117,355 research outputs found

    Interferons in immunity to chlamydia pneumoniae

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    The cytokine IFN-gamma is the architect behind an amazing immunological program of host resistance to intracellular bacterial and protozoan infections. IFN-gamma activates macrophages, making them into inhospitable habitats for parasites attempting to grow inside them. The family of obligate intracellular Gram-negative bacteria Chlamydia is an example of such pathogens. The overall aim of this thesis was to unravel resistance to infection with the human respiratory pathogen C. pneumoniae. Specific focus was placed on innate immune responses to C. pneumoniae and the regulation and role of IFN-gamma in the outcome of infection. An experimental mouse model of lung infection and a macrophage model of in vitro infection were used for this purpose. A protective role for infection-induced IFN-gamma in restricting C. pneumoniae growth in vivo was observed, though IFN-gamma was not required for resolution of infection. IL-12 and/or IL-23 was a necessary but not an absolute requirement for expression of IFN-gamma. IFN-gamma-dependent protection was in part mediated by iNOS expression. TNF-alpha, known to be synergistic with IFN-gamma, was not required for restricting Chlamydial growth. Innate immune cells in the lung constituted an important source of IFN-gamma and were essential for restricting C. pneumoniae growth and for containment of bacteria in the lungs. However, NK cells were not implicated in such protective IFN-gamma release. On the other hand, lung macrophages isolated from C.pneumoniae-infected mice expressed IFN-gamma. Moreover, bone marrow-derived macrophages (BMMphi) conferred upon transfer to RAG-1-/-/IFN-gamma-/-mice, enhanced resistance to C. pneumoniae infection via their ability to release IFN-gamma. Innate IFN-gamma was however not required for protection conferred by CD4+ or CD8+ T cells. Innate and T cell-derived IFN-gamma are also non-redundant (complementary) in protesting mice against C. pneumoniae. C. pneumoniae-infected BMMphi also expressed IFN-gamma in vitro. Such IFN-gamma release was IL-12independent but required instead IFN-alpha/beta and restricted Chlamydial growth. IFN-alpha/beta, and not IFNgamma, was required for iNOS-mediated protection in BMMphi. The molecular details of BMMphi-derived IFNgamma expression revealed a TLR4-MyD88-dependent pathway of IFN-alpha and IFN-gamma induction. Also surprising was the presente of a TLR4- and MyD88-independent, infection-induced NF-kappaB activation and proinflammatory cytokine expression. Phosphorylation of STAT1 during infection was IFN-alpha/beta-dependent, and necessary for increased IFN-gamma expression and for restricting Chlamydial growth. Expression of IFN-gamma and restriction of C. pneumoniae growth also required NF-kappaB activation, but such activation was independent of IFN-alpha/beta, revealing a dual pathway of C.pneumoniae-induced IFN-gamma expression in BMMphi: a TLR4-MyD88-IFNalpha/beta-STAT1 -dependent pathway, and a TLR4-independent pathway leading to NF-kappaB activation. IFN-alpha/beta was also protective in vivo by cooperating with IFN-gamma for activation of STAT1, which was required for restricting Chlamydial growth. Different from the in vitro situation, IFN-gamma was sufficient on its own for this effect and did not require IFN-alpha/beta for its expression. In summary, IFN-gamma is important for restricting C. pneumoniae growth. Innate IFN-gamma is protective both in lungs and in BMMphi. IFN-alpha/beta are pivotal in regulating protective responses in BMMphi, including IFNgamma release, but are dispensable for IFN-gamma expression and protection in vivo. This discrepancy may be a qualitative feature in C. pneumoniae pattern recognition by different cell types; lung cells convey the generation of protective, IL-12-driven responses, while IFN-alpha/beta-driven protection in BMMphi is essential.List of scientific papersI. Rottenberg ME, Gigliotti Rothfuchs AC, Gigliotti D, Svanholm C, Bandholtz L, Wigzell H (1999). "Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified mice. " J Immunol 162(5): 2829-36 https://pubmed.ncbi.nlm.nih.gov/10072530 II. Rottenberg ME, Gigliotti Rothfuchs A, Gigliotti D, Ceausu M, Une C, Levitsky V, Wigzell H (2000). "Regulation and role of IFN-gamma in the innate resistance to infection with Chlamydia pneumoniae. " J Immunol 164(9): 4812-8 https://pubmed.ncbi.nlm.nih.gov/10779789 III. Gigliotti Rothfuchs A, Kreuger MR, Wigzell H, Rottenberg ME (2004). "Macrophages, CD4(+) or CD8(+) Cells Are Each Sufficient for Protection against Chlamydia pneumoniae Infection through their Ability to Secrete IFN-gamma. " J Immunol 172(4): 2407-15 https://pubmed.ncbi.nlm.nih.gov/14764711 IV. Rothfuchs AG, Gigliotti D, Palmblad K, Andersson U, Wigzell H, Rottenberg ME (1970). "IFN-alpha beta-dependent, IFN-gamma secretion by bone marrow-derived macrophages controls an intracellular bacterial infection. " J Immunol 167(11): 6453-61 https://pubmed.ncbi.nlm.nih.gov/11714812 V. Gigliotti Rothfuchs A, Trumstedt C, Wigzell H, Rottenberg ME (2004). "Intracellular bacterial infection-induced IFN-gamma is critically but not solely dependent on TLR-MyD88-IFN-alpha/beta-STAT1 signaling." (Submitted)VI. Gigliotti Rothfuchs A, Trumstedt C, Wigzell H, Rottenberg ME (2004). "Protective role of IFN-alpha/beta against murine infection with Chlamydia pneumoniae." (Manuscript)</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Square Dancing with the Stars to Enhance Dynamic Hirschman Linkages?

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    In this Presidential Address, the author takes the reader on a reconnaissance of his life and time as a regional scientist. He points out scenery he found scintillating along the way, hoping that some may pick up the banner and chew on a few of the ideas for a while. He suggests a revisit to Albert O. Hirschman’s notion of key sectors and more empirical analysis related to Marcus Berliant’s and Masahisa Fujita’s notion of knowledge creation and transfer.Presidential Address, San Antonio, Texas, March 29, 2014 (53rd Meetings of the Southern Regional Science Association

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Letter from unknown writer to Jesse L. Boyce

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    Letter to Jesse L. Boyce from unknown author (possibly Jack) about the investigation into the powder magazine located in the Grand Canyon. Some personal news is included in the letter such as the writer's marriage to the daughter of C.A. Taylor, former Supervisor of Cochise County

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Sarah L. Blum Author Visit - Warrior Nurse: PTSD and Healing

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    Hear Sarah L. Blum, author of Women Under Fire: Abuse in the Military, discuss her newest book, Warrior Nurse: PTSD and Healing followed by a Q&A and book signing. Sarah L. Blum is a decorated Vietnam veteran who served as an operating room nurse during the intense fighting of 1967. In recognition of her service, she was awarded the Army Commendation Medal. Sponsored by CWU Veterans Center and CWU Libraries.https://digitalcommons.cwu.edu/libraryevents/1252/thumbnail.jp

    Lillian L. Lambert, Author, Speaker, and Entrepreneur

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    Lillian L. Lambert, Author, Speaker, and Entrepreneu

    Letter to Alfred L. Shoemaker, February 10, 1948

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    A handwritten letter from an unknown author addressed to Alfred L. Shoemaker, dated February 10, 1948. Within, the author discusses the Pennsylvania Dutch word for Ash Wednesday, along with traditions associated with this day.https://digitalcommons.ursinus.edu/shoemaker_documents/1118/thumbnail.jp
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