806 research outputs found
Different cofactor activities in γ-secretase assembly: evidence for a nicastrin–Aph-1 subcomplex
The γ-secretase complex is required for intramembrane cleavage of several integral membrane proteins, including the Notch receptor, where it generates an active signaling fragment. Four putative γ-secretase components have been identified—presenilin (Psn), nicastrin (Nct), Aph-1, and Pen-2. Here, we use a stepwise coexpression approach to investigate the role of each new component in γ-secretase assembly and activation. Coexpression of all four proteins leads to high level accumulation of mature Psn and increased proteolysis of Notch. Aph-1 and Nct may form a subcomplex that stabilizes the Psn holoprotein at an early step in γ-secretase assembly. Subcomplex levels of Aph-1 are down-regulated by stepwise addition of Psn, suggesting that Aph-1 might not enter the mature complex. In contrast, Pen-2 accumulates proportionally with Psn, and is associated with Psn endoproteolysis during γ-secretase assembly. These results demonstrate that Aph-1 and Pen-2 are essential cofactors for Psn, but that they play different roles in γ-secretase assembly and activation
Disruption of Drosophila melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated with Altered Developmental Signaling.
Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of many developmental pathways is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is critical for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase. Both mutants cause Notch, Wingless, the Epidermal Growth Factor Receptor (EFGR), and Patched to accumulate abnormally in endosomal compartments. In mosaic animals, mutant tissues exhibit an unusual non-cell-autonomous effect whereby mutant cells are functionally rescued by secreted activities emanating from adjacent wildtype tissue. Strikingly, both mutants display prominent tissue overgrowth phenotypes that are partially attributable to altered Notch and Wnt signaling. Our analysis of the mutants demonstrates genetic links between abnormal lipid metabolism, perturbations in developmental signaling, and aberrant cell proliferation
Method of Heating a Foam-Based Catalyst Bed
A method of heating a foam-based catalyst bed has been developed using silicon carbide as the catalyst support due to its readily accessible, high surface area that is oxidation-resistant and is electrically conductive. The foam support may be resistively heated by passing an electric current through it. This allows the catalyst bed to be heated directly, requiring less power to reach the desired temperature more quickly. Designed for heterogeneous catalysis, the method can be used by the petrochemical, chemical processing, and power-generating industries, as well as automotive catalytic converters. Catalyst beds must be heated to a light-off temperature before they catalyze the desired reactions. This typically is done by heating the assembly that contains the catalyst bed, which results in much of the power being wasted and/or lost to the surrounding environment. The catalyst bed is heated indirectly, thus requiring excessive power. With the electrically heated catalyst bed, virtually all of the power is used to heat the support, and only a small fraction is lost to the surroundings. Although the light-off temperature of most catalysts is only a few hundred degrees Celsius, the electrically heated foam is able to achieve temperatures of 1,200 C. Lower temperatures are achievable by supplying less electrical power to the foam. Furthermore, because of the foam s open-cell structure, the catalyst can be applied either directly to the foam ligaments or in the form of a catalyst- containing washcoat. This innovation would be very useful for heterogeneous catalysis where elevated temperatures are needed to drive the reaction
Endosomal entry regulates Notch receptor activation in Drosophila melanogaster
Signaling through the transmembrane receptor Notch is widely used throughout animal development and is a major regulator of cell proliferation and differentiation. During canonical Notch signaling, internalization and recycling of Notch ligands controls signaling activity, but the involvement of endocytosis in activation of Notch itself is not well understood. To address this question, we systematically assessed Notch localization, processing, and signaling in a comprehensive set of Drosophila melanogaster mutants that block access of cargo to different endocytic compartments. We find that γ-secretase cleavage and signaling of endogenous Notch is reduced in mutants that impair entry into the early endosome but is enhanced in mutants that increase endosomal retention. In mutants that block endosomal entry, we also uncover an alternative, low-efficiency Notch trafficking route that can contribute to signaling. Our data show that endosomal access of the Notch receptor is critical to achieve physiological levels of signaling and further suggest that altered residence in distinct endocytic compartments could underlie pathologies involving aberrant Notch pathway activation
Lagrangian planetary equations in Schwarzschild space--time
We have developed a method to study the effects of a perturbation to the
motion of a test point--like object in a Schwarzschild spacetime. Such a method
is the extension of the Lagrangian planetary equations of classical celestial
mechanics into the framework of the full theory of general relativity. The
method provides a natural approach to account for relativistic effects in the
unperturbed problem in an exact way.Comment: 7 pages; revtex; accepted for publication in Class. Quantum Gra
Adhesion of surfaces via particle adsorption: Exact results for a lattice of fluid columns
We present here exact results for a one-dimensional gas, or fluid, of
hard-sphere particles with attractive boundaries. The particles, which can
exchange with a bulk reservoir, mediate an interaction between the boundaries.
