| 11. |
- Keller, Lina, et al.
(author)
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The Obesity Related Gene, FTO, Interacts with APOE and is Associated with Alzheimer's Disease Risk : A Prospective Cohort Study
- 2011
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 23:3, s. 461-469
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Journal article (peer-reviewed)abstract
- The FTO gene has been shown to have a small but robust effect on body mass index (BMI) and to increase the risk for diabetes. Both high BMI and diabetes are vascular risk factors that might play a role in the development of Alzheimer's disease (AD) and dementia. Thus, our aim was to explore the impact of FTO on AD and dementia risk. Nine years of follow-up data was gathered from the Kungsholmen project, a prospective population-based study on 1,003 persons without dementia. Cox-regression models were used to assess the relative risks of developing AD and dementia (DSM-III-R criteria) according to FTO genotypes (rs9939609), taking into account APOE, physical inactivity, BMI, diabetes, and cardiovascular disease (CVD). Compared to carriers of the FTO TT-genotype, AA-carriers had a higher risk for AD (RR 1.58, 95% CI: 1.11-2.24) and for dementia (RR 1.48, 95% CI: 1.09-2.02) after adjustment for age, gender, education, and APOE genotype. This effect remained after additional adjustment for physical inactivity, BMI, diabetes, and CVD. An interaction between FTO and APOE was found, with increased risk for dementia for those carrying both FTO AA and APOE epsilon 4. Importantly, the effect of the AA-genotype on dementia/AD risk seems to act mostly through the interaction with APOE epsilon 4. Our findings suggest that the FTO AA-genotype increases the risk for dementia, and in particular AD, independently of physical inactivity, BMI, diabetes, and CVD measured at baseline. Our results are in line with the recently reported association between FTO and reduced brain volume in cognitively healthy subjects.
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| 12. |
- Lango Allen, Hana, et al.
(author)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Journal article (peer-reviewed)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 13. |
- Lu, Hui, et al.
(author)
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Grain growth behavior, surface morphology evolution, structures, and optical properties of ZnO thin films prepared by RF reactive magnetron sputtering
- 2014
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In: Journal of Optoelectronics and Advanced Materials. - : NATL INST OPTOELECTRONICS. - 1454-4164 .- 1841-7132. ; 16:1-2, s. 170-175
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Journal article (peer-reviewed)abstract
- ZnO thin films were prepared by radio frequency (RF) reactive magnetron sputtering at varying deposition conditions. The effects of RF power (from 40 to 90 W) and substrate temperature (from 100 to 200 degrees C) on the grain growth behavior, surface morphology evolution, and the structural and optical properties of the films were investigated. Atomic force microscopy (AFM) measurements confirmed that the grain size and surface roughness depend mainly on the RF power and increase with increasing it at the initial deposition stage of 5 s, and are strongly affected by the substrate temperature and increase with increasing it at the final deposition stage of 45 min. The influence of both the deposition parameters on the surface structure of the ZnO films at different deposition stages and the mechanism concerning this influence were discussed. The X-ray diffraction (XRD) and optical absorption spectra analysis indicated that all the films deposited for 45 min are in the state of the compressive stress and exhibit polycrystalline nature with the (002) preferential orientation, and they have high optical transparency in the visible range and sharp absorption edges around the wavelength 360 nm corresponding to the ZnO exciton. With the increase of the RF power and substrate temperature, the grain size increases, the residual compressive stress relaxes, and the optical band gaps broaden. In comparison with the RF power, the substrate temperature has more evident influence on the microstructure of the ZnO thin films.
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| 14. |
- Lövdén, Martin, et al.
(author)
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Lifestyle change and the prevention of cognitive decline and dementia : what is the evidence?
