Elongation factor 2-diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions

Elongation factor-2 (eEF2) catalyzes the movement of the ribosome along the mRNA. A single histidine residue in eEF2 (H715) is modified to form diphthamide. A role for eEF2 in cellular stress responses is highlighted by the fact that eEF2 is sensitive to oxidative stress and that it must be active in order to drive the synthesis of proteins that help cells to mitigate the adverse effects of oxidative stress. Many of the latter proteins are encoded by mRNAs containing a sequence called an “internal ribosomal entry site” (IRES). Under high oxidative stress conditions diphthamide-deficient cells were significantly more sensitive to cell death. These results suggest that diphthamide may play a role in protection against the degradation of eEF2. Its protection is especially important under those situations where it is necessary for the re-programming of translation from global to IRES synthesis. Indeed, we found that the expression of X-linked inhibitor of apoptosis (XIAP) and fibroblast growth factor 2 (FGF2), two proteins synthesized from mRNAs with IRES that promote cell survival are deregulated in diphthamide-deficient cells. Our findings therefore suggest that eEF2/diphthamide controls the selective translation of IRES-dependent protein targets XIAP and FGF2, critical for cell survival under conditions of oxidative stress.España, Ministerio de Ciencia e Innovación BFU 2010-20882

Uncertainties in land use data

This paper deals with the description and assessment of uncertainties in land use data derived from Remote Sensing observations, in the context of hydrological studies. Land use is a categorical regionalised variable reporting the main socio-economic role each location has, where the role is inferred from the pattern of occupation of land. The properties of this pattern that are relevant to hydrological processes have to be known with some accuracy in order to obtain reliable results; hence, uncertainty in land use data may lead to uncertainty in model predictions. There are two main uncertainties surrounding land use data, positional and categorical. The first one is briefly addressed and the second one is explored in more depth, including the factors that influence it. We (1) argue that the conventional method used to assess categorical uncertainty, the confusion matrix, is insufficient to propagate uncertainty through distributed hydrologic models; (2) report some alternative methods to tackle this and other insufficiencies; (3) stress the role of metadata as a more reliable means to assess the degree of distrust with which these data should be used; and (4) suggest some practical recommendations

Molecular Control of the Amount, Subcellular Location and Activity State of Translation Elongation Factor 2 (eEF-2) in Neurons Experiencing Stress

Eukaryotic elongation factor 2 (eEF-2) is an important regulator of the protein translation machinery wherein it controls the movement of the ribosome along the mRNA. The activity of eEF-2 is regulated by changes in cellular energy status and nutrient availability, and posttranslational modifications such as phosphorylation and mono-ADP-ribosylation. However, the mechanisms regulating protein translation under conditions of cellular stress in neurons are unknown. Here we show that when rat hippocampal neurons experience oxidative stress (lipid peroxidation induced by exposure to cumene hydroperoxide; CH), eEF-2 is hyperphosphorylated and ribosylated resulting in reduced translational activity. The degradation of eEF-2 requires calpain proteolytic activity and is accompanied by accumulation of eEF-2 in the nuclear compartment. The subcellular localization of both native and phosphorylated forms of eEF-2 is influenced by CRM1 and 14.3.3, respectively. In hippocampal neurons p53 interacts with non-phosphorylated (active) eEF-2, but not with its phosphorylated form. The p53 – eEF-2 complexes are present in cytoplasm and nucleus, and their abundance increases when neurons experience oxidative stress. The nuclear localization of active eEF-2 depends upon its interaction with p53, as cells lacking p53 contain less active eEF-2 in the nuclear compartment. Overexpression of eEF-2 in hippocampal neurons results in increased nuclear levels of eEF-2, and decreased cell death following exposure to CH. Our results reveal novel molecular mechanisms controlling the differential subcellular localization and activity state of eEF-2 that may influence the survival status of neurons during periods of elevated oxidative stress.España, Ministerio de Ciencia e Innovación BFU2010-20882.España, Ministerio de Educación, Cultura y Deporte postdoctoral fellowship (EX2009-0918

Proton to pion ratio at RHIC from dynamical quark recombination

We propose an scenario to study, from a dynamical point of view, the thermal recombination of quarks in the midsts of a relativistic heavy-ion collision. We coin the term dynamical quark recombination to refer to the process of quark-antiquark and three-quark clustering, to form mesons and baryons, respectively, as a function of energy density. Using the string-flip model we show that the probabilities to form such clusters differ. We apply these ideas to the calculation of the proton and pion spectra in a Bjorken-like scenario that incorporates the evolution of these probabilities with proper time and compute the proton to pion ratio, comparing to recent RHIC data at the highest energy. We show that for a standard choice of parameters, this ratio reaches one, though the maximum is very sensitive to the initial evolution proper time.Comment: To appear in the proceedings of the XI Mexican Workshop on Particles and Fields, Tuxtla Gutierrez Chiapas, Mexico, 7-12 Nov. 200

Uric acid enhances longevity and endurance and protects the brain against ischemia

