region was amplified and subcloned into a pJIR418 shuttle vector. The gene transfer of the recombinant plasmid into C. tyrobutyricum JM1 was performed by a modified electrotransformation method. Homologous overexpression of the [FeFe]-hydrogenase gene resulted in a 1.7-fold and 1.5-fold increase in hydrogenase activity and hydrogen yield concomitant with the shift of metabolic pathway. (author)

  20. 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

    2016-01-01

    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.

  1. Physicochemical characterization of the human nail: solvent effects on the permeation of homologous alcohols.

    Science.gov (United States)

    Walters, K A; Flynn, G L; Marvel, J R

    1985-11-01

    To assess how vehicles might influence permeation through human nail, the diffusion of homologous alcohols (methanol to decanol) administered as neat liquids through finger nail plate has been studied using in-vitro diffusion cell methods and compared with permeation data for the same compounds in aqueous media. Permeation rates of the homologous alcohols through lipid depleted nail plate have also been assessed and the influences of dimethylsulphoxide (DMSO) and isopropyl alcohol on permeation rates of methanol and hexanol have been examined. With the exception of methanol, permeability coefficients are uniformly about five-fold smaller when the alcohols are undiluted than when they are applied in water. Overall parallelism in the permeability profiles under these separate circumstances of application is an indication that the external concentrations of the alcohols themselves are a determinant of their permeation velocities through the nail plate matrix. The even separation of the profiles suggests a facilitating role of water within the nail matrix. Chloroform/methanol delipidization of the nail led to increased penetration rates of water, methanol, ethanol and butanol. On the other hand, it caused a six-fold decrease in the permeation rate of decanol. Application of methanol and hexanol in DMSO somewhat retards their rates of permeation. Isopropyl alcohol also slows the permeation rate of hexanol but has little influence on that of methanol. Thus it appears that solvents which tend to promote diffusion through the skin horny layer have little promise as accelerants of nail plate permeability.

  2. Remote homology and the functions of metagenomic dark matter

    Directory of Open Access Journals (Sweden)

    Briallen eLobb

    2015-07-01

    Full Text Available Predicted open reading frames (ORFs that lack detectable homology to known proteins are termed ORFans. Despite their prevalence in metagenomes, the extent to which ORFans encode real proteins, the degree to which they can be annotated, and their functional contributions, remain unclear. To gain insights into these questions, we applied sensitive remote-homology detection methods to functionally analyze ORFans from soil, marine, and human gut metagenome collections. ORFans were identified, clustered into sequence families, and annotated through profile-profile comparison to proteins of known structure.We found that a considerable number of metagenomic ORFans (73,896 of 484,121, 15.3% exhibit significant remote homology to structurally characterized proteins, providing a means for ORFan functional profiling. The extent of detected remote homology significantly exceeds that obtained for artificial protein families (1.4%. In addition, predicted ORFan functions show significant functional consistency with their gene neighbors (p < 0.001 as expected for real genes. Compared to genes annotated through standard homology searches, ORFans have intriguing functional differences such as an enrichment of virus-related functions and biological processes associated with extreme sequence diversity. Each environment also possesses many unique ORFan families that likely play important community roles such as identified ORFan polysaccharide degradation genes unique to the human gut metagenome. Lastly, ORFans are a valuable resource for finding novel enzymes of interest, as we demonstrate by identifying hundreds of ORFan metalloproteases that conserve a catalytic site despite a lack of overall sequence similarity to known proteins. Our ORFan functional predictions are a valuable resource for discovering novel protein families and exploring the boundaries of protein sequence space. Our resource of annotated metagenomic ORFans is available at http://doxey.uwaterloo.ca.

  3. 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.

  4. Illustrating and homology modeling the proteins of the Zika virus

    Science.gov (United States)

    Ekins, Sean; Liebler, John; Neves, Bruno J.; Lewis, Warren G.; Coffee, Megan; Bienstock, Rachelle; Southan, Christopher; Andrade, Carolina H.

    2016-01-01

    The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening. PMID:27746901

  5. 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...... mitochondrial protein. To address the function and relevance of SIRT3 in the regulation of energy metabolism, we generated and phenotypically characterized SIRT3 knockout mice. SIRT3-deficient animals exhibit striking mitochondrial protein hyperacetylation, suggesting that SIRT3 is a major mitochondrial...... deacetylase. In contrast, no mitochondrial hyperacetylation was detectable in mice lacking the two other mitochondrial sirtuins, SIRT4 and SIRT5. Surprisingly, despite this biochemical phenotype, SIRT3-deficient mice are metabolically unremarkable under basal conditions and show normal adaptive thermogenesis...

  6. 53BP1 fosters fidelity of homology-directed DNA repair

    DEFF Research Database (Denmark)

    Ochs, Fena; Somyajit, Kumar; Altmeyer, Matthias;

    2016-01-01

    Repair of DNA double-strand breaks (DSBs) in mammals is coordinated by the ubiquitin-dependent accumulation of 53BP1 at DSB-flanking chromatin. Owing to its ability to limit DNA-end processing, 53BP1 is thought to promote nonhomologous end-joining (NHEJ) and to suppress homology-directed repair...... (HDR). Here, we show that silencing 53BP1 or exhausting its capacity to bind damaged chromatin changes limited DSB resection to hyper-resection and results in a switch from error-free gene conversion by RAD51 to mutagenic single-strand annealing by RAD52. Thus, rather than suppressing HDR, 53BP1...... fosters its fidelity. These findings illuminate causes and consequences of synthetic viability acquired through 53BP1 silencing in cells lacking the BRCA1 tumor suppressor. We show that such cells survive DSB assaults at the cost of increasing reliance on RAD52-mediated HDR, which may fuel genome...

  7. 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.

  8. DNA end resection controls the balance between homologous and illegitimate recombination in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Siniša Ivanković

    Full Text Available Even a partial loss of function of human RecQ helicase analogs causes adverse effects such as a cancer-prone Werner, Bloom or Rothmund-Thompson syndrome, whereas a complete RecQ deficiency in Escherichia coli is not deleterious for a cell. We show that this puzzling difference is due to different mechanisms of DNA double strand break (DSB resection in E. coli and humans. Coupled helicase and RecA loading activities of RecBCD enzyme, which is found exclusively in bacteria, are shown to be responsible for channeling recombinogenic 3' ending tails toward productive, homologous and away from nonproductive, aberrant recombination events. On the other hand, in recB1080/recB1067 mutants, lacking RecBCD's RecA loading activity while preserving its helicase activity, DSB resection is mechanistically more alike that in eukaryotes (by its uncoupling from a recombinase polymerization step, and remarkably, the role of RecQ also becomes akin of its eukaryotic counterparts in a way of promoting homologous and suppressing illegitimate recombination. The sickly phenotype of recB1080 recQ mutant was further exacerbated by inactivation of an exonuclease I, which degrades the unwound 3' tail. The respective recB1080 recQ xonA mutant showed poor viability, DNA repair and homologous recombination deficiency, and very increased illegitimate recombination. These findings demonstrate that the metabolism of the 3' ending overhang is a decisive factor in tuning the balance of homologous and illegitimate recombination in E. coli, thus highlighting the importance of regulating DSB resection for preserving genome integrity. recB mutants used in this study, showing pronounced RecQ helicase and exonuclease I dependence, make up a suitable model system for studying mechanisms of DSB resection in bacteria. Also, these mutants might be useful for investigating functions of the conserved RecQ helicase family members, and congruently serve as a simpler, more defined model system

  9. [Rule of homology and morbid anatomy (author's transl)].

    Science.gov (United States)

    Doerr, W

    1979-07-27

    1. According to J.W. Goethe, morphology is a theory of evolution, H. Braus defined it as a theory of historic incidents, and according to D. Starck morphology is the role of shapes of the organisms. 2. The term homology was coined by morphologic researchers. Of course, it is used nowadays also in mathematics, chemistry, and linguistics and other logic matters. 3. Homologies have a special position in Goethe's work on the theory of types. Goethe's morphologic research and Schiller's aesthetic speculations are considered to be the origin of a 'typologic point of view.' 4. Coherences of Platon's theory of ideas and Goethe's theory of types are scrutinized. The theory of shapes ('Gestalt theory') is inconceivable without Platon's theory, and scientic morphology is inconceivable without shapes, either, and according to C. v. Ehrenfels "Gestaltphilosophie" could not exist without the shapes of Platon's theory. 5. It is shown that without Gestalt philosophy one cannot comprehend the following coherences: Gestalt (shape) as an idea, idea as a type of Goethe's rule, type as an element of the theory of homologies and even of constitution. 6. Homology will be constituted using certain criterions: a) detection of an equal descent, b) equal position of organismic structures in individuals, c) evidence of interpositions, and d) certain qualities of parts which are compared with each other. Homologous structures may be dissimilar in their architecture. 7. The term homology is explained a) by giving an analysis of morphologic and teratologic lines, b) by scrutinizing froms of symmetry, and c) by presenting the histopathology of topographical diverse but according to the morphogenetic mode coinciding tumours which are resembling each other in their microscopic patterns. 8. The application of the rule of homology in the morphologic investigation of diseases proves to be a) valuable from a heuristic point of view, b) an instrument of communication to characterize comparable matters

  10. Hochschild homology, global dimension, and truncated oriented cycles

    CERN Document Server

    Han, Yang

    2010-01-01

    It is shown that a bounded quiver algebra having a 2-truncated oriented cycle is of infinite Hochschild homology dimension and global dimension, which generalizes a result of Solotar and Vigu\\'{e}-Poirrier to nonlocal ungraded algebras having a 2-truncated oriented cycle of arbitrary length. Therefore, a bounded quiver algebra of finite global dimension has no 2-truncated oriented cycles. Note that the well-known "no loops conjecture", which has been proved to be true already, says that a bounded quiver algebra of finite global dimension has no loops, i.e., truncated oriented cycles of length 1. Moreover, it is shown that a monomial algebra having a truncated oriented cycle is of infinite Hochschild homology dimension and global dimension. Consequently, a monomial algebra of finite global dimension has no truncated oriented cycles.

  11. Back-Translation for Discovering Distant Protein Homologies

    Science.gov (United States)

    Gîrdea, Marta; Noé, Laurent; Kucherov, Gregory

    Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins’ common origin. Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level. To cope with this situation, we propose a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences. We design a dynamic programming alignment algorithm over memory-efficient graph representations of the complete set of putative DNA sequences of each protein, with the goal of determining the two putative DNA sequences which have the best scoring alignment under a powerful scoring system designed to reflect the most probable evolutionary process. This allows us to uncover evolutionary information that is not captured by traditional alignment methods, which is confirmed by biologically significant examples.

  12. Identification of rodent homologs of hepatitis C virus and pegiviruses

    DEFF Research Database (Denmark)

    Kapoor, Amit; Simmonds, Peter; Scheel, Troels K H

    2013-01-01

    UNLABELLED: Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity......, and pathogenesis. To address this challenge, we searched for homologous viruses in small mammals, including wild rodents. Here we report the discovery of several new hepaciviruses (HCV-like viruses) and pegiviruses (GB virus-like viruses) that infect wild rodents. Complete genome sequences were acquired...... to those found in human hepaciviruses and pegiviruses suggests the potential for the development of new animal systems with which to model HCV pathogenesis, vaccine design, and treatment. IMPORTANCE: The genetic and biological characterization of animal homologs of human viruses provides insights...

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

    Science.gov (United States)

    Weterings, Eric; Chen, David J

    2008-01-01

    DNA double-strand breaks (DSBs) are introduced in cells by ionizing radiation and reactive oxygen species. In addition, 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.

  14. 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.

  15. Molecular evolution of a Drosophila homolog of human BRCA2.

    Science.gov (United States)

    Bennett, Sarah M; Noor, Mohamed A F

    2009-11-01

    The human cancer susceptibility gene, BRCA2, functions in double-strand break repair by homologous recombination, and it appears to function via interaction of a repetitive region ("BRC repeats") with RAD-51. A putatively simpler homolog, dmbrca2, was identified in Drosophila melanogaster recently and also affects mitotic and meiotic double-strand break repair. In this study, we examined patterns of repeat variation both within Drosophila pseudoobscura and among available Drosophila genome sequences. We identified extensive variation within and among closely related Drosophila species in BRC repeat number, to the extent that variation within this genus recapitulates the extent of variation found across the entire animal kingdom. We describe patterns of evolution across species by documenting recent repeat expansions (sometimes in tandem arrays) and homogenizations within available genome sequences. Overall, we have documented patterns and modes of evolution in a new model system of a gene which is important to human health.

  16. 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.

  17. Levels of homology and the problem of neocortex.

    Science.gov (United States)

    Dugas-Ford, Jennifer; Ragsdale, Clifton W

    2015-07-08

    The neocortex is found only in mammals, and the fossil record is silent on how this soft tissue evolved. Understanding neocortex evolution thus devolves to a search for candidate homologous neocortex traits in the extant nonmammalian amniotes. The difficulty is that homology is based on similarity, and the six-layered neocortex structure could hardly be more dissimilar in appearance from the nuclear organization that is so conspicuous in the dorsal telencephalon of birds and other reptiles. Recent molecular data have, however, provided new support for one prominent hypothesis, based on neuronal circuits, that proposes the principal neocortical input and output cell types are a conserved feature of amniote dorsal telencephalon. Many puzzles remain, the greatest being understanding the selective pressures and molecular mechanisms that underlie such tremendous morphological variation in telencephalon structure.

  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. A New Homologous Series of Lanthanum Copper Oxides

    NARCIS (Netherlands)

    Cava, R.J.; Siegrist, T.; Hessen, B.; Krajewski, J.J.; Peck, Jr.; Batlogg, B.; Tagaki, H.; Waszczak, J.V.; Schneemeyer, L.F.; Zandbergen, H.W.

    1991-01-01

    We report the synthesis and structural characterization of a new homologous series of lanthanum cuprates, with the formula La4+4nCu8+2nO14+8n . The n = 2 and n = 3 members, La2Cu2O5 and La8Cu7O19 , synthesized in the bulk, are stable in very narrow temperature ranges in air and oxygen. The n = 4 mem

  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. 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.

  2. [An homologous recombination strategy to directly clone mammalian telemeres

    Energy Technology Data Exchange (ETDEWEB)

    1992-01-01

    We have pursued three goals over the past year. The first involved determining whether the HARY vector could be used for homologous integration in the human genome. The second was to ascertain whether inserted sequences could be amplified in preference to the endogenous DHFR genes. The third was to determine if the HARY insertion could provide an anchor point for long range restriction mapping. The progress in each goal is described.

  3. 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.

  4. The ATPase activity of Fml1 is essential for its roles in homologous recombination and DNA repair.

    OpenAIRE

    Nandi, S; Whitby, MC

    2012-01-01

    In fission yeast, the DNA helicase Fml1, which is an orthologue of human FANCM, is a key component of the machinery that drives and governs homologous recombination (HR). During the repair of DNA double-strand breaks by HR, it limits the occurrence of potentially deleterious crossover recombinants, whereas at stalled replication forks, it promotes HR to aid their recovery. Here, we have mutated conserved residues in Fml1's Walker A (K99R) and Walker B (D196N) motifs to determine whether its a...

  5. 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.

  6. Overexpression of denticleless E3 ubiquitin protein ligase homolog (DTL) is related to poor outcome in gastric carcinoma

    OpenAIRE

    Kobayashi, Hiroki; Komatsu, Shuhei; Ichikawa, Daisuke; Kawaguchi, Tsutomu; Hirajima, Shoji; Miyamae, Mahito; Okajima, Wataru; Ohashi, Takuma; Kosuga, Toshiyuki; Konishi, Hirotaka; Shiozaki, Atsushi; FUJIWARA, Hitoshi; Okamoto, Kazuma; Tsuda, Hitoshi; Otsuji, Eigo

    2015-01-01

    Background Denticleless E3 ubiquitin protein ligase homolog (DTL) has been identified in amplified region (1q32) of several cancers and has an oncogenic function. In this study, we tested whether DTL acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). Methods We analyzed 7 GC cell lines and 100 primary tumors that were curatively resected in our hospital between 2001 and 2003. Results Overexpression of the DTL protein was detected in GC cell lines (4/...

  7. Ocular toxicity of benzalkonium chloride homologs compared with their mixtures.

    Science.gov (United States)

    Okahara, Akihiko; Tanioka, Hidetoshi; Takada, Koichi; Kawazu, Kouichi

    2013-12-01

    This study was performed to assess the in vivo ocular toxicity of benzalkonium chloride (BAK) homologs compared with commercially available BAK (BAK mixture) and to assess the ocular toxicity of BAK homolog after repeated ocular application. Rabbit eyes were examined by ophthalmology and scanning electron microscopy (SEM) after 10 applications of BAK homologs with C12 (C12-BAK) and C14 (C14-BAK) alkyl chain lengths and a BAK mixture at concentrations of 0.001% (w/v), 0.003% (w/v), 0.005% (w/v), 0.01% (w/v) and 0.03% (w/v). The ocular toxicity of C12-BAK to rabbit eyes was examined by ophthalmology and histopathology after repeated ocular application for 39 weeks. In addition, the antimicrobial activities of C12-BAK and C14-BAK against A. niger, S. aureus and P. aeruginosa were assessed. Ocular toxicity of C12-BAK was less than those of the BAK mixture and C14-BAK. No ocular toxicity was noted after ocular application of 0.01% C12-BAK to rabbits for 39 weeks. C12-BAK showed antimicrobial activities at a concentration of 0.003%. These results suggest that the use of C12-BAK to replace BAK mixture as a preservative in ophthalmic solutions should be considered in order to reduce the incidence of the corneal epithelial cell injury induced clinically by BAK.

  8. Two pathways of homologous recombination in Trypanosoma brucei.

    Science.gov (United States)

    Conway, Colin; Proudfoot, Chris; Burton, Peter; Barry, J David; McCulloch, Richard

    2002-09-01

    African trypanosomes are unicellular parasites that use DNA recombination to evade the mammalian immune response. They do this in a process called antigenic variation, in which the parasites periodically switch the expression of VSG genes that encode distinct Variant Surface Glycoprotein coats. Recombination is used to move new VSG genes into specialised bloodstream VSG transcription sites. Genetic and molecular evidence has suggested that antigenic variation uses homologous recombination, but the detailed reaction pathways are not understood. In this study, we examine the recombination pathways used by trypanosomes to integrate transformed DNA into their genome, and show that they possess at least two pathways of homologous recombination. The primary mechanism is dependent upon RAD51, but a subsidiary pathway exists that is RAD51-independent. Both pathways contribute to antigenic variation. We show that the RAD51-independent pathway is capable of recombining DNA substrates with very short lengths of sequence homology and in some cases aberrant recombination reactions can be detected using such microhomologies.

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

    Science.gov (United States)

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

    2015-10-23

    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.

  10. 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.

  11. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens

    Directory of Open Access Journals (Sweden)

    Shinji Amari

    2013-01-01

    Full Text Available The three-dimensional (3D structures of human leukocyte antigen (HLA molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  12. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens.

    Science.gov (United States)

    Amari, Shinji; Kataoka, Ryoichi; Ikegami, Takashi; Hirayama, Noriaki

    2013-01-01

    The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  13. Three-Dimensional Modeling of Quasi-Homologous Solar Jets

    Science.gov (United States)

    Pariat, E.; Antiochos, S. K.; DeVore, C. R.

    2010-01-01

    Recent solar observations (e.g., obtained with Hinode and STEREO) have revealed that coronal jets are a more frequent phenomenon than previously believed. This higher frequency results, in part, from the fact that jets exhibit a homologous behavior: successive jets recur at the same location with similar morphological features. We present the results of three-dimensional (31)) numerical simulations of our model for coronal jets. This study demonstrates the ability of the model to generate recurrent 3D untwisting quasi-homologous jets when a stress is constantly applied at the photospheric boundary. The homology results from the property of the 3D null-point system to relax to a state topologically similar to its initial configuration. In addition, we find two distinct regimes of reconnection in the simulations: an impulsive 3D mode involving a helical rotating current sheet that generates the jet, and a quasi-steady mode that occurs in a 2D-like current sheet located along the fan between the sheared spines. We argue that these different regimes can explain the observed link between jets and plumes.

  14. 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.

  15. TALEN-mediated homologous recombination in Daphnia magna.

    Science.gov (United States)

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

    2015-12-17

    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.

  16. 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.

  17. Integration of a transfected gene into the genome of Babesia bovis occurs by legitimate homologous recombination mechanisms.

    Science.gov (United States)

    Suarez, Carlos E; Johnson, Wendell C; Herndon, David R; Laughery, Jacob M; Davis, William C

    2015-08-01

    This study examines the patterns of gene integration of gfp-bsd upon stable transfection into the T3Bo strain of Babesia bovis using a plasmid designed to integrate homologous sequences of the parasite's two identical ef-1α A and B genes. While the transfected BboTf-149-6 cell line displayed two distinct patterns of gene integration, clonal lines derived from this strain by cell sorting contained only single gfp-bsd insertions. Whole genome sequencing of two selected clonal lines, E9 and C6, indicated two distinct patterns of gfp-bsd insertion occurring by legitimate homologous recombination mechanisms: one into the expected ef-1α orf B, and another into the ef-1α B promoter. The data suggest that expression of the ef-1α orf B is not required for development of B. bovis in cultured erythrocyte stages. Use of legitimate homologous recombination mechanisms in transfected B. bovis supports the future use of transfection methods for developing efficient gene function assignment experiments using gene knockout techniques.

  18. The third homology of the special linear group of a field

    CERN Document Server

    Hutchinson, Kevin

    2008-01-01

    We prove that for any infinite field homology stability for the third integral homology of the special linear groups $SL(n,F)$ begins at $n=3$. When $n=2$ the cokernel of the map from the third homology of $SL(2,F)$ to the third homology of $SL(3,F)$ is naturally isomorphic to the square of Milnor $K_3$. We discuss applications to the indecomposable $K_3$ of the field and to Milnor-Witt K-theory.

