| 1. |
- Abbasi, R., et al.
(författare)
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SEARCH FOR HIGH-ENERGY MUON NEUTRINOS FROM THE "NAKED-EYE" GRB 080319B WITH THE IceCube NEUTRINO TELESCOPE
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 701:2, s. 1721-1731
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Tidskriftsartikel (refereegranskat)abstract
- We report on a search with the IceCube detector for high-energy muon neutrinos from GRB 080319B, one of the brightest gamma-ray bursts (GRBs) ever observed. The fireball model predicts that a mean of 0.1 events should be detected by IceCube for a bulk Lorentz boost of the jet of 300. In both the direct on-time window of 66 s and an extended window of about 300 s around the GRB, no excess was found above background. The 90% CL upper limit on the number of track-like events from the GRB is 2.7, corresponding to a muon neutrino fluence limit of 9.5 x 10(-3) erg cm(-2) in the energy range between 120 TeV and 2.2 PeV, which contains 90% of the expected events.
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| 2. |
- Abbasi, R, et al.
(författare)
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Extending the Search for Neutrino Point Sources with IceCube above the Horizon
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:22, s. 221102-
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Tidskriftsartikel (refereegranskat)abstract
- Point source searches with the IceCube neutrino telescope have been restricted to one hemisphere, due to the exclusive selection of upward going events as a way of rejecting the atmospheric muon background. We show that the region above the horizon can be included by suppressing the background through energy-sensitive cuts. This improves the sensitivity above PeV energies, previously not accessible for declinations of more than a few degrees below the horizon due to the absorption of neutrinos in Earth. We present results based on data collected with 22 strings of IceCube, extending its field of view and energy reach for point source searches. No significant excess above the atmospheric background is observed in a sky scan and in tests of source candidates. Upper limits are reported, which for the first time cover point sources in the southern sky up to EeV energies.
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| 3. |
- Abbasi, R, et al.
(författare)
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Determination of the atmospheric neutrino flux and searches for new physics with AMANDA-II
- 2009
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 79, s. 102005-
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Tidskriftsartikel (refereegranskat)abstract
- The AMANDA-II detector, operating since 2000 in the deep ice at the geographic South Pole, has accumulated a large sample of atmospheric muon neutrinos in the 100 GeV to 10 TeV energy range. The zenith angle and energy distribution of these events can be used to search for various phenomenological signatures of quantum gravity in the neutrino sector, such as violation of Lorentz invariance or quantum decoherence. Analyzing a set of 5511 candidate neutrino events collected during 1387 days of livetime from 2000 to 2006, we find no evidence for such effects and set upper limits on violation of Lorentz invariance and quantum decoherence parameters using a maximum likelihood method. Given the absence of evidence for new flavor-changing physics, we use the same methodology to determine the conventional atmospheric muon neutrino flux above 100 GeV.
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| 4. |
- Abbasi, R, et al.
(författare)
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FIRST NEUTRINO POINT-SOURCE RESULTS FROM THE 22 STRING ICECUBE DETECTOR
- 2009
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Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 701, s. L47-L51
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Tidskriftsartikel (refereegranskat)abstract
- We present new results of searches for neutrino point sources in the northern sky, using data recorded in 2007-2008 with 22 strings of the IceCube detector (approximately one-fourth of the planned total) and 275.7 days of live time. The final sample of 5114 neutrino candidate events agrees well with the expected background of atmospheric muon neutrinos and a small component of atmospheric muons. No evidence of a point source is found, with the most significant excess of events in the sky at 2.2 sigma after accounting for all trials. The average upper limit over the northern sky for point sources of muon-neutrinos with E-2 spectrum is E-2 Phi(v mu) < 1.4 x 10(-11) TeV cm(-2) s(-1), in the energy range from 3 TeV to 3 PeV, improving the previous best average upper limit by the AMANDA-II detector by a factor of 2.
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| 5. |
- Abbasi, R, et al.
