| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 6. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 7. |
- Chioza, B., et al.
(författare)
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Evaluation of CACNA1H in European patients with childhood absence epilepsy
- 2006
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Ingår i: Epilepsy Res. - : Elsevier BV. - 0920-1211. ; 69:2, s. 177-81
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Tidskriftsartikel (refereegranskat)abstract
- CACNA1H was evaluated in a resource of Caucasian European patients with childhood absence epilepsy by linkage analysis and typing of sequence variants previously identified in Chinese patients. Linkage analysis of 44 pedigrees provided no evidence for a locus in the CACNA1H region and none of the Chinese variants were found in 220 unrelated patients.
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| 8. |
- Care, O., et al.
(författare)
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Creating leadership collectives for sustainability transformations
- 2021
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 16:2, s. 703-708
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Tidskriftsartikel (refereegranskat)abstract
- Enduring sustainability challenges requires a new model of collective leadership that embraces critical reflection, inclusivity and care. Leadership collectives can support a move in academia from metrics to merits, from a focus on career to care, and enact a shift from disciplinary to inter- and trans-disciplinary research. Academic organisations need to reorient their training programs, work ethics and reward systems to encourage collective excellence and to allow space for future leaders to develop and enact a radically re-imagined vision of how to lead as a collective with care for people and the planet.
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| 9. |
- Everett, K. V., et al.
(författare)
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Linkage and association analysis of CACNG3 in childhood absence epilepsy
- 2007
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Ingår i: Eur J Hum Genet. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 15:4, s. 463-72
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Tidskriftsartikel (refereegranskat)abstract
- Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12-p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD = 3.54, alpha = 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum non-parametric linkage score was 2.87 (P < 0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP-based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P < or = 0.01) was found for SNPs within a approximately 35 kb region of high LD encompassing the 5'UTR, exon 1 and part of intron 1 of CACNG3. Re-sequencing of this interval was undertaken in 24 affected individuals. Seventy-two variants were identified: 45 upstream; two 5'UTR; and 25 intronic SNPs. No coding sequence variants were identified, although four variants are predicted to affect exonic splicing. This evidence supports CACNG3 as a susceptibility locus in a subset of CAE patients.
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| 10. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 11. |
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| 16. |
- Knipp, D.J., et al.
(författare)
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Ionospheric Convection Response to Slow, Strong Variations in a Northward Interplanetary Magnetic Field: A Case Study for January 14, 1988
- 1993
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 98, s. 19273-19292
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Tidskriftsartikel (refereegranskat)abstract
- We analyze ionospheric convection patterns over the polar regions during the passage of an interplanetary magnetic cloud on January 14, 1988, when the interplanetary magnetic field (IMF) rotated slowly in direction and had a large amplitude. Using the assimilative mapping of ionospheric electrodynamics (AMIE) procedure, we combine simultaneous observations of ionospheric drifts and magnetic perturbations from many different instruments into consistent patterns of high-latitude electrodynamics, focusing on the period of northward IMF. By combining satellite data with ground-based observations, we have generated one of the most comprehensive data sets yet assembled and used it to produce convection maps for both hemispheres. We present evidence that a lobe convection cell was embedded within normal merging convection during a period when the IMF B(y) and B(z) components were large and positive. As the IMF became predominantly northward, a strong reversed convection pattern (afternoon-to-morning potential drop of around 100 kV) appeared in the southern (summer) polar cap, while convection in the northern (winter) hemisphere became weak and disordered with a dawn-to-dusk potential drop of the order of 30 kV. These patterns persisted for about 3 hours, until the IMF rotated significantly toward the west. We interpret this behavior in terms of a recently proposed merging model for northward IMF under solstice conditions, for which lobe field lines from the hemisphere tilted toward the Sun (summer hemisphere) drape over the dayside magnetosphere, producing reverse convection in the summer hemisphere and impeding direct contact between the solar wind and field lines connected to the winter polar cap. The positive IMF B(x) component present at this time could have contributed to the observed hemispheric asymmetry. Reverse convection in the summer hemisphere broke down rapidly after the ratio \textbackslashB(y)/B(z)\textbackslash exceeded unity, while convection in the winter hemisphere strengthened. A dominant dawn-to-dusk potential drop was established in both hemispheres when the magnitude of B(y) exceeded that of B(z), with potential drops of the order of 100 kV, even while B(z) remained northward. The later transition to southward B(z) produced a gradual intensification of the convection, but a greater qualitative change occurred at the transition through \textbackslashB(y)/B(z)\textbackslash = 1 than at the transition through B(z) = 0. The various convection patterns we derive under northward IMF conditions illustrate all possibilities previously discussed in the literature: nearly single-cell and multicell, distorted and symmetric, ordered and unordered, and sunward and antisunward.
