Over-representation of correlation analysis (ORCA): a method for identifying associations between variable sets.

MOTIVATION: Often during the analysis of biological data, it is of importance to interpret the correlation structure that exists between variables. Such correlations may reveal patterns of co-regulation that are indicative of biochemical pathways or common mechanisms of response to a related set of treatments. However, analyses of correlations are usually conducted by either subjective interpretation of the univariate covariance matrix or by applying multivariate modeling techniques, which do not take prior biological knowledge into account. Over-representation analysis (ORA) is a simple method for objectively deciding whether a set of variables of known or suspected biological relevance, such as a gene set or pathway, is more prevalent in a set of variables of interest than we expect by chance. However, ORA is usually applied to a set of variables differentiating a single experimental variable and does not take into account correlations. RESULTS: Over-representation of correlation analysis (ORCA) is a novel combination of ORA and correlation analysis that provides a means to test whether more associations exist between two specific groups of variables than expected by chance. The method is exemplified by application to drug sensitivity and microRNA expression data from a panel of cancer cell lines (NCI60). ORCA highlighted a previously reported correlation between sensitivity to alkylating anticancer agents and topoisomerase inhibitors. We also used this approach to validate microRNA clusters predicted by mRNA correlations. These observations suggest that ORCA has the potential to reveal novel insights from these data, which are not readily apparent using classical ORA. AVAILABILITY AND IMPLEMENTATION: The R code of the method is available at https://github.com/ORCABioinfo/ORCAcode.

Arabidopsis thaliana AtUTr7 encodes a golgi-localized UDP-glucose/UDP-galactose transporter that affects lateral root emergence.

Nucleotide sugar transporters (NSTs) are antiporters comprising a gene family that plays a fundamental role in the biosynthesis of complex cell wall polysaccharides and glycoproteins in plants. However, due to the limited number of related mutants that have observable phenotypes, the biological function(s) of most NSTs in cell wall biosynthesis and assembly have remained elusive. Here, we report the characterization of AtUTr7 from Arabidopsis (Arabidopsis thaliana (L.) Heynh.), which is homologous to multi-specific UDP-sugar transporters from Drosophila melanogaster, humans, and Caenorhabditis elegans. We show that AtUTr7 possesses the common structural characteristics conserved among NSTs. Using a green fluorescent protein (GFP) tagged version, we demonstrate that AtUTr7 is localized in the Golgi apparatus. We also show that AtUTr7 is widely expressed, especially in the roots and in specific floral organs. Additionally, the results of an in vitro nucleotide sugar transport assay carried out with a tobacco and a yeast expression system suggest that AtUTr7 is capable of transferring UDP-Gal and UDP-Glc, but not a range of other UDP- and GDP-sugars, into the Golgi lumen. Mutants lacking expression of AtUTr7 exhibited an early proliferation of lateral roots as well as distorted root hairs when cultivated at high sucrose concentrations. Furthermore, the distribution of homogalacturonan with a low degree of methyl esterification differed in lateral root tips of the mutant compared to wild-type plants, although additional analytical procedures revealed no further differences in the composition of the root cell walls. This evidence suggests that the transport of UDP-Gal and UDP-Glc into the Golgi under conditions of high root biomass production plays a role in lateral root and root hair development.

Putative glycosyltransferases and other plant Golgi apparatus proteins are revealed by LOPIT proteomics.

The Golgi apparatus is the central organelle in the secretory pathway and plays key roles in glycosylation, protein sorting, and secretion in plants. Enzymes involved in the biosynthesis of complex polysaccharides, glycoproteins, and glycolipids are located in this organelle, but the majority of them remain uncharacterized. Here, we studied the Arabidopsis (Arabidopsis thaliana) membrane proteome with a focus on the Golgi apparatus using localization of organelle proteins by isotope tagging. By applying multivariate data analysis to a combined data set of two new and two previously published localization of organelle proteins by isotope tagging experiments, we identified the subcellular localization of 1,110 proteins with high confidence. These include 197 Golgi apparatus proteins, 79 of which have not been localized previously by a high-confidence method, as well as the localization of 304 endoplasmic reticulum and 208 plasma membrane proteins. Comparison of the hydrophobic domains of the localized proteins showed that the single-span transmembrane domains have unique properties in each organelle. Many of the novel Golgi-localized proteins belong to uncharacterized protein families. Structure-based homology analysis identified 12 putative Golgi glycosyltransferase (GT) families that have no functionally characterized members and, therefore, are not yet assigned to a Carbohydrate-Active Enzymes database GT family. The substantial numbers of these putative GTs lead us to estimate that the true number of plant Golgi GTs might be one-third above those currently annotated. Other newly identified proteins are likely to be involved in the transport and interconversion of nucleotide sugar substrates as well as polysaccharide and protein modification.

