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  1. Article ; Online: Enhanced heat tolerance of viral-infected aphids leads to niche expansion and reduced interspecific competition.

    Porras, Mitzy F / Navas, Carlos A / Marden, James H / Mescher, Mark C / De Moraes, Consuelo M / Pincebourde, Sylvain / Sandoval-Mojica, Andrés / Raygoza-Garay, Juan A / Holguin, German A / Rajotte, Edwin G / Carlo, Tomás A

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 1184

    Abstract: Vector-borne pathogens are known to alter the phenotypes of their primary hosts and vectors, with implications for disease transmission as well as ecology. Here we show that a plant virus, barley yellow dwarf virus, increases the surface temperature of ... ...

    Abstract Vector-borne pathogens are known to alter the phenotypes of their primary hosts and vectors, with implications for disease transmission as well as ecology. Here we show that a plant virus, barley yellow dwarf virus, increases the surface temperature of infected host plants (by an average of 2 °C), while also significantly enhancing the thermal tolerance of its aphid vector Rhopalosiphum padi (by 8 °C). This enhanced thermal tolerance, which was associated with differential upregulation of three heat-shock protein genes, allowed aphids to occupy higher and warmer regions of infected host plants when displaced from cooler regions by competition with a larger aphid species, R. maidis. Infection thereby led to an expansion of the fundamental niche of the vector. These findings show that virus effects on the thermal biology of hosts and vectors can influence their interactions with one another and with other, non-vector organisms.
    MeSH term(s) Animal Distribution ; Animals ; Aphids/physiology ; Aphids/virology ; Feeding Behavior/psychology ; Gene Expression Profiling ; Gene Expression Regulation ; Heat-Shock Proteins/metabolism ; Heat-Shock Response/genetics ; Hordeum/virology ; Host Microbial Interactions/genetics ; Hot Temperature/adverse effects ; Insect Proteins/metabolism ; Insect Vectors/physiology ; Luteovirus/pathogenicity ; Plant Diseases/virology ; Thermotolerance/genetics
    Chemical Substances Heat-Shock Proteins ; Insect Proteins
    Language English
    Publishing date 2020-03-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-14953-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression.

    Kohlmeyer, Jordan L / Lingo, Joshua J / Kaemmer, Courtney A / Scherer, Amanda / Warrier, Akshaya / Voigt, Ellen / Raygoza Garay, Juan A / McGivney, Gavin R / Brockman, Qierra R / Tang, Amy / Calizo, Ana / Pollard, Kai / Zhang, Xiaochun / Hirbe, Angela C / Pratilas, Christine A / Leidinger, Mariah / Breheny, Patrick / Chimenti, Michael S / Sieren, Jessica C /
    Monga, Varun / Tanas, Munir R / Meyerholz, David K / Darbro, Benjamin W / Dodd, Rebecca D / Quelle, Dawn E

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2023  Volume 29, Issue 17, Page(s) 3484–3497

    Abstract: Purpose: Malignant peripheral nerve sheath tumors (MPNST) are lethal, Ras-driven sarcomas that lack effective therapies. We investigated effects of targeting cyclin-dependent kinases 4 and 6 (CDK4/6), MEK, and/or programmed death-ligand 1 (PD-L1) in ... ...

    Abstract Purpose: Malignant peripheral nerve sheath tumors (MPNST) are lethal, Ras-driven sarcomas that lack effective therapies. We investigated effects of targeting cyclin-dependent kinases 4 and 6 (CDK4/6), MEK, and/or programmed death-ligand 1 (PD-L1) in preclinical MPNST models.
    Experimental design: Patient-matched MPNSTs and precursor lesions were examined by FISH, RNA sequencing, IHC, and Connectivity-Map analyses. Antitumor activity of CDK4/6 and MEK inhibitors was measured in MPNST cell lines, patient-derived xenografts (PDX), and de novo mouse MPNSTs, with the latter used to determine anti-PD-L1 response.
    Results: Patient tumor analyses identified CDK4/6 and MEK as actionable targets for MPNST therapy. Low-dose combinations of CDK4/6 and MEK inhibitors synergistically reactivated the retinoblastoma (RB1) tumor suppressor, induced cell death, and decreased clonogenic survival of MPNST cells. In immune-deficient mice, dual CDK4/6-MEK inhibition slowed tumor growth in 4 of 5 MPNST PDXs. In immunocompetent mice, combination therapy of de novo MPNSTs caused tumor regression, delayed resistant tumor outgrowth, and improved survival relative to monotherapies. Drug-sensitive tumors that regressed contained plasma cells and increased cytotoxic T cells, whereas drug-resistant tumors adopted an immunosuppressive microenvironment with elevated MHC II-low macrophages and increased tumor cell PD-L1 expression. Excitingly, CDK4/6-MEK inhibition sensitized MPNSTs to anti-PD-L1 immune checkpoint blockade (ICB) with some mice showing complete tumor regression.
    Conclusions: CDK4/6-MEK inhibition induces a novel plasma cell-associated immune response and extended antitumor activity in MPNSTs, which dramatically enhances anti-PD-L1 therapy. These preclinical findings provide strong rationale for clinical translation of CDK4/6-MEK-ICB targeted therapies in MPNST as they may yield sustained antitumor responses and improved patient outcomes.
    MeSH term(s) Mice ; Humans ; Animals ; Neurofibrosarcoma/drug therapy ; Plasma Cells/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Mitogen-Activated Protein Kinase Kinases ; Cell Line, Tumor ; Tumor Microenvironment ; Cyclin-Dependent Kinase 4
    Chemical Substances CD274 protein, human ; Protein Kinase Inhibitors ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; CDK4 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22)
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-0749
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Jg. 1995 - 2021: Lesesall (2.OG)
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  3. Article: Complete Genome Sequence of Mycobacterium avium subsp. paratuberculosis, Isolated from Human Breast Milk.

