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Exposure to toxic metals and metalloids is an important cause of preventable diseases worldwide. Inorganic arsenic (iAs) affects several organs and tissues, causing neurobehavioral alterations in the central nervous system (CNS) that might lead to neurodegeneration. In this work, we wanted to explore the time- and dose-related changes on glutathione (GSH) levels in several regions of the CNS, such as the cortex, striatum, hippocampus, and cerebellum, to identify the initial cellular changes associated to GSH depletion due to iAs exposure. Mice received a single intraperitoneal injection containing 5 or 14 mg/kg sodium arsenite. Animals were killed at 2, 6, and 24 h. Significant depletion of GSH levels was observed in the cortex at 2 and 6 h, while on the striatum, hippocampus, or cerebellum regions, no significant changes were observed. GSH depletion in the cortex was associated with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NFκB) pathways, which led to the upregulation of xCT, excitatory amino acid carrier 1 (EAAC1), glutamate/aspartate transporter (GLAST), and glial glutamate transporter 1 (GLT-1), and the activation of the transsulfuration pathways, which led to the overproduction of H S in the cortex and increased levels of GSH in the cortex and cerebellum at 24 h. In the cortex, the -methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B were also altered at 24 h. These early effects were not homogeneous among different brain regions and indicate early neurotoxic alterations in the cortex and cerebellum.

Glutathione (GSH) is the most abundant intracellular antioxidant. GSH depletion leads to oxidative stress and neuronal damage in the central nervous system (CNS). In mice, the acute systemic inhibition of GSH synthesis by L-buthionine-S-R-sulfoximine (BSO) triggers a protective response and a subsequent increase in the CNS GSH content. This response might be modulated by a peripheral increment of circulating nerve growth factor (NGF). NGF is an important activator of antioxidant pathways mediated by tropomyosin-related kinase receptor A (TrkA). Here, we report that peripheral administration of BSO increased plasma NGF levels. Additionally, BSO increased NGF levels and activated the NGF/TrkA/Akt pathway in striatal neurons. Moreover, the response in the striatum included an increased transcription of , , , , and , all of which are involved in antioxidant responses, and L-cys/L-cys and glutamate transporters. Using antibody against NGF confirmed that peripheral NGF activated the NGF/TrkA/Akt/Nrf2 pathway in the striatum and subsequently increased the transcription of , , , , and . These results provide evidence that the reduction of peripheral GSH pools increases peripheral NGF circulation that orchestrates a neuroprotective response in the CNS, at least in the striatum, through the NGF/TrkA/Akt/Nrf2 pathway.

Exposure to toxic elements in drinking water, such as arsenic (As) and fluoride (F), starts at gestation and has been associated with memory and learning deficits in children. Studies in which rodents underwent mechanistic single exposure to As or F showed that the neurotoxic effects are associated with their capacity to disrupt redox balance, mainly by diminishing glutathione (GSH) levels, altering glutamate disposal, and altering glutamate receptor expression, which disrupts synaptic transmission. Elevated levels of As and F are common in groundwater worldwide. To explore the neurotoxicity of chronic exposure to As and F in drinking water, pregnant CD-1 mice were exposed to 2 mg/L As (sodium arsenite) and 25 mg/L F (sodium fluoride) alone or in combination. The male litter continued to receive exposure up to 30 or 90 days after birth. The effects of chronic exposure on GSH levels, transsulfuration pathway enzymatic activity, expression of cysteine/cystine transporters, glutamate transporters, and ionotropic glutamate receptor subunits as well as behavioral performance in the object recognition memory task were assessed. Combined exposure resulted in a significant reduction in GSH levels in the cortex and hippocampus at different times, decreased transsulfuration pathway enzyme activity, as well as diminished xCT protein expression. Altered glutamate receptor expression in the cortex and hippocampus and decreased transaminase enzyme activity were observed. These molecular alterations were associated with memory impairment in the object recognition task, which relies on these brain regions.

