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  1. Article ; Online: Uracil-DNA glycosylase of murine gammaherpesvirus 68 binds cognate viral replication factors independently of its catalytic residues.

    Smith, Kyle R / Paul, Somnath / Dong, Qiwen / Anannya, Orchi / Oldenburg, Darby G / Forrest, J Craig / McBride, Kevin M / Krug, Laurie T

    mSphere

    2023  Volume 8, Issue 5, Page(s) e0027823

    Abstract: Herpesviruses are large double-stranded DNA viruses that encode core replication proteins and accessory factors involved in nucleotide metabolism and DNA repair. Mammalian uracil-DNA glycosylases (UNG) excise deleterious uracil residues from their ... ...

    Abstract Herpesviruses are large double-stranded DNA viruses that encode core replication proteins and accessory factors involved in nucleotide metabolism and DNA repair. Mammalian uracil-DNA glycosylases (UNG) excise deleterious uracil residues from their genomic DNA. Each herpesvirus UNG studied to date has demonstrated conservation of the enzymatic function to excise uracil residues from DNA. We previously reported that a murine gammaherpesvirus (MHV68) with a stop codon in
    MeSH term(s) Animals ; Mice ; Uracil-DNA Glycosidase/genetics ; Uracil-DNA Glycosidase/metabolism ; Virus Replication ; DNA Replication ; DNA, Viral/genetics ; Rhadinovirus/genetics ; Rhadinovirus/metabolism ; Gammaherpesvirinae/genetics ; DNA-Directed DNA Polymerase/genetics ; DNA-Directed DNA Polymerase/metabolism ; Uracil ; Mammals
    Chemical Substances Uracil-DNA Glycosidase (EC 3.2.2.-) ; DNA, Viral ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Uracil (56HH86ZVCT)
    Language English
    Publishing date 2023-09-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/msphere.00278-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Uracil-DNA Glycosylase of Murine Gammaherpesvirus 68 Binds Cognate Viral Replication Factors Independently of its Catalytic Residues.

    Smith, Kyle R / Paul, Somnath / Dong, Qiwen / Anannya, Orchi / Oldenburg, Darby G / Forrest, J Craig / McBride, Kevin M / Krug, Laurie T

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Herpesviruses are large double-stranded DNA viruses that encode core replication proteins and accessory factors involved in nucleotide metabolism and DNA repair. Mammalian Uracil-DNA glycosylases (UNG) excise deleterious uracil residues from their ... ...

    Abstract Herpesviruses are large double-stranded DNA viruses that encode core replication proteins and accessory factors involved in nucleotide metabolism and DNA repair. Mammalian Uracil-DNA glycosylases (UNG) excise deleterious uracil residues from their genomic DNA. Each herpesvirus UNG studied to date has demonstrated conservation of the enzymatic function to excise uracil residues from DNA. We previously reported that a murine gammaherpesvirus (MHV68) with a stop codon in
    Importance: Gammaherpesviruses encode a uracil-DNA glycosylase (vUNG) that is presumed to excise uracil residues from viral genomes. We previously identified the vUNG enzymatic activity, but not the protein itself, as dispensable for gammaherpesvirus replication
    Language English
    Publishing date 2023-05-19
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.19.541466
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Interspecific killing of wolverines by one wolf pack.

    Young, Kiana B / Saalfeld, David T / Brandt, Colette / Smith, Kyle R / Spivey, Timothy J / Stantorf, Cory J

    Ecology and evolution

    2023  Volume 13, Issue 12, Page(s) e10758

    Abstract: Interactions between different species of predators are not uncommon, yet they are generally understudied in North America. Across their range, gray wolves ( ...

    Abstract Interactions between different species of predators are not uncommon, yet they are generally understudied in North America. Across their range, gray wolves (
    Language English
    Publishing date 2023-12-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2635675-2
    ISSN 2045-7758
    ISSN 2045-7758
    DOI 10.1002/ece3.10758
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Combinatorial Loss of the Enzymatic Activities of Viral Uracil-DNA Glycosylase and Viral dUTPase Impairs Murine Gammaherpesvirus Pathogenesis and Leads to Increased Recombination-Based Deletion in the Viral Genome.

    Dong, Qiwen / Smith, Kyle R / Oldenburg, Darby G / Shapiro, Maxwell / Schutt, William R / Malik, Laraib / Plummer, Joshua B / Mu, Yunxiang / MacCarthy, Thomas / White, Douglas W / McBride, Kevin M / Krug, Laurie T

    mBio

    2018  Volume 9, Issue 5

    Abstract: Misincorporation of uracil or spontaneous cytidine deamination is a common mutagenic insult to DNA. Herpesviruses encode a viral uracil-DNA glycosylase (vUNG) and a viral dUTPase (vDUT), each with enzymatic and nonenzymatic functions. However, the ... ...

