Study, measurement and mitigation of radon activity concentration in the School of Computer Science ofA Coruñain the North West of Spain.

A study of the radon activity concentration was carried out at the School of Computer Science of 'Universidade da Coruña' (UDC, Spain). For this purpose, building location, the type of soil and the construction materials were analysed. Subsequently, the radon activity concentration was determined using two different techniques: measurement in situ with an on-site ionization chamber detector (short term) and measurement with trace detectors (long term). Based on the results obtained, and according with the Spanish Law (Spanish Official Bulletin-Boletín Oficial del Estado, of 21 December 2011, IS-33 Instruction), corrective works were performed, consisting on the installation of a forced ventilation system underneath the extent of the suspended floor in order to mitigate the high radon specific activity in the building. Four months and 3 years after the works, new measurements were carried out in order to verify the effectiveness of the new ventilation system, obtaining a decrease of the radon gas values ranging between 87% and 90%, which confirmed long term effectivity.

Automated early detection of drops in commercial egg production using neural networks.

1. The purpose of this work was to support decision-making in poultry farms by performing automatic early detection of anomalies in egg production. 2. Unprocessed data were collected from a commercial egg farm on a daily basis over 7 years. Records from a total of 24 flocks, each with approximately 20 000 laying hens, were studied. 3. Other similar works have required a prior feature extraction by a poultry expert, and this method is dependent on time and expert knowledge. 4. The present approach reduces the dependency on time and expert knowledge because of the automatic selection of relevant features and the use of artificial neural networks capable of cost-sensitive learning. 5. The optimum configuration of features and parameters in the proposed model was evaluated on unseen test data obtained by a repeated cross-validation technique. 6. The accuracy, sensitivity, specificity and positive predictive value are presented and discussed at 5 forecasting intervals. The accuracy of the proposed model was 0.9896 for the day before a problem occurs.

Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.

OBJECTIVE: To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements. METHODS: This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR. CONCLUSION: Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Parallel Computing for Brain Simulation.

BACKGROUND: The human brain is the most complex system in the known universe, it is therefore one of the greatest mysteries. It provides human beings with extraordinary abilities. However, until now it has not been understood yet how and why most of these abilities are produced. AIMS: For decades, researchers have been trying to make computers reproduce these abilities, focusing on both understanding the nervous system and, on processing data in a more efficient way than before. Their aim is to make computers process information similarly to the brain. Important technological developments and vast multidisciplinary projects have allowed creating the first simulation with a number of neurons similar to that of a human brain. CONCLUSION: This paper presents an up-to-date review about the main research projects that are trying to simulate and/or emulate the human brain. They employ different types of computational models using parallel computing: digital models, analog models and hybrid models. This review includes the current applications of these works, as well as future trends. It is focused on various works that look for advanced progress in Neuroscience and still others which seek new discoveries in Computer Science (neuromorphic hardware, machine learning techniques). Their most outstanding characteristics are summarized and the latest advances and future plans are presented. In addition, this review points out the importance of considering not only neurons: Computational models of the brain should also include glial cells, given the proven importance of astrocytes in information processing.

The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: Adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor.

Preclinical studies support a critical role of 5-HT4 receptors (5-HT4Rs) in depression and anxiety, but their influence in depression- and anxiety-like behaviours and the effects of antidepressants remain partly unknown. We evaluated 5-HT4R knockout (KO) mice in different anxiety and depression paradigms and mRNA expression of some neuroplasticity markers (BDNF, trkB and Arc) and the functionality of 5-HT1AR. Moreover, the implication of 5-HT4Rs in the behavioural and molecular effects of chronically administered fluoxetine was assessed in naïve and olfactory bulbectomized mice (OBX) of both genotypes. 5-HT4R KO mice displayed few specific behavioural impairments including reduced central activity in the open-field (anxiety), and decreased sucrose consumption and nesting behaviour (anhedonia). In these mice, we measured increased levels of BDNF and Arc mRNA and reduced levels of trkB mRNA in the hippocampus, and a desensitization of 5-HT1A autoreceptors. Chronic administration of fluoxetine elicited similar behavioural effects in WT and 5-HT4R KO mice on anxiety-and depression-related tests. Following OBX, locomotor hyperactivity and anxiety were similar in both genotypes. Interestingly, chronic fluoxetine failed to reverse this OBX-induced syndrome in 5-HT4R KO mice, a response associated with differential effects in hippocampal neuroplasticity biomarkers. Fluoxetine reduced hippocampal Arc and BDNF mRNA expressions in WT but not 5-HT4R KO mice subjected to OBX. These results demonstrate that the absence of 5-HT4Rs triggers adaptive changes that could maintain emotional states, and that the behavioural and molecular effects of fluoxetine under pathological depression appear to be critically dependent on 5-HT4Rs.

