| 1. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Figlioli, G, et al.
(author)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Journal article (peer-reviewed)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 7. |
- Mazzuca, Silvia, et al.
(author)
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Establishing research strategies, methodologies and technologies to link genomics and proteomics to seagrass productivity, community metabolism, and ecosystem carbon fluxes
- 2013
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In: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 4
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Journal article (peer-reviewed)abstract
- A complete understanding of the mechanistic basis of marine ecosystem functioning is only possible through integrative and interdisciplinary research. This enables the prediction of change and possibly the mitigation of the consequences of anthropogenic impacts. One major aim of the European Cooperation in Science and Technology (COST) Action ES0609 Seagrasses productivity. From genes to ecosystem management, is the calibration and synthesis of various methods and the development of innovative techniques and protocols for studying seagrass ecosystems. During 10 days, 20 researchers representing a range of disciplines (molecular biology, physiology, botany, ecology, oceanography, and underwater acoustics) gathered at The Station de Recherches Sous-marines et Oceanographiques (STARESO, Corsica) to study together the nearby Posidonia oceanica meadow. STARESO is located in an oligotrophic area classified as pristine site where environmental disturbances caused by anthropogenic pressure are exceptionally low. The healthy P. oceanica meadow, which grows in front of the research station, colonizes the sea bottom from the surface to 37 m depth. During the study, genomic and proteomic approaches were integrated with ecophysiological and physical approaches with the aim of understanding changes in seagrass productivity and metabolism at different depths and along daily cycles. In this paper we report details on the approaches utilized and we forecast the potential of the data that will come from this synergistic approach not only for P. oceanica but for seagrasses in general.
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| 8. |
- Millan, MJ, et al.
(author)
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S33138 [N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]-benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenylacetamide], a preferential dopamine D3 versus D2 receptor antagonist and potential antipsychotic agent. II. A neurochemical, electrophysiological and behavioral characterization in vivo
- 2008
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In: The Journal of pharmacology and experimental therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-0103 .- 0022-3565. ; 324:2, s. 600-611
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Journal article (peer-reviewed)
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| 9. |
- Opgenoorth, Lars, et al.
(author)
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The GenTree Platform : growth traits and tree-level environmental data in 12 European forest tree species
- 2021
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In: GigaScience. - : Oxford University Press. - 2047-217X. ; 10:3
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Journal article (peer-reviewed)abstract
- Background: Progress in the field of evolutionary forest ecology has been hampered by the huge challenge of phenotyping trees across their ranges in their natural environments, and the limitation in high-resolution environmental information.Findings: The GenTree Platform contains phenotypic and environmental data from 4,959 trees from 12 ecologically and economically important European forest tree species: Abies alba Mill. (silver fir), Betula pendula Roth. (silver birch), Fagus sylvatica L. (European beech), Picea abies (L.) H. Karst (Norway spruce), Pinus cembra L. (Swiss stone pine), Pinus halepensis Mill. (Aleppo pine), Pinus nigra Arnold (European black pine), Pinus pinaster Aiton (maritime pine), Pinus sylvestris L. (Scots pine), Populus nigra L. (European black poplar), Taxus baccata L. (English yew), and Quercus petraea (Matt.) Liebl. (sessile oak). Phenotypic (height, diameter at breast height, crown size, bark thickness, biomass, straightness, forking, branch angle, fructification), regeneration, environmental in situ measurements (soil depth, vegetation cover, competition indices), and environmental modeling data extracted by using bilinear interpolation accounting for surrounding conditions of each tree (precipitation, temperature, insolation, drought indices) were obtained from trees in 194 sites covering the species' geographic ranges and reflecting local environmental gradients.Conclusion: The GenTree Platform is a new resource for investigating ecological and evolutionary processes in forest trees. The coherent phenotyping and environmental characterization across 12 species in their European ranges allow for a wide range of analyses from forest ecologists, conservationists, and macro-ecologists. Also, the data here presented can be linked to the GenTree Dendroecological collection, the GenTree Leaf Trait collection, and the GenTree Genomic collection presented elsewhere, which together build the largest evolutionary forest ecology data collection available.
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| 10. |
- Cherigier-Kovacic, L., et al.
