Knowledge representation for product and processes development planning in collaborative environments

Efficiency in the management of integrated product and processes development is a basic requisite to guarantee competitiveness and success for manufacturing companies. This means that operational management of activities and human and material resources is extremely important, especially in virtual OKP (one-of-a-kind production) systems, and must cover related aspects of their capabilities and social character as well as assignment criteria. In this context, and to facilitate collaborative resources management, an ontology focused on resources and capabilities is proposed in this work. This ontology supports the necessary knowledge for generic and collaborative process planning, providing a shared common semantic for all the members of the virtual company. This work differs from other proposed ontologies in the area of process planning where the resources considered are all those elements that participate in the execution of the different activity types involved in this wide and complex process. The ontology directly covers the shared, social nature of the resources, the agentive behaviour of many of them and a characterisation of their capabilities, thus providing specific solutions to the needs of the collaborative integrated development of products, processes and resources (CIDP2R) process.This work has been possible thanks to funding received from the Ministry of Science and Education through the COAPP Research Project - reference DPI2007-66871-C02-01/02.Solano García, L.; Rosado Castellano, P.; Romero Subirón, F. (2014). Knowledge representation for product and processes development planning in collaborative environments. International Journal of Computer Integrated Manufacturing. 27(8):787-801. doi:10.1080/0951192X.2013.834480S78780127

Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform

The dynamics and coordination between autophagy machinery and selective receptors during mitophagy are unknown. Also unknown is whether mitophagy depends on pre-existing membranes or is triggered on the surface of damaged mitochondria. Using a ubiquitin-dependent mitophagy inducer, the lactone ivermectin, we have combined genetic and imaging experiments to address these questions. Ubiquitination of mitochondrial fragments is required the earliest, followed by auto-phosphorylation of TBK1. Next, early essential autophagy proteins FIP200 and ATG13 act at different steps, whereas ULK1 and ULK2 are dispensable. Receptors act temporally and mechanistically upstream of ATG13 but downstream of FIP200. The VPS34 complex functions at the omegasome step. ATG13 and optineurin target mitochondria in a discontinuous oscillatory way, suggesting multiple initiation events. Targeted ubiquitinated mitochondria are cradled by endoplasmic reticulum (ER) strands even without functional autophagy machinery and mitophagy adaptors. We propose that damaged mitochondria are ubiquitinated and dynamically encased in ER strands, providing platforms for formation of the mitophagosomes

Incorporation of the Arc1p tRNA-binding domain to the catalytic core of MetRS can functionally replace the yeast Arc1p-MetRS complex

The catalytic core of methionyl-tRNA synthetase (MetRS) is conserved among all life kingdoms but, depending on species origin, is often linked to noncatalytic domains appended to its N- or C-terminus. These domains usually contribute to protein-protein or protein-tRNA interactions but their exact biological role and evolutionary purpose is poorly understood. Yeast MetRS contains an N-terminal appendix that mediates its interaction with the N-terminal part of Arc1p. Association with Arc1p controls the subcellular distribution of MetRS. Furthermore, the C-terminal part of Arc1p harbors a conserved tRNA-binding domain (TRBD) required for the Arc1p-dependent stimulation of the catalytic activity of MetRS. The same TRBD is found directly fused to catalytic domains of plant and nematode MetRS as well as human tyrosyl-tRNA synthetase. To investigate the purpose of Arc1p-MetRS complex formation in yeast, we tested the ability of TRBD to assist the function of MetRS independently of Arc1p. We attached the TRBD directly to the C-terminus of the MetRS catalytic core (MC) by constructing the chimeric protein MC-TRBD. The effect of MC-TRBD expression on yeast cell growth as well as its localization and in vitro aminoacylation activity were analyzed and compared to that of MC alone or wild-type MetRS, both in the absence or presence of Arc1p. We show that MC-TRBD exhibits improved enzymatic activity and can effectively substitute the MetRS-Arc1p binary complex in vivo. Moreover, MC-TRBD, being exclusively cytoplasmic, also mimics the MetRS-Arc1p complex in terms of subcellular localization. Our results suggest that the sole role of the N-terminal appended domain of yeast MetRS is to mediate the indirect association with the TRBD, which, nevertheless, can also function effectively in vivo when directly fused to the catalytic MetRS core. (C) 2008 Elsevier Ltd. All rights reserved

