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Sökning: WFRF:(Formisano A)

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1.
  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
  • Forskningsöversikt (refereegranskat)
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2.
  • Bombarda, F., et al. (författare)
  • Runaway electron beam control
  • 2019
  • Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
  • Tidskriftsartikel (refereegranskat)
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3.
  • Krasilnikov, A., et al. (författare)
  • Evidence of 9 Be + p nuclear reactions during 2ω CH and hydrogen minority ICRH in JET-ILW hydrogen and deuterium plasmas
  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The intensity of 9Be + p nuclear fusion reactions was experimentally studied during second harmonic (2ω CH) ion-cyclotron resonance heating (ICRH) and further analyzed during fundamental hydrogen minority ICRH of JET-ILW hydrogen and deuterium plasmas. In relatively low-density plasmas with a high ICRH power, a population of fast H+ ions was created and measured by neutral particle analyzers. Primary and secondary nuclear reaction products, due to 9Be + p interaction, were observed with fast ion loss detectors, γ-ray spectrometers and neutron flux monitors and spectrometers. The possibility of using 9Be(p, d)2α and 9Be(p, α)6Li nuclear reactions to create a population of fast alpha particles and study their behaviour in non-active stage of ITER operation is discussed in the paper.
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  • Murari, A., et al. (författare)
  • A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
  • 2024
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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26.
  • Joffrin, E., et al. (författare)
  • Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
  • Forskningsöversikt (refereegranskat)abstract
    • For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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27.
  • Overview of the JET results
  • 2015
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
  • Tidskriftsartikel (refereegranskat)
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  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
  • Tidskriftsartikel (refereegranskat)
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32.
  • Abel, I, et al. (författare)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Tidskriftsartikel (refereegranskat)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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33.
  • Romanelli, F, et al. (författare)
  • Overview of the JET results
  • 2011
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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34.
  • Arcopinto, M., et al. (författare)
  • Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the TOSCA. GHD Study
  • 2017
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Although mounting evidence supports the concept that growth hormone (GH) deficiency (GHD) affects cardiovascular function, no study has systematically investigated its prevalence and role in a large cohort of chronic heart failure (CHF) patients. Aim of this study is to assess the prevalence of GHD in mild-to-moderate CHF and to explore clinical and functional correlates of GHD. One-hundred thirty CHF patients underwent GH provocative test with GHRH+arginine and accordingly categorized into GH-deficiency (GHD, n = 88, age = 61.6 +/- 1.1 years, 68% men) and GH-sufficiency (GHS, n = 42, age = 63.6 +/- 1.5 years, 81% men) cohorts. Both groups received comprehensive cardiovascular examination and underwent Doppler echocardiography, cardiopulmonary exercise testing, and biochemical and hormonal assay. GHD was detected in roughly 30% of CHF patients. Compared to GHD, GHS patients showed smaller end-diastolic and end-systolic LV volumes (-28%, p=.008 and -24%, p=.015, respectively), lower LV end-systolic wall stress (-21%, p=.03), higher RV performance (+18% in RV area change, p=.03), lower estimated systolic pulmonary artery pressure (-11%, p=.04), higher peak VO2 (+20%, p=.001) and increased ventilatory efficiency (-12% in VE/VCO2 slope, p=.002). After adjusting for clinical covariates (age, gender, and tertiles of LV ejection fraction, IGF-1, peak VO2, VE/VCO2 slope, and NT-proBNP), logistic multivariate analysis showed that peak VO2 (beta = -1.92, SE = 1.67, p=.03), VE/VCO2 slope (beta = 2.23, SE = 1.20, p=.02) and NT-proBNP (beta = 2.48, SE = 1.02, p=.016), were significantly associated with GHD status. Finally, compared to GHS, GHD cohort showed higher all-cause mortality at median follow-up of 3.5 years (40% vs. 25%, p<.001, respectively), independent of age, sex, NT-proBNP, peak VO2 and LVEF. GH deficiency identifies a subgroup of CHF patients characterized by impaired functional capacity, LV remodeling and elevated NT-proBNP levels. GHD is also associated with increased all-cause mortality.
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35.
  • Lauria, F., et al. (författare)
  • Ultra-processed foods consumption and diet quality of European children, adolescents and adults: Results from the I.Family study
  • 2021
  • Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 31:11, s. 3031-3043
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Food processing has been indicated as a factor capable of negatively affecting the global food system, including the profile of consumers' diets. The objectives of the present study were to provide a description of the consumption of ultra-processed foods (UPFs) in the large population of children, adolescents and adults from eight European countries participating to the I.Family study, and to investigate the association between UPFs intake and nutritional quality of the diet. Methods and results: Dietary intake was assessed using a 24-h dietary recall. The quality of the diet was evaluated by the Healthy Dietary Adherence Score (HDAS) using an FFQ. UPFs were classified according to the NOVA classification. Almost half of the daily energy intake of the 7073 participants came from UPFs, and this trend decreased progressively with age. UPFs contributed more than 50 % of the daily intake of total and saturated fat, carbohydrates and about 70 % of sugars intake in children and adolescents. No differences in UPFs consumption were found according to the educational and socio-economic status of the population. Energy intake increased across the quintiles of UPFs intake, while HDAS decreased. The frequency of consumption of fruit and vegetable, fish, and fibre rich foods was low in the fifth quintile of UPFs intake, both in adolescents and in adults. The consumption of foods rich in calories and low in nutritional content, operationally defined as "junk food", was significantly higher in the fifth quintile. Conclusions: In the population of the European I.Family study, UPFs contributed a large proportion of the daily energy intake, especially in children and adolescents. Higher consumption of UPFs was associated with a lower quality of the diet. Registration number for clinical trials: ISRCTN62310987. 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
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  • Perot, B., et al. (författare)
  • The EURITRACK project : Development of a tagged neutron inspection system for cargo containers
  • 2006
  • Ingår i: Proc SPIE Int Soc Opt Eng. - : SPIE. - 0819462691 - 9780819462695
  • Konferensbidrag (refereegranskat)abstract
    • The EURopean Illicit TRAfficing Countermeasures Kit project is part of the 6th European Union Framework Program, and aims at developing a neutron inspection system for detecting threat materials (explosives, drugs, etc.) in cargo containers. Neutron interaction in the container produces specific gamma-rays used to determine the chemical composition of the inspected material. An associated particle sealed tube neutron generator is developed to allow precise location of the interaction point by direction and time-of-flight measurements of the neutrons tagged by alpha-particles. The EURITRACK project consists in developing: a transportable deuterium-tritium neutron generator including a position sensitive alpha detector (8×8 matrix of YAP:Ce crystals coupled to a multi-anode photomultiplier), fast neutron and gamma-ray detectors, front-end electronics to perform coincidence and spectroscopic measurements, and an integrated software which manages neutron generator and detectors positioning, data acquisition and analysis. Hardware components have been developed and tested by the consortium partners. Current status of this work and provisional performances of the system assessed by Monte Carlo calculations are presented.
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37.
  • Formisano, A., et al. (författare)
  • Efficacy of neck circumference to identify metabolic syndrome in 3-10 year-old European children: Results from IDEFICS study
  • 2016
  • Ingår i: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 26:6, s. 510-516
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Several studies demonstrated that larger neck circumference (NC) in children and adolescents may help to identify obesity and cardio-metabolic abnormalities. We aimed to evaluate the correlation between NC and metabolic syndrome (MetS) risk factors and to determine the utility of this anthropometric index to identify MetS in European children. Methods and results: The present cross-sectional analysis includes 15,673 children (3-10 years) participating in the IDEFICS study. A continuous MetS (cMetS) score was calculated summing age and sex standardized z-scores of specific MetS risk factors. Receiver Operating Characteristic analysis, stratified by one-year age groups, was used to determine the ability of NC to identify children with unfavorable metabolic profile, corresponding to cMetS score >= 90th percentile. The areas under the curve values for NC associated with cMetS score values >= 90th percentile were significantly greater in girls than in boys (p < 0.001), except for 5 < 6 years group. For boys, optimal NC cut-off values ranged from 26.2 cm for the lowest age group (3 < 4 years), up to 30.9 cm for the highest age group (9 < 10 years). In girls, corresponding values varied from 24.9 cm to 29.6 cm. Conclusion: The study demonstrated the efficacy of NC in identifying European children with an unfavorable metabolic profile.
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38.
