Reducing the LSQ and L1 data cache power consumption

In most modern processor designs, the HW dedicated to store data and instructions (memory hierarchy) has become a major consumer of power. In order to reduce this power consumption, we propose in this paper two techniques, one to filter accesses to the LSQ (Load-Store Queue) based on both timing and address information, and the other to filter accesses to the first level data cache based on a forwarding predictor. Our simulation results show that the power consumption decreases in 30-40% in each structure, with a negligible performance penalty of less than 0.1%.Presentado en el V Workshop Arquitectura, Redes y Sistemas Operativos (WARSO)Red de Universidades con Carreras en Informática (RedUNCI

Inactivation of Salmonella typhimurium by cold plasma activated water application

[SPA] El plasma frío es definido como el cuarto estado de la materia y es generado por una serie de descargas denominadas Spark y Glow, las cuales originan unas sustancias químicas que pueden interaccionar con microorganismos dando lugar a la inactivación de estos. S. typhimurium ha sido el patógeno elegido para este trabajo, ya que es el segundo serovar de Salmonella spp., con más casos de Salmonelosis en el año 2018. Los resultados aportados en este estudio mostraron un claro efecto sobre la inactivación de S. typhimurium debido a las especies reactivas generada durante los tratamientos PAW.] [ENG] Cold plasma is defined as the fourth state of matter and is generated by a series of discharges called Spark and Glow, which originate chemical substances that can interact with microorganisms resulting in the inactivation of these. S. typhimurium has been the pathogen of choice for this work, since it is the second serovar of Salmonella spp. with more cases of Salmonellosis in 2018. The results provided in this study, showed a clear effect on the inactivation of S. typhimurium due to the reactive species generated during PAW treatments.Gracias al MINECO, AEI y FEDER, por la financiación del proyecto "Validación de nuevas herramientas y procesos para el análisis y la mejora de la seguridad alimentaria microbiológica", con cargo a la partida presupuestaria: 30.05.18.80.79 541A 642.10

Manipulation of feeding regime alters sexual dimorphism for lifespan and reduces sexual conflict in Drosophila melanogaster

Sexual dimorphism for lifespan (SDL) is widespread, but poorly understood. A leading hypothesis, which we test here, is that strong SDL can reduce sexual conflict, by allowing each sex to maximise its sex-specific fitness. We used replicated experimental evolution lines of the fruit fly, Drosophila melanogaster, which had been maintained for over 360 generations on either unpredictable ‘Random’ or predictable ‘Regular’ feeding regimes. This evolutionary manipulation of feeding regime led to robust, enhanced SDL in Random over control, Regular lines. Enhanced SDL was associated with a significant increase in the fitness of focal males, tested with wild type females. This was due to sex-specific changes to male life history, manifested as increased early reproductive output and reduced survival. In contrast, focal female fitness, tested with wild type males, did not differ across regimes. Hence increased SDL was associated with a reduction in sexual conflict, which increased male fitness and maintained fitness in females. Differences in SDL were not associated with developmental time or developmental survival. Overall, the results showed that the expression of enhanced SDL, resulting from experimental evolution of feeding regimes, was associated with male-specific changes in life history, leading to increased fitness and reduced sexual conflict

ISOGO: Functional annotation of protein-coding splice variants

The advent of RNA-seq technologies has switched the paradigm of genetic analysis from a genome to a transcriptome-based perspective. Alternative splicing generates functional diversity in genes, but the precise functions of many individual isoforms are yet to be elucidated. Gene Ontology was developed to annotate gene products according to their biological processes, molecular functions and cellular components. Despite a single gene may have several gene products, most annotations are not isoform-specifc and do not distinguish the functions of the diferent proteins originated from a single gene. Several approaches have tried to automatically annotate ontologies at the isoform level, but this has shown to be a daunting task. We have developed ISOGO (ISOform+GO function imputation), a novel algorithm to predict the function of coding isoforms based on their protein domains and their correlation of expression along 11,373 cancer patients. Combining these two sources of information outperforms previous approaches: it provides an area under precision-recall curve (AUPRC) fve times larger than previous attempts and the median AUROC of assigned functions to genes is 0.82. We tested ISOGO predictions on some genes with isoform-specifc functions (BRCA1, MADD,VAMP7 and ITSN1) and they were coherent with the literature. Besides, we examined whether the main isoform of each gene -as predicted by APPRIS- was the most likely to have the annotated gene functions and it occurs in 99.4% of the genes. We also evaluated the predictions for isoform-specifc functions provided by the CAFA3 challenge and results were also convincing. To make these results available to the scientifc community, we have deployed a web application to consult ISOGO predictions (https://biotecnun.unav. es/app/isogo). Initial data, website link, isoform-specifc GO function predictions and R code is available at https://gitlab.com/icassol/isogo

Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes.

