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24,510 result(s) for "Rodríguez, María I."
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Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export
AMPK is a central energy sensor linking extracellular milieu fluctuations with the autophagic machinery. In the current study we uncover that Poly(ADP-ribosyl)ation (PARylation), a post-translational modification (PTM) of proteins, accounts for the spatial and temporal regulation of autophagy by modulating AMPK subcellular localisation and activation. More particularly, we show that the minority AMPK pool needs to be exported to the cytosol in a PARylation-dependent manner for optimal induction of autophagy, including ULK1 phosphorylation and mTORC1 inactivation. PARP-1 forms a molecular complex with AMPK in the nucleus in non-starved cells. In response to nutrient deprivation, PARP-1 catalysed PARylation, induced the dissociation of the PARP-1/AMPK complex and the export of free PARylated nuclear AMPK to the cytoplasm to activate autophagy. PARP inhibition, its silencing or the expression of PARylation-deficient AMPK mutants prevented not only the AMPK nuclear-cytosolic export but also affected the activation of the cytosolic AMPK pool and autophagosome formation. These results demonstrate that PARylation of AMPK is a key early signal to efficiently convey extracellular nutrient perturbations with downstream events needed for the cell to optimize autophagic commitment before autophagosome formation.
Recovering Sustainable Mobility after COVID-19: The Case of Almeria (Spain)
The COVID-19 pandemic brought about a significant change in mobility habits within cities, leading to a significant decrease in the use of collective urban transport in many countries that has been only partially and unevenly reversed. In this context, many cities are analyzing what factors are hindering this recovery process to design actions to promote sustainable mobility. Thus, this study, carried out in the city of Almeria (Spain), tried to analyze whether the main operating variables of the municipal bus network (frequency, average vehicle occupancy, the length of the lines, urban or suburban character, circularity, nodality, and intermodality) have an impact on the annual number of users recovered in 2022 compared to 2019. Although a strong statistical correlation between variables was not observed, the overall results show that the lines that have recovered the most users on average are suburban lines, as well as the nodal lines that serve key centroids such as the university, highlighting that the dependence of users on public transport might be the most important determinant in the recovery process, more than other variables representative of the service’s intrinsic quality such as frequency or average vehicle occupancy. This result shows the importance of facilitating public transport to those who lack alternatives, as well as the convenience of restrictions on less sustainable transportation alternatives for the prompt recovery of the space lost by urban public transportation.
Planning Resilient Cities: A Methodological Framework for the Integration of Nature-Based Solutions
Climate change arguably constitutes the most significant environmental challenge of our time, making the enhancement of urban resilience a global priority. Nature-based Solutions (NbS) have emerged as effective instruments to mitigate some of its impacts, particularly by reducing flood risk and moderating urban temperatures. However, their implementation is often reactive, focusing on existing problems rather than anticipating future ones. This underscores the need for robust methodological frameworks that enable the proactive integration of NbS within urban planning processes. This study proposes a spatial planning methodology supported by Geographic Information Systems (GIS), which, through the application of opportunity, priority, and feasibility criteria, identifies optimal areas for NbS integration, determines appropriate typologies, and establishes levels of intervention urgency. Although the methodology has been developed for the city of Granada, its structure allows for replication in other urban contexts. The findings reveal that one-third of Granada’s urban area is suitable for NbS implementation, with approximately 7% exhibiting a high or very high risk of surface runoff accumulation. The proposed tool has the potential to strengthen urban resilience and enhance citizens’ quality of life.
