| 1. |
- Amundadottir, Laufey T., et al.
(författare)
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A common variant associated with prostate cancer in European and African populations
- 2006
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Ingår i: Nature Genetics. - DeCODE Genet, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Urol, IS-101 Reykjavik, Iceland. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 38:6, s. 652-658
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Tidskriftsartikel (refereegranskat)abstract
- With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
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| 2. |
- Helgadottir, Anna, et al.
(författare)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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| 3. |
- Aevarsson, Arnthór, et al.
(författare)
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Going to extremes - a metagenomic journey into the dark matter of life
- 2021
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Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12
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Forskningsöversikt (refereegranskat)abstract
- The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
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| 4. |
- Alerstam, Thomas, et al.
(författare)
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A polar system of intercontinental bird migration
- 2007
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Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 274:1625, s. 2523-2530
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Tidskriftsartikel (refereegranskat)abstract
- Studies of birdmigration in the Beringia region of Alaska and eastern Siberia are of special interest for revealing the importance of bird migration between Eurasia and North America, for evaluating orientation principles used by the birds at polar latitudes and for understanding the evolutionary implications of intercontinental migratory connectivity among birds as well as their parasites. We used tracking radar placed onboard the ice-breaker Oden to register bird migratory flights from 30 July to 19 August 2005 and we encountered extensive birdmigration in the whole Beringia range from latitude 64 degrees N in Bering Strait up to latitude 75 degrees N far north of Wrangel Island, with eastward flights making up 79% of all track directions. The results from Beringia were used in combination with radar studies from the Arctic Ocean north of Siberia and in the Beaufort Sea to make a reconstruction of a major Siberian-American birdmigration system in a wide Arctic sector between longitudes 1108 E and 130 degrees W, spanning one-third of the entire circumpolar circle. This system was estimated to involve more than 2 million birds, mainly shorebirds, terns and skuas, flying across the Arctic Ocean at mean altitudes exceeding 1 km (maximum altitudes 3-5 km). Great circle orientation provided a significantly better fit with observed flight directions at 20 different sites and areas than constant geographical compass orientation. The long flights over the sea spanned 40-80 degrees of longitude, corresponding to distances and durations of 1400-2600 km and 26-48 hours, respectively. The birds continued from this eastward migration system over the Arctic Ocean into several different flyway systems at the American continents and the Pacific Ocean. Minimization of distances between tundra breeding sectors and northerly stopover sites, in combination with the Beringia glacial refugium and colonization history, seemed to be important for the evolution of this major polar bird migration system.
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| 5. |
- Alerstam, Thomas, et al.
(författare)
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Great-Circle Migration Of Arctic Passerines
- 2008
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Ingår i: The Auk. - : Oxford University Press (OUP). - 0004-8038 .- 1938-4254. ; 125:4, s. 831-838
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Tidskriftsartikel (refereegranskat)abstract
- Birds can save distance and time on their migratory journeys by following great circles rather than rhumblines, but great-circle routes require more complex orientation with changing courses. Flight directions at different places along the route and in relation to the destination can be used to test whether birds migrate along great circles or rhumblines. Such data have indicated great-circle migration among shorebirds at high latitudes, but no critical tests have been made for passerines. Using tracking radar on board the icebreaker Oden in August 2005, we recorded westerly flight directions of passerine migrants over the Chukchi Sea. The main sector of migratory directions was 237-311 degrees centered oil a mean heading direction of 274 degrees. The most likely species to participate in this westward trans-Beringia migration, mainly departing from Alaska, were Eastern Yellow Wagtail (Motacilla Ischutschensis), Arctic Warbler (Phylloscopus borealis kennicotti), Northern Wheatear (Oenanthe oenanthe), and Bluethroat (Luscinia svecica); all except the Bluethroat were recorded from the ship. Observed flight directions agreed with predicted great-circle courses but not with rhumbline courses for three of these four species with winter quarters in Southeast Asia; no definite conclusion could be drawn for the Northern Wheatear (wintering in East Africa). These results support great-circle migration among passerines traveling between Alaska and Old World winter quarters, though the long-distance precision and orientation mechanisms are Still unknown. The relative importance of different evolutionary causes-such as circumvention of geographic barriers, retracing of ancient colonization ways, or distance reduction by great-circle migration-to complex bird migration routes with changing courses remains to be understood. Received 24 August 2007, accepted 6 March 2008.
