Upregulation of citrullination pathway: From Autoimmune to Idiopathic Lung Fibrosis

Background: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear. Methods: We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and immunohistochemistry. Citrullinated protein levels were also quantified. Results: PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in all groups, with the strongest cytoplasmic expression observed in granulocytes in RA-ILD and IPF. PADI2 mRNA and immunostaining of BAL cells, were similar in all groups among smokers. Overall, stronger staining was observed in current smokers. Citrullinated peptides were significantly increased in IPF compared to RA-ILD and controls. In RA-ILD, protein citrullination strongly correlated with PADI4 expression and anti-citrullinated protein antibodies (ACPAs). Conclusions: These results suggest that the citrullination pathway is upregulated in IPF and in RA-ILD

Diel nectar secretion rhythm in squash (Cucurbita pepo) and its relation with pollinator activity

Most studies of foraging behavior in bees have been performed under artificial conditions. One highly neglected area is the daily nectar secretion rhythm in flowers including how nectar properties may vary with time of day. As a first step in understanding the connections between forager behavior and nectar presentation under more natural conditions, we examined nectar secretion patterns in flowers of the squash Cucurbita pepo. Under greenhouse conditions, squash flowers exhibit consistent diel changes in nectar volume and concentration through anthesis. These temporal patterns are robust, persisting under field conditions as well as simulated drought conditions in the greenhouse. In the presence of active pollinators, diel patterns are evident but with highly variable, severely reduced volumes. The potential consequences of these factors for pollinator behavior are discussed