| 1. |
- Estrada, Karol, et al.
(författare)
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A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.
- 2009
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 18:18, s. 3516-24
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Tidskriftsartikel (refereegranskat)abstract
- Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (P(combined) = 3.4 x 10(-9)). Notably, a second SNP (rs6718438) located approximately 450 bp away and in strong LD (r(2) = 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (P(combined) = 2.1 x 10(-7)). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height.
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| 2. |
- Heijl, Anders, et al.
(författare)
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Nordic research in ophthalmology.
- 2005
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Ingår i: Acta ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 83:3, s. 278-88
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmö in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.
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| 3. |
- Prokopenko, Inga, et al.
(författare)
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Variants in MTNR1B influence fasting glucose levels
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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| 4. |
- Salieb-Beugelaar, Georgette, et al.
(författare)
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DNA movement in sub-20 nm nanoslits
- 2007
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Ingår i: Proceedings of the 11th International Conference on Miniaturized Systems for Chemistry and Life Sciences, uTAS 2007. - 9780979806407 ; , s. 1201-1203
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Konferensbidrag (refereegranskat)abstract
- The movement of XbaI digested O-DNA in 20 nanometer and O-DNA in 12 nanometer high slits was investigated. We found that DNA moved intermittently and following preferential pathways, indicating an important influence of surface roughness. From these intermittent movements two different mobilities were calculated, the total averaged mobilities and averaged mobilities between the intermittent sticking events. The friction coefficient per unit length was calculated from the latter mobilities. A three order of magnitude increase was found for the 12 nm slits compared to the theoretical value. The mobility furthermore differs less than one order of magnitude between 20 nm and 12 nm slits, and the influence of varying the ionic strength of the buffer was not significant. This work is the first time DNA movement in such shallow constrictions is investigated.
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| 5. |
- Salieb-Beugelaar, Georgette, et al.
(författare)
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Field-Dependent DNA Mobility in 20 nm High Nanoslits.
- 2008
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 8:7, s. 1785-1790
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Tidskriftsartikel (refereegranskat)abstract
- The transport behavior of lambda-DNA (48 kbp) in fused silica nanoslits is investigated upon application of electrical fields of different strengths. The slit dimensions are 20 nm in height, 3 microm in width, and 500 microm in length. With fields of 30 kV/m or below, the molecules move fluently through the slits, while at higher electrical fields, the DNA molecules move intermittently, resulting in a strongly reduced mobility. We propose that the behavior can be explained by mechanical and/or field-induced dielectrophoretic DNA trapping due to the surface roughness in the nanoslits. The observation of preferential pathways and trapping sites of the lambda-DNA molecules through the nanoslits supports this hypothesis and indicates that the classical viscous friction models to explain the DNA movement in nanoslits needs to be modified to include these effects. Preliminary experiments with the smaller XbaI-digested litmus-DNA (2.8 kbp) show that the behavior is size-dependent, suggesting that the high field electrophoresis in nanoslits can be used for DNA separation.
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| 6. |
- van Es, Michael A, et al.
(författare)
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Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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| 7. |
- Abdel-Hamid, Mohamed, et al.
(författare)
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Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma
- 2007
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 88:5, s. 1526-1531
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Tidskriftsartikel (refereegranskat)abstract
- Egypt has one of the world's highest prevalences of hepatitis C virus (HCV) infection, with a majority of genotype 4 infections. To explore the genetic diversity of HCV in Egypt, sera from 131 Egyptians [56 from community studies, 37 chronic hepatitis patients, 28 hepatocellular carcinoma (HCC) patients and 10 patients with non-Hodgkin's lymphoma] were genotyped by restriction fragment-length polymorphism and phylogenetic analyses of sequences from the mid-core and non-structural 5B regions. The different genotyping methods showed good agreement. The majority of the viruses (83 of 131; 63 %) were of subtype 4a, but five other subtypes within genotype 4 were also observed, as well as three genotype 1b, five genotype 1g and one genotype 3a samples. Interestingly, subtype 4o, which was easily identifiable in all three genomic regions, 3 showed an association with HCC (P=0.017), which merits further investigation.
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| 8. |
- Andin, Josefine, 1979-, et al.
(författare)
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Rivastigmine as a Modulator of the Neuronal Glutamate Transporter rEAAC1 mRNA Expression
- 2005
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 19:1, s. 18-23
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.
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| 9. |
- Antonelo, Eric Aislan, et al.
(författare)
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Intelligent autonomous navigation for mobile robots : Spatial concept acquisition and object discrimination
- 2005
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Ingår i: 2005 IEEE International Symposium on Computational Intelligence in Robotics and Automation, Proceedings. - New York : IEEE Press. - 0780393554 ; , s. 553-557
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Konferensbidrag (refereegranskat)abstract
- An autonomous system able to construct its own navigation strategy for mobile robots is proposed. The navigation strategy is molded from navigation experiences (succeeding as the robot navigates) according to a classical reinforcement learning procedure. The autonomous system is based on modular hierarchical neural networks. Initially the navigation performance is poor (many collisions occur). Computer simulations show that after a period of learning the autonomous system generates efficient obstacle avoidance and target seeking behaviors. Experiments also offer support for concluding that the autonomous system develops a variety of object discrimination capability and of spatial concepts.
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| 10. |
- Antonelo, Eric A., et al.
(författare)
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Modular Neural Network and Classical Reinforcement Learning for Autonomous Robot Navigation : Inhibiting Undesirable Behaviors
- 2006
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Ingår i: International Joint Conference on Neural Networks, 2006. IJCNN '06. - Piscataway, N.J. : IEEE Press. - 0780394909 ; , s. 498-505
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Konferensbidrag (refereegranskat)abstract
- Classical reinforcement learning mechanisms and a modular neural network are unified for conceiving an intelligent autonomous system for mobile robot navigation. The conception aims at inhibiting two common navigation deficiencies: generation of unsuitable cyclic trajectories and ineffectiveness in risky configurations. Distinct design apparatuses are considered for tackling these navigation difficulties, for instance: 1) neuron parameter for memorizing neuron activities (also functioning as a learning factor), 2) reinforcement learning mechanisms for adjusting neuron parameters (not only synapse weights), and 3) a inner-triggered reinforcement. Simulation results show that the proposed system circumvents difficulties caused by specific environment configurations, improving the relation between collisions and captures.
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