Among mammals, there is a positive correlation between serum uric acid (UA) levels and life span. Humans have high levels of UA because they lack a functional urate oxidase (UOX) enzyme that is present in shorter lived mammals. Here, we show that male and female mice with UOX haploinsufficiency exhibit an age-related elevation of UA levels, and that the life span of female but not male UOX+/− mice is significantly increased compared to wild-type mice. Serum UA levels are elevated in response to treadmill exercise in UOX+/− mice, but not wild-type mice, and the endurance of the UOX+/− mice is significantly greater than wild-type mice. UOX+/− mice exhibit elevated levels of brain-derived neurotrophic factor, reduced brain damage and improved functional outcome in a model of focal ischemic stroke. Levels of oxidative protein nitration and lipid peroxidation are reduced in muscle and brain tissues of UOX+/− mice under conditions of metabolic and oxidative stress (running in the case of muscle and ischemia in the case of the brain), consistent with prior evidence that UA can scavenge peroxynitrite and hydroxyl radical. Our findings reveal roles for UA in life span determination, endurance and adaptive responses to brain injury, and suggest novel approaches for protecting cells against injury and for optimizing physical performance.España, Ministerio de Educación, Cultura y Deporte EX2009–091

From spinons to magnons in explicit and spontaneously dimerized antiferromagnetic chains

We reconsider the excitation spectra of a dimerized and frustrated antiferromagnetic Heisenberg chain. This model is taken as the simpler example of compiting spontaneous and explicit dimerization relevant for Spin-Peierls compounds. The bosonized theory is a two frequency Sine-Gordon field theory. We analize the excitation spectrum by semiclassical methods. The elementary triplet excitation corresponds to an extended magnon whose radius diverge for vanishing dimerization. The internal oscilations of the magnon give rise to a series of excited state until another magnon is emited and a two magnon continuum is reached. We discuss, for weak dimerization, in which way the magnon forms as a result of a spinon-spinon interaction potential.Comment: 5 pages, latex, 3 figures embedded in the tex

Actualización semiautomática de la malla de recintos del Mapa Forestal de España

The principles of the future European Directive on Spatial Data Infrastructures inspire the new Spanish Information System on Land Occupation (SIOSE), where the information from the various existing landcover/landuse maps will be integrated, including that of the Forest Map of Spain (MFE). This work describes a test commissioned by the Nature Database Department of the Ministry of Environment, whose goal is to evaluate the possibility of semiautomatic updating, by means of an image segmentation algorithm developed by the author, of MFE polygon edges. The updated map may be used later to represent forest areas in SIOSE. The result, although needs to be confirmed by further tests, is very positive, because more than 80% of the edges of the final map come from the automatic segmentation, which may represent more than a 40% time-saving in the photointerpretation.Los principios que inspiran la futura Directiva Europea sobre Infraestructuras de Datos Espaciales han dado lugar a la puesta en marcha de un nuevo Sistema de Información sobre Ocupación del Suelo de España (SIOSE), donde se pueda integrar la información de las Bases de Datos de Ocupación del Suelo de las Comunidades Autónomas y de la Administración General del Estado, entre ellas la constituida por el Mapa Forestal de España (MFE). Este trabajo describe una prueba encargada por el Area de Banco de Datos de la Naturaleza del Ministerio de Medio Ambiente cuyo objetivo es evaluar la posibilidad de actualizar de forma semiautomática el contorno de los recintos o teselas del MFE, que se usarán después como base para el SIOSE en zonas forestales, por medio de un segmentador de imágenes desarrollado por el autor. El resultado, si bien necesita ser contrastado con nuevas pruebas, es muy positivo, pues más del 80% de los bordes de teselas de la malla final proceden de la segmentación automática, lo que puede suponer un ahorro de tiempo de más de un 40% en la fotointerpretación

Functional Diversification after Gene Duplication: Paralog Specific Regions of Structural Disorder and Phosphorylation in p53, p63, and p73

Conformational and functional flexibility promote protein evolvability. High evolvability allows related proteins to functionally diverge and perhaps to neostructuralize. p53 is a multifunctional protein frequently referred to as the Guardian of the Genome–a hub for e.g. incoming and outgoing signals in apoptosis and DNA repair. p53 has been found to be structurally disordered, an extreme form of conformational flexibility. Here, p53, and its paralogs p63 and p73, were studied for further insights into the evolutionary dynamics of structural disorder, secondary structure, and phosphorylation. This study is focused on the post gene duplication phase for the p53 family in vertebrates, but also visits the origin of the protein family and the early domain loss and gain events. Functional divergence, measured by rapid evolutionary dynamics of protein domains, structural properties, and phosphorylation propensity, is inferred across vertebrate p53 proteins, in p63 and p73 from fish, and between the three paralogs. In particular, structurally disordered regions are redistributed among paralogs, but within clades redistribution of structural disorder also appears to be an ongoing process. Despite its deemed importance as the Guardian of the Genome, p53 is indeed a protein with high evolvability as seen not only in rearranged structural disorder, but also in fluctuating domain sequence signatures among lineages

Substitution effects on spin fluctuations in the spin-Peierls compound CuGeO_3

Using Raman scattering we studied the effect of substitutions on 1D spin fluctuations in CuGeO_3 observed as a spinon continuum in frustration induced exchange scattering. For temperatures below the spin-Peierls transition (T_{SP}=14K) the intensity of this continuum at 120-500 cm^{-1} is exponentially suppressed and transferred into a 3D two-magnon density of states. Besides a spin-Peierls gap-induced mode at 30 cm^{-1} and additional modes at 105 and 370 cm^{-1} are observed. Substitution of Zn on the Cu-site and Si on the Ge-site of CuGeO_3 quenches easily the spin-Peierls state. Consequently a suppression of the spin-Peierls gap observable below T_{SP}=14K as well as a change of the temperature dependence of the spinon continuum are observed. These effects are discussed in the context of a dimensional crossover of this compound below T_{SP} and strong spin-lattice interaction.Comment: 9 pages, 2 eps figures include