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| 17. |
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| 18. |
- Ehnhage, A, et al.
(författare)
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Corrigendum
- 2016
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Ingår i: Acta oto-laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 136:9, s. 982-982
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Tidskriftsartikel (refereegranskat)
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| 19. |
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| 20. |
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| 21. |
- Gambill, M., et al.
(författare)
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Effects of temperature on the feeding and growth of the larvae of the invasive ctenophore Mnemiopsis leidyi
- 2015
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Ingår i: Journal of Plankton Research. - : Oxford University Press (OUP). - 0142-7873 .- 1464-3774. ; 37:5, s. 1001-1005
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Tidskriftsartikel (refereegranskat)abstract
- Carbon-specific prey clearance and ingestion rates of 1.5-mm tentaculate larvae of the ctenophore Mnemiopsis leidyi increased linearly between 6 and 25 degrees C but declined between 25 and 30 degrees C. Both absolute (length) and carbon-specific growth rate increased linearly with increasing temperature. The latter was 0.87 d(-1) at 25 degrees C. Extremely low or negative growth rates observed at 6 and 30 degrees C help define the thermal limits to population growth of this successful biological invader.
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| 22. |
- Gustavsson, Anders, et al.
(författare)
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Clinical trial : colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
- 2010
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
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| 23. |
- Hermann, Florian M., et al.
(författare)
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An insulin hypersecretion phenotype precedes pancreatic beta cell failure in MODY3 patient-specific cells
- 2023
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Ingår i: Cell Stem Cell. - : Elsevier. - 1934-5909 .- 1875-9777. ; 30:1, s. 38-51
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Tidskriftsartikel (refereegranskat)abstract
- MODY3 is a monogenic hereditary form of diabetes caused by mutations in the transcription factor HNF1A. The patients progressively develop hyperglycemia due to perturbed insulin secretion, but the pathogenesis is unknown. Using patient-specific hiPSCs, we recapitulate the insulin secretion sensitivity to the membrane depolarizing agent sulfonylurea commonly observed in MODY3 patients. Unexpectedly, MODY3 patient -specific HNF1A+/R272C R cells hypersecrete insulin both in vitro and in vivo after transplantation into mice. Consistently, we identified a trend of increased birth weight in human HNF1A mutation carriers compared with healthy siblings. Reduced expression of potassium channels, specifically the KATP channel, in MODY3 0 cells, increased calcium signaling, and rescue of the insulin hypersecretion phenotype by pharmacological targeting ATP-sensitive potassium channels or low-voltage-activated calcium channels suggest that more efficient membrane depolarization underlies the hypersecretion of insulin in MODY3 0 cells. Our findings identify a pathogenic mechanism leading to 0 cell failure in MODY3.
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| 24. |
- Hermann, Florian M., et al.
(författare)
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An insulin hypersecretion phenotype precedes pancreatic β cell failure in MODY3 patient-specific cells
- 2023
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 30:1, s. 8-51
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Tidskriftsartikel (refereegranskat)abstract
- MODY3 is a monogenic hereditary form of diabetes caused by mutations in the transcription factor HNF1A. The patients progressively develop hyperglycemia due to perturbed insulin secretion, but the pathogenesis is unknown. Using patient-specific hiPSCs, we recapitulate the insulin secretion sensitivity to the membrane depolarizing agent sulfonylurea commonly observed in MODY3 patients. Unexpectedly, MODY3 patient-specific HNF1A+/R272C β cells hypersecrete insulin both in vitro and in vivo after transplantation into mice. Consistently, we identified a trend of increased birth weight in human HNF1A mutation carriers compared with healthy siblings. Reduced expression of potassium channels, specifically the KATP channel, in MODY3 β cells, increased calcium signaling, and rescue of the insulin hypersecretion phenotype by pharmacological targeting ATP-sensitive potassium channels or low-voltage-activated calcium channels suggest that more efficient membrane depolarization underlies the hypersecretion of insulin in MODY3 β cells. Our findings identify a pathogenic mechanism leading to β cell failure in MODY3.
