ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?

Among the three human apolipoprotein E (apoE) isoforms, apoE4 increases the risk of Alzheimer’s disease (AD). While transporting cholesterol is a primary function, apoE also regulates amyloid-β (Aβ) metabolism, aggregation, and deposition. Although earlier work suggests that different affinities of apoE isoforms to Aβ might account for their effects on Aβ clearance, recent studies indicate that apoE also competes with Aβ for cellular uptake through apoE receptors. Thus, several factors probably determine the variable effects apoE has on Aβ. In this Review, we examine biochemical, structural, and functional studies and propose testable models that address the complex mechanisms underlying apoE-Aβ interaction and how apoE4 may increase AD risk and also serve as a target pathway for therapy

Power factor contor for a doble-fed induction motor

Orientador: Edson BimDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de ComputaçãoResumo: O objetivo deste trabalho é o de implementar o controle de velocidade e de potência reativa de um motor de indução duplamente alimentado com orientação de fluxo de estator, mediante o ajuste das componentes de eixo direto e em quadratura das correntes de rotor, sendo o estator conectado à rede elétrica trifásica. Para isto foram utilizados quatro controladores PI: dois deles têm a função de gerar as referências dessas correntes a partir dos erros da potência reativa e da velocidade, e os outros dois, a de gerar as referências das tensões de eixo direto e em quadratura, a partir dos erros dessas mesmas correntes. Resultados experimentais do motor operando com fator de potência adiantado, unitário e atrasado são apresentados para validar a proposta. O sistema de controle, implementado por um DSP TMS320F2812, é responsável pela leitura das tensões e correntes de estator, da velocidade e da estimação da posição do eixo, pelas transformações de variáveis, pela implementação dos controladores PI, pela determinação da magnitude e posição do fluxo de estator e pela implementação da modulação do vetor espacialAbstract: The purpose of this work is to present the implementation of the speed control and reactive power of a doubly fed induction motor with stator flux orientation, by adjusting of the direct and quadrature-axis rotor current components, being the stator fed by a triphasic network. With this aim, four PI controllers are used: two of them have the function of generating the direct and quadrature references of the rotor current from the direct and quadrature rotor voltage errors and the others two, of generating the direct and quadrature references of the rotor voltage from the direct and quadrature rotor current errors. Experimental results of the motor operating with leading, lagging and unity power factor are presented to validate the proposal. The control algorithm is implemented with a digital signal processor and it has the following functions: lecture of the voltages and currents of rotor, lecture of speed and estimation of rotor position, transformations of variables, implementation of the PI controllers, calculus of magnitude and position of stator flux and space vector modulationMestradoEnergia EletricaMestre em Engenharia Elétric

Generation of mesenchymal stem cells from induced pluripotent stem cells for regenerative medicine

Adult stem cells represent self-renewing, multipotent cells that are capable of producing mature cells of another tissue through differentiation. Stem cells can be sourced from a variety of tissues such as bone marrow, adipose tissue, and cord blood. Bone-marrow derived mesenchymal stem cells (BM-MSC) have the ability to differentiate, lack of ethical concerns, no teratoma potential, easily cultured and expanded ex vivo, and are immunomodulatory via paracrine effects. Thus, BM-MSCs have been actively used as a therapeutic agent in a variety of clinical trials to treat diverse diseases including neurological diseases, cardiovascular diseases, hepatic diseases, lung injury, renal failure, cancers, wound healing and infections. However, concerns have been raised related to high cell population heterogeneity, poorly understood homing capabilities, and a tendency to lose biological functions in vitro with each passage. Recently, induced pluripotent stem cells (iPSCs) have emerged as a new class of stem cells with greater versatility. iPSC technology allows for potential treatment of any degenerative diseases or injury due to the pluripotent potentials and unlimited manufacturing. In this study, we established a method to generate iPSC-derived MSCs (iMSCs). The International Society for Cellular Therapy (ISCT) have imposed several criteria for MSCs, which include 1) plastic adherence, 2) stable expression of CD90, CD105, and CD73 cell surface markers, and 3) ability to differentiate into adipocytes, chondrocytes, and osteoblasts. Our results demonstrated that iMSCs have similar property to that of BM-MSCs by satisfying the criteria. Future directions include creating clinical grade iMSCs which can be used for future regenerative therapies

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV

Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan

Binding affinity of heparin-apoE3 interaction. (A) Representative dot blot of heparin and apoE3 particles. Heparin was spotted onto nitrocellulose membrane along with mouse monoclonal anti-apoE antibody, WUE4, as a positive control and normal mouse IgG as a background. Membrane strips were incubated with increasing concentrations of apoE3 particles from immortalized astrocytes. Membrane-bound apoE was then visualized by biotin-conjugate anti-apoE antibody and infrared streptavidin secondary antibody. (B) Integrated infrared signal intensities from each dot were obtained and the average intensities from three independent experiments were plotted to acquire binding affinity curve and the dissociation constant (Kd). (TIF 2432 kb