Analysis of agonist and antagonist effects on thyroid hormone receptor conformation by hydrogen/deuterium exchange

Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) with agonists are available, comparable structures without ligand (apo-TR) or with antagonists are not. It remains important to understand apo-LBD conformation and the way that it rearranges with ligands to develop better TR pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on TR LBDs with or without agonist (T 3) or antagonist (NH3). Both ligands reduce deuterium incorporation into LBD amide hydrogens, implying tighter overall folding of the domain. As predicted, mass spectroscopic analysis of individual proteolytic peptides after hydrogen/ deuterium exchange reveals that ligand increases the degree of solvent protection of regions close to the buried ligand-binding pocket. However, there is also extensive ligand protection of other regions, including the dimer surface at H10-H11, providing evidence for allosteric communication between the ligand-binding pocket and distant interaction surfaces. Surprisingly, Cterminal activation helix H12, which is known to alter position with ligand, remains relatively protected from solvent in all conditions suggesting that it is packed against the LBD irrespective of the presence or type of ligand. T 3, but not NH3, increases accessibility of the upper part of H3-H5 to solvent, and we propose that TR H12 interacts with this region in apo-TR and that this interaction is blocked by T 3 but not NH3.Wepresent data from site-directed mutagenesis experiments and molecular dynamics simulations that lend support to this structural model of apo-TR and its ligand-dependent conformational changes. (Molecular Endocrinology 25: 15-31, 2011). Copyright © 2011 by The Endocrine Society.

Gestión de la información y de la tecnología de la información en el gobierno central y local

Este documento constituye el primer producto elaborado a partir del intercambios de opiniones que tuvo lugar en una de las sesiones de la Reunión de expertos sobre nuevas tendencias en gestión de la información y las tecnologías de la información de América Latina y el Caribe, llevada a cabo en la sede de la CEPAL, de Santiago de Chile, del 26 al 28 de noviembre de 1997. El documento reproduce el contenido de la tercera sesión, referida a gestión de la información y la tecnología de la información en el gobierno central y local, tema tratado durante esa sesión por el expositor principal, Pierre Vigier, con los panelistas Claudio Orrego, Luis José Mejía y Edgar Ortegón, y la moderación de Jaime Pérez. La edición y comentarios fueron aportados por el equipo profesional del CLADES. En el presente informe se destaca la importancia de profundizar el conocimiento acerca de las relaciones existentes entre tecnologías, sistemas de gestión pública y gestión de la información, y de iniciar el diseño de políticas y estrategias renovadas de modernización del Estado, sobre la base de una concepción más amplia y sistémica de las interrelaciones que se dan entre el Estado, la sociedad civil y el ámbito internacional.

Isolation and characterization of microsatellite loci for the mud-dauber wasp Trypoxylon (Trypargilum) albitarse (Hymenoptera: Crabronidae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Proyecto de informe de la Reunión Técnica sobre Pobreza en el Caribe = Draft report of the Technical Meeting on Poverty in the Caribbean

Incluye Bibliografía

Propriedades químicas e ópticas de filmes de carbono amorfo halogenados produzidos por deposição a vapor químico assistido por plasma (PECVD) e deposição e implantação iônica por imersão em plasma (DIIIP)

Pós-graduação em Ciência e Tecnologia de Materiais - FC

Análisis de opciones para incrementar las transacciones de energía eléctrica por la interconexión México- Guatemala-Centroamérica

En este documento se presenta un análisis de la situación de compraventa de energía eléctrica entre México y Centroamérica, considerando sus aspectos legales, económicos y técnicos.

Thyroid Hormone Stimulates the Proliferation of Sertoli Cells and Single Type A Spermatogonia in Adult Zebrafish (Danio rerio) Testis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Chromosomal mapping of two Mariner-like elements in the grasshopper Abracris flavolineata (Orthoptera: Acrididae) reveals enrichment in euchromatin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Periodic orbits and non-integrability of Armbruster-Guckenheimer-Kim potential

In this paper we study the periodic orbits of the Hamiltonian system with the Armburster-Guckenheimer Kim potential and its C1 non-integrability in the sense of Liouville-Arnold.