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| 25. |
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| 26. |
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| 27. |
- Lindstrom, L., et al.
(författare)
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High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia
- 2012
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Ingår i: Alimentary Pharmacology and Therapeutics. - Malden : Wiley. - 0269-2813 .- 1365-2036. ; 35:4, s. 451-457
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long-term data and larger trials are lacking. Aim To evaluate the effect of high dose (17-23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD. Methods From our previous 5-year randomised controlled trial of UDCA vs. placebo in PSC, we performed a follow-up of 98 patients with concomitant IBD from entry of the trial 1996-1997 until 2009 for development of colorectal cancer or dysplasia. Results The total follow-up time was 760 person-years. Dysplasia/cancer-free survival was compared between placebo-(n = 50) and UDCA-treated (n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer-free survival (P = 0.46, log rank test). At the end of 2009 no difference in cancer-free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia. Conclusions Long-term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis-associated inflammatory bowel disease.
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| 28. |
- McGlinchey, Aidan J, 1984-, et al.
(författare)
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Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes
- 2020
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- In the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring.
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| 29. |
- Selsing, J., et al.
(författare)
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The X-shooter GRB afterglow legacy sample (XS-GRB)
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 623
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Tidskriftsartikel (refereegranskat)abstract
- In this work we present spectra of all gamma-ray burst (GRB) afterglows that have been promptly observed with the X-shooter spectrograph until 31/03/2017. In total, we have obtained spectroscopic observations of 103 individual GRBs observed within 48 hours of the GRB trigger. Redshifts have been measured for 97 per cent of these, covering a redshift range from 0.059 to 7.84. Based on a set of observational selection criteria that minimise biases with regards to intrinsic properties of the GRBs, the follow-up effort has been focused on producing a homogeneously selected sample of 93 afterglow spectra for GRBs discovered by the Swift satellite. We here provide a public release of all the reduced spectra, including continuum estimates and telluric absorption corrections. For completeness, we also provide reductions for the 18 late-time observations of the underlying host galaxies. We provide an assessment of the degree of completeness with respect to the parent GRB population, in terms of the X-ray properties of the bursts in the sample and find that the sample presented here is representative of the full Swift sample. We have constrained the fraction of dark bursts to be <28 per cent and confirm previous results that higher optical darkness is correlated with increased X-ray absorption. For the 42 bursts for which it is possible, we have provided a measurement of the neutral hydrogen column density, increasing the total number of published HI column density measurements by similar to 33 per cent. This dataset provides a unique resource to study the ISM across cosmic time, from the local progenitor surroundings to the intervening Universe.
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| 30. |
- Sjöberg, Mats, 1965-, et al.
(författare)
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Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis : a retrospective observational study
- 2012
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Ingår i: Inflammatory Bowel Diseases. - : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 18:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. Methods: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n 49) treated with a single infusion of IFX; 2) an Austrian cohort (n 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. Results: At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. Conclusions: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.
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| 31. |
- Strömberg, C. A. E., et al.
(författare)
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Palaeoecology of a Middle Miocene lake in China: preliminary interpretations based on phytoliths from the Shanwang Basin
- 2007
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Ingår i: Vertebrata PalAsiatica. ; 45, s. 145-160
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Tidskriftsartikel (refereegranskat)abstract
- The lacustrine Early to Middle Miocene Shanwang Formation contains an exceptionally well preserved biota including insects, plants, and vertebrates that has been subject to intense study. Palaeoecological work on plant macrofossils and palynofloras indicate that the locality represents a forest under a humid, warm-temperate to subtropical climate that remained rather stable during the deposition of the formation. This interpretation is supported by fossil vertebrates such as bats and tapirs discovered in the Shanwang section. However, to date no information has been available on the presence, abundance, and taxonomic composition of grasses at this locality. Here, we report on phytoliths extracted from six samples from the Shanwang Formation, providing new evidence of the vegetation that grew around the lake. The phytolith assemblages contain well-preserved and abundant grass phytoliths, forest indicator phytoliths from dicotyledonous plants, and infrequent palm phytoliths. The grass phytoliths consist of forms produced by C,IC4 PACCAD grasses and pooids, with a minor component of morphotypes thought to derive from closed-habitat grasses. Our preliminary interpretation of these phytolith assemblages is that they reflect a lake-side wooded habitat and abundant helophytic to mesophytic grasses, with drier areas supporting pooid (and PACCAD) grasses. The data support the reconstruction of the Miocene Shanwang region as more humid and equable than presently. The Shanwang phytolith assemblages contrast with Miocene lacustrine phytolith assemblages from Turkey and the Great Plains of North America, which indicate grass communities characterized by diverse C3 pooids and different types of PACCAD grasses. Future research will determine whether this variability reflects large-scale biogeographic differences in grass communities or local, microclimate-related variation.
