Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β

Extracellular plaques of amyloid-β and intraneuronal neurofibrillary tangles made from tau are the histopathological signatures of Alzheimer's disease. Plaques comprise amyloid-β fibrils that assemble from monomeric and oligomeric intermediates, and are prognostic indicators of Alzheimer's disease. Despite the importance of plaques to Alzheimer's disease, oligomers are considered to be the principal toxic forms of amyloid-β. Interestingly, many adverse responses to amyloid-β, such as cytotoxicity, microtubule loss, impaired memory and learning, and neuritic degeneration, are greatly amplified by tau expression. Amino-terminally truncated, pyroglutamylated (pE) forms of amyloid-β are strongly associated with Alzheimer's disease, are more toxic than amyloid-β, residues 1-42 (Aβ(1-42)) and Aβ(1-40), and have been proposed as initiators of Alzheimer's disease pathogenesis. Here we report a mechanism by which pE-Aβ may trigger Alzheimer's disease. Aβ(3(pE)-42) co-oligomerizes with excess Aβ(1-42) to form metastable low-n oligomers (LNOs) that are structurally distinct and far more cytotoxic to cultured neurons than comparable LNOs made from Aβ(1-42) alone. Tau is required for cytotoxicity, and LNOs comprising 5% Aβ(3(pE)-42) plus 95% Aβ(1-42) (5% pE-Aβ) seed new cytotoxic LNOs through multiple serial dilutions into Aβ(1-42) monomers in the absence of additional Aβ(3(pE)-42). LNOs isolated from human Alzheimer's disease brain contained Aβ(3(pE)-42), and enhanced Aβ(3(pE)-42) formation in mice triggered neuron loss and gliosis at 3 months, but not in a tau-null background. We conclude that Aβ(3(pE)-42) confers tau-dependent neuronal death and causes template-induced misfolding of Aβ(1-42) into structurally distinct LNOs that propagate by a prion-like mechanism. Our results raise the possibility that Aβ(3(pE)-42) acts similarly at a primary step in Alzheimer's disease pathogenesis.     

Human gamma-chain genes are rearranged in leukaemic T cells and map to the short arm of chromosome 7

Three gene families that rearrange during the somatic development of T cells have been identified in the murine genome. Two of these gene families (alpha and beta) encode subunits of the antigen-specific T-cell receptor and are also present in the human genome. The third gene family, designated here as the gamma-chain gene family, is rearranged in murine cytolytic T cells but not in most helper T cells. Here we present evidence that the human genome also contains gamma-chain genes that undergo somatic rearrangement in leukaemia-derived T cells. Murine gamma-chain genes appear to be encoded in gene segments that are analogous to the immunoglobulin gene variable, constant and joining segments. There are two closely related constant-region gene segments in the human genome. One of the constant-region genes is deleted in all three T-cell leukaemias that we have studied. The two constant-region gamma-chain genes reside on the short arm of chromosome 7 (7p15); this region is involved in chromosomal rearrangements identified in T cells from individuals with the immunodeficiency syndrome ataxia telangiectasia and observed only rarely in routine cytogenetic analyses of normal individuals. This region is also a secondary site of beta-chain gene hybridization.     

Relationship of diurnal habitat use of native stream fishes of the eastern Great Basin to pPresence of introduced salmonids

Introduced brown trout, Salmo trutta , are common to many streams of western North America. However, the ecological interactions between brown trout and native stream fishes are not well understood, particularly the nature and extent of antipredator responses of native species. We examined the effects of brown trout presence on diurnal habitat use by 2 small native fishes at a mesohabitat scale (e.g., pool, riffle, run, backwater, etc.). Adult and juvenile southern leatherside chub ( Lepidomeda aliciae , formerly Gila copei ) and juvenile mountain sucker ( Catostomus platyrhynchus ) were located in main channel pools in the absence of brown trout, but they were found almost exclusively in backwaters and cutoff pools (i.e., off-channel habitats) in streams where brown trout were abundant. Off-channel habitat appears to provide a refuge for native fishes in streams with abundant brown trout populations. Altered or degraded streams may not include sufficient off-channel refuge habitats to allow coexistence of native species and introduced brown trout.     

