Leukocyte ADAM17 Regulates Acute Pulmonary Inflammation

The transmembrane protease ADAM17 regulates the release and density of various leukocyte cell surface proteins that modulate inflammation, including L-selectin, TNF-α, and IL-6R. At this time, its in vivo substrates and role in pulmonary inflammation have not been directly examined. Using conditional ADAM17 knock-out mice, we investigated leukocyte ADAM17 in acute lung inflammation. Alveolar TNF-α levels were significantly reduced (>95%) in ADAM17-null mice following LPS administration, as was the shedding of L-selectin, a neutrophil-expressed adhesion molecule. Alveolar IL-6R levels, however, were reduced by only ≈25% in ADAM17-null mice, indicating that ADAM17 is not its primary sheddase in our model. Neutrophil infiltration into the alveolar compartment is a key event in the pathophysiology of acute airway inflammation. Following LPS inhalation, alveolar neutrophil levels and lung inflammation in ADAM17-null mice were overall reduced when compared to control mice. Interestingly, however, neutrophil recruitment to the alveolar compartment occurred earlier in ADAM17-null mice after exposure to LPS. This decrease in alveolar neutrophil recruitment in ADAM17-null mice was accompanied by significantly diminished alveolar levels of the neutrophil-tropic chemokines CXCL1 and CXCL5. Altogether, our study suggests that leukocyte ADAM17 promotes inflammation in the lung, and thus this sheddase may be a potential target in the design of pharmacologic therapies for acute lung injury

Explanations for death by suicide in northern Britain during the long eighteenth century

This article explores how professionals explicated and contextualised the deaths of their clients or subjects, delineated the relationship between madness and death, and advised and counselled families on the deaths of their mentally ill members. It uses coroners’ inquest findings, media such as newspapers, magazines, pamphlets and broadsides, and family correspondence (all drawn from Scotland and the north of England) as well as medical and legal writings to explore perceptions of the link between state of mind and voluntary death. It asks how doctors, families and ‘society’ at large conceptualized, responded to and coped with mental problems culminating in suicide. The aim is to square the apparent simplicity of measured professional understandings with the more emotionally charged yet complex ways those close to attempted or successful suicides related to their situation.PostprintPeer reviewe

Observational evidence for chemical ozone depletion over the Arctic in winter 1991-92

Long-term depletion of ozone has been observed since the early 1980s in the Antarctic polar vortex, and morerecently at midlatitudes in both hemispheres, with most of the ozone loss occurring in the lower stratosphere.Insufficient measurements of ozone exist, however, to determine decadal trends in ozone concentration in the Arcticwinter. Several studies of ozone concentrations in the Arctic vortex have inferred that chemical ozone loss hasoccurred; but because natural variations in ozone concentration at any given location can be large, deducinglong-term trends from time series is fraught with difficulties. The approaches used previously have often been indirect,typically relying on relationships between ozone and long-lived tracers. Most recently Manney et al. used such anapproach, based on satellite measurements, to conclude that the observed ozone decrease of about 20% in the lowerstratosphere in February and March 1993 was caused by chemical, rather than dynamical, processes. Here we report theresults of a new approach to calculate chemical ozone destruction rates that allows us to compare ozone concentrationsin specific air parcels at different times, thus avoiding the need to make assumptions about ozone/tracer ratios. For theArctic vortex of the 1991-92 winter we find that, at 20 km altitude, chemical ozone loss occurred only between earlyJanuary and mid February and that the loss is proportional to the exposure to sunlight. The timing and magnitude arebroadly consistent with existing understanding of photochemical ozone-depletion processes

The effects of geographic expansion on the productivity of Spanish savings banks

Conditional density estimation, Geographic expansion, Malmquist productivity index, Nonparametric regression, Savings bank, C14, C30, C61, G21, L5,