Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide, causing a wide spectrum of conditions with severity classified from the mildest (Class IV) to the ...most severe (Class I). To correlate mutation sites in the G6PD with the resulting phenotypes, we studied four naturally occurring G6PD variants: Yucatan, Nashville, Valladolid and Mexico City. For this purpose, we developed a successful over-expression method that constitutes an easier and more precise method for obtaining and characterizing these enzymes. The k(cat) (catalytic constant) of all the studied variants was lower than in the wild-type. The structural rigidity might be the cause and the most evident consequence of the mutations is their impact on protein stability and folding, as can be observed from the protein yield, the T50 (temperature where 50% of its original activity is retained) values, and differences on hydrophobic regions. The mutations corresponding to more severe phenotypes are related to the structural NADP+ region. This was clearly observed for the Classes III and II variants, which became more thermostable with increasing NADP+, whereas the Class I variants remained thermolabile. The mutations produce repulsive electric charges that, in the case of the Yucatan variant, promote increased disorder of the C-terminus and consequently affect the binding of NADP+, leading to enzyme instability.
Eating disorders (EDs) are a significant health issue in combat sports. This study investigated the differences between the different types of female wrestlers and the frequency at which EDs occur in ...the elite population, and it also sought to establish which factors are predictors of EDs. This study was comprised of 22 elite, female wrestlers who were selected based on the following inclusion criteria: having previously been the Spanish champion, being part of the Spanish national team, participating in at least one international championship, and having a history of ED. Data collection involved five questionnaires: demographic data, the Eating Attitudes Test-26 (EAT-26), the Bulimic Investigatory Test, the Edinburgh (BITE), the Eating Disorders Inventory (EDI-3), and the Depression, Anxiety, and Stress Scale (DASS-21). The results revealed diverse levels of depression, anxiety, and stress, with BITE scores indicating abnormal eating patterns. Group comparisons exposed significant distinctions in eating behaviors based on competition and training experience. Regression analyses showed competition and training experience as predictors of bulimia severity and symptoms. The study revealed prevalent extreme weight-control practices, including fasting, diuretic and laxative use, and binge eating. This research emphasizes the importance of EDs in Olympic wrestling, urging a comprehensive approach involving education, support, and policy implementation by coaches, health professionals, and sports organizations to prioritize athletes' well-being and discourage unhealthy weight-control practices.
Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein ...(CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development in vivo by at least 97%. Crystal structures of antibody fragments (Fabs) 311 and 317 with an (NPNA)₃ peptide illustrate their different binding modes. Notwithstanding, one and three of the three NPNA repeats adopt similar well-defined type I β-turns with Fab311 and Fab317, respectively. Furthermore, to explore antibody binding in the context of P. falciparum CSP, we used negative-stain electron microscopy on a recombinant shortened CSP (rsCSP) construct saturated with Fabs. Both complexes display a compact rsCSP with multiple Fabs bound, with the rsCSP–Fab311 complex forming a highly organized helical structure. Together, these structural insights may aid in the design of a next-generation malaria vaccine.
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which encodes a polyglutamine tract in the HTT ...protein. We found that peroxisome proliferator-activated receptor delta (PPAR-δ) interacts with HTT and that mutant HTT represses PPAR-δ-mediated transactivation. Increased PPAR-δ transactivation ameliorated mitochondrial dysfunction and improved cell survival of neurons from mouse models of HD. Expression of dominant-negative PPAR-δ in the central nervous system of mice was sufficient to induce motor dysfunction, neurodegeneration, mitochondrial abnormalities and transcriptional alterations that recapitulated HD-like phenotypes. Expression of dominant-negative PPAR-δ specifically in the striatum of medium spiny neurons in mice yielded HD-like motor phenotypes, accompanied by striatal neuron loss. In mouse models of HD, pharmacologic activation of PPAR-δ using the agonist KD3010 improved motor function, reduced neurodegeneration and increased survival. PPAR-δ activation also reduced HTT-induced neurotoxicity in vitro and in medium spiny-like neurons generated from stem cells derived from individuals with HD, indicating that PPAR-δ activation may be beneficial in HD and related disorders.
