| 1. |
- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 2. |
- Prince, J.A., et al.
(författare)
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Lack of replication of association findings in complex disease : An analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease
- 2001
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 9:6, s. 437-444
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Tidskriftsartikel (refereegranskat)abstract
- There is considerable enthusiasm for the prospect of using common polymorphisms (primarily single nucleotide polymorphisms, SNPs) in candidate genes to unravel the genetics of complex disease. This approach has generated a number of findings of loci which are significantly associated with sporadic Alzheimer's disease (AD). In the present study, a total of 15 genes of interest were chosen from among the previously published reports of significant association in AD. Genotyping was performed on polymorphisms within those genes (14 SNPs and one deletion) using Dynamic Allele Specific Hybridization (DASH) in 204 Swedish patients with sporadic late-onset AD and 186 Swedish control subjects. The genes chosen for analysis were, low-density lipoprotein receptor-related protein (LRP1), angiotensin converting enzyme (DCP1), alpha-2-macroglobulin (A2M), bleomycin hydrolase (BLMH), dihydrolipoyl S-succinyltransferase (DLST), tumour necrosis factor receptor superfamily member 6 (TNFRSF6), nitric oxide synthase (NOS3), presenilin 1 (PSEN1), presenilin 2 (PSEN2), butyrylcholinesterase (BCHE), Fe65 (APBB1), oestrogen receptor alpha (ESR1), cathepsin D (CTSD), methylenetetrahydrofolate reductase (MTHFR), and interleukin 1A (IL1A). We found no strong evidence of association for any of these loci with AD in this population. While the possibility exists that the genes analysed are involved in AD (ie they have weak effects and/or are population specific), results reinforce the need for extensive replication studies if we are to be successful in defining true risk factors in complex diseases.
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| 3. |
- Blennow, Kaj, 1958, et al.
(författare)
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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
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Tidskriftsartikel (refereegranskat)abstract
- A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
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| 12. |
- Edmonds, K. W., et al.
(författare)
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Magnetism of exposed and Co-capped Fe nanoparticles
- 2000
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Ingår i: Journal of Magnetism and Magnetic Materials. - 0304-8853 .- 1873-4766. ; 220:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- The effect of capping a dilute assembly of nanoscale mass-selected Fe clusters with a Co thin film has been studied using X-ray magnetic circular dichroism (XMCD). The clusters, containing around 400 atoms, were deposited in situ from a gas-aggregation source onto highly oriented pyrolytic graphite. The exposed clusters possess magnetic moments that are enhanced compared to the bulk, by around 4% for m(spin) and around 75% for m(orb). In addition, a surface core level shifted component is observed in the L-3.2 XMCD spectrum. Upon adding the Co layer, the surface component disappears, m(orb) is decreased for the Fe clusters, and m(spin) increases. The exposed clusters are magnetically isotropic but a strong in-plans anisotropy is observed after depositing the Co overlayer. We attribute this to the shape of the Co islands in which the Fe clusters are embedded.
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| 13. |
- Edmonds, K. W., et al.
(författare)
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Size dependence of the magnetic moments of exposed nanoscale iron particles
- 2001
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Ingår i: Journal of Magnetism and Magnetic Materials. - 0304-8853 .- 1873-4766. ; 231:1, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- The magnetic moments in exposed, mass-selected, nanoscale Fe clusters in the size range 1.89-2.20 nm (300-475 atoms), deposited onto graphic in situ have been measured by X-ray magnetic circular dichroism. The smallest clusters possess moments that are enhanced by around 4% for m(spin) and 80% for m(orb) and decrease towards the bulk value with increasing size. The larger clusters show an in-plane anisotropy that is consistent with the anisotropy in the orbital moment. The smallest clusters are, within experimental error, magnetically isotropic. The anisotropy constant in the 475-atom clusters is significantly higher than the bulk value.
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| 16. |
- Ghiringhelli, G., et al.