Distribuição de raízes e a relação com o estado hídrico de laranjeira 'valência' enxertada sobre limoeiro 'cravo'

Pós-graduação em Agronomia (Horticultura) - FCA

Plasma Steroid Dynamics in Late- and Near-term Naturally and Artificially Conceived Bovine Pregnancies as Elucidated by Multihormone High-resolution LC-MS/MS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da aplicação exógena de poliaminas no crescimento de calos de mangabeira (Hancornia speciosa Gomes)

Este trabalho teve como objetivo estudar o efeito das poliaminas espermidina e espermina no crescimento de calos Hancornia speciosa Gomes. Calos com 0,5 cm de diâmetro foram inoculados em meio Murashige & Skoog (1962) (MS) a 50% + 100 mg L-1 de caseína hidrolisada + 200 mg L-1 de levedura de cerveja, variando os tratamentos:A: 1 mmol de espermina + 2 mg L-1 de 2,4-D (ácido 2,4 diclorofenoxiacético) + 0,5 mg L-1 de NAA (ácido naftalenoacético); B: 1 mmol de espermidina + 2 mg L-1 de 2,4-D + 0,5 mg L-1 de NAA; C: 2 mg L-1 de 2,4-D + 0,5 mg L-1 de NAA. Não houve influência das poliaminas no crescimento dos calos. observou-se, nos calos tratados com espermidina, maior concentração celular de putrescina (582,37 µg g mf-1) aos 60 dias, maior teor de espermidina (502,54 µg g mf-1) e espermina (868,53 µg g mf-1) aos 40 dias de cultivo, quando se aplicou a própria poliamina. Conclui-se que a aplicação exógena de poliaminas em Hancornia speciosa não proporciona aumento no crescimento de calos. A oxidação promovida por longos períodos de cultivo in vitro induz aumento nos níveis de putrescina.

Preface to Lesser Known Large dsDNA Viruses. Current Topics in Microbiology and Immunology 328

Several large dsDNA-containing viruses such as poxviruses (smallpox) and herpes viruses are well known among the scientific community, as well as the general populace, because they cause human diseases. The large dsDNA insect-infecting baculoviruses are also well known in the scientific community because they are used both as biological control agents and as protein expression systems. However, there are other large dsDNA-containing viruses, including the giant 1.2-Mb mimivirus, which are less well known even though all of them play important roles in everyday life. Seven of these virus families are reviewed in this book.

Presentation Remarks: Gamma Sigma Delta Award of Merit

I am really pleased to have this opportunity to present the 2008 Gamma Sigma Delta Award of Merit to Alan Baquet. Being here to say "Congratulations, Alan," is a special treat for me - and I do say, "Congratulations, Alan." You are very deserving of this honor.

Double-Stranded RNA-Activated Protein Kinase Is a Key Modulator of Insulin Sensitivity in Physiological Conditions and in Obesity in Mice

The molecular integration of nutrient-and pathogen-sensing pathways has become of great interest in understanding the mechanisms of insulin resistance in obesity. The double-stranded RNA-dependent protein kinase (PKR) is one candidate molecule that may provide cross talk between inflammatory and metabolic signaling. The present study was performed to determine, first, the role of PKR in modulating insulin action and glucose metabolism in physiological situations, and second, the role of PKR in insulin resistance in obese mice. We used Pkr(-/-) and Pkr(+/+) mice to investigate the role of PKR in modulating insulin sensitivity, glucose metabolism, and insulin signaling in liver, muscle, and adipose tissue in response to a high-fat diet. Our data show that in lean Pkr(-/-) mice, there is an improvement in insulin sensitivity, and in glucose tolerance, and a reduction in fasting blood glucose, probably related to a decrease in protein phosphatase 2A activity and a parallel increase in insulin-induced thymoma viral oncogene-1 (Akt) phosphorylation. PKR is activated in tissues of obese mice and can induce insulin resistance by directly binding to and inducing insulin receptor substrate (IRS)-1 serine307 phosphorylation or indirectly through modulation of c-Jun N-terminal kinase and inhibitor of kappa B kinase beta. Pkr(-/-) mice were protected from high-fat diet-induced insulin resistance and glucose intolerance and showed improved insulin signaling associated with a reduction in c-Jun N-terminal kinase and inhibitor of kappa B kinase beta phosphorylation in insulin-sensitive tissues. PKR may have a role in insulin sensitivity under normal physiological conditions, probably by modulating protein phosphatase 2A activity and serine-threonine kinase phosphorylation, and certainly, this kinase may represent a central mechanism for the integration of pathogen response and innate immunity with insulin action and metabolic pathways that are critical in obesity. (Endocrinology 153:5261-5274, 2012)