In this work, we developed a novel heterostructure based on the coupling of a metal organic framework (MOF LEEL-037) with an inorganic semiconductor (SrZrO
3
) for two photocatalytic applications: ...hydrogen evolution from water splitting and the degradation of indigo carmine dye. A complete study of the structural, morphological, textural, optical, electronic, and electrochemical properties of MOF, SrZrO
3
and the heterostructure is presented through X-ray diffraction, scanning electron microscopy, UV–Vis diffuse reflectance spectroscopy (UV–Vis), photoluminescence spectroscopy and electrochemical impedance spectroscopy, evaluating the effect of these parameters on the catalytic performance of the materials. The heterostructure formation was studied by transmission electron microscopy, varying the loading of LEEL-037 from 0.5 to 5%. Microscope images corroborate the effective dispersion of LEEL-037 and the appropriate contact between the metal organic framework and SrZrO
3
particles. It was found that the photocatalytic activity of SrZrO
3
under UV light was significantly enhanced with the incorporation of MOF LEEL-037, which enhances the charge separation and transport, leading to an improved photocatalytic performance. After 1 h of reaction, the heterostructure with the optimal amount of LEEL-037 (5%) exhibited a hydrogen evolution of 66.9 µmol, corresponding to 6 times the activity of pure SrZrO
3
(11.2 µmol). LEEL-037 exhibited an activity of 34.1 µmol, but the rate of hydrogen production was not constant. The stability and efficiency of the charge transference in the bare semiconductors and the heterostructure were studied through photoluminescence and electrochemical analysis, which demonstrated the suitable band coupling between SrZrO
3
with MOF LEEL-037, the enhanced charge separation and injection from one semiconductor to another, and the reduction in the recombination of the electron–hole pairs. These studies and the integral correlation of the properties of the materials allowed to establish the path of the photogenerated charges and to propose the photocatalytic mechanisms involved in the reactions. The photocatalysts were also evaluated for the degradation of indigo carmine, where the highest dye degradation (69%) was exhibited by the heterostructure. Based on our results, we propose the use of the heterostructure SrZrO
3
-5% MOF LEEL-037, obtained by an easy and low cost method, as a suitable new photocatalytic material for environmental and energy applications, highlighting at the same time the promising properties of metal–organic frameworks for their coupling with a variety of inorganic semiconductors.
Thick and homogeneous hybrid film systems based on poly(methyl methacrylate) (PMMA) and CeO2 nanoparticles were synthesized using the melt compounding method to improve thermal stability, mechanical ...and UV-shielding properties, as well as to propose them for use in the multifunctional materials industry. The effect of the inorganic phase on these properties was assessed by using two different weight percentages of synthesized CeO2 nanoparticles (0.5 and 1.0 wt %) with the sol–gel method and thermal treatment at different temperatures (120, 235, 400, 600 and 800 °C). Thereafter, the nanoceria powders were added to the polymer matrix by single screw extrusion. The absorption in the UV region was increased with the crystallite size of the CeO2 nanoparticles and the PMMA/CeO2 weight ratio. Due to the crystallinity of CeO2 nanoparticles, the thermal, mechanical and UV-shielding properties of the PMMA matrix were improved. The presence of CeO2 nanostructures exerts an influence on the mobility of PMMA chain segments, leading to a different glass transition temperature.
Eysenhardtia polystachya is used for the empirical treatment of cancer, infections, diarrhea, inflammation, and pain. This study identified, using GC-MS, the main chemical components in an ethanol ...extract of E. polystachya branches and leaves (EPE) and tested its cytotoxic, antimicrobial, anti-diarrheal, anti-inflammatory, and antinociceptive effects. The in vitro and in vivo toxicity of EPE was evaluated using the comet assay in human peripheral blood mononuclear cells (PBMC) and the acute toxicity test in mice, respectively. The cytotoxic and the antimicrobial effects were performed using the MTT assay and the minimum inhibitory concentration (MIC) test, respectively. The levels of pro-inflammatory mediators in LPS-stimulated macrophages were measured to evaluate the in vitro anti-inflammatory effects of EPE. The antidiarrheal (castor oil test, small intestine transit, and castor oil-induced enteropooling), and anti-inflammatory activities (TPA and carrageenan) of EPE were also performed. The antinociceptive actions of EPE were carried out with the following tests: acetic acid, formalin, and hot plate. The hypnotic and locomotor effects were analyzed using pentobarbital and a rotarod system, respectively. The main component in EPE was D-pinitol (26.93%). The antidiarrheal and antinociceptive effects of D-pinitol were also evaluated. EPE showed low in vitro toxicity (DNA damage in PBMC at concentrations higher than 200 µg/ml), and low in vivo toxicity (LD50 > 2000 mg/kg i.p. and p.o.). Furthermore, EPE lacked cytotoxic activity (IC50 > 300 µg/ml) on human cancer cells, but showed good antimicrobial effects in E. coli (MIC=1.56 µg/ml) and S. aureus (MIC = 0.78 µg/ml). In multi-drug resistant microorganisms, EPE showed MIC> 100 µg/ml. EPE exerted in vitro anti-inflammatory effects, mainly, by the decrease in the production of H2O2 (IC50 = 43.9 ± 3.8 µg/ml), and IL-6 (73.3 ± 6.9 µg/ml). EPE (ED50 =7.5 ± 0.9 mg/kg) and D-pinitol (ED50 = 0.1 ± 0.03 mg/kg) showed antidiarrheal activity, and antinociceptive effects in the acetic acid test with ED50 = 117 ± 14.5 mg/kg for EPE and 33 ± 3.2 mg/kg for D-pinitol. EPE showed also antinociceptive activity in the phase 2 of the formalin test (ED50 = 48.9 ± 3.9 mg/kg), without inducing hypnotic effects or altering the locomotor activity in mice. The results here presented corroborate the folk medicinal use of Eysenhardtia polystachya in the treatment of infections, diarrhea, inflammation, and pain. D-pinitol, the main metabolite of EPE, showed antinociceptive and antidiarrheal effects with similar potency compared to standard drugs.
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Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and lethal disease, whose pathogenesis is associated with fibroblasts/myofibroblasts foci that produce excessive extracellular ...matrix accumulation in lung parenchyma. Hypoxia has been described as a determinant factor in its development and progression. However, the role of distinct members of this pathway is not completely described.
By western blot, quantitative PCR, Immunohistochemistry and Immunocitochemistry were evaluated, the expression HIF alpha subunit isoforms 1, 2 & 3 as well, as their role in myofibroblast differentiation in lung tissue and fibroblast cell lines derived from IPF patients.
Hypoxia signaling pathway was found very active in lungs and fibroblasts from IPF patients, as demonstrated by the abundance of alpha subunits 1 and 2, which further correlated with the increased expression of myofibroblast marker αSMA. In contrast, HIF-3α showed reduced expression associated with its promoter hypermethylation.
This study lends further support to the involvement of hypoxia in the pathogenesis of IPF, and poses HIF-3α expression as a potential negative regulator of these phenomena.
The benefits provided by tropical rainforests are unevenly distributed throughout the landscape and are shaped by abiotic and biotic components that influence the spatial distribution and functional ...traits of the species involved. We tested whether environmental stratification of the rainforest in biophysical Landscape Units (LU), defined by topography and soil, is related to the spatial distribution of diversity, abundance and productivity (standing biomass) of tree assemblages that provide potential forest products (PFP). Considering that different PFP are associated with specific plant traits, we also tested whether a phylogenetic signal exists among the species that comprise specific use categories. Non-metric multidimensional scaling ordinations and permutational analysis of variance were based on the frequency, abundance and productivity of 129 species, the PFP of which were classified as fodder, food, fuelwood, medicinal, melliferous, ornamental, plywood and timber in 15 plots of 0.5 ha each. We constructed a phylogenetic tree of the studied species and analyzed the phylogenetic signal strength (D-statistic) among them. The spatial distribution of diversity and abundance of useful species changes among the LU. Specific PFP can be provided in contrasting habitat conditions, but generally not by the same species. The PFP categories that presented a phylogenetic signal were associated with wood characteristics (fuelwood and plywood) and the palatability of the leaves and reproductive structures (fodder). The Moraceae family was significantly related to fodder and plywood, whereas Meliaceae, Myrtaceae and Sapotaceae were mostly used for fuelwood. The medicinal species presented convergent traits distributed throughout the phylogeny. However, since our study included a broad variety of plant structures, it is possible that phylogenetic dispersion can change if we consider the specific uses within each category. Our findings show that the assemblages of PFP suppliers can be clustered through biophysical units based on soil and topography, and specific categories of PFP are often supplied by phylogenetically related species. This knowledge is fundamental in order to incorporate the high diversity of tree species and their potential uses into productive reforestation and agroforestry programs.
•Soil topographic units capture contrasting habitat mosaics in tropical rain forest.•Diversity and availability of potential forest products change among units.•Potential forest products showed different phylogenetic patterns.•Biophysical and phylogenetic criteria nest useful trees spatial distribution.
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