(författare)
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Limits on a Muon Flux from Neutralino Annihilations in the Sun with the IceCube 22-String Detector
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:20, s. 201302-
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Tidskriftsartikel (refereegranskat)abstract
- A search for muon neutrinos from neutralino annihilations in the Sun has been performed with the IceCube 22-string neutrino detector using data collected in 104.3 days of live time in 2007. No excess over the expected atmospheric background has been observed. Upper limits have been obtained on the annihilation rate of captured neutralinos in the Sun and converted to limits on the weakly interacting massive particle (WIMP) proton cross sections for WIMP masses in the range 250-5000 GeV. These results are the most stringent limits to date on neutralino annihilation in the Sun.
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| 6. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 7. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 8. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 9. |
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| 10. |
- Campoy-Quiles, M., et al.
(författare)
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On the determination of anistropy in polymer thin films : A comparative study of optical techniques
- 2008
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Ingår i: Physica Status Solidi. C: Current Topics in Solid State Physics. - Weinheim, Germany : Wiley-VCH Verlagsgesellschaft. - 1862-6351. ; 5:5, s. 1270-1273
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Tidskriftsartikel (refereegranskat)abstract
- We have used seven different techniques to measure the anisotropic refractive index of poly(vinylcarbazole) films. These techniques are: two types of variable angle spectroscopic ellipsometry (VASE) with multiple sample analysis, Interference enhanced VASE, Transmittance combined with VASE, Polarised Reflectance, beta-scan VASE, and prism coupling. We have found the average ordinary and extraordinary indices at 633 nm to be no = nTE = 1.675 ± 0.008, and ne = nTM = 1.722 ± 0.018, respectively, consistent amongst methods and conclusive on the magnitude of Δn in polymer films.
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| 11. |
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| 12. |
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| 13. |
- Ingelsson, Martin, et al.
(författare)
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No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer's disease brain
- 2006
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 112:4, s. 439-449
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Tidskriftsartikel (refereegranskat)abstract
- Defective splicing of tau mRNA, promoting a shift between tau isoforms with (4R tau) and without (3R tau) exon 10, is believed to be a pathological consequence of certain tau mutations causing frontotemporal dementia. By assessing protein and mRNA levels of 4R tau and 3R tau in 27 AD and 20 control temporal cortex, we investigated whether altered tau splicing is a feature also in Alzheimer's disease (AD). However, apart from an expected increase of sarcosyl-insoluble tau in AD, there were no significant differences between the groups. Next, by laser-capture microscopy and quantitative PCR, we separately analyzed CA1 hippocampal neurons with and without neurofibrillary pathology from six of the AD and seven of the control brains. No statistically significant differences in 4R tau/3R tau mRNA were found between the different subgroups. Moreover, we confirmed the absence of significant ratio differences in a second data set with laser-captured entorhinal cortex neurons from four AD and four control brains. Finally, the 4R tau/3R tau ratio in CA1 neurons was roughly half of the ratio in temporal cortex, indicating region-specific differences in tau mRNA splicing. In conclusion, this study indicated region-specific and possibly cell-type-specific tau splicing but did not lend any support to overt changes in alternative splicing of tau exon 10 being an underlying factor in AD pathogenesis.
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| 14. |
- Blom, Elin S., et al.
(författare)
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Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype.
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 27:5, s. 458-64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. METHODS: Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. RESULTS: The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD. CONCLUSIONS: CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.
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| 15. |
- Bradley, E. L., et al.
