Identificada una molècula que facilitaria l'acció dels antifúngics

A causa de la similitud entre certes proteïnes dels fongs patògens i d'altres humanes, els medicaments antifúngics actuals solen estar dirigits contra característiques que estan presents en els fongs patògens i absents en els éssers humans. Un estudi ha identificat una molècula que afecta les proteïnes fúngiques però no les seves similars humanes, obrint així la possibilitat de desenvolupar fàrmacs amb suficient especificitat com per no provocar efectes secundaris indesitjats en els pacients.Debido a la similitud entre ciertas proteínas de los hongos patógenos y otras humanas, los medicamentos antifúngicos actuales suelen estar dirigidos contra características que están presentes en los hongos patógenos y ausentes en los seres humanos. Un estudio ha identificado una molécula que afecta a las proteínas fúngicas pero no a sus similares humanas, abriendo así la posibilidad de desarrollar fármacos con suficiente especificidad como para no provocar efectos secundarios indeseados en los pacientes.Due to the similarity of certain proteins from pathogenic fungi and human proteins, current antifungals are usually directed to characteristics that are present in the pathogen but absent in humans. A study has identified a molecule that affects fungal proteins but not their human counterparts, thus opening the possibility of developing drugs with sufficient specificity as to not cause unwanted side effects in patients

Ser/Thr protein phosphatases in fungi: structure, regulation and function

Reversible phospho-dephosphorylation of proteins is a major mechanism for the control of cellular functions. By large, Ser and Thr are the most frequently residues phosphorylated in eukaryotes. Removal of phosphate from these amino acids is catalyzed by a large family of well-conserved enzymes, collectively called Ser/Thr protein phosphatases. The activity of these enzymes has an enormous impact on cellular functioning. In this work we present the members of this family in S. cerevisiae and other fungal species, and review the most recent findings concerning their regulation and the roles they play in the most diverse aspects of cell biology

T-RFPred: a nucleotide sequence size prediction tool for microbial community description based on terminal-restriction fragment length polymorphism chromatograms

<p>Abstract</p> <p>Background</p> <p>Terminal-Restriction Fragment Length Polymorphism (T-RFLP) is a technique used to analyze complex microbial communities. It allows for the quantification of unique or numerically dominant phylotypes in amplicon pools and it has been used primarily for comparisons between different communities. T-RFPred, Terminal-Restriction Fragment Prediction, was developed to identify and assign taxonomic information to chromatogram peaks of a T-RFLP fingerprint for a more comprehensive description of microbial communities. The program estimates the expected fragment size of representative 16S rRNA gene sequences (either from a complementary clone library or from public databases) for a given primer and restriction enzyme(s) and provides candidate taxonomic assignments.</p> <p>Results</p> <p>To show the accuracy of the program, T-RFLP profiles of a marine bacterial community were described using artificial bacterioplankton clone libraries of sequences obtained from public databases. For all valid chromatogram peaks, a phylogenetic group could be assigned.</p> <p>Conclusions</p> <p>T-RFPred offers enhanced functionality of T-RFLP profile analysis over current available programs. In particular, it circumvents the need for full-length 16S rRNA gene sequences during taxonomic assignments of T-RF peaks. Thus, large 16S rRNA gene datasets from environmental studies, including metagenomes, or public databases can be used as the reference set. Furthermore, T-RFPred is useful in experimental design for the selection of primers as well as the type and number of restriction enzymes that will yield informative chromatograms from natural microbial communities.</p

Visibility rendering order: Improving energy efficiency on mobile GPUs through frame coherence

During real-time graphics rendering, objects are processed by the GPU in the order they are submitted by the CPU, and occluded surfaces are often processed even though they will end up not being part of the final image, thus wasting precious time and energy. To help discard occluded surfaces, most current GPUs include an Early-Depth test before the fragment processing stage. However, to be effective it requires that opaque objects are processed in a front-to-back order. Depth sorting and other occlusion culling techniques at the object level incur overheads that are only offset for applications having substantial depth and/or fragment shading complexity, which is often not the case in mobile workloads. We propose a novel architectural technique for mobile GPUs, Visibility Rendering Order (VRO), which reorders objects front-to-back entirely in hardware by exploiting the fact that the objects in graphics animated applications tend to keep its relative depth order across consecutive frames (temporal coherence). Since order relationships are already tested by the Depth Test, VRO incurs minimal energy overheads because it just requires adding a small hardware to capture that information and use it later to guide the rendering of the following frame. Moreover, unlike other approaches, this unit works in parallel with the graphics pipeline without any performance overhead. We illustrate the benefits of VRO using various unmodified commercial 3D applications for which VRO achieves 27% speed-up and 14.8% energy reduction on average over a state-of-the-art mobile GPU.Peer ReviewedPostprint (author's final draft

Dynamic sampling rate: harnessing frame coherence in graphics applications for energy-efficient GPUs