  • Mirra, P., et al. (författare)
  • Adipocyte precursor cells from first degree relatives of type 2 diabetic patients feature changes in hsa-mir-23a-5p, -193a-5p, and -193b-5p and insulin-like growth factor 2 expression
  • 2021
  • Ingår i: FASEB Journal. - 0892-6638. ; 35:4
  • Tidskriftsartikel (refereegranskat)abstract
    • First-degree relatives (FDRs) of type 2 diabetics (T2D) feature dysfunction of subcutaneous adipose tissue (SAT) long before T2D onset. miRNAs have a role in adipocyte precursor cells (APC) differentiation and in adipocyte identity. Thus, impaired miRNA expression may contribute to SAT dysfunction in FDRs. In the present work, we have explored changes in miRNA expression associated with T2D family history which may affect gene expression in SAT APCs from FDRs. Small RNA-seq was performed in APCs from healthy FDRs and matched controls and omics data were validated by qPCR. Integrative analyses of APC miRNome and transcriptome from FDRs revealed down-regulated hsa-miR-23a-5p, -193a-5p and -193b-5p accompanied by up-regulated Insulin-like Growth Factor 2 (IGF2) gene which proved to be their direct target. The expression changes in these marks were associated with SAT adipocyte hypertrophy in FDRs. APCs from FDRs further demonstrated reduced capability to differentiate into adipocytes. Treatment with IGF2 protein decreased APC adipogenesis, while over-expression of hsa-miR-23a-5p, -193a-5p and -193b-5p enhanced adipogenesis by IGF2 targeting. Indeed, IGF2 increased the Wnt Family Member 10B gene expression in APCs. Down-regulation of the three miRNAs and IGF2 up-regulation was also observed in Peripheral Blood Leukocytes (PBLs) from FDRs. In conclusion, APCs from FDRs feature a specific miRNA/gene profile, which associates with SAT adipocyte hypertrophy and appears to contribute to impaired adipogenesis. PBL detection of this profile may help in identifying adipocyte hypertrophy in individuals at high risk of T2D.
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  • Parrillo, L., et al. (författare)
  • Altered PTPRD DNA methylation associates with restricted adipogenesis in healthy first-degree relatives of Type 2 diabetes subjects
  • 2020
  • Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 12:10, s. 873-888
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. Methods: FDR pre-adipocyte Methylome and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively. Results:Methylome analysis revealed 2841 differentially methylated regions (DMR) in FDR. Most DMR localized into gene-body and were hypomethylated. The strongest hypomethylation signal was identified in an intronic-DMR at the PTPRD gene. PTPRD hypomethylation in FDR was confirmed by bisulphite sequencing and was responsible for its upregulation. Interestingly, Ptprd-overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Notably, the validated PTPRD-associated DMR was significantly hypomethylated in peripheral blood leukocytes from the same FDR individuals. Finally, PTPRD methylation pattern was also replicated in obese individuals. Conclusion: Our findings indicated a previously unrecognized role of PTPRD in restraining adipogenesis. This abnormality may contribute to increase FDR proclivity toward T2D.
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40.
  • Bornhorst, C., et al. (författare)
  • The effects of hypothetical behavioral interventions on the 13-year incidence of overweight/obesity in children and adolescents
  • 2023
  • Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - 1479-5868. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In view of the high burden of childhood overweight/obesity (OW/OB), it is important to identify targets for interventions that may have the greatest effects on preventing OW/OB in early life. Using methods of causal inference, we studied the effects of sustained behavioral interventions on the long-term risk of developing OW/OB based on a large European cohort.Methods Our sample comprised 10 877 children aged 2 to < 10 years at baseline who participated in the well-phenotyped IDEFICS/I.Family cohort. Children were followed from 2007/08 to 2020/21. Applying the parametric g-formula, the 13-year risk of developing OW/OB was estimated under various sustained hypothetical interventions on physical activity, screen time, dietary intake and sleep duration. Interventions imposing adherence to recommendations (e.g. maximum 2 h/day screen time) as well as interventions 'shifting' the behavior by a specified amount (e.g. decreasing screen time by 30 min/day) were compared to 'no intervention' (i.e. maintaining the usual or so-called natural behavior). Separately, the effectiveness of these interventions in vulnerable groups was assessed.Results The 13-year risk of developing OW/OB was 30.7% under no intervention and 25.4% when multiple interventions were imposed jointly. Meeting screen time and moderate-to-vigorous physical activity (MVPA) recommendations were found to be most effective, reducing the incidence of OW/OB by -2.2 [-4.4;-0.7] and -2.1 [-3.7;-0.8] percentage points (risk difference [95% confidence interval]), respectively. Meeting sleep recommendations (-0.6 [-1.1;-0.3]) had a similar effect as increasing sleep duration by 30 min/day (-0.6 [-0.9;-0.3]). The most effective intervention in children of parents with low/medium educational level was being member in a sports club; for children of mothers with OW/OB, meeting screen time recommendations and membership in a sports club had the largest effects.Conclusions While the effects of single behavioral interventions sustained over 13 years were rather small, a joint intervention on multiple behaviors resulted in a relative reduction of the 13-year OW/OB risk by between 10 to 26%. Individually, meeting MVPA and screen time recommendations were most effective. Nevertheless, even under the joint intervention the absolute OW/OB risk remained at a high level of 25.4% suggesting that further strategies to better prevent OW/OB are required.
