1,721,014 research outputs found
Chlamydia pneumoniae-induced foam cell formation requires MyD88-dependent and -independent signaling and is reciprocally modulated by liver X receptor activation.
Full text linkChlamydia pneumoniae is detected by macrophages and other APCs via TLRs and can exacerbate developing atherosclerotic lesions, but how that occurs is not known. Liver X receptors (LXRs) centrally control reverse cholesterol transport, but also negatively modulate TLR-mediated inflammatory pathways. We isolated peritoneal macrophages from wild-type, TLR2, TLR3, TLR4, TLR2/4, MyD88, TRIF, MyD88/TRIF, and IFN regulatory factor 3 (IRF3) KO mice, treated them with live or UV-killed C. pneumoniae in the presence or absence of oxidized LDL, then measured foam cell formation. In some experiments, the synthetic LXR agonist GW3965 was added to macrophages infected with C. pneumoniae in the presence of oxidized LDL. Both live and UV-killed C. pneumoniae induced IRF3 activation and promoted foam cell formation in wild-type macrophages, whereas the genetic absence of TLR2, TLR4, MyD88, TRIF, or IRF3, but not TLR3, significantly reduced foam cell formation. C. pneumoniae-induced foam cell formation was significantly reduced by the LXR agonist GW3965, which in turn inhibited C. pneumoniae-induced IRF3 activation, suggesting a bidirectional cross-talk. We conclude that C. pneumoniae facilitates foam cell formation via activation of both MyD88-dependent and MyD88-independent (i.e., TRIF-dependent and IRF3-dependent) pathways downstream of TLR2 and TLR4 signaling and that TLR3 is not involved in this process. This mechanism could at least partly explain why infection with C. pneumoniae accelerates the development of atherosclerotic plaque and lends support to the proposal that LXR agonists might prove clinically useful in suppressing atherogenesis
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Assessment of peripheral airway function following chronic allergen challenge in a sheep model of asthma.
Full text linkBACKGROUND: There is increasing evidence that the small airways contribute significantly to the pathophysiology of asthma. However, due to the difficulty in accessing distal lung regions in clinical settings, functional changes in the peripheral airways are often overlooked in studies of asthmatic patients. The aim of the current study was to characterize progressive changes in small airway function in sheep repeatedly challenged with house dust mite (HDM) allergen. METHODOLOGY/PRINCIPAL FINDINGS: Four spatially separate lung segments were utilized for HDM challenges. The right apical, right medial, right caudal and left caudal lung segments received 0, 8, 16 and 24 weekly challenges with HDM respectively. A wedged-bronchoscope technique was used to assess changes in peripheral resistance (R(p)) at rest, and in response to specific and non-specific stimuli throughout the trial. Allergen induced inflammatory cell infiltration into bronchoalveolar lavage and increases in R(p) in response to HDM and methacholine were localized to treated lung segments, with no changes observed in adjacent lung segments. The acute response to HDM was variable between sheep, and was significantly correlated to airway responsiveness to methacholine (r(s) = 0.095, P<0.01). There was no correlation between resting R(p) and the number of weeks of HDM exposure. Nor was there a correlation between the magnitude of early-phase airway response and the number of HDM-challenges. CONCLUSIONS: Our findings indicate that airway responses to allergic and non-allergic stimuli are localized to specific treated areas of the lung. Furthermore, while there was a decline in peripheral airway function with HDM exposure, this decrease was not correlated with the length of allergen challenge
Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness
Full text linkBackground
Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide
(LPS) is a component of the cell wall of Gram negative bacteria and a potent
activator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasal
mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels
in mucosal lining fluid (MLF).
Methods
We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy nonatopic
subjects (n = 14 per protocol). Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl) or
placebo were administered by a single nasal spray to each nostril. Using the recently developed
method of nasosorption with synthetic adsorptive matrices (SAM), a series of samples
were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay
in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1) was quantified
from nasal epithelial curettage samples taken before and after challenge.
Results
Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the
nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-
8) and CCL3 (MIP-1α) (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg
LPS). At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05). Dose-related
changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils
appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels
showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg
and 30μg LPS)
Severe pandemic H1N1 2009 infection is associated with transient NK and T deficiency and aberrant CD8 responses.
Full text linkBACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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