In real-time rendering, a 3D scene is modelled with meshes of triangles that the GPU projects to the screen. They are discretized by sampling each triangle at regular space intervals to generate fragments which are then added texture and lighting effects by a shader program. Realistic scenes require detailed geometric models, complex shaders, high-resolution displays and high screen refreshing rates, which all come at a great compute time and energy cost. This cost is often dominated by the fragment shader, which runs for each sampled fragment. Conventional GPUs sample the triangles once per pixel; however, there are many screen regions containing low variation that produce identical fragments and could be sampled at lower than pixel-rate with no loss in quality. Additionally, as temporal frame coherence makes consecutive frames very similar, such variations are usually maintained from frame to frame. This work proposes Dynamic Sampling Rate (DSR), a novel hardware mechanism to reduce redundancy and improve the energy efficiency in graphics applications. DSR analyzes the spatial frequencies of the scene once it has been rendered. Then, it leverages the temporal coherence in consecutive frames to decide, for each region of the screen, the lowest sampling rate to employ in the next frame that maintains image quality. We evaluate the performance of a state-of-the-art mobile GPU architecture extended with DSR for a wide variety of applications. Experimental results show that DSR is able to remove most of the redundancy inherent in the color computations at fragment granularity, which brings average speedups of 1.68x and energy savings of 40%.This work has been supported by the the CoCoUnit ERC Advanced Grant of the EU’s Horizon 2020 program (Grant No. 833057), Spanish State Research Agency (MCIN/AEI) under Grant PID2020-113172RB-I00, the ICREA Academia program, and the Generalitat de Catalunya under Grant FI-DGR 2016. Funding was provided by Ministerio de Economía, Industria y Competitividad, Gobierno de España (Grant No. TIN2016-75344-R).Peer ReviewedPostprint (published version

Improving the energy efficiency of the graphics pipeline by reducing overshading

The most common task of GPUs is to render images in real time. When rendering a 3D scene, a key step is determining which parts of every object are visible in the final image. There are different approaches to solve the visibility problem, the Z-Test being the most common in modern GPUs. A main factor that significantly penalizes the energy efficiency of a GPU, especially in the mobile arena, is the so-called overshading, which happens when a portion of an object is shaded and rendered but finally occluded by another object. This useless work results in a waste of energy, however, the conventional Z-Test only eliminates a fraction of it. In this paper we present a novel microarchitectural technique, the ¿-Test, to drastically reduce overshading on a Tile-Based Rendering (TBR) architecture. The proposed approach leverages frame-to-frame coherence by taking advantage of the costly and valuable calculations made in previous frames. In particular, we propose to reuse information from the Z-Buffer of the previous frame, which is currently discarded. We make the observation that due to the existing frame-to-frame coherence, the Z-Buffer of a frame will have a high similarity in many areas with that of the previous frame. As a result, the proposed technique avoids many costly computations and off-chip memory accesses. Our experimental evaluation shows that ¿-Test reduces the average energy consumption of the overall GPU/Memory system by 15.7 % and the runtime of the evaluated benchmarks by 10.6 % on average.This work has been supported by the the CoCoUnit ERC Advanced Grant of the EU’s Horizon 2020 program (grant No 833057), the Spanish State Research Agency under grant TIN2016-75344-R (AEI/-FEDER, EU) and the ICREA Academia program. D. Corbal´an-Navarro has been supported by a PhD research fellowship from the University of Murcia.Peer ReviewedPostprint (author's final draft

Report of the Scientific Committee of the Spanish Agency for Food Safety and Nutrition (AESAN) in relation to the effect on the Spanish population of the derogation of national regulation on maximum allowed limits for aflatoxins B1, B2, G1 and G2 in food

