Patients recovering from sepsis have higher rates of CNS morbidities associated with long-lasting impairment of cognitive functions, including neurodegenerative diseases. However, the molecular ...etiology of these sepsis-induced impairments is unclear. Here, we investigated the role of the receptor for advanced glycation end products (RAGE) in neuroinflammation, neurodegeneration-associated changes, and cognitive dysfunction arising after sepsis recovery. Adult Wistar rats underwent cecal ligation and perforation (CLP), and serum and brain (hippocampus and prefrontal cortex) samples were obtained at days 1, 15, and 30 after the CLP. We examined these samples for systemic and brain inflammation; amyloid-β peptide (Aβ) and Ser-202–phosphorylated Tau (p-TauSer-202) levels; and RAGE, RAGE ligands, and RAGE intracellular signaling. Serum markers associated with the acute proinflammatory phase of sepsis (TNFα, IL-1β, and IL-6) rapidly increased and then progressively decreased during the 30-day period post-CLP, concomitant with a progressive increase in RAGE ligands (S100B, Nɛ-carboxymethyllysine, HSP70, and HMGB1). In the brain, levels of RAGE and Toll-like receptor 4, glial fibrillary acidic protein and neuronal nitric-oxide synthase, and Aβ and p-TauSer-202 also increased during that time. Of note, intracerebral injection of RAGE antibody into the hippocampus at days 15, 17, and 19 post-CLP reduced Aβ and p-TauSer-202 accumulation, Akt/mechanistic target of rapamycin signaling, levels of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, and behavioral deficits associated with cognitive decline. These results indicate that brain RAGE is an essential factor in the pathogenesis of neurological disorders following acute systemic inflammation.
Alkylating agents are a key component of cancer chemotherapy. Several cellular mechanisms are known to be important for its survival, particularly DNA repair and xenobiotic detoxification, yet ...genomic screens indicate that additional cellular components may be involved. Elucidating these components has value in either identifying key processes that can be modulated to improve chemotherapeutic efficacy or may be altered in some cancers to confer chemoresistance. We therefore set out to reevaluate our prior Drosophila RNAi screening data by comparison to gene expression arrays in order to determine if we could identify any novel processes in alkylation damage survival. We noted a consistent conservation of alkylation survival pathways across platforms and species when the analysis was conducted on a pathway/process level rather than at an individual gene level. Better results were obtained when combining gene lists from two datasets (RNAi screen plus microarray) prior to analysis. In addition to previously identified DNA damage responses (p53 signaling and Nucleotide Excision Repair), DNA-mRNA-protein metabolism (transcription/translation) and proteasome machinery, we also noted a highly conserved cross-species requirement for NRF2, glutathione (GSH)-mediated drug detoxification and Endoplasmic Reticulum stress (ER stress)/Unfolded Protein Responses (UPR) in cells exposed to alkylation. The requirement for GSH, NRF2 and UPR in alkylation survival was validated by metabolomics, protein studies and functional cell assays. From this we conclude that RNAi/gene expression fusion is a valid strategy to rapidly identify key processes that may be extendable to other contexts beyond damage survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ViaComplex is an open-source application that builds landscape maps of gene expression networks. The motivation for this software comes from two previous publications (Nucleic Acids Res., 35, ...1859–1867, 2007; Nucleic Acids Res., 36, 6269–6283, 2008). The first article presents a network-based model of genome stability pathways where we defined a set of genes that characterizes each genetic system. In the second article we analyzed this model by projecting functional information from several experiments onto the gene network topology. In order to systematize the methods developed in these articles, ViaComplex provides tools that may help potential users to assess different high-throughput experiments in the context of six core genome maintenance mechanisms. This model illustrates how different gene networks can be analyzed by the same algorithm. Availability: http://lief.if.ufrgs.br/pub/biosoftwares/viacomplex Supplementary information: Supplementary data are available at Bioinformatics online. Contact: mauro@ufrgs.br or rita@if.ufrgs.br
Major depressive disorder (MDD) is a common mental disorder associated with a significant negative impact on quality of life, morbidity/mortality, and cognitive function. Individuals who suffer with ...MDD display lower serum/plasmatic total antioxidant potentials and reduced brain GSH levels. Also, F2-isoprostanes circulatory levels are increased in MDD subjects and are correlated with the severity of depressive symptoms. Urinary excretion of 8-OHdG seems to be higher in patients with MDD compared to healthy controls. Despite the fact that antidepressant drugs have been used for more than 50 years, their mechanism of action is still not fully understood. This paper examines preclinical (in vitro and animal model) and clinical literature on oxidative/antioxidant effects associated with antidepressant agents and discusses their potential antioxidant-related effects in the treatment of MDD. Substantial data support that MDD seems to be accompanied by elevated levels of oxidative stress and that antidepressant treatments may reduce oxidative stress. These studies suggest that augmentation of antioxidant defences may be one of the mechanisms underlying the neuroprotective effects of antidepressants in the treatment of MDD.
