Distribution and functional impact of DNA copy number variation in the rat

The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.     

Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation

Many globular and natively disordered proteins can convert into amyloid fibrils. These fibrils are associated with numerous pathologies as well as with normal cellular functions, and frequently form during protein denaturation. Inhibitors of pathological amyloid fibril formation could be useful in the development of therapeutics, provided that the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibrils as templates, we have designed and characterized an all-D-amino-acid inhibitor of the fibril formation of the tau protein associated with Alzheimer's disease, and a non-natural L-amino-acid inhibitor of an amyloid fibril that enhances sexual transmission of human immunodeficiency virus. Our results indicate that peptides from structure-based designs can disrupt the fibril formation of full-length proteins, including those, such as tau protein, that lack fully ordered native structures. Because the inhibiting peptides have been designed on structures of dual-β-sheet 'steric zippers', the successful inhibition of amyloid fibril formation strengthens the hypothesis that amyloid spines contain steric zippers.     

Competitive interactions between endangered kit foxes and nonnative red foxes

We investigated interference and exploitative competition between endangered San Joaquin kit foxes ( Vulpes macrotis mutica ) and nonnative red foxes ( V. vulpes ). Seven kit foxes and 16 red foxes were radio-collared and tracked via radiotelemetry near Lost Hills, California. One kit fox was killed by a red fox. Home ranges of the 2 species did not overlap extensively. Although both species used similar habitats, they used different parcels of land. Kit foxes and red foxes primarily consumed rodents on the study site, and dietary overlap was considerable. Red foxes also may have been using dens formerly used by kit foxes. Thus, red foxes were engaging in both interference and exploitative competition with kit foxes, and red foxes constitute a potentially significant threat to kit foxes. Coyotes ( Canis latrans ) co-occur with kit foxes and may limit red fox abundance and distribution. Therefore, although they occasionally kill kit foxes, the presence of coyotes may benefit kit foxes by excluding red foxes.     

Scientific realism and the semantic incommensurability thesis

This paper reconsiders the challenge presented to scientific realism by the semantic incommensurability thesis. A twofold distinction is drawn between methodological and semantic incommensurability, and between semantic incommensurability due to variation of sense and due to discontinuity of reference. Only the latter presents a challenge to scientific realism. The realist may dispose of this challenge on the basis of a modified causal theory of reference, as argued in the author’s 1994 book, The incommensurability thesis. This referential response has been the subject of a charge of meta-incommensurability by Hoyningen-Huene et al. (1996), who argue that the realist’s referential response begs the question against anti-realist advocates of incommensurability. In reply, it is noted that a tu quoque rejoinder is available to the realist. It is also argued that the dialectical situation favours the scientific realist, since the anti-realist defence of incommensurability depends on an incoherent distinction between phenomenal world and world-in-itself. In light of such incoherence, and a strong commonsense presumption in favour of realism, the referential response to semantic incommensurability may be justifiably based on realism.     

Observations on the prey and nests of seven species of Cerceris (Hymenoptera: Sphecidae)

Cerceris species are remarkably constant in their prey preferences. Records are presented from diverse localities that confirm prey constancy in five species. An apparent exception is noted in the case of C. crotonella Viereck & Cockerell. A mixed aggregation of C. fumipennis Say and C. californica Cresson is reported, both preying upon Buprestidae and using some of the same species. Nest and prey of C. conifrons Mickel are reported for the first time.     

The nest and larva of Diploplectron brunneipes (Cresson) (Hymenoptera: Sphecidae)

Diploplectron brunneipes (Cresson) makes a shallow nest in compact clay - sand containing at least two cells. It is provisioned with immature Heteroptera. The larva resembles that of Astata in a general way but differs in several particulars.