The Experts below are selected from a list of 144 Experts worldwide ranked by ideXlab platform
Colin D Bingle - One of the best experts on this subject based on the ideXlab platform.
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distribution of wfdc2 he4 a putative host Defence Protein in the respiratory tract of normal and diseased mice
European Respiratory Journal, 2013Co-Authors: Olympia Gianfrancesco, Lynne Bingle, Colin D BingleAbstract:WFDC2/HE4 encodes a poorly characterised secretory Protein that shares structural similarity to the multifunctional host Defence Protein, SLPI, through possession of two conserved Whey Acidic Protein/four disulphide-core (WFDC) domains. Like SLPI, WFDC2 is expressed in multiple epithelia within the respiratory tract and although its’ function remains unresolved, recent evidence supports its9 role as an antiProteinase. We have previously shown that it is over-expressed in lung diseases characterised by abnormalities of protease/antiprotease balance, including cystic fibrosis. Nothing is known about the distribution of WFDC2 in the mouse. In this study we have systematically localized the Protein in normal adult mice as well in a number of mouse models characterised by epithelial remodelling. Strong WFDC2 staining is seen throughout the airway epithelium from the trachea down to the smallest airways. Staining is also seen in tracheal submucosal glands. No staining is seen in the peripheral lung. Interestingly, staining is absent from the respiratory epithelium of the nasal passages whereas goblet cells stain strongly in these locations. In bleomycin and OVA treated mice there is elevated staining throughout the remodeled epithelium that is not limited to goblet cells and strikingly there is very strong staining within the alveolar (Type II) cells in these regions. Mouse WFDC2 is elevated in a number of chronic disease models and suggests that the gene exhibits a level of promiscuity relating to its molecular regulation. Knowledge of the complex expression pattern of this Protein will allow the use of tractable mouse models of disease to dissect its’ function.
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Distribution of WFDC2/HE4, a putative host Defence Protein, in the respiratory tract of normal and diseased mice
European Respiratory Journal, 2013Co-Authors: Olympia Gianfrancesco, Lynne Bingle, Colin D BingleAbstract:WFDC2/HE4 encodes a poorly characterised secretory Protein that shares structural similarity to the multifunctional host Defence Protein, SLPI, through possession of two conserved Whey Acidic Protein/four disulphide-core (WFDC) domains. Like SLPI, WFDC2 is expressed in multiple epithelia within the respiratory tract and although its’ function remains unresolved, recent evidence supports its9 role as an antiProteinase. We have previously shown that it is over-expressed in lung diseases characterised by abnormalities of protease/antiprotease balance, including cystic fibrosis. Nothing is known about the distribution of WFDC2 in the mouse. In this study we have systematically localized the Protein in normal adult mice as well in a number of mouse models characterised by epithelial remodelling. Strong WFDC2 staining is seen throughout the airway epithelium from the trachea down to the smallest airways. Staining is also seen in tracheal submucosal glands. No staining is seen in the peripheral lung. Interestingly, staining is absent from the respiratory epithelium of the nasal passages whereas goblet cells stain strongly in these locations. In bleomycin and OVA treated mice there is elevated staining throughout the remodeled epithelium that is not limited to goblet cells and strikingly there is very strong staining within the alveolar (Type II) cells in these regions. Mouse WFDC2 is elevated in a number of chronic disease models and suggests that the gene exhibits a level of promiscuity relating to its molecular regulation. Knowledge of the complex expression pattern of this Protein will allow the use of tractable mouse models of disease to dissect its’ function.
