Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression from bronchial epithelial cells via a heme/meprin/epidermal growth factor receptor/Toll-like receptor pathway.

A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from ΔF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, α(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.</p

Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis

BACKGROUND: Women with cystic fibrosis are at increased risk for mucoid conversion of Pseudomonas aeruginosa, which contributes to a sexual dichotomy in disease severity.METHODS: We evaluated the effects of estradiol and its metabolite estriol on P. aeruginosa in vitro and in vivo and determined the effect of estradiol on disease exacerbations in women with cystic fibrosis.RESULTS: Estradiol and estriol induced alginate production in P. aeruginosa strain 01 and in clinical isolates obtained from patients with and those without cystic fibrosis. After prolonged exposure to estradiol, P. aeruginosa adopted early mucoid morphology, whereas short-term exposure inhibited bacterial catalase activity and increased levels of hydrogen peroxide, which is potentially damaging to DNA. Consequently, a frameshift mutation was identified in mucA, a key regulator of alginate biosynthesis in P. aeruginosa. In vivo levels of estradiol correlated with infective exacerbations in women with cystic fibrosis, with the majority occurring during the follicular phase (P&lt;0.05). A review of the Cystic Fibrosis Registry of Ireland revealed that the use of oral contraceptives was associated with a decreased need for antibiotics. Predominantly nonmucoid P. aeruginosa was isolated from sputum during exacerbations in the luteal phase (low estradiol). Increased proportions of mucoid bacteria were isolated during exacerbations occurring in the follicular phase (high estradiol), with a variable P. aeruginosa phenotype evident in vivo during the course of the menstrual cycle corresponding to fluctuating estradiol levels.CONCLUSIONS: Estradiol and estriol induced mucoid conversion of P. aeruginosa in women with cystic fibrosis through a mutation of mucA in vitro and were associated with selectivity for mucoid isolation, increased exacerbations, and mucoid conversion in vivo. (Funded by the Molecular Medicine Ireland Clinician-Scientist Fellowship Programme)

Pulmonary Proteases in the Cystic Fibrosis Lung Induce Interleukin 8 Expression from Bronchial Epithelial Cells via a Heme/Meprin/Epidermal Growth Factor Receptor/Toll-like Receptor Pathway

A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from ΔF508 CFBE41o(−) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, α(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(−) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention

AusTraits, a curated plant trait database for the Australian flora

We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g.&nbsp;photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g.&nbsp;leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data,&nbsp;which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge

AusTraits: a curated plant trait database for the Australian flora

INTRODUCTION AusTraits is a transformative database, containing measurements on the traits of Australia’s plant taxa, standardised from hundreds of disconnected primary sources. So far, data have been assembled from &gt; 250 distinct sources, describing &gt; 400 plant traits and &gt; 26,000 taxa. To handle the harmonising of diverse data sources, we use a reproducible workflow to implement the various changes required for each source to reformat it suitable for incorporation in AusTraits. Such changes include restructuring datasets, renaming variables, changing variable units, changing taxon names. While this repository contains the harmonised data, the raw data and code used to build the resource are also available on the project’s GitHub repository, http://traitecoevo.github.io/austraits.build/. Further information on the project is available in the associated publication and at the project website austraits.org. Falster, Gallagher et al (2021) AusTraits, a curated plant trait database for the Australian flora. Scientific Data 8: 254, https://doi.org/10.1038/s41597-021-01006-6 CONTRIBUTORS The project is jointly led by Dr Daniel Falster (UNSW Sydney), Dr Rachael Gallagher (Western Sydney University), Dr Elizabeth Wenk (UNSW Sydney), and Dr Hervé Sauquet (Royal Botanic Gardens and Domain Trust Sydney), with input from &gt; 300 contributors from over &gt; 100 institutions (see full list above). The project was initiated by Dr Rachael Gallagher and Prof Ian Wright while at Macquarie University. We are grateful to the following institutions for contributing data Australian National Botanic Garden, Brisbane Rainforest Action and Information Network, Kew Botanic Gardens, National Herbarium of NSW, Northern Territory Herbarium, Queensland Herbarium, Western Australian Herbarium, South Australian Herbarium, State Herbarium of South Australia, Tasmanian Herbarium, Department of Environment, Land, Water and Planning, Victoria. AusTraits has been supported by investment from the Australian Research Data Commons (ARDC), via their “Transformative data collections” (https://doi.org/10.47486/TD044) and “Data Partnerships” (https://doi.org/10.47486/DP720) programs; fellowship grants from Australian Research Council to Falster (FT160100113), Gallagher (DE170100208) and Wright (FT100100910), a grant from Macquarie University to Gallagher. The ARDC is enabled by National Collaborative Research Investment Strategy (NCRIS). ACCESSING AND USE OF DATA The compiled AusTraits database is released under an open source licence (CC-BY), enabling re-use by the community. A requirement of use is that users cite the AusTraits resource paper, which includes all contributors as co-authors: Falster, Gallagher et al (2021) AusTraits, a curated plant trait database for the Australian flora. Scientific Data 8: 254, https://doi.org/10.1038/s41597-021-01006-6 In addition, we encourage users you to cite the original data sources, wherever possible. Note that under the license data may be redistributed, provided the attribution is maintained. The downloads below provide the data in two formats: austraits-3.0.2.zip: data in plain text format (.csv, .bib, .yml files). Suitable for anyone, including those using Python. austraits-3.0.2.rds: data as compressed R object. Suitable for users of R (see below). Both objects contain all the data and relevant meta-data. AUSTRAITS R PACKAGE For R users, access and manipulation of data is assisted with the austraits R package. The package can both download data and provides examples and functions for running queries. STRUCTURE OF AUSTRAITS The compiled AusTraits database has the following main components: austraits ├── traits ├── sites ├── contexts ├── methods ├── excluded_data ├── taxanomic_updates ├── taxa ├── definitions ├── contributors ├── sources └── build_info These elements include all the data and contextual information submitted with each contributed datasets. A schema and definitions for the database are given in the file/component definitions, available within the download. The file dictionary.html provides the same information in textual format. Full details on each of these components and columns are contained within the definition. Similar information is available at http://traitecoevo.github.io/austraits.build/articles/Trait_definitions.html and http://traitecoevo.github.io/austraits.build/articles/austraits_database_structure.html. CONTRIBUTING We envision AusTraits as an on-going collaborative community resource that: Increases our collective understanding the Australian flora; and Facilitates accumulation and sharing of trait data; Builds a sense of community among contributors and users; and Aspires to fully transparent and reproducible research of the highest standard. As a community resource, we are very keen for people to contribute. Assembly of the database is managed on GitHub at traitecoevo/austraits.build. Here are some of the ways you can contribute: Reporting Errors: If you notice a possible error in AusTraits, please post an issue on GitHub. Refining documentation: We welcome additions and edits that make using the existing data or adding new data easier for the community. Contributing new data: We gladly accept new data contributions to AusTraits. See full instructions on how to contribute at http://traitecoevo.github.io/austraits.build/articles/contributing_data.html

AusTraits, a curated plant trait database for the Australian flora

International audienceWe introduce the austraits database-a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual-and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge