Metal dealing at the origin of the Chordata phylum: The metallothionein system and metal overload response in Amphioxus.

Non-vertebrate chordates, specifically amphioxus, are considered of the utmost interest for gaining insight into the evolutionary trends, i.e. differentiation and specialization, of gene/protein systems. In this work, MTs (metallothioneins), the most important metal binding proteins, are characterized for the first time in the cephalochordate subphylum at both gene and protein level, together with the main features defining the amphioxus response to cadmium and copper overload. Two MT genes (BfMT1 and BfMT2) have been identified in a contiguous region of the genome, as well as several ARE (antioxidant response element) and MRE (metal response element) located upstream the transcribed region. Their corresponding cDNAs exhibit identical sequence in the two lancelet species (B. floridae and B. lanceolatum), BfMT2 cDNA resulting from an alternative splicing event. BfMT1 is a polyvalent metal binding peptide that coordinates any of the studied metal ions (Zn, Cd or Cu) rendering complexes stable enough to last in physiological environments, which is fully concordant with the constitutive expression of its gene, and therefore, with a metal homeostasis housekeeping role. On the contrary, BfMT2 exhibits a clear ability to coordinate Cd(II) ions, while it is absolutely unable to fold into stable Cu (I) complexes, even as mixed species. This identifies it as an essential detoxification agent, which is consequently only induced in emergency situations. The cephalochordate MTs are not directly related to vertebrate MTs, neither by gene structure, protein similarity nor metal-binding behavior of the encoded peptides. The closest relative is the echinoderm MT, which confirm proposed phylogenetic relationships between these two groups. The current findings support the existence in most organisms of two types of MTs as for their metal binding preferences, devoted to different biological functions: multivalent MTs for housekeeping roles, and specialized MTs that evolve either as Cd-thioneins or Cu-thioneins, according to the ecophysiological needs of each kind of organisms.

RADIC: un middleware de tolerancia a fallos que preserva el rendimiento

La tolerancia a fallos es una línea de investigación que ha adquirido una importancia relevante con el aumento de la capacidad de cómputo de los súper-computadores actuales. Esto es debido a que con el aumento del poder de procesamiento viene un aumento en la cantidad de componentes que trae consigo una mayor cantidad de fallos. Las estrategias de tolerancia a fallos actuales en su mayoría son centralizadas y estas no escalan cuando se utiliza una gran cantidad de procesos, dado que se requiere sincronización entre todos ellos para realizar las tareas de tolerancia a fallos. Además la necesidad de mantener las prestaciones en programas paralelos es crucial, tanto en presencia como en ausencia de fallos. Teniendo en cuenta lo citado, este trabajo se ha centrado en una arquitectura tolerante a fallos descentralizada (RADIC – Redundant Array of Distributed and Independant Controllers) que busca mantener las prestaciones iniciales y garantizar la menor sobrecarga posible para reconfigurar el sistema en caso de fallos. La implementación de esta arquitectura se ha llevado a cabo en la librería de paso de mensajes denominada Open MPI, la misma es actualmente una de las más utilizadas en el mundo científico para la ejecución de programas paralelos que utilizan una plataforma de paso de mensajes. Las pruebas iniciales demuestran que el sistema introduce mínima sobrecarga para llevar a cabo las tareas correspondientes a la tolerancia a fallos. MPI es un estándar por defecto fail-stop, y en determinadas implementaciones que añaden cierto nivel de tolerancia, las estrategias más utilizadas son coordinadas. En RADIC cuando ocurre un fallo el proceso se recupera en otro nodo volviendo a un estado anterior que ha sido almacenado previamente mediante la utilización de checkpoints no coordinados y la relectura de mensajes desde el log de eventos. Durante la recuperación, las comunicaciones con el proceso en cuestión deben ser retrasadas y redirigidas hacia la nueva ubicación del proceso. Restaurar procesos en un lugar donde ya existen procesos sobrecarga la ejecución disminuyendo las prestaciones, por lo cual en este trabajo se propone la utilización de nodos spare para la recuperar en ellos a los procesos que fallan, evitando de esta forma la sobrecarga en nodos que ya tienen trabajo. En este trabajo se muestra un diseño propuesto para gestionar de un modo automático y descentralizado la recuperación en nodos spare en un entorno Open MPI y se presenta un análisis del impacto en las prestaciones que tiene este diseño. Resultados iniciales muestran una degradación significativa cuando a lo largo de la ejecución ocurren varios fallos y no se utilizan spares y sin embargo utilizándolos se restablece la configuración inicial y se mantienen las prestaciones.