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| 6. |
- Alerstam, Thomas, et al.
(författare)
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Migration Along Orthodromic Sun Compass Routes by Arctic Birds
- 2001
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 291:5502, s. 300-303
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Tidskriftsartikel (refereegranskat)abstract
- Flight directions of birds migrating at high geographic and magnetic latitudes can be used to test bird orientation by celestial or geomagnetic compass systems under polar conditions. Migration patterns of arctic shorebirds, revealed by tracking radar studies during an icebreaker expedition along the Northwest Passage in 1999, support predicted sun compass trajectories but cannot be reconciled with orientation along either geographic or magnetic loxodromes (rhumb lines). Sun compass routes are similar to orthodromes (great circle routes) at high latitudes, showing changing geographic courses as the birds traverse longitudes and their internal clock gets out of phase with local time. These routes bring the shorebirds from high arctic Canada to the east coast of North America, from which they make transoceanic flights to South America. The observations are also consistent with a migration link between Siberia and the Beaufort Sea region by way of sun compass routes across the Arctic Ocean.
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| 7. |
- Bergman, Peter, et al.
(författare)
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Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and meninges after meningococcal infection
- 2006
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 74:12, s. 6982-6991
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides are present in most living species and constitute important effector molecules of innate immunity. Recently, we and others have detected antimicrobial peptides in the brain. This is an organ that is rarely infected, which has mainly been ascribed to the protective functions of the blood-brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB and meninges are not known, we hypothesized that antimicrobial peptides could play a role in these barriers. We addressed this hypothesis by infecting mice with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed for expression of the antimicrobial peptide CRAMP by immunohistochemistry in combination with confocal microscopy. After infection, we observed induction of CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore the functional role of CRAMP in meningococcal disease, we infected mice deficient of the CRAMP gene. Even though CRAMP did not appear to protect the brain from invasion of meningococci, CRAMP knockout mice were more susceptible to meningococcal infection than wild-type mice and exhibited increased meningococcal growth in blood, liver, and spleen. Moreover, we could demonstrate that carbonate, a compound that accumulates in the circulation during metabolic acidosis, makes meningococci more susceptible to CRAMP.
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| 8. |
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| 9. |
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| 10. |
- Boguszewski, M. C. S., et al.
(författare)
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Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement
- 2022
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 186:6
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.
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| 11. |
- Darling, Kate F., et al.
(författare)
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The genetic diversity, phylogeography and morphology of Elphidiidae (Foraminifera) in the Northeast Atlantic
- 2016
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Ingår i: Marine Micropaleontology. - : Elsevier BV. - 0377-8398. ; 129, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- Genetic characterisation (SSU rRNA genotyping) and Scanning Electron Microscope (SEM) imaging of individual tests were used in tandem to determine the modern species richness of the foraminiferal family Elphidiidae (Elphidium, Haynesina and related genera) across the Northeast Atlantic shelf biomes. Specimens were collected at 25 locations from the High Arctic to Iberia, and a total of 1013 individual specimens were successfully SEM imaged and genotyped. Phylogenetic analyses were carried out in combination with 28 other elphidiid sequences from GenBank and seventeen distinct elphidiid genetic types were identified within the sample set, seven being sequenced for the first time. Genetic types cluster into seven main clades which largely represent their general morphological character. Differences between genetic types at the genetic, morphological and biogeographic levels are indicative of species level distinction. Their biogeographic distributions, in combination with elphidiid SSU sequences from GenBank and high resolution images from the literature show that each of them exhibits species-specific rather than clade-specific biogeographies. Due to taxonomic uncertainty and divergent taxonomic concepts between schools, we believe that morphospecies names should not be placed onto molecular phylogenies unless both the morphology and genetic type have been linked to the formally named holotype, or equivalent. Based on strict morphological criteria, we advocate using only a three-stage approach to taxonomy for practical application in micropalaeontological studies. It comprises genotyping, the production of a formal morphological description of the SEM images associated with the genetic type and then the allocation of the most appropriate taxonomic name by comparison with the formal type description. Using this approach, we were able to apply taxonomic names to fifteen genetic types. One of the remaining two may be potentially cryptic, and one is undescribed in the literature. In general, the phylogeographic distribution is in agreement with our knowledge of the ecology and biogeographical distribution of the corresponding morphospecies, highlighting the generally robust taxonomic framework of the Elphidiidae in time and space.