BackgroundFew epidemiologic studies have focused on the specific source of ambient air pollution and adverse health effects in early life. Here, we investigated whether air pollutants from different emission sources were associated with decreased birth anthropometry parameters and increased DNA adduct formation in mother-child pairs residing in the Mexico City Metropolitan Area (MCMA).MethodsThis cross-sectional study included 190 pregnant women recruited during their last trimester of pregnancy from two hospitals at MCMA, and a Modeling Emissions Inventory (MEI) to calculate exposure to ambient air pollutants from different emissions sources (area, point, mobile, and natural) for two geographical buffers 250 and 750 m radii around the participants households.ResultsContaminants were positively correlated with umbilical cord blood (UCB) adducts, but not with maternal blood (MB) adducts. PM10 emissions (area and point sources, overall emissions), PM2.5 (point sources), volatile organic compounds (VOC), total organic compounds (TOC) from point sources were positively correlated with UCB adducts. Air pollutants emitted from natural sources were correlated with a decrease in MB and UCB adducts. PM10 and PM2.5 were correlated (p < 0.05) with a decrease in birth weight (BW), birth length (BL) and gestational age at term (GA). In multivariate analyses adjusted for potential confounders, PM10 was associated with an increase in UCB adducts. PM10 and PM2.5 from overall emissions were associated with a decrease in BW, BL and GA at term.ImpactResults suggested higher susceptibility of newborns compared to mothers to damage related to ambient air pollution. PMs are associated with birth anthropometry parameters and DNA damage in adjusted models, highlighting the need for more strict regulation of PM emissions.

Agave tequilana fructans are the source of fermentable sugars for the production of tequila. Fructans are processed by acid hydrolysis or by cooking in ovens at high temperature. Enzymatic hydrolysis is considered an alternative for the bioconversion of fructans. We previously described the isolation of Aspergillus niger CH-A-2010, an indigenous strain that produces extracellular inulinases. Here we evaluated the potential application of A. niger CH-A-2010 inulinases for the bioconversion of A. tequilana fructans, and its impact on the production of ethanol. Inulinases were analyzed by Western blotting and thin layer chromatography. Optimal pH and temperature conditions for inulinase activity were determined. The efficiency of A. niger CH-A-2010 inulinases was compared with commercial enzymes and with acid hydrolysis. The hydrolysates obtained were subsequently fermented by Saccharomyces cerevisiae to determine the efficiency of ethanol production. Results indicate that A. niger CH-A-2010 predominantly produces an exo-inulinase activity. Optimal inulinase activity occurred at pH 5.0 and 50 °C. Hydrolysis of raw agave juice by CH-A-2010 inulinases yielded 33.5 g/l reducing sugars, compared with 27.3 g/l by Fructozyme® (Novozymes Corp, Bagsværd, Denmark) and 29.4 g/l by acid hydrolysis. After fermentation of hydrolysates, we observed that the conversion efficiency of sugars into ethanol was 97.5 % of the theoretical ethanol yield for enzymatically degraded agave juice, compared to 83.8 % for acid-hydrolyzed juice. These observations indicate that fructans from raw Agave tequilana juice can be efficiently hydrolyzed by using A. niger CH-A-2010 inulinases, and that this procedure impacts positively on the production of ethanol.

Streptomyces sp. DSM 41796 produced four major extracellular xylanases with Mr of 145, 120, 60 and 45 kDa. Those of 145 and 60 kDa formed a heterodimer. All xylanases, except that of 120 kDa, were induced by xylose, d-arabinose or sucrose, while commercial xylans induced the 60 kDa xylanase in a major proportion than others, and sugar-cane bagasse pith or lemon peel induced predominantly the 45 kDa xylanase.[PUBLICATION ABSTRACT]

