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- van der Lee, S. J., et al.
(author)
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A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
- 2019
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 237-250
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Journal article (peer-reviewed)abstract
- The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
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| 2. |
- Manning, Alisa, et al.
(author)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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In: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Journal article (peer-reviewed)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 3. |
- Arneth, A., et al.
(author)
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Historical carbon dioxide emissions caused by land-use changes are possibly larger than assumed
- 2017
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In: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 10:2, s. 79-84
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Research review (peer-reviewed)abstract
- The terrestrial biosphere absorbs about 20% of fossil-fuel CO 2 emissions. The overall magnitude of this sink is constrained by the difference between emissions, the rate of increase in atmospheric CO 2 concentrations, and the ocean sink. However, the land sink is actually composed of two largely counteracting fluxes that are poorly quantified: fluxes from land-use change and CO 2 uptake by terrestrial ecosystems. Dynamic global vegetation model simulations suggest that CO 2 emissions from land-use change have been substantially underestimated because processes such as tree harvesting and land clearing from shifting cultivation have not been considered. As the overall terrestrial sink is constrained, a larger net flux as a result of land-use change implies that terrestrial uptake of CO 2 is also larger, and that terrestrial ecosystems might have greater potential to sequester carbon in the future. Consequently, reforestation projects and efforts to avoid further deforestation could represent important mitigation pathways, with co-benefits for biodiversity. It is unclear whether a larger land carbon sink can be reconciled with our current understanding of terrestrial carbon cycling. Our possible underestimation of the historical residual terrestrial carbon sink adds further uncertainty to our capacity to predict the future of terrestrial carbon uptake and losses.
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| 4. |
- Rowbotham, S. E., et al.
(author)
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Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN) : Study protocol for a randomised controlled trial
- 2017
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In: Trials. - : BioMed Central Ltd.. - 1745-6215. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: An abdominal aortic aneurysm (AAA) is a focal dilation of the abdominal aorta and is associated with a risk of fatal rupture. Experimental studies suggest that myo-inositol may exert beneficial effects on AAAs through favourable changes to biological pathways implicated in AAA pathology. The aim of the Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN) trial is to assess if myo-inositol will reduce AAA growth. Methods/design: IMAGEN is a multi-centre, prospective, parallel-group, randomised, double-blind, placebo-controlled trial. A total of 164 participants with an AAA measuring ≥ 30 mm will be randomised to either 2 g of myo-inositol or identical placebo twice daily for 12 months. The primary outcome measure will be AAA growth estimated by increase in total infrarenal aortic volume measured on computed tomographic scans. Secondary outcome measures will include AAA diameter assessed by computed tomography and ultrasound, AAA peak wall stress and peak wall rupture index, serum lipids, circulating AAA biomarkers, circulating RNAs and health-related quality of life. All analysis will be based on the intention-to-treat principle at the time of randomisation. All patients who meet the eligibility criteria, provide written informed consent and are enrolled in the study will be included in the primary analysis, regardless of adherence to dietary allocation. Discussion: Currently, there is no known medical therapy to limit AAA progression. The IMAGEN trial will be the first randomised trial, to our knowledge, to assess the value of myo-inositol in limiting AAA growth.
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| 9. |
- Cherubini, F., et al.
(author)
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Bridging the gap between impact assessment methods and climate science
- 2016
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In: Environmental Science and Policy. - : Elsevier BV. - 1873-6416 .- 1462-9011. ; 64, s. 129-140
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Research review (peer-reviewed)abstract
- Life-cycle assessment and carbon footprint studies are widely used by decision makers to identify climate change mitigation options and priorities at corporate and public levels. These applications, including the vast majority of emission accounting schemes and policy frameworks, traditionally quantify climate impacts of human activities by aggregating greenhouse gas emissions into the so-called CO2-equivalents using the 100-year Global Warming Potential (GWP100) as the default emission metric. The practice was established in the early nineties and has not been coupled with progresses in climate science, other than simply updating numerical values for GWP100. We review the key insights from the literature surrounding climate science that are at odds with existing climate impact methods and we identify possible improvement options. Issues with the existing approach lie in the use of a single metric that cannot represent the climate system complexity for all possible research and policy contexts, and in the default exclusion of near-term climate forcers such as aerosols or ozone precursors and changes in the Earth's energy balance associated with land cover changes. Failure to acknowledge the complexity of climate change drivers and the spatial and temporal heterogeneities of their climate system responses can lead to the deployment of suboptimal, and potentially even counterproductive, mitigation strategies. We argue for an active consideration of these aspects to bridge the gap between climate impact methods used in environmental impact analysis and climate science.
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| 10. |
- Milleret, V., et al.
(author)
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Rational design and in vitro characterization of novel dental implant and abutment surfaces for balancing clinical and biological needs
- 2019
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In: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 21, s. 15-24
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Journal article (peer-reviewed)abstract
- Background Long-term success and patient satisfaction of dental implant systems can only be achieved by fulfilling clinical as well as biological needs related to maintenance, aesthetics, soft tissue sealing, and osseointegration, among others. Surface properties largely contribute to the biological and clinical performance of implants and abutments. Purpose To decipher the clinical and biological needs in implant dentistry. To address identified needs, next-generation dental implant and abutment surfaces are designed and characterized in vitro. Materials and Methods Novel implant and abutment surface designs were produced and characterized using surface chemical analysis, surface topography analysis, scanning electron microscopy, contact-angle measurements, and cell-culture experiments. Results The novel anodized implant surface was gradually anodized, increasing the surface roughness, surface enlargement, and oxide-layer thickness from platform to apex. The surface was phosphorus enriched, nonporous, and nanostructured at the collar, and showed micropores elsewhere. The novel anodized abutment surface was smooth, nanostructured, nonporous, and yellow. Pristine surfaces with high density of hydroxyl-groups were protected during storage using a removable cell-friendly layer that allowed dry packaging. Conclusions A novel anodized implant system was developed with surface chemistry, topography, nanostructure, color, and surface energy designed to balance the clinical and biological needs at every tissue level.
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