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| 32. |
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| 33. |
- Anundi, Helena, et al.
(författare)
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Air and biological monitoring of solvent exposure during grafitti removal
- 2000
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 73:8, s. 561-569
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The principal aim of the study was to estimate the level of exposure to organic solvents of graffiti removers, and to identify the chemicals used in different cleaning agents. A secondary objective was to inform about the toxicity of various products and to optimise working procedures.METHODS: Exposure to organic solvents was determined by active air sampling and biological monitoring among 38 graffiti removers during an 8-h work shift in the Stockholm underground system. The air samples and biological samples were analysed by gas chromatography. Exposure to organic solvents was also assessed by a questionnaire and interviews.RESULTS: Solvents identified were N-methylpyrrolidone (NMP), dipropylene glycol monomethyl ether (DPGME), propylene glycol monomethyl ether (PGME), diethylene glycol monoethyl ether (DEGEE), toluene, xylene, pseudocumene, hemimellitine, mesitylene, ethylbenzene, limonene, nonane, decane, undecane, hexandecane and gamma-butyrolactone. The 8-h average exposures [time-weighted average (TWA)] were below 20% of the Swedish permissible exposure limit value (PEL) for all solvents identified. In poorly ventilated spaces, e.g. in elevators etc., the short-term exposures exceeded occasionally the Swedish short-term exposure limit values (STEL). The blood and urine concentrations of NMP and its metabolites were low. Glycol ethers and their metabolites (2-methoxypropionic acid (MPA), ethoxy acetic acid (EAA), butoxy acetic acid (BAA), and 2-(2-methoxyethoxy) acetic acid (MEAA)) were found in low concentrations in urine. There were significant correlation between the concentrations of NMP in air and levels of NMP and its metabolites in blood and urine. The use of personal protective equipment, i.e. gloves and respirators, was generally high.CONCLUSIONS: Many different cleaning agents were used. The average exposure to solvents was low, but some working tasks included relatively high short-term exposure. To prevent adverse health effects, it is important to inform workers about the health risks and to restrict the use of the most toxic chemicals. Furthermore, it is important to develop good working procedures and to encourage the use of personal protection equipment.
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| 34. |
- Bak, Nina Friis, et al.
(författare)
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High-dose vitamin D3 supplementation decreases the number of colonic CD103+ dendritic cells in healthy subjects.
- 2018
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Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 57:7, s. 2607-2619
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D may induce tolerance in the intestinal immune system and has been shown to regulate the phenotype of tolerogenic intestinal dendritic cells (DCs) in vitro. It is unknown whether vitamin D supplementation affects human intestinal DCs in vivo, and we aimed to investigate the tolerability and effect on intestinal CD103+DCs of high-dose vitamin D3 treatment in healthy subjects.Ten healthy subjects received a total of 480,000IU oral vitamin D3 over 15days and colonic biopsies were obtained before and after intervention by endoscopy. Lamina propria mononuclear cells (LPMCs) were isolated from the biopsies, stained with DC surface markers and analysed with flow cytometry. Snap-frozen biopsies were analysed with qPCR for DC and regulatory T cell-related genes.No hypercalcemia or other adverse events occurred in the test subjects. Vitamin D decreased the number of CD103+ DCs among LPMCs (p=0.006). Furthermore, vitamin D induced mRNA expression of TGF-β (p=0.048), TNF-α (p=0.006) and PD-L1 (p=0.02) and tended to induce IL-10 expression (p=0.06). Multivariate factor analysis discriminated between pre- and post-vitamin D supplementation with a combined increased qPCR expression of PD1, PD-L1, TGF-β, IL-10, CD80, CD86, FOXP3, NFATc2 and cathelicidin.High-dose vitamin D supplementation is well tolerated by healthy subjects and has a direct effect on the CD103+ DCs, local cytokine and surface marker mRNA expression in the colonic mucosa, suggestive of a shift towards a more tolerogenic milieu.
