979 resultados para METABOLIC END-PRODUCTS
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Mycotoxins are toxic secondary metabolites produced by filamentous fungi that occur naturally in agricultural commodities worldwide. Aflatoxins, ochratoxin A, patulin, fumonisins, zearalenone, trichothecenes and ergot alkaloids are presently the most important for food and feed safety. These compounds are produced by several species that belong to the Aspergillus, Penicillium, Fusarium and Claviceps genera and can be carcinogenic, mutagenic, teratogenic, cytotoxic, neurotoxic, nephrotoxic, estrogenic and immunosuppressant. Human and animal exposure to mycotoxins is generally assessed by taking into account data on the occurrence of mycotoxins in food and feed as well as data on the consumption patterns of the concerned population. This evaluation is crucial to support measures to reduce consumer exposure to mycotoxins. This work reviews the occurrence and levels of mycotoxins in Portuguese food and feed to provide a global overview of this issue in Portugal. With the information collected, the exposure of the Portuguese population to those mycotoxins is assessed, and the estimated dietary intakes are presented.
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Dissertação de mestrado em Engenharia de Telecomunicações e Informática
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Dissertação de mestrado em Biologia Molecular, Biotecnologia e Bioempreendedorismo em Plantas
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Dissertação de mestrado integrado em Engenharia Eletrónica Industrial e Computadores
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Dissertação de mestrado integrado em Engenharia e Gestão de Sistemas de Informação
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Dissertação de mestrado em Sustentabilidade do Ambiente Construído
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Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors.
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Kinetic models have a great potential for metabolic engineering applications. They can be used for testing which genetic and regulatory modifications can increase the production of metabolites of interest, while simultaneously monitoring other key functions of the host organism. This work presents a methodology for increasing productivity in biotechnological processes exploiting dynamic models. It uses multi-objective dynamic optimization to identify the combination of targets (enzymatic modifications) and the degree of up- or down-regulation that must be performed in order to optimize a set of pre-defined performance metrics subject to process constraints. The capabilities of the approach are demonstrated on a realistic and computationally challenging application: a large-scale metabolic model of Chinese Hamster Ovary cells (CHO), which are used for antibody production in a fed-batch process. The proposed methodology manages to provide a sustained and robust growth in CHO cells, increasing productivity while simultaneously increasing biomass production, product titer, and keeping the concentrations of lactate and ammonia at low values. The approach presented here can be used for optimizing metabolic models by finding the best combination of targets and their optimal level of up/down-regulation. Furthermore, it can accommodate additional trade-offs and constraints with great flexibility.
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Software product lines (SPL) are diverse systems that are developed using a dual engineering process: (a)family engineering defines the commonality and variability among all members of the SPL, and (b) application engineering derives specific products based on the common foundation combined with a variable selection of features. The number of derivable products in an SPL can thus be exponential in the number of features. This inherent complexity poses two main challenges when it comes to modelling: Firstly, the formalism used for modelling SPLs needs to be modular and scalable. Secondly, it should ensure that all products behave correctly by providing the ability to analyse and verify complex models efficiently. In this paper we propose to integrate an established modelling formalism (Petri nets) with the domain of software product line engineering. To this end we extend Petri nets to Feature Nets. While Petri nets provide a framework for formally modelling and verifying single software systems, Feature Nets offer the same sort of benefits for software product lines. We show how SPLs can be modelled in an incremental, modular fashion using Feature Nets, provide a Feature Nets variant that supports modelling dynamic SPLs, and propose an analysis method for SPL modelled as Feature Nets. By facilitating the construction of a single model that includes the various behaviours exhibited by the products in an SPL, we make a significant step towards efficient and practical quality assurance methods for software product lines.
