Spectroscopic and Theoretical Study of CuI Binding to His111 in the Human Prion Protein Fragment 106-115

The ability of the cellular prion protein (PrPC) to bind copper in vivo points to a physiological role for PrPC in copper transport. Six copper binding sites have been identified in the nonstructured N-terminal region of human PrPC. Among these sites, the His111 site is unique in that it contains a MKHM motif that would confer interesting CuI and CuII binding properties. We have evaluated CuI coordination to the PrP(106-115) fragment of the human PrP protein, using NMR and X-ray absorption spectroscopies and electronic structure calculations. We find that Met109 and Met112 play an important role in anchoring this metal ion. CuI coordination to His111 is pH-dependent: at pH >8, 2N1O1S species are formed with one Met ligand; in the range of pH 5-8, both methionine (Met) residues bind to CuI, forming a 1N1O2S species, where N is from His111 and O is from a backbone carbonyl or a water molecule; at pH <5, only the two Met residues remain coordinated. Thus, even upon drastic changes in the chemical environment, such as those occurring during endocytosis of PrPC (decreased pH and a reducing potential), the two Met residues in the MKHM motif enable PrPC to maintain the bound CuI ions, consistent with a copper transport function for this protein. We also find that the physiologically relevant CuI-1N1O2S species activates dioxygen via an inner-sphere mechanism, likely involving the formation of a copper(II) superoxide complex. In this process, the Met residues are partially oxidized to sulfoxide; this ability to scavenge superoxide may play a role in the proposed antioxidant properties of PrPC. This study provides further insight into the CuI coordination properties of His111 in human PrPC and the molecular mechanism of oxygen activation by this site.Fil: Arcos López, Trinidad. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Qayyum, Munzarin. University of Stanford; Estados UnidosFil: Rivillas Acevedo, Lina. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Miotto, Marco César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Laboratory for Structural Biology; ArgentinaFil: Grande Aztatzi, Rafael. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Laboratory for Structural Biology; ArgentinaFil: Hedman, Britt. University of Stanford; Estados UnidosFil: Hodgson, Keith O.. University of Stanford; Estados UnidosFil: Vela, Alberto. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Solomon, Edward I.. University of Stanford; Estados UnidosFil: Quintanar, Liliana. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; Méxic

Desarrollo de propuesta de modelo de negocio digital FAST BEAUTY SUPPLY.

La creación de un modelo de negocio digital permitirá al proyecto denominado Fast Beauty Supply aprovechar las nuevas tendencias digitales y además mejorar los servicios, concretado con la creación de propuestas de valor de manera estratégica. Para el modelo de negocio y la comercialización de productos cosméticos para el Cabello en El Salvador se ha creado Fast Beauty Supply ubicada en Calle primera de Julio y av. José María Cornejo en San Vicente. Tomando en cuenta el modelo de negocio y las marcas con las que se trabajarán que son: Tigi, Rusk, Alfaparf, Wella y Bei Essenziale considerando la expansión de más marcas en el futuro, inicialmente se tendrá una inversión de $5,000 que contemplará la adquisición de los productos y pago del primer mes de local. El estudio refleja la importancia de crear proyecciones de ventas que reflejen el futuro de Fast Beauty que además contará con un crecimiento anual del 5%; con estrategias enfocadas en producto, precio, plaza y promoción que aseguren las ventas y motiven la decisión de compra de clientes potenciales y con ello buscar conseguir la misión y visión del proyecto. El modelo destaca puntos específicos como la descripción de los productos, la ventaja competitiva con la que Fast beauty se diferenciará de la competencia, conclusiones sobre el plan de mercadeo, plan financiero y además la forma de distribución de los productos al cliente final. Para llevar a cabo este modelo es necesaria la unión del equipo de trabajo de Fast Beauty combinado con una fuerza de ventas altamente capacitada en el rubro de la cosmética para el cabello y el diseño de estrategias de marketing enfocadas al fortalecimiento de imagen de marca que garantice la confianza y respaldo de los clientes

Second international congress on immunopharmacology : delivery systems and current strategies for drug design

The 2nd International Congress on Immunopharmacology was held in June of 2011 at the Conference Center of Plaza America in Varadero, Cuba. The main goal of this meeting was to provide state-of-the-art communications for scientists, manufacturers, regulators and healthcare workers, to accelerate progress in the development of biological and biotechnological products and to promote exchange/scientific cooperation between researchers. 300 delegates from 22 countries attended the conference. The wide-ranging programme commenced with a plenary session and then split into a series of parallel workshops and symposia, covering “Advances in Immunopharmacology”, “Neuroimmunology”, “Therapeutic Biological Products”, “Prophylaxis and Treatment of Helicobacter pylori”, “Pharmacology of Cytochrome P450”, “Hereditary Ataxias” and “Delivery Systems and Current Strategies for Drug Design”. In this last Symposium, a substantial body of data was presented relating to the development of delivery systems with adjuvant and vaccine potential and also to strategies focused in therapeutic and prophylactic approaches against tuberculosis. This issue is dedicated to some of the results presented in this area