(författare)
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The BIOSAFEPAPER project for in vitro toxicity assessments : Preparation, detailed chemical characterisation and testing of extracts from paper and board samples
- 2008
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 46:7, s. 2498-2509
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Tidskriftsartikel (refereegranskat)abstract
- Nineteen food contact papers and boards and one non-food contact board were extracted following test protocols developed within European Union funded project BIOSAFEPAPER. The extraction media were either hot or cold water, 95% ethanol or Tenax, according to the end use of the sample. The extractable dry matter content of the samples varied from 1200 to 11,800 mg/kg (0.8-35.5 mg/dm2). According to GC-MS the main substances extracted into water were pulp-derived natural products such as fatty acids, resin acids, natural wood sterols and alkanols. Substances extracted into ethanol particularly, were diisopropylnaphthalenes, alkanes and phthalic acid esters. The non-food contact board showed the greatest number and highest concentrations of GC-MS detectable compounds. The extracts were subjected to a battery of in vitro toxicity tests measuring both acute and sublethal cytotoxicity and genotoxic effects. None of the water or Tenax extracts was positive in cytotoxicity or genotoxicity assays. The ethanol extract of the non-food contact board gave a positive response in the genotoxicity assays, and all four ethanol extracts gave positive response(s) in the cytotoxicity assays to some extent. These responses could not be pinpointed to any specific compound, although there appeared a correlation between the total amount of extractables and toxicity.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Foerster, Bradley R., et al.
(författare)
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Value of gadolinium in brain MRI examinations for developmental delay
- 2006
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Ingår i: Pediatric Neurology. - : Elsevier BV. - 0887-8994. ; 35:2, s. 126-130
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging evaluation of developmental delay in children less than 2 years of age. A computerized retrospective study identified all brain magnetic resonance imaging examinations using gadolinium performed at our institution from 1995-2002 for children under the age of 2 years. Review of the clinical records and magnetic resonance imaging reports identified 170 brain magnetic resonance imaging examinations that were performed for developmental delay. Magnetic resonance imaging studies with enhancing lesions were reviewed by two staff neuroradiologists and two radiology residents. Contrast administration was rated as essential, helpful, or not helpful for each study. In the 107 patients in whom developmental delay was the primary concern, there were no cases in which the findings would have been missed without gadolinium administration. In the 63 patients in whom developmental delay was a secondary concern, there were several cases (11%) where contrast was helpful but not essential in reaching a radiologic diagnosis. In conclusion, intravenous gadolinium has an extremely low yield in children under the age of 2 where developmental delay is the primary concern. In young children for whom developmental delay is a secondary concern, we advocate the use of gadolinium particularly where tumor or infection is clinically suspected. (c) 2006 by Elsevier Inc. All rights reserved.
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| 20. |
- Giedraitis, Vilmantas, et al.
(författare)
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The normal equilibrium between CSF and plasma amyloid beta levels is disrupted in Alzheimer's disease
- 2007
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 427:3, s. 127-131
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta (A beta) with 40 (A beta 40) and 42 (A beta 42) amino acids, the main components of amyloid plaques in the Alzheimer's disease (AD) brain, can be measured in human cerebrospinal fluid (CSF) and plasma. Whereas CSF A beta 42 is decreased in AD, some studies have reported changed plasma A beta levels in AD and in subjects with mild cognitive impairment (MCI). To this date it is unclear if and how CSF and plasma levels of A beta correlate with each other in healthy individuals, albeit earlier studies on AD patients found no correlation between CSF and plasma A beta. We have measured A beta 40 and A beta 42 in paired CSF and plasma samples from patients with AD (n=39), MCI (n=29) and healthy control subjects (n= 18). We observed a clear correlation between CSF and plasma levels for both A beta 40 and A beta 42 in healthy individuals, whereas no such correlation could be seen for AD or MCI cases. Similarly to other studies we also found low levels of A beta 42 in AD CSF, whereas there were no significant differences in plasma A beta levels between the diagnostic groups. Our findings suggest that the normal equilibrium between CSF and plasma A beta may be disrupted with the initiation of amyloid deposition in the brain.
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| 21. |
- Ingelsson, Martin, et al.
