Increased autophagy-related 5 gene expression is associated with collagen expression in the airways of refractory asthmatics

Background: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis. Hence, the dysregulation of autophagy may contribute to fibrosis in asthmatic airways. Objective: This study aimed to determine if (1) collagen deposition in asthmatic airways is associated with ATG5 expression and (2) ATG5 protein expression is associated with asthma per se and severity. Methods: Gene expression of transforming growth factor beta 1, various asthma-related collagen types [collagen, type I, alpha 1; collagen, type II, alpha 1; collagen, type III, alpha 1; collagen, type V, alpha 1 (COL5A1) and collagen, type V, alpha 2], and ATG5 were measured using mRNA isolated from bronchial biopsies of refractory asthmatic subjects and assessed for pairwise associations. Protein expression of ATG5 in the airways was measured and associations were assessed for asthma per se, severity, and lung function. Main results: In refractory asthmatic individuals, gene expression of ATG5 was positively associated with COL5A1 in the airways. No association was detected between ATG5 protein expression and asthma per se, severity, and lung function. Conclusion and clinical relevance: Positive correlation between the gene expression patterns of ATG5 and COL5A1 suggests that dysregulated autophagy may contribute to subepithelial fibrosis in the airways of refractory asthmatic individuals. This finding highlights the therapeutic potential of ATG5 in ameliorating airway remodeling in the difficult-to-treat refractory asthmatic individuals

Rewiring of interactions in a changing environment: nettle-feeding butterflies and their parasitoids

Climate and land use change can alter the incidence and strength of biotic interactions, with important effects on the distribution, abundance and function of species. To assess the importance of these effects and their dynamics, studies quantifying how biotic interactions change in space and time are needed. We studied interactions between nettle-feeding butterflies and their shared natural enemies (parasitoids) locally and across 500 km latitudinal gradient in Sweden. We also examined the potential impact of the range-expansion of the butterfly Araschnia levana on resident butterflies via shared parasitoids, by studying how parasitism in resident butterflies covaries with the presence or absence of the newly-established species. We collected 6777 larvae of four nettle-feeding butterfly species (Aglais urticae, Aglais io, Ar. levana and Vanessa atalanta), over two years, at 19 sites distributed along the gradient. We documented the parasitoid complex for each butterfly species and measured their overlap, and analysed how parasitism rates were affected by butterfly species assemblage, variations in abundance, time, and the arrival of Ar. levana. Parasitoids caused high mortality, with substantial overlap in the complex of parasitoids associated with the four host butterflies. Levels of parasitism differed significantly among butterflies and were influenced by the local butterfly species assemblage. Our results also suggest that parasitism in resident butterflies is elevated at sites where Ar. levana has been established for a longer period. In our study system, variations in butterfly species assemblages were associated in a predictable way with substantial variations in rates of parasitism. This relationship is likely to affect the dynamics of the butterfly host species, and potentially cascade to the larger number of species with which they interact. These results highlight the importance of indirect interactions and their potential to reorganise ecological communities, especially in the context of shifts in species distributions in a warmer world.</p

Vestiges of an ancestral host plant: preference and performance in the butterfly Polygonia faunus and its sister species P. c-album

1. In the study of the evolution of insect-host plant interactions, important information is provided by host ranking correspondences among female preference, offspring preference, and offspring performance. Here, we contrast such patterns in two polyphagous sister species in the butterfly family Nymphalidae, the Nearctic Polygonia faunus, and the Palearctic P. c-album. 2. These two species have similar host ranges, but according to the literature P. faunus does not use the ancestral host plant clade-the urticalean rosids'. Comparisons of the species can thus test the effects of a change in insect-plant associations over a long time scale. Cage experiments confirmed that P. faunus females avoid laying eggs on Urtica dioica (the preferred host of P. c-album), instead preferring Salix, Betula, and Ribes.3. However, newly hatched larvae of both species readily accept and grow well on U. dioica, supporting the general theory that evolutionary changes in host range are initiated through shifts in female host preferences, whereas larvae are more conservative and also can retain the capacity to perform well on ancestral hosts over long time spans.4. Similar rankings of host plants among female preference, offspring preference, and offspring performance were observed in P. c-album but not in P. faunus. This is probably a result of vestiges of larval adaptations to the lost ancestral host taxon in the latter species. 5. Female and larval preferences seem to be largely free to evolve independently, and consequently larval preferences warrant more attention