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

Estudio ecológico-edáfico de algunas especies de interés farmacéutico que viven en Sierra Nevada (Granada): II. Los acónitos de Sierra Nevada

Entre las especies interesantes de Sierra Nevada, de interés farmacéutico, hay que destacar dos taxones dentro del género Aconitum, de la familia de las Ranunculáceas, se trata según Flora Europea del Aconitum Nevadense Vechtr. ex Gayer y del Aconitum lamarkii Reichenb. respectivamente. Viven al abrigo de la humedad edáfica en las proximidades de los arroyos, sobre suelos pertenecientes a tres unidades diferentes, de acuerdo con la clasificación de la FAO: Litosoles, Regosoles dístricos y Gleisoles, cuyo denominador común es el presentar un epipedón más o menos profundo y rico en materia orgánica, en el que se desarrolla las raíces del acónito. Se asocian estos dos taxones con una serie de plantas pertenecientes a clases fitosociológicas muy variadas, que se inventarían e incluye dando la relación abundancia-dominancia de cada una de ellas.The more interesting vegetal species with pharmaceutical interest are those two taxons of types Aconitum of the Ranumculaceae family. Acording to Flora European is Aconitum Nevadense Vechtr. ex Gayer so as Aconitum lamarkii Reichenb. respectively. They are loeated proteeted from edaphic humidity near of gutter on soil of the groups Litosols, District Regosol, Gleysol whose eommon eharaeteristics is having a deep epipedon which is rieh in organic matter with degree of humifieation

Efectos del programa educativo GERO-HEALTH sobre el nivel de interiorización de conocimientos de prevención y promoción de la salud en personas mayores

The aim of this paper was to assess the theoretical-practical dimension of the knowledge acquired by 65-year-olds and over according to sex and educational level during a health education program. A cross-sectional quasi-experimental design study was conducted with a sample of 73 senior citizens who completed a questionnaire at the beginning and at the end of the program. The questionnaire measured the level of assimilation of acquired knowledge. The results showed that participants´ knowledge of health issues significantly increased upon completion of the program, particularly in women and in participants with the lowest educational level. The program proved to be effective in promoting active aging, and combined relevant aging-related psychosocial issues such as intergenerational relationships and empowerment processes.El objetivo de este artículo fue evaluar la dimensión teórico-práctica de los conocimientos adquiridos por personas mayores de 65 años, en función del sexo y el nivel educativo, durante un programa de educación para la salud. Se realizó un estudio de tipo cuasi-experimental, transversal, sobre una muestra de 73 mayores, que fueron evaluados al comienzo y al final del programa mediante un cuestionario que determinaba el nivel de interiorización del conocimiento adquirido. Los resultados mostraron que, tras la realización del programa, los sujetos incrementaron significativamente sus conocimientos sobre salud, siendo este efecto mayor en las mujeres, y en los sujetos con menor nivel educativo. El programa se revela, por tanto, como eficaz en la promoción del envejecimiento activo, además de compaginar otros elementos psico-sociales relevantes en la vejez como las relaciones intergeneracionales y los procesos de empoderamiento

Octodon degus: A Model for the Cognitive Impairment Associated with Alzheimer's Disease

Octodon degus (O. degus) is a diurnal rodent that spontaneously develops several physiopathological conditions, analogous in many cases to those experienced by humans. In light of this, O. degus has recently been identified as a very valuable animal model for research in several medical fields, especially those concerned with neurodegenerative diseases in which risk is associated with ageing. O. degus spontaneously develops β-amyloid deposits analogous to those observed in some cases of Alzheimer’s disease (AD). Moreover, these deposits are thought to be the key feature for AD diagnosis, and one of the suggested causes of cell loss and cognitive deficit. This review aims to bring together information to support O. degus as a valuable model for the study of cerebral aging

Approach to the Spanish continental Neogene synthesis and paleoclimatic interpretation

Integrated studies on Neogene geology have been scarce in Spain, but attemps to stratigraphic and sedimentological analysis of continental Tertiary basins have increased considerably lately. The large extent of Neogene basins in Spain, the good quality of the outcrops and the abundance of fossil provide an excellent basis for this kind of studies

Maximizing furfural concentration from wheat straw and Eucalyptus globulus by nonisothermal autohydrolysis