Dioxin receptor regulates aldehyde dehydrogenase to block melanoma tumorigenesis and metastasis
Background The dioxin (AhR) receptor can have oncogenic or tumor suppressor activities depending on the phenotype of the target cell. We have shown that AhR knockdown promotes melanoma primary tumorigenesis and lung metastasis in the mouse and that human metastatic melanomas had reduced AhR levels with respect to benign nevi. Methods Mouse melanoma B16F10 cells were engineered by retroviral transduction to stably downregulate AhR expression, Aldh1a1 expression or both. They were characterized for Aldh1a1 activity, stem cell markers and migration and invasion in vitro. Their tumorigenicity in vivo was analyzed using xenografts and lung metastasis assays as well as in vivo imaging. Results Depletion of aldehyde dehydrogenase 1a1 (Aldh1a1) impairs the pro-tumorigenic and pro-metastatic advantage of melanoma cells lacking AhR expression (sh-AhR). Thus, Aldh1a1 knockdown in sh-AhR cells (sh-AhR + sh-Aldh1a1) diminished their migration and invasion potentials and blocked tumor growth and metastasis to the lungs in immunocompetent AhR+/+ recipient mice. However, Aldh1a1 downmodulation in AhR-expressing B16F10 cells did not significantly affect tumor growth in vivo. Aldh1a1 knockdown reduced the high levels of CD133 + /CD29 + /CD44 + cells, melanosphere size and the expression of the pluripotency marker Sox2 in sh-AhR cells. Interestingly, Sox2 increased Aldh1a1 expression in sh-AhR but not in sh-AhR + sh-Aldh1a1 cells, suggesting that Aldh1a1 and Sox2 may be co-regulated in melanoma cells. In vivo imaging revealed that mice inoculated with AhR + Aldh1a1 knockdown cells had reduced tumor burden and enhanced survival than those receiving Aldh1a1-expressing sh-AhR cells. Conclusions Aldh1a1 overactivation in an AhR-deficient background enhances melanoma progression. Since AhR may antagonize the protumoral effects of Aldh1a1, the AhR low -Aldh1a1 high phenotype could be indicative of bad outcome in melanoma.
Characterization of Profilin Polymorphism in Pollen with a Focus on Multifunctionality
Profilin, a multigene family involved in actin dynamics, is a multiple partners-interacting protein, as regard of the presence of at least of three binding domains encompassing actin, phosphoinositide lipids, and poly-L-proline interacting patches. In addition, pollen profilins are important allergens in several species like Olea europaea L. (Ole e 2), Betula pendula (Bet v 2), Phleum pratense (Phl p 12), Zea mays (Zea m 12) and Corylus avellana (Cor a 2). In spite of the biological and clinical importance of these molecules, variability in pollen profilin sequences has been poorly pointed out up until now. In this work, a relatively high number of pollen profilin sequences have been cloned, with the aim of carrying out an extensive characterization of their polymorphism among 24 olive cultivars and the above mentioned plant species. Our results indicate a high level of variability in the sequences analyzed. Quantitative intra-specific/varietal polymorphism was higher in comparison to inter-specific/cultivars comparisons. Multi-optional posttranslational modifications, e.g. phosphorylation sites, physicochemical properties, and partners-interacting functional residues have been shown to be affected by profilin polymorphism. As a result of this variability, profilins yielded a clear taxonomic separation between the five plant species. Profilin family multifunctionality might be inferred by natural variation through profilin isovariants generated among olive germplasm, as a result of polymorphism. The high variability might result in both differential profilin properties and differences in the regulation of the interaction with natural partners, affecting the mechanisms underlying the transmission of signals throughout signaling pathways in response to different stress environments. Moreover, elucidating the effect of profilin polymorphism in adaptive responses like actin dynamics, and cellular behavior, represents an exciting research goal for the future.
Analysis of the Effects of Polymorphism on Pollen Profilin Structural Functionality and the Generation of Conformational, T- and B-Cell Epitopes
An extensive polymorphism analysis of pollen profilin, a fundamental regulator of the actin cytoskeleton dynamics, has been performed with a major focus in 3D-folding maintenance, changes in the 2-D structural elements, surface residues involved in ligands-profilin interactions and functionality, and the generation of conformational and lineal B- and T-cell epitopes variability. Our results revealed that while the general fold is conserved among profilins, substantial structural differences were found, particularly affecting the special distribution and length of different 2-D structural elements (i.e. cysteine residues), characteristic loops and coils, and numerous micro-heterogeneities present in fundamental residues directly involved in the interacting motifs, and to some extension these residues nearby to the ligand-interacting areas. Differential changes as result of polymorphism might contribute to generate functional variability among the plethora of profilin isoforms present in the olive pollen from different genetic background (olive cultivars), and between plant species, since biochemical interacting properties and binding affinities to natural ligands may be affected, particularly the interactions with different actin isoforms and phosphoinositides lipids species. Furthermore, conspicuous variability in lineal and conformational epitopes was found between profilins belonging to the same olive cultivar, and among different cultivars as direct implication of sequences polymorphism. The variability of the residues taking part of IgE-binding epitopes might be the final responsible of the differences in cross-reactivity among olive pollen cultivars, among pollen and plant-derived food allergens, as well as between distantly related pollen species, leading to a variable range of allergy reactions among atopic patients. Identification and analysis of commonly shared and specific epitopes in profilin isoforms is essential to gain knowledge about the interacting surface of these epitopes, and for a better understanding of immune responses, helping design and development of rational and effective immunotherapy strategies for the treatment of allergy diseases.