(author)
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Electric field induced Lyman-alpha emission of a hydrogen beam for electric field measurements
- 2015
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In: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 86:6
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Journal article (peer-reviewed)abstract
- Electric field induced Lyman-alpha emission is a new way of measuring weak electric fields in vacuum and in a plasma. It is based on the emission of Lyman-alpha radiation (121.6 nm) by a low-energy metastable H atom beam due to Stark-quenching of the 2s level induced by the field. In this paper, we describe the technique in detail. Test measurements have been performed in vacuum between two plates polarized at a controlled voltage. The intensity of emitted radiation, proportional to the square of the field modulus, has been recorded by a lock-in technique, which gives an excellent signal to noise ratio. These measurements provide an in situ calibration that can be used to obtain the absolute value of the electric field. A diagnostic of this type can help to address a long standing challenge in plasma physics, namely, the problem of measuring electric fields without disturbing the equilibrium of the system that is being studied.
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| 11. |
- Lejeune, Erwan, et al.
(author)
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The chromatin-remodeling factor FACT contributes to centromeric heterochromatin independently of RNAi
- 2007
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 17:14, s. 1219-1224
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Journal article (peer-reviewed)abstract
- Centromeres exert vital cellular functions in mitosis and meiosis. A specialized histone and other chromatin-bound factors nucleate a dynamic protein assembly that is required for the proper segregation of sister chromatids. In several organisms, including the fission yeast, Schizosaccharomyces pombe, the RNAi pathway contributes to the formation of silent chromatin in pericentromeric regions. Little is known about how chromatin-remodeling factors contribute to heterochromatic integrity and centromere function. Here we show that the histone chaperone and remodeling complex FACT is required for centromeric-heterochromatin integrity and accurate chromosome segregation. We show that Spt16 and Pob3 are two subunits of the S. pombe FACT complex. Surprisingly, yeast strains deleted for pob3+ are viable and alleviate gene silencing at centromeric repeats and at the silent mating-type locus. Importantly, like heterochromatin and RNAi pathway mutants, Pob3 null strains exhibit lagging chromosomes on anaphase spindles. Whereas the processing of centromeric RNA transcripts into siRNAs is maintained in Pob3 mutants, Swi6-association with the centromere is reduced. Our studies provide the first experimental evidence for a role of the RNA polymerase II cofactor FACT in heterochromatin integrity and in centromere function.
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| 12. |
- Lemercier, P., et al.
(author)
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Association of plasma A beta 40/A beta 42 ratio and brain A beta accumulation: testing a whole-brain PLS-VIP approach in individuals at risk of Alzheimer's disease
- 2021
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 107, s. 57-69
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Journal article (peer-reviewed)abstract
- Molecular and brain regional/network-wise pathophysiological changes at preclinical stages of Alzheimer's disease (AD) have primarily been found through knowledge-based studies conducted in late-stage mild cognitive impairment/dementia populations. However, such an approach may compromise the objective of identifying the earliest spatial-temporal pathophysiological processes. We investigated 261 individuals with subjective memory complaints, a condition at increased risk of AD, to test a whole-brain, non-a-priori method based on partial least squares in unraveling the association between plasma A beta 42/A beta 40 ratio and an extensive set of brain regions characterized through molecular imaging of A beta accumulation and cortical metabolism. Significant associations were mapped onto large-scale networks, identified through an atlas and by knowledge, to elaborate on the reliability of the results. Plasma A beta 42/beta 40 ratio was associated with A beta-PET uptake (but not FDG-PET) in regions generally investigated in preclinical AD such as those belonging to the default mode network, but also in regions/networks normally not accounted including the central executive and salience networks which likely have a selective vulnerability to incipient A beta accumulation. The present whole-brain approach is promising to investigate early pathophysiological changes of AD to fully capture the complexity of the disease, which is essential to develop timely screening, detection, diagnostic, and therapeutic interventions. (C) 2021 Elsevier Inc. All rights reserved.
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| 13. |
- Martinez-Sancho, Elisabet, et al.
(author)
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The GenTree Dendroecological Collection, tree-ring and wood density data from seven tree species across Europe
- 2020
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In: Scientific Data. - : NATURE PUBLISHING GROUP. - 2052-4463. ; 7
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Journal article (peer-reviewed)abstract
- The dataset presented here was collected by the GenTree project (EU-Horizon 2020), which aims to improve the use of forest genetic resources across Europe by better understanding how trees adapt to their local environment. This dataset of individual tree-core characteristics including ring-width series and whole-core wood density was collected for seven ecologically and economically important European tree species: silver birch (Betula pendula), European beech (Fagus sylvatica), Norway spruce (Picea abies), European black poplar (Populus nigra), maritime pine (Pinus pinaster), Scots pine (Pinus sylvestris), and sessile oak (Quercus petraea). Tree-ring width measurements were obtained from 3600 trees in 142 populations and whole-core wood density was measured for 3098 trees in 125 populations. This dataset covers most of the geographical and climatic range occupied by the selected species. The potential use of it will be highly valuable for assessing ecological and evolutionary responses to environmental conditions as well as for model development and parameterization, to predict adaptability under climate change scenarios.
