Superoxide Dismutase (SOD)-mimetic M40403 is protective in cell and fly models of paraquat toxicity: Implications for Parkinson disease

Parkinson disease is a debilitating and incurable neurodegenerative disorder affecting 3c1-2% of people over 65 years of age. Oxidative damage is considered to play a central role in the progression of Parkinson disease and strong evidence links chronic exposure to the pesticide paraquat with the incidence of the disease, most probably through the generation of oxidative damage. In this work, we demonstrated in human SH-SY5Y neuroblastoma cells the beneficial role of superoxide dismutase (SOD) enzymes against paraquat-induced toxicity, as well as the therapeutic potential of the SOD-mimetic compound M40403. Having verified the beneficial effects of superoxide dismutation in cells, we then evaluated the effects using Drosophila melanogaster as an in vivo model. Besides protecting against the oxidative damage induced by paraquat treatment, our data demonstrated that in Drosophila M40403 was able to compensate for the loss of endogenous SOD enzymes, acting both at a cytosolic and mitochondrial level. Because previous clinical trials have indicated that the M40403 molecule is well tolerated in humans, this study may have important implication for the treatment of Parkinson disease

Characterization of the turbulent flame front surface in spark ignition engines during spark ignition operation to identify controlled auto-ignition and abnormal combustion

This is the author's version of a work that was accepted for publication in International Journal of Engine Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published as https://doi.org/10.1177/1468087420933780[EN] The combustion diagnostics and subsequent analysis are standardized tools based on the estimation of the heat release law (HRL). From this estimation, the different combustion parameters can be obtained: combustion phasing and duration, heat release rate, and so on. This analysis might be usually enough to study traditional spark ignition (SI) engines. However, with the new upcoming SI engines, this is probably not the case anymore, since different combustion modes can be operated in the same engine, as for instance a combination of SI and controlled auto-ignition (CAI) combustion modes. When different combustion modes are combined, it seems interesting to study in more depth the HRL, trying to get more data and to study the differences among the diverse combustion modes. Toward this end, a methodology to go deeper in the study of the HRL is proposed in this work, consisting of, mainly quantifying and taking into account the most relevant influencing parameters: the fuel properties (mainly its lower heating value), the in-cylinder oxygen content, the density of the burned and unburned zones, the laminar combustion speed, and the turbulence effect. With the proposed methodology, a standard SI combustion, developed by a flame front, can be characterized at any given operating point. This would allow to predict which the combustion developement would be, at this operating point, assuming it to be developed by a flame front. Subsequently, this SI combustion prediction can be compared to the one obtained experimentally, making it possible to identify and analyze abnormal combustion phenomena, as well as to study the differences between a combustion developed by a flame front (SI) and by auto-ignition (CAI). Derived from this work, an alternative equation to experimentally characterize the laminar combustion velocity has also been proposed, in order to improve its applicability in a wider range of fuel/air ratios and dilution degrees.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: the Spanish Ministry of Science, Innovation and Universities for funding the PhD. studies of Jorge Valero-Marco (contract BES-2016-077610). This work was partly funded by Renault, and by FEDER and the Spanish Government through project TRA2015-67136-R.Macian Martinez, V.; López, JJ.; Martín, J.; Valero-Marco, J. (2021). Characterization of the turbulent flame front surface in spark ignition engines during spark ignition operation to identify controlled auto-ignition and abnormal combustion. International Journal of Engine Research. 22(7):2149-2168. https://doi.org/10.1177/14680874209337802149216822

Levels and patterns of objectively assessed physical activity and compliance with different public health guidelines in university students

