| 1. |
- Akhtar, Monira, et al.
(författare)
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Cell type and context-specific function of PLAG1 for IGF2 P3 promoter activity
- 2012
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 41:6, s. 1959-1966
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Tidskriftsartikel (refereegranskat)abstract
- The fetal transcription factor PLAG1 is found to be overexpressed in cancers, and has been suggested to bind the insulin like growth factor 2 (IGF2) P3 promoter, and to activate the IGF2 gene. The expression of IGF2 has partly been linked to loss of CTCF-dependent chromatin insulator function at the H19 imprinting control region (ICR). We investigated the role of PLAG1 for IGF2 regulation in Hep3B and JEG-3 cell lines. Chromatin immunoprecipitation revealed cell type-specific binding of PLAG1 to the IGF2 P3 promoter, which was substantially insensitive to recombinant PLAG1 overexpression in the endogenous context. We hypothesized that the H19 chromatin insulator may be involved in the cell type-specific PLAG1 response. By using a GFP reporter gene/insulator assay plasmid construct with and without the H19 ICR and/or an SV40 enhancer, we confirm that the effect of the insulator is specifically associated with the activity of the IGF2 P3 promoter in the GFP reporter system, and furthermore, that the reporter insulator is functional in JEG-3 but not in Hep3B cells. FACS analysis was used to assess the function of PLAG1 in low endogenously expressing, but Zn-inducible stable PLAG1 expressing JEG-3 cell clones. Considerable increase in IGF2 expression upon PLAG1 induction with a partial insulator overriding activity was found using the reporter constructs. This is in contrast to the effect of the endogenous IGF2 gene which was insensitive to PLAG1 expression in JEG-3, while modestly induced the already highly expressed IGF2 gene in Hep3B cells. We suggest that the PLAG1 binding to the IGF2 P3 promoter and IGF2 expression is cell type-specific, and that the PLAG1 transcription factor acts as a transcriptional facilitator that partially overrides the insulation by the H19 ICR.
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| 2. |
- Alén, Claes, 1949, et al.
(författare)
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Test Embankments on Lime/Cement Stabilized Clay
- 2005
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Ingår i: Deep Mixing 05.
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Tidskriftsartikel (refereegranskat)abstract
- In a large expansion of the infrastructure in Western Sweden a divided highway and a double railroad track for high speed trains are being planned in the Eastern part of the Göta river valley. Lime/cement columns were considered an attractive method for foundation in many of the cases. In order to improve the accuracy of the settlement calculations, which was considered crucial in the project, four test embankments were constructed. The results from these test embankments are reported in this paper. The embankments, which were constructed in two lifts, about a year and a half apart, were monitored in terms of settlement at the surface as well as at different depths. Measurements were taken in the columns as well as in the clay in between the columns and also below the stabilized soil. A number of piezometers were installed and also a couple of inclinometers. In the paper the overall behaviour of the stabilized soil is analysed and comparison with generally accepted assumptions is made. The results comprise an important base for another paper where a new approach to settlement calculations for lime/cement stabilized soil.
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| 3. |
- Awad, Wael, et al.
(författare)
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Structural Basis for YjbH Adaptor-Mediated Recognition of Transcription Factor Spx
- 2019
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Ingår i: Structure. - : Elsevier BV. - 0969-2126. ; 27:6, s. 6-936
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Tidskriftsartikel (refereegranskat)abstract
- YjbH is a bacterial adaptor protein required for efficient proteolysis of the RNA polymerase-binding transcription factor Spx by the ClpXP protease. We report the structure of YjbH in complex with Spx. YjbH comprises a DsbA-like thioredoxin domain connected via a linker to a C-terminal domain reminiscent of the winged helix-turn-helix fold. The interaction between YjbH and Spx involves a large surface area. Binding to YjbH stabilizes the C-terminal ClpX recognition region of Spx. We show that mutation of critical YjbH contact residues abrogates Spx recognition. Small-angle X-ray scattering and hydrogen-deuterium exchange mass spectrometry analyses determined the existence of a stable heterodimeric complex in solution and provide evidence that binding of Spx to YjbH reduces the overall conformational flexibility of Spx. Our findings provide insights into the molecular basis for Spx recognition and suggest a model for how YjbH stabilizes Spx and displays the C terminus of Spx for engagement by ClpXP. Awad et al. determined the crystal structure of the ClpXP adaptor protein YjbH in complex with the transcription factor Spx. Structural dynamics of the complex were investigated by hydrogen-deuterium exchange mass spectrometry. The insights provided in this work add molecular details to the recognition of Spx by YjbH.
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| 4. |
- Cederkäll, Joakim, et al.
