| 1. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- 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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| 3. |
- Akiba, K., et al.
(författare)
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LHC forward physics
- 2016
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 43:11
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Tidskriftsartikel (refereegranskat)
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| 4. |
- 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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| 5. |
- Borghi, Claudio, et al.
(författare)
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Lack of control of hypertension in primary cardiovascular disease prevention in Europe : Results from the EURIKA study
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 218, s. 83-88
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of and factors associated with uncontrolled hypertension and apparent resistant hypertension were assessed in the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; NCT00882336). Methods: EURIKA was a cross-sectional observational study including patients being treated for the primary prevention of cardiovascular disease in 12 European countries. Patients were assessed if they were being treated for hypertension (N = 5220). Blood pressure control was defined according to European guidelines, with sensitivity analysis taking account of patients' age and diabetes status. Associated factors were assessed using multivariate analysis. Results: In the primary analysis, a total of 2691 patients (51.6%) had uncontrolled hypertension. Factors significantly associated with an increased risk of having uncontrolled hypertension included female sex (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.93-2.73), body mass index (BMI; OR per kg/m(2): 1.03; 95% CI: 1.01-1.04), and geographic location. A total of 749 patients (14.3%) had apparent resistant hypertension. Factors significantly associated with an increased risk of having apparent resistant hypertension included BMI (OR per kg/m(2): 1.06; 95% CI: 1.04-1.08), diabetes (OR: 1.28; 95% CI: 1.06-1.53), use of statins (OR: 1.36; 95% CI: 1.15-1.62), serum uric acid levels (OR: 1.16; 95% CI: 1.09-1.23), and geographic location. Similar results were seen in sensitivity analyses. Conclusions: Over 50% of patients treated for hypertension continued to have uncontrolled blood pressure and 14.3% had apparent resistant hypertension. Positive associations were seen with other cardiovascular risk factors. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 6. |
- Borghi, Claudio, et al.
(författare)
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Serum uric acid levels are associated with cardiovascular risk score : A post hoc analysis of the EURIKA study
- 2018
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 253, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reports are conflicting on whether serum uric acid (sUA) levels are independently associated with increased cardiovascular (CV) death risk. Methods: This post hoc analysis assessed the relationship between sUA levels and CV death risk score in 7531 patients from the cross-sectional, multinational EURIKA study (NCT00882336). Patients had at least one CV risk factor but no clinical CV disease. Ten-year risk of CV death was estimated using SCORE-HDL and SCORE algorithms, categorized as low (<1%), intermediate (1% to <5%), high (>5% to <10%) or very high (>10%). Results: Mean serum sUA levels increased significantly with increasing CV death risk category in the overall population and in subgroups stratified by diuretics use or renal function (all P < 0.0001). Multivariate ordinal logistic regression analyses, adjusted for factors significantly associated with CV death risk in univariate analyses (study country, body mass index, number of CV risk factors and comorbidities, use of lipid lowering therapies, antihypertensives and antidiabetics), showed a significant association between sUA levels and SCORE-HDL category in the overall population (OR: 1.39 [95% CI: 1.34-1.44]) and all subgroups (using diuretics: 1.32 [1.24-1.40]; not using diuretics: 1.46 [1.39-1.53]; estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m(2): 1.30 [1.22-1.38]; eGFR >= 60 ml/min/1.73 m(2): 1.44 [1.38-1.51]; all P < 0.0001). Similar results were obtained when using SCORE. Conclusions: Higher sUA levels are associated with progressively higher 10-year CV death risk score in patients with at least one CV risk factor but no CV disease. (c) 2017 Elsevier B.V. All rights reserved.
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| 7. |
- Borghi, Claudio, et al.
(författare)
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The association between blood pressure and lipid levels in Europe : European study on cardiovascular risk prevention and management in usual daily practice
- 2016
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 34:11, s. 2155-2163
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:Several studies have suggested a positive association between serum lipid levels and blood pressure (BP). This study investigated this association in a large population from 12 European countries.Methods:Data were taken from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (ClinicalTrials.gov identifier: NCT00882336). Associations between BP and lipid levels in patients free from cardiovascular disease and with at least one major cardiovascular disease risk factor (N=7641) were assessed using linear regression analyses.Results:Overall, 72.8 and 64.8% of patients had hypertension and dyslipidaemia, respectively; 47.0% had both conditions. Regression coefficients (95% confidence interval) for the associations of LDL cholesterol, non-HDL cholesterol, total cholesterol and apolipoprotein B levels with SBP, adjusted for age, sex and BMI, were 0.93mmHg/mmol per l (0.54-1.31), 1.07mmHg/mmol per l (0.73-1.40), 1.02mmHg/mmol per l (0.69-1.35) and 4.94mmHg/g per l (3.43-6.46), respectively. The corresponding values (95% confidence interval) for the associations with DBP were 0.96mmHg/mmol per l (0.73-1.19), 0.95mmHg/mmol per l (0.75-1.15), 0.87mmHg/mmol per l (0.67-1.07) and 4.33mmHg/g per l (3.42-5.23), respectively. Most of these associations remained significant whether patients were treated with statins or not.Conclusion:Small but statistically significant associations between lipid levels and BP were observed in a large, multinational European population. Further research is warranted to assess the causality of this association and its implications on the management of patients with both hypertension and dyslipidaemia.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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