84 research outputs found

    Modeling the interannual variability in Maipo and Rapel river plumes off central Chile

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    River plumes have a direct influence on coastal environments, impacting coastal planktonic and benthic communities, including fishery resources. In general, the main drivers of river plume dynamics are the river discharge and the alongshore wind stress, whereas the tides and topography play a secondary role. In central Chile, rivers flowing into the eastern Pacific have a relatively short path on land, with a high slope and a mixed snow–rain regime. This study aims to understand the interannual variability in the plumes of the Maipo and Rapel rivers in the coastal/shelf area off central Chile and their influence on local ocean dynamics. We used the Coastal and Regional Ocean Community (CROCO) model, with 1 km horizontal resolution and 20 sigma levels, to simulate the ocean dynamics for the period 2003–2011. The results show that the plume's area coverage and coastal ocean salinity are strongly correlated with the river discharges. The predominant northeastward winds control the plumes' orientation toward the northwest. However, episodes of southeastward winds in winter can reverse the plumes' direction, promoting their attachment to the coast and southward transport. Results also show a salification trend linked to the severe droughts hitting central Chile during the studied period. This salification determines a change in local dynamics which could be more frequent in future scenarios of climate change with a significant lack of rain and river discharges along central Chile.</p

    Estimation of extreme wave height return periods from short-term interpolation of multi-mission satellite data: application to the South Atlantic

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    We analyzed the spatial pattern of wave extremes in the South Atlantic Ocean by using multiple altimeter platforms spanning the period 1993–2015. Unlike the traditional approach adopted by previous studies, consisting of computing the monthly mean, median or maximum values inside a bin of certain size, we tackled the problem with a different procedure in order to capture more information from short-term events. All satellite tracks occurring during a 2-day temporal window were gathered in the whole area and then gridded data were generated onto a mesh size of 2° × 2° through optimal interpolation. The peaks over threshold (POT) method was applied, along with the generalized Pareto distribution (GPD). The results showed a spatial distribution comparable to previous studies and, additionally, this method allowed for capturing more information on shorter timescales without compromising spatial coverage. A comparison with buoy observations demonstrated that this approach improves the representativeness of short-term events in an extreme events analysis.</p

    Correlations between Background Radiation inside a Multilayer Interleaving Structure, Geomagnetic Activity, and Cosmic Radiation: A Fourth Order Cumulant-based Correlation Analysis

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    In this work, we analyzed time-series of background radiation inside a multilayer interleaving structure, geomagnetic activity and cosmic-ray activity using the Pearson correlation coefficient and a new correlation measure based on the one-dimensional component of the fourth order cumulant. The new method is proposed based on the fact that the cumulant of a random process is zero if it is of Gaussian nature. The results show that this methodology is useful for detecting correlations between the analyzed variables.Comment: 8 pages, 2 figures and 4 table

    S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo

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    BACKGROUND: Oxidative and nitrosative stress have been involved in gentamicin-induced nephrotoxicity. The purpose of this work was to study the effect of S-allylmercaptocysteine, a garlic derived compound, on gentamicin-induced oxidative and nitrosative stress and nephrotoxicity. In addition, the in vitro reactive oxygen species scavenging properties of S-allylmercaptocysteine were studied. RESULTS: S-allylmercaptocysteine was able to scavenge hydroxyl radicals and singlet oxygen in vitro. In rats treated with gentamicin (70 mg/Kg body weight, subcutaneously, every 12 h, for 4 days), renal oxidative stress was made evident by the increase in protein carbonyl content and 4-hydroxy-2-nonenal, and the nitrosative stress was made evident by the increase in 3-nitrotyrosine. In addition, gentamicin-induced nephrotoxicity was evident by the: (1) decrease in creatinine clearance and in activity of circulating glutathione peroxidase, and (2) increase in urinary excretion of N-acetyl-β-D-glucosaminidase, and (3) necrosis of proximal tubular cells. Gentamicin-induced oxidative and nitrosative stress and nephrotoxicity were attenuated by S-allylmercaptocysteine treatment (100 mg/Kg body weight, intragastrically, 24 h before the first dose of gentamicin and 50 mg/Kg body weight, intragastrically, every 12 h, for 4 days along gentamicin-treatment). CONCLUSION: In conclusion, S-allylmercaptocysteine is able to scavenge hydroxyl radicals and singlet oxygen in vitro and to ameliorate the gentamicin-induced nephrotoxicity and oxidative and nitrosative stress in vivo

    Proteomic Analysis of the Cyst Stage of Entamoeba histolytica

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    We used tandem mass spectrometry to identify E. histolytica cyst proteins in 5 cyst positive stool samples. We report the identification of 417 non-redundant E. histolytica proteins including 195 proteins that were not identified in existing trophozoite derived proteome or EST datasets, consistent with cyst specificity. Because the cysts were derived directly from patient samples with incomplete purification, a limited number of proteins were identified (N = 417) that probably represent only a partial proteome. Nevertheless, the study succeeded in identifying proteins that are likely to be abundant in the cyst stage of the parasite. Several of these proteins may play roles in E. histolytica stage conversion or cyst function. Proteins identified in this study may be useful markers for diagnostic detection of E. histolytica cysts. Overall, the data generated in this study promises to aid the understanding of the cyst stage of the parasite which is vital for disease transmission and pathogenesis in E. histolytica

    Inhibitors of trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

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    Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Ã…) to gain insight into the potential specificity of the interaction with the BNIP compounds. In conclusion, the search for TcSir2rp1 specific inhibitors may represent a valuable strategy for drug discovery against T. cruzi

    Senescent cells as a source of inflammatory factors for tumor progression

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    Cellular senescence, which is associated with aging, is a process by which cells enter a state of permanent cell cycle arrest, therefore constituting a potent tumor suppressive mechanism. Recent studies show that, despite the beneficial effects of cellular senescence, senescent cells can also exert harmful effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescent-associated secretory phenotype (SASP), which entails a striking increase in the secretion of pro-inflammatory cytokines. Here, we summarize our knowledge of the SASP and the impact it has on tissue microenvironments and ability to stimulate tumor progression

    X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

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    Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

    Nucleoside/nucleotide reverse transcriptase inhibitor sparing regimen with once daily integrase inhibitor plus boosted darunavir is non-inferior to standard of care in virologically-suppressed children and adolescents living with HIV – Week 48 results of the randomised SMILE Penta-17-ANRS 152 clinical trial

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