| 1. |
- Calderon-González, Karla Gisel, et al.
(författare)
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Cryptic in vitro ubiquitin ligase activity of HDMX towards p53 is probably regulated by an induced fit mechanism
- 2022
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Ingår i: Bioscience Reports. - : Portland Press. - 0144-8463 .- 1573-4935. ; 42:7
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Tidskriftsartikel (refereegranskat)abstract
- HDMX and its homologue HDM2 are two essential proteins for the cell; after genotoxic stress, both are phosphorylated near to their RING domain, specifically at serine 403 and 395, respectively. Once phosphorylated, both can bind the p53 mRNA and enhance its translation; however, both recognize p53 protein and provoke its degradation under normal conditions. HDM2 has been well-recognized as an E3 ubiquitin ligase, whereas it has been reported that even with the high similarity between the RING domains of the two homologs, HDMX does not have the E3 ligase activity. Despite this, HDMX is needed for the proper p53 poly-ubiquitination. Phosphorylation at serine 395 changes the conformation of HDM2, helping to explain the switch in its activity, but no information on HDMX has been published. Here, we study the conformation of HDMX and its phospho-mimetic mutant S403D, investigate its E3 ligase activity and dissect its binding with p53. We show that phospho-mutation does not change the conformation of the protein, but HDMX is indeed an E3 ubiquitin ligase in vitro; however, in vivo, no activity was found. We speculated that HDMX is regulated by induced fit, being able to switch activity accordingly to the specific partner as p53 protein, p53 mRNA or HDM2. Our results aim to contribute to the elucidation of the contribution of the HDMX to p53 regulation.
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| 2. |
- Boquete, María Teresa, et al.
(författare)
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Current and historical factors drive variation of reproductive traits in unisexual mosses in Europe : A case study
- 2023
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Ingår i: Journal of Systematics and Evolution. - : Wiley. - 1674-4918 .- 1759-6831. ; 61:1, s. 213-226
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Tidskriftsartikel (refereegranskat)abstract
- Unisexual bryophytes provide excellent models to study the mechanisms that regulate the frequency of sexual versus asexual reproduction in plants, and their ecological and evolutionary implications. Here, we determined sex expression, phenotypic sex ratio, and individual shoot traits in 242 populations of the cosmopolitan moss Pseudoscleropodium purum spanning its whole distributional range. We tested whether niche differentiation, sex-specific differences in shoot size, and biogeographical history explained the spatial variation of reproductive traits. We observed high levels of sex expression and predominantly female-biased populations, although both traits showed high intraspecific variation among populations. Sex expression and sex ratio were partly explained by current macroscale environmental variation, with male shoots being less frequent at the higher end of the environmental gradients defined by the current distribution of the species. Female bias in population sex ratio was significantly lower in areas recolonized after the last glacial maximum (recent populations) than in glacial refugia (long-term persistent populations). We demonstrated that reproductive trait variation in perennial unisexual mosses is partially driven by macroscale and historical environmental variation. Based on our results, we hypothesize that sexual dimorphism in environmental tolerance and vegetative growth contribute to sex ratio bias over time, constraining the chances of sexual reproduction, especially in long-term persistent populations. Further studies combining genetic analyses and population monitoring should improve our understanding of the implications of the intraspecific variation in the frequency of sexual versus asexual reproduction in bryophyte population fitness and eco-evolutionary dynamics.
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| 3. |
- Cárdenas-Castro, Alicia P., et al.
(författare)
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In Vitro Intestinal Bioaccessibility and Colonic Biotransformation of Polyphenols from Mini Bell Peppers (Capsicum annuum L.)
- 2022
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Ingår i: Plant Foods for Human Nutrition. - : Springer Science and Business Media LLC. - 1573-9104 .- 0921-9668. ; 77:1, s. 77-82
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Tidskriftsartikel (refereegranskat)abstract
- To the best of our knowledge, "sweet mini bell" peppers have not been extensively investigated. In this study, we evaluated the bioaccessible phenolic compounds released during intestinal digestion and identified and quantified the microbial metabolites derived from phenolic compounds bioconversion during the in vitro colonic fermentation. A total of 66 phenolic compounds were determined. The results obtained in this study indicate that hydroxycinnamic acids (22 to 32 mg/100 g dw) and flavonoids (99 to 102 mg/100 g dw) headed by quercetin, luteolin and kaempferol glycosidic derivatives were the main bioaccessible phenolic compounds during in vitro intestinal digestion of mini bell peppers. The yellow variety contained the highest concentration of bioaccessible flavonoids (80 mg/100 g dw). For the first time in mini bell peppers, dihydroferulic acid was detected, in the three varieties studied. 3-(4-hydroxyphenyl)propionic acid was the major metabolite found after 12-24 h fermentation of all samples (44 to 102 µM/L). Further cell culture or in vivo studies are needed to elucidate the biological activities of the phenolic compounds identified in mini bell peppers.