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41.
  • Hunsberger, Monica, 1973, et al. (författare)
  • Overweight in singletons compared to children with siblings: the IDEFICS study.
  • 2012
  • Ingår i: Nutrition and diabetes. - : Springer Science and Business Media LLC. - 2044-4052. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to compare the prevalence of overweight in only children to those with siblings and to explore potential behavioral mediating factors. This study relies upon cross-sectional data collected at survey centers in eight European countries participating in Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS). The present analysis is based on measured anthropometry and parent or guardian-reported socio-demographic characteristics. Subjects include 12720 children aged 2–9 years for whom number of siblings was known. Singletons were more likely (odds ratio 1.52, 95% confidence interval (CI):1.34–1.72) to be overweight than their peers with siblings when controlling for factors related to childhood overweight, including survey country, parental education, parental weight, maternal age, child's age, birth weight and gender. The three southernmost countries have over threefold risk of overweight, dominated by Italy, compared with the north-central countries, which is not explained by the prevalence of singleton children. The excess risk of overweight among children without siblings was robustly observed even when considering behavioral mediating factors (playtime, screen time per day, dietary propensities for sugar or fat, parental attitudes towards food rewards and television in the child's bedroom). Among singletons aged 6–9 years, the excess risk of overweight was 1.70 (95% CI: 1.44–2.01) compared with 1.32 (95% CI: 1.10–1.60) in younger singletons.
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42.
  • Parrillo, L., et al. (författare)
  • Epigenetic Dysregulation of the Homeobox A5 (HOXA5) Gene Associates with Subcutaneous Adipocyte Hypertrophy in Human Obesity
  • 2022
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Along with insulin resistance and increased risk of type 2 diabetes (T2D), lean first-degree relatives of T2D subjects (FDR) feature impaired adipogenesis in subcutaneous adipose tissue (SAT) and subcutaneous adipocyte hypertrophy well before diabetes onset. The molecular mechanisms linking these events have only partially been clarified. In the present report, we show that silencing of the transcription factor Homeobox A5 (HOXA5) in human preadipocytes impaired differentiation in mature adipose cells in vitro. The reduced adipogenesis was accompanied by inappropriate WNT-signaling activation. Importantly, in preadipocytes from FDR individuals, HOXA5 expression was attenuated, with hypermethylation of the HOXA5 promoter region found responsible for its downregulation, as revealed by luciferase assay. Both HOXA5 gene expression and DNA methylation were significantly correlated with SAT adipose cell hypertrophy in FDR, whose increased adipocyte size marks impaired adipogenesis. In preadipocytes from FDR, the low HOXA5 expression negatively correlated with enhanced transcription of the WNT signaling downstream genes NFATC1 and WNT2B. In silico evidence indicated that NFATC1 and WNT2B were directly controlled by HOXA5. The HOXA5 promoter region also was hypermethylated in peripheral blood leukocytes from these same FDR individuals, which was further revealed in peripheral blood leukocytes from an independent group of obese subjects. Thus, HOXA5 controlled adipogenesis in humans by suppressing WNT signaling. Altered DNA methylation of the HOXA5 promoter contributed to restricted adipogenesis in the SAT of lean subjects who were FDR of type 2 diabetics and in obese individuals. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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43.
  • Pedersen, A., et al. (författare)
  • Quasistatic electric field measurements with spherical double probes on the GEOS and ISEE satellites
  • 1984
  • Ingår i: Space Science Reviews. - 0038-6308 .- 1572-9672. ; 37, s. 269-312
  • Tidskriftsartikel (refereegranskat)abstract
    • Spherical double probes for measurements of electric fields on the GEOS-1, GEOS-2, and ISEE-1 satellites are described. An essential feature of these satellites is their conductive surfaces which eliminate errors due to differential charging and enable meaningful diagnostic experiments to be carried out. The result of these experiments is a good understanding of interactions between the plasma, the satellite and the probes, including photo-electron emission on satellite and probes. Electric field measurements are compared with measurements of plasma drift perpendicular to the magnetic field in the solar wind and the magnetosphere and the error bar for the absolute values of the electric field is found to be in the range ±(0.5-1.0) mV m-1 whereas relative variations can be determined with much better accuracy. A useful by-product from a spherical double probe system is the determination of satellite floating potential which is related to the plasma electron flux. This measurement allows high time resolution studies of boundary crossings. Examples of electric field measurements, which reflect the recent scientific results, are given for different regions of the magnetosphere from the bow shock, the inner magnetosphere and the tail. Several examples of simultaneous GEOS-ISEE observations are described. © 1984 D. Reidel Publishing Company.