    Abstract Misincorporation of uracil or spontaneous cytidine deamination is a common mutagenic insult to DNA. Herpesviruses encode a viral uracil-DNA glycosylase (vUNG) and a viral dUTPase (vDUT), each with enzymatic and nonenzymatic functions. However, the coordinated roles of these enzymatic activities in gammaherpesvirus pathogenesis and viral genomic stability have not been defined. In addition, potential compensation by the host UNG has not been examined
    MeSH term(s) Animals ; Gene Deletion ; Genome, Viral ; Genomic Instability ; Herpesviridae Infections/veterinary ; Herpesviridae Infections/virology ; Lung/virology ; Mice ; Pyrophosphatases/genetics ; Pyrophosphatases/metabolism ; Recombination, Genetic ; Rhadinovirus/enzymology ; Rhadinovirus/genetics ; Rhadinovirus/pathogenicity ; Rodent Diseases/virology ; Uracil-DNA Glycosidase/genetics ; Uracil-DNA Glycosidase/metabolism ; Virulence
    Chemical Substances Uracil-DNA Glycosidase (EC 3.2.2.-) ; Pyrophosphatases (EC 3.6.1.-) ; dUTP pyrophosphatase (EC 3.6.1.23)
    Language English
    Publishing date 2018-10-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.01831-18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Maintenance of influenza A viruses and antibody response in mallards (Anas platyrhynchos) sampled during the non-breeding season in Alaska.

    Spivey, Timothy J / Lindberg, Mark S / Meixell, Brandt W / Smith, Kyle R / Puryear, Wendy B / Davis, Kimberly R / Runstadler, Jonathan A / Stallknecht, David E / Ramey, Andrew M

    PloS one

    2017  Volume 12, Issue 8, Page(s) e0183505

    Abstract: Prevalence of influenza A virus (IAV) infections in northern-breeding waterfowl has previously been reported to reach an annual peak during late summer or autumn; however, little is known about IAV infection dynamics in waterfowl populations persisting ... ...

    Abstract Prevalence of influenza A virus (IAV) infections in northern-breeding waterfowl has previously been reported to reach an annual peak during late summer or autumn; however, little is known about IAV infection dynamics in waterfowl populations persisting at high-latitude regions such as Alaska, during winter. We captured mallards (Anas platyrhynchos) throughout the non-breeding season (August-April) of 2012-2015 in Fairbanks and Anchorage, the two largest cities in Alaska, to assess patterns of IAV infection and antibody production using molecular methods and a standard serologic assay. In addition, we used virus isolation, genetic sequencing, and a virus microneutralization assay to characterize viral subtypes and to evaluate the immune response of mallards captured on multiple occasions through time. We captured 923 mallards during three successive sampling years: Fairbanks in 2012/13 and 2013/14, and Anchorage in 2014/15. Prevalence varied by age, season, and year/site with high and relatively stable estimates throughout the non-breeding season. Infected birds were detected in all locations/seasons except early-winter in Fairbanks during 2013/14. IAVs with 17 combinations of hemagglutinin (H1-5, H7-9, H11, H12) and neuraminidase (N1-6, N8, N9) subtypes were isolated. Antibodies to IAVs were detected throughout autumn and winter for all sampling locations and years, however, seroprevalence was higher among adults and varied among years. Mallards exhibited individual heterogeneity with regard to immune response, providing instances of both seroconversion and seroreversion to detected viral subtypes. The probability that an individual transitioned from one serostatus to another varied by age, with juvenile mallards having higher rates of seroconversion and seroreversion than adults. Our study provides evidence that a diversity of IAVs circulate in populations of mallards wintering at urban locations in Alaska, and we suggest waterfowl wintering at high-latitudes may play an important role in maintenance of viruses across breeding seasons.
    MeSH term(s) Alaska ; Animals ; Antibodies, Viral/biosynthesis ; Breeding ; Ducks/physiology ; Ducks/virology ; Influenza A virus/immunology ; Influenza A virus/isolation & purification
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2017-08-24
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0183505
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Modifying the glycosidic linkage in digitoxin analogs provides selective cytotoxins.

    Langenhan, Joseph M / Engle, Jeffery M / Slevin, Lauren K / Fay, Lindsay R / Lucker, Ryan W / Smith, Kyle R / Endo, Matthew M

    Bioorganic & medicinal chemistry letters

    2007  Volume 18, Issue 2, Page(s) 670–673

    Abstract: A chemoselective reaction between oxyamines and unprotected, unactivated reducing sugars was used to construct for the first time a panel of linkage-diversified neoglycosides. This panel of digitoxin analogs included potent and selective tumor cytotoxins; ...

