The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak

Aberrant wound-healing responses to injury have been implicated in the development of pulmonary fibrosis, but the mediators directing these pathologic responses have yet to be fully identified. We show that lysophosphatidic acid levels increase in bronchoalveolar lavage fluid following lung injury in the bleomycin model of pulmonary fibrosis, and that mice lacking one of its receptors, LPA1, are markedly protected from fibrosis and mortality in this model. The absence of LPA1 led to reduced fibroblast recruitment and vascular leak, two responses that may be excessive when injury leads to fibrosis rather than to repair, whereas leukocyte recruitment was preserved during the first week after injury. In persons with idiopathic pulmonary fibrosis, lysophosphatidic acid levels in bronchoalveolar lavage fluid were also increased, and inhibition of LPA1 markedly reduced fibroblast responses to the chemotactic activity of this fluid. LPA1 therefore represents a new therapeutic target for diseases in which aberrant responses to injury contribute to fibrosis, such as idiopathic pulmonary fibrosis.     

Conifer colonization of a 350-year old rock fall at Lassen Volcanic National Park in northern California

Montane conifers of western North America commonly colonize mineral surfaces resulting from landslides, lahars, mudflows, and rock avalanches. This colonization can include shade-tolerant conifers that may eventually dominate the forest in a pattern termed “direct” succession. Documenting examples of this long-term successional process are useful for identifying alternative successional trajectories and indicating potential controlling mechanisms for subsequent experimental analysis. This study (1) analyzes the 1992 status of the conifer colonization on the coarse-textured surface of a 1650 AD rock avalanche in northern California and (2) measures individual growth and survivorship in permanent plots between 1992 and 2003. Increment cores of large trees indicated initial conifer colonization before 1700 AD with continuous subsequent colonization. Mean conifer density in 1992 was 725 (SD = 747) ha⁻¹ with densities increasing with decreasing rock sizes. Densities were not correlated with distances to possible seed sources. Median heights were <1 m, and the mean proportional height growth rate for healthy individuals was 0.0166 year⁻¹. The mortality rate for individuals ≥0.1-m tall was <0.007 year⁻¹. The conifers were more numerous than shrubs, and there was little apparent evidence of facilitation or inhibition of conifers. The species assemblage is mostly (89%) Abies concolor, Pinus monticola, and Pinus ponderosa individuals dispersed across an elevation range of 1870–2040 m a. s. l. This is an atypical species mix for these elevations in this location, and this mix is not readily predicted from species properties such as seed mass, seed flight distance, or drought tolerance.     

EST and Mitochondrial DNA Sequences Support a Distinct Pacific Form of Salmon Louse, <Emphasis Type="Italic">Lepeophtheirus salmonis</Emphasis>

Nuclear deoxyribonucleic acid sequences from approximately 15,000 salmon louse expressed sequence tags (ESTs), the complete mitochondrial genome (16,148bp) of salmon louse, and 16S ribosomal ribonucleic acid (rRNA) and cytochrome oxidase subunit I (COI) genes from 68 salmon lice collected from Japan, Alaska, and western Canada support a Pacific lineage of Lepeophtheirus salmonis that is distinct from that occurring in the Atlantic Ocean. On average, nuclear genes are 3.2% different, the complete mitochondrial genome is 7.1% different, and 16S rRNA and COI genes are 4.2% and 6.1% different, respectively. Reduced genetic diversity within the Pacific form of L. salmonis is consistent with an introduction into the Pacific from the Atlantic Ocean. The level of divergence is consistent with the hypothesis that the Pacific form of L. salmonis coevolved with Pacific salmon (Onchorhynchus spp.) and the Atlantic form coevolved with Atlantic salmonids (Salmo spp.) independently for the last 2.5–11 million years. The level of genetic divergence coincides with the opportunity for migration of fish between the Atlantic and Pacific Ocean basins via the Arctic Ocean with the opening of the Bering Strait, approximately 5 million years ago. The genetic differences may help explain apparent differences in pathogenicity and environmental sensitivity documented for the Atlantic and Pacific forms of L. salmonis. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comparative genome mapping of the deer mouse (<Emphasis Type="Italic">Peromyscus maniculatus</Emphasis>) reveals greater similarity to rat (<Emphasis Type="Italic">Rattus norvegicus</Emphasis>) than to the lab mouse (<Emphasis Type="Italic">Mus musculus</Emphasis>)

Background  

Deer mice (Peromyscus maniculatus) and congeneric species are the most common North American mammals. They represent an emerging system for the genetic analyses of the physiological and behavioral bases of habitat adaptation. Phylogenetic evidence suggests a much more ancient divergence of Peromyscus from laboratory mice (Mus) and rats (Rattus) than that separating latter two. Nevertheless, early karyotypic analyses of the three groups suggest Peromyscus to be exhibit greater similarities with Rattus than with Mus.