(författare)
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Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains
- 2007
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 114:5, s. 471-479
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Tidskriftsartikel (refereegranskat)abstract
- Some cases of familial frontotemporal dementia (FTD) leading to frontotemporal lobar degeneration (FTLD) are caused by mutations in tau on chromosome 17 (FTDP-17). Certain mutations alter the ratio between four (4R tau) and three (3R tau) repeat tau isoforms whereas cases with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) mainly have 4R tau brain pathology. We assessed tau mRNA and protein levels in frontal cortex from 15 sporadic FTLD, 21 PSP, 5 CBD, 15 Alzheimer’s disease (AD) and 16 control brains. Moreover, we investigated the disease association and possible tau splicing effects of the tau H1 haplotype. Cases with FTLD and PSP had lower tau mRNA levels than control brains. When analyzing 4R tau and 3R tau mRNA separately, control subjects displayed a 4R tau/3R tau ratio of 0.48. Surprisingly, FTLD brains displayed a more elevated ratio (1.32) than PSP brains (1.12). Also, several FTLD and PSP cases had higher 4R tau/3R tau mRNA than FTDP-17 cases, included as reference tissues, and the ratio increase was seen regardless of underlying histopathology, i.e. both for tau-positive and tau-negative FTLD cases. Furthermore, total tau protein levels were slightly decreased in both FTLD and AD as compared to control subjects. Finally, we confirmed the association of tau H1 with PSP, but could not find any haplotype-related effect on tau exon 10 splicing. In conclusion, we demonstrated increased but largely variable 4R tau/3R tau mRNA ratios in FTLD and PSP cases, suggesting heterogeneous pathophysiological processes within these disorders.
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| 22. |
- Mach, Henryk, et al.
(författare)
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Structure of heavy Fe nuclei at the point of transition at N simular to 37
- 2009
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Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 40:3, s. 477-480
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Tidskriftsartikel (refereegranskat)abstract
- We have studied energy levels in Fe-63 populated in the beta-decay of Mn-63. A new (preliminary) level scheme of Fe-63 includes 10 excited states connected by 21 gamma-rays. The first excited states at 357 and 451 keV have the level half-lives of 110 ps and 780 ps, respectively. Three states, at 357, 451, and 1132 keV, are strongly beta-fed with log ft similar to 5, while there is only a very week beta-feeding, if any at all, to the ground state. The new results imply that Fe-63 departs from a simple shell model structure observed for heavier N = 37 isotones of Ni-65 and Zn-67.
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| 23. |
- Mach, Henryk, et al.
(författare)
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The single-particle and collective features in the nuclei just above Sn-132
- 2007
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Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 38:4, s. 1213-1218
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Tidskriftsartikel (refereegranskat)abstract
- The Advanced Time Delayed method has been used to measure the lifetimes of excited states in the exotic nuclei Sb-134, Sb-135 and Te-136 populated in the beta decay of Sn-134, Sn-135 and Sn-136, respectively. High purity Sn beams were extracted at the ISOLDE separator using a novel production technique utilizing the molecular SnS+ beams to isolate Sn from contaminating other fission products. Among the new results we have identified the 1/2(+) state in Sb-135 and its E2 transition to the lower-lying 5/2(+) state was found to be surprisingly collective. This measurement represents also one of the first applications of the LaBr3 scintillator to ultra fast timing.
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| 24. |
- Matsui, Toshifumi, et al.
(författare)
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Expression of APP pathway mRNAs and proteins in Alzheimer's disease
- 2007
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1161, s. 116-123
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Tidskriftsartikel (refereegranskat)abstract
- In both trisomy 21 and rare cases of triplication of amyloid precursor protein (APP) Alzheimer's disease (AD) pathological changes are believed to be secondary to increased expression of APP. We hypothesized that sporadic AD may also be associated with changes in transcription of APP or its metabolic partners. To address this issue, temporal neocortex of 27 AD and 21 non-demented control brains was examined to assess mRNA levels of APP isoforms (total APP, APP containing the Kunitz protease inhibitor domain [APP-KPI] and APP770) and APP metabolic enzymatic partners (the APP cleaving enzymes beta-secretase [BACE] and presenilin-1 [PS- 1], and putative clearance molecules, low-density lipoprotein receptor protein [LRP] and apolipoprotein E [apoE]). Furthermore, we evaluated how changes in APP at the mRNA level affect the amount of Tris buffer extractable APP protein and A beta 40 and 42 peptides in AD and control brains. As assessed by quantitative PCR, APP-KPI (p=0.007), APP770 (p=0.004), PS-1 (p = 0.004), LRP (p = 0.003), apoE (p = 0.0002) and GFAP (p < 0.0001) mRNA levels all increased in AD, and there was a shift from APP695 (a neuronal isoform) towards KPI containing isoforms that are present in glia as well. APP-KPI mRNA levels correlated with soluble APP alpha -KPI protein (sAPP alpha -KPI) levels measured by ELISA (T= 0.33, p = 0.015 by Kendall's rank correlation); in turn, soluble APP alpha-KPI protein levels positively correlated with Tris -extractable, soluble A beta 40 (p=0.046) and 42 levels (p=0.007). The ratio of soluble APP alpha-KPI protein levels to total APP protein increased in AD, and also correlated with GFAP protein levels in AD. These results suggest that altered transcription of APP in AD is proportionately associated with A beta peptide, may occur in the context of gliosis, and may contribute to A beta deposition in sporadic AD.
