Three regulatory compliant test systems show no signs of MDMA-related genotoxicity.
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SUBMITTER: Cohen IV
PROVIDER: S-EPMC8600592 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNeurocognitive testing is an important concussion evaluation tool, but for neurocognitive tests to be useful, their psychometric properties must be well established. Test-retest reliability of computerized neurocognitive tests can influence their clinical utility. The reliability for a commonly used computerized neurocognitive test, CNS Vital Signs, is not well established. The purpose of this study was to examine test-retest reliability and reliable change indices for CNS Vital Signs in a healthy, physically active college population.HypothesisCNS Vital Signs yields acceptable test-retest reliability, with greater reliability between the second and third test administration compared with between the first and second administration.Study designCohort study.Level of evidenceLevel 3.MethodsForty healthy, active volunteers (16 men, 24 women; mean age, 21.05 ± 2.17 years) reported to a clinical laboratory for 3 sessions, 1 week apart. At each session, participants were administered CNS Vital Signs. Outcomes included standard scores for the following CNS Vital Signs domains: verbal memory, visual memory, psychomotor speed, cognitive flexibility, complex attention, processing speed, reaction time, executive functioning, and reasoning.ResultsParticipants performed significantly better on the second session and/or third session than they did on the first testing session on 6 of 9 neurocognitive domains. Pearson r test-retest correlations between sessions ranged from 0.11 to 0.87. Intraclass correlation coefficients ranged from 0.10 to 0.86.ConclusionClinicians should consider using reliable change indices to account for practice effects, identify meaningful score changes due to pathology, and inform clinical decisions.Clinical relevanceThis study highlights the importance of clinicians understanding the psychometric properties of computerized neurocognitive tests when using them in the management of sport-related concussion. If CNS Vital Signs is administered twice within a small time frame (such as 1 week), athletes should be expected to improve between the first and second administration.
| S-EPMC4547115 | biostudies-literature
Project description:The present study evaluates the regulatory effect of Nano-Curcumin (Nano-CUR) against tartrazine (TZ)-induced injuries on apoptosis-related gene expression (i.e., p53, CASP-3 and CASP-9), antioxidant status, and DNA damages in bone marrow in treated rats. Male rats were arbitrarily separated into five groups, and each group was comprised of 10 rats each. The 1st group served as control (G1). The 2nd group ingested 7.5 mg TZ/kg. b.w. (body weight). The 3rd group ingested Nano-CUR 1 g/kg b.w. The 4th and 5th groups were respectively administered with (1 g Nano-CUR + 7.5 mg TZ/kg. b.w.) and (2 g Nano-CUR + 7.5 mg TZ/kg. b.w.). At the end of the experiment, blood samples, livers, and kidneys were collected. Livers and kidneys were homogenized and used for the analysis of reduced glutathione, malonaldhyde, total antioxidant capacity, lipid peroxide antioxidant enzyme activities, apoptosis-related gene expression, and genotoxicity by comit test. The ingestion of TZ for 50 days resulted in significant decreases in body, and kidney weights in rats and a relative increase in the liver weight compared to control. In contrast, the ingestion of Nano-CUR with TZ remarkably upgraded the body weight and relative liver weight compared to the normal range in the control. Aditionally, TZ ingestion in rats increased the oxidative stress biomarkers lipid peroxide (LPO) and malonaldehyde (MDA) significantly, whereas it decreased the reduced glutathione (GSH) levels and total antioxidant capacity (TAC). Similarly, the levels of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) significantly deteriorated in response to TZ ingestion. Moreover, the results revealed a remarkable up-regulation in the level of expression for the three examined genes, including p53, CASP-3, and CASP-9 in TZ-ingested rats compared to the control. On the other hand, the comet assay result indicates that the ingestion of TZ induced DNA damage in bone marrow. Notably, the administration of Nano-CUR protected the kidney and liver of TZ-ingested rats as evidenced by a significant elevation in all antioxidant activities of tested enzymes (i.e, SOD, GPx, and CAT), vital recovery in GSH and TAC levels, and a statistical decrease in LPO and MDA compared to TZ-ingested rats. Interestingly, the ingestion of rats with TZ modulates the observed up-regulation in the level of expression for the chosen genes, indicating the interfering role in the signaling transduction process of TZ-mediated poisoning. The results indicate that the administration of Nano-CUR may protect against TZ-induced DNA damage in bone marrow. According to the results, Nano-CUR exerted a potential protective effect against oxidative stress, DNA damage, and the up-regulation of apoptosis-related genes induced by TZ ingested to rats.