- 2013
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In: Current Opinion in Psychiatry. - 0951-7367 .- 1473-6578. ; 26:3, s. 239-243
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Research review (peer-reviewed)abstract
- Purpose of review Effective pharmaceutical treatment of dementia is currently unavailable. Epidemiological work has, however, identified modifiable lifestyle factors, such as poor diet and physical and cognitive inactivity, that are associated with the risk of dementia. These factors may be useful targets for the prevention of cognitive impairment and dementia. Much recent research has, therefore, adopted an interventional focus. We review this work, highlight some methodological limitations, and provide recommendations for future research. Recent findings Change from a sedentary lifestyle to moderate physical activity has beneficial effects on cognitive functioning, and preliminary evidence suggests that such change may reduce the incidence of dementia. The evidence on cognitive benefits of lifestyle changes towards more intellectual engagement is insufficient. Nutritional supplements to treat deficiency may improve cognitive performance, but supplements on top of a healthy diet cannot be recommended. Summary Introduction of physical activity can reduce the risk of cognitive impairment in old age. Future research on nutritional supplements must consider the principle of an inverted U-shaped association between nutritional level and cognitive function. Work on the effects of cognitive training must use transfer tasks as primary outcome measures, and investigate whether effects of cognitive training generalize beyond the trained cognitive tasks.
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| 15. |
- Ma, Tao, et al.
(author)
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Genomic insights into salt adaptation in a desert poplar
- 2013
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2797-
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Journal article (peer-reviewed)abstract
- Despite the high economic and ecological importance of forests, our knowledge of the genomic evolution of trees under salt stress remains very limited. Here we report the genome sequence of the desert poplar, Populus euphratica, which exhibits high tolerance to salt stress. Its genome is very similar and collinear to that of the closely related mesophytic congener, P. trichocarpa. However, we find that several gene families likely to be involved in tolerance to salt stress contain significantly more gene copies within the P. euphratica lineage. Furthermore, genes showing evidence of positive selection are significantly enriched in functional categories related to salt stress. Some of these genes, and others within the same categories, are significantly upregulated under salt stress relative to their expression in another salt-sensitive poplar. Our results provide an important background for understanding tree adaptation to salt stress and facilitating the genetic improvement of cultivated poplars for saline soils.
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| 16. |
- Paillard-Borg, Stéphanie, et al.
(author)
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An active lifestyle postpones dementia onset by more than one year in very old adults
- 2012
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 52, s. 216-216
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Journal article (peer-reviewed)abstract
- The purpose of this study was to test the hypothesis that an active lifestyle delays age at dementia onset. This study included 388 incident dementia cases (DSM-III-R criteria) that developed over a 9-year follow-up period among 1,375 baseline dementia-free community dwellers with good cognitive function (MMSE > 23) (mean age = 81.2) from the Kungsholmen Project. An active lifestyle was defined as participation in mental, physical, or social activity. We used linear regression models to estimate influence of baseline active lifestyle on age at onset of incident dementia and general linear models to estimate mean age at dementia onset. Age at onset of dementia was significantly older in persons who had higher levels of participation in mental, physical, or social activity (beta: 0.18, 0.29 and 0.23 respectively, p < 0.001 for all the activities) independent of education, medical condition, functional status, and other confounders including APOE. When the three types of activities were integrated into an index, we found that the broader the spectrum of participation in the activities, the later the onset of disease (beta = 0.93, p = 0.01 for participating in two activities, and beta = 1.42, p < 0.001 for three activities). There were 17 months difference in mean age at dementia onset between the inactive group and the most active group. An active lifestyle operates as a protective factor for dementia by delaying the clinical onset of the disease. These findings highlight the relevance of encouraging old adults to have active lifestyles, which could have a great impact on public health.
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| 17. |
- Speliotes, Elizabeth K., et al.
(author)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Journal article (peer-reviewed)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 18. |
- Tang, Shi, et al.
(author)
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Small-molecule light-emitting electrochemical cells : evidence for in situ electrochemical doping and functional operation
- 2013
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In: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 49:43, s. 4926-4928
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Journal article (peer-reviewed)abstract
- We demonstrate that non-ionic small molecules (SMs) can function as the doping and emissive compound in light-emitting electrochemical cells (LECs), and that high brightness and decent efficiency can be attained for such devices. It is plausible that the expansion of the LEC library, to include easy-to-purify and tunable non-ionic SM compounds, could represent a viable path towards improved LEC devices.
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| 19. |
- Velikyan, Irina, et al.