Flour from Prosopis alba cotyledons: A natural source of nutrient and bioactive phytochemicals.

The Prosopis alba seed is a waste material in the process to produce pod flour. To suggest a potential use of these seeds it is necessary to determine the nutritional, phytochemical and functional quality of cotyledon flour from Prosopis alba. This flour showed high level of proteins (62%), low content of total carbohydrate and fat. Free polyphenol (1150±20mg GAE/100g flour) and carotenoids (10.55±0.05mg ß-CE/100g flour) compounds were the dominant compounds. The main identified constituents in the polyphenolic extracts were C- glycosyl flavones, including schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin. The extract enriched in polyphenolic compounds exhibited ABTS(+) reducing capacity and scavenging activity of H2O2; and was able to inhibit phospholipase, lipoxygenase and cyclooxygenase, three pro-inflammatory enzymes. According to our results, the P. alba cotyledon flour could be considered as a new alternative in the formulation of functional foods or food supplements.

Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration.

Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting the serotonin transporter (SERT). As a result, ~80% of patients show recurrent or chronic depression, resulting in a poor quality of life and increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used to evoke antidepressant-like responses in experimental animals. However, the main limitation for the medical use of RNAi is the extreme difficulty to deliver oligonucleotides to selected neurons/systems in the mammalian brain. Here we show that the intranasal administration of a sertraline-conjugated small interfering RNA (C-SERT-siRNA) silenced SERT expression/function and evoked fast antidepressant-like responses in mice. After crossing the permeable olfactory epithelium, the sertraline-conjugated-siRNA was internalized and transported to serotonin cell bodies by deep Rab-7-associated endomembrane vesicles. Seven-day C-SERT-siRNA evoked similar or more marked responses than 28-day fluoxetine treatment. Hence, C-SERT-siRNA (i) downregulated 5-HT1A-autoreceptors and facilitated forebrain serotonin neurotransmission, (ii) accelerated the proliferation of neuronal precursors and (iii) increased hippocampal complexity and plasticity. Further, short-term C-SERT-siRNA reversed depressive-like behaviors in corticosterone-treated mice. The present results show the feasibility of evoking antidepressant-like responses by selectively targeting neuronal populations with appropriate siRNA strategies, opening a way for further translational studies.

Evaluation of different bovine muscles to be applied in freeze-drying for instant meal. Study of physicochemical and senescence parameters.

The aim of the present research was to evaluate bovine muscles to be subjected to freeze-drying for an instant meal. Physicochemical and senescence parameters were evaluated. The experimental part was divided into two steps. In the first step, the Semitendinosus muscle was chosen to establish methodology and experimental conditions. Physicochemical, microstructure and senescence parameters were analysed. In the second step, economic bovine muscles such as Semimembranous and Spinalis dorsi were subjected to the same methodology and conditions as in the first step in order to compare them by analysing the same parameters. L* and a* values were statistically significant (P<0.05) for Semimembranous and Spinalis dorsi muscles, showing differences among condition effects and in muscles. Humidity and water activity showed among the muscles analysed that cooked and rehydrated samples did not exhibit differences. Microstructure of Semitendinosus and Semimembranous were not separated and fragmented as occurred with Spinalis dorsi after freeze-drying. Results allowed us to select among the muscles studied that Semimembranous was suitable and economic to be used in an instant meal.

Galanin activated Gi/o-proteins in human and rat central nervous systems.

