Protective role of new nitrogen compounds on ROS/RNS-mediated damage to PC12 cells

Reactive oxygen (ROS) and nitrogen (RNS) species are known to be involved in many degenerative diseases. This study reports four new nitrogen compounds from organic synthesis, identified as FMA4, FMA7, FMA762 and FMA796, which differ mainly by the number of hydroxyl groups within their phenolic unit. Their potential role as antioxidants was evaluated in PC12 cells by assessing their protection against oxidative and nitrosative insults. The four compounds, and particularly FMA762 and FMA796, were able to protect cells against lipid peroxidation and intracellular ROS/RNS formation to a great extent. Their protective effects were likely mediated by their free radicals scavenging ability, as they appeared to be involved neither in the induction of natural antioxidant enzymes like GSH-PX and SOD, nor in the inhibition of NOS. Nevertheless, these results suggest a promising potential for these compounds as ROS/RNS scavengers in pathologies where oxidative/ nitrosative stress are involved.Fundação para a Ciência e Tecnologia (FCT

Oxidative stress protection by newly synthesized nitrogen compounds with pharmacological potential

In this study we used new nitrogen compounds obtained by organic synthesis whose structure predicted an antioxidant potential and then an eventual development as molecules of pharmacological interest in diseases involving oxidative stress. The compounds, identified as FMA4, FMA5, FMA7 and FMA8 differ in the presence of hydroxyl groups located in the C-3 and/or C-4 position of a phenolic unit, which is possibly responsible for their free radicals buffering capacity. Data from the DPPH discoloration method confirm the high antiradical efficiency of the compounds. The results obtained with cellular models (L929 and PC12) show that they are not toxic and really protect from membrane lipid peroxidation induced by the ascorbate-iron oxidant pair. The level of protection correlates with the drugs lipophilic profile and is sometimes superior to trolox and equivalent to that observed for a-tocopherol. The compounds FMA4 and FMA7 presented also a high protection from cell death evaluated in the presence of a staurosporine apoptotic stimulus. That protection results in a significant reduction of caspase-3 activity induced by staurosporine which by its turn seems to result from a protection observed in the membrane receptor pathway (caspase-8) together with a protection observed in the mitochondrial pathway (caspase-9). Taken together the results obtained with the new compounds, with linear chains, open up perspectives for their use as therapeutical agents, namely as antioxidants and protectors of apoptotic pathways. On the other hand the slight pro-oxidant profile obtained with the cyclic structures suggests a different therapeutic potential that is under current investigation.Fundação para a Ciência e a Tecnologia (FCT) - POCTI and/or FEDER programmes, SFRH/BD/17174/2004, SFRH/BD/3185/2000

Global vs. local nonlinear optimization techniques for human-like movement of an anthropomorphic robot

In this paper a comparison between using global and local optimization techniques for solving the problem of generating human-like arm and hand movements for an anthropomorphic dual arm robot is made. Although the objective function involved in each optimization problem is convex, there is no evidence that the admissible regions of these problems are convex sets. For the sequence of movements for which the numerical tests were done there were no significant differences between the optimal solutions obtained using the global and the local techniques. This suggests that the optimal solution obtained using the local solver is indeed a global solution

Quantitative Proteomic Analysis Reveals Changes in the Benchmark Corynebacterium pseudotuberculosis Biovar Equi Exoproteome after Passage in a Murine Host