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| 12. |
- Daugbjerg Christensen, Monica, et al.
(författare)
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Cloning and Characterization of a Novel N-Acetyl-D-galactosamine-4-O-sulfate Sulfatase, SulA1, from a Marine Arthrobacter Strain
- 2024
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Ingår i: Marine Drugs. - 1660-3397. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Sulfation is gaining increased interest due to the role of sulfate in the bioactivity of many polysaccharides of marine origin. Hence, sulfatases, enzymes that control the degree of sulfation, are being more extensively researched. In this work, a novel sulfatase (SulA1) encoded by the gene sulA1 was characterized. The sulA1-gene is located upstream of a chondroitin lyase encoding gene in the genome of the marine Arthrobacter strain (MAT3885). The sulfatase was produced in Escherichia coli. Based on the primary sequence, the enzyme is classified under sulfatase family 1 and the two catalytic residues typical of the sulfatase 1 family—Cys57 (post-translationally modified to formyl glycine for function) and His190—were conserved. The enzyme showed increased activity, but not improved stability, in the presence of Ca2+, and conserved residues for Ca2+ binding were identified (Asp17, Asp18, Asp277, and Asn278) in a structural model of the enzyme. The temperature and pH activity profiles (screened using p-nitrocatechol sulfate) were narrow, with an activity optimum at 40–50 °C and a pH optimum at pH 5.5. The Tm was significantly higher (67 °C) than the activity optimum. Desulfation activity was not detected on polymeric substrates, but was found on GalNAc4S, which is a sulfated monomer in the repeated disaccharide unit (GlcA–GalNAc4S) of, e.g., chondroitin sulfate A. The position of the sulA1 gene upstream of a chondroitin lyase gene and combined with the activity on GalNAc4S suggests that there is an involvement of the enzyme in the chondroitin-degrading cascade reaction, which specifically removes sulfate from monomeric GalNAc4S from chondroitin sulfate degradation products.
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| 13. |
- de Jong, Yde, et al.
(författare)
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PESI - a taxonomic backbone for Europe
- 2015
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Ingår i: Biodiversity Data Journal. - 1314-2836 .- 1314-2828. ; 3, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- Reliable taxonomy underpins communication in all of biology, not least nature conservation and sustainable use of ecosystem resources. The flexibility of taxonomic interpretations, however, presents a serious challenge for end-users of taxonomic concepts. Users need standardised and continuously harmonised taxonomic reference systems, as well as high-quality and complete taxonomic data sets, but these are generally lacking for non-specialists. The solution is in dynamic, expertly curated web-based taxonomic tools.The Pan-European Species-directories Infrastructure (PESI) worked to solve this key issue by providing a taxonomic e-infrastructure for Europe. It strengthened the relevant social (expertise) and information (standards, data and technical) capacities of five major community networks on taxonomic indexing in Europe, which is essential for proper biodiversity assessment and monitoring activities. The key objectives of PESI were: 1) standardisation in taxonomic reference systems, 2) enhancement of the quality and completeness of taxonomic data sets and 3) creation of integrated access to taxonomic information.This paper describes the results of PESI and its future prospects, including the involvement in major European biodiversity informatics initiatives and programs.