(författare)
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Sub-Barrier Coulomb Excitation of ^110Sn and Its Implications for the ^100Sn Shell Closure
- 2007
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Ingår i: Physical Review Letters. - 1079-7114. ; 98:17, s. 172501-
-
Tidskriftsartikel (refereegranskat)abstract
- The first excited 2+ state of the unstable isotope 110Sn has been studied in safe Coulomb excitation at 2.82 MeV/u using the MINIBALL array at the REX-ISOLDE post accelerator at CERN. This is the first measurement of the reduced transition probability of this state using this method for a neutron deficient Sn isotope. The strength of the approach lies in the excellent peak-to-background ratio that is achieved. The extracted reduced transition probability, B(E2:0+-->2+)=0.220±0.022e2b2, strengthens the observation of the evolution of the B(E2) values of neutron deficient Sn isotopes that was observed recently in intermediate-energy Coulomb excitation of 108Sn. It implies that the trend of these reduced transition probabilities in the even-even Sn isotopes is not symmetric with respect to the midshell mass number A=116 as 100Sn is approached.
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| 5. |
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| 6. |
- DiJulio, Douglas, et al.
(författare)
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Coulomb excitation of In-107
- 2013
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 87:1
-
Tidskriftsartikel (refereegranskat)abstract
- The radioactive isotope In-107 was studied using sub-barrier Coulomb excitation at the REX-ISOLDE facility at CERN. Two gamma rays were observed during the experiment, corresponding to the low-lying 11/2(+) and 3/2(-)states. The reduced transition probability of the 11/2(+) state was determined with the semiclassical Coulomb excitation code GOSIA2. The result is discussed in comparison to large-scale shell-model calculations, previous unified-model calculations, and earlier Coulomb excitation measurements in the odd-mass In isotopes. DOI: 10.1103/PhysRevC.87.017301
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| 7. |
- DiJulio, Douglas, et al.
(författare)
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Electromagnetic properties of vibrational bands in Er-170
- 2011
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 47:2, s. 25-
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Tidskriftsartikel (refereegranskat)abstract
- Excited states of the nucleus Er-170 have been studied by Coulomb excitation using the GASP gamma-ray detector system at the Laboratori Nazionali di Legnaro. The ground-state band along with a low-lying K-pi = 0(+) band and gamma-vibrational band were populated during the experiment. Based on the measured gamma-ray yields, a set of interband and intraband matrix elements has been extracted using the Coulomb excitation code GOSIA. The resulting E2 matrix elements are compared to collective model predictions.
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| 8. |
- DiJulio, Douglas, et al.
(författare)
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Excitation strengths in Sn-109: Single-neutron and collective excitations near Sn-100
- 2012
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 86:3
-
Tidskriftsartikel (refereegranskat)abstract
- A set of B(E2) values for the low-lying excited states in the radioactive isotope Sn-109 were deduced from a Coulomb excitation experiment. The 2.87-MeV/u radioactive beam was produced at the REX-ISOLDE facility at CERN and was incident on a secondary Ni-58 target. The B(E2) values were determined using the known 2(+) -> 0(+) reduced transition probability in Ni-58 as normalization with the semiclassical Coulomb excitation code GOSIA2. The transition probabilities are compared to shell-model calculations based on a realistic nucleon-nucleon interaction and the predictions of a simple core-excitation model. This measurement represents the first determination of multiple B(E2) values in a light Sn nucleus using the Coulomb excitation technique with low-energy radioactive beams. The results provide constraints for the single-neutron states relative to Sn-100 and also indicate the importance of both single-neutron and collective excitations in the light Sn isotopes.
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| 9. |
- DiJulio, Douglas, et al.
(författare)
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Shell model based Coulomb excitation gamma-ray intensity calculations in Sn-107
- 2012
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Ingår i: Physica Scripta. - 0031-8949. ; T150
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we present recent shell model calculations, based on a realistic nucleon-nucleon interaction, for the light Sn-107,Sn-109 nuclei. By combining the calculations with the semi-classical Coulomb excitation code GOSIA, a set of gamma-ray intensities has been generated. The calculated intensities are compared with the data from recent Coulomb excitation studies in inverse kinematics at the REX-ISOLDE facility with the nucleus Sn-107. The results are discussed in the context of the ordering of the single-particle orbits relative to Sn-100.
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| 10. |
- DiJulio, Douglas, et al.
(författare)
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Sub-barrier Coulomb excitation of Sn-107
- 2012
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 381, s. 012073-012073
-
Konferensbidrag (refereegranskat)abstract
- A Coulomb excitation experiment in inverse kinematics has been carried out at the REX-ISOLDE facility in order to study the properties of low-lying excited states in Sn-107. The measured gamma ray spectrum has been compared with predicted gamma ray spectra from a combined shell-model and GOSIA analysis. In this approach, a set of matrix elements, generated within the shell-model framework, based on a realistic nucleon-nucleon interaction and a set of single-particle energies relative to Sn-100, is used as input. Comparison between the calculated and predicted spectra can be used to help identify the placement of the single-neutron states in Sn-101. In particular, the results can potentially provide clues on the ordering of the two lowest-lying orbits; the g(7/2) and d(5/2) states.
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| 11. |
- Ekström, Andreas, et al.
(författare)
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0(gs)+ -->2(1)+ transition strengths in 106Sn and 108Sn.
