The impact of acute (48h) and subchronic (14 days) exposures to environmentally realistic atrazine concentrations (2, 10 and 25μgL−1) were evaluated on the gills of Prochilodus lineatus by assessing ...the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), the levels of reduced glutathione (GSH) and lipid peroxide (LPO) as well as the histopathological damage. Acute and subchronic exposure to atrazine at 2 or 25μgL−1 did not change the activities of GST, SOD, CAT or GPx or the concentrations of GSH and LPO; however, subchronic exposure to 10μgL−1 increased the activity of GST, SOD and CAT and the LPO level. Histopathological indexes indicated normal gill function with scattered epithelial changes after acute and chronic exposure to 2 or 10μgL−1 of atrazine; however, fish chronically exposed to 25μgL−1 of atrazine, although had scattered lesions, the severity of lesions resulted in slightly to moderately gill damage. Acute exposure to atrazine decreased the type 3 MCs (containing acid mucosubstances with sulfate esters) in fish exposed to 2 or 10μgL−1 and increased the type 4 MCs (containing all types of mucosubstances) in fish exposed to 25μgL−1. Chronic exposure to atrazine reduced the type 3 MCs in fish exposed to 10 or 25μgL−1. The gills showed a low sensitivity to atrazine after acute exposure. However, the persistence of atrazine in water (subchronic exposure) promoted an increase of LPO levels in the gills and increased the frequency and severity of histopathological changes. The decreased density of type 3 MCs in fish exposed to atrazine suggests a mechanism to wash toxic substances away from the gill surface.
► Acute exposure to realistic concentration of atrazine did not affect gill function. ► Subchronic exposure to atrazine changes the activities of antioxidant enzymes. ► Subchronic exposure to atrazine causes disperse slight to moderate gill damage. ► Atrazine affect mucous cell density after acute and subchronic exposure.
Ballistic impacts are a primary risk in both civil and military defence applications, where successfully predicting the dynamic response of a material or structure to impact crucial to the design of ...safe and fit-for-purpose protective structures. This study proposes a conditional Generative Adversarial Network (cGAN) architecture that can learn directly from available ballistic data and can be conditioned on additional information, such as class labels, to govern its output. A single Multi-Layer Perceptron (MLP) cGAN architecture is trained on a multi-class ballistic training set consisting of 10 classes labelled 0−9 where each class refers to a ballistic curve with a different ballistic limit velocity, vbl. A total of 5 models are trained on datasets consisting of 5, 10, 15, 20 and 25 samples within each class. For integer class labels 0−9, all cGAN models successfully predict the vbl with a maximum error of 4.12%. Additionally, for non-integer class labels between 0−9 the vbl predictions are similar despite not explicitly appearing in the training set. Moreover, each cGAN model is challenged to generate new samples for class labels that exist beyond the scope of the training set for class labels between 9−20. Four of the models predict the vbl with an error of less than 1.5% in all cases. This study showcases how a cGAN model can learn directly from a multi-class ballistic dataset and generate additional samples representative of that data for classes that do not appear explicitly in the training set.
•Conditional Generative Adversarial Networks (cGAN) learn from multi-class datasets.•Paper proposes a unique solution to minimising cost of armour testing and design.•Method predicts ballistic impacts generating accurate ballistic curves.•Proposed cGAN method accurately predicts classes outside the training set.
Xanthine oxidase (XO), an enzyme widely distributed among mammalian tissues, is associated with the oxidation of xanthine and hypoxanthine to form uric acid. Reactive oxygen species are also released ...during this process, leading to oxidative damages and to the pathology called gout. Available treatments mainly based on allopurinol cause serious side effects. Natural products such as flavonoids may represent an alternative. Thus, a series of polymethoxyflavones isolated and hemisynthesized from the bud exudates of Gardenia oudiepe has been evaluated for in vitro XO inhibitory activity. Compounds 1, 2 and 3 were more active than the reference inhibitor, Allopurinol (IC50 = 0.25 ± 0.004 μM) with IC50 values of (0.004 ± 0.001) μM, (0.05 ± 0.01) μM and (0.09 ± 0.003) μM, respectively. Structure-activity relationships were established. Additionally, a molecular docking study using MOE™ tool was carried out to establish the binding mode of the most active flavones with the enzyme, showing important interactions with its catalytic residues.
These promising results, suggest the use of these compounds as potential leads for the design and development of novel XO inhibitors.
Display omitted
•Xanthine oxidase inhibitory activity of polymethoxyflavones from Gardenia oudiepe was determinate.•Some compounds were more actives than Allopurinol, with IC50 in the nanomolar range.•SAR and docking studies were determinate for those compounds for the first time.
Introduction
The innermost relationship of the borderline concept and psychosis has been historically intertwined and can be traced back to the 20th century, but remarkably, to date, they have not ...been the focus of many empirical studies. Likewise, the contributions of empirical research on the DSM-5 dimensional approach to this topic are also uncommon.