Nutritional condition of elk in Rocky Mountain National Park

We tested the hypothesis that elk in Rocky Mountain National Park (RMNP) were at ecological carrying capacity by determining herd-specific levels of nutritional condition and fecundity. Ingesta-free body fat levels in adult cows that were lactating were 10.6% ( s = 1.7; range = 6.2-15.4) and 7.7% ( s = 0.5; range = 5.9-10.1) in November 2001 for the Horseshoe and Moraine Park herds, respectively. Cows that were not lactating were able to accrue significantly more body fat: 14.0% ( s = 1.1; range = 7.7-19.3) and 11.5% ( s = 0.8; range = 8.6-15.1) for the Horseshoe and Moraine Park herds, respectively. Cow elk lost most of their body fat over winter (April 2002 levels were 3.9% [ s = 0.4] and 2.9% [ s = 0.4] for the Horseshoe and Moraine Park herds, respectively). Nutritional condition indicated that both Horseshoe Park and Moraine Park elk were well below condition levels elk can achieve on very good-excellent nutrition (i.e., > 15% body fat; Cook et al. 2004) and were comparable to other free-ranging elk populations. However, condition levels were higher than those expected at a ""food-limited"" carrying capacity, and a proportion of elk in each herd were able to achieve condition levels indicative of very good-excellent nutrition. Elk in RMNP are likely regulated and/or limited by a complex combination of density-independent (including significant heterogeneity in forage conditions across RMNP's landscape) and density-dependent processes, as condition levels contradict a simple density-dependent model of a population at ecological carrying capacity.     

Northern Bobwhite habitat selection in relation to brush management in the Rolling Plains of Texas

Many rangelands in the southwestern United States provide quality habitat for Northern Bobwhites ( Colinus virginianus ). These same habitats are frequently managed for livestock production and thus are subjected to various brush management practices that are meant to enhance forage production. Bobwhites rely on woody cover for food, thermal and loafing cover, and protection from avian predators. Implementing brush management practices that reflect bobwhite requirements is important for managing usable space and viable populations. We described the structural vegetative characteristics associated with bobwhite locations and random locations on native rangelands in the upper Rolling Plains of Texas that are dominated by honey mesquite ( Prosopis glandulosa ) and managed with aerial herbicide and prescribed fire. We also used binary logistic regression to model habitat selection; the initial model was built using 67% of the data ( n = 179 used-random paired points) and then validated using the remaining 33% of the data ( n = 88 used-random paired points). Locations used by bobwhites had significantly larger mean values of percent brush canopy cover, visual obstruction, and angle of obstruction than did random locations; random locations had a greater mean value of percent bare ground than locations used by bobwhites. The resulting logistic regression model contained only the angle of obstruction; the model had an 80% probability of correctly classifying used and random locations based on the area under the receiver operating curve (ROC). The model maintained a high classification probability when applied to the smaller validation data set, with an area under the ROC of 0.78.     

Infection of young Douglas-firs by dwarf mistletoe in the Southwest

Studies in several areas in Arizona and New Mexico show that dwarf mistletoe ( Arceuthobium douglasii ) is rare in young Douglas-firs growing under infected overstories. Less than 5% of the Douglas-firs under 26 years old and less than 6% of those under 1.4m tall were infected in 77 mistletoe-infested stands. Both percent infection and mean dwarf mistletoe rating of young Douglas-firs increased as tree age, height, and stand dwarf mistletoe ratings increased.     

Distribution of the Shoshone scuplin ( Cottus greenei: Cottidae) in the Hagerman Valley of south central Idaho

Cottus greenei, a potentially threatened species endemic to Idaho, was collected from 49 localities in 25 springs/streams in south central Idaho. Most localities were along the north bank of the Snake River in waters of the Thousand Springs formation, Gooding County. One population was found in a spring in the main Snake River. Another sculpin, Cottus bairdi, was collected with C. greenei at 23 locations in 16 springs/streams. Confusion concerning the type locality of Cottus greenei is discussed.