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  1. Article ; Online: Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc.

    Abed, Jawad / Emgård, Johanna E M / Zamir, Gideon / Faroja, Mouhammad / Almogy, Gideon / Grenov, Amalie / Sol, Asaf / Naor, Ronit / Pikarsky, Eli / Atlan, Karine A / Mellul, Anna / Chaushu, Stella / Manson, Abigail L / Earl, Ashlee M / Ou, Nora / Brennan, Caitlin A / Garrett, Wendy S / Bachrach, Gilad

    Cell host & microbe

    2014  Volume 20, Issue 2, Page(s) 215–225

    Abstract: ... and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is ... overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum ... binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase ...

    Abstract Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic tumor formation in preclinical models. However, fusobacteria are core members of the human oral microbiome and less prevalent in the healthy gut, raising questions about how fusobacteria localize to CRC. We identify a host polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells and established CRCs in mice. Additionally, intravenously injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus, targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria potentiation of CRC.
    MeSH term(s) Adenocarcinoma/microbiology ; Adenocarcinoma/pathology ; Adhesins, Bacterial/metabolism ; Animals ; Antigens, Tumor-Associated, Carbohydrate/metabolism ; Bacterial Adhesion ; Cell Line, Tumor ; Colonic Neoplasms/microbiology ; Colonic Neoplasms/pathology ; Disease Models, Animal ; Epithelial Cells/metabolism ; Epithelial Cells/microbiology ; Fusobacterium nucleatum/physiology ; Host-Pathogen Interactions ; Humans ; Lectins/metabolism ; Mice, Inbred BALB C ; Models, Biological ; Protein Binding
    Chemical Substances Adhesins, Bacterial ; Antigens, Tumor-Associated, Carbohydrate ; Lectins ; Thomsen-Friedenreich antigen (3554-90-3)
    Language English
    Publishing date 2014-05-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2016.07.006
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  2. Article ; Online: Superspreaders and the spread pattern of COVID-19: Response to: 'Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19'. Int J Infect Dis 2020;96:461-3.

    Almogy, Gal

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

    2020  Volume 98, Page(s) 381

    MeSH term(s) Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-07-02
    Publishing country Canada
    Document type Letter ; Comment
    ZDB-ID 1331197-9
    ISSN 1878-3511 ; 1201-9712
    ISSN (online) 1878-3511
    ISSN 1201-9712
    DOI 10.1016/j.ijid.2020.06.102
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  3. Article ; Online: Superspreaders and the spread pattern of COVID-19

    Almogy, Gal

    International Journal of Infectious Diseases

    2020  Volume 98, Page(s) 381

    Keywords Microbiology (medical) ; Infectious Diseases ; General Medicine ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 1331197-9
    ISSN 1878-3511 ; 1201-9712
    ISSN (online) 1878-3511
    ISSN 1201-9712
    DOI 10.1016/j.ijid.2020.06.102
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  4. Article: Superspreaders and the spread pattern of COVID-19: Response to: 'Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19'. Int J Infect Dis 2020;96:461-3

    Almogy, Gal

    Int J Infect Dis

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #628361
    Database COVID19

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  5. Article ; Online: Superspreaders and the spread pattern of COVID-19

    Gal Almogy, PhD

    International Journal of Infectious Diseases, Vol 98, Iss , Pp 381- (2020)

    2020  

    Keywords Infectious and parasitic diseases ; RC109-216 ; covid19
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
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  6. Article: Conditional protein stabilization via the small molecules Shld-1 and rapamycin increases the signal-to-noise ratio with tet-inducible gene expression.

    Almogy, Gal / Nolan, Garry P

    BioTechniques

    2009  Volume 46, Issue 1, Page(s) 44–50

    Abstract: Cellular mechanisms control one or more of the three basic levels of regulation (transcription, translation, and protein activity/locality), allowing for finely tuned spatial and temporal regulation of protein expression patterns. Gene regulation ... ...