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| 14. |
- Masson-Delmotte, V., et al.
(author)
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Sensitivity of interglacial Greenland temperature and δ 18O : Ice core data, orbital and increased CO 2 climate simulations
- 2011
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 7:3, s. 1041-1059
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Journal article (peer-reviewed)abstract
- The sensitivity of interglacial Greenland temperature to orbital and CO 2 forcing is investigated using the NorthGRIP ice core data and coupled ocean-atmosphere IPSL-CM4 model simulations. These simulations were conducted in response to different interglacial orbital configurations, and to increased CO 2 concentrations. These different forcings cause very distinct simulated seasonal and latitudinal temperature and water cycle changes, limiting the analogies between the last interglacial and future climate. However, the IPSL-CM4 model shows similar magnitudes of Arctic summer warming and climate feedbacks in response to 2 × CO 2 and orbital forcing of the last interglacial period (126 000 years ago). The IPSL-CM4 model produces a remarkably linear relationship between TOA incoming summer solar radiation and simulated changes in summer and annual mean central Greenland temperature. This contrasts with the stable isotope record from the Greenland ice cores, showing a multi-millennial lagged response to summer insolation. During the early part of interglacials, the observed lags may be explained by ice sheet-ocean feedbacks linked with changes in ice sheet elevation and the impact of meltwater on ocean circulation, as investigated with sensitivity studies. A quantitative comparison between ice core data and climate simulations requires stability of the stable isotope - temperature relationship to be explored. Atmospheric simulations including water stable isotopes have been conducted with the LMDZiso model under different boundary conditions. This set of simulations allows calculation of a temporal Greenland isotope-temperature slope (0.3-0.4% per °C) during warmer-than-present Arctic climates, in response to increased CO 2, increased ocean temperature and orbital forcing. This temporal slope appears half as large as the modern spatial gradient and is consistent with other ice core estimates. It may, however, be model-dependent, as indicated by preliminary comparison with other models. This suggests that further simulations and detailed inter-model comparisons are also likely to be of benefit. Comparisons with Greenland ice core stable isotope data reveals that IPSL-CM4/LMDZiso simulations strongly underestimate the amplitude of the ice core signal during the last interglacial, which could reach +8-10 °C at fixed-elevation. While the model-data mismatch may result from missing positive feedbacks (e.g. vegetation), it could also be explained by a reduced elevation of the central Greenland ice sheet surface by 300-400 m.
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| 15. |
- Nulens, Lukas, et al.
(author)
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Catastrophic magnetic flux avalanches in NbTiN superconducting resonators
- 2023
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In: Communications Physics. - 2399-3650. ; 6:1
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Journal article (peer-reviewed)abstract
- Macroscopic superconducting components are an important building block of various quantum circuits. Since several of the envisioned applications require exposure to magnetic fields, it is of utmost importance to explore the impact of magnetic fields on their performance. Here we explore the complex pattern of magnetic field penetration and identify its impact on the resonance frequency of NbTiN superconducting resonators by combining magneto-optical imaging and high-frequency measurements. At temperatures below approximately half of the superconducting critical temperature, the development of magnetic flux avalanches manifests itself as a noisy response in the field-dependent resonance frequency. Magneto-optical imaging reveals different regimes and distinguishes the impact of avalanches in the ground plane and resonator. Our findings demonstrate that superconducting resonators represent a valuable tool to investigate magnetic flux dynamics. Moreover, the current blooming of niobium-based superconducting radio-frequency devices makes this report timely by unveiling the severe implications of magnetic flux dynamics.
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| 16. |
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| 17. |
- Yoshimatsu, Keiichi, et al.
(author)
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Peptide-imprinted polymer microspheres prepared by precipitation polymerization using a single bi-functional monomer.
- 2009
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In: Analyst. - : Royal Society of Chemistry (RSC). - 1364-5528. ; 134:4, s. 719-724
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Journal article (peer-reviewed)abstract
- A single bi-functional monomer, N,O-bismethacryloyl ethanolamine (NOBE), was used in precipitation polymerization system to synthesize molecularly imprinted polymer (MIP) microspheres. Highly specific binding sites were obtained for N-terminal protected neuropeptides, Boc-Leu-enkephalin and Pyr-Leu-enkephalin. The use of NOBE allowed binding sites to be formed in polymer microspheres that are able to recognize target peptides through the consensus C-terminal sequence. The interesting molecular binding results suggest a new approach for peptide analysis combining in situ chemical modification with MIP recognition under non-aqueous conditions.
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