Cardiovascular disease in childhood: The role of obesity

In recent years, childhood obesity is becoming an epidemic health problem. It is now evident from many studies that childhood obesity is correlated with adult excess weight status and the development of risk factors for cardiovascular diseases in adulthood, including hypertension, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. The exposure to obesity and to the above risk factors during childhood subsequently lead to atherosclerotic development, such as altered vascular structure and function, although the mechanisms are still unclear. Several non-invasive, and thus easy-to-obtain measures of arterial structure and function, have been shown to be clinically useful in providing information about vasculature early in the course of atherosclerosis, including measurement of endothelial function, carotid intima media thickness, and arterial stiffness. The early detection of cardiovascular abnormalities is essential because the control of the atherogenic process is more effective during its early stages. The present review focuses on the cardiovascular consequences of obesity, on the mechanisms and the methods of measurement of endothelial dysfunction in obese children and adolescents, and on the ways of intervention for the improvement of vascular health. © 2013 Springer-Verlag Berlin Heidelberg

Key parameters and practices controlling pesticide degradation efficiency of biobed substrates

We studied the contribution of each of the components of a compost-based biomixture (BX), commonly used in Europe, on pesticide degradation. The impact of other key parameters including pesticide dose, temperature and repeated applications on the degradation of eight pesticides, applied as a mixture, in a BX and a peat-based biomixture (OBX) was compared and contrasted to their degradation in soil. Incubation studies showed that straw was essential in maintaining a high pesticide degradation capacity of the biomixture, whereas compost, when mixed with soil, retarded pesticide degradation. The highest rates of degradation were shown in the biomixture composed of soil/compost/straw suggesting that all three components are essential for maximum biobed performance. Increasing doses prolonged the persistence of most pesticides with biomixtures showing a higher tolerance to high pesticide dose levels compared to soil. Increasing the incubation temperature from 15 degrees C to 25 degrees C resulted in lower t(1/2) values, with biomixtures performing better than soil at the lower temperature. Repeated applications led to a decrease in the degradation rates of most pesticides in all the substrates, with the exception of iprodione and metalaxyl. Overall, our results stress the ability of biomixtures to perform better than soil under unfavorable conditions and extreme pesticide dose levels

Management of coronary artery aneurysms using abciximab in children with Kawasaki disease

Introduction There are limited data regarding the possible benefits of abciximab in children with Kawasaki disease (KD), who developed serious cardiac abnormalities non-responsive to standard treatment. Materials and methods We retrospectively identified children with KD who were treated with abciximab from 2007 to 2015. Data regarding clinical course, treatment, echocardiographic data and follow-up at 1 and 6 months were retrieved. Results During the study period, fifteen children were identified who were diagnosed with KD and were given abciximab. The median age at onset of symptoms was 11 months (range: 2 months-6 years). The median day of disease at admission was 10 days (range: 4-26 days) and the median day of administration of abciximab was 17 days (range: 9-40). Twelve children were diagnosed with complete and three with incomplete KD. Aneurysms were found in 8 children: 2 had ectatic coronary arteries and 5 presented with both ectasia and aneurysms. At 1 month follow-up, echocardiographic findings showed regression in the size of aneurysms in 11 children, resolution of the aneurysms or ectasia of coronary arteries in 3 children, while one child who could not take aspirin because of G6PD deficiency died. After 6 months of follow-up, echocardiographic findings showed resolution of coronary abnormalities in 12 (80%) children, whereas 2 children (13.3%) presented with significant regression of aneurysms. Conclusions Abciximab may have an important role in the management of severe cardiac complications of KD, although prospective randomized controlled studies are needed to fully evaluate its role. © 2016 Published by Elsevier Ireland Ltd