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| 35. |
- Bath, Philip M W, et al.
(författare)
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Tinzaparin in acute ischaemic stroke (TAIST) : A randomised aspirin-controlled trial
- 2001
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 358:9283, s. 702-710
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-molecular-weight heparins and heparinoids are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism, but their safety and efficacy in acute ischaemic stroke are inadequately defined. Methods: This randomised, double-blind, aspirin-controlled trial tested the safety and efficacy of treatment with high-dose tinzaparin (175 anti-Xa IU/kg daily, 487 patients), medium-dose tinzaparin (100 anti-Xa IU/kg daily, 508 patients), or aspirin (300 mg daily, 491 patients) started within 48 h of acute ischaemic stroke and given for up to 10 days. Primary intracerebral haemorrhage was excluded by computed tomography. Outcome was assessed, with treatment allocation concealed, by the modified Rankin scale at 6 months (independence [scores 0-2] vs dependence or death [scores 3-6]). Findings: Of 1486 randomised patients, two did not receive treatment and 46 were lost to follow-up. The proportions independent at 6 months were similar in the groups assigned high-dose tinzaparin (194/468 [41.5%]), medium-dose tinzaparin (206/486 [42.4%]), or aspirin (205/482 [42.5%]). There was no difference in effect in any predefined subgroup, including patients with presumed cardioembolic stroke. Other outcome measures were similar between the treatment groups (disability, case-fatality, and neurological deterioration rates). During the in-hospital treatment period no patient assigned high-dose tinzaparin developed a symptomatic deep-vein thrombosis compared with nine assigned aspirin. Conversely, seven patients assigned high-dose tinzaparin developed symptomatic intracerebral haemorrhage compared with one in the aspirin group. Interpretation: Treatment with tinzaparin, at high or medium dose, within 48 h of acute ischaemic stroke did not improve functional outcome compared with aspirin. Although high-dose tinzaparin was superior in preventing deep-vein thrombosis, it was associated with a higher rate of symptomatic intracranial haemorrhage.
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| 36. |
- Bergman, Lina, 1982, et al.
(författare)
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Preeclampsia and increased permeability over the blood brain barrier - a role of vascular endothelial growth receptor 2.
- 2021
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Ingår i: American journal of hypertension. - : Oxford University Press (OUP). - 1941-7225 .- 0895-7061. ; 34:1, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but the underlying pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia.The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert were exposed (12h) to plasma from women with preeclampsia (n=28), normal pregnancy (n=28) and non-pregnant (n=16) controls. Transendothelial electrical resistance (TEER) and permeability to 70kDa FITC-dextran were measured for assessment of BBB integrity. We explored possible underlying mechanisms, with focus on expression of tight junction proteins and phosphorylation of two tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in order to establish correlations with in vitro results.hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70kDa FITC-dextran. Further, these cells up-regulated the mRNA levels of VEGFR2, as well as pY951-VEGFR2; but reduced pY1175-VEGFR2 (p&0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between gruops. There was no correlation between angiogenic biomarkers and BBB permeability.We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.
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| 37. |
- Caron, Patrick, et al.