  19. The third homology of the special linear group of a field

    OpenAIRE

    Hutchinson, Kevin; Tao, Liqun

    2009-01-01

    We prove that for any infinite field homology stability for the third integral homology of the special linear groups $SL(n,F)$ begins at $n=3$. When $n=2$ the cokernel of the map from the third homology of $SL(2,F)$ to the third homology of $SL(3,F)$ is naturally isomorphic to the square of Milnor $K_3$. We discuss applications to the indecomposable $K_3$ of the field and to Milnor-Witt K-theory.

  20. 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.

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

    DEFF Research Database (Denmark)

    Brown, S; Thon, G; Tolentino, E

    1989-01-01

    the homologs were determined. Since this approach does not require that the homologous genes hybridize with probes generated from the E. coli sequence, the sequences of the homologs were not all similar to the sequence of the E. coli gene. Despite the dissimilarity of the primary sequences of some...

  2. Murine tribbles homolog 2 deficiency affects erythroid progenitor development and confers macrocytic anemia on mice.

    Science.gov (United States)

    Lin, Kou-Ray; Yang-Yen, Hsin-Fang; Lien, Huang-Wei; Liao, Wei-Hao; Huang, Chang-Jen; Lin, Liang-In; Li, Chung-Leung; Yen, Jeffrey Jong-Young

    2016-08-23

    Tribbles homolog 2 (Trib2) is a member of Tribbles protein pseudokinases and involves in apoptosis, autoimmunity, cancer, leukemia and erythropoiesis, however, the physiological function of Trib2 in hematopoietic system remains to be elucidated. Here, we report that Trib2 knockout (KO) mice manifest macrocytic anemia and increase of T lymphocytes. Although Trib2 deficient RBCs have similar half-life as the control RBCs, Trib2 KO mice are highly vulnerable to oxidant-induced hemolysis. Endogenous Trib2 mRNA is expressed in early hematopoietic progenitors, erythroid precursors, and lymphoid lineages, but not in mature RBCs, myeloid progenitors and granulocytes. Consistently, flow cytometric analysis and in vitro colony forming assay revealed that deletion of Trib2 mainly affected erythroid lineage development, and had no effect on either granulocyte or megakaryocyte lineages in bone marrow. Furthermore, a genetic approach using double knockout of Trib2 and C/ebpα genes in mice suggested that Trib2 promotes erythropoiesis independent of C/ebpα proteins in vivo. Finally, ectopic expression of human Trib2 in zebrafish embryos resulted in increased expression of erythropoiesis-related genes and of hemoglobin. Taking all data together, our results suggest that Trib2 positively promotes early erythrocyte differentiation and is essential for tolerance to hemolysis.

  3. The PIKE homolog Centaurin gamma regulates developmental timing in Drosophila.

    Directory of Open Access Journals (Sweden)

    Anna Lisa Gündner

    Full Text Available Phosphoinositide-3-kinase enhancer (PIKE proteins encoded by the PIKE/CENTG1 gene are members of the gamma subgroup of the Centaurin superfamily of small GTPases. They are characterized by their chimeric protein domain architecture consisting of a pleckstrin homology (PH domain, a GTPase-activating (GAP domain, Ankyrin repeats as well as an intrinsic GTPase domain. In mammals, three PIKE isoforms with variations in protein structure and subcellular localization are encoded by the PIKE locus. PIKE inactivation in mice results in a broad range of defects, including neuronal cell death during brain development and misregulation of mammary gland development. PIKE -/- mutant mice are smaller, contain less white adipose tissue, and show insulin resistance due to misregulation of AMP-activated protein kinase (AMPK and insulin receptor/Akt signaling. here, we have studied the role of PIKE proteins in metabolic regulation in the fly. We show that the Drosophila PIKE homolog, ceng1A, encodes functional GTPases whose internal GAP domains catalyze their GTPase activity. To elucidate the biological function of ceng1A in flies, we introduced a deletion in the ceng1A gene by homologous recombination that removes all predicted functional PIKE domains. We found that homozygous ceng1A mutant animals survive to adulthood. In contrast to PIKE -/- mouse mutants, genetic ablation of Drosophila ceng1A does not result in growth defects or weight reduction. Although metabolic pathways such as insulin signaling, sensitivity towards starvation and mobilization of lipids under high fed conditions are not perturbed in ceng1A mutants, homozygous ceng1A mutants show a prolonged development in second instar larval stage, leading to a late onset of pupariation. In line with these results we found that expression of ecdysone inducible genes is reduced in ceng1A mutants. Together, we propose a novel role for Drosophila Ceng1A in regulating ecdysone signaling-dependent second to

  4. 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.

  5. μ-Opioid receptor desensitization: homologous or heterologous?

    Science.gov (United States)

    Llorente, Javier; Lowe, Janet D; Sanderson, Helen S; Tsisanova, Elena; Kelly, Eamonn; Henderson, Graeme; Bailey, Chris P

    2012-12-01

    There is considerable controversy over whether μ-opioid receptor (MOPr) desensitization is homologous or heterologous and over the mechanisms underlying such desensitization. In different cell types MOPr desensitization has been reported to involve receptor phosphorylation by various kinases, including G-protein-coupled receptor kinases (GRKs), second messenger and other kinases as well as perturbation of the MOPr effector pathway by GRK sequestration of G protein βγ subunits or ion channel modulation. Here we report that in brainstem locus coeruleus (LC) neurons prepared from relatively mature rats (5-8 weeks old) rapid MOPr desensitization induced by the high-efficacy opioid peptides methionine enkephalin and DAMGO was homologous and not heterologous to α(2)-adrenoceptors and somatostatin SST(2) receptors. Given that these receptors all couple through G proteins to the same set of G-protein inwardly rectifying (GIRK) channels it is unlikely therefore that in mature neurons MOPr desensitization involves G protein βγ subunit sequestration or ion channel modulation. In contrast, in slices from immature animals (less than postnatal day 20), MOPr desensitization was observed to be heterologous and could be downstream of the receptor. Heterologous MOPr desensitization was not dependent on protein kinase C or c-Jun N-terminal kinase activity, but the change from heterologous to homologous desensitization with age was correlated with a decrease in the expression levels of GRK2 in the LC and other brain regions. The observation that the mechanisms underlying MOPr desensitization change with neuronal development is important when extrapolating to the mature brain results obtained from experiments on expression systems, cell lines and immature neuronal preparations.

  6. The PIKE homolog Centaurin gamma regulates developmental timing in Drosophila.

    Science.gov (United States)

    Gündner, Anna Lisa; Hahn, Ines; Sendscheid, Oliver; Aberle, Hermann; Hoch, Michael

    2014-01-01

    Phosphoinositide-3-kinase enhancer (PIKE) proteins encoded by the PIKE/CENTG1 gene are members of the gamma subgroup of the Centaurin superfamily of small GTPases. They are characterized by their chimeric protein domain architecture consisting of a pleckstrin homology (PH) domain, a GTPase-activating (GAP) domain, Ankyrin repeats as well as an intrinsic GTPase domain. In mammals, three PIKE isoforms with variations in protein structure and subcellular localization are encoded by the PIKE locus. PIKE inactivation in mice results in a broad range of defects, including neuronal cell death during brain development and misregulation of mammary gland development. PIKE -/- mutant mice are smaller, contain less white adipose tissue, and show insulin resistance due to misregulation of AMP-activated protein kinase (AMPK) and insulin receptor/Akt signaling. here, we have studied the role of PIKE proteins in metabolic regulation in the fly. We show that the Drosophila PIKE homolog, ceng1A, encodes functional GTPases whose internal GAP domains catalyze their GTPase activity. To elucidate the biological function of ceng1A in flies, we introduced a deletion in the ceng1A gene by homologous recombination that removes all predicted functional PIKE domains. We found that homozygous ceng1A mutant animals survive to adulthood. In contrast to PIKE -/- mouse mutants, genetic ablation of Drosophila ceng1A does not result in growth defects or weight reduction. Although metabolic pathways such as insulin signaling, sensitivity towards starvation and mobilization of lipids under high fed conditions are not perturbed in ceng1A mutants, homozygous ceng1A mutants show a prolonged development in second instar larval stage, leading to a late onset of pupariation. In line with these results we found that expression of ecdysone inducible genes is reduced in ceng1A mutants. Together, we propose a novel role for Drosophila Ceng1A in regulating ecdysone signaling-dependent second to third instar

  7. A procedure for identifying homologous alternative splicing events

    Directory of Open Access Journals (Sweden)

    Orozco Modesto

    2007-07-01

    Full Text Available Abstract Background The study of the functional role of alternative splice isoforms of a gene is a very active area of research in biology. The difficulty of the experimental approach (in particular, in its high-throughput version leaves ample room for the development of bioinformatics tools that can provide a useful first picture of the problem. Among the possible approaches, one of the simplest is to follow classical protein function annotation protocols and annotate target alternative splice events with the information available from conserved events in other species. However, the application of this protocol requires a procedure capable of recognising such events. Here we present a simple but accurate method developed for this purpose. Results We have developed a method for identifying homologous, or equivalent, alternative splicing events, based on the combined use of neural networks and sequence searches. The procedure comprises four steps: (i BLAST search for homologues of the two isoforms defining the target alternative splicing event; (ii construction of all possible candidate events; (iii scoring of the latter with a series of neural networks; and (iv filtering of the results. When tested in a set of 473 manually annotated pairs of homologous events, our method showed a good performance, with an accuracy of 0.99, a precision of 0.98 and a sensitivity of 0.93. When no candidates were available, the specificity of our method varied between 0.81 and 0.91. Conclusion The method described in this article allows the identification of homologous alternative splicing events, with a good success rate, indicating that such method could be used for the development of functional annotation of alternative splice isoforms.

  8. The Arabidopsis COX11 Homolog is Essential for Cytochrome c Oxidase Activity.

    Science.gov (United States)

    Radin, Ivan; Mansilla, Natanael; Rödel, Gerhard; Steinebrunner, Iris

    2015-01-01

    Members of the ubiquitous COX11 (cytochrome c oxidase 11) protein family are involved in copper delivery to the COX complex. In this work, we characterize the Arabidopsis thaliana COX11 homolog (encoded by locus At1g02410). Western blot analyses and confocal microscopy identified Arabidopsis COX11 as an integral mitochondrial protein. Despite sharing high sequence and structural similarities, the Arabidopsis COX11 is not able to functionally replace the Saccharomyces cerevisiae COX11 homolog. Nevertheless, further analysis confirmed the hypothesis that Arabidopsis COX11 is essential for COX activity. Disturbance of COX11 expression through knockdown (KD) or overexpression (OE) affected COX activity. In KD lines, the activity was reduced by ~50%, resulting in root growth inhibition, smaller rosettes and leaf curling. In OE lines, the reduction was less pronounced (~80% of the wild type), still resulting in root growth inhibition. Additionally, pollen germination was impaired in COX11 KD and OE plants. This effect on pollen germination can only partially be attributed to COX deficiency and may indicate a possible auxiliary role of COX11 in ROS metabolism. In agreement with its role in energy production, the COX11 promoter is highly active in cells and tissues with high-energy demand for example shoot and root meristems, or vascular tissues of source and sink organs. In COX11 KD lines, the expression of the plasma-membrane copper transporter COPT2 and of several copper chaperones was altered, indicative of a retrograde signaling pathway pertinent to copper homeostasis. Based on our data, we postulate that COX11 is a mitochondrial chaperone, which plays an important role for plant growth and pollen germination as an essential COX complex assembly factor.

  9. Colored sl(N) link homology via matrix factorizations

    CERN Document Server

    Wu, Hao

    2011-01-01

    The Reshetikhin-Turaev sl(N) polynomial of links colored by wedge powers of the defining representation has been categorified via several different approaches. Here, we give a concise introduction to the categorification using matrix factorizations, which is a direct generalization of the Khovanov-Rozansky homology. Full details of the construction are given in [arXiv:0907.0695]. We also briefly review deformations and applications of this categorification given in [arXiv:1002.2662, arXiv:1011.2254, arXiv:1102.0586].

  10. Drosophila homolog of the murine Int-1 protooncogene.

    OpenAIRE

    1988-01-01

    We have isolated phage clones from Drosophila melanogaster genomic and cDNA libraries containing a sequence homologous to the murine Int-1 protooncogene. The Drosophila gene is represented by a single locus at position 28A1-2 on chromosome 2. The gene is expressed as a 2.9-kilobase-long polyadenylylated mRNA in embryo, larval, and pupal stages. It is hardly detectable in adult flies. The longest open reading frame of the cDNA clone corresponds to a protein 469 amino acids long. Alignment of t...

  11. Seamless gene tagging by endonuclease-driven homologous recombination.

    Directory of Open Access Journals (Sweden)

    Anton Khmelinskii

    Full Text Available Gene tagging facilitates systematic genomic and proteomic analyses but chromosomal tagging typically disrupts gene regulatory sequences. Here we describe a seamless gene tagging approach that preserves endogenous gene regulation and is potentially applicable in any species with efficient DNA double-strand break repair by homologous recombination. We implement seamless tagging in Saccharomyces cerevisiae and demonstrate its application for protein tagging while preserving simultaneously upstream and downstream gene regulatory elements. Seamless tagging is compatible with high-throughput strain construction using synthetic genetic arrays (SGA, enables functional analysis of transcription antisense to open reading frames and should facilitate systematic and minimally-invasive analysis of gene functions.

  12. 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.

  13. Building Multiclass Classifiers for Remote Homology Detection and Fold Recognition

    Science.gov (United States)

    2006-04-05

    NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS...are thoroughly evaluated for both remote homology prediction and fold recognition using four differ- ent datasets derived from Astral [5]. Our...function may not be the most appropriate as it may lead to models where 5 Table 1: Dataset Statistics. Statistic DS1 DS2 DS3 DS4 ASTRAL filtering 90% 40% 25

  14. The Non-Homologous Nature of Solar Diameter Variations

    CERN Document Server

    Sofia, S; Demarque, P; Li, L; Thuillier, G; Sofia, Sabatino; Basu, Sarbani; Demarque, Pierre; Li, Linghuai; Thuillier, Gerard

    2005-01-01

    We show in this paper that the changes of the solar diameter in response to variations of large scale magnetic fields and turbulence are not homologous. For the best current model, the variation at the photospheric level is over 1000 times larger than the variation at a depth of 5 Mm, which is about the level at which f-mode solar oscillations determine diameter variations. This model is supported by observations that indicate larger diameter changes for high degree f-modes than for low degree f-modes, since energy of the former are concentrated at shallower layers than the latter.

  15. The growth rate of symplectic homology and affine varieties

    CERN Document Server

    McLean, Mark

    2010-01-01

    We will show that the cotangent bundle of an integrally hyperbolic manifold is not symplectomorphic to any smooth affine variety. We will also show that the unit cotangent bundle of such a manifold is not Stein fillable by a Stein domain whose completion is symplectomorphic to a smooth affine variety. For instance, these results hold when our manifolds are simply connected with at least one Betti number greater than the corresponding Betti number of the n torus. We use an invariant called the growth rate of symplectic homology to prove this result.

  16. 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.

  17. Ectopic expression of RNF168 and 53BP1 increases mutagenic but not physiological non-homologous end joining.

    Science.gov (United States)

    Zong, Dali; Callén, Elsa; Pegoraro, Gianluca; Lukas, Claudia; Lukas, Jiri; Nussenzweig, André

    2015-05-26

    DNA double strand breaks (DSBs) formed during S phase are preferentially repaired by homologous recombination (HR), whereas G1 DSBs, such as those occurring during immunoglobulin class switch recombination (CSR), are repaired by non-homologous end joining (NHEJ). The DNA damage response proteins 53BP1 and BRCA1 regulate the balance between NHEJ and HR. 53BP1 promotes CSR in part by mediating synapsis of distal DNA ends, and in addition, inhibits 5' end resection. BRCA1 antagonizes 53BP1 dependent DNA end-blocking activity during S phase, which would otherwise promote mutagenic NHEJ and genome instability. Recently, it was shown that supra-physiological levels of the E3 ubiquitin ligase RNF168 results in the hyper-accumulation of 53BP1/BRCA1 which accelerates DSB repair. Here, we ask whether increased expression of RNF168 or 53BP1 impacts physiological versus mutagenic NHEJ. We find that the anti-resection activities of 53BP1 are rate-limiting for mutagenic NHEJ but not for physiological CSR. As heterogeneity in the expression of RNF168 and 53BP1 is found in human tumors, our results suggest that deregulation of the RNF168/53BP1 pathway could alter the chemosensitivity of BRCA1 deficient tumors.

  18. 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

  19. 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.

  20. The extreme carboxyl terminus of the equine herpesvirus 1 homolog of herpes simplex virus VP16 is essential for immediate-early gene activation.

    OpenAIRE

    Elliott, G D

    1994-01-01

    Gene 12 of equine herpesvirus 1 (EHV-1), the homolog of herpes simplex virus (HSV) VP16 (alpha TIF, Vmw65), was cloned into a eukaryotic expression vector by PCR and used in transactivation studies of both the EHV-1 and HSV-1 IE1 promoters. Results demonstrated that the product of gene 12 is a potent transactivator of immediate-early gene expression of both viruses, which requires sequences in the upstream HSV-1 promoter for activity. Mutational analysis of the gene 12 open reading frame indi...

  1. A spectral sequence in odd Khovanov homology (Eine Spektralsequenz in ungerader Khovanov-Homologie)

    CERN Document Server

    Beier, Simon

    2011-01-01

    Ozsvath, Rasmussen and Szabo constructed odd Khovanov homology. It is a link invariant which has the same reduction modulo 2 as (even) Khovanov homology. Szabo introduced a spectral sequence with mod 2 coefficients from mod 2 Khovanov homology to another link homology. He got his spectral sequence from a chain complex with a filtration. We give an integral lift of Szabo's complex, that provides a spectral sequence from odd Khovanov homology to a link homology, from which one can get Szabo's link homology with the Universal Coefficient Theorem. Szabo has constructed such a lift independently, but has not yet published it. This is my master thesis which I wrote under supervision of Thomas Schick at Georg August University G\\"ottingen in summer 2011. It is in German. I will publish a reworked version in English later.

  2. Nasal pungency and odor of homologous aldehydes and carboxylic acids.

    Science.gov (United States)

    Cometto-Muñiz, J E; Cain, W S; Abraham, M H

    1998-01-01

    Airborne substances can stimulate both the olfactory and the trigeminal nerve in the nose, giving rise to odor and pungent (irritant) sensations, respectively. Nose, eye, and throat irritation constitute common adverse effects in indoor environments. We measured odor and nasal pungency thresholds for homologous aliphatic aldehydes (butanal through octanal) and carboxylic acids (formic, acetic, butanoic, hexanoic, and octanoic). Nasal pungency was measured in subjects lacking olfaction (i.e., anosmics) to avoid odor biases. Similar to other homologous series, odor and pungency thresholds declined (i.e., sensory potency increased) with increasing carbon chain length. A previously derived quantitative structure-activity relationship (QSAR) based on solvation energies predicted all nasal pungency thresholds, except for acetic acid, implying that a key step in the mechanism for threshold pungency involves transfer of the inhaled substance from the vapor phase to the receptive biological phase. In contrast, acetic acid - with a pungency threshold lower than predicted - is likely to produce threshold pungency through direct chemical reaction with the mucosa. Both in the series studied here and in those studied previously, we reach a member at longer chain-lengths beyond which pungency fades. The evidence suggests a biological cut-off, presumably based upon molecular size, across the various series.

  3. Flexible mapping of homology onto structure with Homolmapper

    Directory of Open Access Journals (Sweden)

    Lagarias J Clark

    2007-04-01

    Full Text Available Abstract Background Over the past decade, a number of tools have emerged for the examination of homology relationships among protein sequences in a structural context. Most recent software implementations for such analysis are tied to specific molecular viewing programs, which can be problematic for collaborations involving multiple viewing environments. Incorporation into larger packages also adds complications for users interested in adding their own scoring schemes or in analyzing proteins incorporating unusual amino acid residues such as selenocysteine. Results We describe homolmapper, a command-line application for mapping information from a multiple protein sequence alignment onto a protein structure for analysis in the viewing software of the user's choice. Homolmapper is small (under 250 K for the application itself and is written in Python to ensure portability. It is released for non-commercial use under a modified University of California BSD license. Homolmapper permits facile import of additional scoring schemes and can incorporate arbitrary additional amino acids to allow handling of residues such as selenocysteine or pyrrolysine. Homolmapper also provides tools for defining and analyzing subfamilies relative to a larger alignment, for mutual information analysis, and for rapidly visualizing the locations of mutations and multi-residue motifs. Conclusion Homolmapper is a useful tool for analysis of homology relationships among proteins in a structural context. There is also extensive, example-driven documentation available. More information about homolmapper is available at http://www.mcb.ucdavis.edu/faculty-labs/lagarias/homolmapper_home/homolmapper%20web%20page.htm.

  4. 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.

  5. Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination

    Directory of Open Access Journals (Sweden)

    Kritika Hanamshet

    2016-09-01

    Full Text Available Homologous recombination (HR plays an important role in maintaining genomic integrity. It is responsible for repair of the most harmful DNA lesions, DNA double-strand breaks and inter-strand DNA cross-links. HR function is also essential for proper segregation of homologous chromosomes in meiosis, maintenance of telomeres, and resolving stalled replication forks. Defects in HR often lead to genetic diseases and cancer. Rad52 is one of the key HR proteins, which is evolutionarily conserved from yeast to humans. In yeast, Rad52 is important for most HR events; Rad52 mutations disrupt repair of DNA double-strand breaks and targeted DNA integration. Surprisingly, in mammals, Rad52 knockouts showed no significant DNA repair or recombination phenotype. However, recent work demonstrated that mutations in human RAD52 are synthetically lethal with mutations in several other HR proteins including BRCA1 and BRCA2. These new findings indicate an important backup role for Rad52, which complements the main HR mechanism in mammals. In this review, we focus on the Rad52 activities and functions in HR and the possibility of using human RAD52 as therapeutic target in BRCA1 and BRCA2-deficient familial breast cancer and ovarian cancer.

