Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria

Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear. Here, we report the structural features and functional behavior of a phosphomimetic cytochrome c mutant, which was generated by site-specific incorporation at position 97 of p-carboxymethyl-l-phenylalanine using the evolved tRNA synthetase method. We found that the point mutation does not alter the overall folding and heme environment of cytochrome c, but significantly affects the entire oxidative phosphorylation process. In fact, the electron donation rate of the mutant heme protein to cytochrome c oxidase, or complex IV, within respiratory supercomplexes was higher than that of the wild-type species, in agreement with the observed decrease in reactive oxygen species production. Direct contact of cytochrome c with the respiratory supercomplex factor HIGD1A (hypoxia-inducible domain family member 1A) is reported here, with the mutant heme protein exhibiting a lower affinity than the wild-type species. Interestingly, phosphomimetic cytochrome c also exhibited a lower caspase-3 activation activity. Altogether, these findings yield a better understanding of the molecular basis for mitochondrial metabolism in acute diseases, such as brain ischemia, and thus could allow the use of phosphomimetic cytochrome c as a neuroprotector with therapeutic applications.España, Junta de Andalucía BIO-198España MINECO BFU2015-71017/BM

An MPI-CUDA implementation of an improved Roe method for two-layer shallow water systems

The numerical solution of two-layer shallow water systems is required to simulate accurately stratified fluids, which are ubiquitous in nature: they appear in atmospheric flows, ocean currents, oil spills, . . . Moreover, the implementation of the numerical schemes to solve these models in realistic scenarios imposes huge demands of computing power. In this paper, we tackle the acceleration of these simulations in triangular meshes by exploiting the combined power of several CUDA-enabled GPUs in a GPU cluster. For that purpose, an improvement of a path conservative Roe type finite volume scheme which is specially suitable for GPU implementation is presented, and a distributed implementation of this scheme which uses CUDA and MPI to exploit the potential of a GPU cluster is developed. This implementation overlaps MPI communication with CPU-GPU memory transfers and GPU computation to increase efficiency. Several numerical experiments performed on a cluster of modern CUDA-enabled GPUs show the efficiency of the distributed solver

RNA Binding Protein Regulation and Cross-Talk in the Control of AU-rich mRNA Fate

mRNA metabolism is tightly orchestrated by highly-regulated RNA Binding Proteins (RBPs) that determine mRNA fate, thereby influencing multiple cellular functions across biological contexts. Here, we review the interplay between six well-known RBPs (TTP, AUF-1, KSRP, HuR, TIA-1, and TIAR) that recognize AU-rich elements (AREs) at the 3′ untranslated regions of mRNAs, namely ARE-RBPs. Examples of the links between their cross-regulations and modulation of their targets are analyzed during mRNA processing, turnover, localization, and translational control. Furthermore, ARE recognition can be self-regulated by several factors that lead to the prevalence of one RBP over another. Consequently, we examine the factors that modulate the dynamics of those protein-RNA transient interactions to better understand the final consequences of the regulation mediated by ARE-RBPs. For instance, factors controlling the RBP isoforms, their conformational state or their post-translational modifications (PTMs) can strongly determine the fate of the protein-RNA complexes. Moreover, mRNA specific sequence and secondary structure or subtle environmental changes are also key determinants to take into account. To sum up, the whole understanding of such a fine tuned regulation is a challenge for future research and requires the integration of all the available structural and functional data by in vivo, in vitro and in silico approaches.España, Ministerio de Economía y Competitividad BFU2015-71017-PEspaña, Ministerio de Educación, Cultura y Deporte FPU013/04373, FPU016/0151

Characterization of Healthy and Pathological Voice Through Measures Based on Nonlinear Dynamics

