Deficiency in type 1 insulin-like growth factor receptor in mice protects against oxygen-induced lung injury

BACKGROUND: Cellular responses to aging and oxidative stress are regulated by type 1 insulin-like growth factor receptor (IGF-1R). Oxidant injury, which is implicated in the pathophysiology of a number of respiratory diseases, acutely upregulates IGF-1R expression in the lung. This led us to suspect that reduction of IGF-1R levels in lung tissue could prevent deleterious effects of oxygen exposure. METHODS: Since IGF-1R null mutant mice die at birth from respiratory failure, we generated compound heterozygous mice harboring a hypomorphic (Igf-1r(neo)) and a knockout (Igf-1r(-)) receptor allele. These IGF-1R(neo/- )mice, strongly deficient in IGF-1R, were subjected to hyperoxia and analyzed for survival time, ventilatory control, pulmonary histopathology, morphometry, lung edema and vascular permeability. RESULTS: Strikingly, after 72 h of exposure to 90% O(2), IGF-1R(neo/- )mice had a significantly better survival rate during recovery than IGF-1R(+/+ )mice (77% versus 53%, P < 0.05). The pulmonary injury was consistently, and significantly, milder in IGF-1R(neo/- )mice which developed conspicuously less edema and vascular extravasation than controls. Also, hyperoxia-induced abnormal pattern of breathing which precipitated respiratory failure was elicited less frequently in the IGF-1R(neo/- )mice. CONCLUSION: Together, these data demonstrate that a decrease in IGF-1R signaling in mice protects against oxidant-induced lung injury

High and Dry: New Observations of Tropospheric and Cloud Properties above the Greenland Ice Sheet

Cloud and atmospheric properties strongly influence the mass and energy budgets of the Greenland Ice Sheet (GIS). To address critical gaps in the understanding of these systems, a new suite of cloud- and atmosphere-observing instruments has been installed on the central GIS as part of the Integrated Characterization of Energy, Clouds, Atmospheric State, and Precipitation at Summit (ICECAPS) project. During the first 20 months in operation, this complementary suite of active and passive ground-based sensors and radiosondes has provided new and unique perspectives on important cloud?atmosphere properties. High atop the GIS, the atmosphere is extremely dry and cold with strong near-surface static stability predominating throughout the year, particularly in winter. This low-level thermodynamic structure, coupled with frequent moisture inversions, conveys the importance of advection for local cloud and precipitation formation. Cloud liquid water is observed in all months of the year, even the particularly cold and dry winter, while annual cycle observations indicate that the largest atmospheric moisture amounts, cloud water contents, and snowfall occur in summer and under southwesterly flow. Many of the basic structural properties of clouds observed at Summit, Greenland, particularly for low-level stratiform clouds, are similar to their counterparts in other Arctic regions. The ICECAPS observations and accompanying analyses will be used to improve the understanding of key cloud?atmosphere processes and the manner in which they interact with the GIS. Furthermore, they will facilitate model evaluation and development in this data-sparse but environmentally unique region