Quantitative and qualitative differences in the metabolism of pesticides in biobed substrates and soil

Biobed substrates commonly exhibit high degradation capacity. However, degradation does not always lead to detoxification and information on the metabolic pathways of pesticides in biobeds is scarce. We studied the degradation and metabolism of three pesticides in selected biomixtures and soil. Biomixtures stimulated degradation of terbuthylazine and metribuzin, whereas chlorpyrifos degraded faster in soil. The latter was attributed to the lipophilicity of chlorpyrifos which increased adsorption and limited biodegradation in organic-rich biomixtures. Although the same metabolites were detected in all substrates, qualitative and quantitative differences in the metabolic routes of pesticides in the various substrates were observed. Chlorpyrifos was hydrolyzed to 3,5,6-tricholorpyridinol (TCP) which was further degraded only in compost-biomixture CBX1. Metabolism of terbuthylazine in compost biomixtures (BX) and soil resulted in the formation of desethyl-terbuthylazine (DES) which was fully degraded only in the compost-biomixture CBX2, whereas peat-based biomixture (OBX) promoted the hydroxylation of terbuthylazine. Desamino- (DA) (dominant) and diketo- (DK) metribuzin appear as intermediate metabolites in all substrates and were further transformed to desamino-diketo-metribuzin (DADK) which was fully degraded only in compost-biomixture GSBX. Overall, lower amounts of metabolites were accumulated in biomixtures compared to soil stressing the higher depuration efficiency of biobeds. (C) 2013 Elsevier Ltd. All rights reserved

Microscopic polyangiitis and Kawasaki disease without overt clinical cardiovascular manifestations and with abnormal cardiovascular magnetic resonance findings

Abnormal cardiovascular magnetic resonance findings were found in a patient with microscopic polyangiitis and a patient with Kawasaki disease that presented without overt clinical cardiovascular manifestations. © 2008 Elsevier Ireland Ltd. All rights reserved

Molecular determinants of the yeast Arc1p - Aminoacyl-tRNA synthetase complex assembly

Eukaryotic aminoacyl-tRNA synthetases are usually organized into high-molecular-weight complexes, the structure and function of which are poorly understood. We have previously described a yeast complex containing two aminoacyl-tRNA synthetases, methionyl-tRNA synthetase and glutamyl-tRNA synthetase, and one noncatalytic protein, Arc1p, which can stimulate the catalytic efficiency of the two synthetases. To understand the complex assembly mechanism and its relevance to the function of its components, we have generated specific mutations in residues predicted by a recent structural model to be located at the interaction interfaces of the N-terminal domains of all three proteins. Recombinant wild-type or mutant forms of the proteins, as well as the isolated N-terminal domains of the two synthetases, were overexpressed in bacteria, purified and used for complex formation in vitro and for determination of binding affinities using surface plasmon resonance. Moreover, mutant proteins were expressed as PtA or green fluorescent protein fusion polypeptides in yeast strains lacking the endogenous proteins in order to monitor in vivo complex assembly and their subcellular localization. Our results show that the assembly of the Arc1p-synthetase complex is mediated exclusively by the N-terminal domains of the synthetases and that the two enzymes bind to largely independent sites on Arc1p. Analysis of single-amino-acid substitutions identified residues that are directly involved in the formation of the complex in yeast cells and suggested that complex assembly is mediated predominantly by van der Waals and hydrophobic interactions, rather than by electrostatic forces. Furthermore, mutations that abolish the interaction of methionyl-tRNA synthetase with Arc1p cause entry of the enzyme into the nucleus, proving that complex association regulates its subcellular distribution. The relevance of these findings to the evolution and function of the multienzyme complexes of eukaryotic aminoacyl-tRNA synthetases is discussed. (C) 2007 Elsevier Ltd. All rights reserved