- 2008
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Ingår i: Physical Review Letters. - 1079-7114. ; 101:1
-
Tidskriftsartikel (refereegranskat)abstract
- The reduced transition probabilities, B(E2; 0(gs)+ -->2(1)+), have been measured in the radioactive isotopes (108,106)Sn using subbarrier Coulomb excitation at the REX-ISOLDE facility at CERN. Deexcitation gamma rays were detected by the highly segmented MINIBALL Ge-detector array. The results, B(E2;0(gs)+ -->2(1)+)=0.222(19)e2b2 for 108Sn and B(E2; 0(gs)+-->2(1)+)=0.195(39)e2b2 for 106Sn were determined relative to a stable 58Ni target. The resulting B(E2) values are approximately 30% larger than shell-model predictions and deviate from the generalized seniority model. This experimental result may point towards a weakening of the N=Z=50 shell closure.
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| 12. |
- Ekström, Andreas, et al.
(författare)
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Coulomb excitation of Sn-110 using REX-ISOLDE
- 2006
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Ingår i: Physica Scripta. - 1402-4896 .- 0031-8949. ; T125, s. 190-191
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Konferensbidrag (refereegranskat)abstract
- In this paper, we report the preliminary result from the first Coulomb excitation experiment at REX-ISOLDE (Habs et al 1998 Nucl. Instrum. Methods B 139 128) using neutron-deficient Sn-beams. The motivation of the experiment is to deduce the reduced transition probability, B(E2; 2(+) -> 0(+)), for the sequence of neutron deficient, unstable, even-even Sn- isotopes from Sn-110 to ultimately Sn-110. Safe Coulomb excitation using a radioactive beam opens up a new path to study the lifetime of the first excited 2(+) state in these isotopes. The de-excitation path following fusion-evaporation reactions will for the even-even Sn isotopes pass via an isomeric 6(+) state, located at higher energy, which thus hampers measurements of the lifetime of the first excited state using, e. g., recoil-distance methods. For this reason the reduced transition probability of the first excited 2(+) state has remained unknown in this chain of isotopes although the B(E2) value of the stable isotope Sn-112 was measured approximately 30 years ago (see, e. g., Stelson et al 1970 Phys. Rev. C 2 2015). Our experiment is thus the first to accomplish a measurement of this quantity in Sn-110. It is believed that the determination of the B(E2) value in Sn-110 will indicate the turnover point from a trend of increasing B(E2) values for the heavier isotopes to a trend characterized by less collectivity. Our first preliminary result indicates that this assumption may well be correct.
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| 13. |
- Ekström, Andreas, et al.
(författare)
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Coulomb excitation of the odd-odd isotopes In-106,In-108
- 2010
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 44:3, s. 355-361
-
Tidskriftsartikel (refereegranskat)abstract
- The low-lying states in the odd-odd and unstable isotopes In-106,In-108 have been Coulomb excited from the ground state and the first excited isomeric state at the REX-ISOLDE facility at CERN. With the additional data provided here the pi g(9/2)(-1) circle times nu d(5/2) and pi g(9/2)(-1) circle times nu g7/2 multiplets have been re-analyzed and are modified compared to previous results. The observed gamma-ray de-excitation patterns were interpreted within a shell model calculation based on a realistic effective interaction. The agreement between theory and experiment is satisfactory and the calculations reproduce the observed differences in the excitation pattern of the two isotopes. The calculations exclude a 6(+) ground state in In-106. This is in agreement with the conclusions drawn using other techniques. Furthermore, based on the experimental results, it is also concluded that the ordering of the isomeric and ground state in In-108 is inverted compared to the shell model prediction. Limits on B(E2) values have been extracted where possible. A previously unknown low-lying state at 367 keV in In-106 is also reported.
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| 14. |
- Ekström, Andreas, et al.
(författare)
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Determination of the isomeric fraction in a postaccelerated radioactive ion beam using the coupled decay-chain equations
- 2010
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 614:2, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- A method based on the coupled decay-chain equations for extracting the isotopic and the isomeric composition of a postaccelerated radioactive ion beam is presented and demonstrated on a data set from a Coulomb excitation experiment. This is the first attempt of analyzing the content of a postaccelerated radioactive ion beam using this technique. The beam composition is required for an absolute normalization of the measurement. The strength of the method, as compared to present online-based methods, lies in the determination of the isomeric fraction of a partially isomeric beam using all data accumulated during the experiment. We discuss the limitations and sensitivity of the method with respect to the gamma-ray detection efficiency and the accumulated flux. (C) 2010 Elsevier B.V. All rights reserved.
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| 15. |
- Ekström, Andreas, et al.
