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- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 2. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 4. |
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| 5. |
- Edner, H, et al.
(författare)
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Fluorescence Lidar Multicolor Imaging of Vegetation
- 1994
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Ingår i: Optical Society of America. Journal B: Optical Physics. - 0740-3224. ; 33:13, s. 2471-2479
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Tidskriftsartikel (refereegranskat)abstract
- Multicolor imaging of vegetation fluorescence following laser excitation is reported for distances of 50 m. A mobile laser-radar system equipped with a Nd:YAG laser transmitter and a 40-cm-diameter telescope was utilized. The laser light was Raman shifted to 397 nm with pulse energies of approximately 30 mJ. An image-intensified CCD camera with a specially designed split-mirror Cassegrainian telescope was utilized for the simultaneous recording of fluorescence images of leaves and branches in four different spectral bands. Additionally, fluorescence spectra at selected points within the detection area were measured with an image-intensified diode array system. Image processing permits extraction of information related to the physiological status of the vegetation and might prove useful in forest decline research.
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| 8. |
- Johansson, Jonas, et al.
(författare)
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Remote fluorescence measurements of vegetation spectrally resolved and by multi-colour fluorescence imaging
- 1996
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Ingår i: Journal of Plant Physiology. - 0176-1617. ; 148:5, s. 632-637
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Tidskriftsartikel (refereegranskat)abstract
- A remote sensing system for combined fluorescence spectral recordings and multi-colour fluorescence imaging of vegetation will be presented. The system configuration will be explained and data from several field campaigns will be shown. The excitation light pulses for remote fluorescence detection are produced by a frequency tripled Nd:YAG laser emitting at 355 nm and shifted to 397 nm in a deuterium containing Raman cell. The receiving optics includes a Newtonian telescope and is shared by an optical fibre bundle connected to an OMA system and by a secondary Cassegrainian split-mirror telescope for fluorescence imaging at four wavelength bands simultaneously. The multi colour fluorescence images are computer processed to form images of a ratio at two wavelengths or if necessary a more complex mathematical function including the four wavelength bands is used. Examples of remote multi-colour imaging of vegetation from the past field campaigns will be given. Remote fluorescence spectra from several plant species were recorded at an excitation wavelength of 397 nm. Furthermore, the system was found capable of producing high-quality single-shot spectra at a range of 125 m. Lastly, a recently developed push-broom scanning technique for fluorescence imaging will be discussed and some preliminary data will be shown.
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| 10. |
- Liuba, Petru, et al.
(författare)
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Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets
- 2013
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. Methods: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. Results: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p<0.01 vs. non-cardioplegia group and pre-surgery). cPFV responses to adenosine, but not to serotonin, tended to decrease (p=0.06) after surgery only in cardioplegia group (p=0.06; p=0.8 in non-cardioplegia group vs pre-surgery). Also, cPFV response to atrial pacing was lower in the cardioplegia than in the non-cardioplegia group (p=0.02). Neither vulnerability nor duration of induced Afib after CPB differed between groups (Chi-square p=0.4). Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4). There was no difference in systolic myocardial function between groups at any time point. Conclusion: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB.
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