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

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

Usefulness of species traits in predicting range shifts

Information on species’ ecological traits might improve predictions of climate-driven range shifts. However, the usefulness of traits is usually assumed rather than quantified. We present a framework to identify the most informative traits, based on four key range-shift processes: (i) emigration of individuals or propagules away from the natal location, (ii) the distance a species can move, (iii) establishment of self-sustaining populations, and (iv) proliferation following establishment. We propose a framework that categorises traits according to their contribution to range-shift processes. We demonstrate how the framework enables the predictive value of traits to be evaluated empirically, how this categorisation can be used to better understand range shift processes, and illustrate how range shift estimates can be improved

Two step process for volatile fatty acid production from brewery spent grain: Hydrolysis and direct acidogenic fermentation using anaerobic granular sludge

Brewery spent grain (BSG) is an industrial waste stream with large potential for biorefining purposes. This work evaluated the production of volatile fatty acids (VFAs) by a two-step process using BSG as renewable feedstock by combining a single direct hydrolysis step (without removing the acid or potential inhibiting compounds) with an acidogenic fermentation step of the carbohydrate rich leachate. For the first step, a thermal diluted acid hydrolysis was carried (20 min at 121 °C), using eighteen different combinations in terms of total solid (TS) of BSG (4, 7 and 10 % w/w) and H2SO4 (0.0, 0.5, 1.0, 1.5, 2.0 and 3.0 % v/v). The 7.0 % TS of BSG and 1.5 % of H2SO4 combination was the most efficient in terms of total carbohydrate recovery (0.44 g of total carbohydrates per gram of TS). For the second step, an acidogenic batch fermentation of the hydrolysate was performed using anaerobic granular sludge at five different pH conditions (uncontrolled pH from an initial pH 7.0, and constant pH controlled at 4.5, 5.0, 6.0 and 8.0). The highest VFAs concentration was obtained at pH 6.0 and reached 16.89 (± 1.33) g COD/L, composed of mainly (99.5–99.8 %) acetate and butyrate

De Novo Generation of Infectious Prions In Vitro Produces a New Disease Phenotype

Prions are the proteinaceous infectious agents responsible for Transmissible Spongiform Encephalopathies. Compelling evidence supports the hypothesis that prions are composed exclusively of a misfolded version of the prion protein (PrPSc) that replicates in the body in the absence of nucleic acids by inducing the misfolding of the cellular prion protein (PrPC). The most common form of human prion disease is sporadic, which appears to have its origin in a low frequency event of spontaneous misfolding to generate the first PrPSc particle that then propagates as in the infectious form of the disease. The main goal of this study was to mimic an early event in the etiology of sporadic disease by attempting de novo generation of infectious PrPSc in vitro. For this purpose we analyzed in detail the possibility of spontaneous generation of PrPSc by the protein misfolding cyclic amplification (PMCA) procedure. Under standard PMCA conditions, and taking precautions to avoid cross-contamination, de novo generation of PrPSc was never observed, supporting the use of the technology for diagnostic applications. However, we report that PMCA can be modified to generate PrPSc in the absence of pre-existing PrPSc in different animal species at a low and variable rate. De novo generated PrPSc was infectious when inoculated into wild type hamsters, producing a new disease phenotype with unique clinical, neuropathological and biochemical features. Our results represent additional evidence in support of the prion hypothesis and provide a simple model to study the mechanism of sporadic prion disease. The findings also suggest that prion diversity is not restricted to those currently known, and that likely new forms of infectious protein foldings may be produced, resulting in novel disease phenotypes

Assessment of loaded squat jump height with a free-weight barbell and Smith machine : comparison of the take-off velocity and flight time procedures

The aims of this study were to compare the reliability and magnitude of jump height between the two standard procedures of analysing force platform data to estimate jump height (take-off velocity [TOV] and flight time [FT]) in the loaded squat jump (SJ) exercise performed with a free-weight barbell and in a Smith machine. Twenty-three collegiate men (age 23.1 +/- 3.2 years, body mass 74.7 +/- 7.3 kg, height 177.1 +/- 7.0 cm) were tested twice for each SJ type (free-weight barbell and Smith machine) with 17, 30, 45, 60, and 75 kg loads. No substantial differences in reliability were observed between the TOV (Coefficient of variation [CV]: 9.88%; Intraclass correlation coefficient [ICC]: 0.82) and FT (CV: 8.68%; ICC: 0.88) procedures (CV ratio: 1.14), while the Smith SJ (CV: 7.74%; ICC: 0.87) revealed a higher reliability than the free-weight SJ (CV: 9.88%; ICC: 0.81) (CV ratio: 1.28). The TOV procedure provided higher magnitudes of jump height than the FT procedure for the loaded Smith machine SJ (systematic bias: 2.64 cm; P0.05). Heteroscedasticity of the errors was observed for the Smith machine SJ (r2: 0.177) with increasing differences in favour of the TOV procedure for the trials with lower jump height (i.e. higher external loads). Based on these results the use of a Smith machine in conjunction with the FT more accurately determine jump height during the loaded SJ

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

Particle dispersion processes in two-dimensional turbulence: a comparison with 2-D kinematic simulation.

International audienceWe study numerically the comparison between Lagrangian experiments on turbulent particle dispersion in 2-D turbulent flows performed, on the one hand, on the basis of direct numerical simulations (DNS) and, on the other hand, using kinematic simulations (KS). Eulerian space-time structure of both DNS and KS dynamics are not comparable, mostly due to the absence of strong coherent vortices and advection processes in the KS fields. The comparison allows to refine past studies about the contribution of non-homogeneous space-time 2-D Eulerian structure on the turbulent absolute and relative particle dispersion processes. We particularly focus our discussion on the Richardson's regime for relative dispersion