Rationale: Ineffective repair of a damaged alveolar epithelium has been postulated to cause pulmonary fibrosis. In support of this theory, epithelial cell abnormalities, including hyperplasia, apoptosis, and persistent denudation of the alveolar basement membrane, are found in the lungs of humans with idiopathic pulmonary fibrosis and in animal models of fibrotic lung disease. Furthermore, mutations in genes that affect regenerative capacity or that cause injury/ apoptosis of type II alveolar epithelial cells have been identified in familial forms of pulmonary fibrosis. Although these findings are compelling, there are no studies that demonstrate a direct role for the alveolar epithelium or, more specifically, type II cells in the scarring process. Objectives: To determine if a targeted injury to type II cells would result in pulmonary fibrosis. Methods: A transgenic mouse was generated to express the human diphtheria toxin receptor on type II alveolar epithelial cells. Diphtheria toxin was administered to these animals to specifically target the type II epithelium for injury. Lung fibrosis was assessed by histology and hydroxyproline measurement. Measurements and Main Results: Transgenic mice treated with diphtheria toxin developed an approximately twofold increase in their lung hydroxyproline content on Days 21 and 28 after diphtheria toxin treatment. The fibrosis developed in conjunction with type II cell injury. Histological evaluation revealed diffuse collagen deposition with patchy areas of more confluent scarring and associated alveolar contraction. Conclusions: The development of lung fibrosis in the setting of type II cell injury in our model provides evidence for a causal link between the epithelial defects seen in idiopathic pulmonary fibrosis and the corresponding areas of scarring.
In September 2016, the annual meeting of the International Union for Quaternary Research’s Loess and Pedostratigraphy Focus Group, traditionally referred to as a LoessFest, met in Eau Claire, Wisconsin, USA. The 2016 LoessFest focused on “thin” loess deposits and loess transportation surfaces. This LoessFest included 75 registered participants from 10 countries. Almost half of the participants were from outside the United States, and 18 of the participants were students. This review is the introduction to the special issue forQuaternary Researchthat originated from presentations and discussions at the 2016 LoessFest. This introduction highlights current understanding and ongoing work on loess in various regions of the world and provides brief summaries of some of the current approaches/strategies used to study loess deposits.
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