35 research outputs found

    Immunological corollary of the pulmonary mycobiome in bronchiectasis:The Cameb study

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    Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis. Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes. The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and Clavispora. Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations. The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Published versio

    Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

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    Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles (“immunoallertypes”), were determined. Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionSupported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

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    IgE-binding residues analysis of the house dust mite allergen Der p 23

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    10.1038/s41598-020-79820-ySCIENTIFIC REPORTS11

    Analysis of ESTs generated from inner bark tissue of an Acacia auriculiformis x Acacia mangium hybrid

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    The majority of plant expressed sequence tags (ESTs) available in the public databases are from non-woody species such as Arabidopsis, maize, soybean, and rice, with the exception of the model tree species, Populus. In this study, we report the first EST database constructed from the commercially important tree species Acacia. ESTs were generated from pooled RNA extracted from the mature, intermediate, and young inner bark tissues of an Acacia auriculiformis x Acacia mangium hybrid. Finally, 3,182 high-quality ESTs were analyzed representing a total of 1,982 unique transcripts (663 contigs and 1,319 singletons) for the inner bark cDNA library. A total of 1,053 unigenes (1,750 ESTs) showed similarities with protein sequences in public database where 867 were significant matches (E value ≤ e-10). Further analysis performed on unigenes with significant matches and known functions identified 231 genes including genes involved in cellulose, lignin, and hemicellulose biosynthesis. For cDNA library validation, quantitative real-time RT-PCR was performed to study the expression levels of the cellulose and lignin genes identified from this EST database in the phloem tissue of A. mangium, A. auriculiformis, and A. auriculiformis x A. mangium hybrid. All the seven candidate genes were expressed in all the individuals studied confirming the dependability of the EST database. The cDNA library and the EST database constructed are valuable resources for forest tree research aiming towards understanding the genetic control of wood formation and in the future endeavors to modify wood and fiber profile through marker-assisted breeding programs. © 2010 Springer-Verlag
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