Adsorption of colloidal particles in the presence of external field

We present a new class of sequential adsorption models in which the adsorbing particles reach the surface following an inclined direction (shadow models). Capillary electrophoresis, adsorption in the presence of a shear or on an inclined substrate are physical manifestations of these models. Numerical simulations are carried out to show how the new adsorption mechanisms are responsible for the formation of more ordered adsorbed layers and have important implications in the kinetics, in particular modifying the jamming limit.Comment: LaTex file, 3 figures available upon request, to appear in Phys.Rev.Let

Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

Background: Middle age obesity is recognized as a risk factor for Alzheimer’s disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings: To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance: Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-a and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokin

Adsorption kinetics in the presence of external fields

In this article we present a detailed analysis of the kinetics of a class of sequential adsorption models that take into account the effect of externally applied fields (as an electric field, or a shear rate) on the adsorption. The excluded volume interactions related to the finite size of the adsorbing particles are modified by the external fields. As a result, new adsorption mechanisms appear with respect to the ones used to describe the kinetics in a quiescent fluid. In particular, if the adsorbing particles are allowed to roll over preadsorbed ones, adsorption becomes non local even in the simplest geometry. An exact analytic theory cannot be developed, but we introduce a self-consistent theory that turns out to agree with the simulation results over all the range of the parameters

The airbag problem-a potential culprit for bench-to-bedside translational efforts: relevance for Alzheimer's disease

For the last 20 years, the "amyloid cascade hypothesis" has dominated research aimed at understanding, preventing, and curing Alzheimer's disease (AD). During that time researchers have acquired an enormous amount of data and have been successful, more than 300 times, in curing the disease in animal model systems by treatments aimed at clearing amyloid deposits. However, to date similar strategies have not been successful in human AD patients. Hence, before rushing into further clinical trials with compounds that aim at lowering amyloid-beta (Aβ) levels in increasingly younger people, it would be of highest priority to re-assess the initial assumption that accumulation of Aβ in the brain is the primary pathological event driving AD. Here we question this assumption by highlighting experimental evidence in support of the alternative hypothesis suggesting that APP and Aβ are part of a neuronal stress/injury system, which is up-regulated to counteract inflammation/oxidative stress-associated neurodegeneration that could be triggered by a brain injury, chronic infections, or a systemic disease. In AD, this protective program may be overridden by genetic and other risk factors, or its maintenance may become dysregulated during aging. Here, we provide a hypothetical example of a hypothesis-driven correlation between car accidents and airbag release in analogy to the evolution of the amyloid focus and as a way to offer a potential explanation for the failure of the AD field to translate the success of amyloid-related therapeutic strategies in experimental models to the clinic

Functions of Aβ, sAPPα and sAPPβ : similarities and differences

International audienceAmyloid peptide (Aβ) is derived from the cleavage of amyloid precursor protein (APP), which also generates the soluble peptide APPβ (sAPPβ). An antagonist and major APP metabolic pathway involves cleavage by alpha secretase, which releases sAPPα. Although soluble Aβ oligomers are neurotoxic, Aβ monomers share similar properties with sAPPα. These include neurotrophic and neuroprotective effects, as well as stimulation of neural-progenitor proliferation. The properties of Aβ monomers and the neurotrophic capacity of sAPPβ to stimulate axonal outgrowth suggest that Aβ production is not deleterious per se. Consequently, therapeutic strategies for Alzheimer's disease that are targeted at Aβ-cleaving enzymes should modulate rather than inhibit Aβ generation. These strategies should focus on the factors that induce the conversion of Aβ monomers into toxic soluble oligomers. Another interesting therapeutic approach is to focus on the mechanisms of the different properties of sAPPα. Indeed, increasing sAPPα levels could shift proliferating cells towards tumorigenesis. In contrast to its neuroprotective effects, sAPPα is also able to activate microglia, leading to neurotoxicity. Understanding the mechanisms that underlie the different properties of sAPPα could therefore lead to the development of therapeutic strategies against Alzheimer's disease, which could be curative as well as preventive