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| 14. |
- Dubiel, M, et al.
(författare)
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Blood redistribution in the fetal brain during chronic hypoxia
- 2002
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 20:2, s. 117-121
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Tidskriftsartikel (refereegranskat)abstract
- Background Studies on blood flow velocity in the fetal middle cerebral artery have revealed signs of brain sparing in chronic hypoxia. These signs of brain sparing can disappear in the terminal case, but whether this applies to the whole brain or only parts of it is unknown. Methods Velocity waveforms of the middle cerebral, anterior cerebral and posterior cerebral arteries were recorded in 221 pregnancies complicated by pregnancy-induced hypertension. The presence of brain sparing (pulsatility index < 2 standard deviations) was noted and correlated to outcome of pregnancy, including emergency operative intervention and/or neonatal distress. Results Signs of brain sparing in the anterior cerebral artery were found in 90 fetuses, and in the middle cerebral and posterior cerebral arteries in 52 and 65, respectively. Signs of brain sparing in the anterior cerebral artery showed the strongest relationship to adverse perinatal outcome. The anterior cerebral artery was the only vessel in which signs of brain sparing were predictive of perinatal mortality. Conclusions Velocimetry of the anterior cerebral artery appears to be superior to that of the middle cerebral and posterior cerebral arteries as a means to predict adverse perinatal outcome. Anterior cerebral artery brain sparing may therefore be less transitory than sparing in the middle cerebral and posterior cerebral arteries, possibly suggesting that the frontal lobes are spared longer than the lateral and occipital regions of the fetal brain.
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| 15. |
- Elfgren, Lennart, 1942-, et al.
(författare)
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Quality Control Plans for European Concrete Road Bridges : Experiences from Cooperation within COST Action TU 1406
- 2017
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Ingår i: Proceedings of the 23rd Nordic Concrete Research Symposium, Oslo, Norway. - Oslo : Nordic Concrete Federation. ; , s. 249-252
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Konferensbidrag (refereegranskat)abstract
- The main objective of the COST Action TU1406 is to develop a guideline for the establishment of Quality Control plans for roadway bridges by integrating the most recent knowledge on performance assessment procedures. 36 European countries are working together in this endeavor during 2015-2019.
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| 16. |
- Fahlgren, Anna, 1972-
(författare)
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Defence capabilities of human intestinal epithelial cells
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The epithelial cells lining the intestinal mucosa separate the underlying tissue from components of the intestinal lumen. Innate immunity mediated by intestinal epithelial cells (IECs) provides rapid protective functions against microorganisms. Innate immunity also participates in orchestrating adaptive immunity. Key components in innate defence are defensins.To study the production of defensins and how it is affected by intestinal inflammation IECs were isolated from the small and large intestines of patients suffering from ulcerative colitis (UC), Crohn´s disease (MbC), celiac disease (CD), and from controls, and analyzed by quantitative RT-PCR (qRT-PCR) and immunoflow cytometry. Defensin expressing cells were also studied by in situ hybridization and immunohistochemistry.Normally, only small intestinal Paneth cells express human α-defensin 5 (HD-5) and HD-6. In UC colon IECs, HD-5, HD-6, and lysozyme mRNAs were expressed at high levels. In Crohn´s colitis colon the levels of HD-5 and lysozyme mRNAs were also increased although not to the same extent as in UC. No increase was detected in MbC with ileal localization. Metaplastic Paneth cell differentiation in UC colon was primarily responsible for the expression of the antimicrobial components. Human β-defensin 1 (hBD-1) mRNA was more abundant in large than in small intestine of controls, and remained unchanged in UC and MbC. hBD-2 mRNA was barely detectable in normal intestine and was induced in UC IECs but not in MbC IECs. mRNAs for the recently discovered hBD-3 and hBD-4, were detected in IECs from both small and large intestine. Both hBD-3 and hBD-4 mRNA were significantly increased in IECs of UC patients but not of MbC patients. Bacteria and IL-1β induced hBD-2 but not hBD-1 mRNA in colon carcinoma cell lines. IFN-γ, but not TNF-α or IL-1β, augmented hBD-3 expression in these