| 1. |
- Estrada, Karol, et al.
(author)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Journal article (peer-reviewed)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 2. |
- Massoud, Al-Shimaà A A, 1980, et al.
(author)
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Bis 4,5-diazafluoren-9-one silver(I) nitrate: synthesis, X-ray structures, solution chemistry, hydrogel loading, DNA coupling and anti-bacterial screening
- 2011
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In: New Journal of Chemistry. - : Royal Society of Chemistry (RSC). - 1369-9261 .- 1144-0546. ; 35:3, s. 640-648
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Journal article (peer-reviewed)abstract
- Synthesis of bis-4,5-diazafluoren-9-one silver(I) nitrate I (dafone = 4,5-diazafluoren-9-one) and the low temperature X-ray single crystal structure of [Ag(4,5-diazafluoren-9-one)2NO3], crystal form 1, and a re-determination of [Ag(4,5-diazafluoren-9-one)2]NO3 . H2O, crystal form 2 are presented. Crystal form 1 has a distorted trigonal planar coordination geometry around Ag(I) with an N-Ag-N bond angle of 123.45(7)o. Crystal form 2 has a perfect linear coordination around Ag, with N-Ag-N 180.0o. Compound I was characterized by 1H-NMR, biological activity and ESI-MS in DMSO at room temperature. The biological activity was determined against 6 different resistant clinical isolates; two Gram-positive (Staphylococcus aureus and Streptococcus pyogenes) and four Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella sp.) in comparison with 15 known antibiotics used in the treatment of diabetic foot infections. Compound I showed broad spectrum activity against all the test organisms. P. mirabilis and S. aureus and K. pneumoniae were the most sensitive clinical isolates (MIC = 4, 6 and 4 μg ml-1, respectively). Three different hydrogels containing I or Ag2SO4 were prepared and the antimicrobial activity against Ps. aeruginosa (ATCC 15442) compared, showing more or less equal activity on a weight basis, but I seems to have a significant better performance per silver ion. The Ag(I) complex also binds more effectively to calf thymus DNA than the dafone ligand itself.
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| 3. |
- Rudolph, Dirk, et al.
(author)
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Isospin and Deformation Studies in the Odd-odd N = Z Nucleus 54Co
- 2010
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 82:5
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Journal article (peer-reviewed)abstract
- High-spin states in the odd-odd N = Z nucleus Co-54 have been investigated by the fusion-evaporation reaction Si-28(S-32,1 alpha 1p1n)Co-54. Gamma-ray information gathered with the Ge detector array Gammasphere was correlated with evaporated particles detected in the charged particle detector system Microball and a 1 pi neutron detector array. A significantly extended excitation scheme of Co-54 is presented, which includes a candidate for the isospin T = 1, 6(+) state of the 1f(7/2)(-2) multiplet. The results are compared to large-scale shell-model calculations in the fp shell. Effective interactions with and without isospin-breaking terms have been used to probe isospin symmetry and isospin mixing. A quest for deformed high-spin rotational cascades proved negative. This feature is discussed by means of cranking calculations.
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| 4. |
- Davis, Simon J. M., et al.
(author)
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Molecular and osteometric sexing of cattle metacarpals : a case study from 15th century AD Beja, Portugal
- 2012
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In: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 39:5, s. 1445-1454
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Journal article (peer-reviewed)abstract
- In the course of a zooarchaeological survey of Holocene sites in southern Portugal, a substantial size increase of cattle bones was noted following the Christian reconquista of the 11th-13th centuries AD. A size increase in the course of time within a lineage of domestic livestock is usually considered to represent animal improvement. However several other factors including sex may influence the average size of a sample of mammal bones - cattle exhibit considerable sexual size dimorphism, with bulls being larger than cows. A histogram of the distal widths of a large (n = 44) sample of cattle metacarpals from 15th century Beja (Alentejo, Portugal), revealed a bimodal distribution. It was assumed that the large measurements belonged to males and the small to females. In order to rule out the possibility of a post-Moslem change in the sex ratio of cattle, a sub-sample of 21 cattle metacarpals from Beja was selected and we used genetic markers to identify the sex of the animals to which these metacarpals belonged. The ancient DNA sex of all specimens agreed with the previously assumed sex as determined osteometrically. We conclude that the two nearly separated peaks for the metacarpal distal width measurements do indeed indicate sex. A similar bimodal distribution was obtained from another large but earlier sample of cattle metacarpals from Moslem Alcacova de Santarem (9th-12th century AD). Although these have not been molecularly sexed and since osteometric sexing has now been validated, we conclude that both small (female) and large (male) peaks are smaller than the 15th century ones and that there was an overall size increase or improvement of cattle in this region. Why the Christians improved cattle is unclear, but a selection for larger beeves for meat is one possibility as is the selection of more robust cattle for power. The spread of the quadrangular or chariot plough in Iberia is known to have occurred at this time. We then use the genetically sexed metacarpals to determine which measurements provide reasonable distinction between the sexes. Both the distal width (BFd; as already noted by Svensson et al., 2008; in Swedish medieval cattle) and the width of the lateral condyle (WCL) offer the best distinction. We also used them as a reference 'collection' to sex the medieval and post-medieval cattle metacarpals from Launceston Castle in England. This re-visit of the Launceston data corroborates other evidence indicating increased specialisation (milk and veal) in post-medieval cattle husbandry in England.