(författare)
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Electric quadrupole moments of the 2(1)(+) states in Cd-100,Cd-102,Cd-104
- 2009
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:5
-
Tidskriftsartikel (refereegranskat)abstract
- Using the REX-ISOLDE facility at CERN the Coulomb excitation cross sections for the 0(gs)(+)-> 2(1)(+) transition in the beta-unstable isotopes Cd-100,Cd-102,Cd-104 have been measured for the first time. Two different targets were used, which allows for the first extraction of the static electric quadrupole moments Q(2(1)(+)) in Cd-102,Cd-104. In addition to the B(E2) values in Cd-102,Cd-104, a first experimental limit for the B(E2) value in Cd-100 is presented. The data was analyzed using the maximum likelihood method. The provided probability distributions impose a test for theoretical predictions of the static and dynamic moments. The data are interpreted within the shell-model using realistic matrix elements obtained from a G-matrix renormalized CD-Bonn interaction. In view of recent results for the light Sn isotopes the data are discussed in the context of a renormalization of the neutron effective charge. This study is the first to use the reorientation effect for post-accelerated short-lived radioactive isotopes to simultaneously determine the B(E2) and the Q(2(1)(+)) values.
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| 16. |
- Ekström, Andreas, et al.
(författare)
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Sub-barrier Coulomb excitation of Sn-106,Sn-108,Sn-110
- 2008
-
Ingår i: Frontiers in Nuclear structure, Astrophysics and Reactions - Finustar 2, AIP Conference Proceedings. - : AIP. - 0094-243X .- 1551-7616. ; 1012, s. 296-299
-
Konferensbidrag (refereegranskat)abstract
- The reduced transition probabilities between the first excited 2(+) state and the 0(+) ground state, B(E2; 0(+) -> 2(+)), have been measured in Sn-106,Sn-108,Sn-110 using sub-barrier Coulomb excitation in inverse kinematics at REX-ISOLDE. The results are, B(E2;0(+) -> 2(+)) = 0.220(22),0.226(17), and 0.228(32) e(2)b(2), for Sn-110, Sn-108, and Sn-106, respectively. The results for Sn-106,Sn-108 are preliminary. De-excitation gamma-rays were detected by the MINIBALL Ge-array. The B(E2) reveals detailed information about the nuclear wave function. A shell model prediction based on an effective CD-Bonn interaction in the nu(0g(7/2),2s, 1d, 0h(11/2)) model space using e(eff)(nu) =1.0 e follows the experimental values for the neutron rich Sn isotopes, but fails to reproduce the results presented here.
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| 17. |
- Ekström, Claes, et al.
(författare)
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Evaluation of recombinant human IGF-1/IGFBP-3 on intraventricular hemorrhage prevention and survival in the preterm rabbit pup model
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates processes of vascular maturation. The pathogenesis of intraventricular hemorrhage (IVH) relates to the fragility of the immature capillaries in the germinal matrix, and its inability to resist fluctuations in cerebral blood flow. In this work, using different experimental setups, we aimed to (i) establish an optimal time-point for glycerol-induction of IVH in relation to time-point of recombinant human (rh) IGF-1/rhIGFBP-3 administration, and (ii) to evaluate the effects of a physiologic replacement dose of rhIGF-1/rhIGFBP-3 on prevention of IVH and survival in the preterm rabbit pup. The presence of IVH was evaluated using high-frequency ultrasound and post-mortem examinations. In the first part of the study, the highest incidence of IVH (> 60%), occurred when glycerol was administered at the earliest timepoint, e.g., 6h after birth. At later time-points (18 and 24h) the incidence decreased substantially. In the second part of the study, the incidence of IVH and mortality rate following rhIGF-1/rhIGFBP-3 administration was not statistically different compared to vehicle treated animals. To evaluate the importance of maintaining intrauterine serum levels of IGF-1 following preterm birth, as reported in human interventional studies, additional studies are needed to further characterize and establish the potential of rhIGF-1/rhIGFBP-3 in reducing the prevalence of IVH and improving survival in the preterm rabbit pup.
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| 18. |
- Ekström, Claes, et al.