Adsorption of Direct Blue 78 Using Chitosan and Cyclodextrins as Adsorbents
The dyeing industry is one of the most polluting in the world. The adsorption of dyes by polymeric matrixes can be used to minimize the discharge of dyes into the environment. In the present study, chitosan-NaOH and β-cyclodextrin-epichlorohydrin polymers were used to remove the dye Direct Blue 78 from a wastewater model. To understand the adsorption behavior of Direct Blue 78 onto the polymers, adsorption rate and maximum adsorption capacity were calculated using kinetic tests and isotherm curves respectively. The kinetic data and mechanism of the adsorption process were analyzed by three models and the equilibrium data by three adsorption isotherms; also the different thermodynamic parameters were calculated. Results showed that the adsorption process follows pseudo-second-order kinetics in both polymers and the Langmuir isotherm best-fitted data for chitosan-NaOH polymer and the Freundlich isotherm for the β-CDs-EPI polymer. The adsorption process is exothermic in both cases and spontaneous for the β-CDs-EPI polymer to a certain temperature and not spontaneous for the chitosan-NaOH polymer and β-CDs-EPI polymer at higher temperatures. The complementary action of an advanced oxidation process eliminated >99% of the dye from water. The coupled process seems to be suitable for reducing the environmental impact of the dyeing industry.
Thiol-based redox regulation in sexual plant reproduction: new insights and perspectives
The success of sexual reproduction in plants involves (i) the proper formation of the plant gametophytes (pollen and embryo sac) containing the gametes, (ii) the accomplishment of specific interactions between pollen grains and the stigma, which subsequently lead to (iii) the fusion of the gametes and eventually to (iv) the seed setting. Owing to the lack of mobility, plants have developed specific regulatory mechanisms to control all developmental events underlying the sexual plant reproduction according to environmental challenges. Over the last decade, redox regulation and signaling have come into sight as crucial mechanisms able to manage critical stages during sexual plant reproduction. This regulation involves a complex redox network which includes reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione and other classic buffer molecules or antioxidant proteins, and some thiol/disulphide-containing proteins belonging to the thioredoxin superfamily, like glutaredoxins (GRXs) or thioredoxins (TRXs). These proteins participate as critical elements not only in the switch between the mitotic to the meiotic cycle but also at further developmental stages of microsporogenesis. They are also implicated in the regulation of pollen rejection as the result of self-incompatibility. In addition, they display precise space-temporal patterns of expression and are present in specific localizations like the stigmatic papillae or the mature pollen, although their functions and subcellular localizations are not clear yet. In this review we summarize insights and perspectives about the presence of thiol/disulphide-containing proteins in plant reproduction, taking into account the general context of the cell redox network.
Evaluation of Pulsed Light to Inactivate Brettanomyces bruxellensis in White Wine and Assessment of Its Effects on Color and Aromatic Profile
Brettanomyces bruxellensis is a wine spoilage yeast that could be inactivated by pulsed light (PL); however, this technology may induce changes in the quality of this alcoholic drink. The present research aimed to determine the potential of PL to inactivate B. bruxellensis inoculated in white wine and to assess the effect of this technology on the color and aromatic profile of the wine. For this, a cocktail of B. bruxellensis strains was inoculated into the wine and its inactivation by PL was determined and fitted to a microbial inactivation model. Along with this, the effect of PL on instrument-measured color, and the volatile compounds of the wine were evaluated by GC/MS and descriptive sensory analysis, respectively. B. bruxellensis was inactivated according to the Geeraerd model including the tail effect, with a maximum inactivation of 2.10 log reduction at 10.7 J/cm2; this fluence was selected for further studies. PL affected wine color but the total color difference was below the just noticeable difference at 10.7 J/cm2. The concentration of 13 out of 15 volatile compounds decreased due to the PL, which was noticeable by the panel. It is not clear if these compounds were photolyzed or volatilized in the open reactor during treatment. In conclusion, PL is able to inactivate B. bruxellensis in white wine but the treatment impairs the volatile profile. The use of a closed reactor under turbulent flow is recommended for disaggregating yeast clumps that may cause the tailing of the inactivation curve, and to avoid the possible escape of volatile compounds during treatment.