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| 5. |
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| 6. |
- Svensson, Emma M., 1979-, et al.
(author)
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Coat colour and sex identification in horses from Iron Age Sweden
- 2012
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In: Annals of Anatomy. - : Elsevier BV. - 0940-9602 .- 1618-0402. ; 194:1, s. 82-87
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Journal article (peer-reviewed)abstract
- Domestication of animals and plants marked a turning point in human prehistory. To date archaeology, archaeozoology and genetics have shed light on when and where all of our major livestock species were domesticated. Phenotypic changes associated with domestication have occurred in all farm animals. Coat colour is one of the traits that have been subjected to the strongest human selection throughout history. Here we use genotyping of coat colour SNPs in horses to investigate whether there were any regional differences or preferences for specific colours associated with specific cultural traditions in Iron Age Sweden. We do this by identifying the sex and coat colour of horses sacrificed at Skedemosse, Oland (Sweden) during the Iron Age, as well as in horses from two sites in Uppland, Ultuna and Valsgarde (dated to late Iron Age). We show that bay, black and chestnut colours were all common and two horses with tobiano spotting were found. We also show how the combination of sex identification with genotyping of just a few SNPs underlying the basic coat colours can be used to identify the minimum number of individuals at a site on a higher level than morphological methods alone. Although separated by 500 km and from significantly different archaeological contexts the horses at Skedemosse and Ultuna are quite homogenous when it comes to coat colour phenotypes, indicating that there were no clear geographical variation in coat colouration in Sweden during the late Iron Age and early Viking Age.
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| 7. |
- Svensson, Emma M., 1979-, et al.
(author)
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Medieval cattle in Bern (Switzerland) : An archaeozoological, genetic and historical Approach
- 2014
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In: Schweizer Archiv für Tierheilkunde. - : Gesellschaft Schweizer Tierarztinnen und Tierarzte. - 0036-7281 .- 1664-2848. ; 156:1, s. 17-26
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Journal article (peer-reviewed)abstract
- This study deals with genetic analyses of an assemblage of mediaeval (1361 century) cattle metapodials from Bern that had previously been osteometrically examined regarding sex, shape and wither height. The results from the genetic sexing of these small (height 100 to 120 cm) cattle correlate well with the osteometric interpretations. Some few exceptions we interpreted as cows used as draft animals with stouter bones and thus osteometrically determined as males. Two morphologically different groups of cow metatarsals however, we took as proof of the historical fact that Bern relied on livestock from different geographical origins: the town's vicinity and the alpine pastures with their favourable grazing conditions. It was not possible to distinguish them genetically. An analysis of one single nucleotide polymorphism (SNP) in the melanocortin receptor 1 (MC1R) showed that predominant coat colour most likely was red-brown. Furthermore, an analysis of the SNP in the Y-chromosomal intron UTY19 that divide modern taurine cattle in two major haplogroups (Y1 and Y2) showed that the mediaeval cattle belonged to the haplogroup Y2 with one single exception of a Yl.
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| 8. |
- Andersen, Marie Louise M., et al.