A two-dimensional lattice of such one-dimensional gas `columns' represents a
discrete approximation of a three-dimensional gas of particles between two
surfaces. The effective particle-mediated interaction potential of the
boundaries, or surfaces, is calculated from the grand-canonical partition
function of the one-dimensional gas of particles, which is an extension of the
well-studied Tonks gas. The effective interaction potential exhibits two
minima. The first minimum at boundary contact reflects depletion interactions,
while the second minimum at separations close to the particle diameter results
from a single adsorbed particle that crosslinks the two boundaries. The second
minimum is the global minimum for sufficiently large binding energies of the
particles. Interestingly, the effective adhesion energy corresponding to this
minimum is maximal at intermediate concentrations of the particles.Comment: to appear in Journal of Statistical Mechanics: Theory and Experimen
Phase behavior and structure of model colloid-polymer mixtures confined between two parallel planar walls
Using Gibbs ensemble Monte Carlo simulations and density functional theory we
investigate the fluid-fluid demixing transition in inhomogeneous
colloid-polymer mixtures confined between two parallel plates with separation
distances between one and ten colloid diameters covering the complete range
from quasi two-dimensional to bulk-like behavior. We use the
Asakura-Oosawa-Vrij model in which colloid-colloid and colloid-polymer
interactions are hard-sphere like, whilst the pair potential between polymers
vanishes. Two different types of confinement induced by a pair of parallel
walls are considered, namely either through two hard walls or through two
semi-permeable walls that repel colloids but allow polymers to freely
penetrate. For hard (semi-permeable) walls we find that the capillary binodal
is shifted towards higher (lower) polymer fugacities and lower (higher) colloid
fugacities as compared to the bulk binodal; this implies capillary condensation
(evaporation) of the colloidal liquid phase in the slit. A macroscopic
treatment is provided by a novel symmetric Kelvin equation for general binary
mixtures, based on the proximity in chemical potentials of statepoints at
capillary coexistence and the reference bulk coexistence. Results for capillary
binodals compare well with those obtained from the classic version of the
Kelvin equation due to Evans and Marini Bettolo Marconi [J. Chem. Phys. 86,
7138 (1987)], and are quantitatively accurate away from the fluid-fluid
critical point, even at small wall separations. For hard walls the density
profiles of polymers and colloids inside the slit display oscillations due to
packing effects for all statepoints. For semi-permeable walls either similar
structuring or flat profiles are found, depending on the statepoint considered.Comment: 15 pages, 13 figure
Complete characterization of convergence to equilibrium for an inelastic Kac model
Pulvirenti and Toscani introduced an equation which extends the Kac
caricature of a Maxwellian gas to inelastic particles. We show that the
probability distribution, solution of the relative Cauchy problem, converges
weakly to a probability distribution if and only if the symmetrized initial
distribution belongs to the standard domain of attraction of a symmetric stable
law, whose index is determined by the so-called degree of
inelasticity, , of the particles: . This result is
then used: (1) To state that the class of all stationary solutions coincides
with that of all symmetric stable laws with index . (2) To determine
the solution of a well-known stochastic functional equation in the absence of
extra-conditions usually adopted
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