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Differential epithelial expression of the putative innate immune molecule SPLUNC1 in Cystic Fibrosis
Respiratory Research, 2007Co-Authors: Lynne Bingle, Frances A. Barnes, Simon S. Cross, Doris Rassl, William A. Wallace, Michael A Campos, Colin D BingleAbstract:Introduction Short PLUNC1 (SPLUNC1) is the founding member of a family of Proteins (PLUNCS) expressed in the upper respiratory tract and oral cavity, which may function in host Defence. It is one of the most highly expressed genes in the upper airways and the Protein has been detected in sputum and nasal secretions. The biology of the PLUNC family is poorly understood but in keeping with the putative function of the Protein as an immune Defence Protein, a number of RNA and Protein studies have indicated that SPLUNC1 is increased in inflammatory/infectious conditions such as Cystic Fibrosis (CF), COPD and allergic rhinitis.
John P Carr - One of the best experts on this subject based on the ideXlab platform.
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A cucumber mosaic virus mutant lacking the 2b counter-Defence Protein gene provides protection against wild-type strains.
The Journal of general virology, 2020Co-Authors: Heiko Ziebell, Tina Payne, James O Berry, John A Walsh, John P CarrAbstract:Several plant virus mutants, in which genes encoding silencing suppressor Proteins have been deleted, are known to induce systemic or localized RNA silencing against themselves and other RNA molecules containing homologous sequences. Thus, it is thought that many cases of cross-protection, in which infection with a mild or asymptomatic virus mutant protects plants against challenge infection with closely related virulent viruses, can be explained by RNA silencing. We found that a cucumber mosaic virus (CMV) mutant of the subgroup IA strain Fny (Fny-CMVDelta2b), which cannot express the 2b silencing suppressor Protein, cross-protects tobacco (Nicotiana tabacum) and Nicotiana benthamiana plants against disease induction by wild-type Fny-CMV. However, protection is most effective only if inoculation with Fny-CMVDelta2b and challenge inoculation with wild-type CMV occurs on the same leaf. Unexpectedly, Fny-CMVDelta2b also protected plants against infection with TC-CMV, a subgroup II strain that is not closely related to Fny-CMV. Additionally, in situ hybridization revealed that Fny-CMVDelta2b and Fny-CMV can co-exist in the same tissues but these tissues contain zones of Fny-CMVDelta2b-infected host cells from which Fny-CMV appears to be excluded. Taken together, it appears unlikely that cross-protection by Fny-CMVDelta2b occurs by induction of systemic RNA silencing against itself and homologous RNA sequences in wild-type CMV. It is more likely that protection occurs through either induction of very highly localized RNA silencing, or by competition between strains for host cells or resources.
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effects of dicer like endoribonucleases 2 and 4 on infection of arabidopsis thaliana by cucumber mosaic virus and a mutant virus lacking the 2b counter Defence Protein gene
Journal of General Virology, 2009Co-Authors: Heiko Ziebell, John P CarrAbstract:In tobacco and Nicotiana benthamiana, limited cross-protection against cucumber mosaic virus strain Fny (Fny-CMV) was provided by prior inoculation with a deletion mutant lacking the 2b silencing-suppressor Protein gene (Fny-CMVΔ2b). Cross-protection by Fny-CMVΔ2b did not result from induction of systemic RNA silencing. We investigated whether protection occurs through induction of localized RNA silencing by using Arabidopsis thaliana plants harbouring mutations in genes encoding the dicer-like (DCL) endoribonucleases 2, 3 and 4 involved in antiviral silencing. In wild-type A. thaliana (Col-0) plants, Fny-CMVΔ2b was symptomless and cross-protected against Fny-CMV infection. Cross-protection by Fny-CMVΔ2b against Fny-CMV infection was not abolished in dcl2, dcl3 or dcl4 mutant plants and was strongest in dcl2/4 double mutants, although in these plants and in dcl4 mutants, Fny-CMVΔ2b replicated to high levels and induced strong symptoms. The results suggest that Fny-CMVΔ2b/Fny-CMV cross-protection is not completely dependent on RNA silencing and also involves competition between these viruses.