Ultra wide-band localization and SLAM: a comparative study for mobile robot navigation.

In this work, a comparative study between an Ultra Wide-Band (UWB) localization system and a Simultaneous Localization and Mapping (SLAM) algorithm is presented. Due to its high bandwidth and short pulses length, UWB potentially allows great accuracy in range measurements based on Time of Arrival (TOA) estimation. SLAM algorithms recursively estimates the map of an environment and the pose (position and orientation) of a mobile robot within that environment. The comparative study presented here involves the performance analysis of implementing in parallel an UWB localization based system and a SLAM algorithm on a mobile robot navigating within an environment. Real time results as well as error analysis are also shown in this work.

Absence of branches from xylan in Arabidopsis gux mutants reveals potential for simplification of lignocellulosic biomass.

As one of the most abundant polysaccharides on Earth, xylan will provide more than a third of the sugars for lignocellulosic biofuel production when using grass or hardwood feedstocks. Xylan is characterized by a linear ß(1,4)-linked backbone of xylosyl residues substituted by glucuronic acid, 4-O-methylglucuronic acid or arabinose, depending on plant species and cell types. The biological role of these decorations is unclear, but they have a major influence on the properties of the polysaccharide. Despite the recent isolation of several mutants with reduced backbone, the mechanisms of xylan synthesis and substitution are unclear. We identified two Golgi-localized putative glycosyltransferases, GlucUronic acid substitution of Xylan (GUX)-1 and GUX2 that are required for the addition of both glucuronic acid and 4-O-methylglucuronic acid branches to xylan in Arabidopsis stem cell walls. The gux1 gux2 double mutants show loss of xylan glucuronyltransferase activity and lack almost all detectable xylan substitution. Unexpectedly, they show no change in xylan backbone quantity, indicating that backbone synthesis and substitution can be uncoupled. Although the stems are weakened, the xylem vessels are not collapsed, and the plants grow to normal size. The xylan in these plants shows improved extractability from the cell wall, is composed of a single monosaccharide, and requires fewer enzymes for complete hydrolysis. These findings have implications for our understanding of the synthesis and function of xylan in plants. The results also demonstrate the potential for manipulating and simplifying the structure of xylan to improve the properties of lignocellulose for bioenergy and other uses.

Proteomic complex detection using sedimentation (ProCoDeS): screening for proteins in stable complexes and their candidate interaction partners.

Over the last few years, our view of cellular organization has changed from one in which enzymes and proteins usually act independently to the situation at present where we commonly accept that many, if not all, enzymes act in close association with others. Co-precipitation using an antibody against a test protein is the standard assay for the identification of members of protein complexes [Musso, Zhang and Emili (2007) Chem. Rev. 107, 3585-3600]. The introduction of TAP (tandem affinity purification) tagging enhanced original approaches in order to analyse protein complexes on a larger scale with reduced false discoveries of interacting partners due to more efficient purification of complexes. However, this technique has some limitations as a high-throughput tool for systems biology: the requirement for genetic manipulation to express the tagged protein excludes studies of non-transformable organisms and intact tissue. In those cases where TAP is applicable, a considerable amount of work is required to generate the baits and to optimize experimental conditions. A technique developed in our laboratories, ProCoDeS (Proteomic Complex Detection using Sedimentation), focuses on the detection of endogenous complexes. Protein samples are separated by centrifugation and then different fractions from the resulting gradient are analysed using quantitative MS. The identification of possible protein partners is based on statistical analysis of the co-fractionation of proteins, without any need for purification of individual complexes. The prospects of ProCoDeS and similar techniques based on quantitative MS for measurement of protein complex composition are reviewed in the present article.

Hernia estrangulada. ¿Todavía mortal en el siglo XXI? / Strangulated hernia. Still fatal in the XXI century?