cells, while none of the agents induced hBD-4. High antimicrobial activity of IECs in UC may be a consequence of changes in the epithelial lining, which permit the adherence of microorganisms.Unexpectedly, in situ hybridization revealed expression of hBD-3 and hBD-4 mRNAs by numerous lamina propria cells in colonic tissue from UC patients. These cells were identified as plasma cells (CD138+). hBD-3 and hBD-4 mRNAs were also demonstrated in the plasmacytoma cell line U266. This is the first demonstration of defensins in plasma cells.The four prominent constituents of the intestinal glycocalyx, carcinoembryonic antigen (CEA), CEA cell adhesion molecule 1 (CEACAM1), CEACAM6 and CEACAM7 all seem to play a critical role in innate defence of the intestinal mucosa by trapping and expelling microorganisms at the epithelial surface. The inducibility of these molecules in colonic epithelial cell lines was analyzed by qRT-PCR, immunoflow cytometry, and immunoelectron microscopy. IFN-g but not bacteria, LPS, TNF-α, or IL-1β modified the expression of CEA, CEACAM1 and CEACAM6. None of these agents modified CEACAM7 expression. IFN-γ was shown to have two effects: a direct effect on CEACAM1 transcription, and promotion of cell differentiation resulting in increased CEA and CEACAM6 and decreased CEACAM7 expression.Scanning electron microscopy of jejunal biopsies from children with CD revealed the presence of rod shaped bacteria in ~40% of patients with active CD, but only in 2% of controls. 19% of treated CD patients still had adhering bacteria. Presence of bacteria is not due to lack of antimicrobial factors. In fact, HD-5, HD-6, and lysozyme mRNA levels were significantly increased in IECs of patients with active CD. hBD-1 and hBD-2 were unchanged. Lack of induction of hBD-2 may reflect disturbed signalling in IECs of CD patients. Analysis of CEA and CEACAM1 mRNA/protein expression showed no differences between CD patients and controls. Analysis of the mucins MUC2 and MUC3 revealed significantly increased MUC2 levels in active disease and unchanged MUC3. Immunohistochemistry demonstrated goblet cell metaplasia as well as staining of the apical portion of absorptive cells. Glycosylation status of proteins was studied by lectin histochemistry. Goblet cells in the mucosa of CD patients were stained by the lectin UEAI. This was not seen in controls. The lectin PNA stained the glycocalyx of controls but not that of CD patients. Thus, unique carbohydrate structures of the glycocalyx/mucous layer are likely discriminating features of CD patients and may allow bacterial binding.We conclude that the intestinal epithelium is heavily involved in the innate defence of the mucosa and that its reactive pattern is affected by intestinal inflammation.Keywords: human intestinal mucosa; epithelial cells; innate immunity; defensin; ulcerative colitis; Crohn´s disease; celiac disease; glycoαcalyx; mucin
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Kiemeney, Lambertus A, et al.
(författare)
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A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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| 21. |
- Kristjansdottir, Thordis, et al.
(författare)
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Engineering the carotenoid biosynthetic pathway in Rhodothermus marinus for lycopene production
- 2020
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Ingår i: Metabolic Engineering Communications. - : Elsevier BV. - 2214-0301. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Rhodothermus marinus has the potential to be well suited for biorefineries, as an aerobic thermophile that produces thermostable enzymes and is able to utilize polysaccharides from different 2nd and 3rd generation biomass. The bacterium produces valuable chemicals such as carotenoids. However, the native carotenoids are not established for industrial production and R. marinus needs to be genetically modified to produce higher value carotenoids. Here we genetically modified the carotenoid biosynthetic gene cluster resulting in three different mutants, most importantly the lycopene producing mutant TK-3 (ΔtrpBΔpurAΔcruFcrtB::trpBcrtBT.thermophilus). The genetic modifications and subsequent structural analysis of carotenoids helped clarify the carotenoid biosynthetic pathway in R. marinus. The nucleotide sequences encoding the enzymes phytoene synthase (CrtB) and the previously unidentified 1′,2′-hydratase (CruF) were found fused together and encoded by a single gene in R. marinus. Deleting only the cruF part of the gene did not result in an active CrtB enzyme. However, by deleting the entire gene and inserting the crtB gene from Thermus thermophilus, a mutant strain was obtained, producing lycopene as the sole carotenoid. The lycopene produced by TK-3 was quantified as 0.49 g/kg CDW (cell dry weight).