(författare)
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3d spin-orbit photoemission spectrum of nonferromagnetic materials : The test cases of CoO and Cu
- 2002
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 66:7
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Tidskriftsartikel (refereegranskat)abstract
- The x-ray photoemission spectrum of the valence states of 3d transition-metal systems is spin polarized when using circularly polarized photons. The integral of the spin-orbit spectrum is proportional to the expectation value of the angular part of the 3d spin-orbit operator in the initial state. We show that this quantity can be used to get an estimate of the atomic orbital moment. While the measurement is sensitive to the magnetization axis, it does not require a net macroscopic magnetization nor the presence of a long-range magnetic order, and is therefore suitable for any transition-metal systems being antiferromagnetic or paramagnetic or magnetically disordered. In the case of full 3d shell the integral of the spin-orbit spectrum is zero, but the spectral shape can give a direct estimate of the 3d spin-orbit energy splitting DeltaE(SO). We have used Cu and CoO to experimentally test this technique. As expected Cu provides a vanishing result for , whereas for Co2+ in CoO we find =1.36h at 0 K. On the other hand we find DeltaE(SO)similar or equal to280 meV for Cu.
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| 17. |
- J.Lindner, A.Scherz, P.Poulopoulos, C.Rudt, A.N.Anisimov, H.Wende, K.Baberschke, P.Blomquist, R.Wäppling, F.Wilhelm, N.B.Brookes
(författare)
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Ultrathin Fe-limit in Fe/V(001) superlattices
- 2003
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Ingår i: Journal of Magnetism and Magnetic Materials. ; 256:1-3, s. 404-411
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Tidskriftsartikel (refereegranskat)
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| 18. |
- Johansson, Annica, 1969, et al.
(författare)
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Variants of CYP46A1 may interact with age and APOE to influence CSF Abeta42 levels in Alzheimer's disease.
- 2004
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Ingår i: Human genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 114:6, s. 581-7
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have suggested that variants of CYP46A1, encoding cholesterol 24-hydroxylase (CYP46), confer risk for Alzheimer's disease (AD), a prospect substantiated by evidence of genetic association from several quantitative traits related to AD pathology, including cerebrospinal fluid (CSF) levels of the 42 amino-acid cleavage product of beta-amyloid (Abeta42) and the tau protein. In the present study, these claims have been explored by the genotyping of previously associated markers in CYP46A1 in three independent northern European case-control series encompassing 1323 individuals and including approximately 400 patients with measurements of CSF Abeta42 and phospho-tau protein levels. Tests of association in case-control models revealed limited evidence that CYP46A1 variants contributed to AD risk across these samples. However, models testing for potential effects upon CSF measures suggested a possible interaction of an intronic marker (rs754203) with age and APOE genotype. In stratified analyses, significant effects were evident that were restricted to elderly APOE epsilon4 carriers for both CSF Abeta42 ( P=0.0009) and phospho-tau ( P=0.046). Computational analyses indicate that the rs754203 marker probably does not impact the binding of regulatory factors, suggesting that other polymorphic sites underlie the observed associations. Our results provide an important independent replication of previous findings, supporting the existence of CYP46A1 sequence variants that contribute to variability in beta-amyloid metabolism.
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| 19. |
- Marangolo, M, et al.
(författare)
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Magnetism of the Fe/ZnSe(001) interface
- 2002
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 88:21, s. 217202-
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Tidskriftsartikel (refereegranskat)abstract
- The magnetism of epitaxial ultrathin films of Fe on ZnSe(001) has been investigated by x-ray magnetic circular dichroism down to the submonolayer regime. In contrast to other metallic ferromagnet/semiconductor interfaces, no reduction of the Fe magnetic moment was found at the Fe/ZnSe(001) interface. Furthermore, a significant enhancement of the Fe magnetic moment compared to the bulk value was observed for coverages up to one monolayer in agreement with theoretical predictions. We also demonstrate that the magnetic properties of the Fe/ZnSe(001) interface remain stable against thermal annealing up to 300 degrees C, a prerequisite for the future development of efficient spintronics devices.
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| 20. |
- Minar, J., et al.