The purpose of this study was to evaluate the bioactive compounds and antioxidant activity of extracts from araçá (Psidium cattleianum), butiá (Butia eriospatha), and pitanga (Eugenia uniflora) ...fruits with different flesh colors (i.e., purple, red, and orange), and blackberries (Rubus sp.; cv. Xavante and Cherokee) collected in the southern region of Brazil. The content of ascorbic acid, total carotenoids, and phenolics were determined. The profile of the phenolic compounds was assessed by high-performance liquid chromatography combined with diode array detection (HPLC-DAD). The antioxidant activity was determined using the ferric-reducing antioxidant power (FRAP) assay, 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH) assay, total reactive antioxidant potential (TRAP) assay, and total antioxidant reactivity (TAR) assay. The Xavante blackberry and purple-fleshed pitanga showed the highest total phenolic content 816.50 mg gallic acid equivalents (GAE)/100g and 799.80 mg GAE/100g, respectively. The araçá and red-fleshed pitanga showed the highest carotenoid content (6.27 ug β-carotene/g and 5.86 ug β-carotene/g, respectively). The fruits contained several phenolic compounds such as quercetin derivatives, quercitrin, isoquercitrin, and cyanidin derivatives, which may contribute differentially to the antioxidant capacity. The highest scavenging activity in the DPPH assay was found for purple-fleshed pitanga (IC50 36.78 mg/L), blackberries IC50 44.70 (Xavante) and IC50 78.25 mg/L (Cherokee), and araçá (IC50 48.05 mg/L), which also showed the highest FRAP, followed by orange- and red-fleshed pitanga. Our results revealed that some fruits grown in southern Brazil such as purple-fleshed pitanga, blackberries, and araçá are rich sources of phenolic compounds and have great antioxidant activity.
Nitrogen Removal from Landfill Leachate by Microalgae Pereira, Sérgio F L; Gonçalves, Ana L; Moreira, Francisca C ...
International journal of molecular sciences,
11/2016, Letnik:
17, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Landfill leachates result from the degradation of solid residues in sanitary landfills, thus presenting a high variability in terms of composition. Normally, these effluents are characterized by high ...ammoniacal-nitrogen (N-NH₄⁺) concentrations, high chemical oxygen demands and low phosphorus concentrations. The development of effective treatment strategies becomes difficult, posing a serious problem to the environment. Phycoremediation appears to be a suitable alternative for the treatment of landfill leachates. In this study, the potential of
for biomass production and nutrients (mainly nitrogen and phosphorus) removal from different compositions of a landfill leachate was evaluated. Since microalgae also require phosphorus for their growth, different loads of this nutrient were evaluated, giving the following N:P ratios: 12:1, 23:1 and 35:1. The results have shown that
was able to grow in the different leachate compositions assessed. However, microalgal growth was higher in the cultures presenting the lowest N-NH₄⁺ concentration. In terms of nutrients uptake, an effective removal of N-NH₄⁺ and phosphorus was observed in all the experiments, especially in those supplied with phosphorus. Nevertheless, N-NO₃
removal was considered almost negligible. These promising results constitute important findings in the development of a bioremediation technology for the treatment of landfill leachates.