  6. Change of gene structure and function by non-homologous end-joining, homologous recombination, and transposition of DNA.

    Directory of Open Access Journals (Sweden)

    Wolfgang Goettel

    2009-06-01

    Full Text Available An important objective in genome research is to relate genome structure to gene function. Sequence comparisons among orthologous and paralogous genes and their allelic variants can reveal sequences of functional significance. Here, we describe a 379-kb region on chromosome 1 of maize that enables us to reconstruct chromosome breakage, transposition, non-homologous end-joining, and homologous recombination events. Such a high-density composition of various mechanisms in a small chromosomal interval exemplifies the evolution of gene regulation and allelic diversity in general. It also illustrates the evolutionary pace of changes in plants, where many of the above mechanisms are of somatic origin. In contrast to animals, somatic alterations can easily be transmitted through meiosis because the germline in plants is contiguous to somatic tissue, permitting the recovery of such chromosomal rearrangements. The analyzed region contains the P1-wr allele, a variant of the genetically well-defined p1 gene, which encodes a Myb-like transcriptional activator in maize. The P1-wr allele consists of eleven nearly perfect P1-wr 12-kb repeats that are arranged in a tandem head-to-tail array. Although a technical challenge to sequence such a structure by shotgun sequencing, we overcame this problem by subcloning each repeat and ordering them based on nucleotide variations. These polymorphisms were also critical for recombination and expression analysis in presence and absence of the trans-acting epigenetic factor Ufo1. Interestingly, chimeras of the p1 and p2 genes, p2/p1 and p1/p2, are framing the P1-wr cluster. Reconstruction of sequence amplification steps at the p locus showed the evolution from a single Myb-homolog to the multi-gene P1-wr cluster. It also demonstrates how non-homologous end-joining can create novel gene fusions. Comparisons to orthologous regions in sorghum and rice also indicate a greater instability of the maize genome, probably due to

  7. 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.

  8. Overexpression of OsRecQl4 and/or OsExo1 enhances DSB-induced homologous recombination in rice.

    Science.gov (United States)

    Kwon, Yong-Ik; Abe, Kiyomi; Osakabe, Keishi; Endo, Masaki; Nishizawa-Yokoi, Ayako; Saika, Hiroaki; Shimada, Hiroaki; Toki, Seiichi

    2012-12-01

    During homologous recombination (HR)-mediated DNA double-strand break (DSB) repair in eukaryotes, an initial step is the creation of a 3'-single-stranded DNA (ssDNA) overhang via resection of a 5' end. Rad51 polymerizes on this ssDNA to search for a homologous sequence, and the gapped sequence is then repaired using an undamaged homologous DNA strand as template. Recent studies in eukaryotes indicate that resection of the DSB site is promoted by the cooperative action of RecQ helicase family proteins: Bloom helicase (BLM) in mammals or Sgs1 in yeast, and exonuclease 1 (Exo1). However, the role of RecQ helicase and exonuclease during the 5'-resection process of HR in plant cells has not yet been defined. Here, we demonstrate that overexpression of rice proteins OsRecQl4 (BLM counterpart) and/or OsExo1 (Exo1 homolog) can enhance DSB processing, as evaluated by recombination substrate reporter lines in rice. These results could be applied to construct an efficient gene targeting system in rice.

  9. 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.

  10. B7 Homolog 3 Promote Inflammatory Response and Pathological Injury of Streptococcus Pneumoniae Meningitis via A Toll- Like Receptor 2 Dependent Mechanism in Mice%B7同源体3经Toll样受体2依赖性机制增强肺炎链球菌脑膜炎小鼠的炎性反应和病理损伤

    Institute of Scientific and Technical Information of China (English)

    陈旭勤; 汪江淮; 张学光; 包关水

    2012-01-01

    Objective To investigate the impact of B7 homolog 3( B7 - H3) on inflammatory response and blood - brain barrier integrity during streptococcus pneumoniae (SP) meningitis, and explore its mechanism. Methods SP meningitis was established by intracerebral ventricular injection of SP suspension. Wild — type mice were randomly divided into 5 groups and received following injections:PBS,SP alone,SP plus recombinant murine B7 — H3 ,SP plus control IgG mAb, or SP plus anti — B7 — H3 blocking mAb. Toll — like receptor 2( TI.R2) - deficient mice were divided into 3 groups and received PBS.SP alone,or SP plus recombinant murine B7 - H3 injection. At 6 h, 18 h.and 30 h post infection,mice anesthetized,blood sample in mice eyes and brains were collected,and brain homogenates were prepared. Tumor necrosis factor-alpha(TNF-α) ,interleukin -6( IL-6) ,interleukin - 1 beta (IL - 1β), and monocyte chemoattractant protein - 1 ( MCP - 1 ) levels in serum, and albumin and IgG levels in brain homogenates were assessed by enzyme — linked immunosorbent assay ( ELISA). Results 1. In wild - type mice, injection with SP alone and SP plus recombinant murine B7 - H3 led to higher TN F — α, IL — 6 and MCP - 1 levels in serum at 18 h,and higher TNF -α,IL -6,IL - 1β and MCP-1 levels in serum at 30 h,as compared with PBS injection group(Pa <0.05). Compared with SP injection group,levels of any cytokines in serum at each time point were not changed after SP plus control IgG mAb group ( Pa >0.05). SP plus recombinant murine B7 - H3 injection induced higher MCP - 1 level at 18 h ,and higher TNF - a and IL30 h in serum,as compared with SP injection group[ MCP - 1: (42.010 ±3.880) ng · L-1 vs (29.620 ±3. 830) ng · L-l ;TNF-α:(37.550 ± 3.232) ng · L-1 vs (24.570 ±2. 377) ng · L-1 ;IL -6: (66. 160 ±5.766) ng · L-1 us (48.630 ±4.418) ng · L-1 ,P. <0. 05 ]. 2. In SP plus anti -B7 -H3 blocking mAb group,at 30 h,TNF-ex and IL-6 levels in serum were lower than those in

  11. Two Lectures On The Jones Polynomial And Khovanov Homology

    CERN Document Server

    Witten, Edward

    2014-01-01

    In the first of these two lectures, I describe a gauge theory approach to understanding quantum knot invariants as Laurent polynomials in a complex variable q. The two main steps are to reinterpret three-dimensional Chern-Simons gauge theory in four dimensional terms and then to apply electric-magnetic duality. The variable q is associated to instanton number in the dual description in four dimensions. In the second lecture, I describe how Khovanov homology can emerge upon adding a fifth dimension. (Based on lectures presented at the Clay Research Conference at Oxford University, and also at the Galileo Galilei Institute in Florence, the University of Milan, Harvard University, and the University of Pennsylvania.)

  12. 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...

  13. Homological mirror symmetry on noncommutative two-tori

    CERN Document Server

    Kajiura, H

    2004-01-01

    Homological mirror symmetry is a conjecture that a category constructed in the A-model and a category constructed in the B-model are equivalent in some sense. We construct a cyclic differential graded (DG) category of holomorphic vector bundles on noncommutative two-tori as a category in the B-model side. We define the corresponding Fukaya's category in the A-model side, and prove the equivalence of the two categories at the level of cyclic categories. We further write down explicitly Feynman rules for higher Massey products derived from the cyclic DG category. As a background of these arguments, a physical explanation of the mirror symmetry for noncommutative two-tori is also given.

  14. Refined homology model of monoacylglycerol lipase: toward a selective inhibitor

    Science.gov (United States)

    Bowman, Anna L.; Makriyannis, Alexandros

    2009-11-01

    Monoacylglycerol lipase (MGL) is primarily responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), an endocannabinoid with full agonist activity at both cannabinoid receptors. Increased tissue 2-AG levels consequent to MGL inhibition are considered therapeutic against pain, inflammation, and neurodegenerative disorders. However, the lack of MGL structural information has hindered the development of MGL-selective inhibitors. Here, we detail a fully refined homology model of MGL which preferentially identifies MGL inhibitors over druglike noninhibitors. We include for the first time insight into the active-site geometry and potential hydrogen-bonding interactions along with molecular dynamics simulations describing the opening and closing of the MGL helical-domain lid. Docked poses of both the natural substrate and known inhibitors are detailed. A comparison of the MGL active-site to that of the other principal endocannabinoid metabolizing enzyme, fatty acid amide hydrolase, demonstrates key differences which provide crucial insight toward the design of selective MGL inhibitors as potential drugs.

  15. Sequence analysis and homology modeling of laccase from Pycnoporus cinnabarinus.

    Science.gov (United States)

    Meshram, Rohan J; Gavhane, Aj; Gaikar, Rb; Bansode, Ts; Maskar, Au; Gupta, Ak; Sohni, Sk; Patidar, Ma; Pandey, Tr; Jangle, Sn

    2010-09-20

    Industrial effluents of textile, paper, and leather industries contain various toxic dyes as one of the waste material. It imparts major impact on human health as well as environment. The white rot fungus Pycnoporus cinnabarinus Laccase is generally used to degrade these toxic dyes. In order to decipher the mechanism of process by which Laccase degrade dyes, it is essential to know its 3D structure. Homology modeling was performed in presented work, by satisfying Spatial restrains using Modeller Program, which is considered as standard in this field, to generate 3D structure of Laccase in unison, SWISSMODEL web server was also utilized to generate and verify the alternative models. We observed that models created using Modeller stands better on structure evaluation tests. This study can further be used in molecular docking techniques, to understand the interaction of enzyme with its mediators like 2, 2-azinobis (3-ethylbenzthiazoline-6-sulfonate) (ABTS) and Vanillin that are known to enhance the Laccase activity.

  16. CHSMiner: a GUI tool to identify chromosomal homologous segments

    Directory of Open Access Journals (Sweden)

    Liu Lei

    2009-01-01

    Full Text Available Abstract Background The identification of chromosomal homologous segments (CHS within and between genomes is essential for comparative genomics. Various processes including insertion/deletion and inversion could cause the degeneration of CHSs. Results Here we present a Java software CHSMiner that detects CHSs based on shared gene content alone. It implements fast greedy search algorithm and rigorous statistical validation, and its friendly graphical interface allows interactive visualization of the results. We tested the software on both simulated and biological realistic data and compared its performance with similar existing software and data source. Conclusion CHSMiner is characterized by its integrated workflow, fast speed and convenient usage. It will be useful for both experimentalists and bioinformaticians interested in the structure and evolution of genomes.

  17. On the homology of the shoulder girdle in turtles.

    Science.gov (United States)

    Nagashima, Hiroshi; Sugahara, Fumiaki; Takechi, Masaki; Sato, Noboru; Kuratani, Shigeru

    2015-05-01

    The shoulder girdle in turtles is encapsulated in the shell and has a triradiate morphology. Due to its unique configuration among amniotes, many theories have been proposed about the skeletal identities of the projections for the past two centuries. Although the dorsal ramus represents the scapular blade, the ventral two rami remain uncertain. In particular, the ventrorostral process has been compared to a clavicle, an acromion, and a procoracoid based on its morphology, its connectivity to the rest of the skeleton and to muscles, as well as with its ossification center, cell lineage, and gene expression. In making these comparisons, the shoulder girdle skeleton of anurans has often been used as a reference. This review traces the history of the debate on the homology of the shoulder girdle in turtles. And based on the integrative aspects of developmental biology, comparative morphology, and paleontology, we suggest acromion and procoracoid identities for the two ventral processes.

  18. 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.

  19. Homology of head sclerites in Burgess Shale euarthropods.

    Science.gov (United States)

    Ortega-Hernández, Javier

    2015-06-15

    The Cambrian fossil record of euarthropods (extant arachnids, myriapods, crustaceans, hexapods) has played a major role in understanding the origins of these successful animals and indicates that early ancestors underwent an evolutionary transition from soft-bodied taxa (lobopodians) to more familiar sclerotized forms with jointed appendages [1-3]. Recent advances in paleoneurology and developmental biology show that this major transformation is reflected by substantial changes in the head region of early euarthropods, as informed by the segmental affinity of the cephalic appendages [1, 4-6]. However, data on the implications of this reorganization for non-appendicular exoskeletal structures are lacking, given the difficulty of inferring the precise segmental affinities of these features. Here, I report neurological remains associated with the stalked eyes and "anterior sclerite" in the (middle Cambrian) Burgess Shale euarthropods Helmetia expansa and Odaraia alata and provide evidence that these features are associated with nerve traces originating from the anterior brain region, the protocerebrum. The position of the protocerebral ganglia in exceptionally preserved Cambrian euarthropods indicates the homology of the anterior sclerite in extinct groups (e.g., fuxianhuiids, bivalved forms, artiopodans [7, 8]) and allows new comparisons with the dorsal cephalic plate of radiodontans, large nektonic predators whose anterior segmental organization bears fundamental similarities to that of Paleozoic lobopodians [1, 6, 9, 10]. These observations allow reconstruction of the segmental architecture of the head region in the earliest sclerotized euarthropods and demonstrate the deep homology between exoskeletal features in an evolutionary continuum of taxa with distinct types of body organization.

  20. 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...... and discrete logarithms, in particular, we investigate the density of conjugacy classes with relatively prime discrete logarithms....

  1. 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.

  2. 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.

  3. An oleate 12-hydroxylase from Ricinus communis L. is a fatty acyl desaturase homolog

    Energy Technology Data Exchange (ETDEWEB)

    Van De Loo, F.J. [Univ. of Kentucky, Lexington, KY (United States); Broun, P.; Turner, S.; Somerville, C. [Carnegie Institution of Washington, Stanford, CA (United States)

    1995-07-18

    Recent spectroscopic evidence implicating a binuclear iron site at the reaction center of fatty acyl desaturases suggested to us that certain fatty acyl hydroxylases may share significant amino acid sequence similarity with desaturases. To test this theory, we prepared a cDNA library from developing endosperm of the castor-oil plant (Ricinus communis L.) and obtained partial nucleotide sequences for 468 anonymous clones that were not expressed at high levels in leaves, a tissue deficient in 12-hydroxyoleic acid. This resulted in the identification of several cDNA clones encoding a polypeptide of 387 amino acids with a predicted molecular weight of 44,407 and with {approx}67% sequence homology to microsomal oleate desaturase from Arabidopsis. Expression of a full-length clone under control of the cauliflower mosaic virus 35S promoter in transgenic tobacco resulted in the accumulation of low levels of 12-hydroxyoleic acid in seeds, indicating that the clone encodes the castor oleate hydroxylase. These results suggest that fatty acyl desaturases and hydroxylases share similar reaction mechanisms and provide an example of enzyme evolution. 26 refs., 6 figs., 1 tab.

  4. Rhes, the Ras homolog enriched in striatum, is reduced under conditions of dopamine supersensitivity.

    Science.gov (United States)

    Harrison, L M; LaHoste, G J

    2006-01-01

    Striatal dopamine receptors become supersensitive when dopaminergic input is removed through either surgical denervation or pharmacological depletion. Although alterations such as increased D2 receptor binding and increased receptor-G protein coupling have been described in supersensitive striatal tissue, their roles in the mechanism of supersensitivity remain uncertain. The Ras Homolog Enriched in Striatum (Rhes) is expressed in brain areas that receive dopaminergic input, and here we test whether alterations in its expression accompany treatments that promote dopamine receptor supersensitivity in rats. Removal of dopamine input to the striatum by surgical denervation with 6-hydroxydopamine resulted in a decrease in rhes mRNA expression throughout striatum, as measured with quantitative in situ hybridization. The decrease was detected as early as two weeks and as late as seven months after surgery. Furthermore, a decrease in rhes mRNA was evident after repeated or acute reserpine treatment. Chronic daily injection of rats with the D2 antagonist eticlopride, which is known to up-regulate D2 receptors without inducing profound receptor supersensitivity, did not alter the expression of rhes mRNA in striatum. Thus, changes in rhes mRNA expression are strictly correlated with receptor supersensitivity, perhaps as a result of continuous removal of dopaminergic input. These findings suggest that rhes mRNA expression is maintained by dopamine and may play a role in determining normal dopamine receptor sensitivity.

  5. 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.

  6. A New First Class Algebra, Homological Perturbation and Extension of Pure Spinor Formalism for Superstring

    CERN Document Server

    Aisaka, Y; Aisaka, Yuri; Kazama, Yoichi

    2003-01-01

    Based on a novel first class algebra, we develop an extension of the pure spinor (PS) formalism of Berkovits, in which the PS constraints are removed. By using the homological perturbation theory in an essential way, the BRST-like charge $Q$ of the conventional PS formalism is promoted to a bona fide nilpotent charge $\\hat{Q}$, the cohomology of which is equivalent to the constrained cohomology of $Q$. This construction requires only a minimum number (five) of additional fermionic ghost-antighost pairs and the vertex operators for the massless modes of open string are obtained in a systematic way. Furthermore, we present a simple composite "$b$-ghost" field $B(z)$ which realizes the important relation $T(z) = \\{\\hat{Q}, B(z)\\} $, with $T(z)$ the Virasoro operator, and apply it to facilitate the construction of the integrated vertex. The present formalism utilizes U(5) parametrization and the manifest Lorentz covariance is yet to be achieved.

  7. Employing libraries of zinc finger artificial transcription factors to screen for homologous recombination mutants in Arabidopsis.

    Science.gov (United States)

    Lindhout, Beatrice I; Pinas, Johan E; Hooykaas, Paul J J; van der Zaal, Bert J

    2006-11-01

    A library of genes for zinc finger artificial transcription factors (ZF-ATF) was generated by fusion of DNA sequences encoding three-finger Cys(2)His(2) ZF domains to the VP16 activation domain under the control of the promoter of the ribosomal protein gene RPS5A from Arabidopsis thaliana. After introduction of this library into an Arabidopsis homologous recombination (HR) indicator line, we selected primary transformants exhibiting multiple somatic recombination events. After PCR-mediated rescue of ZF sequences, reconstituted ZF-ATFs were re-introduced in the target line. In this manner, a ZF-ATF was identified that led to a 200-1000-fold increase in somatic HR (replicated in an independent second target line). A mutant plant line expressing the HR-inducing ZF-ATF exhibited increased resistance to the DNA-damaging agent bleomycin and was more sensitive to methyl methanesulfonate (MMS), a combination of traits not described previously. Our results demonstrate that the use of ZF-ATF pools is highly rewarding when screening for novel dominant phenotypes in Arabidopsis.

  8. Origin and concept of medicine food homology and its application in modern functional foods.

    Science.gov (United States)

    Hou, Yan; Jiang, Jian-Guo

    2013-12-01

    The viewpoints of "medicine food homology" (MFH) conform to today's food requirements of returning to a natural and green healthy life. This paper aims to introduce the concept of MFH and its origin and evolution, and analyze the relationship between food and Chinese medicine. In this review, more than 80 MFH materials approved by China's Ministry of Health are listed and their effective ingredients are summarized in detail. Their treatment mechanism in TCM and western medicine are summarized too. Moreover, some new MFH resources that have been gradually developed are also introduced. MFH materials are a treasure house of functional factors for current functional foods. Innovative ideas for the development of MFH resources in current functional foods are prospected and discussed, such as taking advantage of Chinese diet theory, building a database for MFH varieties and developing new methods and technologies. At present, modern research for the development of MFH functional foods is still in its primary stage, there is still much work required in the popularization of the MFH concept and the development of new products. Knowledge and technological innovations in this area should be accelerated in the future to promote the modernization of MFH.

  9. 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.

  10. Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.

    Science.gov (United States)

    Wan, Li; Han, Jinhua; Liu, Ting; Dong, Shunli; Xie, Feng; Chen, Hongxia; Huang, Jun

    2013-06-25

    The Bloom syndrome gene product, BLM, is a member of the highly conserved RecQ family. An emerging concept is the BLM helicase collaborates with the homologous recombination (HR) machinery to help avoid undesirable HR events and to achieve a high degree of fidelity during the HR reaction. However, exactly how such coordination occurs in vivo is poorly understood. Here, we identified a protein termed SPIDR (scaffolding protein involved in DNA repair) as the link between BLM and the HR machinery. SPIDR independently interacts with BLM and RAD51 and promotes the formation of a BLM/RAD51-containing complex of biological importance. Consistent with its role as a scaffolding protein for the assembly of BLM and RAD51 foci, cells depleted of SPIDR show increased rate of sister chromatid exchange and defects in HR. Moreover, SPIDR depletion leads to genome instability and causes hypersensitivity to DNA damaging agents. We propose that, through providing a scaffold for the cooperation of BLM and RAD51 in a multifunctional DNA-processing complex, SPIDR not only regulates the efficiency of HR, but also dictates the specific HR pathway.

  11. TraR, a homolog of a RNAP secondary channel interactor, modulates transcription.

    Directory of Open Access Journals (Sweden)

    Matthew D Blankschien

    2009-01-01

    Full Text Available Recent structural and biochemical studies have identified a novel control mechanism of gene expression mediated through the secondary channel of RNA Polymerase (RNAP during transcription initiation. Specifically, the small nucleotide ppGpp, along with DksA, a RNAP secondary channel interacting factor, modifies the kinetics of transcription initiation, resulting in, among other events, down-regulation of ribosomal RNA synthesis and up-regulation of several amino acid biosynthetic and transport genes during nutritional stress. Until now, this mode of regulation of RNAP was primarily associated with ppGpp. Here, we identify TraR, a DksA homolog that mimics ppGpp/DksA effects on RNAP. First, expression of TraR compensates for dksA transcriptional repression and activation activities in vivo. Second, mutagenesis of a conserved amino acid of TraR known to be critical for DksA function abolishes its activity, implying both structural and functional similarity to DksA. Third, unlike DksA, TraR does not require ppGpp for repression of the rrnB P1 promoter in vivo and in vitro or activation of amino acid biosynthesis/transport genes in vivo. Implications for DksA/ppGpp mechanism and roles of TraR in horizontal gene transfer and virulence are discussed.