In this paper, we propose to quantify the quality of the recorded voice through objective nonlinear measures. Quantification of speech signal quality has been traditionally carried out with linear techniques since the classical model of voice production is a linear approximation. Nevertheless, nonlinear behaviors in the voice production process have been shown. This paper studies the usefulness of six nonlinear chaotic measures based on nonlinear dynamics theory in the discrimination between two levels of voice quality: healthy and pathological. The studied measures are first- and second-order Renyi entropies, the correlation entropy and the correlation dimension. These measures were obtained from the speech signal in the phase-space domain. The values of the first minimum of mutual information function and Shannon entropy were also studied. Two databases were used to assess the usefulness of the measures: a multiquality database composed of four levels of voice quality (healthy voice and three levels of pathological voice); and a commercial database (MEEI Voice Disorders) composed of two levels of voice quality (healthy and pathological voices). A classifier based on standard neural networks was implemented in order to evaluate the measures proposed. Global success rates of 82.47% (multiquality database) and 99.69% (commercial database) were obtained.Publicad

A Cellular Sudoku Solver

Sudoku is a very popular puzzle which consists on placing several numbers in a squared grid according to some simple rules. In this paper we present an efficient family of P systems which solve sudoku puzzles of any order verifying a specific property. The solution is searched by using a simple human-style method. If the sudoku cannot be solved by using this strategy, the P system detects this drawback and then the computations stops and returns No. Otherwise, the P system encodes the solution and returns Yes in the last computation step.Ministerio de Ciencia e Innovación TIN2008-04487-EMinisterio de Ciencia e Innovación TIN-2009-13192Junta de Andalucía P08-TIC-0420

Cutting down on the grog: the crystallisation of Neolithic ceramic traditions at Cova d’En Pardo (Alicante, Spain) and cultural change in the western Mediterranean basin (mid-6th and 5th millennia cal. BC)

This paper presents the characterisation of 48 ceramic samples from Cova d’En Pardo (Alicante, Spain). Provenance and technology analysis are carried out on materials dated back to different Early and Middle Neolithic cultural phases, including pioneer and Epicardial levels, poorly known in the area. The techniques employed are optical petrography and scanning electron microscope. Two main fabrics were identified, characterised by the heavy presence of temper (grog and calcite), along with five minor petrographic classes, including two imports, one of them probably from southern Iberia. The comparison among occupational phases within the site reveals changes along the stratigraphic series, especially during the transition from the 6th to 5th millennia cal. BC, which is reflected in temper choice. Evidence from the earliest occupation of the site also agrees with the picture of discontinuity previously observed on nearby contexts between pioneer and traditional Cardial ceramic technology, which might be connected to neolithization routes. Firing technology is characterised by the occurrence of microstructure gradients and signs of fast heating rates.Sample preparation and analyses were funded by the projects NEOMEDPOT (Marie Skłodowska-Curie program, European Commission, grant number 659466) and Espacios sociales y espacios de frontera durante el calcolítico y la Edad del Bronce en el Levante de la península Ibérica (HAR2016-76586-P, Ministerio de Economía y Competitividad and FEDER). Miguel del Pino is a postdoctoral researcher within the Viera y Clavijo program, funded by the Universidad de Las Palmas de Gran Canaria (Spain). The initial draft of the paper was finished while a postdoctoral researcher within the APOSTD program funded by the Generalitat Valenciana and FEDER funds (Spain)

An approach to patents of prestressed concrete in 20th Century's arquitecture

Around 1906, there was a discussion in the various publications on reinforced concrete about the problem of how to avoid the cracks on it, due to tension that occurred inside. First attempts to avert it failed since the tension applied to the steel was lost with the passage of time, as much for the hydraulic retraction of the concrete as for the use of not very high strength steels, and also because of the stress imposed were insufficient for targeted outcomes. In 1928, E. Freyssinet registered the first patent of prestressed concrete, and this originated a new constructive technology, which subsequently consolidated due to the rehabilitation of the foundations of the harbor of Le Havre (1933-1935). When making a previous prestressed of the oncrete reinforcement, forces created on-demand in the construction are placed compensating the effect of its own weight and of the permanents loads acting on the structure. With this consideration, the deformation that the system takes may become non-existing, reducing their stress state to a single longitudinal compression. The material with this technology becomes a tough mechanism with a system according to the structural features appropriate to concrete as material. Prestressed concrete is considered the major structural invention of the twentieth century and for several authors it proves to be a new material different than concrete, due to is own conception. According to José Antonio Fernández Ordoñez, "only the appearance of the arch is comparable in importance to the invention of Freyssinet". (Fernandez Ordoñez 1978). Using a technique of control of the force lines, the prestressed, they will develop a construction technology able to control the geometry of the shape (Anaya 2011). The present text attempts to establish whether individual prestressed concrete systems give rise to new types of construction, or whether they are systematically used in the same building typologies. Moreover, attempts to evaluate how, a control of the shape geometry has been achieved by utilizing this prestressed technique, which offers a project liberty ampler than previously maintained without the introduction of these stress

Efficient GPU implementation of a two waves TVD-WAF method for the two-dimensional one layer Shallow Water system on structured meshes.