    Abstract Cellular mechanisms control one or more of the three basic levels of regulation (transcription, translation, and protein activity/locality), allowing for finely tuned spatial and temporal regulation of protein expression patterns. Gene regulation constructs in wide use today often employ a constitutively expressed transcription factor whose activity is determined by the presence or absence of a small molecule. A case in point is the tet transcription system, wherein transcription is regulated by doxycycline (Dox), allowing the researcher to turn protein expression on or off depending on the presence/absence of Dox. However in many applications of that system, there is basal transcription from the promoter element that is independent of Dox. Moreover, in vivo, heterogeneous distribution of Dox leads to concurrent differences in gene expression. We addressed these limitations by introducing conditional destabilizing elements to the system. First, we created a transactivator protein fusion regulated at the additional level of protein stability. This modification enabled a system that demonstrated an off state that is less sensitive to variations in Dox concentrations. We also regulated the stability of the protein expressed from the tet operator cassette, observing greatly improved signal-to-noise ratios. The results underscore how investigator-defined regulation at multiple levels of protein expression can attain afiner degree of control over the final expression of introduced genes.
    MeSH term(s) Animals ; Doxycycline/pharmacology ; Gene Expression Regulation ; Gene Transfer Techniques ; Genetic Vectors ; Green Fluorescent Proteins/analysis ; Mice ; Morpholines/pharmacology ; NIH 3T3 Cells ; Protein Stability/drug effects ; Recombinant Fusion Proteins/analysis ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/chemistry ; Repressor Proteins/metabolism ; Response Elements ; Sirolimus/pharmacology ; Trans-Activators/metabolism ; Transcriptional Activation ; Transfection
    Chemical Substances Morpholines ; Recombinant Fusion Proteins ; Repressor Proteins ; Shield-1 compound ; Trans-Activators ; enhanced green fluorescent protein ; tetracycline resistance-encoding transposon repressor protein ; Green Fluorescent Proteins (147336-22-9) ; Doxycycline (N12000U13O) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2009-03-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 48453-2
    ISSN 1940-9818 ; 0736-6205
    ISSN (online) 1940-9818
    ISSN 0736-6205
    DOI 10.2144/000113030
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  7. Article ; Online: Conditional protein stabilization via the small molecules Shld-1 and rapamycin increases the signal-to-noise ratio with tet-inducible gene expression

    Gal Almogy / Garry P. Nolan

    BioTechniques, Vol 46, Iss 1, Pp 44-

    2009  Volume 50

    Abstract: Cellular mechanisms control one or more of the three basic levels of regulation (transcription, translation, and protein activity/locality), allowing for finely tuned spatial and temporal regulation of protein expression patterns. Gene regulation ... ...

    Abstract Cellular mechanisms control one or more of the three basic levels of regulation (transcription, translation, and protein activity/locality), allowing for finely tuned spatial and temporal regulation of protein expression patterns. Gene regulation constructs in wide use today often employ a constitutively expressed transcription factor whose activity is determined by the presence or absence of a small molecule. A case in point is the tet transcription system, wherein transcription is regulated by doxycycline (Dox), allowing the researcher to turn protein expression on or off, depending on the presence/absence of Dox. However, in many applications of that system, there is basal transcription from the promoter element that is independent of Dox. Moreover, in vivo, heterogeneous distribution of Dox leads to concurrent differences in gene expression. We addressed these limitations by introducing conditional destabilizing elements to the system. First, we created a transactivator protein fusion regulated at the additional level of protein stability. This modification enabled a system that demonstrated an off state that is less sensitive to variations in Dox concentrations. We also regulated the stability of the protein expressed from the tet operator cassette, observing greatly improved signal-to-noise ratios. The results underscore how investigator-defined regulation at multiple levels of protein expression can attain a finer degree of control over the final expression of introduced genes.
    Keywords Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2009-01-01T00:00:00Z
    Publisher Future Science Ltd
    Document type Article ; Online
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  8. Article ; Online: Analysis of Influenza and RSV dynamics in the community using a 'Local Transmission Zone' approach.

    Almogy, Gal / Stone, Lewi / Bernevig, B Andrei / Wolf, Dana G / Dorozko, Marina / Moses, Allon E / Nir-Paz, Ran

    Scientific reports

    2017  Volume 7, Page(s) 42012

    Abstract: Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases. At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks ... ...

    Abstract Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases. At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks dominate the dynamics of pathogen transmission; yet, the effective boundaries of these micro-scale groups are generally not known and often ignored. Using clinical test results from hospital admitted patients we analyze the spatio-temporal distribution of Influenza Like Illness (ILI) in the city of Jerusalem over a period of three winter seasons. We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy.
    MeSH term(s) Cities ; Humans ; Influenza, Human/epidemiology ; Influenza, Human/transmission ; Models, Statistical ; Residence Characteristics ; Respiratory Syncytial Virus Infections/epidemiology ; Respiratory Syncytial Virus Infections/transmission ; Seasons
    Keywords covid19
    Language English
    Publishing date 2017-02-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep42012
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  9. Article: Immune response and virus population composition: HIV as a case study.

