Regulation of Phosphatidic Acid Levels in <Emphasis Type="Italic">Trypanosoma cruzi</Emphasis>

Lipid kinases and phosphatases play essential roles in signal transduction processes involved in cytoskeletal rearrangement, membrane trafficking, and cellular differentiation. Phosphatidic acid (PtdOH) is an important mediator lipid in eukaryotic cells, but little is known regarding its regulation in the parasite Trypanosoma cruzi, an agent of Chagas disease. In order to clarify the relationship between PtdOH metabolism and developmental stages of T. cruzi, epimastigotes in culture were subjected to hyperosmotic stress (~1,000 mOsm/L), mimicking the environment in the rectum of vector triatomine bugs. These experimental conditions resulted in differentiation to an intermediate form between epimastigotes and trypomastigotes. Morphological changes of epimastigotes were correlated with an increase in PtdOH mass accomplished by increased enzyme activity of diacylglycerol kinase (DAGK, E.C. 2.7.1.107) and concomitant decreased activity of phosphatidate phosphatases type 1 and type 2 (PAP1, PAP2, E.C. 3.1.3.4). Our results indicate progressive increases of PtdOH levels during the differentiation process, and suggest that the regulation of PtdOH metabolism is an important mechanism in the transition from T. cruzi epimastigote to intermediate form.     

Identification of Hck Inhibitors As Hits for the Development of Antileukemia and Anti‐HIV Agents

Hematopoietic cell kinase (Hck) is a member of the Src family of non‐receptor protein tyrosine kinases. High levels of Hck are associated with drug resistance in chronic myeloid leukemia. Furthermore, Hck activity has been connected with HIV‐1. Herein, structure‐based drug design efforts were aimed at identifying novel Hck inhibitors. First, an in‐house library of pyrazolo[3,4‐d]pyrimidine derivatives, which were previously shown to be dual Abl and c‐Src inhibitors, was analyzed by docking studies within the ATP binding site of Hck to select the best candidates to be tested in a cell‐free assay. Next, the same computational protocol was applied to screen a database of commercially available compounds. As a result, most of the selected compounds were found active against Hck, with K_i values ranging from 0.14 to 18.4 μM , confirming the suitability of the computational approach adopted. Furthermore, selected compounds showed an interesting antiproliferative activity profile against the human leukemia cell line KU‐812, and one compound was found to block HIV‐1 replication at sub‐toxic concentrations.     

Precision and accuracy in the color specification of virgin olive oils from the bromthymol blue method

Twenty experienced observers with nondefective color vision judged 27 virgin olive oil samples within an acceptable color range, using the bromthymol blue (BTB) method, under controlled observation conditions (daylight source with a correlated color temperature of 6500 K, and standard gray back-ground). On the average, 44.8% of the observers agreed in their selections of the BTB standard solution matching a given oil sample, and this percentage increased to 88.2% considering ±one step in the two dimensions (pH and concentration) of the BTB scale. On the average, the lowest color difference between oil samples and available BTB solutions was 6.6 Commission Internationale de l'éclairage 1976-(L^*a^*b^*) (CIELAB) units, but this color difference was approximately two times greater for the color difference between oil samples and BTB solutions selected by our observers. The colors of the BTB standard solutions in the CIELAB space are not uniformly distributed, and thus one step in pH or concentration is equivalent to CIELAB color differences varying in a wide range (1.7–13.5 and 1.7–26.3 CIELAB units, respectively). From these values, indicating low precision, accuracy, and uniformity, some suggestions are made for future improvements of the current BTB method.     

Electrospinning of poly (2-ethyl-2-oxazoline)

Poly (2-ethyl-2-oxazoline) (PEOZ) is one of the commercial members of a family of materials that have shown significant application potential in a large number of technological contexts, most of them related with biomedical problems where water-soluble polymer systems are highly desirable. Polymeric fibers with diameters in the 200–800 nm range of PEOZ were prepared by electrospinning of its water solutions. Processing and solution parameters effects on the morphology and the diameter of the fibers were investigated. SEM results showed that the polymer concentration and the applied voltage might be used as variables to control the morphology and the diameter of the electrospun fibers. Solutions of the same polymer in other two organic solvents (N,N-dimethylformamide (DMF) and tetrahydrofurane (THF)) were also processed by the same technique but without the promising results of the water solutions.     