The neuropeptide galanin (GAL) is involved in the control of hormone secretion, nociception, feeding behavior, attention, learning and memory. The anatomical localization of galanin receptors in the brain has been described using autoradiography and immunohistochemistry, but both techniques are limited by the availability of specific radioligands or antibodies. Functional autoradiography provides an alternative method by combining anatomical resolution and information of the activity mediated by G-protein coupled receptors. The present study analyzes the functional GAL receptors coupled to Gi/o-proteins in human and rat brain nuclei using [(35)S]GTPγS autoradiography. The results show the anatomical distribution of Gi/o-proteins activated by GAL receptors that trigger intracellular signaling mechanisms. The activity mediated by GAL receptors in human and rat brain showed a good correlation of the net stimulation in areas such as spinal cord, periaqueductal gray, putamen, CA3 layers of hippocampus, substantia nigra and diverse thalamic nuclei. The functional GAL receptors coupled to Gi/o-proteins showed a similar pattern for both species in most of the areas analyzed, but some discrete nuclei showed differences in the activity mediated by GAL, such as the ventroposteromedial thalamic nucleus, or areas that regulate learning and memory processes in the hippocampus. Taken into consideration the present results, the rat could be used as an experimental model for the study of the physiological role of GAL-mediated neurotransmission and the modulation of GAL receptors activity in the human CNS.

Three-year longitudinal population-based volumetric MRI study in first-episode schizophrenia spectrum patients.

BACKGROUND: Schizophrenia is a chronic brain disorder associated with structural brain abnormalities already present at the onset of the illness. Whether these brain abnormalities might progress over time is still under debate. METHOD: The aim of this study was to investigate likely progressive brain volume changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The study included 109 patients with a schizophrenia spectrum disorder and a control group of 76 healthy subjects. Subjects received detailed clinical and cognitive assessment and structural magnetic resonance imaging (MRI) at regular time points during a 3-year follow-up period. The effects of brain changes on cognitive and clinical variables were examined along with the impact of potential confounding factors. RESULTS: Overall, patients and healthy controls exhibited a similar pattern of brain volume changes. However, patients showed a significant lower progressive decrease in the volume of the caudate nucleus than control subjects (F 1,307.2 = 2.12, p = 0.035), with healthy subjects showing a greater reduction than patients during the follow-up period. Clinical and cognitive outcomes were not associated with progressive brain volume changes during the early years of the illness. CONCLUSIONS: Brain volume abnormalities that have been consistently observed at the onset of non-affective psychosis may not inevitably progress, at least over the first years of the illness. Taking together with clinical and cognitive longitudinal data, our findings, showing a lack of brain deterioration in a substantial number of individuals, suggest a less pessimistic and more reassuring perception of the illness.

Region-specific regulation of 5-HT1B receptors in the rat brain by chronic venlafaxine treatment.

RATIONALE: Venlafaxine is a non-selective serotonin and noradrenaline reuptake inhibitor antidepressant drug for which clinical studies have suggested a high level efficacy and a possible early action onset compared to the classical antidepressants. Its therapeutic effects might be due, at least in part, to adaptive changes in serotonergic neurotransmission, through the activation of the different 5-HT receptor subtypes. 5-HT(1B) receptors are located in the axon terminals of both serotonergic and non-serotonergic neurons, where they act as inhibitory autoreceptors or heteroreceptors, respectively. However, the information about the involvement of this subtype in the mechanism of action of antidepressants is limited and quite controversial. OBJECTIVES: The aim of this study was to evaluate the effect of venlafaxine (10 mg kg⁻¹ day⁻¹, p.o.) after 21 days of treatment on the density of 5-HT(1B) receptors and their functionality in rat brain. METHODS: Effects of chronic venlafaxine were evaluated at different levels of 5-HT(1B) receptor by using receptor autoradiography, [³5S]GTPγS binding, and the regulation of body temperature induced by selective 5-HT(1B) agonist. RESULTS: Our results show that venlafaxine induced an increase in sensitivity of 5-HT(1B) receptors in hypothalamus both at G-protein level and the control of core temperature without affecting the receptor density. CONCLUSIONS: These results demonstrate that adaptive changes on 5-HT(1B) receptors induced by chronic administration of venlafaxine exhibit regional differences suggesting that the hypothalamus might be an important site of drug action.

Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia.

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D(1) receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia. The animal could provide valuable insights into phenotypic aspects of this psychiatric disorder.

RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis.

Current antidepressants, which inhibit the serotonin transporter (SERT), display limited efficacy and slow onset of action. Here, we show that partial reduction of SERT expression by small interference RNA (SERT-siRNA) decreased immobility in the tail suspension test, displaying an antidepressant potential. Moreover, short-term SERT-siRNA treatment modified mouse brain variables considered to be key markers of antidepressant action: reduced expression and function of 5-HT(1A)-autoreceptors, elevated extracellular serotonin in forebrain and increased neurogenesis and expression of plasticity-related genes (BDNF, VEGF, Arc) in hippocampus. Remarkably, these effects occurred much earlier and were of greater magnitude than those evoked by long-term fluoxetine treatment. These findings highlight the critical role of SERT in serotonergic function and show that the reduction of SERT expression regulates serotonergic neurotransmission more potently than pharmacological blockade of SERT. The use of siRNA-targeting genes in serotonin neurons (SERT, 5-HT(1A)-autoreceptor) may be a novel therapeutic strategy to develop fast-acting antidepressants.

Hybrid model based on Genetic Algorithms and SVM applied to variable selection within fruit juice classification.

Given the background of the use of Neural Networks in problems of apple juice classification, this paper aim at implementing a newly developed method in the field of machine learning: the Support Vector Machines (SVM). Therefore, a hybrid model that combines genetic algorithms and support vector machines is suggested in such a way that, when using SVM as a fitness function of the Genetic Algorithm (GA), the most representative variables for a specific classification problem can be selected.

Nanoinformatics: developing new computing applications for nanomedicine.

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended "nanotype" to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

Data Integration in Genomic Medicine: Trends and Applications. Contribution of the IMIA Working Group on Informatics in Genomic Medicine.

OBJECTIVES: In a near future, each person will incorporate his/her own sequenced genome in his/her electronic health record. In that precise moment, genomic medicine will be fundamental for clinical practice, as an essential key of personalized medicine. All the genomic data, as well as other 'omics' and clinical data necessary for personalized medicine, are stored in several distributed databases. Research and patient care require each time more biomedical data integration of several distributed heterogeneous datasources. METHODS: This work develops a comprehensive review of the most relevant works in biomedical data integration, specifically in genomic medical data, analyzing the evolution of architecture and integration techniques during the last 20 years, and its usage. CONCLUSION: Most of these solutions, based on cross-linking, data warehouse or federated approaches, are suitable for specific domains. However, none of the models found in the literature is completely appropriate for a general biomedical data integration problem.

Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, ß-catenin and antidepressant-like effects.

BACKGROUND AND PURPOSE: 5-HT(2A) receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically. EXPERIMENTAL APPROACH: Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2'-deoxyuridine (BrdU) incorporation, and ß-catenin protein expression in different cellular fractions, as well as 5-HT(1A) receptor function were measured in the hippocampus of rats treated with fluoxetine, ketanserin and fluoxetine + ketanserin for 7 days, followed by a forced swimming test (FST) to analyse antidepressant efficacy. KEY RESULTS: mRNA for BDNF was increased in the CA3 field and dentate gyrus of the hippocampus by combined treatment with fluoxetine + ketanserin. Expression of ß-catenin was increased in total hippocampal homogenate and in the membrane fraction, but unchanged in the nuclear fraction after combined treatment with fluoxetine + ketanserin. These effects were paralleled by a decreased immobility time in the FST. There were no changes in BrdU incorporation, TrkB expression and 5-HT(1A) receptor function in any of the groups studied. CONCLUSIONS AND IMPLICATIONS: The antidepressant-like effect induced by subchronic co-treatment with a SSRI and a 5-HT(2A) receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane-associated ß-catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5-HT(1A) receptor desensitization in the dorsal raphe nucleus.

Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats.

