| 1. |
|
|
| 2. |
- Setlur, Sunita R., et al.
(författare)
-
Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer
- 2008
-
Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:11, s. 815-825
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. METHODS: We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians(') Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. RESULTS: We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P < .001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERbeta agonist (ERbeta agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ERbeta agonist treatment (fold change over internal control, ERbeta agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). CONCLUSIONS: TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism.
|
|
| 3. |
- Azad, A.K., et al.
(författare)
-
Structural and magnetic properties of LaFe0.5Cr0.5O3 studied by neutron diffraction, electron diffraction and magnetometry
- 2005
-
Ingår i: Materials Research Bulletin. - 0025-5408. ; 40(10), s. 1633-1644
-
Tidskriftsartikel (refereegranskat)abstract
- The structural and magnetic properties of the perovskite type compound LaFe0.5Cr0.5O3 have been studied by temperature dependent neutron powder diffraction and magnetization measurements. Rietveld refinement of the neutron diffraction data shows that the compound crystallizes in an orthorhombic perovskite structure with a random positioning of the Fe and Cr cations at the B sublattice. The magnetic structure at 10 K is a collinear antiferromagnetic one with the magnetic moment per site being equal to 2.79(4) mu(B). Magnetisation measurements confirm the overall antiferromagnetic behaviour. Moreover, it indicates a weak uncompensated magnetic moment close to the transition temperature T-N approximate to 265 K. This moment can be described by a magnetic cluster state, which remains up to 550 K. Electron diffraction patterns along with high-resolution transmission electron microscopy images reveal that the crystallites are composed by domains of different orientation, which share the same cubic perovskite sub-cell reflections. (C) 2005 Elsevier Ltd. All rights reserved
|
|
| 4. |
- Flanagan, K. T., et al.
(författare)
-
Nuclear Spins and Magnetic Moments of Cu-71,Cu-73,Cu-75 : Inversion of pi 2p(3/2) and pi 1f(5/2) Levels in Cu-75
- 2009
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:14, s. 142501-
-
Tidskriftsartikel (refereegranskat)abstract
- We report the first confirmation of the predicted inversion between the pi 2p(3/2) and pi 1f(5/2) nuclear states in the nu g(9/2) midshell. This was achieved at the ISOLDE facility, by using a combination of in-source laser spectroscopy and collinear laser spectroscopy on the ground states of Cu-71,Cu-73,Cu-75, which measured the nuclear spin and magnetic moments. The obtained values are mu(Cu-71)=+2.2747(8)mu(N), mu(Cu-73)=+1.7426(8)mu(N), and mu(Cu-75)=+1.0062(13)mu(N) corresponding to spins I=3/2 for Cu-71,Cu-73 and I=5/2 for Cu-75. The results are in fair agreement with large-scale shell-model calculations.
|
|
| 5. |
- Ye, F, et al.
(författare)
-
Electronic Self-Organization in the Single-Layer Manganite Pr1-xCa1+xMnO4
- 2009
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:16
-
Tidskriftsartikel (refereegranskat)abstract
- We use neutron scattering to investigate the doping evolution of the magnetic correlations in the single-layer manganite Pr1-xCa1-xMnO4, away from the x = 0.5 composition where the CE-type commensurate antiferromagnetic (AF) structure is stable. We find that short-range incommensurate spin correlations develop as the system is electron doped (x < 0.5), which coexist with the CE-type AF order. This suggests that electron doping in this system induces an inhomogeneous electronic self-organization, where commensurate AF patches with x = 0.5 are separated by electron-rich domain walls with short-range magnetic correlations. This behavior is strikingly different than for the perovskite Pr1-xCaxMnO3, where the long-range CE-type commensurate AF structure is stable over a wide range of electron or hole doping around x = 0.5.
|
|
| 6. |
|
|
| 7. |
- Christian, Kyle J., et al.
