Assembly, trafficking and function of gamma-secretase

gamma-Secretase catalyzes the final cleavage of the beta-amyloid precursor protein to generate amyloid-beta peptide, the principal component of amyloid plaques in the brains of patients suffering from Alzheimer's disease. Here, we review the identification of gamma-secretase as a protease complex and its assembly and trafficking to its site(s) of cellular function. In reconstitution experiments, gamma-secretase was found to be composed of four integral membrane proteins, presenilin (PS), nicastrin (NCT), PEN-2 and APH-1 that are essential and sufficient for gamma-secretase activity. PS, which serves as a catalytic subunit of gamma-secretase, was identified as a prototypic member of novel aspartyl proteases of the GxGD type. In human cells, gamma-secretase could be further defined as a heterogeneous activity consisting of distinct complexes that are composed of PS1 or PS2 and APH-1a or APH-1b homologues together with NCT and PEN-2. Using green fluorescent protein as a reporter we localized PS and gamma-secretase activity at the plasma membrane and endosomes. Investigation of gamma-secretase complex assembly in knockdown and knockout cells of the individual subunits allowed us to develop a model of complex assembly in which NCT and APH-1 first stabilize PS before PEN-2 assembles as the last component. Furthermore, we could map domains in PS and PEN-2 that govern assembly and trafficking of the complex. Finally, Rer1 was identified as a PEN-2-binding protein that serves a role as an auxiliary factor for gamma-secretase complex assembly. Copyright (c) 2006 S. Karger AG, Basel

A Probabilistic Analysis of Kademlia Networks

Kademlia is currently the most widely used searching algorithm in P2P (peer-to-peer) networks. This work studies an essential question about Kademlia from a mathematical perspective: how long does it take to locate a node in the network? To answer it, we introduce a random graph K and study how many steps are needed to locate a given vertex in K using Kademlia's algorithm, which we call the routing time. Two slightly different versions of K are studied. In the first one, vertices of K are labelled with fixed IDs. In the second one, vertices are assumed to have randomly selected IDs. In both cases, we show that the routing time is about c*log(n), where n is the number of nodes in the network and c is an explicitly described constant.Comment: ISAAC 201

On The Evolution of Magnetic White Dwarfs

We present the first radiation magnetohydrodynamics simulations of the atmosphere of white dwarf stars. We demonstrate that convective energy transfer is seriously impeded by magnetic fields when the plasma-beta parameter, the thermal to magnetic pressure ratio, becomes smaller than unity. The critical field strength that inhibits convection in the photosphere of white dwarfs is in the range B = 1-50 kG, which is much smaller than the typical 1-1000 MG field strengths observed in magnetic white dwarfs, implying that these objects have radiative atmospheres. We have then employed evolutionary models to study the cooling process of high-field magnetic white dwarfs, where convection is entirely suppressed during the full evolution (B > 10 MG). We find that the inhibition of convection has no effect on cooling rates until the effective temperature (Teff) reaches a value of around 5500 K. In this regime, the standard convective sequences start to deviate from the ones without convection owing to the convective coupling between the outer layers and the degenerate reservoir of thermal energy. Since no magnetic white dwarfs are currently known at the low temperatures where this coupling significantly changes the evolution, effects of magnetism on cooling rates are not expected to be observed. This result contrasts with a recent suggestion that magnetic white dwarfs with Teff < 10,000 K cool significantly slower than non-magnetic degenerates.Comment: 11 pages, 12 figures, accepted for publication in the Astrophysical Journa

BE Ursae Majoris: A detached binary with a unique reprocessing spectrum

New infrared photometry, optical and UV spectrophotometry, and a photographic ephemeris are presented for the detached binary BE UMa. Results show the primary to be a DO white dwarf with an effective temperature of 80,000 + or - 15,000 K and a mass of 0.6 + or - 0.1 solar masses. No evidence is found for variability of the primary. The main sequence secondary star is shown to be of early M spectral type, with a formal range of M1 to M5 being possible. A reflection effect in reprocessed line and continuum radiation is produced by EUV radiation from the primary incident on the secondary atmosphere. It is suggested that the temperature of the reprocessed component of the secondary's atmosphere is in the 5000 to 8500 K range, and that emission lines of decreasing ionization form deeper in the irradiated envelope. Relatively narrow He II and high excitation metal lines are formed from recombination and continuum fluorescence processes