The numerical solutions of shallow water equations are useful for applications related to geophysical flows that usually take place in large computational domains and could require real time calculation. Therefore, parallel versions of accurate and efficient numerical solvers for high performance platforms are needed to be able to deal with these simulation scenarios in reasonable times. In this paper we present an efficient CUDA implementation of a first and second order HLL methods and a two-waves TVD-WAF one. We propose to write all these methods under a common framework, such as, their CUDA implementations share the same structure. In particular, the reformulation of TVD-WAF numerical flux and the improved definition of the flux limiter allows us to obtain a more robust solver in situations like wet/dry fronts. Finally, some numerical tests are presented showing that the TVD-WAF method is slightly slower that the first order HLL method and two times faster than the second order HLL method, but it provides numerical results almost as accurate as the second order HLL scheme

Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48

Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation—in particular, at tyrosine 48—is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methylL-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects.España, MINECO BFU2015-71017-P/BMC and BFU2015- 19451/BMCUnión Europea, Bio-NMR-00130 and CALIPSO-312284España, Ministerio de Educación AP2009-409

CARTOGRAFIA ECOLÓGICA DE LA FAUNA Y ORGANIZACIÓN DEL TERRITORIO: APROXIMACIÓN AL CASO DEL MAR MENOR Y SISTEMAS ADYACENTES

The need for including faunistic and ecological aspects in studies of land use has been analyzed, either from a methodological point of view or taking into account animal populations of great interest. This survey has been located the in Mar Menor lagoon and its ecological surroundings. Essentially, populations of molluscs, crustaceans, reptiles, fishes, birds and mammals have been used. The method of work has been based on characterizing homogeneous environmental sectors with regard to subatratum, relief, vegetation and degree of human activity. By field extensive prospection analysis of available bibliographical sources, as well as information obtained from other investigators, the ecological characterization of these animal communities has been obtained. Twenty eight faunistic units have been considered in all, whose description comprises structure. Functioning, dynamics and environmental conditions, closely related to the taxonomic operational components of the study. Finally besides aspects of conservation and exploitation in relation to the studied animal populations, the present day environmental conditions along the coast of the Mar Menor lagoon have been studied too.Se analiza la necesidad de incluir en los estudios de utilización del territorio los factores ecológicos y faunísticos, tanto desde el punto de vista metodológico como desde la consideración de las taxocenosis animales de mayor interés. El trabajo se ha realizado en el área del Mar Menor y su entorno ecológico. Se han tenido en cuenta, fundamentalmente, las taxocenosis de crustáceos, moluscos, reptiles, peces, aves y mamíferos. El método de estudio se ha basado en la caracterización de sectores ambientales internamente homogéneos en cuanto a sustrato, relieve, vegetación y grado de influencia humana. Mediante la prospección extensiva de campo y el análisis de la información bibliográfica disponible, junto con el conocimiento obtenido de otros investigadores, se ha llegado a una tipificación de las comunidades animales que habitan cada sector. En total, se han delimitado 28 unidades, cuya descripción comprende la estructura, funcionamiento, dinámica y estado ambiental de las mismas, siempre en estrecha relación con las componentes taxonómicas operacionales que se han tenido en cuenta, y que quedan claramente establecidas en el trabajo. Por último, además de aspectos de conservación y explotación de los ecosistemas, en relación a las poblaciones animales estudiadas, se analiza el estado actual de la calidad ambiental de este tramo del litoral murciano, incidiendo a través de aspectos puntuales en el marco global del planeamiento con bases ecológicas, que con carácter de urgencia precisa el área estudiada