  12. 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.

  13. RICE SUCROSE SYNTHASE PROMOTER

    DEFF Research Database (Denmark)

    2000-01-01

    A promoter is described. The promoter comprises a nucleotide sequence corresponding to that shown as SEQ ID No. 1 or a variant, homologue or derivative thereof.......A promoter is described. The promoter comprises a nucleotide sequence corresponding to that shown as SEQ ID No. 1 or a variant, homologue or derivative thereof....

  14. Chromosome painting reveals asynaptic full alignment of homologs and HIM-8-dependent remodeling of X chromosome territories during Caenorhabditis elegans meiosis.

    Directory of Open Access Journals (Sweden)

    Kentaro Nabeshima

    2011-08-01

    Full Text Available 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.

  15. Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas.

    Science.gov (United States)

    Pryor, Jennifer G; Simon, Rochelle A; Bourne, Patricia A; Spaulding, Betsy O; Scott, Glynis A; Xu, Haodong

    2009-02-01

    Merkel cell carcinoma is an uncommon and aggressive primary cutaneous neuroendocrine carcinoma with a high rate of recurrence and metastasis. Optimal management is controversial; consequently, it is imperative to identify the signaling pathways involved in the pathogenesis of Merkel cell carcinoma so that effective therapeutic targeting agents can be developed. We previously reported that K homology domain-containing protein overexpressed in cancer is expressed in high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. The K homology domain-containing protein overexpressed in cancer (KOC), also known as L523S and IMP-3, is an insulin-like growth factor II messenger RNA-binding protein that promotes tumor cell proliferation by enhancing insulin-like growth factor II protein expression. Expression of KOC in Merkel cell carcinoma has not been investigated. We studied 20 Merkel cell carcinomas by immunohistochemistry using a monoclonal antibody against L523S/KOC. Of 20 Merkel cell carcinomas, 18 (90%) overexpressed KOC, with 11 (55%) overexpressing KOC in greater than 90% of tumor cells, 3 (15%) overexpressing KOC in 50% to 90% of tumor cells, 3 (15%) overexpressing KOC in 10% to 50% of tumor cells, and 1 (5%) overexpressing KOC in less than 10% of tumor cells. The immunostaining intensity was variable, with moderate to strong staining in 14 cases and weak staining in the remaining 4. Extent of expression of K homology domain-containing protein overexpressed in cancer predicted metastasis (P = .04) and was weakly correlated with increased tumor size (P = .08). In conclusion, Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer with an expression pattern similar to high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. We propose K homology domain-containing protein overexpressed in cancer as a potential target molecule for the treatment of high

  16. 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

  17. 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

  18. Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53

    Science.gov (United States)

    Chao, Tengfei; Zhou, Xiang; Cao, Bo; Liao, Peng; Liu, Hongbing; Chen, Yun; Park, Hee-Won; Zeng, Shelya X.; Lu, Hua

    2016-01-01

    The tumour suppressor p53 transactivates the expression of its target genes to exert its functions. Here, we identify a pleckstrin homology domain-containing protein (PHLDB3)-encoding gene as a p53 target. PHLDB3 overexpression increases proliferation and restrains apoptosis of wild-type p53-harboring cancer cells by reducing p53 protein levels. PHLDB3 binds to MDM2 (mouse double minute 2 homolog) and facilitates MDM2-mediated ubiquitination and degradation of p53. Knockdown of PHLDB3 more efficiently inhibits the growth of mouse xenograft tumours derived from human colon cancer HCT116 cells that contain wild type p53 compared with p53-deficient HCT116 cells, and also sensitizes tumour cells to doxorubicin and 5-Fluorouracil. Analysis of cancer genomic databases reveals that PHLDB3 is amplified and/or highly expressed in numerous human cancers. Altogether, these results demonstrate that PHLDB3 promotes tumour growth by inactivating p53 in a negative feedback fashion and suggest PHLDB3 as a potential therapeutic target in various human cancers. PMID:28008906

  19. 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.

  20. Mapping of wheat mitochondrial mRNA termini and comparison with breakpoints in DNA homology among plants.

    Science.gov (United States)

    Choi, Boyoung; Acero, Maria M; Bonen, Linda

    2012-11-01

    Mitochondrial DNA rearrangements occur very frequently in flowering plants and when close to genes there must be concomitant acquisition of new regulatory cis-elements. To explore whether there might be limits to such DNA shuffling, we have mapped the termini of mitochondrial mRNAs in wheat, a monocot, and compared them to the known positions for counterpart genes in the eudicot Arabidopsis. Nine genes share homologous 3' UTRs over their full-length and for six of them, the termini map very close to the site of wheat/Arabidopsis DNA rearrangements. Only one such case was seen for comparisons of 5' UTRs, and the 5' ends of mRNAs are typically more heterogeneous than 3' termini. Approximately half of the thirty-one wheat mitochondrial transcriptional units are preceded by CRTA promoter-like motifs, and of the potential stem-loop or tRNA-like structures identified as candidate RNA processing/stability signals near the 5' or 3' ends, several are shared with Arabidopsis. Comparison of the mitochondrial gene flanking sequences from normal fertile wheat (Triticum aestivum) with those of Aegilops kotschyi which is the source of mitochondria present in K-type cytoplasmic male sterile wheat, revealed six cases where mRNAs are precluded from sharing full-length homologous UTRs because of genomic reorganization events, and the presence of short repeats located at the sites of discontinuity points to a reciprocal recombination-mediated mode of rearrangement.

  1. Biological activities of the homologous loop regions in the laminin α chain LG modules.

    Science.gov (United States)

    Katagiri, Fumihiko; Hara, Toshihiro; Yamada, Yuji; Urushibata, Shunsuke; Hozumi, Kentaro; Kikkawa, Yamato; Nomizu, Motoyoshi

    2014-06-10

    Each laminin α chain (α1-α5 chains) has chain-specific diverse biological functions. The C-terminal globular domain of the α chain consists of five laminin-like globular (LG1-5) modules and plays a critical role in biological activities. The LG modules consist of a 14-stranded β-sheet (A-N) sandwich structure. Previously, we described the chain-specific biological activities of the loop regions between the E and F strands in the LG4 modules using five homologous peptides (G4EF1-G4EF5). Here, we further analyze the biological activities of the E-F strands loop regions in the rest of LG modules. We designed 20 homologous peptides (approximately 20 amino acid length), and 17 soluble peptides were used for the cell attachment assay. Thirteen peptides promoted cell attachment activity with different cell morphologies. Cell attachment to peptides G1EF1, G1EF2, G2EF1, G3EF4, and G5EF4 was inhibited by heparin, and peptides G1EF1, G1EF2, and G2EF1 specifically bound to syndecan-overexpressing cells. Cell attachment to peptides G2EF3, G3EF1, G3EF3, G5EF1, G5EF3, and G5EF5 was inhibited EDTA. Further, cell attachment to peptides G3EF3, G5EF1, and G5EF5 was inhibited by both anti-integrin α2 and β1 antibodies, whereas cell attachment to peptide G5EF3 was inhibited by only anti-integrin β1 antibody. Cell attachment to peptides G1EF4, G3EF4, and G5EF4 was inhibited by both heparin and EDTA and was not inhibited by anti-integrin antibodies. The active peptide sequence alignments suggest that the syndecan-binding peptides contain a "basic amino acid (BAA)-Gly-BAA" motif in the middle of the molecule and that the integrin-binding peptides contain an "acidic amino acid (AAA)"-Gly-BAA motif. Core-switched peptide analyses suggested that the "BAA-Gly-BAA" motif is critical for binding to syndecans and that the "AAA-Gly-BAA" motif has potential to recognize integrins. These findings are useful for understanding chain-specific biological activities of laminins and to evaluate

  2. Hd3a promotes lateral branching in rice.

    Science.gov (United States)

    Tsuji, Hiroyuki; Tachibana, Chika; Tamaki, Shojiro; Taoka, Ken-Ichiro; Kyozuka, Junko; Shimamoto, Ko

    2015-04-01

    Accumulating evidence indicates that the FLOWERING LOCUS T (FT) protein is the mobile floral signal known as florigen. A rice FT homolog, Heading date 3a (Hd3a), is transported from the phloem to shoot apical cells, where it interacts with 14-3-3 proteins and transcription factor OsFD1 to form a florigen activation complex (FAC) that activates a rice homolog of the floral identity gene APETALA1. Recent studies showed that florigen has roles in plant development beyond flowering; however, the exact nature of these roles is not well understood. It is not clear whether FT is transported to organs outside the shoot apex, and whether FAC formation is required for processes other than flowering. We show here that the Hd3a protein accumulates in axillary meristems to promote branching, and that FAC formation is required. Analysis of transgenic plants revealed that Hd3a promotes branching through lateral bud outgrowth. Hd3a protein produced in the phloem reached the axillary meristem in the lateral bud, and its transport was required for promotion of branching. Moreover, mutant Hd3a proteins defective in FAC formation but competent with respect to transport did not promote branching. Finally, we show that Hd3a promotes branching independently from strigolactone and FC1, a transcription factor that inhibits branching in rice. Together, these results suggest that Hd3a functions as a mobile signal for branching in rice.

  3. Human SIRT6 promotes DNA end resection through CtIP deacetylation

    DEFF Research Database (Denmark)

    Kaidi, Abderrahmane; Weinert, Brian T; Choudhary, Chunaram

    2010-01-01

    SIRT6 belongs to the sirtuin family of protein lysine deacetylases, which regulate aging and genome stability. We found that human SIRT6 has a role in promoting DNA end resection, a crucial step in DNA double-strand break (DSB) repair by homologous recombination. SIRT6 depletion impaired...... the accumulation of replication protein A and single-stranded DNA at DNA damage sites, reduced rates of homologous recombination, and sensitized cells to DSB-inducing agents. We identified the DSB resection protein CtIP [C-terminal binding protein (CtBP) interacting protein] as a SIRT6 interaction partner...... and showed that SIRT6-dependent CtIP deacetylation promotes resection. A nonacetylatable CtIP mutant alleviated the effect of SIRT6 depletion on resection, thus identifying CtIP as a key substrate by which SIRT6 facilitates DSB processing and homologous recombination. These findings further clarify how SIRT6...

  4. A somatic origin of homologous Robertsonian translocations and isochromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Schinzel, A.A. (Univ. of Zurich (Switzerland)); Basaran, S.; Yueksel-Apak, M. (Univ. of Istanbul (Turkey)); Neri, G. (Universita Cattolica, Rome (Italy)); Serville, F. (Hopital d' Enfants Pellegrin, Bordeaux (France)); Balicek, P.; Haluza, R. (Univ. Hospital of Hradeck Kralove, Hradec Kralove (Czech Republic)); Farah, L.M.S. (Escuola Paulista de Medicina, Sao Paulo (Brazil)) (and others)

    1994-02-01

    One t(14q 14q), three t(15q 15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange. 75 refs., 1 fig., 4 tabs.

  5. Cytoarchitecture of mouse and rat cingulate cortex with human homologies.

    Science.gov (United States)

    Vogt, Brent A; Paxinos, George

    2014-01-01

    A gulf exists between cingulate area designations in human neurocytology and those used in rodent brain atlases with a major underpinning of the former being midcingulate cortex (MCC). The present study used images extracted from the Franklin and Paxinos mouse atlas and Paxinos and Watson rat atlas to demonstrate areas comprising MCC and modifications of anterior cingulate (ACC) and retrosplenial cortices. The laminar architecture not available in the atlases is also provided for each cingulate area. Both mouse and rat have a MCC with neurons in all layers that are larger than in ACC and layer Va has particularly prominent neurons and reduced neuron densities. An undifferentiated ACC area 33 lies along the rostral callosal sulcus in rat but not in mouse and area 32 has dorsal and ventral subdivisions with the former having particularly large pyramidal neurons in layer Vb. Both mouse and rat have anterior and posterior divisions of retrosplenial areas 29c and 30, although their cytology is different in rat and mouse. Maps of the rodent cingulate cortices provide for direct comparisons with each region in the human including MCC and it is significant that rodents do not have a posterior cingulate region composed of areas 23 and 31 like the human. It is concluded that rodents and primates, including humans, possess a MCC and this homology along with those in ACC and retrosplenial cortices permit scientists inspired by human considerations to test hypotheses on rodent models of human diseases.

  6. Tomato FRUITFULL homologs regulate fruit ripening via ethylene biosynthesis.

    Science.gov (United States)

    Shima, Yoko; Fujisawa, Masaki; Kitagawa, Mamiko; Nakano, Toshitsugu; Kimbara, Junji; Nakamura, Nobutaka; Shiina, Takeo; Sugiyama, Junichi; Nakamura, Toshihide; Kasumi, Takafumi; Ito, Yasuhiro

    2014-01-01

    Certain MADS-box transcription factors play central roles in regulating fruit ripening. RIPENING INHIBITOR (RIN), a tomato MADS-domain protein, acts as a global regulator of ripening, affecting the climacteric rise of ethylene, pigmentation changes, and fruit softening. Previously, we showed that two MADS-domain proteins, the FRUITFULL homologs FUL1 and FUL2, form complexes with RIN. Here, we characterized the FUL1/FUL2 loss-of-function phenotype in co-suppressed plants. The transgenic plants produced ripening-defective fruits accumulating little or no lycopene. Unlike a previous study on FUL1/FUL2 suppressed tomatoes, our transgenic fruits showed very low levels of ethylene production, and this was associated with suppression of the genes for 1-aminocyclopropane-1-carboxylic acid synthase, a rate-limiting enzyme in ethylene synthesis. FUL1/FUL2 suppression also caused the fruit to soften in a manner independent of ripening, possibly due to reduced cuticle thickness in the peel of the suppressed tomatoes.

  7. 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.

  8. 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.

  9. 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.

  10. A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation

    DEFF Research Database (Denmark)

    Luijsterburg, Martijn S; Typas, Dimitris; Caron, Marie-Christine

    2017-01-01

    DNA double-strand breaks (DSB) elicit a ubiquitylation cascade that controls DNA repair pathway choice. This cascade involves the ubiquitylation of histone H2A by the RNF168 ligase and the subsequent recruitment of RIF1, which suppresses homologous recombination (HR) in G1 cells. The RIF1-dependent...... recognizes histone ubiquitylation by physically associating with ubiquitin-bound RNF168. This direct interaction is mediated by the newly identified PALB2-interacting domain (PID) in RNF168 and the WD40 domain in PALB2, and drives DNA repair by facilitating the assembly of PALB2-containing HR complexes...... at DSBs. Our findings demonstrate that RNF168 couples PALB2-dependent HR to H2A ubiquitylation to promote DNA repair and preserve genome integrity....

  11. 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.

  12. Three Approaches in Computational Geometry and Topology : Persistent Homology, Discrete Differential Geometry and Discrete Morse Theory

    OpenAIRE

    Botnan, Magnus Bakke

    2011-01-01

    We study persistent homology, methods in discrete differential geometry and discrete Morse theory. Persistent homology is applied to computational biology and range image analysis. Theory from differential geometry is used to define curvature estimates of triangulated hypersurfaces. In particular, a well-known method for triangulated surfacesis generalised to hypersurfaces of any dimension. The thesis concludesby discussing a discrete analogue of Morse theory.

  13. Non-O1 Vibrio cholerae in Thailand: homology with cloned cholera toxin genes.

    OpenAIRE

    Hanchalay, S; Seriwatana, J; Echeverria, P.; Holmgren, J.; Tirapat, C.; Moseley, S L; Taylor, D N

    1985-01-01

    We examined 281 non-O1 Vibrio cholerae isolates from Thailand for homology with genes coding for cholera toxin. Five isolates from environmental sources were homologous with the cholera toxin gene probe and produced both the A and B subunits of cholera toxin.

  14. 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...

  15. In vivo importance of homologous recombination DNA repair for mouse neural stem and progenitor cells

    NARCIS (Netherlands)

    L. Rousseau (Laure); O. Etienne (Olivier); T. Roque (Telma); C. Desmaze (Chantal); C. Haton (Céline); M.-A. Mouthon (Marc-André.); J. Bernardino-Sgherri (Jacqueline); J. Essers (Jeroen); R. Kanaar (Roland); F.D. Boussin (François)

    2012-01-01

    textabstractWe characterized the in vivo importance of the homologous recombination factor RAD54 for the developing mouse brain cortex in normal conditions or after ionizing radiation exposure. Contrary to numerous homologous recombination genes, Rad54 disruption did not impact the cortical developm

  16. Nuclear dynamics of RAD52 group homologous recombination proteins in response to DNA damage.

    NARCIS (Netherlands)

    J. Essers (Jeroen); A.B. Houtsmuller (Adriaan); L.R. van Veelen (Lieneke); C. Paulusma (Coen); A.L. Nigg (Alex); A. Pastink (Albert); W. Vermeulen (Wim); J.H.J. Hoeijmakers (Jan); R. Kanaar (Roland)

    2002-01-01

    textabstractRecombination between homologous DNA molecules is essential for the proper maintenance and duplication of the genome, and for the repair of exogenously induced DNA damage such as double-strand breaks. Homologous recombination requires the RAD52 group proteins, including Rad51, Rad52 and

  17. Semi-algebraic partition and basis of Borel-Moore homology of hyperplane arrangements

    CERN Document Server

    Ito, Ko-Ki

    2011-01-01

    We describe an explicit semi-algebraic partition for the complement of the hyperplane arrangement such that each piece is contractible and forms a basis of Borel-Moore homology. We also give explicit correspondence between the de Rham cohomology and the Borel-Moore homology.

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

    CERN Document Server

    Kumjian, Alex; 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 of a k-graph by a T-valued 2-cocycle and demonstrate that examples include all noncommutative tori. In the appendices, we construct a cubical set \\tilde{Q}(\\Lambda) from a k-graph {\\Lambda} and demonstrate that the homology and topological realisation of {\\Lambda} coincide with those of \\tilde{Q}(\\Lambda) as defined by Grandis.

  19. Intraspecies biodiversity of the genetically homologous species Brucella microti.

    Science.gov (United States)

    Al Dahouk, Sascha; Hofer, Erwin; Tomaso, Herbert; Vergnaud, Gilles; Le Flèche, Philippe; Cloeckaert, Axel; Koylass, Mark S; Whatmore, Adrian M; Nöckler, Karsten; Scholz, Holger C

    2012-03-01

    Brucellosis is one of the major bacterial zoonoses worldwide. In the past decade, an increasing number of atypical Brucella strains and species have been described. Brucella microti in particular has attracted attention, because this species not only infects mammalian hosts but also persists in soil. An environmental reservoir may pose a new public health risk, leading to the reemergence of brucellosis. In a polyphasic approach, comprising conventional microbiological techniques and extensive biochemical and molecular techniques, all currently available Brucella microti strains were characterized. While differing in their natural habitats and host preferences, B. microti isolates were found to possess identical 16S rRNA, recA, omp2a, and omp2b gene sequences and identical multilocus sequence analysis (MLSA) profiles at 21 different genomic loci. Only highly variable microsatellite markers of multiple-locus variable-number tandem repeat (VNTR) analysis comprising 16 loci (MLVA-16) showed intraspecies discriminatory power. In contrast, biotyping demonstrated striking differences within the genetically homologous species. The majority of the mammalian isolates agglutinated only with monospecific anti-M serum, whereas soil isolates agglutinated with anti-A, anti-M, and anti-R sera. Bacteria isolated from animal sources were lysed by phages F1, F25, Tb, BK2, Iz, and Wb, whereas soil isolates usually were not. Rough strains of environmental origin were lysed only by phage R/C. B. microti exhibited high metabolic activities similar to those of closely related soil organisms, such as Ochrobactrum spp. Each strain was tested with 93 different substrates and showed an individual metabolic profile. In summary, the adaptation of Brucella microti to a specific habitat or host seems to be a matter of gene regulation rather than a matter of gene configuration.

  20. Homologous recombination in Sulfolobus acidocaldarius: genetic assays and functional properties.

    Science.gov (United States)

    Grogan, Dennis W

    2009-02-01

    HR (homologous recombination) is expected to play important roles in the molecular biology and genetics of archaea, but, so far, few functional properties of archaeal HR have been measured in vivo. In the extreme thermoacidophile Sulfolobus acidocaldarius, a conjugational mechanism of DNA transfer enables quantitative analysis of HR between chromosomal markers. Early studies of this system indicated that HR occurred frequently between closely spaced mutations within the pyrE gene, and this result was later supported by various analyses involving defined point mutations and deletions. These properties of intragenic HR suggested a non-reciprocal mechanism in which donor sequences become incorporated into the recipient genome as short segments. Because fragmentation of donor DNA during cell-to-cell transfer could not be excluded from contributing to this result, subsequent analyses have focused on electroporation of selectable donor DNA directly into recipient strains. For example, S. acidocaldarius was found to incorporate synthetic ssDNA (single-stranded DNA) of more than approximately 20 nt readily into its genome. With respect to various molecular properties of the ssDNA substrates, the process resembled bacteriophage lambdaRed-mediated 'recombineering' in Escherichia coli. Another approach used electroporation of a multiply marked pyrE gene to measure donor sequence tracts transferred to the recipient genome in individual recombination events. Initial results indicate multiple discontinuous tracts in the majority of recombinants, representing a relatively broad distribution of tract lengths. This pattern suggests that properties of the HR process could, in principle, account for many of the apparent peculiarities of intragenic recombination initiated by S. acidocaldarius conjugation.

  1. Homologous radioimmunoassay for human epidermal growth factor (urogastrone)

    Energy Technology Data Exchange (ETDEWEB)

    Dailey, G.E.; Kraus, J.W.; Orth, D.N.

