1,170 research outputs found
A new look at the pathogenesis of asthma
No full textAsthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.<br/
Applications of UAVS for coastal monitoring: Holgate, Long Beach township, New Jersey
No full textCoastal zones are dynamic environments that support a large percentage of populations and hold cultural, economic, and social importance. Erosion from nuisance flooding and storms are already a threat to coastlines and are further exacerbated by the effects of climate change and rising seas. Coastal monitoring can inform of these environmental changes, but frequent high resolution spatial and temporal data is needed to better understand the morphological impact. By modifying an existing monitoring protocol, this study utilizes UAVs (unmanned aerial vehicles) to collect high resolution imagery, real time kinematic ground control points (RTK; GCPs), and measurement of five cross-shore beach transects monthly from October 2020 to May 2021 at Holgate beach, Long Beach Township, New Jersey. With this information, a monthly sediment volumetric change analysis, custom volumetric change calculations, and an oceanographic forcings model to relate water levels with geomorphological changes were all created. A correlation between increased water levels due to periods of storminess and beach erosion was found. Overall, storminess (October 2020 to February 2021) related to net erosion of Holgate, while periods of quiescence (February 2021 to May 2021) related to net accumulation. However, sediment was overall lost from the beginning to end of the study, affirming volume loss of the dry beach and dunes at Holgate.M.S.Includes bibliographical reference
Introduction to the proceedings of the Workshop on Topology and Topological Groups (WTTG2023) held at the African Institute for Mathematical Sciences (AIMS) in Muizenberg (South Africa) on the 16th and 17th of November 2023
No full textWe illustrate briefly the nature of the scientific contributions, which appear in the proceedings of WTTG2023 held at AIMS in Muizenberg (South Africa) on the 16th and 17th of November 2023. We also mention the history of this series of meetings and the motivations for the interactions between Topological Group Theory and other branches of mathematics; the connections with Lie Theory and Topological Algebra characterized WTTG2023. Finally, we survey the relevance of the supporting institutions and the role of their corresponding projects in the academic formation of young researchers within the initiatives of WTTG2023 (and its past editions in 2021 and 2017)
Developing consensus on national respiratory research priorities: Key findings from the UK Respiratory Research Collaborative's e-Delphi exercise
No full textCytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transduction
No full textIL (interleukin)-4 and IL-13 are key cytokines in the pathogenesis of allergic inflammatory disease. IL-4 and IL-13 share many functional properties as a result of their utilization of a common receptor complex comprising IL-13Ralpha1 (IL-13 receptor alpha-chain 1) and IL-4Ralpha. The second IL-13R (IL-13 receptor) has been identified, namely IL-13Ralpha2. This has been thought to be a decoy receptor due to its short cytoplasmic tail and its high binding affinity for IL-13 but not IL-4. IL-13Ralpha2 exists on the cell membrane, intracellularly and in a soluble form. Recent reports revealed that membrane IL-13Ralpha2 may have some signalling capabilities, and a soluble form of IL-13Ralpha2 can be generated in the presence of environmental allergens such as DerP. Interestingly, IL-13Ralpha2 has also been shown to regulate both IL-13 and IL-4 response in primary airway cells, despite the fact that IL-13Ralpha2 does not bind IL-4. The regulator mechanism is still unclear but the physical association of IL-13Ralpha2 with IL-4Ralpha appears to be a key regulatory step. These results suggest that the cytoplasmic tail of IL-13Ralpha2 may interfere with the association or activation of signalling molecules, such as JAK1 (Janus kinase 1), on IL-4Ralpha and thus prevents downstream signal cascade. The receptor has more complicated functions than a simple decoy receptor. In this review, we discuss newly revealed functions of IL-13Ralpha2.</p
Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response
No full textRhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3
A single-nucleotide polymorphism in intelectin 1 is associated with increased asthma risk
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ADAM33: a cellular model of over-expression. From full length to soluble
No full textPolymorphic variation in the A Disintegrin And Metalloprotease 33 (ADAM33) genehas been associated with asthma and bronchial hyperresponsiveness. The ADAMfamily of proteins has a multi-domain structure and has diverse biological functionswhich can include growth factor shedding, cell migration and cell adhesion.Evidence for a soluble form of ADAM33 has been found in BAL fluid of asthmaticpatients and there is evidence that ADAM33 has a function in angiogenesis.To determine the possible function(s) of the full length ADAM33 protein, it wasover expressed in HEK293 that do not normally express ADAM33 and thephenotypic consequences analyzed. Cells stably expressing full length ADAM33under the control of a CMV promoter were obtained by selection with the antibiotic,G418. The expression of ADAM33 was confirmed by western blot analysis. Controlcells were transfected with an empty vector control encoding G418 resistance only.Cells were examined for changes in cell phenotype and ability to produce solubleADAM33.Cells stably expressing ADAM33 grew more quickly than mock transfected cellsbut this effect was lost over time. However, processed (ie. active) ADAM33 proteincould not be detected by western blot. In order to determine whether asubpopulation of cells was able to produce active ADAM33, the cells were clonedand re-cloned by limiting dilution. This allowed isolation of a number of ADAM33clones that produced processed protein. Furthermore, these experiments revealedthat ADAM33 expression increased the clonogenic potential of the cells.Supernatant from cloned cells was pulled down with ConA and samples analysed bywestern blot which showed a band at 50-55kDa in the ADAM33 clones using anantibody to the metalloproteinase domain. This soluble ADAM33 was active andpromoted angiogenesis using a HUVEC capillary tube forming assay. SolubleADAM33 was upregulated in the presence of TGF-?2 and its shedding is unliky tobe autocatalytic.Over expression of ADAM33 in HEK293 cells alters the clonogenic potential andsurvival of HEK293 cells in low density cultures. This property may contribute tothe behaviour of mesenchymal cells in asthmatic airways. Soluble ADAM33 isreleased into culture media and has functional activity. Its release is up regulated inthe presence of TGF-?2
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