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- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Bousquet, J, et al.
(författare)
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Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
- 2012
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
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Tidskriftsartikel (refereegranskat)abstract
- Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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- Baccini, M., et al.
(författare)
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Impact of heat on mortality in 15 european cities : attributable deaths under different weather scenarios
- 2011
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ Publishing Group Ltd. - 0143-005X .- 1470-2738. ; 65:1, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- Background: High ambient summer temperatures have been shown to influence daily mortality in cities across Europe. Quantification of the population mortality burden attributable to heat is crucial to the development of adaptive approaches. The impact of summer heat on mortality for 15 European cities during the 1990s was evaluated, under hypothetical temperature scenarios warmer and cooler than the mean and under future scenarios derived from the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios (SRES).Methods: A Monte Carlo approach was used to estimate the number of deaths attributable to heat for each city. These estimates rely on the results of a Bayesian random-effects meta-analysis that combines city-specific heat-mortality functions.Results: The number of heat-attributable deaths per summer ranged from 0 in Dublin to 423 in Paris. The mean attributable fraction of deaths was around 2%. The highest impact was in three Mediterranean cities (Barcelona, Rome and Valencia) and in two continental cities (Paris and Budapest). The largest impact was on persons over 75 years; however, in some cities, important proportions of heat-attributable deaths were also found for younger adults. Heat-attributable deaths markedly increased under warming scenarios. The impact under SRES scenarios was slightly lower or comparable to the impact during the observed hottest year.Conclusions: Current high summer ambient temperatures have an important impact on European population health. This impact is expected to increase in the future, according to the projected increase of mean ambient temperatures and frequency, intensity and duration of heat waves.
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- Fuente, A., et al.
(författare)
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Gas phase Elemental abundances in Molecular cloudS (GEMS) I. The prototypical dark cloud TMC 1
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 624
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Tidskriftsartikel (refereegranskat)abstract
- GEMS is an IRAM 30 m Large Program whose aim is determining the elemental depletions and the ionization fraction in a set of prototypical star-forming regions. This paper presents the first results from the prototypical dark cloud Taurus molecular cloud (TMC) 1. Extensive millimeter observations have been carried out with the IRAM 30 m telescope (3 and 2mm) and the 40 m Yebes telescope (1.3 cm and 7 mm) to determine the fractional abundances of CO, HCO+, HCN, CS, SO, HCS+, and N2H+ in three cuts which intersect the dense filament at the well-known positions TMC 1-CP, TMC 1-NH3, and TMC 1-C, covering a visual extinction range from A(v) similar to 3 to similar to 20 mag. Two phases with differentiated chemistry can be distinguished: (i) the translucent envelope with molecular hydrogen densities of 1-5 x 10(3) cm(-3); and (ii) the dense phase, located at A(v) > 10 mag, with molecular hydrogen densities >10(4) cm(-3). Observations and modeling show that the gas phase abundances of C and O progressively decrease along the C+/C/CO transition zone (A(v) similar to 3 mag) where C/H similar to 8 x 10(-5) and C/O similar to 0.8-1, until the beginning of the dense phase at A(v) similar to 10 mag. This is consistent with the grain temperatures being below the CO evaporation temperature in this region. In the case of sulfur, a strong depletion should occur before the translucent phase where we estimate an S/H similar to (0.4-2.2) x 10(-6), an abundance similar to 7-40 times lower than the solar value. A second strong depletion must be present during the formation of the thick icy mantles to achieve the values of S/H measured in the dense cold cores (S/H similar to 8 x 10(-8)). Based on our chemical modeling, we constrain the value of zeta(H2) to similar to(0.5-1.8) x 10(-16) s(-1) in the translucent cloud.
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| 20. |
- Analitis, A, et al.
(författare)
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Effects of cold weather on mortality : results from 15 European cities within the PHEWE project.