    1978-06-01

    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) ..mu..g/total vol, or 29.7 +- 1.1 and 39.8 +- 1.7 ..mu..g/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +- 2.7 ..mu..g/g creatinine; P < 0.01) than that by females who were not. Recent evidence suggests the probable identity of hEGF and ..beta..-urogastrone, a potent inhibitor of gastric acid secretion. Adult males with active peptic ulcer disease appeared to have lower urinary RIA-hEGF excretion (22.9 +- 2.6 ..mu..g/g creatinine) than normal men, but this was not significant (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.

  2. 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.

  3. Homology between nucleotide sequences of promoter regions of nah and sal operons of NAH7 plasmid of Pseudomonas putida.

    OpenAIRE

    1986-01-01

    The in vivo transcription start sites of the nah and sal operons of the NAH7 plasmid were determined by S1 nuclease mapping and the nucleotide sequence surrounding these transcription start sites was determined. Since expression of both of these operons is coordinately controlled by the product of the transcriptional activator gene nahR, the sequences were compared to locate potential sites involved in common regulation. In the 100-base-pair region preceding transcription start sites of both ...

  4. 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

    repair (HRR), their precise role(s) within this pathway remains poorly understood. Here, we have identified a specific role for the Shu proteins in a Rad51/Rad54-dependent HRR pathway(s) to repair MMS-induced lesions during S-phase. We show that, although mutation of RAD51 or RAD54 prevented...

  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)

    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.

  6. Promoting preschool reading

    OpenAIRE

    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 ...

  7. Archaeal Tuc1/Ncs6 homolog required for wobble uridine tRNA thiolation is associated with ubiquitin-proteasome, translation, and RNA processing system homologs.

    Directory of Open Access Journals (Sweden)

    Nikita E Chavarria

    Full Text Available While cytoplasmic tRNA 2-thiolation protein 1 (Tuc1/Ncs6 and ubiquitin-related modifier-1 (Urm1 are important in the 2-thiolation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U at wobble uridines of tRNAs in eukaryotes, the biocatalytic roles and properties of Ncs6/Tuc1 and its homologs are poorly understood. Here we present the first report of an Ncs6 homolog of archaea (NcsA of Haloferax volcanii that is essential for maintaining cellular pools of thiolated tRNA(LysUUU and for growth at high temperature. When purified from Hfx. volcanii, NcsA was found to be modified at Lys204 by isopeptide linkage to polymeric chains of the ubiquitin-fold protein SAMP2. The ubiquitin-activating E1 enzyme homolog of archaea (UbaA was required for this covalent modification. Non-covalent protein partners that specifically associated with NcsA were also identified including UbaA, SAMP2, proteasome activating nucleotidase (PAN-A/1, translation elongation factor aEF-1α and a β-CASP ribonuclease homolog of the archaeal cleavage and polyadenylation specificity factor 1 family (aCPSF1. Together, our study reveals that NcsA is essential for growth at high temperature, required for formation of thiolated tRNA(LysUUU and intimately linked to homologs of ubiquitin-proteasome, translation and RNA processing systems.

  8. 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…

  9. Physicochemical property distributions for accurate and rapid pairwise protein homology detection

    Directory of Open Access Journals (Sweden)

    Oehmen Christopher S

    2010-03-01

    Full Text Available Abstract Background The challenge of remote homology detection is that many evolutionarily related sequences have very little similarity at the amino acid level. Kernel-based discriminative methods, such as support vector machines (SVMs, that use vector representations of sequences derived from sequence properties have been shown to have superior accuracy when compared to traditional approaches for the task of remote homology detection. Results We introduce a new method for feature vector representation based on the physicochemical properties of the primary protein sequence. A distribution of physicochemical property scores are assembled from 4-mers of the sequence and normalized based on the null distribution of the property over all possible 4-mers. With this approach there is little computational cost associated with the transformation of the protein into feature space, and overall performance in terms of remote homology detection is comparable with current state-of-the-art methods. We demonstrate that the features can be used for the task of pairwise remote homology detection with improved accuracy versus sequence-based methods such as BLAST and other feature-based methods of similar computational cost. Conclusions A protein feature method based on physicochemical properties is a viable approach for extracting features in a computationally inexpensive manner while retaining the sensitivity of SVM protein homology detection. Furthermore, identifying features that can be used for generic pairwise homology detection in lieu of family-based homology detection is important for applications such as large database searches and comparative genomics.

  10. Statistical inference of chromosomal homology based on gene colinearity and applications to Arabidopsis and rice

    Directory of Open Access Journals (Sweden)

    Zhu Qihui

    2006-10-01

    Full Text Available Abstract Background The identification of chromosomal homology will shed light on such mysteries of genome evolution as DNA duplication, rearrangement and loss. Several approaches have been developed to detect chromosomal homology based on gene synteny or colinearity. However, the previously reported implementations lack statistical inferences which are essential to reveal actual homologies. Results In this study, we present a statistical approach to detect homologous chromosomal segments based on gene colinearity. We implement this approach in a software package ColinearScan to detect putative colinear regions using a dynamic programming algorithm. Statistical models are proposed to estimate proper parameter values and evaluate the significance of putative homologous regions. Statistical inference, high computational efficiency and flexibility of input data type are three key features of our approach. Conclusion We apply ColinearScan to the Arabidopsis and rice genomes to detect duplicated regions within each species and homologous fragments between these two species. We find many more homologous chromosomal segments in the rice genome than previously reported. We also find many small colinear segments between rice and Arabidopsis genomes.

  11. Loss of glial lazarillo, a homolog of apolipoprotein D, reduces lifespan and stress resistance in Drosophila.

    Science.gov (United States)

    Sanchez, Diego; López-Arias, Begoña; Torroja, Laura; Canal, Inmaculada; Wang, Xiaohui; Bastiani, Michael J; Ganfornina, Maria D

    2006-04-01

    The vertebrate Apolipoprotein D (ApoD) is a lipocalin secreted from subsets of neurons and glia during neural development and aging . A strong correlation exists between ApoD overexpression and numerous nervous system pathologies as well as obesity, diabetes, and many forms of cancer . However, the exact relationship between the function of ApoD and the pathophysiology of these diseases is still unknown. We have generated loss-of-function Drosophila mutants for the Glial Lazarillo (GLaz) gene , a homolog of ApoD in the fruit fly, mainly expressed in subsets of adult glial cells. The absence of GLaz reduces the organism's resistance to oxidative stress and starvation and shortens male lifespan. The mutant flies exhibit a smaller body mass due to a lower amount of neutral lipids stored in the fat body. Apoptotic neural cell death increases in aged flies or upon paraquat treatment, which also impairs neural function as assessed by behavioral tests. The higher sensitivity to oxidative stress and starvation and the reduced fat storage revert to control levels when a GFP-GLaz fusion protein is expressed under the control of the GLaz natural promoter. Finally, GLaz mutants have a higher concentration of lipid peroxidation products, pointing to a lipid peroxidation protection or scavenging as the mechanism of action for this lipocalin. In agreement with Walker et al. (, in this issue of Current Biology), who analyze the effects of overexpressing GLaz, we conclude that GLaz has a protective role in stress situations and that its absence reduces lifespan and accelerates neurodegeneration.

  12. 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.

  13. Notch signaling induces rapid degradation of achaete-scute homolog 1.

    Science.gov (United States)

    Sriuranpong, Virote; Borges, Michael W; Strock, Christopher L; Nakakura, Eric K; Watkins, D Neil; Blaumueller, Christine M; Nelkin, Barry D; Ball, Douglas W

    2002-05-01

    In neural development, Notch signaling plays a key role in restricting neuronal differentiation, promoting the maintenance of progenitor cells. Classically, Notch signaling causes transactivation of Hairy-enhancer of Split (HES) genes which leads to transcriptional repression of neural determination and differentiation genes. We now report that in addition to its known transcriptional mechanism, Notch signaling also leads to rapid degradation of the basic helix-loop-helix (bHLH) transcription factor human achaete-scute homolog 1 (hASH1). Using recombinant adenoviruses expressing active Notch1 in small-cell lung cancer cells, we showed that the initial appearance of Notch1 coincided with the loss of hASH1 protein, preceding the full decay of hASH1 mRNA. Overexpression of HES1 alone was capable of down-regulating hASH1 mRNA but could not replicate the acute reduction of hASH1 protein induced by Notch1. When adenoviral hASH1 was coinfected with Notch1, we still observed a dramatic and abrupt loss of the exogenous hASH1 protein, despite high levels of ongoing hASH1 RNA expression. Notch1 treatment decreased the apparent half-life of the adenoviral hASH1 protein and increased the fraction of hASH1 which was polyubiquitinylated. The proteasome inhibitor MG132 reversed the Notch1-induced degradation. The Notch RAM domain was dispensable but a lack of the OPA and PEST domains inactivated this Notch1 action. Overexpression of the hASH1-dimerizing partner E12 could protect hASH1 from degradation. This novel function of activated Notch to rapidly degrade a class II bHLH protein may prove to be important in many contexts in development and in cancer.

  14. ATM limits incorrect end utilization during non-homologous end joining of multiple chromosome breaks.

    Science.gov (United States)

    Bennardo, Nicole; Stark, Jeremy M

    2010-11-04

    Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ) repair of multiple chromosomal double-strand breaks (DSBs). We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ) or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs). In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI-resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ) factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ.

  15. ATM limits incorrect end utilization during non-homologous end joining of multiple chromosome breaks.

    Directory of Open Access Journals (Sweden)

    Nicole Bennardo

    2010-11-01

    Full Text Available Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ repair of multiple chromosomal double-strand breaks (DSBs. We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs. In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI-resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ.

  16. Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases.

    Science.gov (United States)

    Remy, Séverine; Tesson, Laurent; Menoret, Séverine; Usal, Claire; De Cian, Anne; Thepenier, Virginie; Thinard, Reynald; Baron, Daniel; Charpentier, Marine; Renaud, Jean-Baptiste; Buelow, Roland; Cost, Gregory J; Giovannangeli, Carine; Fraichard, Alexandre; Concordet, Jean-Paul; Anegon, Ignacio

    2014-08-01

    The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%-5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner.

  17. CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor.

    Science.gov (United States)

    Inohara, N; Koseki, T; Chen, S; Wu, X; Núñez, G

    1998-05-01

    DFF45 is a subunit of the DNA fragmentation factor (DFF) that is cleaved by caspase-3 during apoptosis. However, the mechanism by which DFF45 regulates apoptotic cell death remains poorly understood. Here we report the identification and characterization of two mammalian genes, CIDE-A and CIDE-B, encoding highly related proteins with homology to the N-terminal region of DFF45. CIDE-A and CIDE-B were found to activate apoptosis in mammalian cells, which was inhibited by DFF45 but not by caspase inhibitors. Expression of CIDE-A induced DNA fragmentation in 293T cells, which was inhibited by DFF45, further suggesting that DFF45 inhibits the apoptotic activities of CIDEs. In addition to mammalian CIDE-A and CIDE-B, we identified DREP-1, a Drosophila melanogaster homolog of DFF45 that could inhibit CIDE-A-mediated apoptosis. Mutant analysis revealed that the C-terminal region of CIDE-A was necessary and sufficient for killing whereas the region with homology to DFF45 located in the N-terminus was required for DFF45 to inhibit CIDE-A-induced apoptosis. CD95/Fas-mediated apoptosis was enhanced by CIDEs but inhibited by DFF45. These studies suggest that DFF45 is evolutionarily conserved and implicate CIDEs as DFF45-inhibitable effectors that promote cell death and DNA fragmentation.

  18. A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF) and Liver Receptor Homolog-1 (LRH-1).

    Science.gov (United States)

    Weikum, Emily R; Tuntland, Micheal L; Murphy, Michael N; Ortlund, Eric A

    2016-10-27

    Oct4 is a transcription factor required for maintaining pluripotency and self-renewal in stem cells. Prior to differentiation, Oct4 must be silenced to allow for the development of the three germ layers in the developing embryo. This fine-tuning is controlled by the nuclear receptors, liver receptor homolog-1 and germ cell nuclear factor. Liver receptor homolog-1 is responsible for driving the expression of Oct4 where germ cell nuclear factor represses its expression upon differentiation. Both receptors bind to a DR0 motif located within the Oct4 promoter. Here, we present the first structure of mouse germ cell nuclear factor DNA binding domain in complex with the Oct4 DR0. The overall structure revealed two molecules bound in a head-to-tail fashion on opposite sides of the DNA. Additionally, we solved the structure of the human liver receptor homolog-1 DNA binding domain bound to the same element. We explore the structural elements that govern Oct4 recognition by these two nuclear receptors.

  19. Structure/function relationships in RecA protein-mediated homology recognition and strand exchange.

    Science.gov (United States)

    Prentiss, Mara; Prévost, Chantal; Danilowicz, Claudia

    2015-01-01

    RecA family proteins include RecA, Rad51, and Dmc1. These recombinases are responsible for homology search and strand exchange. Homology search and strand exchange occur during double-strand break repair and in eukaryotes during meiotic recombination. In bacteria, homology search begins when RecA binds an initiating single-stranded DNA (ssDNA) in the primary DNA-binding site to form the presynaptic filament. The filament is a right-handed helix, where the initiating strand is bound deep within the filament. Once the presynaptic filament is formed, it interrogates nearby double-stranded DNA (dsDNA) to find a homologous sequence; therefore, we provide a detailed discussion of structural features of the presynaptic filament that play important functional roles. The discussion includes many diagrams showing multiple filament turns. These diagrams illustrate interactions that are not evident in single turn structures. The first dsDNA interactions with the presynaptic filament are insensitive to mismatches. The mismatch insensitive interactions lead to dsDNA deformation that triggers a homology testing process governed by kinetics. The first homology test involves ∼8 bases. Almost all interactions are rejected by this initial rapid test, leading to a new cycle of homology testing. Interactions that pass the initial rapid test proceed to a slower testing stage. That slower stage induces nonhomologous dsDNA to reverse strand exchange and begin a new cycle of homology testing. In contrast, homologous dsDNA continues to extend the heteroduplex strand-exchange product until ATP hydrolysis makes strand exchange irreversible.

  20. 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.

  1. Sequence Conversion by Single Strand Oligonucleotide Donors via Non-homologous End Joining in Mammalian Cells*

    OpenAIRE

    Liu, Jia; Majumdar, Alokes; Liu, Jilan; Thompson, Lawrence H.; Seidman, Michael M.

    2010-01-01

    Double strand breaks (DSBs) can be repaired by homology independent nonhomologous end joining (NHEJ) pathways involving proteins such as Ku70/80, DNAPKcs, Xrcc4/Ligase 4, and the Mre11/Rad50/Nbs1 (MRN) complex. DSBs can also be repaired by homology-dependent pathways (HDR), in which the MRN and CtIP nucleases produce single strand ends that engage homologous sequences either by strand invasion or strand annealing. The entry of ends into HDR pathways underlies protocols for genomic manipulatio...

  2. Health Promotion Education

    DEFF Research Database (Denmark)

    Lehn-Christiansen, Sine

    The paper discusses the implications of health promotion in education. The paper is based on my PhD project entitled “Health promotion education seen through a power/knowledge and subjectification perspective” (in prep). The PhD project explores how professional health promotion skills...... are conceived in a specific educational setting; namely the Danish social and health education programme. Here, health promotion is formally conceived as a qualification aimed at citizens and patients - and not at the students themselves. However, as the paper will demonstrate, conceptions of student...... health promotion workers should ideally act as health promotion role models. This claim leads to a series of educational and morally anchored dilemmas and challenges. Inspired by Foucault and others who have developed this line of thinking (eg. Signild Vallgårde) health promotion is viewed as a heartfelt...

  3. Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1

    Directory of Open Access Journals (Sweden)

    Hwa Young Ahn

    2015-12-01

    Full Text Available BackgroundExpression of hepatic cholesterol 7α-hydroxylase (CYP7A1 is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP. In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1.MethodsWe injected thyroid hormone (triiodothyronine, T3 to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR. Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA were also performed using human hepatoma cell lineResultsInitial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.ConclusionWe found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

  4. Mutations in the human naked cuticle homolog NKD1 found in colorectal cancer alter Wnt/Dvl/beta-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Jianhui Guo

    Full Text Available BACKGROUND: Mutation of Wnt signal antagonists Apc or Axin activates beta-catenin signaling in many cancers including the majority of human colorectal adenocarcinomas. The phenotype of apc or axin mutation in the fruit fly Drosophila melanogaster is strikingly similar to that caused by mutation in the segment-polarity gene, naked cuticle (nkd. Nkd inhibits Wnt signaling by binding to the Dishevelled (Dsh/Dvl family of scaffold proteins that link Wnt receptor activation to beta-catenin accumulation and TCF-dependent transcription, but human NKD genes have yet to be directly implicated in cancer. METHODOLOGY/PRINCIPAL FINDINGS: We identify for the first time mutations in NKD1--one of two human nkd homologs--in a subset of DNA mismatch repair-deficient colorectal tumors that are not known to harbor mutations in other Wnt-pathway genes. The mutant Nkd1 proteins are defective at inhibiting Wnt signaling; in addition, the mutant Nkd1 proteins stabilize beta-catenin and promote cell proliferation, in part due to a reduced ability of each mutant Nkd1 protein to bind and destabilize Dvl proteins. CONCLUSIONS/SIGNIFICANCE: Our data raise the hypothesis that specific NKD1 mutations promote Wnt-dependent tumorigenesis in a subset of DNA mismatch-repair-deficient colorectal adenocarcinomas and possibly other Wnt-signal driven human cancers.

  5. CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes.

    Directory of Open Access Journals (Sweden)

    Hideaki Ogiwara

    Full Text Available Histone acetylation at DNA double-strand break (DSB sites by CBP and p300 histone acetyltransferases (HATs is critical for the recruitment of DSB repair proteins to chromatin. Here, we show that CBP and p300 HATs also function in DSB repair by transcriptionally activating the BRCA1 and RAD51 genes, which are involved in homologous recombination (HR, a major DSB repair system. siRNA-mediated depletion of CBP and p300 impaired HR activity and downregulated BRCA1 and RAD51 at the protein and mRNA levels. Chromatin immunoprecipitation assays showed that CBP and p300 bind to the promoter regions of the BRCA1 and RAD51 genes, and that depletion of CBP and/or p300 reduces H3 and H4 acetylation and inhibits binding of the transcription factor E2F1 to these promoters. Depletion of CBP and p300 impaired DNA damage-induced phosphorylation and chromatin binding of the single-strand DNA-binding protein RPA following BRCA1-mediated DNA end resection. Consistent with this, subsequent phosphorylation of CHK1 and activation of the G2/M damage checkpoint were also impaired. These results indicate that the HATs CBP and p300 play multiple roles in the activation of the cellular response to DSBs.

  6. SETD2-Dependent Histone H3K36 Trimethylation Is Required for Homologous Recombination Repair and Genome Stability

    Directory of Open Access Journals (Sweden)

    Sophia X. Pfister

    2014-06-01

    Full Text Available Modulating chromatin through histone methylation orchestrates numerous cellular processes. SETD2-dependent trimethylation of histone H3K36 is associated with active transcription. Here, we define a role for H3K36 trimethylation in homologous recombination (HR repair in human cells. We find that depleting SETD2 generates a mutation signature resembling RAD51 depletion at I-SceI-induced DNA double-strand break (DSB sites, with significantly increased deletions arising through microhomology-mediated end-joining. We establish a presynaptic role for SETD2 methyltransferase in HR, where it facilitates the recruitment of C-terminal binding protein interacting protein (CtIP and promotes DSB resection, allowing Replication Protein A (RPA and RAD51 binding to DNA damage sites. Furthermore, reducing H3K36me3 levels by overexpressing KDM4A/JMJD2A, an oncogene and H3K36me3/2 demethylase, or an H3.3K36M transgene also reduces HR repair events. We propose that error-free HR repair within H3K36me3-decorated transcriptionally active genomic regions promotes cell homeostasis. Moreover, these findings provide insights as to why oncogenic mutations cluster within the H3K36me3 axis.

  7. Excess Polθ functions in response to replicative stress in homologous recombination-proficient cancer cells

    Science.gov (United States)

    de Rugy, T. Goullet; Bashkurov, M.; Datti, A.; Betous, R.; Guitton-Sert, L.; Cazaux, C.; Durocher, D.

    2016-01-01

    ABSTRACT DNA polymerase theta (Polθ) is a specialized A-family DNA polymerase that functions in processes such as translesion synthesis (TLS), DNA double-strand break repair and DNA replication timing. Overexpression of POLQ, the gene encoding Polθ, is a prognostic marker for an adverse outcome in a wide range of human cancers. While increased Polθ dosage was recently suggested to promote survival of homologous recombination (HR)-deficient cancer cells, it remains unclear whether POLQ overexpression could be also beneficial to HR-proficient cancer cells. By performing a short interfering (si)RNA screen in which genes encoding druggable proteins were knocked down in Polθ-overexpressing cells as a means to uncover genetic vulnerabilities associated with POLQ overexpression, we could not identify genes that were essential for viability in Polθ-overexpressing cells in normal growth conditions. We also showed that, upon external DNA replication stress, Polθ expression promotes cell survival and limits genetic instability. Finally, we report that POLQ expression correlates with the expression of a set of HR genes in breast, lung and colorectal cancers. Collectively, our data suggest that Polθ upregulation, besides its importance for survival of HR-deficient cancer cells, may be crucial also for HR-proficient cells to better tolerate DNA replication stress, as part of a global gene deregulation response, including HR genes. PMID:27612511

  8. Excess Polθ functions in response to replicative stress in homologous recombination-proficient cancer cells

    Directory of Open Access Journals (Sweden)

    T. Goullet de Rugy

    2016-10-01

    Full Text Available DNA polymerase theta (Polθ is a specialized A-family DNA polymerase that functions in processes such as translesion synthesis (TLS, DNA double-strand break repair and DNA replication timing. Overexpression of POLQ, the gene encoding Polθ, is a prognostic marker for an adverse outcome in a wide range of human cancers. While increased Polθ dosage was recently suggested to promote survival of homologous recombination (HR-deficient cancer cells, it remains unclear whether POLQ overexpression could be also beneficial to HR-proficient cancer cells. By performing a short interfering (siRNA screen in which genes encoding druggable proteins were knocked down in Polθ-overexpressing cells as a means to uncover genetic vulnerabilities associated with POLQ overexpression, we could not identify genes that were essential for viability in Polθ-overexpressing cells in normal growth conditions. We also showed that, upon external DNA replication stress, Polθ expression promotes cell survival and limits genetic instability. Finally, we report that POLQ expression correlates with the expression of a set of HR genes in breast, lung and colorectal cancers. Collectively, our data suggest that Polθ upregulation, besides its importance for survival of HR-deficient cancer cells, may be crucial also for HR-proficient cells to better tolerate DNA replication stress, as part of a global gene deregulation response, including HR genes.