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| 4. |
- Colon-Mesa, Ignacio, et al.
(författare)
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p27Kip1 Deficiency Impairs Brown Adipose Tissue Function Favouring Fat Accumulation in Mice
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:3
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to investigate the effect of the whole-body deletion of p27 on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. p27 knockout (p27−/−) and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by 18F-fluorodeoxyglucose (18FDG) uptake with microPET. p27−/− mice were more prone to develop obesity and insulin resistance, exhibiting increased size of all fat depots. p27−/− mice displayed a higher respiratory exchange ratio. iBAT presented larger adipocytes in p27−/− HFD mice, accompanied by downregulation of both Glut1 and uncoupling protein 1 (UCP1) in parallel with defective insulin signalling. Moreover, p27−/− HFD mice exhibited impaired response to cold exposure, characterized by a reduced iBAT 18FDG uptake and difficulty to maintain body temperature when exposed to cold compared to WT HFD mice, suggesting reduced thermogenic capacity. These data suggest that p27 could play a role in BAT activation and in the susceptibility to develop obesity and insulin resistance.
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| 5. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 6. |
- Fernandez-Prieto, Armando, et al.
(författare)
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Glide Symmetry Applied to the Design of Common-Mode Rejection Filters Based on Complementary Split-Ring Resonators
- 2023
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Ingår i: IEEE Transactions on Circuits and Systems - II - Express Briefs. - : Institute of Electrical and Electronics Engineers (IEEE). - 1549-7747 .- 1558-3791. ; 70:6, s. 1911-1915
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Tidskriftsartikel (refereegranskat)abstract
- In this brief, glide symmetry is applied to design common-mode rejection filters based on defected ground structures with bandstop response. To this aim, complementary split-ring resonators are chosen as the basic components for common-mode rejection. To illustrate the advantages of using glide symmetry, three implementations are studied and compared. The results reveal that glide symmetry offers the best performance in terms of common-mode rejection level and fractional bandwidth. Furthermore, glide symmetry barely affects the integrity of the differential mode. A prototype of each of the considered symmetries has been designed, simulated, and tested for practical validation. Good agreement is observed between the simulated and measured results, experimentally demonstrating the advantages of glide symmetry.
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| 7. |
- Mouris, Boules Atef, et al.
(författare)
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Glide Symmetry Applied to Printed Common-Mode Rejection Filters
- 2022
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Ingår i: IEEE transactions on microwave theory and techniques. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9480 .- 1557-9670. ; 70:2, s. 1198-1210
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we present a novel application of glide symmetry to differential lines with common-mode (CM) rejection filter properties. Two different topologies are investigated. First, glide symmetry is applied to a pair of differential lines where ground-connected mushrooms are employed as a CM rejection structure. The same idea is also used in a pair of differential lines where defective ground structures are introduced to stop the CM propagation. It is demonstrated that the CM rejection bandwidth is drastically increased when glide symmetry is exploited in both topologies when compared with their corresponding structures without glide symmetry. Furthermore, we show that the differential-mode propagation is hardly affected by the use of glide symmetry, ensuring the good integrity of the transmitted information. Experimental demonstration for both mushroom and defected ground structure is provided. Good agreement between simulations and measurements results is observed.
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| 8. |
- Onate, Angelo, et al.
(författare)
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Characterization of Nb-Si-doped low-carbon steel treated by quenching and partitioning : Thermic treatment in two stages supported by computational thermodynamical simulation and controlled sample dimensions
- 2023
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Ingår i: Materials Today Communications. - : Elsevier BV. - 2352-4928. ; 34
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Tidskriftsartikel (refereegranskat)abstract
- Quench and partition steels find wide use in the automotive industry because of their high capability of energy absorption. Industrial demands have prompted the expansion of this research field because of the influence these materials have on components that can absorb high energy of impact to reduce passenger damage, for example. The partition process's difficulties lie mainly in controlling the thermodynamics and the kinetics of the phase transformation. Both affect achieving adequate austenite retention and optimal mechanical properties. Many researchers have attempted to increase these materials' energy absorption efficiency by incorporating micro -alloying elements that control phase transformation during the partitioning process, typically done in three steps. However, no research has been carried out on this topic using Nb and Si microalloying on low-carbon steels in two stages. Therefore, an alloy was designed and modelled with mechanical reinforcement by precipitation and transformation-induced plasticity (TRIP), doping the steel with Nb and Si in a two-stage quenching and parti-tioning process. Then, steel samples were fabricated to validate the model. There were two groups of samples with different dimensions to evaluate the sensitivity of austenite retention concerning the sample thickness. The main results showed that 10.75% of retained austenite allows an energy absorption of 30.55 GPa% with a two -stage quenching and partitioning heat treatment. Sample thickness influences austenite retention due to diffusion kinetics during the partitioning process. Finally, virtual tests quantified the unit strain energy absorption of the retained austenite at 1.9 mJ at 25 degrees C.
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