(author)
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Robust labeling and comparative preclinical characterization of DOTA-TOC and DOTA-TATE
- 2012
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In: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 39:5, s. 628-639
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Journal article (peer-reviewed)abstract
- Objectives: Various radionuclide-labeled somatostatin analogues are used currently for diagnosis and therapy of neuroendocrine tumors. In particular, [Ga-68]Ga-DOTA-TOC is commonly used for diagnosis, while [Lu-177]Lu-DOTA-TATE is used for therapy. With the development of theranostics and personalized medicine where the imaging diagnosis is tailored to the subsequent radiotherapy, it is of paramount importance to investigate the relevance of the ligand exchange. The aim of this study was to compare binding capacity of [Ga-67/68]Ga-DOTA-TOC ([Ga-67/68]Ga-N-(4,7,10-(tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetyl-D-Phe-c[Cys-D-Tyr-Trp-Lys-Thr-Cys]-Thr(ol)) and [Ga-67/68]Ga-DOTA-TATE ([Ga-67/68]Ga-N-(4,7, 10-(tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetyl-D-Phe-c[Cys-D-Tyr-Trp-Lys-Thr-Cys]-Thr) in vitro in monkey brain cryosections and in vivo in the rat, where, in contrast to transfected cell lines, there is a heterogeneous distribution of somatostatin receptor (SSTR) subtypes. The influence of various production methods of [Ga-68]Ga-DOTA-TOC and [Ga-68]Ga-DOTA-TATE on the biological performance of the tracers was also studied. Material and Methods: [Ga-67]Ga-DOTA-TOC, [Ga-68]Ga-DOTA-TOC, [Ga-67]Ga-DOTA-TATE and [Ga-68]Ga-DOTA-TATE were synthesized including preconcentration and purification of the generator eluate. The binding of the radioligands was assessed in vitro using autoradiography on cryosections of Rhesus monkey brains and in vivo/ex vivo using organ distribution studies in rats. Results and Discussion: The tracer production method was improved in terms of higher robustness, simplification and good manufacturing practice (GMP) relevance. The synthesis variation did not influence the biological performance of the tracers. There was no statistically significant difference observed in the binding of [Ga-67/68]Ga-DOTA-TOC and [Ga-67/68]Ga-DOTA-TATE either in brain cortex in vitro or in rat biodistribution and uptake in SSTR-positive tissues such as pancreas, adrenals and pituitary. The uptake in these organs was precluded by the excess of octreotide (Sandostatin). The 10-fold higher affinity to SSTR2 of DOTA-TATE as compared to DOTA-TOC known from studies in transfected cells was reflected in a slightly more intense binding of [Ga-67/68]Ga-DOTA-TATE than of [Ga-67/68]Ga-DOTA-TOC in the monkey brain sections in vitro, but not in vivo in the rat. Conclusion: A robust Ga-68-labeling method was introduced. The difference in the uptake of [Ga-67/68]Ga-DOTA-TOC and [Ga-67/68]Ga-DOTA-TATE in SSTR2-positive organs was not statistically significant either in vitro in tissue studies or in vivo/ex vivo in rat experiments. The results indicate that the more complex environment in vitro and in vivo diminishes the difference observed in transfected cell line binding.
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| 20. |
- Wang, Hui-Xin, et al.
(author)
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Leisure activities, cognition and dementia
- 2012
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In: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier BV. - 0925-4439 .- 1879-260X. ; 1822:3, s. 482-491
-
Research review (peer-reviewed)abstract
- Accumulated evidence shows that leisure activities have a positive impact on cognitive function and dementia. This review aimed to systematically summarize the current evidence on this topic taking into account the limitations of the studies and biological plausibility for the underlying mechanisms linking cognition, dementia and leisure activities, with special attention on mental, physical and social activities. We included only longitudinal studies, with a follow-up time of at least 2 years, published in English from 1991 to March 2011 on leisure activities and cognition (n = 29) or dementia (n = 23) and provided some evidence from intervention studies on the topic. A protective effect of mental activity on cognitive function has been consistently reported in both observational and interventional studies. The association of mental activity with the risk of dementia was robust in observational studies but inconsistent in clinical trials. The protective effect of physical activity on the risk of cognitive decline and dementia has been reported in most observational studies, but has been less evident in interventional studies. Current evidence concerning the beneficial effect of other types of leisure activities on the risk of dementia is still limited and results are inconsistent. For future studies it is imperative that the assessment of leisure activities is standardized, for example, the frequency, intensity, duration and the type of activity: and also that the cognitive test batteries and the definition of cognitive decline are harmonized/standardized. Further, well designed studies with long follow-up times are necessary. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
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