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44.
  • Spinelli, R., et al. (författare)
  • ZMAT3 hypomethylation contributes to early senescence of preadipocytes from healthy first-degree relatives of type 2 diabetics
  • 2022
  • Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 21:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Senescence of adipose precursor cells (APC) impairs adipogenesis, contributes to the age-related subcutaneous adipose tissue (SAT) dysfunction, and increases risk of type 2 diabetes (T2D). First-degree relatives of T2D individuals (FDR) feature restricted adipogenesis, reflecting the detrimental effects of APC senescence earlier in life and rendering FDR more vulnerable to T2D. Epigenetics may contribute to these abnormalities but the underlying mechanisms remain unclear. In previous methylome comparison in APC from FDR and individuals with no diabetes familiarity (CTRL), ZMAT3 emerged as one of the top-ranked senescence-related genes featuring hypomethylation in FDR and associated with T2D risk. Here, we investigated whether and how DNA methylation changes at ZMAT3 promote early APC senescence. APC from FDR individuals revealed increases in multiple senescence markers compared to CTRL. Senescence in these cells was accompanied by ZMAT3 hypomethylation, which caused ZMAT3 upregulation. Demethylation at this gene in CTRL APC led to increased ZMAT3 expression and premature senescence, which were reverted by ZMAT3 siRNA. Furthermore, ZMAT3 overexpression in APC determined senescence and activation of the p53/p21 pathway, as observed in FDR APC. Adipogenesis was also inhibited in ZMAT3-overexpressing APC. In FDR APC, rescue of ZMAT3 methylation through senolytic exposure simultaneously downregulated ZMAT3 expression and improved adipogenesis. Interestingly, in human SAT, aging and T2D were associated with significantly increased expression of both ZMAT3 and the P53 senescence marker. Thus, DNA hypomethylation causes ZMAT3 upregulation in FDR APC accompanied by acquisition of the senescence phenotype and impaired adipogenesis, which may contribute to FDR predisposition for T2D.
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45.
  • Formisano, Annarita, et al. (författare)
  • Family structure and childhood obesity: results of the IDEFICS project
  • 2014
  • Ingår i: Public Health Nutrition. - 1368-9800. ; 17:10, s. 2307-2315
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To analyze the association between family structure and adiposity in children. Design: Cross-sectional and longitudinal analysis of the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study cohort. Setting: Primary schools and kindergartens. Subjects: Children (n 12 350; aged 7 to 9 (SD 1.8) years) for the cross-sectional analysis and children (n 5236; at baseline: normal weight, aged 5 to 9 (SD 1.8) years) for the longitudinal study underwent anthropometry. Family structure was analyzed as (i) number and type of cohabiting adults and (ii) number of siblings. Results: In the cross-sectional analysis, after controlling for covariates, children living with grandparents had significantly higher BMI Z-score than those living with both parents (0.63; 95% CI 0.33, 0.92 v. 0.19; 95% CI 0.17, 0.22; P,0.01); in addition, the higher the number of siblings, the lower the BMI Z-score (only child 50.31; 95% CI 0.24, 0.38; 1 sibling 50.19; 95% CI 0.16, 0.23; 2 siblings 50.15; 95% CI 0.09, 0.20; >2 siblings 50.07, 95% CI 0.04, 0.19;P,0.001). Over the 2-year follow-up, differences in weight gain were observed across family-structure categories. Further, the risk of incidence of overweight/ obesity was significantly lower the higher the number of siblings living in the household (v. only child: 1 sibling 50.74, 95% CI 0.57, 0.96; 2 siblings 50.63, 95% CI 0.45, 0.88; >2 siblings 50.40, 95% CI 0.21, 0.77), independently of confounders. Conclusions: The study suggests that an independent association between family structure and childhood obesity exists.
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46.
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47.
  • Longo, Michele, et al. (författare)
  • Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity.
