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Editorial. ADAM 33: just another asthma gene or a breakthrough in understanding the origins of bronchial hyperresponsiveness?
No full textADAM 33, the latest of the ADAM proteins to be described, has been identified as a major susceptibility gene in asthma linked to bronchial hyperresponsiveness. It provides an important breakthrough in our understanding of this complex disorder and its variable clinical and physiological presentations
Enhanced upregulation of smooth muscle-related transcripts by TGF??in asthmatic (myo)fibroblasts
No full textBackground: Transforming growth factor beta (TGFß) upregulates a number of smooth muscle specific genes in (myo)fibroblasts. As asthma is characterised by an increase in airway smooth muscle, we postulated that TGFß? favours differentiation of asthmatic (myo)fibroblasts towards a smooth muscle phenotype.Methods: Primary fibroblasts were grown from bronchial biopsy specimens from normal (n = 6) and asthmatic (n = 7) donors and treated with TGFß? to induce myofibroblast differentiation. The most stable genes for normalisation were identified using RT-qPCR and the geNorm software applied to a panel of 12 "housekeeping" genes. Expression of ?-smooth muscle actin (?SMA), heavy chain myosin (HCM), calponin 1 (CPN 1), desmin, and ?-actin were measured by RT-qPCR. Protein expression was assessed by immunocytochemistry and western blotting.Results: Phospholipase A2 and ubiquitin C were identified as the most stably expressed and practically useful genes for normalisation of gene expression during myofibroblast differentiation. TGFß? induced mRNA expression for all five smooth muscle related transcripts; ?SMA, HCM and CPN 1 protein were also increased but desmin protein was not detectable. Although there was no difference in basal expression, HCM, CPN 1 and desmin were induced to a significantly greater extent in asthmatic fibroblasts than in those from normal controls (p = 0.041 and 0.011, respectively).Conclusions: Although TGFß? induced the transcription of several smooth muscle related genes, not all were translated into protein. Thus, while TGFß? is unable to induce a bona fide smooth muscle cell phenotype, it may "prime" (myo)fibroblasts for further differentiation, especially if the cells are derived from asthmatic airways.Abbreviations: CPN 1, calponin 1; DMEM, Dulbecco’s modified Eagle’s medium; FBS, fetal bovine serum; HCM, heavy chain myosin; RT-qPCR, reverse transcription quantitative polymerase chain reaction; SFM, serum free medium; SMA, smooth muscle actin; TGFß, transforming growth factor
ADAM33: a newly identified protease involved in airway remodelling
No full textAsthma is a complex disorder in which major genetic and environmental factors interact to both initiate the disease and modify its progression. While asthma is recognised as a disorder of the conducting airways characterised by Th2-directed inflammation, it is being increasingly apparent that alteration of the structural cells of the airways (airway remodelling) is also fundamental to disease chronicity and severity. The gene ADAM33, encoding a novel member of a identified as an asthma susceptibility gene as the result of a positional cloning effort in a cohort of families recruited form the UK and USA. Subsequent genetic studies have now provided evidence that ADAM33 may be involved in determining lung function throughout life, associated with early life lung function as well as increased decline therapeutic intervention in asthma and future work will focus on the mechanisms by which it alters lung function and bronchial hyperresponsiveness
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
ADAM33 in embryonic lungs
No full textRationale: ADAM33 is an asthma susceptibility gene with polymorphic variation that is strongly associated with asthma and bronchial hyperresponsiveness ( Van Eerdewegh et al. Nature 2002;418:426–30[CrossRef][Medline]). Single nucleotide polymorphisms (SNPs) in ADAM33 also predict impaired lung function in COPD ( van Diemen et al. Am J Respir Crit Care Med 2005;172:329–33[Abstract/Free Full Text]) and in young children ( Simpson et al. Am J Respir Crit Care Med 2005;172:55–60[Abstract/Free Full Text]). To study the link between maternal atopy and development of asthma, we postulated that ADAM33 is expressed during embryonic lung development and is affected by Th2 cytokines.Methods: Mouse lungs were harvested at embryonic day (ED) 11–19 and human embryonic lungs (HEL) (7–10 weeks) were collected following the Polkinghorne Committee guidelines after informed consent and ethical approval. Lung explants were cultured in vitro for 3–18 days±interleukin (IL)-13. Samples were processed for mRNA, protein, and image analysis.Results: ADAM33 mRNA increased during embryonic development in mouse and human lungs. ADAM33 splice variants were detected in HELs but the ß-isoform and the metalloprotease domain were rare. Western blotting confirmed the presence of multiple isoforms of ADAM33. Immunomicroscopy showed ADAM33 around alpha smooth muscle actin ({alpha}SMA) positive tubular structures within the undifferentiated mesenchyme. In vitro, ADAM33 and {alpha}SMA mRNA expression in ED12 lung explants cultured with IL-13 were increased after 48 hours (p = 0.015) and 72 hours (p = 0.026) compared with lungs cultured in medium alone. HELs cultured for 6, 12, and 18 days in the presence of IL-13 showed cystic phenotypic changes compared with medium alone.Conclusion: The expression of ADAM33 in developing embryonic lungs and its interaction with IL-13 suggests a key role in airway modelling that may contribute to the pathogenesis of chronic lung disease
Chronological expression of ciliated bronchial epithelim 1 in mouse and human pulmonary differentiation
No full textLocal genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms
No full textWhile asthma is an inflammatory disorder of the airways usually associated with atopy, an important additional component is involvement of the epithelium and underlying mesenchyme acting as a trophic unit (EMTU). In addition to allergens, a wide range of environmental factors interact with the EMTU, such as virus infections, environmental tobacco smoke and pollutants, to initiate tissue damage and aberrant repair responses that are translated into remodelling of the airways. While candidate gene association studies have revealed polymorphic variants that influence asthmatic inflammation, positional cloning of previously unknown genes is identifying a high proportion of novel genes in the EMTU. Dipeptidyl peptidase (DPP) 10 and disintegrin and metalloproteinase (ADAM)33 are newly identified genes strongly associated with asthma that are preferentially expressed in the airway epithelium and underlying mesenchyme, respectively. Also of increasing importance is the recognition that genes associated with asthma and atopy have important interactions with the environment through epigenetic mechanisms that influence their expression. This type of research will not only identify biomarkers of different types of asthma across the full range of phenotypic expression, but will also identify novel therapeutic targets that could influence the natural history of the heterogenes lung disease
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
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