BACKGROUND AND PURPOSE: The 5-HT(4) receptor may be a target for antidepressant drugs. Here we have examined the effects of the dual antidepressant, venlafaxine, on 5-HT(4) receptor-mediated signalling events. EXPERIMENTAL APPROACH: The effects of 21 days treatment (p.o.) with high (40 mg·kg(-1)) and low (10 mg·kg(-1)) doses of venlafaxine, were evaluated at different levels of 5-HT(4) receptor-mediated neurotransmission by using in situ hybridization, receptor autoradiography, adenylate cyclase assays and electrophysiological recordings in rat brain. The selective noradrenaline reuptake inhibitor, reboxetine (10 mg·kg(-1), 21 days) was also evaluated on 5-HT(4) receptor density. KEY RESULTS: Treatment with a high dose (40 mg·kg(-1)) of venlafaxine did not alter 5-HT(4) mRNA expression, but decreased the density of 5-HT(4) receptors in caudate-putamen (% reduction = 26 ± 6), hippocampus (% reduction = 39 ± 7 and 39 ± 8 for CA1 and CA3 respectively) and substantia nigra (% reduction = 49 ± 5). Zacopride-stimulated adenylate cyclase activation was unaltered following low-dose treatment (10 mg·kg(-1)) while it was attenuated in rats treated with 40 mg·kg(-1) of venlafaxine (% reduction = 51 ± 2). Furthermore, the amplitude of population spike in pyramidal cells of CA1 of hippocampus induced by zacopride was significantly attenuated in rats receiving either dose of venlafaxine. Chronic reboxetine did not modify 5-HT(4) receptor density. CONCLUSIONS AND IMPLICATIONS: Our data indicate a functional desensitization of 5-HT(4) receptors after chronic venlafaxine, similar to that observed after treatment with the classical selective inhibitors of 5-HT reuptake.

Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis.

ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in tissue remodeling and angiogenesis associated with physiological and pathological processes. To elucidate the in vivo functions of ADAMTS-12, we have generated a knockout mouse strain (Adamts12(-/-)) in which Adamts12 gene was deleted. The mutant mice had normal gestations and no apparent defects in growth, life span and fertility. By applying three different in vivo models of angiogenesis (malignant keratinocyte transplantation, Matrigel plug and aortic ring assays) to Adamts12(-/-) mice, we provide evidence for a protective effect of this host enzyme toward angiogenesis and cancer progression. In the absence of Adamts-12, both the angiogenic response and tumor invasion into host tissue were increased. Complementing results were obtained by using medium conditioned by cells overexpressing human ADAMTS-12, which inhibited vessel outgrowth in the aortic ring assay. This angioinhibitory effect of ADAMTS-12 was independent of its enzymatic activity as a mutated inactive form of the enzyme was similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay than the wild-type form. Altogether, our results show that ADAMTS-12 displays antiangiogenic properties and protect the host toward tumor progression.

3D entropy and moments prediction of enzyme classes and experimental-theoretic study of peptide fingerprints in Leishmania parasites.

The number of protein 3D structures without function annotation in Protein Data Bank (PDB) has been steadily increased. This fact has led in turn to an increment of demand for theoretical models to give a quick characterization of these proteins. In this work, we present a new and fast Markov chain model (MCM) to predict the enzyme classification (EC) number. We used both linear discriminant analysis (LDA) and/or artificial neural networks (ANN) in order to compare linear vs. non-linear classifiers. The LDA model found is very simple (three variables) and at the same time is able to predict the first EC number with an overall accuracy of 79% for a data set of 4755 proteins (859 enzymes and 3896 non-enzymes) divided into both training and external validation series. In addition, the best non-linear ANN model is notably more complex but has an overall accuracy of 98.85%. It is important to emphasize that this method may help us to predict not only new enzyme proteins but also to select peptide candidates found on the peptide mass fingerprints (PMFs) of new proteins that may improve enzyme activity. In order to illustrate the use of the model in this regard, we first report the 2D electrophoresis (2DE) and MADLI-TOF mass spectra characterization of the PMF of a new possible malate dehydrogenase sequence from Leishmania infantum. Next, we used the models to predict the contribution to a specific enzyme action of 30 peptides found in the PMF of the new protein. We implemented the present model in a server at portal Bio-AIMS (http://miaja.tic.udc.es/Bio-AIMS/EnzClassPred.php). This free on-line tool is based on PHP/HTML/Python and MARCH-INSIDE routines. This combined strategy may be used to identify and predict peptides of prokaryote and eukaryote parasites and their hosts as well as other superior organisms, which may be of interest in drug development or target identification.