Introducción. El conocimiento de los factores que predisponen a la aparición de complicaciones tras cirugía herniaria urgente es de gran importancia tanto para la priorización de la cirugía electiva como para seleccionar los casos que pueden ser susceptibles de seguimiento clínico. Objetivos. Analizar los factores que condicionan la morbilidad y la mortalidad de la resección intestinal asociada a la reparación herniaria urgente. Pacientes y método. Revisión retrospectiva de las historias clínicas de los pacientes intervenidos urgentemente por afección herniaria desde enero de 2000 hasta diciembre de 2005. Se compararon los resultados obtenidos en función de si fue o no necesaria una resección intestinal. Resultados. De un total de 2.367 pacientes intervenidos por hernias en ese período, en 362 (15,3%; media de edad, 69,5 años; 146 varones y 216 mujeres) fue de forma urgente. Precisaron resección intestinal 60 (16,6%). Presentaron complicaciones 108 (29,8%) y 17 (4,7%) fallecieron tras la intervención. El límite de 70 años discriminó una mortalidad significativamente mayor (el 7 frente al 2%, entre mayores y menores de 70 años, respectivamente; p = 0,01). El grupo de pacientes que precisó resección intestinal tenía una media de edad mayor (75,4 frente a 68,3 años; p = 0,002), más prevalencia de complicaciones totales (el 40,7 frente al 6,2%; p < 0,0001) y una mortalidad significativamente mayor (el 20 frente al 1,6%; p < 0,0001). El análisis de discriminación identificó la resección intestinal como variable independiente predictiva de mortalidad (l de Wilks = 0,89; p = 0,0001; valor predictivo del 85%). Conclusiones. La morbilidad y la mortalidad de la cirugía herniaria urgente que precisa resección intestinal son muy elevadas, especialmente en pacientes de edad avanzada y cuando se trata de hernias crurales (AU)

Introduction. Knowledge of the risk factors that may lead to complications after emergency hernia repair is of great importance, as much for the prioritisation of the elective surgery, as selecting those cases that require clinical follow up. Objectives. To analyse the factors conditioning the morbidity and mortality of bowel resection associated to emergency hernia repair. Patients and method. A retrospective review was carried out on the clinical histories of patients who had emergency operations for hernia problems from January 2000 to December of 2005. The clinical results obtained were compared based on whether or not a bowel resection was required. Results. A total of 2367 patients were operated for hernia in this period, 362 of them (15.3%); for a complicated hernia (mean age 69.5 years; 146 males/216 females); 60 patients needed bowel resection. Complications appeared in 108 patients (29.8%) and 17 (4.7%) died after operation. The limit of 70 years discriminated a significantly greater mortality (> 70: 7% vs < 70 2%; p = 0.01).The group of patients who needed bowel resection showed differences in statistical analysis both in age (75.4 vs 68.3 years; p = 0.002), prevalence of complications (40.7% vs 6.2%; p < 0.0001), and mortality (20% vs 1.6%; p < 0.0001). The discriminant analysis identified bowel resection as the only predictive independent variable of mortality (l Wilks = 0.89; p = 0.0001; predictive value, 85%). Conclusions. Morbidity and the mortality of urgent hernia surgery, when bowel resection was required, are elevated; especially in older patients, and in crural hernias (AU)

[Strangulated hernia. Still fatal in the XXI century?]. / Hernia estrangulada. Todavía mortal en el siglo XXI?

INTRODUCTION: Knowledge of the risk factors that may lead to complications after emergency hernia repair is of great importance, as much for the prioritisation of the elective surgery, as selecting those cases that require clinical follow up. OBJECTIVES: To analyse the factors conditioning the morbidity and mortality of bowel resection associated to emergency hernia repair. PATIENTS AND METHOD: A retrospective review was carried out on the clinical histories of patients who had emergency operations for hernia problems from January 2000 to December of 2005. The clinical results obtained were compared based on whether or not a bowel resection was required. RESULTS: A total of 2367 patients were operated for hernia in this period, 362 of them (15.3%); for a complicated hernia (mean age 69.5 years; 146 males/216 females); 60 patients needed bowel resection. Complications appeared in 108 patients (29.8%) and 17 (4.7%) died after operation. The limit of 70 years discriminated a significantly greater mortality (> 70: 7% vs < 70 2%; p = 0.01). The group of patients who needed bowel resection showed differences in statistical analysis both in age (75.4 vs 68.3 years; p = 0.002), prevalence of complications (40.7% vs 6.2%; p < 0.0001), and mortality (20% vs 1.6%; p < 0.0001). The discriminant analysis identified bowel resection as the only predictive independent variable of mortality (lambda Wilks = 0.89; p = 0.0001; predictive value, 85%). CONCLUSIONS: Morbidity and the mortality of urgent hernia surgery, when bowel resection was required, are elevated; especially in older patients, and in crural hernias.