Impact of glucocorticoid on a cellular model of parkinson’s disease: Oxidative stress and mitochondrial function

Stress seems to contribute to the neuropathology of Parkinson’s disease (PD), possibly by dysregulation of the hypothalamic–pituitary–adrenal axis. Oxidative distress and mitochondrial dysfunction are key factors involved in the pathophysiology of PD and neuronal glucocorticoid-induced toxicity. Animal PD models have been generated to study the effects of hormonal stress, but no in vitro model has yet been developed. Our aim was to examine the impact of corticosterone (CORT) administration on a dopaminergic neuronal cell model of PD induced by the neurotoxin MPP+, as a new combined PD model based on the marker of endocrine response to stress, CORT, and oxidative-mitochondrial damage. We determined the impact of CORT, MPP+ and their co-incubation on reactive oxygen species production (O2−• ), oxidative stress cellular markers (advanced-oxidation protein products and total antioxidant status), mitochondrial function (mitochondrial membrane potential and mitochondrial oxygen consumption rate) and neurodegeneration (Fluoro-Jade staining). Accordingly, the administration of MPP+ or CORT individually led to cell damage compared to controls (p < 0.05), as determined by several methods, whereas their co-incubation produced strong cell damage (p < 0.05). The combined model described here could be appropriate for investigating neuropathological hallmarks and for evaluating potential new therapeutic tools for PD patients suffering mild to moderate emotional stress

Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage

Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from oxidative damage, and the preservation of different sources of energy production is essential to preserve neuronal function. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of multiple sclerosis. This work was performed in a model of oxidative damage on neuronal cell cultures exposed to menadione in the presence or absence of fingolimod phosphate. We studied the mitochondrial function, antioxidant enzymes, protein nitrosylation, and several pathways related with glucose metabolism and glycolytic and pentose phosphate in neuronal cells cultures. Our results showed that menadione produces a decrease in mitochondrial function, an imbalance in antioxidant enzymes, and an increase in nitrosylated proteins with a decrease in glycolysis and glucose-6-phosphate dehydrogenase. All these effects were counteracted when fingolimod phosphate was present in the incubation media. These effects were mediated, at least in part, by the interaction of this drug with its specific S1P receptors. These actions would make this drug a potential tool in the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms

TweetLID : a benchmark for tweet language identification

Language identification, as the task of determining the language a given text is written in, has progressed substantially in recent decades. However, three main issues remain still unresolved: (1) distinction of similar languages, (2) detection of multilingualism in a single document, and (3) identifying the language of short texts. In this paper, we describe our work on the development of a benchmark to encourage further research in these three directions, set forth an evaluation framework suitable for the task, and make a dataset of annotated tweets publicly available for research purposes. We also describe the shared task we organized to validate and assess the evaluation framework and dataset with systems submitted by seven different participants, and analyze the performance of these systems. The evaluation of the results submitted by the participants of the shared task helped us shed some light on the shortcomings of state-of-the-art language identification systems, and gives insight into the extent to which the brevity, multilingualism, and language similarity found in texts exacerbate the performance of language identifiers. Our dataset with nearly 35,000 tweets and the evaluation framework provide researchers and practitioners with suitable resources to further study the aforementioned issues on language identification within a common setting that enables to compare results with one another

Rapid tree carbon stock recovery in managed Amazonian forests.

While around 20% of the Amazonian forest has been cleared for pastures and agriculture, one fourth of the remaining forest is dedicated to wood production [1] . Most of these production forests have been or will be selectively harvested for commercial timber, but recent studies show that even soon after logging, harvested stands retain much of their tree-biomass carbon and biodiversity [2,3] . Comparing species richness of various animal taxa among logged and unlogged forests across the tropics, Burivalova et al.[4] found that despite some variability among taxa, biodiversity loss was generally explained by logging intensity (the number of trees extracted). Here, we use a network of 79 permanent sample plots (376 ha total) located at 10 sites across the Amazon Basin [5] to assess the main drivers of time-to-recovery of post-logging tree carbon ( Table S1 ). Recovery time is of direct relevance to policies governing management practices (i.e., allowable volumes cut and cutting cycle lengths), and indirectly to forest-based climate change mitigation interventions

The tropical managed forests observatory: a research network addressing the future of tropical logged forests.

