25 research outputs found

    Aether scalar tensor theory: Hamiltonian Formalism

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    The Aether Scalar Tensor (AeST) theory is an extension of General Relativity (GR), proposed for addressing galactic and cosmological observations without dark matter. By casting the AeST theory into a 3+13+1 form, we determine its full non-perturbative Hamiltonian formulation and analyse the resulting constraints. We find the presence of four first class and four second class constraints and show that the theory propagates six degrees of freedom on general backgrounds. We determine the case of small perturbations around Minkowski space as an example stemming from our analysis.Comment: 15 pages, 1 tabl

    Respiratory Syncytial Virus Binds and Undergoes Transcription in Neutrophils From the Blood and Airways of Infants With Severe Bronchiolitis

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    Background. Neutrophils are the predominant cell in the lung inflammatory infiltrate of infants with respiratory syncytial virus (RSV) bronchiolitis. Although it has previously been shown that neutrophils from both blood and bronchoalveolar lavage (BAL) are activated, little is understood about their role in response to RSV infection. This study investigated whether RSV proteins and mRNA are present in neutrophils from blood and BAL of infected infants

    Macrophages Are Required for Dendritic Cell Uptake of Respiratory Syncytial Virus from an Infected Epithelium

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    We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells

    A novel immunomodulatory function of neutrophils on rhinovirus-Activated monocytes in vitro

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    © 2016 Published by the BMJ Publishing Group Limited. Background Rhinovirus (RV) infections are the major precipitant of asthma exacerbations. While neutrophilic lung inflammation occurs during such infections, its role remains unclear. Neutrophilic inflammation is associated with increased asthma severity and steroid refractory disease. Neutrophils are vital for controlling infections but also have immunomodulatory functions. Previously, we found that neutrophils respond to viral mimetics but not replication competent RV. We aimed to investigate if neutrophils are activated and/or modulate immune responses of monocytes during RV16 infection. Methods Primary human monocytes and autologous neutrophils were cocultured with or without RV16, in direct contact or separated by transwells. RV16-stimulated monocytes were also exposed to lysed neutrophils, neutrophil membrane components or soluble neutrophil intracellular components. Interleukin 6 (IL-6) and C-X-C motif (CXC)L8 mRNA and proteins were measured by quantitative PCR and ELISA at 24â €..hours. Results RV16 induced IL-6 and CXCL8 in monocytes, but not neutrophils. RV16-induced IL-6 and CXCL8 from monocytes was reduced in the presence of live neutrophils. Transwell separation abolished the inhibitory effects. Lysed neutrophils inhibited RV16-induced IL-6 and CXCL8 from monocytes. Neutrophil intracellular components alone effectively inhibited RV16-induced monocyte-derived IL-6 and CXCL8. Neutrophil intracellular components reduced RV16-induced IL-6 and CXCL8 mRNA in monocytes. Conclusions Cell contact between monocytes and neutrophils is required, and preformed neutrophil mediator(s) are likely to be involved in the suppression of cytokine mRNA and protein production. This study demonstrates a novel regulatory function of neutrophils on RV-Activated monocytes in vitro, challenging the paradigm that neutrophils are predominantly proinflammatory

    Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway epithelial cells and activates neutrophils via Toll-like receptor (TLR)-4

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    <p>Abstract</p> <p>Background</p> <p>Neutrophils play an important role in the pathophysiology of RSV, though RSV does not appear to directly activate neutrophils in the lower airways. Therefore locally produced cytokines or other molecules released by virally-infected airway epithelial cells are likely responsible for recruiting and activating neutrophils. Heat shock proteins (HSPs) are generally regarded as intracellular proteins acting as molecular chaperones; however, HSP72 can also be released from cells, and the implications of this release are not fully understood.</p> <p>Methods</p> <p>Human bronchial epithelial cells (16HBE14o-) were infected with RSV and Hsp72 levels were measured by Western blot and ELISA. Tracheal aspirates were obtained from critically ill children infected with RSV and analyzed for Hsp72 levels by ELISA. Primary human neutrophils and differentiated HL-60 cells were cultured with Hsp72 and supernatants analyzed for cytokine production. In some cases, cells were pretreated with polymyxin B prior to treatment with Hsp72. IκBα was assessed by Western blot and EMSA's were performed to determine NF-κB activation. HL-60 cells were pretreated with neutralizing antibody against TLR4 prior to Hsp72 treatment. Neutrophils were harvested from the bone marrow of wild type or TLR4-deficient mice prior to treatment with Hsp72.</p> <p>Results</p> <p>Infection of 16HBE14o- with RSV showed an induction of intracellular Hsp72 levels as well as extracellular release of Hsp72. Primary human neutrophils from normal donors and differentiated HL-60 cells treated with increasing concentrations of Hsp72 resulted in increased cytokine (IL-8 and TNFα) production. This effect was independent of the low levels of endotoxin in the Hsp72 preparation. Hsp72 mediated cytokine production via activation of NF-κB translocation and DNA binding. Using bone marrow-derived neutrophils from wild type and TLR4-mutant mice, we showed that Hsp72 directly activates neutrophil-derived cytokine production via the activation of TLR4.</p> <p>Conclusion</p> <p>Collectively these data suggest that extracellular Hsp72 is released from virally infected airway epithelial cells resulting in the recruitment and activation of neutrophils.</p

