Oxidative Stress in Neurodegenerative Diseases: Mechanisms and Therapeutic Perspectives

The incidence and prevalence of neurodegenerative diseases (ND) increase with life expectancy. This paper reviews the role of oxidative stress (OS) in ND and pharmacological attempts to fight against reactive oxygen species (ROS)-induced neurodegeneration. Several mechanisms involved in ROS generation in neurodegeneration have been proposed. Recent articles about molecular pathways involved in ROS generation were reviewed. The progress in the development of neuroprotective therapies has been hampered because it is difficult to define targets for treatment and determine what should be considered as neuroprotective. Therefore, the attention was focused on researches about pharmacological targets that could protect neurons against OS. Since it is necessary to look for genes as the ultimate controllers of all biological processes, this paper also tried to identify gerontogenes involved in OS and neurodegeneration. Since neurons depend on glial cells to survive, recent articles about the functioning of these cells in aging and ND were also reviewed. Finally, clinical trials testing potential neuroprotective agents were critically reviewed. Although several potential drugs have been screened in in vitro and in vivo models of ND, these results were not translated in benefit of patients, and disappointing results were obtained in the majority of clinical trials

Extração de Dados do Twitter para aplicação na Análise de Sentimentos

This work has as objective collect data from the social network Twitter, with the idea to make a Portuguese database to be applied in Sentiment Analysis. Besides the data extracting, a classification algorithm was created based on the emoticons found. This database will be used in future Sentiment Analysis works like the application of others kinds of classification algorithms such as machine learning algorithms

Exploring the connection between the stellar wind and the non-thermal emission in LS 5039

LS 5039 has been observed with several X-ray instruments so far. The source presents X-ray variability at orbital timescales in flux and photon index. The system harbors an O-type main sequence star with moderate mass loss. At present, the link between the X-rays and the stellar wind is unclear. New XMM-Newton observations have been performed around periastron and apastron passages in September 2005, when the stellar wind activity was apparently higher. April 2005 Chandra observations on LS 5039 are also revisited. Moreover, a compilation of Halpha EW data obtained since 1992, from which the stellar mass loss evolution can be approximately inferred, is carried out. XMM-Newton observations show higher and harder emission around apastron than around periastron. No signatures of thermal emission or a reflection iron line indicating the presence of an accretion disk are found in the spectrum, and the hydrogen column density (NH) is compatible with being the same in both observations and consistent with the interstellar value. 2005 Chandra observations show a hard X-ray spectrum, and possibly high fluxes. The Halpha EW shows yearly variations of a ~ 10%, and does not seem to be correlated with X-ray fluxes obtained at similar phases, unlike it would be expected in the wind accretion scenario. 2005 XMM-Newton and Chandra observations are consistent with 2003 RXTE/PCA results. The constancy of the NH seems to imply that either the X-ray emitter is located at >~ 1012 cm from the compact object, or the real N_H is 3-27 times smaller than the one predicted by a spherical symmetric wind model. We suggest that the multiwavelength non-thermal emission of LS 5039 is related to the radio jets and unlikely produced inside the binary system.Comment: 7 pages, 3 figures, 3 Tables, accepted for publication in A&A (short abstract version, see abstract paper!), Table 2 will only appear on-line in the journa

Phylogenetic and functional diversity of metagenomic libraries of phenol degrading sludge from petroleum refinery wastewater treatment system

In petrochemical refinery wastewater treatment plants (WWTP), different concentrations of pollutant compounds are received daily in the influent stream, including significant amounts of phenolic compounds, creating propitious conditions for the development of particular microorganisms that can rapidly adapt to such environment. In the present work, the microbial sludge from a refinery WWTP was enriched for phenol, cloned into fosmid vectors and pyrosequenced. The fosmid libraries yielded 13,200 clones and a comprehensive bioinformatic analysis of the sequence data set revealed a complex and diverse bacterial community in the phenol degrading sludge. The phylogenetic analyses using MEGAN in combination with RDP classifier showed a massive predominance of Proteobacteria, represented mostly by the genera Diaphorobacter, Pseudomonas, Thauera and Comamonas. The functional classification of phenol degrading sludge sequence data set generated by MG-RAST showed the wide metabolic diversity of the microbial sludge, with a high percentage of genes involved in the aerobic and anaerobic degradation of phenol and derivatives. In addition, genes related to the metabolism of many other organic and xenobiotic compounds, such as toluene, biphenyl, naphthalene and benzoate, were found. Results gathered herein demonstrated that the phenol degrading sludge has complex phylogenetic and functional diversities, showing the potential of such community to degrade several pollutant compounds. This microbiota is likely to represent a rich resource of versatile and unknown enzymes which may be exploited for biotechnological processes such as bioremediation