| S-EPMC7763955 | biostudies-literature
Project description:We present a re-examination of mass spectral data obtained from the Pioneer Venus Large Probe Neutral Mass Spectrometer. Our interpretations of differing trace chemical species are suggestive of redox disequilibria in Venus' middle clouds. Assignments to the data (at 51.3 km) include phosphine, hydrogen sulfide, nitrous acid, nitric acid, carbon monoxide, hydrochloric acid, hydrogen cyanide, ethane, and potentially ammonia, chlorous acid, and several tentative PxOy species. All parent ions were predicated upon assignment of corresponding fragmentation products, isotopologues, and atomic species. The data reveal parent ions at varying oxidation states, implying the presence of reducing power in the clouds, and illuminating the potential for chemistries yet to be discovered. When considering the hypothetical habitability of Venus' clouds, the assignments reveal a potential signature of anaerobic phosphorus metabolism (phosphine), an electron donor for anoxygenic photosynthesis (nitrite), and major constituents of the nitrogen cycle (nitrate, nitrite, ammonia, and N2).
| S-EPMC8244101 | biostudies-literature
Project description:This study investigated the genotoxicity of Lapachol (LAP) evaluated by wing spot test of Drosophila melanogaster in the descendants from standard (ST) and high bioactivation (HB) crosses. This assay detects the loss of heterozygosity of marker genes expressed phenotypically on the fly's wings. Drosophila has extensive genetic homology to mammals, which makes it a suitable model organism for genotoxic investigations. Three-day-old larvae from ST crosses (females flr(3)/TM3, Bd(s) x males mwh/mwh), with basal levels of the cytochrome P450 and larvae of high metabolic bioactivity capacity (HB cross) (females ORR; flr(3)/TM3, Bd(s) x males mwh/mwh), were used. The results showed that LAP is a promutagen, exhibiting genotoxic activity in larvae from the HB cross. In other words, an increase in the frequency of spots is exclusive of individuals with a high level of the cytochrome P450. The results also indicate that recombinogenicity is the main genotoxic event induced by LAP.
| S-EPMC3036112 | biostudies-other
Project description:Specific immunotherapy (SIT) is the only specific remedy for the treatment of allergic diseases currently. B cells are important immune cells in the immunity. The role of B cells in immune regulatory activities has not been fully understood yet. This study aims to elucidate the role of the thrombospondin (TSP)1-producing B cells in the immune regulatory role of SIT. The results showed that after SIT, the frequency of CD35(+) B cells was increased in the intestine of mice with food allergy. The CD35(+) B cells expressed TSP1 after exposure to specific antigens. Co-culture with the TSP1-producing CD35(+) B cells decreased the levels of CD80/CD86 in dendritic cells; the cells convert naïve CD4(+) T cells to regulatory T cells to inhibit allergic inflammation in the intestine.
| S-EPMC4002291 | biostudies-literature
Project description:This is the report of the first workshop "Validation of Toxicogenomics-Based Test Systems" held 11-12 December 2003 in Ispra, Italy. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and organized jointly by ECVAM, the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The primary aim of the workshop was for participants to discuss and define principles applicable to the validation of toxicogenomics platforms as well as validation of specific toxicologic test methods that incorporate toxicogenomics technologies. The workshop was viewed as an opportunity for initiating a dialogue between technologic experts, regulators, and the principal validation bodies and for identifying those factors to which the validation process would be applicable. It was felt that to do so now, as the technology is evolving and associated challenges are identified, would be a basis for the future validation of the technology when it reaches the appropriate stage. Because of the complexity of the issue, different aspects of the validation of toxicogenomics-based test methods were covered. The three focus areas include a) biologic validation of toxicogenomics-based test methods for regulatory decision making, b) technical and bioinformatics aspects related to validation, and c) validation issues as they relate to regulatory acceptance and use of toxicogenomics-based test methods. In this report we summarize the discussions and describe in detail the recommendations for future direction and priorities.
| S-EPMC1392237 | biostudies-literature
Project description:The yeast Lachancea thermotolerans (previously Kluyveromyces thermotolerans) is a species of large, yet underexplored, oenological potential. This study delivers comprehensive oenological phenomes of 94?L. thermotolerans strains obtained from diverse ecological niches worldwide, classified in nine genetic groups based on their pre-determined microsatellite genotypes. The strains and the genetic groups were compared for their alcoholic fermentation performance, production of primary and secondary metabolites and pH modulation in Chardonnay grape juice fermentations. The common oenological features of L. thermotolerans strains were their glucophilic character, relatively extensive fermentation ability, low production of acetic acid and the formation of lactic acid, which significantly affected the pH of the wines. An untargeted analysis of volatile compounds, used for the first time in a population-scale phenotyping of a non-Saccharomyces yeast, revealed that 58 out of 90 volatiles were affected at an L. thermotolerans strain level. Besides the remarkable extent of intra-specific diversity, our results confirmed the distinct phenotypic performance of L. thermotolerans genetic groups. Together, these observations provide further support for the occurrence of domestication events and allopatric differentiation in L. thermotolerans population.