    Abstract A chemoselective reaction between oxyamines and unprotected, unactivated reducing sugars was used to construct for the first time a panel of linkage-diversified neoglycosides. This panel of digitoxin analogs included potent and selective tumor cytotoxins; cytotoxicity was dependent on the structure of the glycosidic linkage. These results validate linkage diversification through neoglycosylation as a unique and simple strategy to powerfully complement existing methods for the optimization of glycoconjugates.
    MeSH term(s) Amines/chemistry ; Carbohydrates/chemistry ; Cytotoxins/chemistry ; Cytotoxins/pharmacology ; Digitoxin/analogs & derivatives ; Digitoxin/chemistry ; Glycoconjugates/chemistry ; Glycosylation
    Chemical Substances Amines ; Carbohydrates ; Cytotoxins ; Glycoconjugates ; Digitoxin (E90NZP2L9U)
    Language English
    Publishing date 2007-10-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2007.11.058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3203: Show issues Location:
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  7. Article ; Online: Synthesis and biological evaluation of RON-neoglycosides as tumor cytotoxins.

    Langenhan, Joseph M / Endo, Matthew M / Engle, Jeffrey M / Fukumoto, Liane L / Rogalsky, Derek R / Slevin, Lauren K / Fay, Lindsay R / Lucker, Ryan W / Rohlfing, James R / Smith, Kyle R / Tjaden, Anja E / Werner, Halina M

    Carbohydrate research

    2011  Volume 346, Issue 17, Page(s) 2663–2676

    Abstract: Cardenolides such as digitoxin have been shown to inhibit cancer cell growth, to reduce cancer metastasis, and to induce apoptosis in tumor cells. Among the most potent digitoxin-based cytotoxins identified to date are MeON-neoglycosides generated via ... ...

    Abstract Cardenolides such as digitoxin have been shown to inhibit cancer cell growth, to reduce cancer metastasis, and to induce apoptosis in tumor cells. Among the most potent digitoxin-based cytotoxins identified to date are MeON-neoglycosides generated via oxyamine neoglycosylation. Here, we report our studies of oxyamine neoglycosylation aimed at facilitating the elucidation of linkage-diversified digitoxin neoglycoside structure-activity relationships. We identified conditions suitable for the convenient synthesis of digitoxin neoglycosides and found that sugar structure, rather than RON-glycosidic linkage, exerts the strongest influence on neoglycoside yield and stereochemistry. We synthesized a library of digitoxin neoglycosides and assessed their cytotoxicity against eight human cancer cell lines. Consistent with previous findings, our data show that the structure of RON-neoglycosidic linkages influences both the potency and selectivity of digitoxin neoglycosides.
    MeSH term(s) Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/pharmacology ; Apraxia, Ideomotor ; Cardenolides/chemical synthesis ; Cardenolides/pharmacology ; Cell Line, Tumor ; Glycosides/chemical synthesis ; Glycosides/pharmacology ; Glycosylation ; Humans ; Hydrolysis ; Inhibitory Concentration 50 ; Small Molecule Libraries/chemical synthesis ; Small Molecule Libraries/pharmacology ; Stereoisomerism
    Chemical Substances Antineoplastic Agents ; Cardenolides ; Glycosides ; Small Molecule Libraries
    Language English
    Publishing date 2011-12-13
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1435-7
    ISSN 1873-426X ; 0008-6215
    ISSN (online) 1873-426X
    ISSN 0008-6215
    DOI 10.1016/j.carres.2011.09.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Bonn / Germany

    Z 2002/704: Show issues
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  8. Article: Synthesis and biological evaluation of RON-neoglycosides as tumor cytotoxins

    Langenhan, Joseph M. / Endo, Matthew M. / Engle, Jeffrey M. / Fukumoto, Liane L. / Rogalsky, Derek R. / Slevin, Lauren K. / Fay, Lindsay R. / Lucker, Ryan W. / Rohlfing, James R. / Smith, Kyle R. / Tjaden, Anja E. / Werner, Halina M.

    Carbohydrate research

    Volume v. 346,, Issue no. 1

    Abstract: Cardenolides such as digitoxin have been shown to inhibit cancer cell growth, to reduce cancer metastasis, and to induce apoptosis in tumor cells. Among the most potent digitoxin-based cytotoxins identified to date are MeON-neoglycosides generated via ... ...

    Abstract Cardenolides such as digitoxin have been shown to inhibit cancer cell growth, to reduce cancer metastasis, and to induce apoptosis in tumor cells. Among the most potent digitoxin-based cytotoxins identified to date are MeON-neoglycosides generated via oxyamine neoglycosylation. Here, we report our studies of oxyamine neoglycosylation aimed at facilitating the elucidation of linkage-diversified digitoxin neoglycoside structure–activity relationships. We identified conditions suitable for the convenient synthesis of digitoxin neoglycosides and found that sugar structure, rather than RON-glycosidic linkage, exerts the strongest influence on neoglycoside yield and stereochemistry. We synthesized a library of digitoxin neoglycosides and assessed their cytotoxicity against eight human cancer cell lines. Consistent with previous findings, our data show that the structure of RON-neoglycosidic linkages influences both the potency and selectivity of digitoxin neoglycosides.
    Keywords structure-activity relationships ; apoptosis ; metastasis ; cytotoxicity ; digitoxin ; stereochemistry ; humans ; cell growth ; cytotoxins ; neoplasm cells ; cardenolides ; sugars
    Language English
    Document type Article
    ISSN 0008-6215
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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