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| 5. |
- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 8. |
- Martin-Sanchez, F., et al.
(författare)
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Synergy between medical informatics and bioinformatics : Facilitating genomic medicine for future health care
- 2004
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Ingår i: Journal of Biomedical Informatics. - : Elsevier BV. - 1532-0464 .- 1532-0480. ; 37:1, s. 30-42
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we review the results of BIOINFOMED, a study funded by the European Commission (EC) with the purpose to analyse the different issues and challenges in the area where Medical Informatics and Bioinformatics meet. Traditionally, Medical Informatics has been focused on the intersection between computer science and clinical medicine, whereas Bioinformatics have been predominantly centered on the intersection between computer science and biological research. Although researchers from both areas have occasionally collaborated, their training, objectives and interests have been quite different. The results of the Human Genome and related projects have attracted the interest of many professionals, and introduced new challenges that will transform biomedical research and health care. A characteristic of the 'post genomic' era will be to correlate essential genotypic information with expressed phenotypic information. In this context, Biomedical Informatics (BMI) has emerged to describe the technology that brings both disciplines (BI and MI) together to support genomic medicine. In recognition of the dynamic nature of BMI, institutions such as the EC have launched several initiatives in support of a research agenda, including the BIOINFOMED study.
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| 9. |
- Aguiar, A., et al.
(författare)
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Practices in prescribing protein substitutes for PKU in Europe : No uniformity of approach
- 2015
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192 .- 1096-7206. ; 115:1, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: There appears little consensus concerning protein requirements in phenylketonuria (PKU). Methods: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. Results: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n = 24 centres) (infants <1 year, >2-3 g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n = 10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n = 4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n = 25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). Conclusions: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.
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- Chauvin, G., et al.
(författare)
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Investigating the young solar system analog HD 95086 A combined HARPS and SPHERE exploration
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
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Tidskriftsartikel (refereegranskat)abstract
- Context. HD 95086 (A8V, 17 Myr) hosts a rare planetary system for which a multi-belt debris disk and a giant planet of 4-5 Mjup have been directly imaged.Aims. Our study aims to characterize the global architecture of this young system using the combination of radial velocity and direct imaging observations. We want to characterize the physical and orbital properties of HD 95086 b, search for additional planets at short and wide orbits and image the cold outer debris belt in scattered light.Methods. We used HARPS at the ESO 3.6 m telescope to monitor the radial velocity of HD 95086 over two years and investigate the existence of giant planets at less than 3 au orbital distance. With the IRDIS dual-band imager and the IFS integral field spectrograph of SPHERE at VLT, we imaged the faint circumstellar environment beyond 10 au at six epochs between 2015 and 2017.Results. We do not detect additional giant planets around HD 95086. We identify the nature (bound companion or background contaminant) of all point-like sources detected in the IRDIS field of view. None of them correspond to the ones recently discovered near the edge of the cold outer belt by ALMA. HD 95086 b is resolved for the first time in J-band with IFS. Its near-infrared spectral energy distribution is well fitted by a few dusty and/or young L7-L9 dwarf spectral templates. The extremely red 1-4 mu m spectral distribution is typical of low-gravity objects at the L/T spectral type transition. The planet's orbital motion is resolved between January 2015 and May 2017. Together with past NaCo measurements properly re-calibrated, our orbital fitting solutions favor a retrograde low to moderate-eccentricity orbit e = 0.2(-0.2)(+0.3), with a semi-major axis similar to 52 au corresponding to orbital periods of similar to 288 yr and an inclination that peaks at i = 141 degrees, which is compatible with a planet-disk coplanar configuration. Finally, we report the detection in polarimetric differential imaging of the cold outer debris belt between 100 and 300 au, consistent in radial extent with recent ALMA 1.3 mm resolved observations.
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- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 16. |
- Demenais, F, et al.
(författare)
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Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study.
- 2010
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 1568-1583
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Tidskriftsartikel (refereegranskat)abstract
- Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10(-6) ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 × 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10(-6) ≤ P ≤ .02). Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.
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| 18. |
- Duffy, DL, et al.
(författare)
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Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 299-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
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| 20. |
- Miremadi, S. R., et al.