Objectives
In this study the framework of psychosis superspectrum were put closely in relation to both DSM-5 psychoticism/detachment domains, personality traits and psychopathological symptoms features in borderline personality disorder (PD).
Methods
A cross-sectional study of a borderline PD sample of 58 participants (
M
age
=39.76 years,
SD
=11.37;
M
schooling
=9 years), mainly male (58.5%). Self-reported assessment: PID-5; BSI; NEO-FFI. A multiple linear regression was computed.
Results
In borderline PD, the PID-5 disinhibition (β=.51), BSI psychoticism (β=.43), BSI depression (β=-.24) and NEO neuroticism (β=.29) predicted psychosis superspectrum, explaining 94% of the variance. Also, stands out as a complement that, the BSI psychoticism was predicted by PID-5 detachment and PID-5 psychoticism, explaining 82% of the variance.
Conclusions
Evidence appears to be emerging for the underlying psychosis superspectrum trough borderline PD. There is a closer dialogue between the state-of-art view of a dimensional pathological personality-symptoms and the borderline pathology.
Disclosure of Interest
None Declared
Osteosynthesis is an alternative treatment for stabilizing femur-bone traumas. The initial stability of the fixation systems is one of the biomechanical parameters affecting implant failure and bone ...union, especially in surgeries of intercalary reconstructions after the removal of bone tumors. This study aimed to investigate the initial biomechanical effect of using one or two osteosynthesis plate configurations for femoral fixation and the effect of fastening the allograft to the osteosynthesis plate in the case of femoral allograft reconstructions.
Three finite-element models of a femur with three different fixation conditions for a transverse osteotomy in the middle of the diaphysis, i.e., using one and two osteosynthesis plates and an intercalary allograft, were constructed. An eight-hole compression plate and a six-hole second plate were used to simulate osteosynthesis plates. The plate screws were tightened previously to the loading, and the tightening sequences simulate the bolt-tightening procedure in a surgical environment. The models were imported into the ADINA System for nonlinear analysis, using compression loads applied over the femur head.
Models with the dual fixation systems had the most outstanding compression stiffness. The femur head movement in the dual plate system was 24.8% smaller than in the single plate system. A statistical analysis of a region of interest (VOI) placed in the femur diaphysis showed that the biomechanical effect of using the dual plate system is smaller in the osteotomy region than at the femur head, e.g., a displacement average decrease of only 5% between the two systems, while the maximum value decreases by 26.8%. The allograft fixation to the second osteosynthesis plate leads to an improvement in the system stability.
The results presented in this work show that including the bolt analysis in the femoral diaphysis osteotomy fixation will allow for capturing the nonlinear behavior of the osteotomy region more realistically. The stability of the intercalary reconstruction of the femoral diaphysis was higher when the allograft was fastened to the second osteosynthesis plate.
► We investigate the gills of a neotropical fish after atrazine exposure. ► Atrazine exposure inhibited the carbonic anhydrase activity. ► Na+/Cl− ratio did not change after atrazine exposure. ► ...Atrazine did not change Na+/K+-ATPase activity. ► Morphological gill cells responses maintained ionic homeostase.
The effects of the herbicide atrazine on the gill of the freshwater fish Prochilodus lineatus were evaluated after exposure of fish to 2, 10 and 25μgL−1 atrazine during 48h (acute exposure) and 14d (subchronic exposure). Ions and osmolality were measured in plasma and gill samples were taken to determine the Na+/K+-ATPase (NKA) and carbonic anhydrase (CA) activities and for morphological analysis. Plasma osmolality and Na+ and Cl− ions changed depending on atrazine concentration, but atrazine exposure had no effect on the Na+/Cl− ratio. NKA activity did not change after atrazine exposure, but CA activity decreased in fish exposed to 25μgL−1 for 14d. Gill MRC density decreased after acute exposure but did not change in fish exposed to the subchronic treatment. The MRC density at the epithelial surface increased in fish exposed to 25μgL−1, and the MRC fractional area (MRCFA) increased in fish exposed to 10μgL−1. The changes in MRCs provide evidence of morphological adjustments to maintain ionic homeostasis in spite of the inhibition of CA activity at the highest atrazine concentration.
Glioblastoma (GB) is the most common and lethal type of primary brain tumor. Clinical outcome remains poor and is essentially palliative due to the highly invasive nature of the disease. A more ...thorough understanding of the molecular mechanisms that drive glioma invasion is required to limit dispersion of malignant glioma cells.