(författare)
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Food systems for sustainable development : proposals for a profound four-part transformation
- 2018
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Ingår i: Agronomy for Sustainable Development. - : Springer Science and Business Media LLC. - 1774-0746 .- 1773-0155. ; 38:4
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Forskningsöversikt (refereegranskat)abstract
- Evidence shows the importance of food systems for sustainable development: they are at the nexus that links food security, nutrition, and human health, the viability of ecosystems, climate change, and social justice. However, agricultural policies tend to focus on food supply, and sometimes, on mechanisms to address negative externalities. We propose an alternative. Our starting point is that agriculture and food systems' policies should be aligned to the 2030 Agenda for Sustainable Development. This calls for deep changes in comparison with the paradigms that prevailed when steering the agricultural change in the XXth century. We identify the comprehensive food systems transformation that is needed. It has four parts: first, food systems should enable all people to benefit from nutritious and healthy food. Second, they should reflect sustainable agricultural production and food value chains. Third, they should mitigate climate change and build resilience. Fourth, they should encourage a renaissance of rural territories. The implementation of the transformation relies on (i) suitable metrics to aid decision-making, (ii) synergy of policies through convergence of local and global priorities, and (iii) enhancement of development approaches that focus on territories. We build on the work of the Milano Group, an informal group of experts convened by the UN Secretary General in Milan in 2015. Backed by a literature review, what emerges is a strategic narrative linking climate, agriculture and food, and calling for a deep transformation of food systems at scale. This is critical for achieving the Sustainable Development Goals and the Paris Agreement. The narrative highlights the needed consistency between global actions for sustainable development and numerous local-level innovations. It emphasizes the challenge of designing differentiated paths for food systems transformation responding to local and national expectations. Scientific and operational challenges are associated with the alignment and arbitration of local action within the context of global priorities.
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| 38. |
- Carstensen, B., et al.
(författare)
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Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:5, s. 980-988
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Tidskriftsartikel (refereegranskat)abstract
- An excess cancer incidence of 20-25% has been identified among persons with diabetes, most of whom have type 2 diabetes. We aimed to describe the association between type 1 diabetes and cancer incidence. Persons with type 1 diabetes were identified from five nationwide diabetes registers: Australia (2000-2008), Denmark (1995-2014), Finland (1972-2012), Scotland (1995-2012) and Sweden (1987-2012). Linkage to national cancer registries provided the numbers of incident cancers in people with type 1 diabetes and in the general population. We used Poisson models with adjustment for age and date of follow up to estimate hazard ratios for total and site-specific cancers. A total of 9,149 cancers occurred among persons with type 1 diabetes in 3.9 million person-years. The median age at cancer diagnosis was 51.1 years (interquartile range 43.5-59.5). The hazard ratios (HRs) (95% CIs) associated with type 1 diabetes for all cancers combined were 1.01 (0.98, 1.04) among men and 1.07 (1.04, 1.10) among women. HRs were increased for cancer of the stomach (men, HR 1.23 [1.04, 1.46]; women, HR 1.78 [1.49, 2.13]), liver (men, HR 2.00 [1.67, 2.40]; women, HR 1.55 [1.14, 2.10]), pancreas (men, HR 1.53 [1.30, 1.79]; women, HR 1.25 [1.02,1.53]), endometrium (HR 1.42 [1.27, 1.58]) and kidney (men, HR 1.30 [1.12, 1.49]; women, HR 1.47 [1.23, 1.77]). Reduced HRs were found for cancer of the prostate (HR 0.56 [0.51, 0.61]) and breast (HR 0.90 [0.85, 0.94]). HRs declined with increasing diabetes duration. Type 1 diabetes was associated with differences in the risk of several common cancers; the strength of these associations varied with the duration of diabetes.
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| 39. |
- Celis, Julio E., et al.