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a cucumber mosaic virus mutant lacking the 2b counter Defence Protein gene provides protection against wild type strains
Journal of General Virology, 2007Co-Authors: Heiko Ziebell, Tina Payne, James O Berry, John A Walsh, John P CarrAbstract:Several plant virus mutants, in which genes encoding silencing suppressor Proteins have been deleted, are known to induce systemic or localized RNA silencing against themselves and other RNA molecules containing homologous sequences. Thus, it is thought that many cases of cross-protection, in which infection with a mild or asymptomatic virus mutant protects plants against challenge infection with closely related virulent viruses, can be explained by RNA silencing. We found that a cucumber mosaic virus (CMV) mutant of the subgroup IA strain Fny (Fny-CMVΔ2b), which cannot express the 2b silencing suppressor Protein, cross-protects tobacco (Nicotiana tabacum) and Nicotiana benthamiana plants against disease induction by wild-type Fny-CMV. However, protection is most effective only if inoculation with Fny-CMVΔ2b and challenge inoculation with wild-type CMV occurs on the same leaf. Unexpectedly, Fny-CMVΔ2b also protected plants against infection with TC-CMV, a subgroup II strain that is not closely related to Fny-CMV. Additionally, in situ hybridization revealed that Fny-CMVΔ2b and Fny-CMV can co-exist in the same tissues but these tissues contain zones of Fny-CMVΔ2b-infected host cells from which Fny-CMV appears to be excluded. Taken together, it appears unlikely that cross-protection by Fny-CMVΔ2b occurs by induction of systemic RNA silencing against itself and homologous RNA sequences in wild-type CMV. It is more likely that protection occurs through either induction of very highly localized RNA silencing, or by competition between strains for host cells or resources.
Olympia Gianfrancesco - One of the best experts on this subject based on the ideXlab platform.
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distribution of wfdc2 he4 a putative host Defence Protein in the respiratory tract of normal and diseased mice
European Respiratory Journal, 2013Co-Authors: Olympia Gianfrancesco, Lynne Bingle, Colin D BingleAbstract:WFDC2/HE4 encodes a poorly characterised secretory Protein that shares structural similarity to the multifunctional host Defence Protein, SLPI, through possession of two conserved Whey Acidic Protein/four disulphide-core (WFDC) domains. Like SLPI, WFDC2 is expressed in multiple epithelia within the respiratory tract and although its’ function remains unresolved, recent evidence supports its9 role as an antiProteinase. We have previously shown that it is over-expressed in lung diseases characterised by abnormalities of protease/antiprotease balance, including cystic fibrosis. Nothing is known about the distribution of WFDC2 in the mouse. In this study we have systematically localized the Protein in normal adult mice as well in a number of mouse models characterised by epithelial remodelling. Strong WFDC2 staining is seen throughout the airway epithelium from the trachea down to the smallest airways. Staining is also seen in tracheal submucosal glands. No staining is seen in the peripheral lung. Interestingly, staining is absent from the respiratory epithelium of the nasal passages whereas goblet cells stain strongly in these locations. In bleomycin and OVA treated mice there is elevated staining throughout the remodeled epithelium that is not limited to goblet cells and strikingly there is very strong staining within the alveolar (Type II) cells in these regions. Mouse WFDC2 is elevated in a number of chronic disease models and suggests that the gene exhibits a level of promiscuity relating to its molecular regulation. Knowledge of the complex expression pattern of this Protein will allow the use of tractable mouse models of disease to dissect its’ function.