The Association Between Muscle Deoxygenation and Muscle Hypertrophy to Blood Flow Restricted Training Performed at High and Low Loads

The metabolic stress induced by blood flow restriction (BFR) during resistance training (RT) might maximize muscle growth. However, it is currently unknown whether metabolic stress are associated with muscle hypertrophy after RT protocols with high- or low load. Therefore, the aim of the study was to compare the effect of high load RT (HL-RT), high load BFR (HL-BFR), and low load BFR (LL-BFR) on deoxyhemoglobin concentration [HHb] (proxy marker of metabolic stress), muscle cross-sectional area (CSA), activation, strength, architecture and edema before (T1), after 5 (T2), and 10 weeks (T3) of training with these protocols. Additionally, we analyzed the occurrence of association between muscle deoxygenation and muscle hypertrophy. Thirty young men were selected and each of participants’ legs was allocated to one of the three experimental protocols in a randomized and balanced way according to quartiles of the baseline CSA and leg extension 1-RM values of the dominant leg. The dynamic maximum strength was measured by 1-RM test and vastus lateralis (VL) muscle cross-sectional area CSA echo intensity (CSAecho) and pennation angle (PA) were performed through ultrasound images. The measurement of muscle activation by surface electromyography (EMG) and [HHb] through near-infrared spectroscopy (NIRS) of VL were performed during the training session with relative load obtained after the 1-RM, before (T1), after 5 (T2), and 10 weeks (T3) training. The training total volume (TTV) was greater for HL-RT and HL-BFR compared to LL-BFR. There was no difference in 1-RM, CSA, CSAecho, CSAecho/CSA, and PA increases between protocols. Regarding the magnitude of the EMG, the HL-RT and HL-BFR groups showed higher values than and LL-BFR. On the other hand, [HHb] was higher for HL-BFR and LL-BFR. In conclusion, our results suggest that the addition of BFR to exercise contributes to neuromuscular adaptations only when RT is performed with low-load. Furthermore, we found a significant association between the changes in [HHb] (i.e., metabolic stress) and increases in muscle CSA from T2 to T3 only for the LL-BFR, when muscle edema was attenuated

Restauració de les pedreres de roca calcària en clima Mediterrani: procés i avaluació

Postprint (published version

Contribution of S6K1/MAPK signaling pathways in the response to oxidative stress: activation of RSK and MSK by hydrogen peroxide

Trobareu correccions de l'article a: http://dx.doi.org/10.1371/annotation/0b485bd9-b1b2-4c60-ab22-3ac5d271dc59Cells respond to different kind of stress through the coordinated activation of signaling pathways such as MAPK or p53. To find which molecular mechanisms are involved, we need to understand their cell adaptation. The ribosomal protein, S6 kinase 1 (S6K1), is a common downstream target of signaling by hormonal or nutritional stress. Here, we investigated the initial contribution of S6K1/MAPK signaling pathways in the cell response to oxidative stress produced by hydrogen peroxide (H2O2). To analyze S6K1 activation, we used the commercial anti-phospho-Thr389-S6K1 antibody most frequently mentioned in the bibliography. We found that this antibody detected an 80-90 kDa protein that was rapidly phosphorylated in response to H2O2 in several human cells. Unexpectedly, this phosphorylation was insensitive to both mTOR and PI3K inhibitors, and knock-down experiments showed that this protein was not S6K1. RSK and MSK proteins were candidate targets of this phosphorylation. We demonstrated that H2O2 stimulated phosphorylation of RSK and MSK kinases at residues that are homologous to Thr389 in S6K1. This phosphorylation required the activity of either p38 or ERK MAP kinases. Kinase assays showed activation of RSK and MSK by H2O2. Experiments with mouse embryonic fibroblasts from p38 animals" knockout confirmed these observations. Altogether, these findings show that the S6K1 signaling pathway is not activated under these conditions, clarify previous observations probably misinterpreted by non-specific detection of proteins RSK and MSK by the anti-phospho-Thr389-S6K1 antibody, and demonstrate the specific activation of MAPK signaling pathways through ERK/p38/RSK/MSK by H2O2