Crónica de Alfonso III

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201

Allosteric Inhibition of Human Ribonucleotide Reductase by dATP Entails the Stabilization of a Hexamer

Ribonucleotide reductases (RNRs) are responsible for all de novo biosynthesis of DNA precursors in nature by catalyzing the conversion of ribonucleotides to deoxyribonucleotides. Because of its essential role in cell division, human RNR is a target for a number of anticancer drugs in clinical use. Like other class Ia RNRs, human RNR requires both a radical-generation subunit (β) and nucleotide-binding subunit (α) for activity. Because of their complex dependence on allosteric effectors, however, the active and inactive quaternary forms of many class Ia RNRs have remained in question. Here, we present an X-ray crystal structure of the human α subunit in the presence of inhibiting levels of dATP, depicting a ring-shaped hexamer (α[subscript 6]) where the active sites line the inner hole. Surprisingly, our small-angle X-ray scattering (SAXS) results indicate that human α forms a similar hexamer in the presence of ATP, an activating effector. In both cases, α[subscript 6] is assembled from dimers (α[subscript 2]) without a previously proposed tetramer intermediate (α[subscript 4]). However, we show with SAXS and electron microscopy that at millimolar ATP, the ATP-induced α[subscript 6] can further interconvert with higher-order filaments. Differences in the dATP- and ATP-induced α[subscript 6] were further examined by SAXS in the presence of the β subunit and by activity assays as a function of ATP or dATP. Together, these results suggest that dATP-induced α[subscript 6] is more stable than the ATP-induced α6 and that stabilization of this ring-shaped configuration provides a mechanism to prevent access of the β subunit to the active site of α.National Institutes of Health (U.S.) (GM100008)National Institutes of Health (U.S.) (Grant GM29595)Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra

Vaccine-induced mucosal immunity to poliovirus: analysis of cohorts from an open-label, randomised controlled trial in Latin American infants.

BACKGROUND: Identification of mechanisms that limit poliovirus replication is crucial for informing decisions aimed at global polio eradication. Studies of mucosal immunity induced by oral poliovirus (OPV) or inactivated poliovirus (IPV) vaccines and mixed schedules thereof will determine the effectiveness of different vaccine strategies to block virus shedding. We used samples from a clinical trial of different vaccination schedules to measure intestinal immunity as judged by neutralisation of virus and virus-specific IgA in stools. METHODS: In the FIDEC trial, Latin American infants were randomly assigned to nine groups to assess the efficacy of two schedules of bivalent OPV (bOPV) and IPV and challenge with monovalent type 2 OPV, and stools samples were collected. We selected three groups of particular interest-the bOPV control group (serotypes 1 and 3 at 6, 10, and 14 weeks), the trivalent attenuated OPV (tOPV) control group (tOPV at 6, 10, and 14 weeks), and the bOPV-IPV group (bOPV at 6, 10, and 14 weeks plus IPV at 14 weeks). Neutralising activity and poliovirus type-specific IgA were measured in stool after a monovalent OPV type 2 challenge at 18 weeks of age. Mucosal immunity was measured by in-vitro neutralisation of a type 2 polio pseudovirus (PV2). Neutralisation titres and total and poliovirus-type-specific IgG and IgA concentrations in stools were assessed in samples collected before challenge and 2 weeks after challenge from all participants. FINDINGS: 210 infants from Guatemala and Dominican Republic were included in this analysis. Of 38 infants tested for mucosal antibody in the tOPV group, two were shedding virus 1 week after challenge, compared with 59 of 85 infants receiving bOPV (p<0·0001) and 53 of 87 infants receiving bOPV-IPV (p<0·0001). Mucosal type 2 neutralisation and type-specific IgA were noted primarily in response to tOPV. An inverse correlation was noted between virus shedding and both serum type 2 neutralisation at challenge (p<0·0001) and mucosal type 2 neutralisation at challenge (p<0·0001). INTERPRETATION: Mucosal type-2-specific antibodies can be measured in stool and develop in response to receipt of OPV type 2 either in the primary vaccine series or at challenge. These mucosal antibodies influence the amount of virus that is shed in an established infection. FUNDING: Bill & Melinda Gates Foundation

Development of strength models for prediction of unconfined compressive strength of cement/byproduct material improved soils

© 2017 ASTM International. All rights reserved. This paper presents the possible inclusion of pulverized fuel ash (PFA) and ground granulated blast slag (GGBS) in cement deep soil mixing for enhancement of unconfined compressive strength (UCS) of weak soil materials for construction purposes. The main focus of this paper was to investigate the UCS of cement-, cement/PFA-and cement/PFA/GGBS-improved soils, and development of mathematical and graphical models for prediction of UCS for use in design and construction. Samples of cement, blends of cement and PFA, and cement/PFA/GGBS were prepared using 5 %, 10 %, 15 %, and 20 % by weight of dry soil and tested for UCS after 7, 14, 28, and 56 days. A multiple regression analysis was conducted using the SPSS computer program. The results showed that soil materials with lower plasticity show higher strength development compared to those of higher plasticity for cement improvement. The study has also revealed that the inclusion of PFA and GGBS can cause a reduction in the amount of cement in deep soil mixing, which can result to reduced cost and emission of carbon dioxide (CO2) during construction. The developed mathematical and graphical models could give reliable predictions of UCS for weak soil materials with initial UCS less than or equal to 25 kPa and for water to binder ratio of unity based on the observed agreement between experimental and predicted data. The developed multiple regression models have also been validated using different mixtures of 6 %, 8 %, 12 %, and 16 % of binders

[Vuelta a Asturias 1979] [Material gráfico]

Contiene fotografías pertenecientes al archivo fotográfico del diario "Región", publicadas en 1979Algunas no indican autoría. El resto de las fotografías firmadas por Rubio Fotógrafo (Oviedo), Foto Marcos (Avilés), Foto E. Gar (Oviedo), y Ángel Ricardo (Oviedo

Spatial and temporal variations of trace element distribution in soils and street dust of an industrial town in NW Spain: 15years of study

Extensive spatial and temporal surveys, over 15 years, have been conducted in soil in urban parks and street dusts in one of the most polluted cities in western Europe, Avilés (NW Spain). The first survey was carried out in 1996, and since then monitoring has been undertaken every five years. Whilst the sampling site is a relatively small town, industrial activities (mainly the steel industry and Zn and Al metallurgy) and other less significant urban sources, such as traffic, strongly affect the load of heavy metals in the urban aerosol. Elemental tracers have been used to characterise the influence of these sources on the composition of soil and dust. Although PM10 has decreased over these years as a result of environmental measures undertaken in the city, some of the “industrial” elements still remain in concentrations of concern for example, up to 4.6% and 0.5% of Zn in dust and soil, respectively. Spatial trends in metals such as Zn and Cd clearly reflect sources from the processing industries. The concentrations of these elements across Europe have reduced over time, however the most recent results from Avilés revealed an upward trend in concentration for Zn, Cd, Hg and As. A risk assessment of the soil highlighted As as an element of concern since its cancer risk in adults was more than double the value above which regulatory agencies deem it to be unacceptable. If children were considered to be the receptors, then the risk nearly doubles from this element