Normalització del volum d'arxius de so en format MP3

L'estàndard MPEG-1 Layer III va ser creat fa poc més de 10 anys i en aquest curt espai de temps ha revolucionat el fins aleshores estable món de la música. El fet de poder comprimir tota una cançó en uns pocs 'megues' (3 o 4) sense una pèrdua apreciable de qualitat i la proliferació d'ordinadors connectats a Internet va fer que el tràfic de fitxers en aquest format col·lapsés més d'un servidor. Per això, no és estrany que apareguessin autèntiques col·leccions de fitxers musicals en format MP3 procedents de les fonts més variades. Aquest fet (la diversitat de les fonts) i la variabilitat entre els diferents codificadors fa que el volum del so d'aquests fitxers disti molt de ser semblant. I això és precisament el que procura aconseguir aquest projecte: fer que tota col·lecció de fitxers MP3 soni igual de fort.

The size and distribution of donations: Effects of numbers of potential recipients

Whereas much literature exists on choice overload, little is known about effects of numbers of alternatives in donation decisions. How do these affect both the size and distribution of donations? We hypothesize that donations are affected by the reputation of recipients and increase with their number, albeit at a decreasing rate. Allocations to recipients reflect different concepts of fairness equity and equality. Both may be employed but, since they differ in cognitive and emotional costs, numbers of recipients are important. Using a cognitive (emotional) argument, distributions become more uniform (skewed) as numbers increase. In a survey, respondents indicated how they would donate lottery winnings of 50 Euros. Results indicated that more was donated to NGO s that respondents knew better. Second, total donations increased with the number of recipients albeit at a decreasing rate. Third, distributions of donations became more skewed as numbers increased. We comment on theoretical and practical implications.

Utilization of dietary glucose in the metabolic syndrome

This review is focused on the fate of dietary glucose under conditions of chronically high energy (largely fat) intake, evolving into the metabolic syndrome. We are adapted to carbohydrate-rich diets similar to those of our ancestors. Glucose is the main energy staple, but fats are our main energy reserves. Starvation drastically reduces glucose availability, forcing the body to shift to fatty acids as main energy substrate, sparing glucose and amino acids. We are not prepared for excess dietary energy, our main defenses being decreased food intake and increased energy expenditure, largely enhanced metabolic activity and thermogenesis. High lipid availability is a powerful factor decreasing glucose and amino acid oxidation. Present-day diets are often hyperenergetic, high on lipids, with abundant protein and limited amounts of starchy carbohydrates. Dietary lipids favor their metabolic processing, saving glucose, which additionally spares amino acids. The glucose excess elicits hyperinsulinemia, which may derive, in the end, into insulin resistance. The available systems of energy disposal could not cope with the excess of substrates, since they are geared for saving not for spendthrift, which results in an unbearable overload of the storage mechanisms. Adipose tissue is the last energy sink, it has to store the energy that cannot be used otherwise. However, adipose tissue growth also has limits, and the excess of energy induces inflammation, helped by the ineffective intervention of the immune system. However, even under this acute situation, the excess of glucose remains, favoring its final conversion to fat. The sum of inflammatory signals and deranged substrate handling induce most of the metabolic syndrome traits: insulin resistance, obesity, diabetes, liver steatosis, hyperlipidemia and their compounded combined effects. Thus, a maintained excess of energy in the diet may result in difficulties in the disposal of glucose, eliciting inflammation and the development of the metabolic syndrome

Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.

Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.