Genetic susceptibility to nickel-induced acute lung injury

Human exposure to insoluble and soluble nickel compounds is extensive. Besides wide usage in many industries, nickel compounds are contained in cigarette smoke and, in low levels, in ambient particulate matter. Soluble nickel particulate, especially nickel sulfate (NiSO₄), has been associated with acute lung injury. To begin identifying genes controlling susceptibility to NiSO₄, mean survival times (MSTs) of eight inbred mouse strains were determined after aerosol exposure. Whereas A/J (A) mice were sensitive, C57BL/6J (B6) mice survived nearly twice as long (resistant). Their offspring were similarly resistant, demonstrating heritability as a dominant trait. Quantitative trait locus (QTL) analysis of backcross mice generated from these strains identified a region on chromosome 6 significantly linked to survival time. Regions on chromosomes 1 and 12 were suggestive of linkage and regions on chromosomes 8, 9, and 16 contributed to the response. Haplotype analysis demonstrated that QTLs on chromosomes 6, 9, 12, and 16 could explain the MST difference between the parental strains. To complement QTL analysis results, cDNA microarray analysis was assessed following NiSO₄ exposure of A and B6 mice. Significant expression changes were identified in one or both strains for >100 known genes. Closer evaluation of these changes revealed a temporal pattern of increased cell proliferation, extracellular matrix repair, hypoxia, and oxidative stress, followed by diminished surfactant proteins. Certain expressed sequence tags clustered with known genes, suggesting possible co-regulation and novel roles in pulmonary injury. Together, results from QTL and microarray analyses of nickel-induced acute lung injury survival allowed us to generate a short list of candidate genes.     

Multispecies and Multiscale Conservation Planning: Setting Quantitative Targets for Red‐Listed Lichens on Ancient Oaks

Abstract: Species occurrence in a habitat patch depends on local habitat and the amount of that habitat in the wider landscape. We used predictions from empirical landscape studies to set quantitative conservation criteria and targets in a multispecies and multiscale conservation planning effort. We used regression analyses to compare species richness and occurrence of five red‐listed lichens on 50 ancient oaks (Quercus robur; 120–140 cm in diameter) with the density of ancient oaks in circles of varying radius from each individual oak. Species richness and the occurrence of three of the five species were best explained by increasing density of oaks within 0.5 km; one species was best explained by the density of oaks within 2 km, and another was best predicted by the density of oaks within 5 km. The minimum numbers of ancient oaks required for “successful conservation” was defined as the number of oaks required to obtain a predicted local occurrence of 50% for all species included or a predicted local occurrence of 80% for all species included. These numbers of oaks were calculated for two relevant landscape scales (1 km² and 13 km²) that corresponded to various species responses, in such a way that calculations also accounted for local number of oaks. Ten and seven of the 50 ancient oaks surveyed were situated in landscapes that already fulfilled criteria for successful conservation when the 50% and 80% criteria, respectively, were used to define the level of successful conservation. For cost‐efficient conservation, oak stands in the landscapes most suitable for successful conservation should be prioritized for conservation and management (e.g., grazing and planting of new oaks) at the expense of oak stands situated elsewhere.