    Bannantine, John P / Li, Lingling / Mwangi, Michael / Cote, Rebecca / Raygoza Garay, Juan A / Kapur, Vivek

    Genome announcements

    2014  Volume 2, Issue 1

    Abstract: Mycobacterium avium subsp. paratuberculosis is the etiologic agent of Johne's disease in ruminants and has also been associated with human Crohn's disease. We report the complete genome sequence of M. avium subsp. paratuberculosis, isolated from the ... ...

    Abstract Mycobacterium avium subsp. paratuberculosis is the etiologic agent of Johne's disease in ruminants and has also been associated with human Crohn's disease. We report the complete genome sequence of M. avium subsp. paratuberculosis, isolated from the breast milk of a Crohn's disease patient. This sequence has high identity with characterized strains recovered from cattle.
    Language English
    Publishing date 2014-02-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2704277-7
    ISSN 2169-8287
    ISSN 2169-8287
    DOI 10.1128/genomeA.01252-13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Complete Genome Sequence of Mycobacterium avium subsp. paratuberculosis, Isolated from Human Breast Milk

    Bannantine, John P / Li, Lingling / Mwangi, Michael / Cote, Rebecca / Raygoza Garay, Juan A / Kapur, Vivek

    Genome announcements. 2014 Feb. 27, v. 2, no. 1

    2014  

    Abstract: Mycobacterium avium subsp. paratuberculosis is the etiologic agent of Johne’s disease in ruminants and has also been associated with human Crohn’s disease. We report the complete genome sequence of M. avium subsp. paratuberculosis, isolated from the ... ...

    Abstract Mycobacterium avium subsp. paratuberculosis is the etiologic agent of Johne’s disease in ruminants and has also been associated with human Crohn’s disease. We report the complete genome sequence of M. avium subsp. paratuberculosis, isolated from the breast milk of a Crohn’s disease patient. This sequence has high identity with characterized strains recovered from cattle.
    Keywords Crohn disease ; Mycobacterium avium subsp. paratuberculosis ; breast milk ; cattle ; etiology ; humans ; nucleotide sequences ; paratuberculosis ; patients
    Language English
    Dates of publication 2014-0227
    Size p. e01252-13.
    Publishing place American Society for Microbiology
    Document type Article
    ZDB-ID 2704277-7
    ISSN 2169-8287
    ISSN 2169-8287
    DOI 10.1128/genomeA.01252-13
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Comparison of O-Antigen Gene Clusters of All O-Serogroups of Escherichia coli and Proposal for Adopting a New Nomenclature for O-Typing.

    DebRoy, Chitrita / Fratamico, Pina M / Yan, Xianghe / Baranzoni, GianMarco / Liu, Yanhong / Needleman, David S / Tebbs, Robert / O'Connell, Catherine D / Allred, Adam / Swimley, Michelle / Mwangi, Michael / Kapur, Vivek / Raygoza Garay, Juan A / Roberts, Elisabeth L / Katani, Robab

    PloS one

    2016  Volume 11, Issue 1, Page(s) e0147434

    Abstract: Escherichia coli strains are classified based on O-antigens that are components of the lipopolysaccharide (LPS) in the cell envelope. O-antigens are important virulence factors, targets of both the innate and adaptive immune system, and play a role in ... ...

    Abstract Escherichia coli strains are classified based on O-antigens that are components of the lipopolysaccharide (LPS) in the cell envelope. O-antigens are important virulence factors, targets of both the innate and adaptive immune system, and play a role in host-pathogen interactions. Because they are highly immunogenic and display antigenic specificity unique for each strain, O-antigens are the biomarkers for designating O-types. Immunologically, 185 O-serogroups and 11 OX-groups exist for classification. Conventional serotyping for O-typing entails agglutination reactions between the O-antigen and antisera generated against each O-group. The procedure is labor intensive, not always accurate, and exhibits equivocal results. In this report, we present the sequences of 71 O-antigen gene clusters (O-AGC) and a comparison of all 196 O- and OX-groups. Many of the designated O-types, applied for classification over several decades, exhibited similar nucleotide sequences of the O-AGCs and cross-reacted serologically. Some O-AGCs carried insertion sequences and others had only a few nucleotide differences between them. Thus, based on these findings, it is proposed that several of the E. coli O-groups may be merged. Knowledge of the O-AGC sequences facilitates the development of molecular diagnostic platforms that are rapid, accurate, and reliable that can replace conventional serotyping. Additionally, with the scientific knowledge presented, new frontiers in the discovery of biomarkers, understanding the roles of O-antigens in the innate and adaptive immune system and pathogenesis, the development of glycoconjugate vaccines, and other investigations, can be explored.
    MeSH term(s) Agglutination Tests ; Cross Reactions ; Escherichia coli/classification ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics ; Glycosyltransferases/genetics ; Humans ; Immune Sera/chemistry ; Membrane Transport Proteins/genetics ; Multigene Family ; Nucleotidyltransferases/genetics ; O Antigens/classification ; O Antigens/genetics ; Phylogeny ; Sequence Analysis, DNA ; Serogroup ; Serotyping/methods ; Terminology as Topic
    Chemical Substances Escherichia coli Proteins ; Immune Sera ; Membrane Transport Proteins ; O Antigens ; Wzx protein, E coli ; Glycosyltransferases (EC 2.4.-) ; Wzy polymerase, E coli (EC 2.4.1.-) ; Nucleotidyltransferases (EC 2.7.7.-)
    Language English
    Publishing date 2016-01-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0147434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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