(författare)
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Theoretical description of the Fano effect in the angle-integrated valence-band photoemission of paramagnetic solids
- 2001
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 6314:14
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Tidskriftsartikel (refereegranskat)abstract
- A theoretical description of the Fano effect in the angle-integrated valence-band photoemission of paramagnetic solids is presented that is based on the one-step model of photoemission and relativistic multiple-scattering theory. Applications to fcc-Cu led to a very satisfying agreement with recent experimental data that show the Fano effect, i.e., a finite spin-polarization for the spectra is found for excitation with circularly polarized radiation. As can be demonstrated by model calculations. this finding is caused by the presence of spin-orbit coupling. To allow for a more detailed discussion of the spectra a simplified description of the Fano effect is presented that treats spin-orbit coupling as a perturbation.
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| 22. |
- Olsson, Catharina, 1968, et al.
(författare)
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Neurochemical characterisation of extrinsic innervation of the guinea pig rectum.
- 2004
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Ingår i: The Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 470:4, s. 357-371
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Tidskriftsartikel (refereegranskat)abstract
- The presence of markers for parasympathetic, sympathetic, and glutamatergic or peptidergic sensory innervation was investigated by using in vitro tracing with biotinamide, combined with immunohistochemistry, to characterise quantitatively extrinsic axons to myenteric ganglia of the guinea pig rectum. Of biotinamide-filled varicose axons, 3.6 ± 1.3% were immunoreactive for tyrosine hydroxylase (TH) and 16.0 ± 4.8% for vesicular acetylcholine transporter (VAChT). TH and vesicular monoamine transporter (VMAT1) showed high coexistence (83-100%), indicating that varicosities lacking TH immunoreactivity also lacked VMAT1. VAChT was detectable in 77% of choline acetyltransferase (ChAT)-immunoreactive varicosities. Calcitonin gene-related peptide (CGRP) was detected in 5.3 ± 1.6% of biotinamide-labeled varicosities, the vesicular glutamate transporter (VGluT) 1 in 2.8 ± 0.8%, and VGluT2 in 11.3 ± 4.2% of varicosities of extrinsic origin. Varicosities from the same axon showed consistent immunoreactivity. A novel type of nerve ending was identified, with branching, flattened lamellar endings, similar to the intraganglionic laminar endings (IGLEs) of the proximal gut. Rectal IGLEs were frequently immunoreactive for VGluT1 and VGluT2. Thus most varicose axons of extrinsic origin, which innervate rectal myenteric ganglia, lack detectable levels of immunoreactivity for TH, VMAT1, VAChT, ChAT, VGluT1/2, or CGRP, under conditions in which these markers are readily detectable in other axons. Although some unlabeled varicosities may belong to afferent axons that lack detectable CGRP or VGluT1/2 in the periphery, this suggests that a large proportion of axons do not release any of the major autonomic or sensory transmitters. We speculate that this may vary under particular circumstances, for example, inflammation or obstruction of the gut. J. Comp. Neurol. 470:357-371, 2004. © 2004 Wiley-Liss, Inc.
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| 24. |
- Prokunina, Ludmila, et al.
(författare)
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A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans
- 2002
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 32:4, s. 666-669
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women. A number of susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes and mutations is yet to be identified. We previously reported a susceptibility locus (SLEB2) for Nordic multi-case families. Within this locus, the programmed cell death 1 gene (PDCD1, also called PD-1) was considered the strongest candidate for association with the disease. Here, we analyzed 2,510 individuals, including members of five independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that we identified in PDCD1. We show that one intronic SNP in PDCD1 is associated with development of SLE in Europeans (found in 12% of affected individuals versus 5% of controls; P = 0.00001, r.r. (relative risk) = 2.6) and Mexicans (found in 7% of affected individuals versus 2% of controls; P = 0.0009, r.r. = 3.5). The associated allele of this SNP alters a binding site for the runt-related transcription factor 1 (RUNX1, also called AML1) located in an intronic enhancer, suggesting a mechanism through which it can contribute to the development of SLE in humans.
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