ArticleBackground Physical activity (PA) is associated with health enhancement. The aim of this study was to assess: 1) levels and patterns of PA in university students by using accelerometers; and 2) the percentage of fulfilment of PA recommendations for adults, according to different public health guidelines. Methods Observational cross-sectional study (Cuenca’s Adults Study) involving 296 (206 women) healthy Spanish university students aged 18–25 years old. Participants wore the ActiGraph GT1M accelerometer for seven consecutive days. Total PA, steps and time spent in sedentary time, light, moderate, vigorous, and moderate to vigorous PA (MVPA) was assessed, and the prevalence of sufficient PA was calculated according to various public health guidelines. Results No sex differences in total PA were found. University students were more sedentary during weekend days than weekdays (p<0.05). Only 30.3% of participants accumulated 30 min/day at least five days a week of MVPA. A total of 5.4% of students met the recommendation of 150 min/week of MVPA or 75 min/week of vigorous PA, in PA bouts of at least 10 min. using the same definition, but on five or more days a week, only 0.5% students were found to meet the recommendation. In addition, only 0.5% of students met the recommendation of 30 min/day of MVPA, at least five days a week and in bouts of at least 10 min. Finally, 28.1% of the students met the recommendation of 10,000 steps/day. Conclusions Our study shows a high incidence of sedentary time in university students. The number of students meeting PA recommendations significantly differed depending on the recommendation proposed. Specific strategies to promote PA in this population are necessary as well as an agreement as to which PA guidelines should be used.Fundación para la Investigación SanitariaMinistry of Health and Consumer AffairsInstituto de Salud Carlos IIIRed de Investigación en Actividades Preventivas y de Promoción de Salu

Phase-Field Model of Silicon Carbide Growth During Isothermal Condition

Silicon carbide (SiC) emerges as a promising ceramic material for high-temperature structural applications, especially within the aerospace sector. The utilization of SiC-based ceramic matrix composites (CMCs) instead of superalloys in components like engine shrouds, combustors, and nozzles offers notable advantages, including a 25% improvement in fuel efficiency, over 10% enhanced thrust, and the capability to withstand up to 500$^{\circ}$C higher operating temperatures. Employing a CALPHAD-reinforced multi-phase-field model, our study delves into the evolution of the SiC layer under isothermal solidification conditions. By modeling the growth of SiC between liquid Si and solid C at 1450$^{\circ}$C, we compared results with experimental microstructures and quantitatively examined the evolution of SiC thickness over time. Efficient sampling across the entire model space mitigated uncertainty in high-temperature kinetic parameters, allowing us to predict a range of growth rates and morphologies for the SiC layer. The model accounts for parameter uncertainty stemming from limited experimental knowledge and successfully predicts relevant morphologies for the system. Experimental results validated the kinetic parameters of the simulations, offering valuable insights and potential constraints on the reaction kinetics. We further explored the significance of multi-phase-field model parameters on two key outputs, and found that the diffusion coefficient of liquid Si emerges as the most crucial parameter significantly impacting the SiC average layer thickness and grain count over time. This study provides valuable insights into the microstructure evolution of the Si-C binary system, offering pertinent information for the engineering of CMCs in industrial applications

Geometrodynamical Formulation of Two-Dimensional Dilaton Gravity

Two-dimensional matterless dilaton gravity with arbitrary dilatonic potential can be discussed in a unitary way, both in the Lagrangian and canonical frameworks, by introducing suitable field redefinitions. The new fields are directly related to the original spacetime geometry and in the canonical picture they generalize the well-known geometrodynamical variables used in the discussion of the Schwarzschild black hole. So the model can be quantized using the techniques developed for the latter case. The resulting quantum theory exhibits the Birkhoff theorem at the quantum level.Comment: 15 pages, LATE

Quantum gravity corrections to the Schwarzschild mass

Vacuum spherically symmetric Einstein gravity in $N\ge 4$ dimensions can be cast in a two-dimensional conformal nonlinear sigma model form by first integrating on the $(N-2)$-dimensional (hyper)sphere and then performing a canonical transformation. The conformal sigma model is described by two fields which are related to the Arnowitt-Deser-Misner mass and to the radius of the $(N-2)$-dimensional (hyper)sphere, respectively. By quantizing perturbatively the theory we estimate the quantum corrections to the ADM mass of a black hole.Comment: 18 pages, 8 figures, LaTeX2e, uses epsfig package, accepted for publication in Phys. Rev.