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Distribution of WFDC2/HE4, a putative host Defence Protein, in the respiratory tract of normal and diseased mice
European Respiratory Journal, 2013Co-Authors: Olympia Gianfrancesco, Lynne Bingle, Colin D BingleAbstract:WFDC2/HE4 encodes a poorly characterised secretory Protein that shares structural similarity to the multifunctional host Defence Protein, SLPI, through possession of two conserved Whey Acidic Protein/four disulphide-core (WFDC) domains. Like SLPI, WFDC2 is expressed in multiple epithelia within the respiratory tract and although its’ function remains unresolved, recent evidence supports its9 role as an antiProteinase. We have previously shown that it is over-expressed in lung diseases characterised by abnormalities of protease/antiprotease balance, including cystic fibrosis. Nothing is known about the distribution of WFDC2 in the mouse. In this study we have systematically localized the Protein in normal adult mice as well in a number of mouse models characterised by epithelial remodelling. Strong WFDC2 staining is seen throughout the airway epithelium from the trachea down to the smallest airways. Staining is also seen in tracheal submucosal glands. No staining is seen in the peripheral lung. Interestingly, staining is absent from the respiratory epithelium of the nasal passages whereas goblet cells stain strongly in these locations. In bleomycin and OVA treated mice there is elevated staining throughout the remodeled epithelium that is not limited to goblet cells and strikingly there is very strong staining within the alveolar (Type II) cells in these regions. Mouse WFDC2 is elevated in a number of chronic disease models and suggests that the gene exhibits a level of promiscuity relating to its molecular regulation. Knowledge of the complex expression pattern of this Protein will allow the use of tractable mouse models of disease to dissect its’ function.
Lynne Bingle - One of the best experts on this subject based on the ideXlab platform.
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distribution of wfdc2 he4 a putative host Defence Protein in the respiratory tract of normal and diseased mice
European Respiratory Journal, 2013Co-Authors: Olympia Gianfrancesco, Lynne Bingle, Colin D BingleAbstract:WFDC2/HE4 encodes a poorly characterised secretory Protein that shares structural similarity to the multifunctional host Defence Protein, SLPI, through possession of two conserved Whey Acidic Protein/four disulphide-core (WFDC) domains. Like SLPI, WFDC2 is expressed in multiple epithelia within the respiratory tract and although its’ function remains unresolved, recent evidence supports its9 role as an antiProteinase. We have previously shown that it is over-expressed in lung diseases characterised by abnormalities of protease/antiprotease balance, including cystic fibrosis. Nothing is known about the distribution of WFDC2 in the mouse. In this study we have systematically localized the Protein in normal adult mice as well in a number of mouse models characterised by epithelial remodelling. Strong WFDC2 staining is seen throughout the airway epithelium from the trachea down to the smallest airways. Staining is also seen in tracheal submucosal glands. No staining is seen in the peripheral lung. Interestingly, staining is absent from the respiratory epithelium of the nasal passages whereas goblet cells stain strongly in these locations. In bleomycin and OVA treated mice there is elevated staining throughout the remodeled epithelium that is not limited to goblet cells and strikingly there is very strong staining within the alveolar (Type II) cells in these regions. Mouse WFDC2 is elevated in a number of chronic disease models and suggests that the gene exhibits a level of promiscuity relating to its molecular regulation. Knowledge of the complex expression pattern of this Protein will allow the use of tractable mouse models of disease to dissect its’ function.
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Distribution of WFDC2/HE4, a putative host Defence Protein, in the respiratory tract of normal and diseased mice
European Respiratory Journal, 2013Co-Authors: Olympia Gianfrancesco, Lynne Bingle, Colin D BingleAbstract:WFDC2/HE4 encodes a poorly characterised secretory Protein that shares structural similarity to the multifunctional host Defence Protein, SLPI, through possession of two conserved Whey Acidic Protein/four disulphide-core (WFDC) domains. Like SLPI, WFDC2 is expressed in multiple epithelia within the respiratory tract and although its’ function remains unresolved, recent evidence supports its9 role as an antiProteinase. We have previously shown that it is over-expressed in lung diseases characterised by abnormalities of protease/antiprotease balance, including cystic fibrosis. Nothing is known about the distribution of WFDC2 in the mouse. In this study we have systematically localized the Protein in normal adult mice as well in a number of mouse models characterised by epithelial remodelling. Strong WFDC2 staining is seen throughout the airway epithelium from the trachea down to the smallest airways. Staining is also seen in tracheal submucosal glands. No staining is seen in the peripheral lung. Interestingly, staining is absent from the respiratory epithelium of the nasal passages whereas goblet cells stain strongly in these locations. In bleomycin and OVA treated mice there is elevated staining throughout the remodeled epithelium that is not limited to goblet cells and strikingly there is very strong staining within the alveolar (Type II) cells in these regions. Mouse WFDC2 is elevated in a number of chronic disease models and suggests that the gene exhibits a level of promiscuity relating to its molecular regulation. Knowledge of the complex expression pattern of this Protein will allow the use of tractable mouse models of disease to dissect its’ function.