  • 2018
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 61:2, s. 369-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcutaneous adipocyte hypertrophy is associated with insulin resistance and increased risk of type 2 diabetes, and predicts its future development independent of obesity. In humans, subcutaneous adipose tissue hypertrophy is a consequence of impaired adipocyte precursor cell recruitment into the adipogenic pathway rather than a lack of precursor cells. The zinc finger transcription factor known as zinc finger protein (ZFP) 423 has been identified as a major determinant of pre-adipocyte commitment and maintained white adipose cell function. Although its levels do not change during adipogenesis, ectopic expression of Zfp423 in non-adipogenic murine cells is sufficient to activate expression of the gene encoding peroxisome proliferator-activated receptor γ (Pparγ; also known as Pparg) and increase the adipogenic potential of these cells. We investigated whether the Zfp423 gene is under epigenetic regulation and whether this plays a role in the restricted adipogenesis associated with hypertrophic obesity.Murine 3T3-L1 and NIH-3T3 cells were used as fibroblasts committed and uncommitted to the adipocyte lineage, respectively. Human pre-adipocytes were isolated from the stromal vascular fraction of subcutaneous adipose tissue of 20 lean non-diabetic individuals with a wide adipose cell size range. mRNA levels were measured by quantitative real-time PCR, while methylation levels were analysed by bisulphite sequencing. Chromatin structure was analysed by micrococcal nuclease protection assay, and DNA-methyltransferases were chemically inhibited by 5-azacytidine. Adipocyte differentiation rate was evaluated by Oil Red O staining.Comparison of uncommitted (NIH-3T3) and committed (3T3-L1) adipose precursor cells revealed that Zfp423 expression increased (p<0.01) in parallel with the ability of the cells to differentiate into mature adipocytes owing to both decreased promoter DNA methylation (p<0.001) and nucleosome occupancy (nucleosome [NUC] 1 p<0.01; NUC2 p<0.001) in the 3T3-L1 compared with NIH-3T3 cells. Interestingly, non-adipogenic epigenetic profiles can be reverted in NIH-3T3 cells as 5-azacytidine treatment increased Zfp423 mRNA levels (p<0.01), reduced DNA methylation at a specific CpG site (p<0.01), decreased nucleosome occupancy (NUC1, NUC2: p<0.001) and induced adipocyte differentiation (p<0.05). These epigenetic modifications can also be initiated in response to changes in the pre-adipose cell microenvironment, in which bone morphogenetic protein 4 (BMP4) plays a key role. We finally showed that, in human adipocyte precursor cells, impaired epigenetic regulation of zinc nuclear factor (ZNF)423 (the human orthologue of murine Zfp423) was associated with inappropriate subcutaneous adipose cell hypertrophy. As in NIH-3T3 cells, the normal ZNF423 epigenetic profile was rescued by 5-azacytidine exposure.Our results show that epigenetic events regulate the ability of precursor cells to commit and differentiate into mature adipocytes by modulating ZNF423, and indicate that dysregulation of these mechanisms accompanies subcutaneous adipose tissue hypertrophy in humans.
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48.
  • Sina, Elida, et al. (författare)
  • Digital media exposure and cognitive functioning in European children and adolescents of the I.Family study
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The digital environment can pose health risks through exposure to unhealthy content. Yet, little is known about its relation to children’s cognitive functioning. This study investigates the association between digital media (DM) exposure and children’s cognitive functioning. This cross-sectional study is based on examinations of children aged 8–18 years (N = 8673) of the I.Family cohort (2013–2014). Exposure to television, computer, smartphone and internet was self-reported (hours/day). Media multitasking (MMT) was defined as simultaneous use of computers with other digital or non-screen-based activities. Standard instruments were used to assess cognitive inflexibility (score: 0–39), decision-making ability (− 100 to + 100) and impulsivity (12–48). Adjusted regression coefficients and 99.9%CIs were calculated by generalized linear mixed-effects models. In total, 3261 participants provided data for impulsivity, 3441 for cognitive inflexibility and 4046 for decision-making. Exposure to smartphones and media multitasking were positively associated with impulsivity (βsmartphone = 0.74; 99.9%CI = 0.42–1.07; βMMT = 0.73; 99.9%CI = 0.35–1.12) and cognitive inflexibility (βsmartphone = 0.32; 99.9%CI = -0.02–0.66; βMMT = 0.39; 99.9%CI = 0.01–0.77) while being inversely associated with decision-making ability. Extensive smartphone/internet exposure combined with low computer/medium TV exposure was associated with higher impulsivity and cognitive inflexibility scores, especially in girls. DM exposure is adversely associated with cognitive functioning in children and adolescents. Children require protection against the likely adverse impact of digital environment. 
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