While attention on logging in the tropics has been increasing, studies on the long-term effects of silviculture on forest dynamics and ecology remain scare and spatially limited. Indeed, most of our knowledge on tropical forests arises from studies carried out in undisturbed tropical forests. This biasis problematic given that logged and disturbed tropical forests are now covering a larger area thantheso-alled primary forests. A new network of permanent sample plots in logged forests, the Tropical managed Forests Observatory (TmFO), aims to ?ll this gap by providing unprecedented opportunities to examine long-term data on the resilience of logged tropical forests at regional and global scales. TmFO currently includes 24 experimental sites distributed across three tropical regions, with a total of 490 permanent plots and 921 ha of forest inventories

A broad distribution of the alternative oxidase in microsporidian parasites

Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome

Role of Condom Negotiation on Condom use among Women of Reproductive Age in three Districts in Tanzania.

ABSTRACT: BACKGROUND: HIV/AIDS remains being a disease of great public health concern worldwide. In regions such as sub-Saharan Africa (SSA) where women are disproportionately infected with HIV, women are reportedly less likely capable of negotiating condom use. However, while knowledge of condom use for HIV prevention is extensive among men and women in many countries including Tanzania, evidence is limited about the role of condom negotiation on condom use among women in rural Tanzania. METHODS: Data originate from a cross-sectional survey of random households conducted in 2011 in Rufiji, Kilombero and Ulanga districts in Tanzania. The survey assessed health-seeking behaviour among women and children using a structured interviewer-administered questionnaire. A total of 2,614 women who were sexually experienced and aged 15--49 years were extracted from the main database for the current analysis. Linkage between condom negotiation and condom use at the last sexual intercourse was assessed using multivariate logistic regression. RESULTS: Prevalence of condom use at the last sexual intercourse was 22.2% overall, ranging from12.2% among married women to 54.9% among unmarried (single) women. Majority of the women (73.4%) reported being confident to negotiate condom use, and these women were significantly more likely than those who were not confident to have used a condom at the last sexual intercourse (OR = 3.13, 95% CI 2.22-4.41). This effect was controlled for marital status, age, education, religion, number of sexual partners, household wealth and knowledge of HIV prevention by condom use. CONCLUSION: Confidence to negotiate condom use is a significant predictor of actual condom use among women in rural Tanzania. Women especially unmarried ones or those in multiple partnerships should be empowered with condom negotiation skills to enhance their sexual and reproductive health outcomes

A Combination of Compositional Index and Genetic Algorithm for Predicting Transmembrane Helical Segments

Transmembrane helix (TMH) topology prediction is becoming a focal problem in bioinformatics because the structure of TM proteins is difficult to determine using experimental methods. Therefore, methods that can computationally predict the topology of helical membrane proteins are highly desirable. In this paper we introduce TMHindex, a method for detecting TMH segments using only the amino acid sequence information. Each amino acid in a protein sequence is represented by a Compositional Index, which is deduced from a combination of the difference in amino acid occurrences in TMH and non-TMH segments in training protein sequences and the amino acid composition information. Furthermore, a genetic algorithm was employed to find the optimal threshold value for the separation of TMH segments from non-TMH segments. The method successfully predicted 376 out of the 378 TMH segments in a dataset consisting of 70 test protein sequences. The sensitivity and specificity for classifying each amino acid in every protein sequence in the dataset was 0.901 and 0.865, respectively. To assess the generality of TMHindex, we also tested the approach on another standard 73-protein 3D helix dataset. TMHindex correctly predicted 91.8% of proteins based on TM segments. The level of the accuracy achieved using TMHindex in comparison to other recent approaches for predicting the topology of TM proteins is a strong argument in favor of our proposed method. Availability: The datasets, software together with supplementary materials are available at: http://faculty.uaeu.ac.ae/nzaki/TMHindex.htm

Plasmodium falciparum Hep1 is required to prevent the self aggregation of PfHsp70-3

The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria