The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells

Lipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. In vitro and in vivo genetic and pharmacological studies have demonstrated PPARalpha regulates lipid catabolism. In contrast, PPARgamma regulates the conflicting process of lipid storage. However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. PPARbeta/delta, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Consequently, it has a significant role in insulin sensitivity, the blood-lipid profile, and lipid homeostasis. Surprisingly, the role of PPARbeta/delta in skeletal muscle has not been investigated. We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARgamma induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyltransferase-1 promoter is directly regulated by PPARbeta/delta, and not PPARalpha in skeletal muscle cells in a PPARgamma coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Moreover, we surmise that PPARgamma/delta agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARbeta/delta may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity.

Conformational changes in SP-B as a function of surface pressure

X-ray reflectivity of bovine and sheep surfactant-associated protein B (SP-B) monolayers is used in conjunction with pressure-area isotherms and protein models to suggest that the protein undergoes changes in its tertiary structure at the air/water interface under the influence of surface pressure, indicating the likely importance of such changes to the phenomena of protein squeeze out as well as lipid exchange between the air-water interface and subphase structures. We describe an algorithm based on the well-established box- or layer-models that greatly assists the fitting of such unknown scattering-length density profiles, and which takes the available instrumental resolution into account. Scattering-length density profiles from neutron reflectivity of bovine SP-B monolayers on aqueous subphases are shown to be consistent with the exchange of a large number of labile protons as well as the inclusion of a significant amount of water, which is partly squeezed out of the protein monolayer at elevated surface pressures.

Identification of cholinoceptive glycinergic neurons in the mammalian retina

The light-evoked release of acetylcholine (ACh) affects the responses of many retinal ganglion cells, in part via nicotinic acetylcholine receptors (nAChRs). nAChRs that contain beta2alpha3 neuronal nicotinic acetylcholine receptors have been identified and localized in the rabbit retina; these nAChRs are recognized by the monoclonal antibody mAb210. We have examined the expression of beta2alpha3 nAChRs by glycinergic amacrine cells in the rabbit retina and have identified different subpopulations of nicotinic cholinoceptive glycinergic cells using double and triple immunohistochemistry with quantitative analysis. Here we demonstrate that about 70% of the cholinoceptive amacrine cells in rabbit retina are glycinergic cells. At least three nonoverlapping subpopulations of mAb210 glycine-immunoreactive cells can be distinguished with antibodies against calretinin, calbindin, and gamma-aminobutyric acid (GABA)(A) receptors. The cholinergic cells in rabbit retina are thought to synapse only on other cholinergic cells and ganglion cells. Thus, the expression of beta2alpha3 nAChRs on diverse populations of glycinergic cells is puzzling. To explore this finding, the subcellular localization of beta2alpha3 was studied at the electron microscopic level. mAb210 immunoreactivity was localized on the dendrites of amacrines and ganglion cells throughout the inner plexiform layer, and much of the labeling was not associated with recognizable synapses. Thus, our findings indicate that ACh in the mammalian retina may modulate glycinergic circuits via extrasynaptic beta2alpha3 nAChRs. (C) 2002 Wiley-Liss, Inc.

A class B switch-mode assisted linear amplifier

A switch-mode assisted linear amplifier (SMALA) combining a linear (Class B) and a switch-mode (Class D) amplifier is presented. The usual single hysteretic controlled half-bridge current dumping stage is replaced by two parallel buck converter stages, in a parallel voltage controlled topology. These operate independently: one buck converter sources current to assist the upper Class B output device, and a complementary converter sinks current to assist the lower device. This topology lends itself to a novel control approach of a dead-band at low power levels where neither class D amplifier assists, allowing the class B amplifier to supply the load without interference, ensuring high fidelity. A 20 W implementation demonstrates 85% efficiency, with distortion below 0.08% measured across the full audio bandwidth at 15 W. The class D amplifier begins assisting at 2 W, and below this value, the distortion was below 0.03%. Complete circuitry is given, showing the simplicity of the additional class D amplifier and its corresponding control circuitry.

Redox active macrocyclic receptors for neutral guests

A novel series of triazine-appended macrocyclic complexes has been investigated as potential hydrogen bonding receptors for complementarily disposed heterocycles. Cocrystallization of a melamine-appended azacyclam complex of Cull has been achieved with barbitone, the barbiturate anion and thymine. In each case, a complementary DAD/ADA hydrogen bonding motif between the melamine group and the heterocycle has been identified by X-ray crystallography. Electrochemical studies of the copper macrocycles in both nonaqueous and aqueous solution show anodic shifts of the CuII/I redox couple of more than 60 mV upon addition of guest molecules with matching H-bonding motifs. The Zn-II analogues have been synthesized via transmetalation of the Cull complex, and their guest binding properties investigated by NMR spectroscopy. H-1 NMR shifts of up to 0.8 ppm were observed upon addition of guest, and stability constants are similar to those obtained electrochemically.

A protective effect of early pregnancy factor on experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein

Experimental antoimmune encephalomyelitis (EAE) is an organ-specific autoimmune disease characterised by inflammation and demyelination of the central nervous system and is the best available animal model of multiple sclerosis (MS). Since previous studies have shown that EAE is less severe or is delayed in onset during pregnancy and that administration of the pregnancy hormone early pregnancy factor (EPF) down-regulates EAE, experiments in the present study were designed to explore further the role of EPF in EAE. By using the rosette inhibition test, the standard bioassay for EPF and, by semi-quantitative RT-PCR techniques, we have now shown that inflammatory cells from the spinal cord of rats with EAE can produce and secrete EPF, with production being greatest during recovery from disease. Administration of EPF to rats with EAE resulted in a significant increase in the expression of IL-4 and IL-10 mRNA and a significant decrease in IFN-gamma mRNA expression in spinal cord inflammatory cells. Encephalitogenic MBP-specific T cell lines were prepared from popliteal lymph nodes of rats with EAE. Proliferation assays using these cells demonstrated the ability of exogenous EPF to down-regulate the responses of T lymphocytes to MBP. (C) 2003 Elsevier B.V. All rights reserved.

Agenda social registro civil de nascimento e documenta????o b??sica: comit??s gestores da agenda social

Esta ?? uma iniciativa de gest??o para implementa????o da Agenda Social Registro Civil de Nascimento e Documenta????o B??sica, envolvendo uma rede de ??rg??os e institui????es de diversos poderes da Rep??blica nos tr??s n??veis administrativos do estado brasileiro, bem como institui????es da sociedade civil e organismos internacionais, a partir da atua????o de comit??s gestores em n??vel central e descentralizados. A agenda possibilitou intervir na forma????o de uma cultura de inclus??o a partir da documenta????o civil, com base na realiza????o das campanhas em n??vel nacional. Um dos resultados da implementa????o da agenda ?? a queda do ??ndice de sub-registro de nascidos vivos, que era de 20,9% em 2002, e passou para 12,2% em 2007

Sistema de coleta on-line do Censo Escolar da Educa????o B??sica (Educacenso)

O Educacenso ?? um sistema eletr??nico de coleta de informa????es educacionais composto por um aplicativo web, que permite a coleta, migra????o e altera????o de dados educacionais das escolas em todo o territ??rio nacional, e por um banco de dados relacional, que armazena de forma sistem??tica todas estas informa????es. O Educacenso representa uma inova????o, pois se trata de um banco de dados ??nico, de base nacional, alimentado por dados e informa????es que v??m diretamente das escolas, por meio da internet. Constitui-se no mais completo cadastro de escolas, alunos e docentes do pa??s. A constru????o de um banco de dados com informa????es individualizadas amplia as possibilidades de comunica????o com outras bases de dados do governo federal. O novo desenho metodol??gico e a utiliza????o de recursos de tecnologia da informa????o permitiram ampliar a precis??o e a fidedignidade dos dados do Censo Escolar, o que possibilita realiza????o de ajustes na pol??tica educacional e maior efetividade do gasto p??blico com a educa????o b??sica

??ndice de desenvolvimento da educa????o b??sica (Ideb)

O ??ndice de Desenvolvimento da Educa????o B??sica (Ideb) ?? um indicador que combina informa????es de fluxo e de desempenho dos alunos, criado para promover um sistema de accountability visando a melhoria da qualidade da educa????o no pa??s. Ao elaborar metas detalhadas para cada rede e escola ??? com as quais governadores e prefeitos se comprometeram por meio do Compromisso Todos Pela Educa????o ??? ao calcular e divulgar amplamente os resultados do Ideb, o Instituto Nacional de Estudos e Pesquisas Educacionais An??sio Teixeira (Inep) possibilitou que os atores educacionais pudessem ser responsabilizados pelos resultados de sua unidade e que o Minist??rio da Educa????o (MEC) identificasse e premiasse as escolas que atingem as metas, mas tamb??m oferecesse assist??ncia t??cnica e financeira para as redes com piores resultados. Entre os principais resultados j?? alcan??ados, pode-se destacar que o Ideb do pa??s para os anos iniciais do ensino fundamental cresceu de 3,8, em 2005, para 4,2, em 2007

Projeto b??sico: oficina de reflex??o e alinhamento das pol??ticas de promo????o e incentivo ?? leitura em nosso pa??s

Contrata????o de servi??os t??cnicos profissionais especializados de doc??ncia para modera????o na Oficina, sob medida, de reflex??o e alinhamento das pol??ticas de promo????o e incentivo ?? leitura em nosso Pa??s, sendo a execu????o da Oficina norteada pelas diretrizes expressas no inciso I do art. 2?? da Resolu????o n?? 01 de 31 de janeiro de 2013 e nos incisos I do art. 2?? do Decreto n?? 8.091, de 03 de setembro de 2013

Projeto b??sico: oficina de discuss??o: leitura e escrita de qualidade para todos

Contrata????o de servi??os t??cnicos profissionais especializados de doc??ncia para modera????o na Oficina, sob medida, de reflex??o e alinhamento das pol??ticas de promo????o e incentivo ?? leitura em nosso Pa??s

Projeto b??sico: oficina de avalia????o do Programa Estudante Conv??nio de Gradua????o -PEC-G

Contrata????o de servi??os t??cnicos profissionais especializados de modera????o de Oficina Sob Medida, objetivando a realiza????o de Oficina de Avalia????o

Projeto B??sico: oficina para desenho do programa de capacita????o em acessibilidade e direitos humanos

Contrata????o de servi??os t??cnicos profissionais especializados para elabora????o e revis??o de material did??tico, bem como instrutoria em sala de aula, objetivando o desenvolvimento do Programa de Capacita????o em Acessibilidade e Direitos Humanos

Projeto b??sico: oficina de fundamentos para supervis??o da presta????o de servi??os de consultoria em melhoria de processos

Servi??os t??cnicos profissionais especializados de treinamento e aperfei??oamento de pessoal de instrutoria em sala de aula, objetivando a realiza????o de curso de desenvolvimento t??cnico gerencial