(författare)
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THE INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) SYSTEM IN THE PRETERM RABBIT PUP : A CHARACTERIZATION OF THE IGF-1 MRNA EXPRESSION IN LIVER, IGF-1 PROTEIN LEVELS IN SERUM AND BRAIN DISTRIBUTION OF IGF-1 RECEPTORS
- 2019
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Konferensbidrag (refereegranskat)abstract
- IGF-1 is an essential regulator of fetal growth and brain development. Preterm birth in the human is followed by a rapid decrease in serum levels of IGF-1 and decreased levels of IGF-1 have been associated with development of severemorbidity. A recent clinical trial indicated that supplementation with IGF-1 prevented development of severe intraventricular hemorrhage (IVH) in extremely preterm infants. In order to better understand possible mechanisms involved in IGF-1-induced IVH prevention, we evaluated important aspects of the endogenous IGF-1 system; IGF-I mRNA expression in the liver and associated serum protein levels and brain IGF-1 receptor (IGFR) distribution in the preterm rabbit.Rabbit pups were delivered by cesarean section at E29 (preterm) or by vaginal delivery (term = E32), housed in a controlled environment and fed twice daily with bovine colostrum via a gastric tube. Serum concentrations of IGF-1protein and liver expression of IGF-1 mRNA were determined at 0, 2, 6, 12, 24, 48 and 72 h of age in preterm pups. Paraffin brain sections from perfusion fixed untreated animals (preterm pups at 20 h and term pups at 5-7 h and 96 h) were prepared for immunohistochemistry against IGF1R, by labeling with primary antibodies against IGF1R, and processed for chromogen visualization and density/quantitation analysis with confocal microscopy. Mean (SD) serum concentrations of IGF-1 decreased from 166 (33) ng/ml at birth (E29) to 28 (9) ng/ml at day 3 (P0). Hepatic expression of IGF-1 mRNA did not vary over time. The IGF1R was widely distributed in multiple brain regions in both preterm and term pups (Fig). The most abundant density of IGF1R was observed in the choroid plexus, the subfornical organ, the meninges, major fiber tracts, the cortex and sub-ependymal germinal zones. The IGF1R, was mainly localized on outer cell membranes, on cell bodies and along nerve fibers. Quantitative analysis of IGF1R immunoreactivity showed similar IGF1R densities in preterm and term pups of corresponding ages. IGF1R density decreased with increasing postnatal age in term pups.In line with what is observed in the preterm human infant, serum protein levels of IGF-1 in the preterm rabbit pup decrease rapidly following birth. The IGF1R is widely expressed in the brain following birth, with high expressions in regions and structures relevant for vessel rupture in IVH. The preterm rabbit thus presents a well-suited model for characterization and evaluation of mechanisms involved in IGF-1 induced prevention of IVH.
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| 19. |
- Ekström, Magnus, et al.
(författare)
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Comorbidity and Sex-Related Differences in Mortality in Oxygen-Dependent Chronic Obstructive Pulmonary Disease
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is not known why survival differs between men and women in oxygen-dependent chronic obstructive pulmonary disease (COPD). The present study evaluates differences in comorbidity between men and women, and tests the hypothesis that comorbidity contributes to sex-related differences in mortality in oxygen-dependent COPD. Methods: National prospective study of patients aged 50 years or older, starting long-term oxygen therapy (LTOT) for COPD in Sweden between 1992 and 2008. Comorbidities were obtained from the Swedish Hospital Discharge Register. Sex-related differences in comorbidity were estimated using logistic regression, adjusting for age, smoking status and year of inclusion. The effect of comorbidity on overall mortality and the interaction between comorbidity and sex were evaluated using Cox regression, adjusting for age, sex, Pa-O2 breathing air, FEV1, smoking history and year of inclusion. Results: In total, 8,712 patients (55% women) were included and 6,729 patients died during the study period. No patient was lost to follow-up. Compared with women, men had significantly more arrhythmia, cancer, ischemic heart disease and renal failure, and less hypertension, mental disorders, osteoporosis and rheumatoid arthritis (P<0.05 for all odds ratios). Comorbidity was an independent predictor of mortality, and the effect was similar for the sexes. Women had lower mortality, which remained unchanged even after adjusting for comorbidity; hazard ratio 0.73 (95% confidence interval, 0.68-0.77; P<0.001). Conclusions: Comorbidity is different in men and women, but does not explain the sex-related difference in mortality in oxygen-dependent COPD.
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| 20. |
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| 21. |
- Ekström, Ulf, et al.
(författare)
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An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F)
- 1999
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 55:5, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.
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| 22. |
- Ekström, Ulf, et al.
(författare)
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Mutations in the low-density lipoprotein receptor gene in Swedish familial hypercholesterolaemia patients: clinical expression and treatment response
- 1998
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972. ; 28:9, s. 740-747
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Familial hypercholesterolaemia, an autosomal co-dominant disorder caused by defects in the low-density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular disease. METHODS: In this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order to describe the genetic background of the disease in southern Sweden. These patients were studied with the aim of relating the presence of the different mutations to the clinical expression of the disease and to the response to pharmacological treatment. RESULTS: In 16 out of 21 patients, potentially disease-causing low-density lipoprotein receptor gene defects were found, including five not previously described alterations (C240-->F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122-->stop and another group of patients (n = 4) a mutation causing the substitution W66-->G. Patients in the two genotype subgroups were very similar with respect to lipid levels before treatment. CONCLUSION: A tendency towards differential susceptibility to treatment with statins was observed for the patient groups, encouraging further comparative studies of heterozygous FH patients.
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| 23. |
- Ekström, Ylva, 1971-, et al.