    Inflammatory responses to respiratory syncytial virus

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    SIGLEAvailable from British Library Document Supply Centre- DSC:DXN058671 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    Υπερσυμμετρική Σκοτεινή &apos;Υλη, άμεση και έμμεση ανίχνευσή της

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    Στην εργασία αυτή μελετάται η εφαρμογή της Θεωρίας της Υπερσυμμετρίας σε ένα μοντέλο Σκοτεινής Ύλης βασισμένο στο σωματίδιο neutralino, το οποίο στα πλαίσια του MSSM θεωρούμε να είναι το LSP (Lightest Supersymmetric Particle). Υποθέτουμε ότι η περίσσεια πυκνότητάς του μετά την αποσύνδεση από το θερμικό υπόβαθρο είναι ανιχνεύσιμη και επιπλέον ότι μπορεί να υπάρξει ασθενής αλληλεπίδραση με σωματίδια από το Καθιερωμένο Πρότυπο. Στην αρχή μελετάμε τον τρόπο υπολογισμού μιας τέτοιας πυκνότητας σωματιδίων, για τα οποία θεωρούμε ότι εξακολουθεί να υπάρχει μια ενεργός διατομή και ένας ρυθμός διάσπασης σε σωματίδια του Καθιερωμένου Πρότυπου, ώστε η αριθμητική τους πυκνότητα να βρίσκεται σε συμφωνία με τις κοσμολογικές παραμέτρους πυκνότητας μέχρι στιγμής. Στη συνέχεια αναλύουμε τους τρόπους άμεσης και έμμεσης ανίχνευσης σκοτεινής ύλης, για την οποία υποθέτουμε μια κατανομή πυκνότητας στην άλω του Γαλαξία, και σε άλλες περιοχές όπως το εσωτερικό του Ήλιου. Τέλος, μελετάμε μοντέλα Υπερσυμμετρίας και Υπερβαρύτητας που προτείνουν συνιστώσες σκοτεινής ύλης, και κάνουμε μια φαινομενολογική ανάλυση με βάση το περιορισμένο υπερσυμμετρικό πρότυπο (CMSSM).In this master thesis we study the application of Supersymmetry on a Dark Matter model, where the Lightest Supersymmetric Particle (LSP) is the lightest neutralino. We assume that its relic density after the decoupling from the thermal background, contributes to the matter density of the Universe, and that there is a weak interaction between the LSP and the Standard Model particles. At the beginning, we study the calculation of the dark mat- ter relic density, supposing that there exists a cross section and a decay rate into Standard Model particles, such that the number density of the Dark Matter particles is in accordance with the current cosmological density. Next, we examine the direct and indirect detection of the Dark Matter, assuming that there is a density distribution in the Galactic halo, as well as in other regions in the universe, especially in the Sun. Finally, we perform a phe- nomenological analysis based on the Constrained Minimal Supersymmetric Standard Model, including various cosmological and accelerator data

    Antimicrobial susceptibility testing of Chlamydia trachomatis using a reverse transcriptase PCR-based method.

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    The conventional method for antimicrobial susceptibility testing of Chlamydia trachomatis is subjective and potentially misleading. We have developed a reverse transcriptase PCR (RT-PCR)-based method which is more sensitive and less subjective than the conventional method. Using 16 strains of C. trachomatis in triplicate assays, we found the RT-PCR method consistently more sensitive than the conventional technique for all eight antimicrobials tested, with resultant MICs determined by RT-PCR ranging from 1.6-fold higher (erythromycin) to >/=195-fold higher (amoxicillin)

    T Lymphocytes Contribute to Antiviral Immunity and Pathogenesis in Experimental Human Metapneumovirus Infection▿

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    Human metapneumovirus (hMPV), a member of the family Paramyxoviridae, is a leading cause of lower respiratory tract infections in children, the elderly, and immunocompromised patients. Virus- and host-specific mechanisms of pathogenesis and immune protection are not fully understood. By an intranasal inoculation model, we show that hMPV-infected BALB/c mice developed clinical disease, including airway obstruction and hyperresponsiveness (AHR), along with histopathologic evidence of lung inflammation and viral replication. hMPV infection protected mice against subsequent viral challenge, as demonstrated by undetectable viral titers, lack of body weight loss, and a significant reduction in the level of lung inflammation. No cross-protection with other paramyxoviruses, such as respiratory syncytial virus, was observed. T-lymphocyte depletion studies showed that CD4+ and CD8+ T cells cooperate synergistically in hMPV eradication during primary infection, but CD4+ more than CD8+ T cells also enhanced clinical disease and lung pathology. Concurrent depletion of CD4+ and CD8+ T cells completely blocked airway obstruction as well as AHR. Despite impaired generation of neutralizing anti-hMPV antibodies in the absence of CD4+ T cells, mice had undetectable viral replication after hMPV challenge and were protected from clinical disease, suggesting that protection can be provided by an intact CD8+ T-cell compartment. Whether these findings have implications for naturally acquired human infections remains to be determined
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