    Almogy, Gal / Cohen, Netta / Stöcker, Sabine / Stone, Lewi

    Proceedings. Biological sciences

    2002  Volume 269, Issue 1493, Page(s) 809–815

    Abstract: Based on the current understanding of the immune response, we present what we believe to be a new model of intrahost virus dynamics. The model takes into account the relationship between virus replication rate and the level of antigen displayed by ... ...

    Abstract Based on the current understanding of the immune response, we present what we believe to be a new model of intrahost virus dynamics. The model takes into account the relationship between virus replication rate and the level of antigen displayed by infected cells, and shows how the cell-directed immune response controls both virus load and virus replication rate. In contrast to conventional wisdom, it shows that the predominant virus variant does not necessarily have the highest replication rate. A strong immune response produces a selective advantage for latent viruses, whereas a deteriorating immune response invites in viruses of higher replication rates. The model is analysed in light of the well-studied HIV/AIDS disease progression, and shows how a wide range of major, seemingly unrelated issues in the study of HIV may be accounted for in a simple and unified manner.
    MeSH term(s) Antiretroviral Therapy, Highly Active ; HIV/pathogenicity ; HIV/physiology ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/virology ; Humans ; Models, Biological ; Virus Replication/drug effects
    Language English
    Publishing date 2002-04-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209242-6
    ISSN 1471-2954 ; 0962-8452 ; 0080-4649 ; 0950-1193
    ISSN (online) 1471-2954
    ISSN 0962-8452 ; 0080-4649 ; 0950-1193
    DOI 10.1098/rspb.2001.1895
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  10. Article ; Online: Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack.

    Gur, Chamutal / Ibrahim, Yara / Isaacson, Batya / Yamin, Rachel / Abed, Jawad / Gamliel, Moriya / Enk, Jonatan / Bar-On, Yotam / Stanietsky-Kaynan, Noah / Coppenhagen-Glazer, Shunit / Shussman, Noam / Almogy, Gideon / Cuapio, Angelica / Hofer, Erhard / Mevorach, Dror / Tabib, Adi / Ortenberg, Rona / Markel, Gal / Miklić, Karmela /
    Jonjic, Stipan / Brennan, Caitlin A / Garrett, Wendy S / Bachrach, Gilad / Mandelboim, Ofer

    Immunity

    2015  Volume 42, Issue 2, Page(s) 344–355

    Abstract: Bacteria, such as Fusobacterium nucleatum, are present in the tumor microenvironment. However, the immunological consequences of intra-tumoral bacteria remain unclear. Here, we have shown that natural killer (NK) cell killing of various tumors is ... ...

    Abstract Bacteria, such as Fusobacterium nucleatum, are present in the tumor microenvironment. However, the immunological consequences of intra-tumoral bacteria remain unclear. Here, we have shown that natural killer (NK) cell killing of various tumors is inhibited in the presence of various F. nucleatum strains. Our data support that this F. nucleatum-mediated inhibition is mediated by human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. Using a library of F. nucleatum mutants, we found that the Fap2 protein of F. nucleatum directly interacted with TIGIT, leading to the inhibition of NK cell cytotoxicity. We have further demonstrated that tumor-infiltrating lymphocytes expressed TIGIT and that T cell activities were also inhibited by F. nucleatum via Fap2. Our results identify a bacterium-dependent, tumor-immune evasion mechanism in which tumors exploit the Fap2 protein of F. nucleatum to inhibit immune cell activity via TIGIT.
    MeSH term(s) Adenocarcinoma/immunology ; Adenocarcinoma/microbiology ; Animals ; Bacterial Outer Membrane Proteins/immunology ; Cell Line ; Cell Proliferation ; Colonic Neoplasms/immunology ; Colonic Neoplasms/microbiology ; Fusobacterium nucleatum/immunology ; Humans ; Killer Cells, Natural/immunology ; Lymphocytes, Tumor-Infiltrating/immunology ; Mice ; Protein Binding ; Receptors, Immunologic/immunology ; Tumor Escape/immunology ; Tumor Microenvironment/immunology
    Chemical Substances Bacterial Outer Membrane Proteins ; Receptors, Immunologic ; TIGIT protein, human
    Language English
    Publishing date 2015-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2015.01.010
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