(författare)
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En studie om att leda digitala transformationer i komplexa verksamheter : Institutionella normer, fysiska rum och digitala verktyg
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Föreliggande rapport sammanfattar forskningsprojektet “Att leda digital transformation av fysiska rum” som genomförts av forskare vid Uppsala universitet i samverkan med tre partnerorganisationer: Uppsala stadsteater, Svenska Kyrkan, och en nordeuropeisk finanskoncern med huvudkontor i Sverige; projektet samfinansierades av Vinnova under åren 2019-2020. Projektets syfte var att utveckla kunskap om, och verktyg för förståelse av, hur det fysiska rummet och dess digitalisering påverkar interaktionen mellan aktörer bland annat med avseende på kommunikation, tillit och legitimitet. Projektet har genomförts som en komparativ studie av dessa tre tämligen skilda organisationer, som kommit olika långt i relation till digital transformation av deras respektive verksamheter. Forskarna har genomfört intervjuer och observationer på de tre partnerorganisationerna samt gemensamma och organisations-överskridande diskussioner och analyser vid ett flertal workshoppar, där såväl forskare som representanter från partnerorganisationerna deltagit. Rapporten presenterar resultat i form av beskrivningar av specifika situationer i respektive partnerorganisation med betoning på digitaliseringsprocesser med direkt inverkan på det fysiska rummet och de utmaningar som detta leder till. Vidare presenteras analyser och insikter i relation till utmaningarna som digitaliseringen kan ge upphov till och generella, normativa rekommendationer för att vägleda organisationer genom digitala transformationsprocesser. I analysen har framför allt institutionella logiker tillämpats som teoretiskt perspektiv. Studien påvisar betydelsen som de fysiska platserna (t.ex. kontor, scen) utgör för skilda verksamheter, och att användningen av digitala verktyg med syfte att eliminera användningen av fysiska platser kan ge upphov till oförutsedda konsekvenser.
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| 24. |
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En båge genom tiden - ritualer kring en göteborgshistoria. Om Flickläroverket i Artisten
- 2024
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- 1929 bildades Göteborgs första Högre allmänna läroverk för Flickor – Flickläroverket som fick en byggnad 1935 i det kulturella centrumet, Götaplatsen. Efter några år som Kjellbergska gymnasiet, sedan Komvux, blev byggnaden del av Artisten, Högskolan för scen och musik, HSM 1992. Byggnaden har burit kvinnors utbildning, konst och kultur över många generationer, en minneskedja som nu är bruten. Boken - En båge genom tiden – ritualer kring en göteborgshistoria – en konst- och forskningsantologi – är resultatet av de offentliga minnesdagar där de deltagande drygt 200 kvinnorna (70– 97 år) som varit elever på Flickläroverket, studenter vid Artisten, konstnärer och forskare – bidrog till och deltog i gestaltande ritualer, minnesrum, dans, utställningar och samtal som gav liv åt en utbildningskultur och konst som berört samhället i generationer. I boken bidrar ett 20-tal Göteborgsbaserade konstnärer och forskare med olika perspektiv på byggnadens poetiska, sociala och konstnärliga dimensioner. Bland annat beskrivs återskapandet av Bågdansen, som dansades varje år vid Lucia mellan 1934-1972. Här beskrivs även den medie-debatt som ledde till räddningen av målningen Dansen av Nils Nilsson från 1935 och hur nedtagningen gick till. Tillsammans med ett rikt foto- och bildmaterial, filmdokumentationer och ett ljudarkiv utgör boken ett tidsdokument där konst fungerar som minnesbärare över tid och rum.
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| 25. |
- Gram, Magnus, et al.
(författare)
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Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following Administration of Recombinant Human Insulin-Like Growth Factor 1/Insulin-Like Growth Factor 1-Binding Protein 3
- 2021
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Ingår i: Developmental Neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 43:5, s. 281-295
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Tidskriftsartikel (refereegranskat)abstract
- Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a preterm rabbit pup model, we characterized endogenous serum and hepatic IGF-1, along with brain distribution of IGF-1 and IGF-1 receptor (IGF1R). We then evaluated the effects of rhIGF-1/rhIGFBP-3 on gene expression of regulators of cerebrovascular maturation and structure. Similar to preterm infants, serum IGF-1 concentrations decreased rapidly after preterm birth in the rabbit pup. Administration of rhIGF-1/rhIGFBP-3 restored in utero serum levels but was rapidly eliminated. Immunolabeled IGF1R was widely distributed in multiple brain regions, displaying an abundant density in the choroid plexus and sub-ependymal germinal zones. Increased IGF-1 immunoreactivity, distributed as IGF1R, was detected 4 h after rhIGF-1/rhIGFBP-3 administration. The rhIGF-1/rhIGFBP-3 treatment led to upregulation of choroid plexus genes involved in vascular maturation and structure, with corresponding protein translation for most of these genes. The preterm rabbit pup model is well suited for evaluation of IGF-1-based prevention of IVH. Administration of rhIGF-1/rhIGFBP-3 affects cerebrovascular maturation, suggesting a role for it in preventing preterm IVH.
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| 26. |
- Jakobsson, J, et al.
(författare)
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A novel polymorphism in the 17beta-hydroxysteroid dehydrogenase type 5 (aldo-keto reductase 1C3) gene is associated with lower serum testosterone levels in caucasian men.
