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  1. Article ; Online: Spatiotemporal characterization of endothelial cell motility and physical forces during exposure to

    Muenkel, Marie / Aparicio-Yuste, Raul / Tal, Michal Caspi / Kraiczy, Peter / Bastounis, Effie E

    STAR protocols

    2022  Volume 3, Issue 4, Page(s) 101832

    Abstract: Cell motility and biomechanics are critical in various (patho)physiological processes, including the regulation of vascular barrier integrity, which can be subverted by bacterial pathogens. Here, we present a protocol on how to expose endothelial cells ( ... ...

    Abstract Cell motility and biomechanics are critical in various (patho)physiological processes, including the regulation of vascular barrier integrity, which can be subverted by bacterial pathogens. Here, we present a protocol on how to expose endothelial cells (ECs) to vector-borne
    MeSH term(s) Borrelia burgdorferi/physiology ; Endothelial Cells/metabolism ; Biomechanical Phenomena
    Language English
    Publishing date 2022-11-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101832
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Spatiotemporal characterization of endothelial cell motility and physical forces during exposure to Borrelia burgdorferi

    Marie Muenkel / Raul Aparicio-Yuste / Michal Caspi Tal / Peter Kraiczy / Effie E. Bastounis

    STAR Protocols, Vol 3, Iss 4, Pp 101832- (2022)

    2022  

    Abstract: Summary: Cell motility and biomechanics are critical in various (patho)physiological processes, including the regulation of vascular barrier integrity, which can be subverted by bacterial pathogens. Here, we present a protocol on how to expose ... ...

    Abstract Summary: Cell motility and biomechanics are critical in various (patho)physiological processes, including the regulation of vascular barrier integrity, which can be subverted by bacterial pathogens. Here, we present a protocol on how to expose endothelial cells (ECs) to vector-borne Borrelia burgdorferi (Bb) and characterize EC kinematics and dynamics during exposure to live or heat-inactivated Bb through traction force and monolayer stress microscopy. Modifications to this protocol may be necessary for studying how different cell types interact with Bb or other microorganisms.For complete details on the use and execution of this protocol, please refer to Yuste et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords Biophysics ; Cell Biology ; Cell culture ; Cell-based Assays ; Microbiology ; Microscopy ; Science (General) ; Q1-390
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS-CoV-2 infection.

    Sheikh-Mohamed, Salma / Sanders, Erin C / Gommerman, Jennifer L / Tal, Michal Caspi

    Immunological reviews

    2022  Volume 309, Issue 1, Page(s) 75–85

    Abstract: In early 2020, a global emergency was upon us in the form of the coronavirus disease 2019 (COVID-19) pandemic. While horrific in its health, social and economic devastation, one silver lining to this crisis has been a rapid mobilization of cross- ... ...

    Abstract In early 2020, a global emergency was upon us in the form of the coronavirus disease 2019 (COVID-19) pandemic. While horrific in its health, social and economic devastation, one silver lining to this crisis has been a rapid mobilization of cross-institute, and even cross-country teams that shared common goals of learning as much as we could as quickly as possible about the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and how the immune system would respond to both the virus and COVID-19 vaccines. Many of these teams were formed by women who quickly realized that the classical model of "publish first at all costs" was maladaptive for the circumstances and needed to be supplanted by a more collaborative solution-focused approach. This review is an example of a collaboration that unfolded in separate countries, first Canada and the United States, and then also Israel. Not only did the collaboration allow us to cross-validate our results using different hands/techniques/samples, but it also took advantage of different vaccine types and schedules that were rolled out in our respective home countries. The result of this collaboration was a new understanding of how mucosal immunity to SARS-CoV-2 infection vs COVID-19 vaccination can be measured using saliva as a biofluid, what types of vaccines are best able to induce (limited) mucosal immunity, and what are potential correlates of protection against breakthrough infection. In this review, we will share what we have learned about the mucosal immune response to SARS-CoV-2 and to COVID-19 vaccines and provide a perspective on what may be required for next-generation pan-sarbecoronavirus vaccine approaches.
    MeSH term(s) Antibodies, Viral ; COVID-19 ; COVID-19 Vaccines ; Female ; Humans ; Immunoglobulin A ; SARS-CoV-2 ; Vaccination ; Viral Vaccines
    Chemical Substances Antibodies, Viral ; COVID-19 Vaccines ; Immunoglobulin A ; Viral Vaccines
    Language English
    Publishing date 2022-07-11
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: SIRPα controls CD47-dependent platelet clearance in mice and humans.

    Shoham, Maia / Yiu, Ying Ying / Hansen, Paige S / Subramaniam, Aanya / Broberg, Martin / Gars, Eric / Raveh, Tal / FinnGen / Weissman, Irving L / Sinnott-Armstrong, Nasa / Krishnan, Anandi / Ollila, Hanna M / Tal, Michal Caspi

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Over the last decade, more data has revealed that increased surface expression of the "don't eat me" CD47 protein on cancer cells plays a role in immune evasion and tumor progression, with CD47 blockade emerging as a new therapy in immuno-oncology. CD47 ... ...