(författare)
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15-Prostaglandin Dehydrogenase Expression Alone or in Combination with ACSM1 Defines a Subgroup of the Apocrine Molecular Subtype of Breast Carcinoma
- 2008
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Ingår i: Molecular & Cellular Proteomics. - 1535-9484. ; 7:10, s. 1795-1809
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Tidskriftsartikel (refereegranskat)abstract
- Established histopathological criteria divide invasive breast carcinomas into defined groups. Ductal of no specific type and lobular are the two major subtypes accounting for around 75 and 15% of all cases, respectively. The remaining 10% include rarer types such as tubular, cribriform, mucinous, papillary, medullary, metaplastic, and apocrine breast carcinomas. Molecular profiling technologies, on the other hand, subdivide breast tumors into five subtypes, basal-like, luminal A, luminal B, normal breast tissue-like, and ERBB2-positive, that have different prognostic characteristics. An additional subclass termed "molecular apocrine" has recently been described, but these lesions did not exhibit all the histopathological features of classical invasive apocrine carcinomas (IACs). IACs make up 0.5-3% of the invasive ductal carcinomas, and despite the fact that they are morphologically distinct from other breast lesions, there are presently no standard molecular criteria available for their diagnosis and as a result no precise information as to their prognosis. Toward this goal our laboratories have embarked in a systematic proteomics endeavor aimed at identifying biomarkers that may characterize and subtype these lesions as well as targets that may lead to the development of novel targeted therapies and chemoprevention strategies. By comparing the protein expression profiles of apocrine macrocysts and non-malignant breast epithelial tissue we have previously reported the identification of a few proteins that are specifically expressed by benign apocrine lesions as well as by the few IACs that were available to us at the time. Here we reiterate our strategy to reveal apocrine cell markers and present novel data, based on the analysis of a considerably larger number of samples, establishing that IACs correspond to a distinct molecular subtype of breast carcinomas characterized by the expression of 15-prostaglandin dehydrogenase alone or in combination with a novel form of acyl-CoA synthetase medium-chain family member 1 (ACSM1). Moreover we show that 15-prostaglandin dehydrogenase is not expressed by other breast cancer types as determined by gel-based proteomics and immunohistochemistry analysis and that antibodies against this protein can identify IACs in an unbiased manner in a large breast cancer tissue microarray making them potentially useful as a diagnostic aid. Molecular & Cellular Proteomics 7: 1795-1809, 2008.
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| 40. |
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| 41. |
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| 42. |
- Chioza, Barry A., et al.
(författare)
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Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14
- 2009
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 87:2-3, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance and the genes involved are yet to be fully established. A genome wide single nucleotide polymorphism (SNP)-based high density linkage scan was carried out using 41 nuclear pedigrees with at least two affected members. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9, p<0.0001; HLOD=3.3, alpha=0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Dinasquet, Julie, et al.
(författare)
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Cascading effects of the ctenophore Mnemiopsis leidyi on the planktonic food web in a nutrient-limited estuarine system
- 2012
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Ingår i: Marine Ecology Progress Serie. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 460, s. 49-61
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Tidskriftsartikel (refereegranskat)abstract
- Increasing biomasses of gelatinous zooplankton presumably have major implications for the structure and function of marine food webs at large; however, current data on lower trophic levels are scarce, as most studies have focused on the immediate effects on zooplankton and fish larvae only. We examined the short-term impact of larvae and adults of the invasive ctenophore Mnemiopsis leidyi on a summer planktonic food web in the estuarine southern Baltic Sea, with special emphasis on the microbial loop. Grazing by M. leidyi reduced the mesozooplankton biomass, followed by increased dinoflagellate biomass in treatments with M. leidyi. While chlorophyll a increased most in the treatments with M. leidyi, small phytoplankton and ciliates decreased in all treatments. M. leidyi had a slight effect on bacterial abundance, but not on bacterial production, ectoenzymatic activities, or community composition. Undetectable levels of phosphate and a gradual accumulation of dissolved organic carbon during the experiment suggested a malfunctioning microbial loop scenario. The experiment shows that direct and indirect short-term effects of M. leidyi on the estuarine food web are limited to higher trophic levels and indicates that top-down and bottom-up consequences of M. leidyi expansions on the microbial loop will likely depend on local nutrient conditions.
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| 48. |
- Flores-Morales, Amilcar, et al.
(författare)
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Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer
- 2019
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 25:2, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: An increasing number of castration-resistant prostate cancer (CRPC) tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor prognosis, and its development is poorly understood. Experimental Design: We applied mass spectrometry–based proteomics to a unique set of 17 prostate cancer patient–derived xenografts (PDX) to characterize the effects of castration in vivo, and the proteome differences between NEPC and prostate adenocarcinomas. Genome-wide profiling of REST-occupied regions in prostate cancer cells was correlated to the expression changes in vivo to investigate the role of the transcriptional repressor REST in castration-induced NEPC differentiation. Results: An average of 4,881 proteins were identified and quantified from each PDX. Proteins related to neurogenesis, cell-cycle regulation, and DNA repair were found upregulated and elevated in NEPC, while the reduced levels of proteins involved in mitochondrial functions suggested a prevalent glycolytic metabolism of NEPC tumors. Integration of the REST chromatin bound regions with expression changes indicated a direct role of REST in regulating neuronal gene expression in prostate cancer cells. Mechanistically, depletion of REST led to cell-cycle arrest in G1, which could be rescued by p53 knockdown. Finally, the expression of the REST-regulated gene secretagogin (SCGN) correlated with an increased risk of suffering disease relapse after radical prostatectomy. Conclusions: This study presents the first deep characterization of the proteome of NEPC and suggests that concomitant inhibition of REST and the p53 pathway would promote NEPC. We also identify SCGN as a novel prognostic marker in prostate cancer.