- 2007
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Ingår i: The pharmacogenomics journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 7:4, s. 282-9
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variation in the androgen metabolizing enzymes is important to identify and feature as they may influence the risk of prostate cancer and help clarify the etiology of the disease. Human 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3) is highly expressed in the prostate gland and plays a major role in the formation and metabolism of androgens. We identified five novel polymorphisms in the AKR1C3 gene. One of those an A>G substitution in exon 2 that confers a Glu77Gly change occurred in 4.8% in Caucasians but was completely absent in Orientals. Interestingly, the testosterone level in serum was significantly lower in subjects with the Gly77 allele. A promoter A>G polymorphism was associated with significantly altered promoter activity in reporter constructs, but was not associated with any change in testosterone levels. In conclusion, the Glu77Gly polymorphism is associated with lower testosterone levels in serum.
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| 27. |
- Jakobsson, Jenny, et al.
(författare)
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Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:2, s. 687-93
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. OBJECTIVE: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. METHODS AND RESULTS: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. CONCLUSIONS: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.
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| 28. |
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| 29. |
- Jungner, Åsa, et al.
(författare)
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White Matter Brain Development after Exposure to Circulating Cell-Free Hemoglobin and Hyperoxia in a Rat Pup Model
- 2020
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Ingår i: Developmental Neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 41:3-4, s. 234-246
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Tidskriftsartikel (refereegranskat)abstract
- Neonates born with critical congenital heart defects are at risk of diffuse white matter injuries and neurodevelopmental impairments. This study aimed to determine the impact of circulating cell-free hemoglobin and hyperoxia, both present during cardiopulmonary bypass circulation, on white matter brain development. Postnatal day 6 rat pups were injected intraperitoneally with cell-free Hb or vehicle and exposed to hyperoxia (fiO2 = 0.8) or normoxia (fiO2 = 0.21) for 24 h. We evaluated apoptosis, myelination, and oligodendrocyte maturation with immunohistochemistry, gene and protein analyses, and in vivo diffusion tensor magnetic resonance imaging (MRI). Consistent with previous studies, we found an increase in apoptosis of oligodendrocytes as determined by TUNEL+ staining in Olig2+ cells in white matter, cortex, thalamus, and hippocampus following exposure to hyperoxia with no additional effect of cell-free Hb. A transient increase in the mRNA expression of intercellular adhesion molecule 1 at 6 h was observed following combined exposure to cell-free Hb and hyperoxia. No indications of oligodendrocyte maturational delay or hypomyelination were observed after either insult, delivered separately or combined, as determined by immunohistochemistry, Western blot, and diffusion tensor MRI. In our model, exposure to circulatory cell-free Hb, with or without concomitant hyperoxia, did not significantly alter brain white matter development.
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| 30. |
- Lundberg, Martin, et al.
(författare)
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Multiplexed Homogeneous Proximity Ligation Assays for High-throughput Protein Biomarker Research in Serological Material
- 2011
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 10:4, s. M110.004978-
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Tidskriftsartikel (refereegranskat)abstract
- A high throughput protein biomarker discovery tool has been developed based on multiplexed proximity ligation assays in a homogeneous format in the sense of no washing steps. The platform consists of four 24-plex panels profiling 74 putative biomarkers with sub-pM sensitivity each consuming only 1 mu l of human plasma sample. The system uses either matched monoclonal antibody pairs or the more readily available single batches of affinity purified polyclonal antibodies to generate the target specific reagents by covalently linking with unique nucleic acid sequences. These paired sequences are united by DNA ligation upon simultaneous target binding forming a PCR amplicon. Multiplex proximity ligation assays thereby converts multiple target analytes into real-time PCR amplicons that are individually quantified using microfluidic high capacity qPCR in nano liter volumes. The assay shows excellent specificity, even in multiplex, by its dual recognition feature, its proximity requirement, and most importantly by using unique sequence specific reporter fragments on both antibody-based probes. To illustrate the potential of this protein detection technology, a pilot biomarker research project was performed using biobanked plasma samples for the detection of colorectal cancer using a multivariate signature.
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| 31. |
- Löfdahl, Claes-Göran, et al.
(författare)
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COPD health care in Sweden - A study in primary and secondary care
- 2010
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 104:3, s. 404-411
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To map out-patients with Chronic Obstructive Pulmonary Disease (COPD) with special reference to patients suffering from acute exacerbations, and to describe COPI) health care structure and process in Swedish clinical. practice in a real life setting. Design: Retrospective, non-interventional, epidemiological survey. Setting: 141 hospital based out patient clinics (OPC, n = 30) and primary health care clinics (PC, n = 111) were included in the structure evaluation. Subjects: 1004 COPI) diagnosed patients from 100 of the centres (OPC, n = 26) participated in the process evaluation. Methods: All Swedish OPC (n = 40) and a random sample of 180 PC were asked to answer a questionnaire regarding COPI) care. In addition, data from 10 randomly selected patients with a documented COPI) disease were analysed from the centres. Results: Spirometers were available at all OPCs and at 99% of the PCs. Spirometry had been performed in 52% of PC-patients and in 89% of OPC-patients during the last 2 years prior to the study. More severe patients, as judged by investigator and lung function data, were treated at OPCs than at PCs. Physiotherapists, occupational therapists and dieticians were available at >80% of centres. Exacerbation rate was higher at PCs without a specialized nurse, 2.2/year versus 0.9/year at centres with a specialized nurse. Conclusions: Special attention to COPD, marked by a specialised nurse in primary care improves the quality, as assessed by a tower number of exacerbations. The structure of COPD care in Sweden for diagnosed individuals seems satisfactory, but could be improved mainly through higher availability and educational activities.
