273 research outputs found

    Site directed mutagenesis as a tool to understand the catalytic mechanism of human cytidine deaminase.

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    Cytidine deaminase (CDA), is one of the enzymes involved in the pyrimidine salvage pathways, which catalyzes the formation of uridine and deoxyuridine by the hydrolytic deamination of cytidine and deoxycytidine, respectively. Human CDA is a tetrameric enzyme of identical 15 kDa subunits, each containing an essential zinc atom in the active site. The substrate binds to each active site independently and the cooperativity between subunits has not been reported. CDA is able to recognize as substrates some antitumor and antiviral cytidine analogs rendering them pharmacologically inactive. In light of the role played by this enzyme, a deep knowledge of CDA active site and mechanism of catalysis is required. Site-directed mutagenesis, associated with molecular modeling studies, may be an important tool to discover the active site structure of an enzyme and consequently its mechanism of action. In this review are summarized the site-directed mutagenesis experiments performed on human CDA: through these studies it was possible to understand the role exerted by specific amino acid residues in CDA active site and in the contacts between subunits. The obtained results may open a way for designing new cytidine based drugs or more potent CDA inhibitors

    miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

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    MicroRNAs (miRNAs) are small, non-coding RNAs about 22 nucleotides in length that regulate the expression of target genes post-transcriptionally, and are highly involved in cancer progression. They are able to impact a variety of cell processes such as proliferation, apoptosis and differentiation and can consequently control tumor initiation, tumor progression and metastasis formation. miRNAs can regulate, at the same time, metabolic gene expression which, in turn, influences relevant traits of malignancy such as cell adhesion, migration and invasion. Since the interaction between metabolism and adhesion or cell movement has not, to date, been well understood, in this review, we will specifically focus on miRNA alterations that can interfere with some metabolic processes leading to the modulation of cancer cell movement. In addition, we will analyze the signaling pathways connecting metabolism and adhesion/migration, alterations that often affect cancer cell dissemination and metastasis formation

    Pengaruh Komposisi Media Terhadap Pertumbuhan Kalus Dan Kadar Tannin Dari Daun Jati Belanda (Guazuma Ulmifolia Lamk) Secara in Vitro

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    West Indian Elm ( Guazuma ulmifolia Lamk.) is one of potentialplant producing tannin which is useful for controlling obesity. Tannin canbe produced through in vitro and this compound could be increased bycalli culture. The medium composition for calli induction was necessary toproduce the optimal calli. The aim of this research was to obtain themedium composition for calli induction through in vitro. Young leaves ofWest Indian Elm from glass house were used as explants. Murashige andSkoog (MS) medium enriched with B vitamin group was used as basicmedium. The experiments were arranged in completely randomized designin factorial pattern with ten replications. For calli induction, variousconcentration of 2,4-D (0.1; 0.3; and 0.5 mg/l) and its combination withBenzyl Adenin of 0.1 and 0.3 mg/l were used as treatments. Parametersobserved were calli diameter, structure, colour, fresh weight andperformance during culture. Analysis of tannin was conducted by usingdried samples both (in vitro and leaves from glass house) and thenextracted. The result showed that there was interaction between 2,4-D 0.3mg/l and Benzyl Adenin 0.1 mg/l on calli diameter (28.7 mm), the biggestcalli diameter after sub culture (31.9 mm), and fresh calli weight (5.02 g)eight weeks after treatments. Tannin content obtained from all of the invitro treatments (3.72 – 4.27%) was higher than tannin from leaves(2.24%)

    VENTILAÇÃO CONTROLADA COM PRESSÃO EXPIRATÓRIA FINAL POSITIVA EM SUÍNOS ANESTESIADOS COM ISOFLURANO OU HALOTANO E SUBMETIDOS A PNEUMOPERITÔNIO OU PNEUMOTÓRAX COM CO2