  9. CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes.

    Science.gov (United States)

    Ogiwara, Hideaki; Kohno, Takashi

    2012-01-01

    Histone acetylation at DNA double-strand break (DSB) sites by CBP and p300 histone acetyltransferases (HATs) is critical for the recruitment of DSB repair proteins to chromatin. Here, we show that CBP and p300 HATs also function in DSB repair by transcriptionally activating the BRCA1 and RAD51 genes, which are involved in homologous recombination (HR), a major DSB repair system. siRNA-mediated depletion of CBP and p300 impaired HR activity and downregulated BRCA1 and RAD51 at the protein and mRNA levels. Chromatin immunoprecipitation assays showed that CBP and p300 bind to the promoter regions of the BRCA1 and RAD51 genes, and that depletion of CBP and/or p300 reduces H3 and H4 acetylation and inhibits binding of the transcription factor E2F1 to these promoters. Depletion of CBP and p300 impaired DNA damage-induced phosphorylation and chromatin binding of the single-strand DNA-binding protein RPA following BRCA1-mediated DNA end resection. Consistent with this, subsequent phosphorylation of CHK1 and activation of the G2/M damage checkpoint were also impaired. These results indicate that the HATs CBP and p300 play multiple roles in the activation of the cellular response to DSBs.

  10. What do health-promoting schools promote?

    DEFF Research Database (Denmark)

    Simovska, Venka

    2012-01-01

    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...... review process, nine submissions were accepted for publication. Five of these are selected to be published in this issue and the rest will be published in a future issue of the journal. Findings – The five articles in this issue take a comprehensive approach to health promotion in schools and reflect...

  11. 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

  12. A structural and functional homolog supports a general role for frataxin in cellular iron chemistry.

    Science.gov (United States)

    Qi, Wenbin; Cowan, J A

    2010-02-01

    Bacillus subtilis YdhG lacks sequence homology, but demonstrates structural and functional similarity to the frataxin family, supporting a general cellular role for frataxin-type proteins in cellular iron homeostasis.

  13. Competition between replicative and translesion polymerases during homologous recombination repair in Drosophila.

    Directory of Open Access Journals (Sweden)

    Daniel P Kane

    Full Text Available In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood. Specifically, the identities of the polymerase(s that carry out repair synthesis and how they are recruited to repair sites are unclear. Here, we have investigated the roles of several different polymerases during homologous recombination repair in Drosophila melanogaster. Using a gap repair assay, we found that homologous recombination is impaired in Drosophila lacking DNA polymerase zeta and, to a lesser extent, polymerase eta. In addition, the Pol32 protein, part of the polymerase delta complex, is needed for repair requiring extensive synthesis. Loss of Rev1, which interacts with multiple translesion polymerases, results in increased synthesis during gap repair. Together, our findings support a model in which translesion polymerases and the polymerase delta complex compete during homologous recombination repair. In addition, they establish Rev1 as a crucial factor that regulates the extent of repair synthesis.

  14. CPHmodels-3.0--remote homology modeling using structure-guided sequence profiles

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Lund, Ole;

    2010-01-01

    CPHmodels-3.0 is a web server predicting protein 3D structure by use of single template homology modeling. The server employs a hybrid of the scoring functions of CPHmodels-2.0 and a novel remote homology-modeling algorithm. A query sequence is first attempted modeled using the fast CPHmodels-2.......0 profile-profile scoring function suitable for close homology modeling. The new computational costly remote homology-modeling algorithm is only engaged provided that no suitable PDB template is identified in the initial search. CPHmodels-3.0 was benchmarked in the CASP8 competition and produced models.......3 A. These performance values place the CPHmodels-3.0 method in the group of high performing 3D prediction tools. Beside its accuracy, one of the important features of the method is its speed. For most queries, the response time of the server is...

  15. A novel PTEN gene promoter mutation and untypical Cowden syndrome

    Institute of Scientific and Technical Information of China (English)

    Chen Liu; Guangbing Li; Rongrong Chen; Xiaobo Yang; Xue Zhao; Haitao Zhao

    2013-01-01

    Cowden syndrome (CS),an autosomal dominant disorder,is one of a spectrum of clinical disorders that have been linked to germline mutations in the phosphatase and tensin homolog (PTEN) gene.Although 70-80% of patients with CS have an identifiable germline PTEN mutation,the clinical diagnosis presents many challenges because of the phenotypic and genotypic variations.In the present study,we sequenced the exons and the promoter of PTEN gene,mutations and variations in the promoter and exons were identified,and a PTEN protein expression negative region was determined by immunohistochemistry (IHC).In conclusion,a novel promoter mutation we found in PTEN gene may turn off PTEN protein expression occasionally,leading to the disorder of PTEN and untypical CS manifestations.

  16. Homologous recombination in human telomerase-positive and ALT cells occurs with the same frequency

    OpenAIRE

    Bechter, Oliver E.; Zou, Ying; Shay, Jerry W.; Woodring E. Wright

    2003-01-01

    Homologous recombination is thought to be the molecular mechanism for maintaining telomere length in alternative lengthening of telomeres (ALT) cells. We used a recombination reporter system to show that the frequency of homologous recombination is the same for ALT- and telomerase-positive cells, suggesting that if ALT cells have a recombination defect it specifically involves telomeric sequences. We compared internal and telomere-adjacent positions of our ...

  17. 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....

  18. 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...

  19. Functional mapping of cannabinoid receptor homologs in mammals, other vertebrates, and invertebrates.

    Science.gov (United States)

    McPartland, John M; Glass, Michelle

    2003-07-17

    Over the past decade, several putative homologs of cannabinoid receptors (CBRs) have been identified by homology screening. Homology screening utilizes sequence alignment search engines to recognize homologs. We investigated these putative CBR homologs further by 'functional mapping' of their deduced amino acid sequences. The entire pharmacophore of a CBR has not yet been elucidated, but point-mutation studies have identified over 20 amino acid residues that impart CBR specificity for ligand recognition and/or signal transduction. Twenty point-mutation studies were used to construct a CBR functionality matrix. Sixteen putative CBR homologs were then mapped over the matrix. Several putative homologs did not hold up to this analysis: human GPR3, GPR6, GPR12, and Caenorhabditis elegans C02H7.2 expressed a series of crippling substitutions in the matrix, strongly suggesting they do not encode functional CBRs. Mapping the contested leech (Hirudo medicinalis) CBR sequence suggests that it encodes a functional CB1; it expresses fewer substitutions than the sea squirt (Ciona intestinalis) CB1 sequence. Mapping a putative CB2 ortholog in the puffer fish (Fugu rubripes T012234) suggests it may encode a CBR other than CB2. These findings are consistent with the lack of experimental data proving these putative CBRs have affinity for cannabinoid ligands. Matrix analysis also reveals that SR144528, a 'CB2-specific' synthetic antagonist, has affinity for non-mammalian CB1 receptors, and that L3.45 appears to be CB2-specific, its cognate in CB1 receptors is F3.45. In conclusion, functional mapping, utilizing point-mutation studies, may improve the specificity of homology screening performed by sequence alignment search engines.

  20. Gene Disruption by Homologous Recombination in the Xylella fastidiosa Citrus Variegated Chlorosis Strain

    Science.gov (United States)

    Gaurivaud, Patrice; Souza, Leonardo C. A.; Virgílio, Andrea C. D.; Mariano, Anelise G.; Palma, Renê R.; Monteiro, Patrícia B.

    2002-01-01

    Mutagenesis by homologous recombination was evaluated in Xylella fastidiosa by using the bga gene, coding for β-galactosidase, as a model. Integration of replicative plasmids by homologous recombination between the cloned truncated copy of bga and the endogenous gene was produced by one or two crossover events leading to β-galactosidase mutants. A promoterless chloramphenicol acetyltransferase gene was used to monitor the expression of the target gene and to select a cvaB mutant. PMID:12200328

  1. Effect of chromosome homology an plasmid transformation and plasmid conjugal transfer in Haemophilus influenzae

    Energy Technology Data Exchange (ETDEWEB)

    Balganesh, M.; Setlow, J.K.

    1984-05-14

    The pairing between plasmid and the homologous part of the chromosome associated with plasmid establishment may differ from the pairing which results from integration of a homologous region of the plasmid into the chromosome. Thus the rate of novobiocin transformation decreases with duplication of the chromosomal portion in pMB2, but the rate of establishment of the plasmid increases with this duplication. A model to explain these data is given. 17 references, 5 figures, 4 tables.

  2. Is Lamb Promotion Working?

    OpenAIRE

    Capps, Oral, Jr.; Williams, Gary W.

    2007-01-01

    This objective of this study is to determine whether the advertising and promotion dollars collected and spent by the American Lamb Board on lamb promotion since the inception of the Lamb Checkoff Program have effectively increased lamb consumption in the United States. The main conclusion is that program has resulted in roughly 7.6 additional pounds of total lamb consumption per dollar spent on advertising and promotion and $41.59 in additional lamb sales per dollar spent on advertising and ...

  3. 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.

  4. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    Science.gov (United States)

    Sowd, Gregory A; Mody, Dviti; Eggold, Joshua; Cortez, David; Friedman, Katherine L; Fanning, Ellen

    2014-12-01

    Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs) kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs) and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

  5. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    Directory of Open Access Journals (Sweden)

    Gregory A Sowd

    2014-12-01

    Full Text Available Simian virus 40 (SV40 and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs kinase activity, facilitates some aspects of double strand break (DSB repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR and do not colocalize with non-homologous end joining (NHEJ factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

  6. Health promotion in Brazil.

    Science.gov (United States)

    Buss, Paulo Marchiori; de Carvalho, Antonio Ivo

    2007-01-01

    The evolution of health promotion within the Brazilian health system is examined, including an assessment of the intersectoral and development policies that have influenced the process. Particular attention is paid to the legal characteristics of the Unified Health System. Human resources formation and research initiatives in health promotion are outlined, with a summary of the obstacles that need to be overcome in order to ensure the effective implementation of health promotion in the future. Up to the end of the 20th Century health promotion was not used as a term in the Brazilian public heath context. Health promoting activities were concentrated in the area of health education, although targeting the social determinants of health and the principle of intersectoral action were part of the rhetoric. The situation has changed during the last decade, with the publication of a national policy of health promotion, issued by the Ministry of Health and jointly implemented with the States and Municipals Health Secretaries. More recently there has been a re-emergence of the discourse on the social determinants of health and the formation of intersectoral public policies as the basis of a comprehensive health promotion. Health promotion infrastructure, particularly around human resources and financing, requires strengthening in order to ensure capacity and sustainability in health promotion practice.

  7. Analysis of promotions

    Directory of Open Access Journals (Sweden)

    V.V. Bozhkova

    2011-03-01

    Full Text Available Article describes the classification of promotions and determining the effectiveness of specific measures to stimulate sales (which isnt possible practically in most advertising companies.

  8. The extreme carboxyl terminus of the equine herpesvirus 1 homolog of herpes simplex virus VP16 is essential for immediate-early gene activation.

    Science.gov (United States)

    Elliott, G D

    1994-08-01

    Gene 12 of equine herpesvirus 1 (EHV-1), the homolog of herpes simplex virus (HSV) VP16 (alpha TIF, Vmw65), was cloned into a eukaryotic expression vector by PCR and used in transactivation studies of both the EHV-1 and HSV-1 IE1 promoters. Results demonstrated that the product of gene 12 is a potent transactivator of immediate-early gene expression of both viruses, which requires sequences in the upstream HSV-1 promoter for activity. Mutational analysis of the gene 12 open reading frame indicated that removal of the C-terminal 7 amino acids, which contain a short region of homology with the extreme C terminus of VP16, inactivated the protein. Within this region, only a single methionine residue appeared to be essential for activity, implying that gene 12 may have a modular array of organization similar to that of VP16. However, fusion of the gene 12 C terminus to a truncated form of VP16, which contained the complex formation domain, did not restore activity to the HSV-1 protein. These data demonstrate that the EHV-1 immediate-early transactivator may not be functionally colinear with VP16, with transactivation requiring both the C terminus and another region(s) present within the N-terminal portion.

  9. Promoter reuse in prokaryotes

    NARCIS (Netherlands)

    Nijveen, H.; Matus-Garcia, M.; Passel, van M.W.J.

    2012-01-01

    Anecdotal evidence shows promoters being reused separate from their downstream gene, thus providing a mechanism for the efficient and rapid rewiring of a gene’s transcriptional regulation. We have identified over 4000 groups of highly similar promoters using a conservative sequence similarity search

  10. Health-promoting schools

    DEFF Research Database (Denmark)

    Kwan, Stella Y L; Petersen, Poul Erik; Pine, Cynthia M

    2005-01-01

    Schools provide an important setting for promoting health, as they reach over 1 billion children worldwide and, through them, the school staff, families and the community as a whole. Health promotion messages can be reinforced throughout the most influential stages of children's lives, enabling...... them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School...... Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated...

  11. Evolution and targeting of Omp85 homologs in the chloroplast outer envelope membrane

    Directory of Open Access Journals (Sweden)

    Philip Michael Day

    2014-10-01

    Full Text Available Translocon at the outer-envelope-membrane of chloroplasts 75 (Toc75 is the core component of the chloroplast protein import machinery. It belongs to the Omp85 family whose members exist in various Gram-negative bacteria, mitochondria and chloroplasts of eukaryotes. Chloroplasts of Viridiplantae contain another Omp85 homolog called outer envelope protein 80 (OEP80, whose exact function is unknown. In addition, the Arabidopsis thaliana genome encodes truncated forms of Toc75 and OEP80. Multiple studies have shown a common origin of the Omp85 homologs of cyanobacteria and chloroplasts but their results about evolutionary relationships among cyanobacterial Omp85 (cyanoOmp85, Toc75 and OEP80 are inconsistent. The bipartite targeting sequence-dependent sorting of Toc75 has been demonstrated but the targeting mechanisms of other chloroplast Omp85 homologs remain largely unexplored. This study was aimed to address these unresolved issues in order to further our understanding of chloroplast evolution. Sequence alignments and recently determined structures of bacterial Omp85 homologs were used to predict structures of chloroplast Omp85 homologs. The results enabled us to identify amino acid residues that may indicate functional divergence of Toc75 from cyanoOmp85 and OEP80. Phylogenetic analyses using Omp85 homologs from various cyanobacteria and chloroplasts provided strong support for the grouping of Toc75 and OEP80 sister to cyanoOmp85. However, this support was diminished when the analysis included Omp85 homologs from other bacteria and mitochondria. Finally, results of import assays using isolated chloroplasts support outer membrane localization of OEP80tr and indicate that OEP80 may carry a cleavable targeting sequence.

  12. Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Lazarus, Kyren A. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Environmental and Biotechnology Centre, Swinburne University, Hawthorn, Victoria 3122 (Australia); Zhao, Zhe; Knower, Kevin C. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); To, Sarah Q. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia); Chand, Ashwini L. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Clyne, Colin D., E-mail: Colin.clyne@princehenrys.org [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia)

    2013-08-30

    Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E{sub 2}), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E{sub 2}, showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E{sub 2} treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer.

  13. Assembly and dynamics of the bacteriophage T4 homologous recombination machinery

    Directory of Open Access Journals (Sweden)

    Morrical Scott W

    2010-12-01

    Full Text Available Abstract Homologous recombination (HR, a process involving the physical exchange of strands between homologous or nearly homologous DNA molecules, is critical for maintaining the genetic diversity and genome stability of species. Bacteriophage T4 is one of the classic systems for studies of homologous recombination. T4 uses HR for high-frequency genetic exchanges, for homology-directed DNA repair (HDR processes including DNA double-strand break repair, and for the initiation of DNA replication (RDR. T4 recombination proteins are expressed at high levels during T4 infection in E. coli, and share strong sequence, structural, and/or functional conservation with their counterparts in cellular organisms. Biochemical studies of T4 recombination have provided key insights on DNA strand exchange mechanisms, on the structure and function of recombination proteins, and on the coordination of recombination and DNA synthesis activities during RDR and HDR. Recent years have seen the development of detailed biochemical models for the assembly and dynamics of presynaptic filaments in the T4 recombination system, for the atomic structure of T4 UvsX recombinase, and for the roles of DNA helicases in T4 recombination. The goal of this chapter is to review these recent advances and their implications for HR and HDR mechanisms in all organisms.

  14. Homologous recombination and gene replacement at the dihydrofolate reductase-thymidylate synthase locus in Toxoplasma gondii.

    Science.gov (United States)

    Donald, R G; Roos, D S

    1994-02-01

    To investigate the feasibility of genomic transgene expression and gene targeting in Toxoplasma gondii, parasites have been transfected with constructs differing in the length of contiguous genomic sequence spanning the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene. We have previously reported that vectors derived from a DHFR-TS cDNA 'minigene' containing mutations in the DHFR coding sequence confer pyrimethamine resistance to transfected parasites (Donald and Roos, 1993). Stably resistant parasite clones arise at high frequency, generally by virtue of transgene integration into parasite chromosomes at locations scattered throughout the genome. In contrast, using a vector which contains 8 kb of contiguous genomic sequence (vs. homologous recombination. Homologous recombination appears to occur at even higher frequency when a 16 kb genomic clone is used. Circular plasmids were more efficient than linearized molecules at producing homologous recombination in this system, integrating by reciprocal crossing-over to produce a duplication of the DHFR-TS locus. Double crossing-over (or gene conversion) was also observed at low frequency, resulting in complete allelic replacement in this haploid stage of the parasite. The ability to produce either homologous or non-homologous recombinants, by the selection of appropriate transformation constructs, has considerable genetic potential.

  15. A homolog of the RPS2 disease resistance gene is constitutively expressed in Brassica oleracea

    Directory of Open Access Journals (Sweden)

    Malvas Celia C.

    2003-01-01

    Full Text Available In this study, we identified disease resistance gene homologs in Brassica oleracea and assessed their expression in lines resistant and susceptible to Xanthomonas campestris pv. campestris (Xcc. Two DNA fragments of approximately 2.5 kb (BI-16/RPS2 and Lc201/RPS2 were amplified by PCR from two Brassica lines using primers based on an RPS2 homologous sequence previously described in the Brassica oleracea ecotype B117. The sequences of these fragments shared high similarity (95-98% with RPS2 homologs from various Brassica species. The digestion of these fragments with restriction enzymes revealed polymorphisms at the Xba I restriction sites. The length polymorphisms were used as a co-dominant marker in an F2 population developed to segregate for resistance to Xcc, the causal agent of black rot. Linkage analysis showed no significant association between the marker and quantitative trait loci for black rot. RT-PCR with specific primers yielded an expected 453 bp fragment that corresponded to the RPS2 homologs in both resistant and susceptible lines inoculated with the pathogen, as well as in non-inoculated control plants. These results suggest that these homologs are constitutively expressed in B. oleracea.

  16. The evolutionary fate of alternatively spliced homologous exons after gene duplication.

    Science.gov (United States)

    Abascal, Federico; Tress, Michael L; Valencia, Alfonso

    2015-04-29

    Alternative splicing and gene duplication are the two main processes responsible for expanding protein functional diversity. Although gene duplication can generate new genes and alternative splicing can introduce variation through alternative gene products, the interplay between the two processes is complex and poorly understood. Here, we have carried out a study of the evolution of alternatively spliced exons after gene duplication to better understand the interaction between the two processes. We created a manually curated set of 97 human genes with mutually exclusively spliced homologous exons and analyzed the evolution of these exons across five distantly related vertebrates (lamprey, spotted gar, zebrafish, fugu, and coelacanth). Most of these exons had an ancient origin (more than 400 Ma). We found examples supporting two extreme evolutionary models for the behaviour of homologous axons after gene duplication. We observed 11 events in which gene duplication was accompanied by splice isoform separation, that is, each paralog specifically conserved just one distinct ancestral homologous exon. At other extreme, we identified genes in which the homologous exons were always conserved within paralogs, suggesting that the alternative splicing event cannot easily be separated from the function in these genes. That many homologous exons fall in between these two extremes highlights the diversity of biological systems and suggests that the subtle balance between alternative splicing and gene duplication is adjusted to the specific cellular context of each gene.

  17. A SRS2 homolog from Arabidopsis thaliana disrupts recombinogenic DNA intermediates and facilitates single strand annealing.

    Science.gov (United States)

    Blanck, Sandra; Kobbe, Daniela; Hartung, Frank; Fengler, Karin; Focke, Manfred; Puchta, Holger

    2009-11-01

    Genetic and biochemical analyses of SRS2 homologs in fungi indicate a function in the processing of homologous recombination (HR) intermediates. To date, no SRS2 homologs have been described and analyzed in higher eukaryotes. Here, we report the first biochemical characterization of an SRS2 homolog from a multicellular eukaryote, the plant Arabidopsis thaliana. We studied the basic properties of AtSRS2 and were able to show that it is a functional 3'- to 5'-helicase. Furthermore, we characterized its biochemical function on recombinogenic intermediates and were able to show the unwinding of nicked Holliday junctions (HJs) and partial HJs (PX junctions). For the first time, we demonstrated strand annealing activity for an SRS2 homolog and characterized its strand pairing activity in detail. Our results indicate that AtSRS2 has properties that enable it to be involved in different steps during the processing of recombination intermediates. On the one hand, it could be involved in the unwinding of an elongating invading strand from a donor strand, while on the other hand, it could be involved in the annealing of the elongated strand at a later step.