(författare)
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Effects of root surface debridement using Er:YAG Laser versus ultrasonic scaling : a SEM study
- 2014
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Ingår i: International Journal of Dental Hygiene. - : John Wiley & Sons. - 1601-5029 .- 1601-5037. ; 12:4, s. 273-284
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Despite promising results of Er:YAG laser in periodontal debridement, to date there is no consensus about the ideal settings for clinical use. This experimental clinical trial aimed to determine the effects of debridement using Er:YAG laser and to compare with ultrasonic treatment. Materials and methods: Sixty-four teeth were divided into two in vivo and in vitro subgroups. Each tooth received ultrasonic treatment on one side and Er:YAG laser debridement at either 60, 100, 160 or 250mJpulse(-1) and at 10Hz on the other side on a random basis. All samples were morphologically analyzed afterwards under scanning electron microscope for surface changes and dentinal tubules exposure. Treatment duration (d) was also recorded. Results: Laser debridement produced an irregular, rough and flaky surface free of carbonization or meltdown while ultrasound produced a relatively smoother surface. The number of exposed dentinal tubules (n) followed an energy-dependent trend. The number of exposed tubules among the in vivo laser groups was n60mJ=n100mJd100mJ>dUltrasound=d160mJ>d250mJ (P0.046), while for the in vitro groups it was d60mJ>d100mJ=dUltrasound=d160mJ>d250mJ (P0.046). Conclusions: Due to excessive treatment duration and surface damage, Er:YAG laser debridement at 60 and 250mJpulse(-1), respectively, is not appropriate for clinical use. Although laser debridement at 100 and 160mJpulse(-1) seems more suitable for clinical application, compared to ultrasound the former is more time-consuming and the latter is more aggressive. Using a feedback device or lower pulse energies are recommended when using laser in closed field.
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| 21. |
- Moor, Kathrin, et al.
(författare)
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High-avidity IgA protects the intestine by enchaining growing bacteria
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 544:7651, s. 498-
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Tidskriftsartikel (refereegranskat)abstract
- Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by directly neutralizing virulence factors or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues ('immune exclusion')(1-3). IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (>= 10(8) non-motile bacteria per gram). In typical infections, much lower densities(4,5) (10(0)-10(7) colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo. Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.
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| 22. |
- Olofsson, J., et al.
(författare)
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Azimuthal asymmetries in the debris disk around HD61005 A massive collision of planetesimals?
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 591
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Tidskriftsartikel (refereegranskat)abstract
- Context. Debris disks off er valuable insights into the latest stages of circumstellar disk evolution, and can possibly help us to trace the outcomes of planetary formation processes. In the age range 10 to 100 Myr, most of the gas is expected to have been removed from the system, giant planets (if any) must have already been formed, and the formation of terrestrial planets may be on-going. Pluto-sized planetesimals, and their debris released in a collisional cascade, are under their mutual gravitational influence, which may result into non-axisymmetric structures in the debris disk. Aims. High angular resolution observations are required to investigate these effects and constrain the dynamical evolution of debris disks. Furthermore, multi-wavelength observations can provide information about the dust dynamics by probing different grain sizes. Methods. Here we present new VLT/SPHERE and ALMA observations of the debris disk around the 40 Myr-old solar-type star HD61005. We resolve the disk at unprecedented resolution both in the near-infrared (in scattered and polarized light) and at millimeter wavelengths. We perform a detailed modeling of these observations, including the spectral energy distribution. Results. Thanks to the new observations, we propose a solution for both the radial and azimuthal distribution of the dust grains in the debris disk. We find that the disk has a moderate eccentricity (e similar to 0.1) and that the dust density is two times larger at the pericenter compared to the apocenter. Conclusions. With no giant planets detected in our observations, we investigate alternative explanations besides planet-disk interactions to interpret the inferred disk morphology. We postulate that the morphology of the disk could be the consequence of a massive collision between similar to 1000 km-sized bodies at similar to 61 au. If this interpretation holds, it would put stringent constraints on the formation of massive planetesimals at large distances from the star.
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| 25. |
- Cataldi, Gianni, et al.
(författare)
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The Surprisingly Low Carbon Mass in the Debris Disk around HD 32297
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 892:2
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Tidskriftsartikel (refereegranskat)abstract
- Gas has been detected in a number of debris disks. It is likely secondary, i.e., produced by colliding solids. Here, we report ALMA Band 8 observations of neutral carbon in the CO-rich debris disk around the 15-30 Myr old A-type star HD 32297. We find that C-0 is located in a ring at similar to 110 au with an FWHM of similar to 80 au and has a mass of (3.5 0.2) x 10(-3) M-circle plus. Naively, such a surprisingly small mass can be accumulated from CO photodissociation in a time as short as similar to 10(4) yr. We develop a simple model for gas production and destruction in this system, properly accounting for CO self-shielding and shielding by neutral carbon, and introducing a removal mechanism for carbon gas. We find that the most likely scenario to explain both C-0 and CO observations is one where the carbon gas is rapidly removed on a timescale of order a thousand years and the system maintains a very high CO production rate of similar to 15 M-circle plus Myr(-1), much higher than the rate of dust grind-down. We propose a possible scenario to meet these peculiar conditions: the capture of carbon onto dust grains, followed by rapid CO re-formation and rerelease. In steady state, CO would continuously be recycled, producing a CO-rich gas ring that shows no appreciable spreading over time. This picture might be extended to explain other gas-rich debris disks.
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