Gallic acid production with mouldy polyurethane particles obtained from solid state culture of Aspergillus niger GH1

Gallic acid production in a batch bioreactor was evaluated using as catalytic material the mouldy polyurethane solids (MPS) obtained from a solid-state fermentation (SSF) bioprocess carried out for tannase production by Aspergillus niger GH1 on polyurethane foam powder (PUF) with 5 % (v/w) of tannic acid as inducer. Fungal biomass, tannic acid consumption and tannase production were kinetically monitored. SSF was stopped when tannase activity reached its maximum level. Effects of washing with distilled water and drying on the tannase activity of MPS were determined. Better results were obtained with dried and washed MPS retaining 84 % of the tannase activity. Maximum tannase activity produced through SSF after 24 h of incubation was equivalent to 130 U/gS with a specific activity of 36 U/mg. The methylgallate was hydrolysed (45 %) in an easy, cheap and fast bioprocess (30 min). Kinetic parameters of tannase self-immobilized on polyurethane particles were calculated to be 5 mM and 04.1×102 mM/min for K M and V max, respectively. Results demonstrated that the MPS, with tannase activity, can be successfully used for the production of the antioxidant gallic acid from methyl-gallate substrate. Direct use of PMS to produce gallic acid can be advantageous as no previous extraction of enzyme is required, thus reducing production costs.Authors thank the National Council for Science and Technology (CONACYT-Mexico) for the financial support. The present work was performed as part of a cooperative agreement between DIA-Universidad Autonoma de Coahuila (Mexico) and IBB-Universidade do Minho (Portugal) within a specific training stay undertaken at the DEB-UM. Part of the research was funded by a project SEP-CONACYT-CB-2011

Open strings, 2D gravity and AdS/CFT correspondence

We present a detailed discussion of the duality between dilaton gravity on AdS_2 and open strings. The correspondence between the two theories is established using their symmetries and field theoretical, thermodynamic, and statistical arguments. We use the dual conformal field theory to describe two-dimensional black holes. In particular, all the semiclassical features of the black holes, including the entropy, have a natural interpretation in terms of the dual microscopic conformal dynamics. The previous results are discussed in the general framework of the Anti-de Sitter/Conformal Field Theory dualities.Comment: 22 pages, Typeset using REVTE

Damage Associated Molecular Pattern Molecule-Induced microRNAs (DAMPmiRs) in Human Peripheral Blood Mononuclear Cells

Endogenous damage associated molecular pattern molecules (DAMPs) released from necrotic, damaged or stressed cells are associated with an inflammatory response. Whether the microRNA (miR) expression signature of this response is different from that of a pathogen associated molecular pattern (PAMP)-stimulated inflammatory response is unknown. We report here that miR-34c and miR-214 are significantly expressed in fresh human peripheral blood mononuclear cells (PBMCs) exposed to DAMP-containing freeze-thaw lysates, or to conditioned media from serum-starved and glucose-deprived cells (p<6×10−4 and p<3.7×10−3), respectively. Interestingly, only miR-34c expression was differentially expressed in PBMCs exposed to freeze-thaw lysates or conditioned media from wildtype High Mobility Group B1 (HMGB1+/+) mouse embryonic fibroblast (MEF) cells, when compared to cultures exposed to lysates or conditioned media from HMGB1−/− MEFs. miR-155 expression in these cultures was negligible, but was significantly expressed in PBMCs stimulated with Lipopolysaccahride (LPS) or most other Toll-like receptor (TLR) ligands, making it the prototypic “PAMPmiR”. Exposure to a damaged human colorectal carcinoma cell line lysate (HCT116) similarly resulted in increased miR-34c and miR-214 levels. When PBMCs were pre-transfected with anti-miR-34c and then exposed to lysate, expression levels of IKKγ mRNA, a putative target of miR-34c, increased, while protein levels of IKKγ in cultures transfected with a pre-miR-34c were abrogated. Levels of miR-34c expression (as well as pro-inflammatory cytokines, IL-1β and TNFα) decreased when PBMC cultures were briefly pre-incubated with the K+ channel (inflammasome) inhibitor, glybenclamide, suggesting that inflammasome activation is upstream of miR-34c expression in response to DAMPs. Our findings demonstrate that a specific microRNA expression signature is associated with the inflammatory response to damaged/injured cells and carries implications for many acute and chronic inflammatory disorders