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| 22. |
- Odeberg, Jacob, et al.
(författare)
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A novel cysteine-linked antibacterial surface coating significantly inhibits bacterial colonization of nasal silicone prongs in a phase one pre-clinical trial
- 2018
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Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems. - : ELSEVIER SCIENCE BV. - 0928-4931 .- 1873-0191. ; 93, s. 782-789
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Tidskriftsartikel (refereegranskat)abstract
- Ventilator associated pneumonia and sepsis are frequent complications in neonatal care. Bacterial colonization of medical devices and interfaces used for respiratory support may contribute by functioning as a bacterial reservoir seeding bacteria into airways. We have developed an antibacterial surface coating based on a cysteine ligand covalently coupled via a spacer to a carboxylic backbone layer on an acrylic acid grafted silicone surface. This coating was applied on a commercially available nasal prong and the antibacterial effect was evaluated both in vitro and in vivo in a first-in-human phase 1 trial. The coated nasal prongs had strong antibacterial activity against both Gram-negative and Gram-positive bacteria in vitro. In a randomized pre-clinical trial study of 24 + 24 healthy adult volunteers who carried coated or non-coated nasal prongs for 18 h, a (10)log difference in mean bacterial colonization of 5.82 (p < 0.0001) was observed. These results show that this coating technique can prevent colonization by the normal skin and mucosal flora, and thus represent a promising novel technology for reduction of medical device-associated hospital acquired infections.
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| 23. |
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| 24. |
- Rafnar, Thorunn, et al.
(författare)
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European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
- 2011
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 20:21, s. 4268-81
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Tidskriftsartikel (refereegranskat)abstract
- Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
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- Ron, Emanuel, et al.
(författare)
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Characterization of carotenoids in Rhodothermus marinus
- 2018
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Ingår i: MicrobiologyOpen. - : Wiley. - 2045-8827. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Rhodothermus marinus, a marine aerobic thermophile, was first isolated from an intertidal hot spring in Iceland. In recent years, the R. marinus strain PRI 493 has been genetically modified, which opens up possibilities for targeted metabolic engineering of the species, such as of the carotenoid biosynthetic pathway. In this study, the carotenoids of the R. marinus type-strain DSM 4252T, strain DSM 4253, and strain PRI 493 were characterized. Bioreactor cultivations were used for pressurized liquid extraction and analyzed by ultra-high performance supercritical fluid chromatography with diode array and quadropole time-of-flight mass spectrometry detection (UHPSFC-DAD-QTOF/MS). Salinixanthin, a carotenoid originally found in Salinibacter ruber and previously detected in strain DSM 4253, was identified in all three R. marinus strains, both in the hydroxylated and nonhydroxylated form. Furthermore, an additional and structurally distinct carotenoid was detected in the three strains. MS/MS fragmentation implied that the mass difference between salinixanthin and the novel carotenoid structure corresponded to the absence of a 4-keto group on the ß-ionone ring. The study confirmed the lack of carotenoids for the strain SB-71 (ΔtrpBΔpurAcrtBI’::trpB) in which genes encoding two enzymes of the proposed pathway are partially deleted. Moreover, antioxidant capacity was detected in extracts of all the examined R. marinus strains and found to be 2–4 times lower for the knock-out strain SB-71. A gene cluster with 11 genes in two operons in the R. marinusDSM 4252T genome was identified and analyzed, in which several genes were matched with carotenoid biosynthetic pathway genes in other organisms.
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