  18. Randomly dividing homologous samples leads to overinflated accuracies for emotion recognition.

    Science.gov (United States)

    Liu, Shuang; Zhang, Di; Xu, Minpeng; Qi, Hongzhi; He, Feng; Zhao, Xin; Zhou, Peng; Zhang, Lixin; Ming, Dong

    2015-04-01

    There are numerous studies measuring the brain emotional status by analyzing EEGs under the emotional stimuli that have occurred. However, they often randomly divide the homologous samples into training and testing groups, known as randomly dividing homologous samples (RDHS), despite considering the impact of the non-emotional information among them, which would inflate the recognition accuracy. This work proposed a modified method, the integrating homologous samples (IHS), where the homologous samples were either used to build a classifier, or to be tested. The results showed that the classification accuracy was much lower for the IHS than for the RDHS. Furthermore, a positive correlation was found between the accuracy and the overlapping rate of the homologous samples. These findings implied that the overinflated accuracy did exist in those previous studies where the RDHS method was employed for emotion recognition. Moreover, this study performed a feature selection for the IHS condition based on the support vector machine-recursive feature elimination, after which the average accuracies were greatly improved to 85.71% and 77.18% in the picture-induced and video-induced tasks, respectively.

  19. Sequence homology of polymorphic AFLP markers in garlic (Allium sativum L.).

    Science.gov (United States)

    Ipek, Meryem; Ipek, Ahmet; Simon, Philipp W

    2006-10-01

    Linkage mapping and genetic diversity studies with DNA markers in plant species assume that comigrating bands are identical, or at least that they have homologous sequences. To test this assumption in a plant with a large genome, sequence identities of 7 polymorphic amplified fragment length polymorphism (AFLP) markers of garlic, previously used to estimate similarity in genetic diversity studies, were characterized. Among 37 diverse garlic clones, 87 bands from these 7 polymorphisms were excised, amplicons were cloned, and 2 to 6 colonies were sequenced from each band, to yield a total of 191 DNA amplicons. Of these 87 bands, 83 bands (95.4%) contained AFLP amplicons that were identical or highly homologous to the typical marker of that band; only 4 bands contained amplicons with little homology to the same-sized amplicons of other garlic clones. Of these 83 bands, 64 (73.6%) contained only highly homologous amplicons (>90% sequence identity), whereas 19 (21.8%) contained both homologous and nonhomologous amplicons, with sequence identities less than 60%. Of the 37 nonhomologous amplicons identified, 25 (67.5%) differed in length from other amplicons in the band. Sequence conservation of AFLP amplicons followed patterns similar to phylogenetic relationships among garlic clones, making them useful for developing simple PCR-based markers in genetic mapping and diversity assessment.

  20. 77 FR 47820 - Invention Promoters/Promotion Firms Complaints

    Science.gov (United States)

    2012-08-10

    ... United States Patent and Trademark Office Invention Promoters/Promotion Firms Complaints ACTION: Proposed... concerning invention promoters and responses from the invention promoters to these complaints. An individual may submit a complaint concerning an invention promoter to the USPTO, which will forward the...

  1. Regulation of ALF promoter activity in Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Dan Li

    Full Text Available BACKGROUND: In this report we evaluate the use of Xenopus laevis oocytes as a matched germ cell system for characterizing the organization and transcriptional activity of a germ cell-specific X. laevis promoter. PRINCIPAL FINDINGS: The promoter from the ALF transcription factor gene was cloned from X. laevis genomic DNA using a PCR-based genomic walking approach. The endogenous ALF gene was characterized by RACE and RT-PCR for transcription start site usage, and by sodium bisulfite sequencing to determine its methylation status in somatic and oocyte tissues. Homology between the X. laevis ALF promoter sequence and those from human, chimpanzee, macaque, mouse, rat, cow, pig, horse, dog, chicken and X. tropicalis was relatively low, making it difficult to use such comparisons to identify putative regulatory elements. However, microinjected promoter constructs were very active in oocytes and the minimal promoter could be narrowed by PCR-mediated deletion to a region as short as 63 base pairs. Additional experiments using a series of site-specific promoter mutants identified two cis-elements within the 63 base pair minimal promoter that were critical for activity. Both elements (A and B were specifically recognized by proteins present in crude oocyte extracts based on oligonucleotide competition assays. The activity of promoter constructs in oocytes and in transfected somatic Xenopus XLK-WG kidney epithelial cells was quite different, indicating that the two cell types are not functionally equivalent and are not interchangeable as assay systems. CONCLUSIONS: Overall the results provide the first detailed characterization of the organization of a germ cell-specific Xenopus promoter and demonstrate the feasibility of using immature frog oocytes as an assay system for dissecting the biochemistry of germ cell gene regulation.

  2. A developmental approach to homology and brain evolution Un enfoque embriológico a la homología y la evolución cerebral

    OpenAIRE

    FRANCISCO ABOITIZ

    2010-01-01

    Although homology is central to evolutionary interpretations, establishing it has become a highly disputed issue in some instances. Here I argüe for a developmental understanding of evolution, where modifications of the developmental programs are a key source of evolutionary novelty. Although this perspective is not new, in comparative neurobiology it has remained controversial. Specifically, the evolutionary origin of the mammalian neocortex has been a particularly debated point. I propose a...

  3. Promoting Renewable Energy Technologies

    DEFF Research Database (Denmark)

    Olsen, Ole Jess; Skytte, Klaus

    % of its annual electricity production. In this paper, we present and discuss the Danish experience as a case of promoting renewable energy technologies. The development path of the two technologies has been very different. Wind power is considered an outright success with fast deployment to decreasing...... technology and its particular context, it is possible to formulate some general principles that can help to create an effective and efficient policy for promoting new renewable energy technologies....

  4. The action of the affine diffeomorphisms on the relative homology group of certain exceptionally symmetric origamis

    CERN Document Server

    Matheus, Carlos

    2009-01-01

    We compute explicitly the action of the group of affine diffeomorphisms on the relative homology of two remarkable origamis discovered respectively by Forni (in genus 3) and Forni-Matheus (in genus 4). We show that, in both cases, the action on the non trivial part of the homology is through finite groups. In particular, the action on some 4-dimensional invariant subspace of the homology leaves invariant a root system of $D_4$ type. This provides as a by-product a new proof of (slightly stronger versions of) the results of Forni and Matheus: the non trivial Lyapunov exponents of the Kontsevich-Zorich cocycle for the Teichmuller disks of these two origamis are equal to zero.

  5. Mutagenesis and homologous recombination in Drosophila cell lines using CRISPR/Cas9

    Directory of Open Access Journals (Sweden)

    Andrew R. Bassett

    2013-12-01

    We have applied the CRISPR/Cas9 system to Drosophila S2 cells to generate targeted genetic mutations in more than 85% of alleles. By targeting a constitutive exon of the AGO1 gene, we demonstrate homozygous mutation in up to 82% of cells, thereby allowing the study of genetic knockouts in a Drosophila cell line for the first time. We have shown that homologous gene targeting is possible at 1–4% efficiency using this system, allowing for the construction of defined insertions and deletions. We demonstrate that a 1 kb homology arm length is optimal for integration by homologous gene targeting, and demonstrate its efficacy by tagging the endogenous AGO1 protein. This technology enables controlled genetic manipulation in Drosophila cell lines, and its simplicity offers the opportunity to study cellular phenotypes genome-wide.

  6. Increase and saturation of the third order hyperpolarizabilities in homologous series of symmetric cyanines

    Science.gov (United States)

    Werncke, W.; Pfeiffer, M.; Johr, T.; Lau, A.; Grahn, W.; Johannes, H.-H.; Dähne, L.

    1997-04-01

    The chain length dependencies of the static third order hyperpolarizabilities γSTAT for the homologous series of benzthiacyanine dyes and of simple bis(dimethylamino)methine dyes were extrapolated from nondegenerate four wave mixing dispersion measurements and compared with theoretical values. Up to the heptamethine the π-electron contributions γSTATπ of both homologous series show a similar increase with the growing number of π-electrons ( N) of the chain ( γSTATπ ˜ - N8 ± 2). However, the absolute values of the benzthiacyanines are considerable higher than of the corresponding bis(dimethylamino)methines. Negative valued hyperpolarizabilities γSTATπ in the homologous series increasing up to γSTATπ = - 850 × 10 -36 esu were determined. For the first time a saturation of the nonlinearity could be observed experimentally in the series of benzthiacyanines for the longest chain (benzthicyanine nonamethine).

  7. [Construction of Frankia genomic libraries and isolation of clones homologous to nodulation genes from Rhizobium leguminosarum].

    Science.gov (United States)

    Cui, Y H; Qin, M; Wang, Y L; Ding, J; Ma, Q S

    1990-01-01

    High molecular genomic DNAs were isolated by using the lysozyme plus achromopeptidase system from Frankia strains At4, Ccol and Hr16, the root nodule endophytes of Alnus, Casuarina and Hippophae respectively, and used to construct genomic libraries in pLAFR1, a broad host range cosmid vector within many gram-negative hosts. The genomic libraries were screened by in situ colony hybridization to identify clones homologous to common nodulation genes of Rhizobium leguminosarum, based on the sequence homology of EcoRI-digested Frankia total DNA to nodABC from Rhizobium meliloti. Several clones showing relatively strong hybridization were found, the recombinant plasmid was isolated, and their homology with Rhizobium nodulation genes was confirmed by spot hybridization. Further work on these positive clones is now underway.

  8. Identification of a mammalian mitochondrial homolog of ribosomal protein S7.

    Science.gov (United States)

    Cavdar Koc, E; Blackburn, K; Burkhart, W; Spremulli, L L

    1999-12-01

    Bovine mitochondrial small subunit ribosomal proteins were separated by two-dimensional electrophoresis. The region containing the most basic protein(s) was excised and the protein(s) present subjected to in-gel digestion with trypsin. Electrospray tandem mass spectrometry was used to provide sequence information on some of the peptide products. Searches of the human EST database using the sequence of the longest peptide analyzed indicated that this peptide was from the mammalian mitochondrial homolog of prokaryotic ribosomal protein S7 (MRP S7(human)). MRP S7(human) is a 28-kDa protein with a pI of 10. Significant homology to bacterial S7 is observed especially in the C-terminal half of the protein. Surprisingly, MRP S7(human) shows less homology to the corresponding mitochondrial proteins from plants and fungi than to bacterial S7.

  9. Analysis of ultraviolet and X-ray observations of three homologous solar flares from SMM

    Science.gov (United States)

    Cheng, Chung-Chieh; Pallavicini, Roberto

    1987-01-01

    Three homologous flares observed in the UV lines of Fe XXI and O V and in X-rays from the SMM were studied. It was found that: (1) the homology of the flares was most noticeable in Fe XXI and soft X-ray emissions; (2) the three flares shared many of the same loop footprints which were located in O V bright kernals associated with hard X-ray bursts; and (3) in spite of the strong spatial homology, the temporal evolution in UV and X-ray emissions varied from flare to flare. A comparison between the UV observations and photospheric magnetograms revealed that the basic flare configuration was a complex loop system consisting of many loops or bundles of loops.

  10. Symplectic geometry of the moduli space of projective structures in homological coordinates

    CERN Document Server

    Bertola, Marco; Norton, Chaya

    2015-01-01

    We introduce a natural symplectic structure on the moduli space of quadratic differentials with simple zeros and describe its Darboux coordinate systems in terms of so-called homological coordinates. We then show that this structure coincides with the canonical Poisson structure on the cotangent bundle of the moduli space of Riemann surfaces, and therefore the homological coordinates provide a new system of Darboux coordinates. We define a natural family of commuting "homological flows" on the moduli space of quadratic differentials and find the corresponding action-angle variables. The space of projective structures over the moduli space can be identified with the cotangent bundle upon selection of a reference projective connection that varies holomorphically and thus can be naturally endowed with a symplectic structure. Different choices of projective connections of this kind (Bergman, Schottky, Wirtinger) give rise to equivalent symplectic structures on the space of projective connections but different sym...

  11. The Promoted Sibling

    DEFF Research Database (Denmark)

    Visholm, Steen

    PRESENTATION No 72 Steen Visholm Associate professor, M.Psych., Ph. D., Roskilde University Private adress: Krystalgade 6 II DK-1172 København K Denmark svisholm@ruc.dk THE PROMOTED SIBLING By their writings about sibling relations Mitchell and Coles has added fruitful complexity to the psychodyn......PRESENTATION No 72 Steen Visholm Associate professor, M.Psych., Ph. D., Roskilde University Private adress: Krystalgade 6 II DK-1172 København K Denmark svisholm@ruc.dk THE PROMOTED SIBLING By their writings about sibling relations Mitchell and Coles has added fruitful complexity...... to the psychodynamic understanding of families, groups and organisations. With a point of departure in a study of self-governing groups in a factory the paper introduces the concept: ‘the promoted sibling’ which provide quite some understanding of the middle managers challenges in his or her role and the challenges...... in democracy in general. The middle manager can be seen as ‘a sibling promoted from above’ and democracy can be seen as siblings promoting a sibling to be ‘a temporary parent’ (Winnicott) or ‘a sibling promoted from below’. The extension of the family dynamics with the sibling relations provides a way...

  12. Long-term use and follow-up of autologous and homologous cartilage graft in rhinoplasty

    Directory of Open Access Journals (Sweden)

    Ghasemali Khorasani

    2016-05-01

    Full Text Available Background: Cartilage grafting is used in rhinoplasty and reconstructive surgeries. Autologous rib and nasal septum cartilage (auto graft is the preferred source of graft material in rhinoplasty, however, homologous cartilage (allograft has been extensively used to correct the nasal framework in nasal deformities. Autologous cartilage graft usage is restricted with complication of operation and limiting availability of tissue for extensive deformities. Alternatively, preserved costal cartilage allograft represents a readily available and easily contoured material. The current study was a formal systematic review of complications associated with autologous versus homologous cartilage grafting in rhinoplasty patients. Methods: In this cohort retrospective study, a total of 124 patients undergone primary or revision rhinoplasty using homologous or autologus grafts with postoperative follow-up ranging from 6 to 60 months were studied. The types of grafts and complications related to the grafts were evaluated. This included evaluation for warping, infection, resorption, mobility and fracture. Results: The total complications related to the cartilage grafts were 7 cases, which included 1 warped in auto graft group, three cases of graft displacement (two in allograft group and one in auto graft group and three fractures in allograft group. No infection and resorption was recorded. Complication rate (confidence interval 0.95 in autologous and homologous group were 1.25(0.4-3.88 and 2.08(0.78-5.55 in 1000 months follow up. There was no statistically significant difference between autologous and homologous group complications. Onset of complication in autologous and homologous group were 51.23(49.27-53.19 and 58.7(54.51-62.91 month respectively (P=0.81. Conclusion: The allograft cartilage has the advantage of avoiding donor-site scar. Moreover, it provides the same benefits as autologous costal cartilage with comparable complication rate. Therefore, it

  13. Oral region homologies in paleozoic crinoids and other plesiomorphic pentaradial echinoderms.

    Science.gov (United States)

    Kammer, Thomas W; Sumrall, Colin D; Zamora, Samuel; Ausich, William I; Deline, Bradley

    2013-01-01

    The phylogenetic relationships between major groups of plesiomorphic pentaradial echinoderms, the Paleozoic crinoids, blastozoans, and edrioasteroids, are poorly understood because of a lack of widely recognized homologies. Here, we present newly recognized oral region homologies, based on the Universal Elemental Homology model for skeletal plates, in a wide range of fossil taxa. The oral region of echinoderms is mainly composed of the axial, or ambulacral, skeleton, which apparently evolved more slowly than the extraxial skeleton that forms the majority of the body. Recent phylogenetic hypotheses have focused on characters of the extraxial skeleton, which may have evolved too rapidly to preserve obvious homologies across all these groups. The axial skeleton conserved homologous suites of characters shared between various edrioasteroids and specific blastozoans, and between other blastozoans and crinoids. Although individual plates can be inferred as homologous, no directly overlapping suites of characters are shared between edrioasteroids and crinoids. Six different systems of mouth (peristome) plate organization (Peristomial Border Systems) are defined. These include four different systems based on the arrangement of the interradially-positioned oral plates and their peristomial cover plates, where PBS A1 occurs only in plesiomorphic edrioasteroids, PBS A2 occurs in plesiomorphic edrioasteroids and blastozoans, and PBS A3 and PBS A4 occur in blastozoans and crinoids. The other two systems have radially-positioned uniserial oral frame plates in construction of the mouth frame. PBS B1 has both orals and uniserial oral frame plates and occurs in edrioasterid and possibly edrioblastoid edrioasteroids, whereas PBS B2 has exclusively uniserial oral frame plates and is found in isorophid edrioasteroids and imbricate and gogiid blastozoans. These different types of mouth frame construction offer potential synapomorphies to aid in parsimony-based phylogenetics for

  14. Oral region homologies in paleozoic crinoids and other plesiomorphic pentaradial echinoderms.

    Directory of Open Access Journals (Sweden)

    Thomas W Kammer

    Full Text Available The phylogenetic relationships between major groups of plesiomorphic pentaradial echinoderms, the Paleozoic crinoids, blastozoans, and edrioasteroids, are poorly understood because of a lack of widely recognized homologies. Here, we present newly recognized oral region homologies, based on the Universal Elemental Homology model for skeletal plates, in a wide range of fossil taxa. The oral region of echinoderms is mainly composed of the axial, or ambulacral, skeleton, which apparently evolved more slowly than the extraxial skeleton that forms the majority of the body. Recent phylogenetic hypotheses have focused on characters of the extraxial skeleton, which may have evolved too rapidly to preserve obvious homologies across all these groups. The axial skeleton conserved homologous suites of characters shared between various edrioasteroids and specific blastozoans, and between other blastozoans and crinoids. Although individual plates can be inferred as homologous, no directly overlapping suites of characters are shared between edrioasteroids and crinoids. Six different systems of mouth (peristome plate organization (Peristomial Border Systems are defined. These include four different systems based on the arrangement of the interradially-positioned oral plates and their peristomial cover plates, where PBS A1 occurs only in plesiomorphic edrioasteroids, PBS A2 occurs in plesiomorphic edrioasteroids and blastozoans, and PBS A3 and PBS A4 occur in blastozoans and crinoids. The other two systems have radially-positioned uniserial oral frame plates in construction of the mouth frame. PBS B1 has both orals and uniserial oral frame plates and occurs in edrioasterid and possibly edrioblastoid edrioasteroids, whereas PBS B2 has exclusively uniserial oral frame plates and is found in isorophid edrioasteroids and imbricate and gogiid blastozoans. These different types of mouth frame construction offer potential synapomorphies to aid in parsimony

  15. Relation between the equalized molecular chemical potential and the ionization potential of organic homologs

    Institute of Scientific and Technical Information of China (English)

    曹晨忠

    1995-01-01

    The ionization potential of organic homologs can be expressed as I_p=(∑X_i)/(a+bn).Here,X_i is the electronegativity(the average energy of valence electrons in a ground-state free atom)of the ith atomin an organic homologous molecule;n,the number of repeating units in the molecule;and(a+bn),the electronmoving range in the molecule orbit.The results of linear regression analysis show that the correlationcoefficients r are all "excellent"(r>0.990)for the 146 sets of photo electron spectroscopy data of 42 organichomologous series.

  16. A Betabaculovirus-Encoded gp64 Homolog Codes for a Functional Envelope Fusion Protein

    Science.gov (United States)

    Ardisson-Araújo, Daniel M. P.; Melo, Fernando L.; Clem, Rollie J.; Wolff, José L. C.

    2015-01-01

    The GP64 envelope fusion protein is a hallmark of group I alphabaculoviruses. However, the Diatraea saccharalis granulovirus genome sequence revealed the first betabaculovirus species harboring a gp64 homolog (disa118). In this work, we have shown that this homolog encodes a functional envelope fusion protein and could enable the infection and fusogenic abilities of a gp64-null prototype baculovirus. Therefore, GP64 may complement or may be in the process of replacing F protein activity in this virus lineage. PMID:26537678

  17. Chromosomal localization of the human apolipoprotein B gene and detection of homologous RNA in monkey intestine

    Energy Technology Data Exchange (ETDEWEB)

    Deeb, S.S.; Disteche, C.; Motulsky, A.G.; Lebo, R.V.; Kan, Y.W.

    1986-01-01

    A cDNA clone of the human apolipoprotein B-100 was used as a hybridization probe to detect homologous sequences in both flow-sorted and in situ metaphase chromosomes. The results indicate that the gene encoding this protein is on the distal end of the short arm of chromosome 2 (2p23-2p24). RNA isolated from monkey small intestine contained sequences (6.5 and 18 kilobases) homologous to the cDNA of apolipoprotein B-100. These results are consistent with the hypothesis that one gene codes for both the intestinal (B-48) and the hepatic (B-100) forms.

  18. Higher orbital integrals, Shalika germs, and the Hochschild homology of Hecke algebras

    Directory of Open Access Journals (Sweden)

    Victor Nistor

    2001-01-01

    Full Text Available We give a detailed calculation of the Hochschild and cyclic homology of the algebra 𝒞c∞(G of locally constant, compactly supported functions on a reductive p-adic group G. We use these calculations to extend to arbitrary elements the definition of the higher orbital integrals introduced by Blanc and Brylinski (1992 for regular semi-simple elements. Then we extend to higher orbital integrals some results of Shalika (1972. We also investigate the effect of the “induction morphism” on Hochschild homology.