(författare)
-
Interaction of heterogeneous nuclear ribonucleoprotein C1/C2 with a novel cis-regulatory element within p53 mRNA as a response to cytostatic drug treatment
- 2008
-
Ingår i: Molecular Pharmacology. - : Aspet. - 0026-895X .- 1521-0111. ; 73:5, s. 1558-1567
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a novel cis-element in the 5' coding region of p53 mRNA and its interaction with heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. This element is located in a putative hairpin loop structure, within the first 101 nucleotides downstream of the start codon. The binding of hnRNPC1/C2 is strongly enhanced in response to the DNA-damaging drug cisplatin [cis-diamminedichloroplatinum(II)] and the cytostatic transcriptional inhibitor actinomycin D (dactinomycin), both known inducers of apoptosis and p53. Strongly stimulated binding is observed in both nuclear and cytoplasmic compartments, and it is accompanied by a cytoplasmic increase of hnRNPC1/C2. Changes in hnRNPC1/C2 protein levels are not proportional to binding activity, suggesting qualitative changes in hnRNPC1/C2 upon activation. Phosphorylation studies reveal contrasting characteristics of the cytoplasmic and nuclear hnRNPC1/C2 interaction with p53 mRNA. Results from chimeric p53-luciferase reporter constructs suggest that hnRNPC1/C2 regulates p53 expression via this binding site. Our results are consistent with a mechanism in which the interaction of hnRNPC1/C2 with a cis-element within the coding region of the p53 transcript regulates the expression of p53 mRNA before and during apoptosis. In addition, we report that preapoptotic signals induced by transcriptional inhibition trigger the appearance of a truncated, exclusively cytoplasmic 43-kDa variant of p53 before apoptosis.
|
|
| 8. |
|
|
| 9. |
- Gisselbrecht, Mathieu, et al.
(författare)
-
Size dependent fragmentation of argon clusters in the soft x-ray ionization regime.
- 2008
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 128:4
-
Tidskriftsartikel (refereegranskat)abstract
- Photofragmentation of argon clusters of average size ranging from 10 up to 1000 atoms is studied using soft x-ray radiation below the 2p threshold and multicoincidence mass spectroscopy technique. For small clusters (N=10), ionization induces fast fragmentation with neutral emission imparting a large amount of energy. While the primary dissociation takes place on a picosecond time scale, the fragments undergo slow degradation in the spectrometer on a microsecond time scale. For larger clusters (N>/=100) we believe that we observe the fragmentation pattern of multiply charged species on a time-scale which lasts a few hundred nanoseconds. The reason for these slower processes is the large number of neutral atoms which act as an efficient cooling bath where the excess energy ("heat") dissipates among all degrees of freedom. Further degradation of the photoionic cluster in spectrometer then takes place on the microsecond time scale, similar to small clusters.
|
|
| 10. |
|
|
| 11. |
- Jönsson, Petra, et al.
(författare)
-
Absence of conventional spin-glass transition in the Ising dipolar system LiHo(x)Y(1-x)F(4)
- 2007
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 98:25, s. 256403-
-
Tidskriftsartikel (refereegranskat)abstract
- The magnetic properties of single crystals of LiHo(x)Y(1-x)F(4) with x=16.5% and x=4.5% were recorded down to 35 mK using a micro-SQUID magnetometer. While this system is considered as the archetypal quantum spin glass, the detailed analysis of our magnetization data indicates the absence of a phase transition, not only in a transverse applied magnetic field, but also without field. A zero-Kelvin phase transition is also unlikely, as the magnetization seems to follow a noncritical exponential dependence on the temperature. Our analysis thus unmasks the true, short-ranged nature of the magnetic properties of the LiHo(x)Y(1-x)F(4) system, validating recent theoretical investigations suggesting the lack of phase transition in this system.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Linares, Mathieu, et al.