    Abstract Over the last decade, more data has revealed that increased surface expression of the "don't eat me" CD47 protein on cancer cells plays a role in immune evasion and tumor progression, with CD47 blockade emerging as a new therapy in immuno-oncology. CD47 is critical in regulating cell homeostasis and clearance, as binding of CD47 to the inhibitory receptor SIRPα can prevent phagocytosis and macrophage-mediated cell clearance. The purpose of this study was to examine the role of the CD47-SIRPα signal in platelet homeostasis and clearance. Therapeutic reagents targeting the CD47-SIRPα axis are very promising for treatment of hematologic malignancies and solid tumors, but lead to transient anemia or thrombocytopenia in a subset of patients. We found that platelet homeostatic clearance is regulated through the CD47-SIRPα axis and that therapeutic blockade to disrupt this interaction in mice and in humans has a significant impact on platelet levels. Furthermore, we identified genetic variations at the
    Language English
    Publishing date 2023-12-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.09.570874
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Borrelia burgdorferi

    Yuste, Raúl Aparicio / Muenkel, Marie / Axarlis, Konstantinos / Gómez Benito, María J / Reuss, Annalena / Blacker, Grace / Tal, Michal Caspi / Kraiczy, Peter / Bastounis, Effie E

    iScience

    2022  Volume 25, Issue 8, Page(s) 104793

    Abstract: ... Borrelia ... ...

    Abstract Borrelia burgdorferi
    Language English
    Publishing date 2022-07-20
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.104793
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: CSBFinder: discovery of colinear syntenic blocks across thousands of prokaryotic genomes.

    Svetlitsky, Dina / Dagan, Tal / Chalifa-Caspi, Vered / Ziv-Ukelson, Michal

    Bioinformatics (Oxford, England)

    2018  Volume 35, Issue 10, Page(s) 1634–1643

    Abstract: Motivation: Identification of conserved syntenic blocks across microbial genomes is important for several problems in comparative genomics such as gene annotation, study of genome organization and evolution and prediction of gene interactions. Current ... ...

    Abstract Motivation: Identification of conserved syntenic blocks across microbial genomes is important for several problems in comparative genomics such as gene annotation, study of genome organization and evolution and prediction of gene interactions. Current tools for syntenic block discovery do not scale up to the large quantity of prokaryotic genomes available today.
    Results: We present a novel methodology for the discovery, ranking and taxonomic distribution analysis of colinear syntenic blocks (CSBs)-groups of genes that are consistently located close to each other, in the same order, across a wide range of taxa. We present an efficient algorithm that identifies CSBs in large genomic datasets. The algorithm is implemented and incorporated in a novel tool with a graphical user interface, denoted CSBFinder, that ranks the discovered CSBs according to a probabilistic score and clusters them to families according to their gene content similarity. We apply CSBFinder to data mine 1487 prokaryotic genomes including chromosomes and plasmids. For post-processing analysis, we generate heatmaps for visualizing the distribution of CSB family members across various taxa. We exemplify the utility of CSBFinder in operon prediction, in deciphering unknown gene function and in taxonomic analysis of colinear syntenic blocks.
    Availability and implementation: CSBFinder software and code are publicly available at https://github.com/dinasv/CSBFinder.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Algorithms ; Genome, Microbial ; Genomics ; Software ; Synteny
    Language English
    Publishing date 2018-09-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/bty861
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease.

    Strausz, Satu / Abner, Erik / Blacker, Grace / Galloway, Sarah / Hansen, Paige / Feng, Qingying / Lee, Brandon T / Jones, Samuel E / Haapaniemi, Hele / Raak, Sten / Nahass, George Ronald / Sanders, Erin / Soodla, Pilleriin / Võsa, Urmo / Esko, Tõnu / Sinnott-Armstrong, Nasa / Weissman, Irving L / Daly, Mark / Aivelo, Tuomas /
    Tal, Michal Caspi / Ollila, Hanna M

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2041

    Abstract: Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we ... ...

    Abstract Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease.
    MeSH term(s) Mice ; Animals ; Humans ; Borrelia burgdorferi/genetics ; Lyme Disease/microbiology ; Ixodes/microbiology ; Secretoglobins
    Chemical Substances SCGB1D2 protein, human ; Secretoglobins
    Language English
    Publishing date 2024-03-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45983-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: CD47 Blockade Leads to Chemokine-Dependent Monocyte Infiltration and Loss of B Cells from the Splenic Marginal Zone.