  19. Homologation of α-aryl amino acids through quinone-catalyzed decarboxylation/Mukaiyama-Mannich addition.

    Science.gov (United States)

    Haugeberg, Benjamin J; Phan, Johnny H; Liu, Xinyun; O'Connor, Thomas J; Clift, Michael D

    2017-03-09

    A new method for amino acid homologation by way of formal C-C bond functionalization is reported. This method utilizes a 2-step/1-pot protocol to convert α-amino acids to their corresponding N-protected β-amino esters through quinone-catalyzed oxidative decarboxylation/in situ Mukaiyama-Mannich addition. The scope and limitations of this chemistry are presented. This methodology provides an alternative to the classical Arndt-Eistert homologation for accessing β-amino acid derivatives. The resulting N-protected amine products can be easily deprotected to afford the corresponding free amines.

  20. Evolution of homologous sequences on the human X and Y chromosomes, outside of the meiotic pairing segment.

    OpenAIRE

    Bickmore, W A; Cooke, H J

    1987-01-01

    A sequence isolated from the long arm of the human Y chromosome detects a highly homologous locus on the X. This homology extends over at least 50 kb of DNA and is postulated to be the result of a transposition event between the X and Y chromosomes during recent human evolution, since homologous sequences are shown to be present on the X chromosome alone in the chimpanzee and gorilla.

  1. The ATPase activity of Fml1 is essential for its roles in homologous recombination and DNA repair

    Science.gov (United States)

    Nandi, Saikat; Whitby, Matthew C.

    2012-01-01

    In fission yeast, the DNA helicase Fml1, which is an orthologue of human FANCM, is a key component of the machinery that drives and governs homologous recombination (HR). During the repair of DNA double-strand breaks by HR, it limits the occurrence of potentially deleterious crossover recombinants, whereas at stalled replication forks, it promotes HR to aid their recovery. Here, we have mutated conserved residues in Fml1’s Walker A (K99R) and Walker B (D196N) motifs to determine whether its activities are dependent on its ability to hydrolyse ATP. Both Fml1K99R and Fml1D196N are proficient for DNA binding but totally deficient in DNA unwinding and ATP hydrolysis. In vivo both mutants exhibit a similar reduction in recombination at blocked replication forks as a fml1Δ mutant indicating that Fml1’s motor activity, fuelled by ATP hydrolysis, is essential for its pro-recombinogenic role. Intriguingly, both fml1K99R and fml1D196N mutants exhibit greater sensitivity to genotoxins and higher levels of crossing over during DSB repair than a fml1Δ strain. These data suggest that without its motor activity, the binding of Fml1 to its DNA substrate can impede alternative mechanisms of repair and crossover avoidance. PMID:22844101

  2. A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation

    Science.gov (United States)

    Luijsterburg, Martijn S; Typas, Dimitris; Caron, Marie-Christine; Wiegant, Wouter W; van den Heuvel, Diana; Boonen, Rick A; Couturier, Anthony M; Mullenders, Leon H; Masson, Jean-Yves; van Attikum, Haico

    2017-01-01

    DNA double-strand breaks (DSB) elicit a ubiquitylation cascade that controls DNA repair pathway choice. This cascade involves the ubiquitylation of histone H2A by the RNF168 ligase and the subsequent recruitment of RIF1, which suppresses homologous recombination (HR) in G1 cells. The RIF1-dependent suppression is relieved in S/G2 cells, allowing PALB2-driven HR to occur. With the inhibitory impact of RIF1 relieved, it remains unclear how RNF168-induced ubiquitylation influences HR. Here, we uncover that RNF168 links the HR machinery to H2A ubiquitylation in S/G2 cells. We show that PALB2 indirectly recognizes histone ubiquitylation by physically associating with ubiquitin-bound RNF168. This direct interaction is mediated by the newly identified PALB2-interacting domain (PID) in RNF168 and the WD40 domain in PALB2, and drives DNA repair by facilitating the assembly of PALB2-containing HR complexes at DSBs. Our findings demonstrate that RNF168 couples PALB2-dependent HR to H2A ubiquitylation to promote DNA repair and preserve genome integrity. DOI: http://dx.doi.org/10.7554/eLife.20922.001 PMID:28240985

  3. Grasshopper Lazarillo, a GPI-anchored Lipocalin, increases Drosophila longevity and stress resistance, and functionally replaces its secreted homolog NLaz.

    Science.gov (United States)

    Ruiz, Mario; Wicker-Thomas, Claude; Sanchez, Diego; Ganfornina, Maria D

    2012-10-01

    Lazarillo (Laz) is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein first characterized in the developing nervous system of the grasshopper Schistocerca americana. It belongs to the Lipocalins, a functionally diverse family of mostly secreted proteins. In this work we test whether the protective capacity known for Laz homologs in flies and vertebrates (NLaz, GLaz and ApoD) is evolutionarily conserved in grasshopper Laz, and can be exerted from the plasma membrane in a cell-autonomous manner. First we demonstrate that extracellular forms of Laz have autocrine and paracrine protecting effects for oxidative stress-challenged Drosophila S2 cells. Then we assay the effects of overexpressing GPI-linked Laz in adult Drosophila and whether it rescues both known and novel phenotypes of NLaz null mutants. Local effects of GPI-linked Laz inside and outside the nervous system promote survival upon different stress forms, and extend lifespan and healthspan of the flies in a cell-type dependent manner. Outside the nervous system, expression in fat body cells but not in hemocytes results in protection. Within the nervous system, glial cell expression is more effective than neuronal expression. Laz actions are sexually dimorphic in some expression domains. Fat storage promotion and not modifications in hydrocarbon profiles or quantities explain the starvation-desiccation resistance caused by Laz overexpression. This effect is exerted when Laz is expressed ubiquitously or in dopaminergic cells, but not in hemocytes. Grasshopper Laz functionally restores the loss of NLaz, rescuing stress-sensitivity as well as premature accumulation of aging-related damage, monitored by advanced glycation end products (AGEs). However Laz does not rescue NLaz courtship behavioral defects. Finally, the presence of two new Lipocalins with predicted GPI-anchors in mosquitoes shows that the functional advantages of GPI-linkage have been commonly exploited by Lipocalins in the arthropodan lineage.

  4. Flightless I (Drosophila) homolog facilitates chromatin accessibility of the estrogen receptor α target genes in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Kwang Won, E-mail: kwjeong@gachon.ac.kr

    2014-04-04

    Highlights: • H3K4me3 and Pol II binding at TFF1 promoter were reduced in FLII-depleted MCF-7 cells. • FLII is required for chromatin accessibility of the enhancer of ERalpha target genes. • Depletion of FLII causes inhibition of proliferation of MCF-7 cells. - Abstract: The coordinated activities of multiple protein complexes are essential to the remodeling of chromatin structure and for the recruitment of RNA polymerase II (Pol II) to the promoter in order to facilitate the initiation of transcription in nuclear receptor-mediated gene expression. Flightless I (Drosophila) homolog (FLII), a nuclear receptor coactivator, is associated with the SWI/SNF-chromatin remodeling complex during estrogen receptor (ER)α-mediated transcription. However, the function of FLII in estrogen-induced chromatin opening has not been fully explored. Here, we show that FLII plays a critical role in establishing active histone modification marks and generating the open chromatin structure of ERα target genes. We observed that the enhancer regions of ERα target genes are heavily occupied by FLII, and histone H3K4me3 and Pol II binding induced by estrogen are decreased in FLII-depleted MCF-7 cells. Furthermore, formaldehyde-assisted isolation of regulatory elements (FAIRE)-quantitative polymerase chain reaction (qPCR) experiments showed that depletion of FLII resulted in reduced chromatin accessibility of multiple ERα target genes. These data suggest FLII as a key regulator of ERα-mediated transcription through its role in regulating chromatin accessibility for the binding of RNA Polymerase II and possibly other transcriptional coactivators.

  5. Isolation of a CENTRORADIALIS/TERMINAL FLOWER1 homolog in saffron (Crocus sativus L.): characterization and expression analysis.

    Science.gov (United States)

    Tsaftaris, Athanasios; Pasentsis, Konstantinos; Kalivas, Apostolos; Michailidou, Sofia; Madesis, Panagiotis; Argiriou, Anagnostis

    2012-08-01

    Genes in the phosphatidyl-ethanolamine-binding protein (PEBP) family are instrumental in regulating the fate of meristems and flowering time. To investigate the role of these genes in the monocotyledonous plant Crocus (Crocus sativus L), an industrially important crop cultivated for its nutritional and medicinal properties, we have cloned and characterized a CENTRORADIALIS/TERMINAL FLOWER1 (CEN/TFL1) like gene, named CsatCEN/TFL1-like, the first reported CEN/TFL1 gene characterized from such a perennial geophyte. Sequence analysis revealed that CsatCEN/TFL1 shows high similarity to its homologous PEBP family genes CEN/TFL1, FT and MFT from a variety of plant species and maintains the same exon/intron organization. Phylogenetic analysis of the CsatCEN/TFL1 amino acid sequence confirmed that the isolated sequences belong to the CEN/TFL1 clade of the PEBP family. CsatCEN/TFL1 transcripts could be detected in corms, flower and flower organs but not in leaves. An alternative spliced transcript was also detected in the flower. Comparison of expression levels of CsatCEN/TFL1 and its alternative spliced transcript in wild type flower and a double flower mutant showed no significant differences. Overexpression of CsatCEN/TFL1 transcript in Arabidopsis tfl1 plants reversed the phenotype of early flowering and terminal flowering of the tfl1 plants to a normal one. Computational analysis of the obtained promoter sequences revealed, next to common binding motifs in CEN/TFL1-like genes as well as other flowering gene promoters, the presence of two CArG binding sites indicative of control of CEN/TFL1 by MADS-box transcription factors involved in crocus flowering and flower organ formation.

  6. GmFT2a, a soybean homolog of FLOWERING LOCUS T, is involved in flowering transition and maintenance.

    Directory of Open Access Journals (Sweden)

    Hongbo Sun

    Full Text Available BACKGROUND: Flowering reversion can be induced in soybean (Glycine max L. Merr., a typical short-day (SD dicot, by switching from SD to long-day (LD photoperiods. This process may involve florigen, putatively encoded by FLOWERING LOCUS T (FT in Arabidopsis thaliana. However, little is known about the potential function of soybean FT homologs in flowering reversion. METHODS: A photoperiod-responsive FT homologue GmFT (renamed as GmFT2a hereafter was cloned from the photoperiod-sensitive cultivar Zigongdongdou. GmFT2a gene expression under different photoperiods was analyzed by real-time quantitative PCR. In situ hybridization showed direct evidence for its expression during flowering-related processes. GmFT2a was shown to promote flowering using transgenic studies in Arabidopsis and soybean. The effects of photoperiod and temperature on GmFT2a expression were also analyzed in two cultivars with different photoperiod-sensitivities. RESULTS: GmFT2a expression is regulated by photoperiod. Analyses of GmFT2a transcripts revealed a strong correlation between GmFT2a expression and flowering maintenance. GmFT2a transcripts were observed continuously within the vascular tissue up to the shoot apex during flowering. By contrast, transcripts decreased to undetectable levels during flowering reversion. In grafting experiments, the early-flowering, photoperiod-insensitive stock Heihe27 promotes the appearance of GmFT2a transcripts in the shoot apex of scion Zigongdongdou under noninductive LD conditions. The photothermal effects of GmFT2a expression diversity in cultivars with different photoperiod-sensitivities and a hypothesis is proposed. CONCLUSION: GmFT2a expression is associated with flowering induction and maintenance. Therefore, GmFT2a is a potential target gene for soybean breeding, with the aim of increasing geographic adaptation of this crop.

  7. Analysis of four achaete-scute homologs in Bombyx mori reveals new viewpoints of the evolution and functions of this gene family

    Directory of Open Access Journals (Sweden)

    Yi Yongzhu

    2008-03-01

    Full Text Available Abstract Background achaete-scute complexe (AS-C has been widely studied at genetic, developmental and evolutional levels. Genes of this family encode proteins containing a highly conserved bHLH domain, which take part in the regulation of the development of central nervous system and peripheral nervous system. Many AS-C homologs have been isolated from various vertebrates and invertebrates. Also, AS-C genes are duplicated during the evolution of Diptera. Functions besides neural development controlling have also been found in Drosophila AS-C genes. Results We cloned four achaete-scute homologs (ASH from the lepidopteran model organism Bombyx mori, including three proneural genes and one neural precursor gene. Proteins encoded by them contained the characteristic bHLH domain and the three proneural ones were also found to have the C-terminal conserved motif. These genes regulated promoter activity through the Class A E-boxes in vitro. Though both Bm-ASH and Drosophila AS-C have four members, they are not in one by one corresponding relationships. Results of RT-PCR and real-time PCR showed that Bm-ASH genes were expressed in different larval tissues, and had well-regulated expressional profiles during the development of embryo and wing/wing disc. Conclusion There are four achaete-scute homologs in Bombyx mori, the second insect having four AS-C genes so far, and these genes have multiple functions in silkworm life cycle. AS-C gene duplication in insects occurs after or parallel to, but not before the taxonomic order formation during evolution.

  8. Floer homology for negative line bundles and Reeb chords in pre-quantization spaces

    CERN Document Server

    Albers, Peter

    2008-01-01

    In this article we prove existence of Reeb orbits for Bohr-Sommerfeld Legendrians in certain pre-quantization spaces. We give a quantitative estimate from below. These estimates are obtained by studying Floer homology for fibre-wise quadratic Hamiltonian functions on negative line bundles.

  9. Homological evolutionary vector fields in Korteweg-de Vries, Liouville, Maxwell, and several other models

    NARCIS (Netherlands)

    Kiselev, Arthemy V.

    2012-01-01

    We review the construction of homological evolutionary vector fields on infinite jet spaces and partial differential equations. We describe the applications of this concept in three tightly inter-related domains: the variational Poisson formalism (e.g., for equations of Korteweg-de Vries type), geom

  10. Detecting Sequence Homology at the Gene Cluster Level with MultiGeneBlast

    NARCIS (Netherlands)

    Medema, Marnix H.; Takano, Eriko; Breitling, Rainer; Nowick, Katja

    2013-01-01

    The genes encoding many biomolecular systems and pathways are genomically organized in operons or gene clusters. With MultiGeneBlast, we provide a user-friendly and effective tool to perform homology searches with operons or gene clusters as basic units, instead of single genes. The contextualizatio

  11. Are Homologous Radio Bursts Driven by Solar Post-Flare Loops?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Three particularly complex radio bursts (2001 October 19, 2001 April 10 and 2003 October 26) obtained with the spectrometers (0.65-7.6 GHz) at the National Astronomical Observatories, Chinese Academy of Sciences (NAOC, Beijing and Yunnan) and other instruments (NoRH, TRACE and SXT) are presented. They each have two groups of peaks occurring in different frequency ranges (broad-band microwave and narrow-band decimeter wavelengths). We stress that the second group of burst peaks that occurred in the late phase of the flares and associated with post-flare loops may be homologous radio bursts. We think that they are driven by the post-flare loops. In contrast to the time profiles of the radio bursts and the images of coronal magnetic polarities, we are able to find that the three events are caused by the active regions including main single-bipole magnetic structures, which are associated with multipole magnetic structures during the flare evolutions. In particular, we point out that the later decimetric radio bursts are possibly the radio counterparts of the homologous flares (called "homologous radio bursts" by us), which are also driven by the single-bipole magnetic structures. By examining the evolutions of the magnetic polarities of sources (17 GHz),we could presume that the drivers of the homologous radio bursts are new and/or recurring appearances/disappearances of the magnetic polarities of radio sources, and that the triggers are the magnetic reconnections of single-bipole configurations.

  12. Construction of yellow fever virus subgenomic replicons by yeast-based homologous recombination cloning technique

    Directory of Open Access Journals (Sweden)

    Sabrina R.A. Queiroz

    2013-03-01

    Full Text Available RNA replicon derived from Flavivirus genome is a valuable tool for studying viral replication independent of virion assembly and maturation, besides being a great potencial for heterologous gene expression. In this study we described the construction of subgenomic replicons of yellow fever virus by yeast-based homologous recombination technique. The plasmid containing the yellow fever 17D strain replicon (pBSC-repYFV-17D, previously characterized, was handled to heterologous expression of the green fluorescent protein (repYFV-17D-GFP and firefly luciferase (repYFV-17D-Luc reporter genes. Both replicons were constructed by homologous recombination between the linearized vector pBSC-repYFV-17D and the PCR product containing homologous 25 nucleotides ends incorporated into PCR primers. The genomic organization of these constructs is similar to repYFV-17D, but with insertion of the reporter gene between the remaining 63 N-terminal nucleotides of the capsid protein and 72 C-terminal nucleotides of the E protein. The replicons repYFV-17D-GFP and repYFV-17D-Luc showed efficient replication and expression of the reporter genes. The yeast-based homologous recombination technique used in this study proved to be applicable for manipulation of the yellow fever virus genome in order to construct subgenomic replicons.

  13. Refinement of homology-based protein structures by molecular dynamics simulation techniques

    NARCIS (Netherlands)

    Fan, H; Mark, AE

    2004-01-01

    The use of classical molecular dynamics simulations, performed in explicit water, for the refinement of structural models of proteins generated ab initio or based on homology has been investigated. The study involved a test set of 15 proteins that were previously used by Baker and coworkers to asses

  14. Homology Modelling of the GABA Transporter and Analysis of Tiagabine Binding

    DEFF Research Database (Denmark)

    Skovstrup, S.; Taboureau, Olivier; Bräuner-Osborne, H.

    2010-01-01

    A homology model of the human GABA transporter (GAT-1) based on the recently reported crystal structures of the bacterial leucine transporter from Aquifex aeolicus (LeuT) was developed. The stability of the resulting model embedded in a membrane environment was analyzed by extensive molecular...

  15. "药食同源"源流探讨%Theoretical Origination of Medicine and Food Homology

    Institute of Scientific and Technical Information of China (English)

    朱建平; 邓文祥; 吴彬才; 向茗; 贺妍; 黄惠勇; 谢梦洲

    2015-01-01

    The theory of medicine and food homology was put forward between 1920s and 1930s, whereas, the formation of its theory was a very long course. The origination and development on theory of medicine and food homology of dietary therapy, medicated food and food prevention from ancient China to people's republic of China were reviewed by searching some history materials. It explicated the theoretical components of homology of medicine and food, providing the theoretical foundation for developing functional food of homology of medicine and food.%本文通过对历史文献的挖掘,简述从上古时期到新中国成立之间,食养、食疗、药膳等"药食同源"理论核心内容的起源与发展,梳理"药食同源"理论的形成基础,明确"药食同源"理论的组成,为开发药食同源功能性食品提供理论依据.

  16. Establishment of an anther clone of high regenerative frequency by anther culture of homologous tetraploidy rice

    Institute of Scientific and Technical Information of China (English)

    QINRuizhen; SHANXueyan

    1993-01-01

    By in vitro anther culture of various generational hybrids of homologous tetraploidy rices, we established an anther clone A87203 with high regenerative frequency from the combination H3774 in 1987. It possesses tbe characteristics of rapid growth, high multiplying ability, having a bud multiplication rate of 150-200times,

  17. Schizosaccharomyces pombe Mms1 channels repair of perturbed replication into Rhp51 independent homologous recombination

    DEFF Research Database (Denmark)

    Vejrup-Hansen, Rasmus; Mizuno, Ken'Ichi; Miyabe, Izumi;

    2011-01-01

    -like protein, Rtt101/Cul8, a potential paralog of Cullin 4. We performed epistasis analysis between ¿mms1 and mutants of pathways with known functions in genome integrity, and measured the recruitment of homologous recombination proteins to blocked replication forks and recombination frequencies. We show that...

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

    Science.gov (United States)

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

    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 female flagellum in Hubbardiinae with association of segment III of tri-segmented species to segments III + IV of tetra-segmented species. Considerations about the dorsal microsetae on the male flagellum are made. The genus Surazomus in Ecuador is revised. The sympatric species Surazomus palenque sp. nov. and S. kitu sp. nov. (Ecuador, Pichincha) are described and illustrated. The female of S. cuenca (Rowland and Reddell, 1979) is described, with two new distributional records for the species. Surazomus cumbalensis (Kraus, 1957) is recorded for the first time from Ecuador (Pichincha).

  19. Germline Chromothripsis Driven by L1-Mediated Retrotransposition and Alu/Alu Homologous Recombination

    DEFF Research Database (Denmark)

    Nazaryan-Petersen, Lusine; Bertelsen, Birgitte; Bak, Mads;

    2016-01-01

    L1-endonuclease potential target sites in other breakpoints. In addition, we found four Alu elements flanking the 110-kb deletion and associated with an inversion. We suggest that chromatin looping mediated by homologous Alu elements may have brought distal DNA regions into close proximity...

  20. Impact of template choice on homology model efficiency in virtual screening.

    Science.gov (United States)

    Rataj, Krzysztof; Witek, Jagna; Mordalski, Stefan; Kosciolek, Tomasz; Bojarski, Andrzej J

    2014-06-23

    Homology modeling is a reliable method of predicting the three-dimensional structures of proteins that lack NMR or X-ray crystallographic data. It employs the assumption that a structural resemblance exists between closely related proteins. Despite the availability of many crystal structures of possible templates, only the closest ones are chosen for homology modeling purposes. To validate the aforementioned approach, we performed homology modeling of four serotonin receptors (5-HT1AR, 5-HT2AR, 5-HT6R, 5-HT7R) for virtual screening purposes, using 10 available G-Protein Coupled Receptors (GPCR) templates with diverse evolutionary distances to the targets, with various approaches to alignment construction and model building. The resulting models were further validated in two steps by means of ligand docking and enrichment calculation, using Glide software. The final quality of the models was determined in virtual screening-like experiments by the AUROC score of the resulting ROC curves. The outcome of this research showed that no correlation between sequence identity and model quality was found, leading to the conclusion that the closest phylogenetic relative is not always the best template for homology modeling.