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| 49. |
- Friis, Anna M C
(författare)
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The EBV-HIV interrelationship and the value of EBV-DNA analysis
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epstein-Barr virus (EBV) infects the vast majority of humans and resides latently in B-cells. This virus carries genes that can induce and sustain mature B cell growth. EBV is associated with a wide range of B-cell lymphomas including Burkitt lymphoma and non Hodgkin lymphoma (NHL) in human immunodeficiency virus 1 (HIV-1) infected patients. Latent EBV infection in B lymphocytes is a risk factor for B-cell lymphomas in conditions of combined antigen stimulation and immunosuppression as with Burkitts lymphoma in malaria endemic African regions and non Hodgkin lymphoma in HIV-1 infected patients. In the era of modern combination antiretroviral therapy (cART) there has been an impressive reduction of Acquired Immunodeficiency syndrome (AIDS)-related opportunistic infections and lymphomas, although patients still suffer an increased risk for NHL. This work is based on EBV-DNA load measurement in blood as a tool to analyse EBV-host relationship in HIV-1 infection. In general HIV-1 infected individuals have a higher EBV-DNA load and symptomatic HIV-1 infected even higher. Individual variables, immunological factors and treatments as cART affect this pattern. In one of our studies we identified one group and one risk factor that influenced EBV-DNA load. HIV-1 infected individuals with a history of a symptomatic primary infection in combination with induced immune stimulation by therapeutic vaccination/adjuvant showed an increased load. Without the vaccination/adjuvant stimuli this group did not show the same increase. HIV-1 infected patients with a history of a symptomatic primary infection might therefore be at risk for developing NHL. Therapeutic vaccination/adjuvant increases the EBV- DNA load and we regard this immunomodulation as a risk factor. Different pattern of EBV- host restoration by cART was seen in a long term follow of patients with increased EBV-DNA load after vaccination. The EBV-host relation seems to be reconditioned by successful cART treatment, measured by the CD4+ cell count returning to normal levels, with some reservation for the functional restoration, together with remaining undetectable HIV-1 RNA. For individuals with unsuccessful cART treatment the distinct decrease of EBV-DNA could not be seen. In a patient treated for EBV positive plasmablastic lymphoma we observed a sharp increase of EBV-DNA load before clinical signs of recurrence. Measurement of EBV-DNA load is valuable in monitoring disease progression in HIV-1 infected patients. After cART treatment the dynamics of EBV-DNA load reveal if the antiviral treatment is suboptimal, even if breakthroughs detected as HIV RNA peaks are missed. When an EBV positive tumour is treated successfully EBV-DNA monitoring can be of importance to observe early signs of relapse. Monitoring EBV-DNA load during therapeutic vaccination studies seems highly motivated. In conclusion EBV-DNA load analysis is a useful additional instrument to monitor different groups of HIV-1 patients with increased risk for lymphoma development.
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| 50. |
- Friis, M., et al.
(författare)
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The PoGO+ balloon-borne hard X-ray polarimetry mission
- 2018
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Ingår i: Galaxies. - : MDPI AG. - 2075-4434. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The PoGO mission, including the PoGOLite Pathfinder and PoGO+, aims to provide polarimetric measurements of the Crab system and Cygnus X-1 in the hard X-ray band. Measurements are conducted from a stabilized balloon-borne platform, launched on a 1 million cubic meter balloon from the Esrange Space Center in Sweden to an altitude of approximately 40 km. Several flights have been conducted, resulting in two independent measurements of the Crab polarization and one of Cygnus X-1. Here, a review of the PoGO mission is presented, including a description of the payload and the flight campaigns, and a discussion of some of the scientific results obtained to date.
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