The unconventional secretion of stress-inducible protein 1 by a heterogeneous population of extracellular vesicles

The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrP^C). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrP^C. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrP^C-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrP^C signaling.     

Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma

Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O-glycosylation, although different for MUC1 and IgA1, include dysregulation in glycosyltransferase expression, stability, and/or intracellular localization. Moreover, these aberrant glycoproteins are recognized by antibodies, although with different consequences. In breast cancer, elevated levels of antibodies recognizing aberrant MUC1 are associated with better outcome, whereas in IgA nephropathy, the antibodies recognizing aberrant IgA1 are part of the pathogenetic process.     

Metaphysics and population genetics: Karl Pearson and the background to Fisher's multi-factorial theory of inheritance

This paper traces the background to R. A. Fisher's multi-factorial theory of inheritance. It is argued that the traditional account is incomplete, and that Karl Pearson's well-known pre-Fisherian objections to the theory were in fact overcome by Pearson himself. It is further argued that Pearson's stated reasons for not accepting his own achievement has to be seen as a rationalization, standing in for deeper-seated metaphysical objections to the Mendelian paradigm of a type not readily discussed in a formal scientific paper. The apparent, post-Fisherian, continued acceptance of Pearson's objections is presented as an interesting problem for the historian and sociologist.     

Colony isolation and isozyme variability of the western seep fritillary, Speyeria nokomis apacheana (Nymphalidae), in the western Great Basin

Thirteen Speyeria nokomis apacheana (Edwards) (Nymphalidae) populations from the western Great Basin were assayed for isozyme variability using starch-gel electrophoresis. Eight of the 25 presumptive isozyme loci analyzed were found to be polymorphic. Collections made in 1991and 1992 allowed for between-year comparisons of heterozygosity and the estimation of effective population size for five of the sampled populations. Speyeria nokomis apacheana populations exhibit lower mean heterozygosity levels than other nymphalids. This may be attributed to genetic drift in apparently isolated populations with small effective sizes.     

Regional and seasonal diet of the Western Burrowing Owl in south central Nevada

We examined diets of Western Burrowing Owls ( Athene cunicularia hypugaea ) based on contents of pellets and large prey remains collected year-round at burrows in each of the 3 regions in south central Nevada (Mojave Desert, Great Basin Desert, and Transition region). The most common prey items, based on percent frequency of occurrence, were crickets and grasshoppers, beetles, rodents, sun spiders, and scorpions. The most common vertebrate prey was kangaroo rats ( Dipodomys spp.). True bugs (Hemiptera), scorpions, and western harvest mice ( Reithrodontomys megalotis ) occurred most frequently in pellets from the Great Basin Desert region. Kangaroo rats ( Dipodomys spp.) and pocket mice (Perognathinae) were the most important vertebrate prey items in the Transition and Mojave Desert regions, respectively. Frequency of occurrence of any invertebrate prey was high (>80%) in samples year-round but dropped in winter samples, with scorpions and sun spiders exhibiting the steepest declines. Frequency of occurrence of any vertebrate prey peaked in spring samples, was intermediate for winter and summer samples, and was lowest in fall samples. With the possible exception of selecting for western harvest mice in the Great Basin Desert region, Western Burrowing Owls in our study appeared to be opportunistic foragers with a generalist feeding strategy.     

Dispersal and extraterritorial movements of swift foxes ( Vulpes velox ) in northwestern Texas

Dispersal plays an important role in the population dynamics of many carnivores, yet little information exists about the dispersal and movement patterns of swift foxes ( Vulpes velox ). We radio-collared and monitored 68 swift foxes for dispersal at 2 study sites in northwestern Texas from January 2002 to April 2004. Dispersal distance for juveniles (13.1 ± 0.3 km, s ), adults (10 ± 4.7 km) and transients (25.4 ± 9.1 km) did not differ by age class ( F = 1.49, df = 2, P = 0.24) or sex ( F = 0.23, df = 1, P = 0.63) but differed by study site ( F = 4.72, df = 1, P = 0.04). Mean dispersal distance from private ranches (PR) was greater than from National Grasslands (NG). Peak dispersal occurred during October– November (13 individuals) and January–February (7 individuals). Dispersal direction was influenced by land-use practices (i.e., toward rangelands and away from anthropogenic features). Direction of dispersal among foxes that occupied the NG was uniform ( n = 16, P = 0.08), whereas foxes from PR dispersed in a northwesterly direction ( n = 18, P ≤ 0.001) away from a town and croplands. Three resident adult foxes made extraterritorial movements. Distances of these movements ranged from 0.2 km to 11.4 km. Distance of extraterritorial movements did not differ by sex ( F = 0.05, P = 0.83), nor by duration of movement ( F = 1.11, P = 0.32). Knowledge of movement distances and patterns is important for conservation and protection of swift foxes and their habitats.     

Shorebird predation on benthic macroinvertebrates in an irrigation reservoir

American Falls Reservoir in southeastern Idaho is an irrigation reservoir used as an inland feeding stopover by many shorebird species. Six exclosure experiments were conducted during the 1990 drawdown period to investigate shorebird predation impact on benthic macroinvertebrate populations. The study sites differed in sediment composition, sediment slope, invertebrate densities, and shorebird abundance. Shorebird predation significantly affected invertebrate densities in only 1 of 6 experiments (Aberdeen Mouth). This site had higher sediment slope and a lower water recedence than other study sites, resulting in concentration of shorebird predation on a small area of newly exposed sediment. Shorebird predation had the greatest impact on medium size class chironomid larvae at Aberdeen Mouth. Our results suggest that inland sites such as American Falls Reservoir represent viable shorebird habitat and may be managed to insure consistent prey availability. Drawdown rate, sediment slope, invertebrate densities, and shorebird abundance are all important factors influencing shorebird predation. Monitoring shorebird abundance and predation impact on invertebrate densities may help in manipulating drawdown rate to provide adequate shorebird prey. Management of inland sites for shorebird use may become more important in the future as human encroachment in coastal areas continues.