Eastern Europe and Central Asia (EECA) is one of the regions where the HIV epidemic continues to grow at a concerning rate. Antiretroviral therapy (ART) coverage in EECA countries has significantly increased during the last decade, which can lead to an increase in the risk of emergence, transmission, and spread of HIV variants with drug resistance (DR) that cannot be controlled. Because HIV genotyping cannot be performed in these countries, data about HIV DR are limited or unavailable. To monitor circulating HIV-1 genetic variants, assess the prevalence of HIV DR among patients starting antiretroviral therapy, and reveal potential transmission clusters among patients in six EECA countries: Armenia, Azerbaijan, Belarus, Russia, Tajikistan, and Uzbekistan. We analyzed 1071 HIV-1 pol-gene fragment sequences (2253-3369 bp) from patients who were initiating or reinitiating first-line ART in six EECA counties, i.e., Armenia (n = 120), Azerbaijan (n = 96), Belarus (n = 158), Russia (n = 465), Tajikistan (n = 54), and Uzbekistan (n = 178), between 2017 and 2019. HIV Pretreatment DR (PDR) and drug resistance mutation (DRM) prevalence was estimated using the Stanford HIV Resistance Database. The PDR level was interpreted according to the WHO standard PDR survey protocols. HIV-1 subtypes were determined using the Stanford HIV Resistance Database and subsequently confirmed by phylogenetic analysis. Transmission clusters were determined using Cluster Picker. Analyses of HIV subtypes showed that EECA, in general, has the same HIV genetic variants of sub-subtype A6, CRF63_02A1, and subtype B, with different frequencies and representation for each country. The prevalence of PDR to any drug class was 2.8% in Uzbekistan, 4.2% in Azerbaijan, 4.5% in Russia, 9.2% in Armenia, 13.9% in Belarus, and 16.7% in Tajikistan. PDR to protease inhibitors (PIs) was not detected in any country. PDR to nucleoside reverse-transcriptase inhibitors (NRTIs) was not detected among patients in Azerbaijan, and was relatively low in other countries, with the highest prevalence in Tajikistan (5.6%). The prevalence of PDR to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was the lowest in Uzbekistan (2.8%) and reached 11.1% and 11.4% in Tajikistan and Belarus, respectively. Genetic transmission network analyses identified 226/1071 (21.1%) linked individuals, forming 93 transmission clusters mainly containing two or three sequences. We found that the time since HIV diagnosis in clustered patients was significantly shorter than that in unclustered patients (1.26 years vs 2.74 years). Additionally, the K103N/S mutation was mainly observed in clustered sequences (6.2% vs 2.8%). Our study demonstrated different PDR prevalence rates and DR dynamics in six EECA countries, with worrying levels of PDR in Tajikistan and Belarus, where prevalence exceeded the 10% threshold recommended by the WHO for immediate public health action. Because DR testing for clinical purposes is not common in EECA, it is currently extremely important to conduct surveillance of HIV DR in EECA due to the increased ART coverage in this region.

Steady state flow boiling experiments were carried out on several heated tubes with outer diameter 9.14 mm at outlet pressures 120, 200 and 300 kPa, inlet temperatures 64, 78 and 91 °C and approximately 400, 500, 600 and 800 kg/(m2·s) mass flux entering the vertically aligned test annulus until critical heat flux (CHF) was reached. The tubes were made of Inconel 625 with a length of 400 mm. The Inconel tubes were tested in three different modifications as smooth, abraded with 150 grit sandpaper and bead blasted. Multiple experiments were repeated on the same specimen to investigate the effect of surface characteristic changes (i.e., wettability, roughness and oxide layer morphology) on the occurrence of CHF. Despite the changes in initial wettability, the CHF dependency was not clearly observed, however, the changes in roughness led to an increase in CHF. The total number of 115 experimental runs were collected and the results were also compared with other literature experimental data.

The article considers the calculation of the ultimate rupture load of multilayer floor slabs supported on three sides (two short and one long). The calculation is carried out taking into account three fracture schemes: the first scheme consists of three main destructive cracks that converge at one point, forming an \"envelope\"; the second scheme consists of two main inclined cracks passing from the corners towards the non-supported side and not converging on the plate field; the third scheme consists of a horizontal crack forming trapezoid in combination with angular cracks, which is the case when testing prototypes. The reduction of a three-layer section to a single-layer section is carried out according to the elasticity modules of the concretes that make up the section. The value of the rupture load is determined from the condition of equilibrium of external and internal forces. The results of the VAT analysis of multilayer reinforced concrete structures according to the proposed schemes were carried out by the authors on the basis of static tests of prototypes of flat reinforced concrete three-layer slabs. The obtained research results allow us to determine rational parameters for the design of multilayer slab structures with reinforced concrete layers of various strength.

[This corrects the article DOI: 10.1371/journal.pone.0257731.].