    Yiu, Ying Ying / Hansen, Paige S / Torrez Dulgeroff, Laughing Bear / Blacker, Grace / Myers, Lara / Galloway, Sarah / Gars, Eric / Colace, Olivia / Mansfield, Paul / Hasenkrug, Kim J / Weissman, Irving L / Tal, Michal Caspi

    Journal of immunology (Baltimore, Md. : 1950)

    2022  Volume 208, Issue 6, Page(s) 1371–1377

    Abstract: CD47 is an important innate immune checkpoint through its interaction with its inhibitory receptor on macrophages, signal-regulatory protein α (SIRPα). Therapeutic blockade of CD47-SIRPα interactions is a promising immuno-oncology treatment that promotes ...

    Abstract CD47 is an important innate immune checkpoint through its interaction with its inhibitory receptor on macrophages, signal-regulatory protein α (SIRPα). Therapeutic blockade of CD47-SIRPα interactions is a promising immuno-oncology treatment that promotes clearance of cancer cells. However, CD47-SIRPα interactions also maintain homeostatic lymphocyte levels. In this study, we report that the mouse splenic marginal zone B cell population is dependent on intact CD47-SIRPα interactions and blockade of CD47 leads to the loss of these cells. This depletion is accompanied by elevated levels of monocyte-recruiting chemokines CCL2 and CCL7 and infiltration of CCR2
    MeSH term(s) Animals ; Antigens, Differentiation ; CD47 Antigen ; Chemokines ; Mice ; Monocytes/metabolism ; Phagocytosis ; Receptors, Immunologic
    Chemical Substances Antigens, Differentiation ; CD47 Antigen ; Chemokines ; Receptors, Immunologic
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2100352
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Borrelia burgdorferi modulates the physical forces and immunity signaling in endothelial cells

    Raúl Aparicio Yuste / Marie Muenkel / Konstantinos Axarlis / María J. Gómez Benito / Annalena Reuss / Grace Blacker / Michal Caspi Tal / Peter Kraiczy / Effie E. Bastounis

    iScience, Vol 25, Iss 8, Pp 104793- (2022)

    2022  

    Abstract: Summary: Borrelia burgdorferi (Bb), a vector-borne bacterial pathogen and the causative agent of Lyme disease, can spread to distant tissues in the human host by traveling in and through monolayers of endothelial cells (ECs) lining the vasculature. To ... ...

    Abstract Summary: Borrelia burgdorferi (Bb), a vector-borne bacterial pathogen and the causative agent of Lyme disease, can spread to distant tissues in the human host by traveling in and through monolayers of endothelial cells (ECs) lining the vasculature. To examine whether Bb alters the physical forces of ECs to promote its dissemination, we exposed ECs to Bb and observed a sharp and transient increase in EC traction and intercellular forces, followed by a prolonged decrease in EC motility and physical forces. All variables returned to baseline at 24 h after exposure. RNA sequencing analysis revealed an upregulation of innate immune signaling pathways during early but not late Bb exposure. Exposure of ECs to heat-inactivated Bb recapitulated only the early weakening of EC mechanotransduction. The differential responses to live versus heat-inactivated Bb indicate a tight interplay between innate immune signaling and physical forces in host ECs and suggest their active modulation by Bb.
    Keywords Immunology ; Microbiology ; Cell biology ; Biophysics ; Transcriptomics ; Science ; Q
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Thesis ; Online: Autophagy, ROS and aging impact cytosolic antiviral immunity

    Tal, Michal Caspi

    2012  

    Abstract: In this thesis we show that pro-inflammatory cytokine production in response to viral ligands is increased in several situations: (1) in the absence of autophagy, (2) during increased oxidative stress, and (3) in the elderly. We find that autophagy is ... ...

    Abstract In this thesis we show that pro-inflammatory cytokine production in response to viral ligands is increased in several situations: (1) in the absence of autophagy, (2) during increased oxidative stress, and (3) in the elderly. We find that autophagy is essential for maintaining the integrity of, and the appropriate amount of, mitochondria. Mitochondria serve as an integral platform whereby antiviral defense initiation pathways are coordinated with sensing of cellular stress, and thereby autophagy is critical for regulating the signaling emanating from the mitochondria. Accumulation of damaged mitochondria within a cell leads to increased mitochondrial reactive oxygen species production, and our studies show that this leads in increased cytosolic antiviral signaling and confers some protection from viral infection. Further, we find evidence for defective autophagy in human aging, as well as increased levels of mitochondrial ROS with age. We find this even in hematopoietic stem cells and throughout the progeny hematopoietic cells and we investigate the functional implications for the accumulation of damaged mitochondria and elevated levels of oxidative stress on the innate immune response to viral infection in the elderly. The implications of this study are that modulation of autophagy levels or the dysregulated pro-inflammatory cytokine production that results from defects in autophagy could possibly benefit the aging antiviral immune response.
    Keywords Aging|Virology|Immunology
    Subject code 571
    Language ENG
    Publishing date 2012-01-01 00:00:01.0
    Publisher Yale University
    Publishing country us
    Document type Thesis ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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