Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: Evidence for a proximal role in Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent form of dementia, resulting in progressive neuronal death and debilitating damage to brain loci that mediate memory and higher cognitive function. While pathogenic genetic mutations have been implicated in approximately 2% of AD cases, the proximal events that underlie the common, sporadic form of the disease are incompletely understood. Converging lines of evidence from human neuropathology, basic biology, and genetics have implicated loss of the multifunctional receptor LR11 (also known as SORLA and SORL1) in AD pathogenesis. Cell-based studies suggest that LR11 reduces the formation of beta-amyloid (Abeta), the molecule believed to be a primary toxic species in AD. Recently, mutant mice deficient in LR11 were shown to upregulate murine Abeta in mouse brain. In the current study, LR11-deficient mice were crossed with transgenic mice expressing autosomal-dominant human AD genes, presenilin-1 (PS1DeltaE9) and amyloid precursor protein (APPswe). Here, we show that LR11 deficiency in this AD mouse model significantly increases Abeta levels and exacerbates early amyloid pathology in brain, causing a forward shift in disease onset that is LR11 gene dose-dependent. Loss of LR11 increases the processing of the APP holo-molecule into alpha-, beta-, and gamma-secretase derived metabolites. We propose that LR11 regulates APP processing and Abeta accumulation in vivo and is of proximal importance to the cascade of pathological amyloidosis. The results of the current study support the hypothesis that control of LR11 expression may exert critical effects on Alzheimer's disease susceptibility in humans

Scaling limits of a tagged particle in the exclusion process with variable diffusion coefficient

We prove a law of large numbers and a central limit theorem for a tagged particle in a symmetric simple exclusion process in the one-dimensional lattice with variable diffusion coefficient. The scaling limits are obtained from a similar result for the current through -1/2 for a zero-range process with bond disorder. For the CLT, we prove convergence to a fractional Brownian motion of Hurst exponent 1/4.Comment: 9 page

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed

X-ray diffraction and doping studies of Ga(AsP)/GaP strained-layer superlattices grown by metal organic chemical vapor deposition

Metal organic chemical vapor deposition has been used to prepare strained-layer superlattices in the GaAs + GaP system. Both the composition and the layer thickness can be determined by x-ray diffraction. For very thick layers a direct measure of the strain in the layers can be obtained by x-ray diffraction. H/sub 2/Se and Zn(C/sub 2/H/sub 5/)/sub 2/ have been used to prepare n- and p-type superlattices, respectively. Carrier concentrations in the range of 5 x 10/sup 16/ to 5 x 10/sup 18/ cm/sup -3/ have been achieved for n-type superlattices and 1 x 10/sup 17/ to 1 x 10/sup 18/ cm/sup -3/ for p-type superlattices with mobilities of 46 to 183 cm/sup 2/ V sec. The growth and characterization of these materials will be discussed

Recarbonation of metamorphosed marls, Jordan.

The Maqarin area, northern Jordan, hosts some unusual, hyperalkaline (pH= 12.5) groundwaters discharging from thermally metamorphosed bituminous marls which formed through spontaneous, in situ combustion of the bitumen. The groundwaters have evolved geochemically through hydration, recarbonation and sulphatization of high temperature minerals. Mineralogical relations of the carbonate phases were examined by XRD and cathodoluminescence in conjunction with a detailed investigation of stable isotope ratios by Nd-YAG laser microsampling. Carbon-13 contents trace the sequence of alteration reactions, involving high temperature decarbonation of host biomic marl, followed by in situ recarbonation of secondary calcium hydroxide and calcium-silicate-hydrates (CSH).Carbonation took place shortly after thermal metamorphism, when non-saturated conditions allowed an atmosphere rich in CO2 from adjacent combustion zones to access reaction sites. Low δ18OCaCO3 values suggest that the earliest phase of recarbonation took place by reaction with hydroxide at elevated temperatures while later phases formed at cooler temperatures. Variable14 activities show that soil CO2 was a component of the later recarbonating atmosphere. Once saturated conditions prevailed in the alteration zone, recarbonation ended and alteration evolved to hydroxide and sulphate dissolution reactions. The recarbonation reactions are a field-scale analogue of recarbonation and14C attenuation in cementitious barriers for radioactive waste repositories