We investigated the potential role of differential expression of microRNAs (miRNA) in glioma invasion by comparing the matched large-scale, genome-wide miRNA expression profiles of migrating and migration-restricted human glioma cells. Migratory and migration-restricted cell populations from seven glioma cell lines were isolated and profiled for miRNA expression. Statistical analyses revealed a set of miRNAs common to all seven glioma cell lines that were significantly down regulated in the migrating cell population relative to cells in the migration-restricted population. Among the down-regulated miRNAs, miR-23b has been reported to target potential drivers of cell migration and invasion in other cell types. Over-expression of miR-23b significantly inhibited glioma cell migration and invasion. A bioinformatics search revealed a conserved target site within the 3' untranslated region (UTR) of Pyk2, a non-receptor tyrosine kinase previously implicated in the regulation of glioma cell migration and invasion. Increased expression of miR-23b reduced the protein expression level of Pyk2 in glioma cells but did not significantly alter the protein expression level of the related focal adhesion kinase FAK. Expression of Pyk2 via a transcript variant missing the 3'UTR in miR-23b-expressing cells partially rescued cell migration, whereas expression of Pyk2 via a transcript containing an intact 3'UTR failed to rescue cell migration.
Reduced expression of miR-23b enhances glioma cell migration in vitro and invasion ex vivo via modulation of Pyk2 protein expression. The data suggest that specific miRNAs may regulate glioma migration and invasion to influence the progression of this disease.
Highlights • The RMS errors of predicted strains showed that modeling cortical bone with isotropic material properties led to higher errors. • The strain level of the cancellous bone can be ...significantly affected by the material properties of the cortical bone. • These results suggest that, in comparison with FE models, the µFE models will tend to decrease the fraction of cancellous tissue that is under low-loaded and increase the SD values. • The local behavior of femur-implanted systems can only be realistically improved if the composite behavior of cortical bone is numerically accounted for.
This study evaluates the levels of messenger RNA (mRNA) for eIF4E, PARN, H1FOO, cMOS, GDF9, and CCNB1 in oocytes from secondary and antral follicles at different stages of development. The effects of ...in vitro culture, in vitro prematuration, and in vitro maturation on the expression of these genes on oocytes were also analyzed. The results showed that mRNA levels for H1FOO, GDF9, and PARN were higher in oocytes from small, medium, and large antral follicles, respectively, than those seen in secondary follicles. Oocytes from small, medium, and large antral follicles had higher levels of CCNB1 than oocytes from secondary follicles. Oocytes from cultured secondary follicles had higher levels of GDF9, CMOS, PARN, eIF4E, CCNB1, and H1FOO than before culture. Prematured oocytes from small antral follicles had higher levels of mRNA for GDF9, PARN, and eIF4E than before culture. In addition, higher levels of cMOS and H1FOO were identified in prematured oocytes from medium antral follicles. In conclusion, follicular growth is associated with an increase in the expression of H1FOO, GDF9, CCNB1, and PARN. The culture of secondary follicles, prematuration, and maturation of oocytes from antral follicles increase the expression of eIF4E, PARN, H1FOO, cMOS, GDF9, and CCNB1.
Follicular growth increases expression of maturation‐related genes in vitro culture of preantral follicles increase gene expression prematuration and maturation of oocytes increases gene expression.
This study aims to investigate the effects of melatonin on follicular growth, viability and ultrastructure, as well as on the levels of mRNA for antioxidant enzymes, reactive oxygen species (ROS) and ...meiotic progression in oocytes from in vitro cultured bovine early antral follicles. To this end, isolated early antral follicles (500–600 μm) were cultured in TCM‐199+ alone or supplemented with 10−6, 10−7 or 10−8 M melatonin at 38.5°C with 5% CO2 for 8 days. Follicle diameters were evaluated at days 0, 4 and 8 of culture. At the end of culture, ultrastructure, chromatin configuration, viability (calcein‐AM and ethidium homodimer‐1 staining), and the levels of ROS and mRNA for catalase (CAT), superoxide dismutase (SOD) and peroxiredoxin 6 (PRDX6) and glutathione peroxidase (GPx) were investigated in oocyte‐granulosa cell complexes (OGCs). The results showed that early antral follicles cultured with 10−6 and 10−8 M melatonin had a progressive and significant increase in their diameters throughout the culture period (p < .05). Additionally, oocytes from follicles cultured with 10−7 or 10−8 M melatonin had increased fluorescence for calcein‐AM, while those cultured with 10−6 or 10−7 M had reduced fluorescence for ethidium homodimer‐1. Different from follicles cultured in other treatments, those cultured with 10−8 M melatonin had well‐preserved ultrastructure of oocyte and granulosa cells. Melatonin, however, did not influence the levels of ROS, the mitochondrial activity, oocyte meiotic resumption and expression mRNA for SOD, CAT, GPX1 and PRDX6. In conclusion, the presence of 10−8 M melatonin in culture medium improves viability and preserves the ultrastructure of oocyte and granulosa cells of early antral follicles cultured in vitro.
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