Membrane Incorporation, Channel Formation, and Disruption of Calcium Homeostasis by Alzheimer's β-Amyloid Protein

Oligomerization, conformational changes, and the consequent neurodegeneration of Alzheimer's β-amyloid protein (AβP) play crucial roles in the pathogenesis of Alzheimer's disease (AD). Mounting evidence suggests that oligomeric AβPs cause the disruption of calcium homeostasis, eventually leading to neuronal death. We have demonstrated that oligomeric AβPs directly incorporate into neuronal membranes, form cation-sensitive ion channels (“amyloid channels”), and cause the disruption of calcium homeostasis via the amyloid channels. Other disease-related amyloidogenic proteins, such as prion protein in prion diseases or α-synuclein in dementia with Lewy bodies, exhibit similarities in the incorporation into membranes and the formation of calcium-permeable channels. Here, based on our experimental results and those of numerous other studies, we review the current understanding of the direct binding of AβP into membrane surfaces and the formation of calcium-permeable channels. The implication of composition of membrane lipids and the possible development of new drugs by influencing membrane properties and attenuating amyloid channels for the treatment and prevention of AD is also discussed

External Finance and Investment Climate in East Asia and Other Emerging Markets: What Really Matters?

Developing countries are facing new competitive challenges to attract sufficient external financing to sustain their growth. This paper attempts to answer the question: How can a country attract more long-term, stable foreign investment? Our study shows the increasing role of a political risk factor as a driver of foreign direct investment (FDI) inflows, and suggests that reduced financial risk after the East Asian crisis might have led to a substitution of FDI with capital market flows. Our study also shows the importance of fostering sound regulatory systems and good institutions for attracting FDI, for example, establishing a stable government that implements economic policy effectively and reduces uncertainty associated with internal disorder and a lack of democratic regime. The simulation exercise suggests that an improved investment climate would increase FDI by 7 percent and would benefit China most. (c) 2007 The Earth Institute at Columbia University and the Massachusetts Institute of Technology.

THE ROLE OF CROSS-BORDER MERGERS AND ACQUISITIONS IN ASIAN RESTRUCTURING

Asset purchases by international firms in developing countries (cross-border mergers and acquisitions or M&A), involving more than a 50 percent stake, rose sharply in value from $19 billion in 1996 to$43 billion and 47 billion in 1997 and 1998, and fell slightly in 1999. The rise was fuelled in part by the purchase of distressed assets in the East Asian crisis countries (especially in Korea and Thailand). East Asian M&A deals jumped from 2 billion in 1996 to $7 billion in 1997, and further up to$10 billion in 1998. Latin America M&A deals also increased rapidly but, in contrast to East Asia, were the result of asset acquisition by foreigners under privatization programs. The increased capital flows through M&A deals were welcome as capital market inflows fell sharply and foreign direct investment in new projects remained stable, or even declined. Though on the rise, cross-border M&A in developing countries form less than 20 percent of global cross-border M&A activity. International mega-mergers, which are integrating activities across borders to exploit technological and marketing synergies and are thus potentially transforming several major industrial sectors, are yet to have a significant influence on developing countries. Recent developing country M&A may be characterized as a first step in the integration process. That first step entails a restructuring of production and marketing activities to bring the developing country partner in line with the best operating procedures. In principle, cross-border M&A can facilitate corporate and financial restructuring by improving the efficiency of operations as well as by reducing excess capacity. The new management and financial resources made available through international M&As can be especially useful following a syste..

Role of Interleukin-6 in the Antigen-Specific Mucosal Immunoglobulin A Responses Induced by CpG Oligodeoxynucleotide-Loaded Cationic Liposomes

An advantage of mucosal vaccines over conventional parenteral vaccines is that they can induce protective immune responses not only at mucosal surfaces but also in systemic compartments. Despite this advantage, few live attenuated or inactivated mucosal vaccines have been developed and applied clinically. We recently showed that the intranasal immunization of ovalbumin (OVA) with class B synthetic oligodeoxynucleotides (ODNs) containing immunostimulatory CpG motif (CpG ODN)-loaded cationic liposomes synergistically exerted both antigen-specific mucosal immunoglobulin A (IgA) and systemic immunoglobulin G (IgG) responses in mice. However, the mechanism underlying the mucosal adjuvant activity of CpG ODN-loaded liposomes remains unknown. In the present study, we showed that the intranasal administration of CpG ODN-loaded cationic liposomes elicited interleukin (IL)-6 release in nasal tissues. Additionally, pre-treatment with an anti-IL-6 receptor (IL-6R) antibody attenuated antigen-specific nasal IgA production but not serum IgG responses. Furthermore, the intranasal administration of OVA and CpG ODN-loaded cationic liposomes increased the number of IgA+/CD138+ plasma cells and IgA+/B220+ B cells in the nasal passages. This increase was markedly suppressed by pre-treatment with anti-IL-6R blocking antibody. In conclusion, IL-6 released by CpG ODN-loaded cationic liposomes at the site of administration may play a role in the induction of antigen-specific IgA responses by promoting differentiation into IgA+ plasma cells for IgA secretion from B cells