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    A homeostase hemodinâmica e respiratória nas vídeo cirurgias onde se emprega insuflação abdominal ou torácica requer métodos especiais de ventilação como a pressão expiratória final positiva (PEEP). Este experimento teve por objetivo avaliar a hemodinâmica e a oxigenação de suínos submetidos anestesia geral com isoflurano ou halotano onde foi realizado pneumoperitôneo a uma pressão constante de 15 mmHg ou pneumotórax de 5 mmHg com CO2 e ventilados com pressão expiratória zero ou 10 cm de H2O. Foram estudadas as variáveis pressão arterial (sistólica, média e diastólica), freqüência cardíaca e respiratória, saturação de oxigênio na hemoglobina (SpO2), volume corrente e minuto, eletrocardiografia e ainda pressão parcial de dióxido de carbono expirado. Onde foram observados valores de SpO2 mais elevados nos grupos submetidos a PEEP e maior hipotensão nos suínos anestesiados com halotano, nos permitindo concluir que quando comparado com o grupo que recebeu pressão expiratória final zero o uso de 10 cm de água de PEEP melhora a SpO2 e o isoflurano é superior ao halotano na manutenção da função cardiovascular de suínos submetidos à insuflação intra-abdominal ou intratorácica com CO2. Controlled ventilation with Positive End-Expiratory Pressure in isoflurane or halotane anesthetized pigs submitted to pneumoperitoneum or pneumothorax with CO2 Abstract Hemodynamic and respiratory homeostasy in the video surgeries need special ventilatory methods as positive end-expiratory pressure (PEEP). This study aimed to investigate the hemodynamic and oxygenation effects in isoflurane or halotane anesthetized pigs, submitted to constant 15 mm Hg CO2 abdominal pressure or 5 mm Hg CO2 intrathoracic pressure of 10 cm of H2O of PEEP or 0 cm of H2O (ZEEP). Variables studied were arterial pressure (systolic, diastolic and mean) heart rate, respiratory rate, SpO2, tidal volume, minute volume, electrocardiogram and expiratory end-tidal carbon dioxide. Were observed improved in SpO2 with 10 cm of H2O PEEP and more hypotension in the halotane anesthetized group. We conclude that when compared to ZEEP group, 10 cm of H2O PEEP ventilation improves SPO2, while isoflurane is better to maintain the cardiovascular function to anesthetized pigs submitted to 15 mm Hg intra-abdominal and 5 mm Hg intratoracic pressure insufflations with CO2

    Design of a modular Autonomous Underwater Vehicle for archaeological investigations

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    MARTA (MARine Tool for Archaeology) is a modular AUV (Autonomous Underwater Vehicle) designed and developed by the University of Florence in the framework of the ARROWS (ARchaeological RObot systems for the World's Seas) FP7 European project. The ARROWS project challenge is to provide the underwater archaeologists with technological tools for cost affordable campaigns: i.e. ARROWS adapts and develops low cost AUV technologies to significantly reduce the cost of archaeological operations, covering the full extent of an archaeological campaign (underwater mapping, diagnosis and cleaning tasks). The tools and methodologies developed within ARROWS comply with the "Annex" of the 2001 UNESCO Convention for the protection of Underwater Cultural Heritage (UCH). The system effectiveness and MARTA performance will be demonstrated in two scenarios, different as regards the environment and the historical context, the Mediterranean Sea (Egadi Islands) and the Baltic Sea

    Global food security and food riots – an agent-based modelling approach

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    Due to negative consequences of climate change for agriculture and food production shocks affecting different areas of the world, the past two decades saw the conditions of global food security increasingly worsen. This has resulted in negative consequences for the world economy, partly causing international food price spikes and social upheavals. In this paper we present statistical findings along with a preliminary version of an original agent-based model called the Dawe Global Security Model that simulates the global food market and the political fragility of countries. The model simulates the effects of food insecurity on international food prices and how these, coupled with national political fragility and international food trade can, in turn, increase the probability of food riots in countries. The agents in the model are the 213 countries of the world whose characteristics reflect empirical data and the international trade of food is also simulated based on real trade partnerships and data. The model has been informed, calibrated and validated using real data and the results of these procedures are presented in the paper. To further test the model we also present the model’s forecasts for the near future in terms of food prices and incidence of food riots. The Dawe Global Security Model can be used to test scenarios on the evolution of shocks to global food production and analyse consequences for food riots. Further developments of the model can include national responses to food crises to investigate how countries can influence the spread of global food crises

    Prediction of arterial pressure increase after fluid challenge

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    <p>Abstract</p> <p>Background</p> <p>Mean arterial pressure above 65 mmHg is recommended for critically ill hypotensive patients whereas they do not benefit from supranormal cardiac output values. In this study we investigated if the increase of mean arterial pressure after volume expansion could be predicted by cardiovascular and renal variables. This is a relevant topic because unnecessary positive fluid balance increases mortality, organ dysfunction and Intensive Care Unit length of stay.</p> <p>Methods</p> <p>Thirty-six hypotensive patients (mean arterial pressure < 65 mmH) received a fluid challenge with hydroxyethyl starch. Patients were excluded if they had active bleeding and/or required changes in vasoactive agents infusion rate in the previous 30 minutes. Responders were defined by the increase of mean arterial pressure value to over 65 mmHg or by more than 20% with respect to the value recorded before fluid challenge. Measurements were performed before and at one hour after the end of fluid challenge.</p> <p>Results</p> <p>Twenty-two patients (61%) increased arterial pressure after volume expansion. Baseline heart rate, arterial pressure, central venous pressure, central venous saturation, central venous to arterial PCO<sub>2 </sub>difference, lactate, urinary output, fractional excretion of sodium and urinary sodium/potassium ratio were similar between responder and non-responder. Only 7 out of 36 patients had valuable dynamic indices and then we excluded them from analysis. When the variables were tested as predictors of responders, they showed values of areas under the ROC curve ranging between 0.502 and 0.604. Logistic regression did not reveal any association between variables and responder definition.</p> <p>Conclusions</p> <p>Fluid challenge did not improve arterial pressure in about one third of hypotensive critically ill patients. Cardiovascular and renal variables did not enable us to predict the individual response to volume administration.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00721604">NCT00721604</a>.</p
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