| S-EPMC6172252 | biostudies-literature
Project description:In grasslands, overgrazing by domestic livestock, fertilization, and introduction of exotic forage species leads to plant communities consisting of a mixture of native and exotic species. These degraded grasslands present a problem for land managers, farmers, and restoration ecologists concerned with improving biodiversity while continuing to use the land for livestock production. Here we assessed the response of butterfly and plant community composition to the use of fire and moderate grazing by domestic cattle on degraded grasslands dominated by exotic plants. We evaluated change by comparing experimental pastures to two reference sites that were grasslands dominated by native plants. We used two burning and grazing treatments: 1) patch-burn graze, a heterogeneously managed treatment, where one third of the pasture is burned each year and cattle have free access to the entire pasture, and 2) graze-and-burn, a homogenously managed treatment, where the entire pasture is grazed each year and burned in its entirety every three years. We tested for change in the butterfly and plant community composition over seven years using Bray-Curtis dissimilarity measures. Over the course of seven years, degraded pastures in both treatments became more similar to reference sites with respect to the butterfly and plant communities. Only two butterfly species and two plant functional guilds exhibited significant linear trends over time, with varying responses. Compositional changes in both the butterfly and plant communities indicate that the use of moderate grazing and fire may shift butterfly and plant communities of exotic-dominated grasslands to be more similar to reference tallgrass prairies over time.
| S-EPMC5098731 | biostudies-literature
Project description:Human disturbance to wildlife is on the rise and disturbance management is a key activity in conservation. Although disturbance can be controlled with relative ease in nature reserves that are properly resourced and managed by employed staff, most reserves do not fall into this category, and most wildlife exists outside managed reserves entirely. Thus, developing and demonstrating the effectiveness of simple, low-cost approaches to minimising disturbance is an important objective in conservation. In this study we examine the effectiveness of regulatory signs in controlling the behaviour and impacts of visitors on a colonial island-nesting bird, the Northern gannet (Morus bassanus), on an unmanaged island. First, we found that the percentage of successful nests declined with proximity to the disturbed edge of the colony, and was much higher in an undisturbed control area. Second, the number of birds displaced by visitors correlated negatively with the minimum visitor approach distance. Third, visitor proximity to the colony was dramatically reduced in the presence of a regulatory sign in comparison to periods without signs, which resulted in fewer birds being displaced from their nests. Photographers were the only visitor group who didn't always comply with the sign. Our results show that breeding success in a species often thought to be well adapted to human presence, suffers from tourist pressure, and that simple and informative regulatory signs can be a cost-effective way of reducing the disturbance caused by visitors at unmanaged wildlife sites.
| S-EPMC7546240 | biostudies-literature
Project description:Naked mole rat (NMR) is a valuable model for aging and cancer research due to its exceptional longevity and resistance to tumorigenesis. In an effort to generate NMR induced pluripotent stem cells (iPSCs) we observed that reprogramming efficiency of NMR fibroblasts in repsonse to OSKM overexpression was drasticaly lower than that of mouse fibroblasts. To understand the cause of NMR resistance to reprogramming we screened for factors that improve reprogramming effciency. We identified that expression of SV40 Large T (LT) dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was suffcient to improve reprogramming effciency suggesting that NMR chromatin structure is refractory to reprogramming. Analysis of global histone landscape using quantitative mass spectrometry revealed that NMR fibroblasts had higer levels of repressive H3K27 methylation marks, and lower levels of activating H3K27 acetylation mark than the mouse fibroblasts. Furthermore, the NMR cells had lower levels of permissive H2A.Z acetylation marks. ChIP showed that of E-cadherin had repressive H3K9me3 histone mark in the NMR, but was poised with a bivalent H3K4me3/H3K27me3 in the mouse. Expression of LT reduced the levels of H3K9me3 mark on E-cadherin promoter. ATAC-seq revealed that NMR had more open chromatin globally, however, NMR promoters were more closed than mouse promoters. Expression of LT antigen led to massive opening of the NMR promoters including gene promoters required for reprogramming. Cumulatively, these data suggest that NMR has more stable epigenome than mouse, which resists reprogramming and may contribute to NMR longevity and cancer resistance.
2017-06-21 | GSE83585 | GEO