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OBJECTIVE: To evaluate the biochemical and nutritional status of smokers in treatment for smoking cessation and its association with anthropometric parameters. METHODS: This is a cross-sectional study with convenience sample. Adult smokers were assessed at the start of treatment in the Interdisciplinary Center for Tobacco Research and Intervention of the University Hospital of the Federal University of Juiz de Fora (CIPIT/HU-UFJF). We evaluated the body mass index (BMI), conicity index (CI); waist circumference (WC), percentage of body fat (%BF), fasting glycemia, cortisol, insulin, total cholesterol (TC), LDL-c, HDL-c, triglycerides (TG) and metabolic syndrome (MS). RESULTS: Most participants (52.2%) had MS and high cardiovascular risk. The fasting glycemia was abnormal in 30.4%. There was a significant positive correlation between BMI and WC (r = 0.90; p = 0.0001), %BF (r = 0.79; p = 0.0001), CI (r = 0.65; p = 0.0001), glycemia (r = 0.42; p = 0.04) and TG (r = 0.47; p = 0.002). The CI presented positive correction with insulin (r = 0.60; p = 0.001), glycemia (r = 0.55; p = 0.007), TG (r = 0.54; p = 0.008) and %BF (r = 0.43; p = 0.004). Patients with longer duration of smoking had a higher risk of developing MS (OR = 9.6, p = 0.016). CONCLUSION: The smokers evaluated had increased risk for developing MS, especially those with longer duration of smoking, requiring urgent smoking cessation.
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Dissertação de mestrado integrado em Engenharia Civil
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DNA strand-breaks (SBs) with non-ligatable ends are generated by ionizing radiation, oxidative stress, various chemotherapeutic agents, and also as base excision repair (BER) intermediates. Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing activities. Two common dirty ends, 3'-P and 5'-OH, are processed by mammalian polynucleotide kinase 3'-phosphatase (PNKP), a bifunctional enzyme with 3'-phosphatase and 5'-kinase activities. We have made the unexpected observation that PNKP stably associates with Ataxin-3 (ATXN3), a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD). This disease is one of the most common dominantly inherited ataxias worldwide; the defect in SCA3 is due to CAG repeat expansion (from the normal 14-41 to 55-82 repeats) in the ATXN3 coding region. However, how the expanded form gains its toxic function is still not clearly understood. Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity. Furthermore, transgenic mice conditionally expressing the pathological form of human ATXN3 also showed decreased 3'-phosphatase activity of PNKP, mostly in the deep cerebellar nuclei, one of the most affected regions in MJD patients' brain. Finally, long amplicon quantitative PCR analysis of human MJD patients' brain samples showed a significant accumulation of DNA strand breaks. Our results thus indicate that the accumulation of DNA strand breaks due to functional deficiency of PNKP is etiologically linked to the pathogenesis of SCA3/MJD.
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Dissertação de mestrado em Direito dos Contratos e das Empresas
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[Excerpt] Academic spin-offs, technological ventures born inside Universities, have increasingly strengthen the connections between the scholarship and the economy, by fostering the role of technology transfer and knowledge commercialization. This presentation will outline the major steps in taking an idea or a technology to market, growing the venture and aiming at securing a successful exit. Also, it will present BCTechnologies (Bacterial Cellulose Technologies), a spin-off from the University of Minho (Portugal). (...)
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Genome-scale metabolic models are valuable tools in the metabolic engineering process, based on the ability of these models to integrate diverse sources of data to produce global predictions of organism behavior. At the most basic level, these models require only a genome sequence to construct, and once built, they may be used to predict essential genes, culture conditions, pathway utilization, and the modifications required to enhance a desired organism behavior. In this chapter, we address two key challenges associated with the reconstruction of metabolic models: (a) leveraging existing knowledge of microbiology, biochemistry, and available omics data to produce the best possible model; and (b) applying available tools and data to automate the reconstruction process. We consider these challenges as we progress through the model reconstruction process, beginning with genome assembly, and culminating in the integration of constraints to capture the impact of transcriptional regulation. We divide the reconstruction process into ten distinct steps: (1) genome assembly from sequenced reads; (2) automated structural and functional annotation; (3) phylogenetic tree-based curation of genome annotations; (4) assembly and standardization of biochemistry database; (5) genome-scale metabolic reconstruction; (6) generation of core metabolic model; (7) generation of biomass composition reaction; (8) completion of draft metabolic model; (9) curation of metabolic model; and (10) integration of regulatory constraints. Each of these ten steps is documented in detail.