- 2008
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Ingår i: American journal of epidemiology. - : Oxford University Press (OUP). - 1476-6256 .- 0002-9262. ; 168:12, s. 1397-408
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Tidskriftsartikel (refereegranskat)abstract
- Weather-related health effects have attracted renewed interest because of the observed and predicted climate change. The authors studied the short-term effects of cold weather on mortality in 15 European cities. The effects of minimum apparent temperature on cause- and age-specific daily mortality were assessed for the cold season (October-March) by using data from 1990-2000. For city-specific analysis, the authors used Poisson regression and distributed lag models, controlling for potential confounders. Meta-regression models summarized the results and explored heterogeneity. A 1 degrees C decrease in temperature was associated with a 1.35% (95% confidence interval (CI): 1.16, 1.53) increase in the daily number of total natural deaths and a 1.72% (95% CI: 1.44, 2.01), 3.30% (95% CI: 2.61, 3.99), and 1.25% (95% CI: 0.77, 1.73) increase in cardiovascular, respiratory, and cerebrovascular deaths, respectively. The increase was greater for the older age groups. The cold effect was found to be greater in warmer (southern) cities and persisted up to 23 days, with no evidence of mortality displacement. Cold-related mortality is an important public health problem across Europe. It should not be underestimated by public health authorities because of the recent focus on heat-wave episodes.
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| 23. |
- Lozano, Manuel, et al.
(författare)
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DNA methylation changes associated with prenatal mercury exposure : A meta-analysis of prospective cohort studies from PACE consortium
- 2022
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 204
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Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10−4, p-value = 5.87 × 10−5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10−5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10−7) in GRK1 and cg02212000 (β = −0.001, p-value = 8.13 × 10−7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
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| 24. |
- Rachmeler, L. A., et al.
(författare)
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Quiet Sun Center to Limb Variation of the Linear Polarization Observed by CLASP2 Across the Mg ıı h and k Lines
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 936:1
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Tidskriftsartikel (refereegranskat)abstract
- The CLASP2 (Chromospheric LAyer Spectro-Polarimeter 2) sounding rocket mission was launched on 2019 April 11. CLASP2 measured the four Stokes parameters of the Mg ıı h and k spectral region around 2800 Å along a 200'' slit at three locations on the solar disk, achieving the first spatially and spectrally resolved observations of the solar polarization in this near-ultraviolet region. The focus of the work presented here is the center-to-limb variation of the linear polarization across these resonance lines, which is produced by the scattering of anisotropic radiation in the solar atmosphere. The linear polarization signals of the Mg ıı h and k lines are sensitive to the magnetic field from the low to the upper chromosphere through the Hanle and magneto-optical effects. We compare the observations to theoretical predictions from radiative transfer calculations in unmagnetized semiempirical models, arguing that magnetic fields and horizontal inhomogeneities are needed to explain the observed polarization signals and spatial variations. This comparison is an important step in both validating and refining our understanding of the physical origin of these polarization signatures, and also in paving the way toward future space telescopes for probing the magnetic fields of the solar upper atmosphere via ultraviolet spectropolarimetry.
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| 25. |
- Soler-Blasco, R., et al.
(författare)
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Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort
- 2023
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Ingår i: Science of the Total Environment. - 0048-9697. ; 900
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy.Methods: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide poly-morphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multi-variate linear regression models. Results: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher%MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (& beta; 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele).Conclusions: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations.
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| 26. |
- Yannuzzi, M., et al.
(författare)
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TEFIS: A Single Access Point for Conducting Multifaceted Experiments on Heterogeneous Test Facilities
- 2014
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Ingår i: Computer Networks. - : Elsevier BV. - 1389-1286 .- 1872-7069. ; 63, s. 147-172
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Tidskriftsartikel (refereegranskat)abstract
- A few years ago, an experimental facility composed of networking gear and simulation tools was sufficient for testing the main features of a prototype before the final product could be launched to the Internet market. This paradigm has certainly changed, but the lack of platforms enabling the realistic assessment of the different facets of a product, including cross-cutting trials across different testbeds, poses strong limitations for researchers and developers. In light of this, we present an open platform that offers a versatile combination of heterogeneous experimental facilities called “TEstbed for Future Internet Services” (TEFIS). TEFIS provides a single access point for conducting cutting-edge experiments on testbeds that supply different capabilities, including testbeds dedicated to network performance, software performance, grid computing, and living labs. We shall show that TEFIS covers the entire life-cycle of a multifaceted experiment, with the advantage that a single testrun can seamlessly execute across different experimental facilities. In order to demonstrate the potential and versatility of the TEFIS platform, we describe the deployment of four distinct experiments and provide a set of results highlighting the benefits of using TEFIS. The experiments described in this article cover: i) the experimentation with an open API called OPENER (which is an open and programmable environment for managing experimentation with SDN applications); ii) an application for skiers and tourists at the Megève ski resort in France; iii) an application that can dynamically adapt the Quality of Experience (QoE) of multimedia services for mobile users; and iv) an augmented reality workspace for remote education and learning purposes based on videoconferencing.
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