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| 32. |
- Ortenlöf, Niklas, et al.
(författare)
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Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3
- 2023
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Ingår i: Fluids and Barriers of the CNS. - 2045-8118. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time.
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| 33. |
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| 34. |
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| 35. |
- Schulze, Jenny Jakobsson, et al.
(författare)
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Genetic aspects of epitestosterone formation and androgen disposition: influence of polymorphisms in CYP17 and UGT2B enzymes.
- 2008
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Ingår i: Pharmacogenetics and genomics. - 1744-6872. ; 18:6, s. 477-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Testosterone is a commonly abused androgen in sports and in the gym culture of the society. Its abuse is conventionally disclosed by urinary assay of the testosterone/epitestosterone (T/E) glucuronide ratio, which should not exceed 4. A noteworthy number of athletes, however, have higher natural ratios than 4, most likely because of decreased excretion of epitestosterone glucuronide. Falsely positive doping test results are of great concern for the legal rights of the sportsman. Our objective was to study the genetic aspects of epitestosterone formation, and to elucidate the impact of genetic variation in androgen-metabolizing enzymes. METHODS: Urine from different study populations was analysed for androgen glucuronides by gas chromatography-mass spectrometry. All men were genotyped for the uridine diphospho-glucuronosyltransferase (UGT) 2B17 deletion polymorphism and single nucleotide polymorphisms in the cytochrome P-450c17alpha (CYP17), UGT2B15 and UGT2B7 genes. Expression of UGT2B15 mRNA in human liver samples was analysed using real-time PCR. RESULTS: A T>C (A1>A2) promoter polymorphism in the CYP17 gene was associated with the urinary glucuronide levels of epitestosterone and its putative precursor androstene-3beta, 17alpha-diol, resulting in 64% higher T/E ratios in A1/A1 homozygotes. Individuals devoid of UGT2B17 had significantly higher UGT2B15 mRNA levels in liver than individuals carrying two functional UGT2B17 alleles. CONCLUSION: The CYP17 promoter polymorphism may partly explain high natural (>4) T/E ratios. Our data indicate that 5-androstene-3beta, 17alpha-diol is an important precursor of epitestosterone and that CYP17 is involved in its production. In addition, we found that lack of the UGT2B17 enzyme may be compensated for by increase in UGT2B15 transcription.
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| 36. |
- Ström, Kristoffer, et al.
(författare)
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Genetic variation at RAB3GAP2 and its role in exercise-related adaptation and recovery
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Skeletal muscle fiber composition and capillary density influence physical performance and whole-body metabolic properties. ~45% of the variance in fiber type is heritable, which motivated us to perform a genome-wide association study of skeletal muscle histology from 656 Swedish men. Four independent variants were associated (p
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| 37. |
- Ställberg, Björn, et al.
(författare)
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A real-life cost-effectiveness evaluation of budesonide/formoterol maintenance and reliever therapy in asthma
- 2008
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 102:10, s. 1360-1370
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate direct asthma-related costs in Swedish primary care in a real-life setting. DESIGN: 12-month open-label study. SETTING Swedish primary care in a real-life setting. PARTICIPANTS 1776 patients with persistent asthma. INTERVENTIONS Patients with persistent asthma were randomised to one of three treatments: a free adjustable combination of budesonide (100-400 microg/inhalation) and formoterol (4.5 or 9 microg/inhalation) via separate inhalers plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, two inhalations twice daily) plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, one inhalation twice daily or two inhalations once daily), for maintenance plus additional inhalations as needed. Doses depended on previous inhaled corticosteroid dose. Patients attended the clinic at 0, 1.5, and 12 months. Telephone interviews were conducted at 4, 6, 8, and 10 months. MAIN OUTCOME MEASURES The primary endpoint was direct asthma-related healthcare costs. RESULTS Statistically significant reductions in annual direct costs per patient were observed with budesonide/formoterol maintenance and reliever therapy compared with the free adjustable combination of budesonide and formoterol (-13%, P<0.001) and fixed-dose budesonide/formoterol plus terbutaline (-20%, P<0.001). Time to first severe exacerbation did not differ significantly across treatment groups, with a mean reduction of 28% versus the free adjustable combination of budesonide and formoterol (P=0.076). Patients receiving budesonide/formoterol maintenance and reliever therapy used a significantly lower daily dose of budesonide compared with the conventional (P<0.001). CONCLUSIONS This study reports direct cost savings with budesonide/formoterol maintenance and reliever therapy compared with conventional treatment regimens with at least equivalent efficacy.
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| 38. |
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