In vivo, mammalian cells proliferate within 3D environments consisting of numerous microcavities and channels, which contain a variety of chemical and physical cues. External environments often differ between normal and pathological states, such as the unique spatial constraints that metastasizing cancer cells experience as they circulate the vasculature through arterioles and narrow capillaries, where they can divide and acquire elongated cylindrical shapes. While metastatic tumors cause most cancer deaths, factors impacting early cancer cell proliferation inside the vasculature and those that can promote the formation of secondary tumors remain largely unknown. Prior studies investigating confined mitosis have mainly used 2D cell culture systems. Here, we mimic aspects of metastasizing tumor cells dividing inside blood capillaries by investigating single-cell divisions of living human cancer cells, trapped inside 3D rolled-up, transparent nanomembranes. We assess the molecular effects of tubular confinement on key mitotic features, using optical high- and super-resolution microscopy. Our experiments show that tubular confinement affects the morphology and dynamics of the mitotic spindle, chromosome arrangements, and the organization of the cell cortex. Moreover, we reveal that membrane blebbing and/or associated processes act as a potential genome-safety mechanism, limiting the extent of genomic instability caused by mitosis in confined circumstances, especially in tubular 3D microenvironments. Collectively, our study demonstrates the potential of rolled-up nanomembranes for gaining molecular insights into key cellular events occurring in tubular 3D microenvironments in vivo.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 311529 (S.S.) and the Volkswagen Foundation no. 86 362 (S.S. and W.X.), a FEBS Return-to-Europe fellowship (C.K.S.), the Wellcome Trust (092096/Z/10/Z for N.L.; 094587/Z/10/Z for R.B.), and a European Research Council (ERC) Starting Researcher Grant (R.E.C.-S.; SYSGRO). O.G.S. acknowledges financial support from the DFG Research Unit 1713 “Sensorische Mikro und Nanosysteme”. D.H.G. acknowledges funding from the Alexander von Humboldt Foundation and the U.S. National Science Foundation (Grants: CMMI 1200241 and CBET-1442014). Research in the S.P.J. laboratory is funded by Cancer Research U.K., the ERC, and the European Community Seventh Framework Programme (DDResponse), with core infrastructure provided by Cancer Research U.K. and the Wellcome Trust.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acsnano.6b0046

Pea PSII-LHCII supercomplexes form pairs by making connections across the stromal gap

In higher plant thylakoids, the heterogeneous distribution of photosynthetic protein complexes is a determinant for the formation of grana, stacks of membrane discs that are densely populated with Photosystem II (PSII) and its light harvesting complex (LHCII). PSII associates with LHCII to form the PSII-LHCII supercomplex, a crucial component for solar energy conversion. Here, we report a biochemical, structural and functional characterization of pairs of PSII-LHCII supercomplexes, which were isolated under physiologically-relevant cation concentrations. Using single-particle cryo-electron microscopy, we determined the three-dimensional structure of paired C2S2M PSII-LHCII supercomplexes at 14 angstrom resolution. The two supercomplexes interact on their stromal sides through a specific overlap between apposing LHCII trimers and via physical connections that span the stromal gap, one of which is likely formed by interactions between the N-terminal loops of two Lhcb4 monomeric LHCII subunits. Fast chlorophyll fluorescence induction analysis showed that paired PSII-LHCII supercomplexes are energetically coupled. Molecular dynamics simulations revealed that additional flexible physical connections may form between the apposing LHCII trimers of paired PSII-LHCII supercomplexes in appressed thylakoid membranes. Our findings provide new insights into how interactions between pairs of PSII-LHCII supercomplexes can link adjacent thylakoids to mediate the stacking of grana membranes

Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?

Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. Results: Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. Conclusions: In subjects with persistent hypophosphatasaemia -secondary causes excluded- one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variantGenetic testing was supported by a grant from Alexion Pharmaceuticals Inc., which had no role in the study design or data analysi

Organising multi-dimensional biological image information: The BioImage Database

Nowadays it is possible to unravel complex information at all levels of cellular organization by obtaining multi-dimensional image information. at the macromolecular level, three-dimensional (3D) electron microscopy, together with other techniques, is able to reach resolutions at the nanometer or subnanometer level. The information is delivered in the form of 3D volumes containing samples of a given function, for example, the electron density distribution within a given macromolecule. The same situation happens at the cellular level with the new forms of light microscopy, particularly confocal microscopy, all of which produce biological 3D volume information. Furthermore, it is possible to record sequences of images over time (videos), as well as sequences of volumes, bringing key information on the dynamics of living biological systems. It is in this context that work on bioimage started two years ago, and that its first version is now presented here. In essence, Bioimage is a database specifically designed to contain multi-dimensional images, perform queries and interactively work with the resulting multi-dimensional information on the World Wide Web, as well as accomplish the required cross-database links. Two sister home pages of bioimage can be accessed at http://www.bioimage.org and http://www-embl.bioimage.or

Occurrence of antibiotics in Lettuce (Lactuca sativa L.) and Radish (Raphanus sativus L.) following organic soil fertilisation under plot-scale conditions: Crop and human health implications

Recent studies have demonstrated the crop uptake of antibiotics (ABs) from soils treated with AB-carrying fertilisers. However, there is a lack of plot-scale studies linking their effects at the agronomic and metabolomic/transcriptomic level to their impact on human health. This paper assesses the plant uptake of 23 ABs following two productive cycles of lettuce and radish cropped with sewage sludge, pig slurry, the organic fraction of municipal solid waste, or chemical fertilisation under plot-scale conditions (32 plots spanning 3-10 m2 each). AB uptake by plants depended on both the vegetable and the AB class and was higher in radish than in lettuce edible parts. Levels ranged from undetectable to up to 76 ng/g (fresh weight). Repetitive organic fertilisation resulted in an increase in the concentration of ABs in lettuce leaves, but not in radish roots. Significant metabolomic and transcriptomic changes were observed following soil fertilisation. Nevertheless, a human health risk assessment indicates that the occurrence of ABs in lettuce or radish edible parts does not pose any risk. To our knowledge, this is the first holistic plot-scale study demonstrating that the use of organic fertilisers containing ABs is safe for crop security and human health.The authors gratefully acknowledge the financial support of the Spanish Ministry of Science and Innovation through projects AGL2017- 89518-R and RTI2018-096175-B-I00. IDAEA-CSIC is a Severo Ochoa Centre of Excellence (Spanish Ministry of Science and Innovation, Project CEX2018-000794-S). Mònica Escolà Casas wishes to thank the Beatriu de Pinós 2018 grant programme (MSCA grant agreement number 801370) for the funding.Peer ReviewedPostprint (published version