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The focus of this article is a re-count of Richard Carrington’s original sunspot observations from his book drawings (Carrington in Observations of the Spots on the Sun from November 9, 1853, to March 24, 1861 Made at Redhill, Williams and Norgate, London, 1863) by an observer from the World Data Center-SILSO (WDC-SILSO, http://www.sidc.be/silso/home) network, Thomas H. Teague (UK). This modern re-count will enable the recomputation of the entire Sunspot Number series in a way Carrington’s original counts (Casas and Vaquero in Solar Phys. 289(1), 79, 2014) did not. Here we present comparison studies of the new re-counted series with contemporary observations, new data extracted from the Journals of the Zürich Observatory and other sources of Carrington’s own observations and conclude that Carrington’s group counting is very close to the modern way of counting while his method for counting individual spots lags significantly behind modern counts. We also test the quality and robustness of the new recount with methods developed in Mathieu et al. (Astrophys. J. 886(1), 7, 2019)., SCOPUS: ar.j, info:eu-repo/semantics/published

// Tobias Muller 1, 2, * , Susanne Fay 1, * , Rodolfo Paula Vieira 1, * , Harry Karmouty-Quintana 3 , Sanja Cicko 1 , Korcan Ayata 1 , Gernot Zissel 1 , Torsten Goldmann 4 , Giuseppe Lungarella 5 , Davide Ferrari 6 , Francesco Di Virgilio 6 , Bernard Robaye 7 , Jean-Marie Boeynaems 7 , Michael R. Blackburn 3 , Marco Idzko 1 1 University Hospital Freiburg, Department of Pneumology, Freiburg, Germany 2 University Hospital RWTH Aachen, Division of Pneumology, Aachen, Germany 3 Department of Biochemistry and Molecular Biology, Houston Medical School, University of Texas, Houston, USA 4 Research Center Borstel, Clinical and Experimental Pathology, Borstel, Germany 5 Department of Physiopathology and Experimental Medicine, University of Siena, Siena, Italy 6 Department of Experimental and Diagnostic Medicine, Section of General Pathology and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Ferrara, Italy 7 IRIBHM and Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium * These authors contributed equally to this work Correspondence to: Tobias Muller, email: tobmueller@ukaachen.de Keywords: ATP, chemotaxis, neutrophils, nucleotides, pulmonary fibrosis Received: November 16, 2016 Accepted: March 10, 2017 Published: March 21, 2017 ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available treatment options. Recently, the involvement of purinergic receptor subtypes in the pathogenesis of different lung diseases has been demonstrated. Here we investigated the role of the purinergic receptor subtype P2Y 2 in the context of fibrotic lung diseases. The concentration of different nucleotides was measured in the broncho-alveolar lavage (BAL) fluid derived from IPF patients and animals with bleomycin-induced pulmonary fibrosis. In addition expression of P2Y 2 receptors by different cell types was determined. To investigate the functional relevance of P2Y 2 receptors for the pathogenesis of the disease the bleomycin model of pulmonary fibrosis was used. Finally, experiments were performed in pursuit of the involved mechanisms. Compared to healthy individuals or vehicle treated animals, extracellular nucleotide levels in the BAL fluid were increased in patients with IPF and in mice after bleomycin administration, paralleled by a functional up-regulation of P2Y 2 R expression. Both bleomycin-induced inflammation and fibrosis were reduced in P2Y 2 R-deficient compared to wild type animals. Mechanistic studies demonstrated that recruitment of neutrophils into the lungs, proliferation and migration of lung fibroblasts as well as IL6 production are key P2Y 2 R mediated processes. Our results clearly demonstrate the involvement of P2Y 2 R subtypes in the pathogenesis of fibrotic lung diseases in humans and mice and hence support the development of selective P2Y 2 R antagonists for the treatment of IPF.

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6 R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL) cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6 R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6 R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6 R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6 R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6 R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6 R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6 R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF., SCOPUS: ar.j, info:eu-repo/semantics/published