The autohydrolysis process as a method for selective extraction of hemicelluloses and conversion to furfural was proposed for lignocellulosic raw materials. Samples of wheat straw (WS) and Eucalyptus globulus (EG) were subjected to nonisothermal autohydrolysis, defined by temperature 180–240°C. Within a biorefinery scheme for the selected materials, the aim of this study is both (a) to optimize furfural processing technology to enable higher yields and improved productivity from EG and WS by autohydrolysis and (b) to not excessively degrade the remaining polymeric constituents (glucan) in solid to facilitate a potential later use. Differences in the rate of the dehydration reaction of xylose to furfural have been observed, and it is faster in the case of WS with respect to that observed for eucalyptus. In that form, 4.25 g/100 g raw material (26% of the initial xylan in WS) could be found at 220°C, and an increase in the temperature (240°C) yielded 4.54 g/100 g raw material, 28% of the initial xylan. In EG, the increase in the hydrolysis temperature (240°C) yielded liquor with higher contents of furfural (4.45 g/100 g raw material, 25% of the initial xylan) and acetic acid (4.49 g/100 g raw material) and smaller contents of arabinose and xylan. In WS, a faster dehydration is found

Nonconventional Wastewater Treatment for the Degradation of Fuel Oxygenated (MTBE, ETBE, and TAME)

Catalytic wet air oxidation (CWAO) is a nonconventional wastewater treatment, consisting of oxygen pressure releasing inside a reactor in order to degrade organic compounds dissolved in water, using a solid catalyst in the presence of an activated O2 species, usually at temperatures ranges of 125–250°C and pressures of 10–50 bar. CWAO can reduce operating costs of conventional treatment due to the use of ideal catalyst that is able to improve reaction conditions at temperatures and pressures as mild as possible, simultaneously setting high catalytic activity and long-term stability of heterogeneous catalysts. Oxygenated fuels are gasoline additives in reformulated gasoline and oxyfuels. In the beginning, they provided an alternative solution of environmental problems, such as greenhouse gas emissions and octane enhancement, caused by fossil fuel use. The oxygenated fuels frequently used are methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME). However, there is environmental impact from oxygenated fuel hydrocarbons related to widespread contamination of groundwater and other natural waters. Our research group developed a wide study in order to evaluate several catalysts (Ru, Au, Cu, and Ag supported on Al2O3, Al2O3-CeO2, and TiO2-CeO2) and to obtain the best for the efficiency of the oxidation process

Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients

OBJECTIVE: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION: ABA appears to be an effective in RA-associated ILD.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from ‘‘Instituto de Salud Carlos III’’ (ISCIII), Spain

The CARMENES search for exoplanets around M dwarfs High-resolution optical and near-infrared spectroscopy of 324 survey stars

The CARMENES radial velocity (RV) survey is observing 324 M dwarfs to search for any orbiting planets. In this paper, we present the survey sample by publishing one CARMENES spectrum for each M dwarf. These spectra cover the wavelength range 520–1710 nm at a resolution of at least R >80 000, and we measure its RV, Hα emission, and projected rotation velocity. We present an atlas of high-resolution M-dwarf spectra and compare the spectra to atmospheric models. To quantify the RV precision that can be achieved in low-mass stars over the CARMENES wavelength range, we analyze our empirical information on the RV precision from more than 6500 observations. We compare our high-resolution M-dwarf spectra to atmospheric models where we determine the spectroscopic RV information content, Q, and signal-to-noise ratio. We find that for all M-type dwarfs, the highest RV precision can be reached in the wavelength range 700–900 nm. Observations at longer wavelengths are equally precise only at the very latest spectral types (M8 and M9). We demonstrate that in this spectroscopic range, the large amount of absorption features compensates for the intrinsic faintness of an M7 star. To reach an RV precision of 1 m s−1 in very low mass M dwarfs at longer wavelengths likely requires the use of a 10 m class telescope. For spectral types M6 and earlier, the combination of a red visual and a near-infrared spectrograph is ideal to search for low-mass planets and to distinguish between planets and stellar variability. At a 4 m class telescope, an instrument like CARMENES has the potential to push the RV precision well below the typical jitter level of 3–4 m s−1