Corynebacterium pseudotuberculosis biovar equi is the etiologic agent of ulcerative lymphangitis. To investigate proteins that could be related to the virulence of this pathogen, we combined an experimental passage process using a murine model and high-throughput proteomics with a mass spectrometry, data-independent acquisition (LC-MSE) approach to identify and quantify the proteins released into the supernatants of strain 258_equi. To our knowledge, this approach allowed characterization of the exoproteome of a C. pseudotuberculosis equi strain for the first time. Interestingly, the recovery of this strain from infected mouse spleens induced a change in its virulence potential, and it became more virulent in a second infection challenge. Proteomic screening performed from culture supernatant of the control and recovered conditions revealed 104 proteins that were differentially expressed between the two conditions. In this context, proteomic analysis of the recovered condition detected the induction of proteins involved in bacterial pathogenesis, mainly related to iron uptake. In addition, KEGG enrichment analysis showed that ABC transporters, bacterial secretion systems and protein export pathways were significantly altered in the recovered condition. These findings show that secretion and secreted proteins are key elements in the virulence and adaptation of C. pseudotuberculosis. Collectively, bacterial pathogenesis-related proteins were identified that contribute to the processes of adherence, intracellular growth and evasion of the immune system. Moreover, this study enhances our understanding of the factors that may influence the pathogenesis of C. pseudotuberculosis.Fil: Marques Da Silva, Wanderson. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; Brasil. Institut National de la Recherche Agronomique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carvalho, Rodrigo D. De Oliveira. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Dorella, Fernanda A.. Universidade Federal de Minas Gerais; BrasilFil: Folador, Edson L.. Universidade Federal da Paraíba. Centro de Biotecnologia; BrasilFil: Souza, Gustavo H. M. F.. Waters Corporation; BrasilFil: Pimenta, Adriano M. C.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Figueiredo, Henrique C. P.. Universidade Federal de Minas Gerais; BrasilFil: Le Loir, Yves. Institut National de la Recherche Agronomique; FranciaFil: Silva, Artur. Universidade Federal do Pará; BrasilFil: Azevedo, Vasco. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; Brasi

Nonlinear optimization for human-like movements of a high degree of freedom robotics arm-hand system

The design of autonomous robots, able to closely cooperate with human users in shared tasks, provides many new challenges for robotics research. Compared to industrial applications, robots working in human environments will need to have human-like abilities in their cognitive and motor behaviors. Here we present a model for generating trajectories of a high degree of freedom robotics arm-hand system that reflects optimality principles of human motor control. The process of finding a human-like trajectory among all possible solutions is formalized as a large-scale nonlinear optimization problem. We compare numerically three existing solvers, IPOPT, KNITRO and SNOPT, in terms of their real-time performance in different reach-to-grasp problems that are part of a human-robot interaction task. The results show that the SQP methods obtain better results than the IP methods. SNOPT finds optimal solutions for all tested problems in competitive computational times, thus being the one that best serves our purpose.Eliana Costa e Silva was supported by FCT (grant: SFRH/BD/23821/2005). The resources and equipment were financed by FCT and UM through project "Anthropomorphic robotic systems: control based on the processing principles of the human and other primates motor system and potential applications in service robotics and biomedical engineering" (Ref. CONC-REEQ/17/2001) and by EC through project "JAST: Joint-Action Science and Technology" (Ref. IST- 2-003747-IP).We thank the Mobile and Anthropomorphic Robotics Laboratory at University of Minho for constant good work environment. Finally, we would like to thank Carl Laird and Andreas Wachter for making available IPOPT, and AMPL for making available an unrestricted 30 days trial version of AMPL, KNITRO and SNOPT executables

Human-like movement of an anthropomorphic robot: problem revisited

Human-like movement is fundamental for natural human-robot interaction and collaboration. We have developed in a model for generating arm and hand movements an anthropomorphic robot. This model was inspired by the Posture-Based Motion-Planning Model of human reaching and grasping movements. In this paper we present some changes to the model we have proposed in [4] and test and compare different nonlinear constrained optimization techniques for solving the large-scale nonlinear constrained optimization problem that rises from the discretization of our time-continuous model. Furthermore, we test different time discretization steps.Eliana Costa e Silva was supported by FCT (grant: SFRH/BD/23821/2005)

Química mineral de encraves ultramáficos nas lavas da erupção de 2014 na Ilha do Fogo (Cabo Verde) : resultados preliminares

Resumo alargad

Analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer

Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. Results: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels. Conclusion: Quantitative promoter methylation of RAD51B and XRCC3 constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings.publishersversionpublishe

Antioxidant properties and fruit quality during long-term storage of “rocha” pear: effects of maturity and storage conditions

Free radical scavenging activity and the content of ascorbic acid and glutathione were investigated during long-term storage of the pear (Pyrus communis L. ‘Rocha’) fruit harvested at different maturity stages, stored in air or under controlled atmosphere and subjected to postharvest treatments with diphenylamine (DPA) and 1-methylcyclopropene (1-MCP). Harvest maturity had a significant effect on storage disorders, fruit firmness, soluble solids content and acidity. Differences in ascorbate content and free radical scavenging activity at harvest did not persist during storage. Controlled atmosphere and DPA strongly reduced the incidence and severity of browning disorders and superficial scald, whereas 1-MCP provided the most effective control. Neither DPA nor 1-MCP affected the free radical scavenging activityinfo:eu-repo/semantics/publishedVersio