Environmental and economic profile of six typologies of wastewater treatment plants

The objective of wastewater treatment plants (WWTPs) is to prevent pollution. However, it is necessary to assess their sustainability in order to ensure that pollution is being removed, not displaced. In this research, the performance of 24 WWTPs has been evaluated using a streamlined Life Cycle Assessment (LCA) with Eutrophication Potential (EP) and Global Warming Potential (GWP) as environmental indicators, and operational costs as economic indicators. WWTPs were further classified in six typologies by their quality requirements according to their final discharge point or water reuse. Moreover, two different functional units (FU), one based on volume (m³) and the other on eutrophication reduction (kg PO₄³⁻ removed) were used to further determine sustainability. A correlation between legal requirements and technologies used to achieve them was found: Organic matter removal plants were found to be less costly both in environmental and economic terms if volume was used as the functional unit, while more demanding typologies such as reuse plants showed a trade-off between lower EP and higher cost and GWP; however, this is overcome if the second FU is used instead, proving the sustainability of these options and that this FU better reflects the objectives of a WWTP.     

Multi-environmental cooperative parallel metaheuristics for solving dynamic optimization problems

In dynamic optimization problems, changes occur over time. These changes could be related to the optimization objective, the problem instance, or involve problem constraints. In most cases, they are seen as an ordered sequence of sub-problems or environments that must be solved during a certain time interval. The usual approaches tend to solve each sub-problem when a change happens, dealing always with one single environment at each time instant. In this paper, we propose a multi-environmental cooperative model for parallel meta-heuristics to tackle dynamic optimization problems. It consists in dealing with different environments at the same time, using different algorithms that exchange information coming from these environments. A parallel multi-swarm approach is presented for solving the Dynamic Vehicle Routing Problem. The effectiveness of the proposed approach is tested on a well-known set of benchmarks, and compared with other meta-heuristics from the literature. Experimental results show that our multi-environmental approach outperforms conventional meta-heuristics on this problem.     

Effectiveness of antioxidants in preventing oxidation of palm oil enriched with heme iron: A model for iron fortification in baked products

Bakery products such as biscuits, cookies, and pastries represent a good medium for iron fortification in food products, since they are consumed by a large proportion of the population at risk of developing iron deficiency anemia, mainly children. The drawback, however, is that iron fortification can promote oxidation. To assess the extent of this, palm oil added with heme iron and different antioxidants was used as a model for evaluating the oxidative stability of some bakery products, such as baked goods containing chocolate. The palm oil samples were heated at 220°C for 10 min to mimic the conditions found during a typical baking processing. The selected antioxidants were a free radical scavenger (tocopherol extract (TE), 0 and 500 mg/kg), an oxygen scavenger (ascorbyl palmitate (AP), 0 and 500 mg/kg), and a chelating agent (citric acid (CA), 0 and 300 mg/kg). These antioxidants were combined using a factorial design and were compared to a control sample, which was not supplemented with antioxidants. Primary (peroxide value and lipid hydroperoxide content) and secondary oxidation parameters (p‐anisidine value, p‐AnV) were monitored over a period of 200 days in storage at room temperature. The combination of AP and CA was the most effective treatment in delaying the onset of oxidation. TE was not effective in preventing oxidation. The p‐AnV did not increase during the storage period, indicating that this oxidation marker was not suitable for monitoring oxidation in this model.     

The Metabolic Role of Gut Microbiota in the Development of Nonalcoholic Fatty Liver Disease and Cardiovascular Disease

The prevalence of metabolic disorders, such as type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD), which are common risk factors for cardiovascular disease (CVD), has dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.     

Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.     

Exploratory analytics on patent data sets using the SIMPLE platform

Exploratory Analytics is the process of analyzing data for the purpose of forming hypotheses. Patent data sets, because they are relatively large and diverse and because they consist of a mixture of structured and unstructured information present a formidable challenge and a great opportunity in applying exploratory analytics techniques. In this paper we describe methods we have implemented for effective exploratory analytics on patent data sets using an interactive approach and a web based software tool called SIMPLE. We use real-world case studies to demonstrate the effectiveness of our exploratory analytics approach in the discovery of useful information from the patent corpus.