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| 25. |
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| 26. |
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| 27. |
- Smith, D. L., et al.
(författare)
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Lifetime measurements of the negative-parity 7(-) and 8(-) states in Cd-122
- 2008
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 77:1, s. 014309-
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Tidskriftsartikel (refereegranskat)abstract
- The Advanced Time-Delayed beta gamma gamma(t) method was used to measure lifetimes of selected high-spin states in Cd-122 populated from beta(-) decay of the J(pi)=(9(-)) isomer in Ag-122. From the gamma gamma coincidences, a new energy level was established at 2616.6 keV with a suggested spin-parity assignment of 8(-). Lifetimes were determined for the high-spin states at 2616.6 and 2502.7 keV as T-1/2=1.35(29) ns and 0.24(6) ns, respectively. The transition rates for gamma rays de-exciting the 7(-) states in the N=74 isotones of Cd-122, Sn-124, and Te-126 were found to be very similar.
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| 28. |
- Soranzo, Nicole, et al.
(författare)
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A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 38-1182
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Tidskriftsartikel (refereegranskat)abstract
- The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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| 29. |
- Sundelöf, Johan, et al.
(författare)
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Plasma β Amyloid and the Risk of Alzheimer Disease and Dementia in Elderly Men : A Prospective, Population-Based Cohort Study
- 2008
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Ingår i: Archives of Neurology. - : American Medical Association (AMA). - 0003-9942 .- 1538-3687. ; 65:2, s. 256-63
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Beta amyloid (Abeta) protein accumulates in the brains of individuals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma. OBJECTIVE: To examine plasma levels of Abeta peptides Abeta(40) and Abeta(42) as predictors of incident AD and other types of dementia. DESIGN: Prospective, population-based cohort study. SETTING: The Uppsala Longitudinal Study of Adult Men. PARTICIPANTS: Plasma Abeta(40) and Abeta(42) levels were analyzed as predictors of incident AD in 1045 men at age 70 years and 680 men at age 77 years using Cox proportional hazards analyses. Alzheimer disease and other types of dementia were diagnosed by standardized screening, clinical evaluation, and medical record review. MAIN OUTCOME MEASURES: Hazard ratios of AD (primary outcome) and vascular dementia or other dementia (secondary outcomes) according to baseline levels of plasma Abeta(40) and Abeta(42). RESULTS: From the age of 77 years at baseline, 46 individuals developed AD at follow-up (median, 5.3 years). A low plasma Abeta(40) level at age 77 years was associated with higher incidence of AD. The multivariate-adjusted hazard ratio was 4.87 (95% confidence interval, 1.63-14.6) for the lowest Abeta(40) tertile compared with the highest tertile. On follow-up from age 70 years at baseline (median, 11.2 years), 82 individuals developed AD. Plasma Abeta(40) and Abeta(42) levels measured at age 70 years were not significantly associated with incident AD. CONCLUSIONS: Low plasma Abeta(40) levels predicted incident AD in elderly men independently of potential confounders. Plasma Abeta(42) levels were not significantly associated with AD incidence. The clinical value of Abeta measurement in plasma remains to be established in future studies.
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| 31. |
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