Quantum walks: a comprehensive review

Quantum walks, the quantum mechanical counterpart of classical random walks, is an advanced tool for building quantum algorithms that has been recently shown to constitute a universal model of quantum computation. Quantum walks is now a solid field of research of quantum computation full of exciting open problems for physicists, computer scientists, mathematicians and engineers. In this paper we review theoretical advances on the foundations of both discrete- and continuous-time quantum walks, together with the role that randomness plays in quantum walks, the connections between the mathematical models of coined discrete quantum walks and continuous quantum walks, the quantumness of quantum walks, a summary of papers published on discrete quantum walks and entanglement as well as a succinct review of experimental proposals and realizations of discrete-time quantum walks. Furthermore, we have reviewed several algorithms based on both discrete- and continuous-time quantum walks as well as a most important result: the computational universality of both continuous- and discrete- time quantum walks.Comment: Paper accepted for publication in Quantum Information Processing Journa

Technical and vocational education and training (TVET) for young people in low- and middle-income countries: a systematic review and meta-analysis

The world is facing a worsening youth employment crisis. In response, technical and vocational education and training (TVET) is back on the development agenda after years of neglect. This systematic review examined the evidence from studies evaluating the impacts of TVET interventions for young people in low- and middle-income countries (LMICs). The 26 included studies evaluated 20 different interventions, predominantly from Latin America. Meta-analyses of the effectiveness of TVET on five outcome measure categories were conducted. The overall mean effects on overall paid employment, formal employment, and monthly earnings were small, positive, and significant; however, significant heterogeneity was observed. Moderator analysis was performed in an attempt to explain between-study differences in effects. The overall paucity of research in this area, together with specific gaps and methodological limitations, affirm the need for strengthening the evidence base. Implications for policy, practice and research are discussed

Financial Structure and Economic Welfare: Applied General Equilibrium Development Economics

This review provides a common framework for researchers thinking about the next generation of micro-founded macro models of growth, inequality, and financial deepening, as well as direction for policy makers targeting microfinance programs to alleviate poverty. Topics include treatment of financial structure general equilibrium models: testing for as-if-complete markets or other financial underpinnings; examining dual-sector models with both a perfectly intermediated sector and a sector in financial autarky, as well as a second generation of these models that embeds information problems and other obstacles to trade; designing surveys to capture measures of income, investment/savings, and flow of funds; and aggregating individuals and households to the level of network, village, or national economy. The review concludes with new directions that overcome conceptual and computational limitations.National Science Foundation (U.S.)National Institutes of Health (U.S.)Templeton FoundationBill & Melinda Gates Foundatio

Spatial distribution and risk factors of Brucellosis in Iberian wild ungulates

<p>Abstract</p> <p>Background</p> <p>The role of wildlife as a brucellosis reservoir for humans and domestic livestock remains to be properly established. The aim of this work was to determine the aetiology, apparent prevalence, spatial distribution and risk factors for brucellosis transmission in several Iberian wild ungulates.</p> <p>Methods</p> <p>A multi-species indirect immunosorbent assay (iELISA) using <it>Brucella </it>S-LPS antigen was developed. In several regions having brucellosis in livestock, individual serum samples were taken between 1999 and 2009 from 2,579 wild bovids, 6,448 wild cervids and4,454 Eurasian wild boar (<it>Sus scrofa</it>), and tested to assess brucellosis apparent prevalence. Strains isolated from wild boar were characterized to identify the presence of markers shared with the strains isolated from domestic pigs.</p> <p>Results</p> <p>Mean apparent prevalence below 0.5% was identified in chamois (<it>Rupicapra pyrenaica</it>), Iberian wild goat (<it>Capra pyrenaica</it>), and red deer (<it>Cervus elaphus</it>). Roe deer (<it>Capreolus capreolus</it>), fallow deer (<it>Dama dama</it>), mouflon (<it>Ovis aries</it>) and Barbary sheep (<it>Ammotragus lervia</it>) tested were seronegative. Only one red deer and one Iberian wild goat resulted positive in culture, isolating <it>B. abortus </it>biovar 1 and <it>B. melitensis </it>biovar 1, respectively. Apparent prevalence in wild boar ranged from 25% to 46% in the different regions studied, with the highest figures detected in South-Central Spain. The probability of wild boar being positive in the iELISA was also affected by age, age-by-sex interaction, sampling month, and the density of outdoor domestic pigs. A total of 104 bacterial isolates were obtained from wild boar, being all identified as <it>B. suis </it>biovar 2. DNA polymorphisms were similar to those found in domestic pigs.</p> <p>Conclusions</p> <p>In conclusion, brucellosis in wild boar is widespread in the Iberian Peninsula, thus representing an important threat for domestic pigs. By contrast, wild ruminants were not identified as a significant brucellosis reservoir for livestock.</p