The aim of the present study was to compare the efficiency of vitrification and slow freezing techniques for the cryopreservation of zebrafish ovarian tissue containing immature follicles. In ...Experiment 1, assessment of cell membrane integrity by trypan blue exclusion staining was used to select the best cryoprotectant solution for each cryopreservation method. Primary growth (PG) oocytes showed the best percentage of membrane integrity (63.5 ± 2.99%) when SF4 solution (2 M methanol + 0.1 M trehalose + 10% egg yolk solution) was employed. The vitrification solution, which presented the highest membrane integrity (V2; 1.5 M methanol + 5.5 M Me
SO + 0.5 M sucrose + 10% egg yolk solution) was selected for Experiment 2. Experiment 2 aimed to compare the vitrification and slow freezing techniques in the following parameters: morphology, oxidative stress, mitochondrial activity, and DNA damage. Frozen ovarian tissue showed higher ROS levels and lower mitochondrial activity than vitrified ovarian tissue. Ultrastructural observations of frozen PG oocytes showed rupture of the plasma membrane, loss of intracellular contents and a large number of damaged mitochondria, while vitrified PG oocytes had intact mitochondria and cell plasma membranes. We conclude that vitrification may be more effective than slow freezing for the cryopreservation of zebrafish ovarian tissue.
Whole genome protein-protein association networks are not random and their topological properties stem from genome evolution mechanisms. In fact, more connected, but less clustered proteins are ...related to genes that, in general, present more paralogs as compared to other genes, indicating frequent previous gene duplication episodes. On the other hand, genes related to conserved biological functions present few or no paralogs and yield proteins that are highly connected and clustered. These general network characteristics must have an evolutionary explanation. Considering data from STRING database, we present here experimental evidence that, more than not being scale free, protein degree distributions of organisms present an increased probability for high degree nodes. Furthermore, based on this experimental evidence, we propose a simulation model for genome evolution, where genes in a network are either acquired de novo using a preferential attachment rule, or duplicated with a probability that linearly grows with gene degree and decreases with its clustering coefficient. For the first time a model yields results that simultaneously describe different topological distributions. Also, this model correctly predicts that, to produce protein-protein association networks with number of links and number of nodes in the observed range for Eukaryotes, it is necessary 90% of gene duplication and 10% of de novo gene acquisition. This scenario implies a universal mechanism for genome evolution.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present study evaluated the alterations of the oxidative stress markers in adult dogs fed with high levels of PUFA from the mixture of soybean oil enriched with docosahexaenoic acid (DHA) and ...supplemented with a natural algae-based antioxidant (AOX). Twelve healthy adult (2 years old) Beagle dogs (6 males and 6 females, 11.20 ± 1.92 kg BW), were distributed in 2 completely randomized blocks design and fed with 4 experimental diets coated with 2 lipid sources: saturated (13% bovine tallow) or unsaturated (13% soybean oil enriched with DHA), supplemented or not with 500 mg of AOX for 4 wk, intercalated with a 4-wk adaptation period. Blood samples were collected on days 0, 15, and 30 of each block. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), sulfhydryl group (SH), protein carbonylation, thiobarbituric acid reactive substances (TBARS), and total reactive antioxidant potential (TRAP) were evaluated in the serum, while GSH-Px, SOD, glutathione S-transferase (GST), catalase (CAT), SH, and TBARS were measured in erythrocytes. There was no significant difference in most of the oxidative markers evaluated. In contrast, GST activity in erythrocytes was greater in the animals that consumed the diets coated with bovine tallow compared to dogs that consumed diets coated with soybean oil enriched with DHA (P < 0.05). Serum from dogs fed on diets supplemented with AOX presented greater TRAP values (P < 0.05). These data demonstrate that the concentrations of unsaturated fatty acids (UNS) used in the diets for dogs were not sufficient to cause large changes in the oxidative status. It was not possible to evaluate the efficiency of the natural antioxidant in maintaining the oxidative balance of the animals as it appears that the oxidative status of the dogs was not challenged by the unsaturated diets. Our findings also suggest that dogs, as descendants from carrion carnivores, may have some natural protection against oxidation.