Identification of multiple quantitative trait loci linked to prion disease incubation period in mice

Polymorphisms in the prion protein gene are known to affect prion disease incubation times and susceptibility in humans and mice. However, studies with inbred lines of mice show that large differences in incubation times occur even with the same amino acid sequence of the prion protein, suggesting that other genes may contribute to the observed variation. To identify these loci we analyzed 1,009 animals from an F2 intercross between two strains of mice, CAST/Ei and NZW/OlaHSd, with significantly different incubation periods when challenged with RML scrapie prions. Interval mapping identified three highly significantly linked regions on chromosomes 2, 11, and 12; composite interval mapping suggests that each of these regions includes multiple linked quantitative trait loci. Suggestive evidence for linkage was obtained on chromosomes 6 and 7. The sequence conservation between the mouse and human genome suggests that identification of mouse prion susceptibility alleles may have direct relevance to understanding human susceptibility to bovine spongiform encephalopathy (BSE) infection, as well as identifying key factors in the molecular pathways of prion pathogenesis. However, the demonstration of other major genetic effects on incubation period suggests the need for extreme caution in interpreting estimates of variant Creutzfeldt–Jakob disease epidemic size utilizing existing epidemiological models.

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

The incubation period (IP) and the neuropathology of transmissible spongiform encephalopathies (TSEs) have been extensively used to distinguish prion isolates (or strains) inoculated into panels of inbred mouse strains. Such studies have shown that the bovine spongiform encephalopathy (BSE) agent is indistinguishable from the agent causing variant Creutzfeldt–Jakob disease (vCJD), but differs from isolates of sporadic CJD, reinforcing the idea that the vCJD epidemic in Britain results from consumption of contaminated beef products. We present a mouse model for genetic and environmental factors that modify the incubation period of BSE cross-species transmission. We have used two mouse strains that carry the same prion protein (PrP) allele, but display a 100-day difference in their mean IP following intracerebral inoculation with primary BSE isolate. We report genetic effects on IP that map to four chromosomal regions, and in addition we find significant factors of host environment, namely the age of the host's mother, the age of the host at infection, and an X-cytoplasm interaction in the host.

The accretion environment in Vela X-1 during a flaring period using XMM-Newton

We present analysis of 100 ks contiguous XMM-Newton data of the prototypical wind accretor Vela X-1. The observation covered eclipse egress between orbital phases 0.134 and 0.265, during which a giant flare took place, enabling us to study the spectral properties both outside and during the flare. This giant flare with a peak luminosity of 3.92+0.42-0.09 × 1037 erg s-1 allows estimates of the physical parameters of the accreted structure with a mass of ~1021 g. We have been able to model several contributions to the observed spectrum with a phenomenological model formed by three absorbed power laws plus three emission lines. After analysing the variations with orbital phase of the column density of each component, as well as those in the Fe and Ni fluorescence lines, we provide a physical interpretation for each spectral component. Meanwhile, the first two components are two aspects of the principal accretion component from the surface of the neutron star, the third component seems to be the X-ray light echo formed in the stellar wind of the companion.

Villages before aggregation : the Merrigan Site (LA 110971), a developmental period hamlet, El Rancho, New Mexico / Winifred Creamer, Jonathan Haas.

n.s. no.35(2003)

Notes of cases decided in the Superior and Supreme Judicial Courts of Massachusetts from 1772 to 1789: taken by the Hon. William Cushing, one of the judges during that period and most of the time Chief Justice

Notes of cases taken by Judge William Cushing during his tenure on the Massachusetts superior and supreme courts. (Formerly MS 2141.)

Dynamical Equations For The Period Vectors In A Periodic System Under Constant External Stress

The purpose of this paper is to derive the dynamical equations for the period vectors of a periodic system under constant external stress. The explicit starting point is Newton’s second law applied to halves of the system. Later statistics over indistinguishable translated states and forces associated with transport of momentum are applied to the resulting dynamical equations. In the final expressions, the period vectors are driven by the imbalance between internal and external stresses. The internal stress is shown to have both full interaction and kinetic-energy terms.

Chemical Sensor Based on a Long-Period Fibre Grating Modified by a Functionalized Polydimethylsiloxane Coating

A chemical sensor based on a coated long-period grating has been prepared and characterized. Designer coatings based on polydimethylsiloxane were prepared by the incorporation of diphenylsiloxane and titanium cross-linker in order to provide enhanced sensitivity for a variety of key environmental pollutants and optimal refractive index of the coating. Upon microextraction of the analyte into the polymer matrix, an increase in the refractive index of the coating resulted in a change in the attenuation spectrum of the long-period grating. The grating was interrogated using ring-down detection as a means to amplify the optical loss and to gain stability against misalignment and power fluctuations. Chemical differentiation of cyclohexane and xylene was achieved and a detection limit of 300 ppm of xylene vapour was realized.