Las aflatoxinas son metabolitos tóxicos producidos por varias especies de hongos del género Aspergillus que crecen en plantas y alimentos de origen vegetal. De entre todas ellas (B1, B2, G1, G2, M1 y M2), destaca desde el punto de vista de la seguridad alimentaria la aflatoxina B1, tanto por ser la más prevalente en alimentos como la más tóxica para los seres humanos. La Unión Europea, debido a la toxicidad de estos compuestos y con el fin de garantizar una protección eficaz de la salud pública, ha establecido mediante el Reglamento (CE) Nº 1881/2006 contenidos máximos para la aflatoxina B1 y la suma de aflatoxinas B1, B2, G1 y G2 en diversos alimentos, entre los que se incluyen aquellos en los cuales la contaminación por este tipo de toxinas resulta más frecuente y puede resultar más peligrosa para la salud humana. En España, previamente a lo establecido por el Reglamento (CE) Nº 1881/2006, ya se dispone de una norma reguladora, el Real Decreto 475/1988, en el cual se establecen límites máximos permitidos de aflatoxinas B1, B2, G1 y G2 en alimentos para consumo humano de 10 μg/kg para la suma de dichas aflatoxinas y de 5 μg/kg para la aflatoxina B1. Si bien es cierto que el Reglamento (CE) Nº 1881/2006 cubre los alimentos que de manera más habitual pueden representar un riesgo para la salud humana originado por la presencia de aflatoxinas, existen trabajos científicos en los cuales se ha demostrado la presencia tanto de aflatoxinas totales como de aflatoxina B1 en alimentos no incluídos en el Reglamento (CE) Nº 1881/2006 en cantidades superiores a las establecidas como límites en el Real Decreto 475/1988. Por este motivo, y sin perjuicio de las medidas de gestión que sean pertinentes, el Comité Científico considera que, en este momento y hasta que se disponga de datos representativos de la presencia de aflatoxinas en algunos alimentos no incluídos en la legislación europea tales como la chufa, el Real Decreto 475/1988 que regula los límites máximos permitidos de aflatoxinas B1, B2, G1 y G2 ofrece un nivel de protección significativo para el consumidor respecto a determinados alimentos no regulados por el Reglamento (CE) Nº 1881/2006.Aflatoxins are toxic metabolites produced by some species of molds belonging to the genus Aspergillus which grow on plants and vegetable-origin foods. Among the aflatoxins that can be found (B1, B2, G1, G2, M1 and M2), from a food safety point of view the most remarkable is aflatoxin B1, because it is the most prevalent in foods and toxic for humans. Due to the toxicity of these substances and to protect consumers’ health, the European Union has stated maximum residue limits (MRL) for aflatoxins in foods, in the Commission Regulations (EC) No 1881/2006. MRL have been established for aflatoxin B1 and the sum of B1, B2, G1 and G2 in different foods, including those in which contamination with these kind of toxins is more frequent and can be more dangerous for human health. The Spanish Royal Decree 475/1988, approved before the Commission Regulation (EC) No 1881/ 2006, sets MRL for the aflatoxins in food for human consumption; 5 μg/kg for aflatoxin B1 and 10 μg/ kg for the sum of aflatoxin B1, B2, G1 and G2. Despite the Commission Regulation (EC) No 1881/2006 includes food which most could usually pose a risk for human health, specific papers have demonstrated the presence of total aflatoxins and aflatoxin B1 in foods not included in the Commission Regulation (EC) No 1881/2006, even at higher concentrations than those set up by the Spanish Royal Decree 475/1988. For this reason, notwithstanding the management measures that are pertinent, the scientific committee considers that, while there are no more data about maximum limits for these substances other food samples different than those included in the previously mentioned legislations (as tiger nuts or other doubtful foods regarding their producing conditions) the Royal Decree 475/1988 offers a significant protection for consumers

Yeast Ppz1 protein phosphatase toxicity involves the alteration of multiple cellular targets

Control of the protein phosphorylation status is a major mechanism for regulation of cellular processes, and its alteration often lead to functional disorders. Ppz1, a protein phosphatase only found in fungi, is the most toxic protein when overexpressed in Saccharomyces cerevisiae. To investigate the molecular basis of this phenomenon, we carried out combined genome-wide transcriptomic and phosphoproteomic analyses. We have found that Ppz1 overexpression causes major changes in gene expression, affecting ~ 20% of the genome, together with oxidative stress and increase in total adenylate pools. Concurrently, we observe changes in the phosphorylation pattern of near 400 proteins (mainly dephosphorylated), including many proteins involved in mitotic cell cycle and bud emergence, rapid dephosphorylation of Snf1 and its downstream transcription factor Mig1, and phosphorylation of Hog1 and its downstream transcription factor Sko1. Deletion of HOG1 attenuates the growth defect of Ppz1-overexpressing cells, while that of SKO1 aggravates it. Our results demonstrate that Ppz1 overexpression has a widespread impact in the yeast cells and reveals new aspects of the regulation of the cell cycle

Une synthèse sur la restauration fluviale dans le bassin de l’Èbre

L’état écologique et la fonctionnalité des cours d’eau du bassin de l’Èbre ont subi une détérioration remarquable au cours des dernières décennies, à cause du changement global et des pressions anthropiques directes. Face à cette problématique les initiatives de restauration sont encore peu abondantes, locales et très dispersées dans le territoire. Dans le contexte espagnol, le bassin de l’Èbre n’est pas moteur dans le développement de la restauration fluviale. L’administration hydrologique a préféré fondamentalement la récupération de zones humides. Cependant, des bases consolidées existent pour pouvoir développer une restauration fluviale dans l’avenir : des paradigmes théoriques associés aux groupes de travail, la mise en pratique de quelques actions comme exemples de démonstration et la possibilité de travailler de façon intégrée avec la conservation (des réserves naturelles fluviales) et la gestion d’inondations (l’espace de mobilité ou territoire fluvial)