(author)
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Association between autoantibodies to the Arginine variant of the Zinc transporter 8 (ZnT8) and stimulated C-peptide levels in Danish children and adolescents with newly diagnosed type 1 diabetes
- 2012
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 13:6, s. 454-462
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Journal article (peer-reviewed)abstract
- Background The zinc transporter 8 (ZnT8) was recently identified as a common autoantigen in type 1 diabetes (T1D) and inclusion of ZnT8 autoantibodies (ZnT8Ab) was found to increase the diagnostic specificity of T1D. Objectives The main aims were to determine whether ZnT8Ab vary during follow-up 1 year after diagnosis, and to relate the reactivity of three types of ZnT8Ab to the residual stimulated C-peptide levels during the first year after diagnosis. Subjects A total of 129 newly diagnosed T1D patients <15 years was followed prospectively 1, 3, 6, and 12 months after diagnosis. Methods Hemoglobin A1c, meal-stimulated C-peptide, ZnT8Ab, and other pancreatic autoantibodies were measured at each visit. Patients were genotyped for the rs13266634 variant at the SLC30A8 gene and HLA-DQ alleles. Results The levels of all ZnT8Ab [ZnT8Arg (arginine), ZnT8Trp (tryptophan), ZnT8Gln (glutamine)] tended to decrease during disease progression. A twofold higher level of ZnT8Arg and ZnT8Gln was associated with 4.6%/5.2% (p = 0.02), 5.3%/8.2% (p = 0.02) and 8.9%/9.7% (p = 0.004) higher concentrations of stimulated C-peptide 3, 6, and 12 months after diagnosis. The TT genotype carriers of the SLC30A8 gene had 45.8% (p = 0.01) and 60.1% (p = 0.002) lower stimulated C-peptide 6 and 12 months after diagnosis compared to the CC and the CT genotype carriers in a recessive model. Conclusions The levels of the Arg variant of the ZnT8 autoantibodies are associated with higher levels of stimulated C-peptide after diagnosis of T1D and during follow-up. Carriers of the TT genotype of the SLC30A8 gene predict lower stimulated C-peptide levels 12 months after diagnosis.
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| 9. |
- Burman, Joachim, et al.
(author)
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The cerebrospinal fluid cytokine signature of multiple sclerosis : A homogenous response that does not conform to the Th1/Th2/Th17 convention
- 2014
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In: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 277:1-2, s. 153-159
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Journal article (peer-reviewed)abstract
- In this cross-sectional study, we wanted to identify key cytokines characteristic of different stages of multiple sclerosis (MS). To this end, cerebrospinal fluid from patients with MS was investigated with a multiplexed fluorescent bead-based immunoassay. In total 43 cytokines were assessed and related to clinical and imaging data. Increased levels of CCL22, CXCL10 and sCD40L characterized relapsing-remitting MS patients with the presence of gadolinium-enhancing lesions; decreased CCL2 and increased CXCL1 and CCL5 were typical of relapsing-remitting MS patients irrespectively of the presence of gadolinium-enhancing lesions. These homogenous patterns of cytokine activation do not conform to conventional Th1/Th2/Th17 responses. (C) 2014 Elsevier B.V. All rights reserved.
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| 10. |
- Eklund, D. Magnus, et al.
(author)
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Physcomitrella patens : a model to investigate the role of RAC/ROP GTPase signalling in tip growth
- 2010
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In: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 61:7, s. 1917-1937
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Research review (peer-reviewed)abstract
- Polarized cell expansion plays an important role in plant morphogenesis. Tip growth is a dramatic form of this process, which is widely used as a model to study its regulation by RAC/ROP GTPase signalling. During the dominant haploid phase of its life cycle, the moss Physcomitrella patens contains different types of cells that expand by tip growth. Physcomitrella is a highly attractive experimental system because its genome has been sequenced, and transgene integration by homologous recombination occurs in this plant at frequencies allowing effective gene targeting. Furthermore, together with the vascular spikemoss Selaginella moellendorffii, whose genome has also been sequenced, the non-vascular moss Physcomitrella provides an evolutionary link between green algae and angiosperms. BLAST searches established that the Physcomitrella and Selaginella genomes encode not only putative RAC/ROP GTPases, but also homologues of all known regulators of polarized RAC/ROP signalling, as well as of key effectors acting in signalling cascades downstream of RAC/ROP activity. Nucleotide sequence relationships within seven different families of Physcomitrella, Selaginella, Arabidopsis thaliana and Nicotiana tabacum (tobacco) genes with distinct functions in RAC/ROP signalling were characterized based on extensive maximum likelihood and Neighbor-Joining analyses. The results of these analyses are interpreted in the light of current knowledge concerning expression patterns and molecular functions of RAC/ROP signalling proteins in angiosperms. A key aim of this study is to facilitate the use of Physcomitrella as a model to investigate the molecular control of tip growth in plants.
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