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Differential epithelial expression of the putative innate immune molecule SPLUNC1 in Cystic Fibrosis
Respiratory Research, 2007Co-Authors: Lynne Bingle, Frances A. Barnes, Simon S. Cross, Doris Rassl, William A. Wallace, Michael A Campos, Colin D BingleAbstract:Introduction Short PLUNC1 (SPLUNC1) is the founding member of a family of Proteins (PLUNCS) expressed in the upper respiratory tract and oral cavity, which may function in host Defence. It is one of the most highly expressed genes in the upper airways and the Protein has been detected in sputum and nasal secretions. The biology of the PLUNC family is poorly understood but in keeping with the putative function of the Protein as an immune Defence Protein, a number of RNA and Protein studies have indicated that SPLUNC1 is increased in inflammatory/infectious conditions such as Cystic Fibrosis (CF), COPD and allergic rhinitis.
W Eddie K Ip - One of the best experts on this subject based on the ideXlab platform.
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low serum mannose binding lectin level increases the risk of death due to pneumococcal infection
Clinical Infectious Diseases, 2008Co-Authors: Damon P Eisen, Melinda M Dean, Marja A Boermeester, Katy Fidler, Anthony C Gordon, Gitte Kronborg, Antonis Payeras, H Valdimarsson, Stephen J Brett, W Eddie K IpAbstract:BACKGROUND Previous studies have shown associations between low mannose-binding lectin (MBL) level or variant MBL2 genotype and sepsis susceptibility. However, MBL deficiency has not been rigorously defined, and associations with sepsis outcomes have not been subjected to multivariable analysis. METHODS We reanalyzed MBL results in a large cohort with use of individual data from 4 studies involving a total of 1642 healthy control subjects and systematically defined a reliable deficiency cutoff. Subsequently, data were reassessed to extend previous MBL and sepsis associations, with adjustment for known outcome predictors. We reanalyzed individual data from 675 patients from 5 adult studies and 1 pediatric study of MBL and severe bacterial infection. RESULTS XA/O and O/O MBL2 genotypes had the lowest median MBL concentrations. Receiver operating characteristic analysis revealed that an MBL cutoff value of 0.5 microg/mL was a reliable predictor of low-producing MBL2 genotypes (sensitivity, 82%; specificity, 82%; negative predictive value, 98%). MBL deficiency was associated with increased likelihood of death among patients with severe bacterial infection (odds ratio, 2.11; 95% confidence interval, 1.30-3.43). In intensive care unit-based studies, there was a trend toward increased risk of death among MBL-deficient patients (odds ratio, 1.58; 95% confidence interval, 0.90-2.77) after adjustment for Acute Physiology and Chronic Health Enquiry II score. The risk of death was increased among MBL-deficient patients with Streptococcus pneumoniae infection (odds ratio, 5.62; 95% confidence interval, 1.27-24.92) after adjustment for bacteremia, comorbidities, and age. CONCLUSIONS We defined a serum level for MBL deficiency that can be used with confidence in future studies of MBL disease associations. The risk of death was increased among MBL-deficient patients with severe pneumococcal infection, highlighting the pathogenic significance of this innate immune Defence Protein.