(författare)
-
Expression of chirality in molecular layers at surfaces : Insights from modelling
- 2009
-
Ingår i: Chemical Society Reviews. - : Royal Society of Chemistry (RSC). - 0306-0012 .- 1460-4744. ; 38:3, s. 806-816
-
Tidskriftsartikel (refereegranskat)abstract
- This tutorial review illustrates how modelling can be used to understand the structure and properties of chiral surfaces formed by adsorption of molecular layers. The two major theoretical approaches for such modelling (Density Functional Theory and classical force-field methods) are briefly described and compared. A few examples of their use are given, focussing on: (i) the expression of chirality at the local and global scale in layers of chiral molecules, (ii) the appearance of chirality in layers of achiral molecules on achiral surfaces, and (iii) the molecular organisation in layers formed from racemic mixtures.
|
|
| 15. |
- Lindgren, Andreas, et al.
(författare)
-
Molecular alignment of ammonia studied by electron-ion-ion coincidence spectroscopy
- 2005
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 122:11
-
Tidskriftsartikel (refereegranskat)abstract
- Electron-ion-ion coincidence measurements carried out at discrete resonances near the N 1s threshold in ammonia are reported. The measured coincidence spectra show clear alignment of the molecule upon resonant core-electron excitation. The coincidence data are analyzed to extract information about the molecule in the excited state by simulating the alignment and the dissociation processes. Dynamic changes in molecular geometry are found as the photon energy is scanned through the N 1s -> 4a(1) resonance, whereas for the N 1s -> 2e state the geometry and kinetic energy released upon dissociation remain unchanged. The alignment of the core-excited molecules is found to be preserved even in two-step dissociation processes.
|
|
| 16. |
- Mathieu, Roland, et al.
(författare)
-
Bandwidth-disorder phase diagram of half-doped layered manganites
- 2006
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 74:2
-
Tidskriftsartikel (refereegranskat)abstract
- Phase diagrams in the plane of rA (the average ionic radius, related to the one-electron bandwidth W) and σ2 (the ionic radius variance, measuring the quenched disorder), or bandwidth-disorder phase diagrams, have been established for perovskite manganites, with a three-dimensional (3D) Mn-O network. Here we establish the intrinsic bandwidth-disorder phase diagram of half-doped layered manganites with a two-dimensional (2D) Mn-O network, examining in detail the parent state of the colossal magnetoresistance phenomenon in crystals without ferromagnetic instability. The consequences of the reduced dimensionality, from 3D to 2D, for the order-disorder phenomena in the charge-orbital sectors are also highlighted.
|
|
| 17. |
|
|
| 18. |
- Mathieu, Roland, et al.
(författare)
-
Coexistence of long-ranged charge and orbital order and spin-glass state in single-layered manganites with weak quenched disorder
- 2007
-
Ingår i: Europhysics letters. - : IOP Publishing. - 0295-5075 .- 1286-4854. ; 80:3, s. 37001-
-
Tidskriftsartikel (refereegranskat)abstract
- The relationship between orbital and spin degrees of freedom in the single crystals of the hole-doped Pr1-xCa1+xMnO4, 0.3 <= x <= 0.7 has been investigated by means of ac-magnetometry and charge transport. We show that in an intermediate underdoped region, with 0.35 <= x < 0.5, the "orbital-master spin-slave" relationship commonly observed in half-doped manganites does not take place. The long-ranged charge-orbital order is not accompanied by an antiferromagnetic transition at low temperatures, but by a frustrated short-ranged magnetic state bringing forth a spin-glass phase. We discuss in detail the nature and origin of this true spin-glass state, which, as in the half-doped manganites with large quenched disorder, is not related to the macroscopic phase separation observed in crystals with minor defects or impurities.
|
|
| 19. |
- Mathieu, Roland, et al.
(författare)
-
Logarithmic growth law in the two-dimensional Ising spin glass state resulting from the electron doping in single-layered manganites
- 2007
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 76:1, s. 014436-
-
Tidskriftsartikel (refereegranskat)abstract
- The ac susceptibility of the electron-doped single-layered manganite La1.1 Sr0.9 Mn O4 is analyzed in detail. A quasi-two-dimensional antiferromagnetic (AFM) order with Ising anisotropy is stabilized below TN ∼80 K. We show that below TN, a rare two-dimensional (2D) spin-glass (SG) correlation develops with the same Ising anisotropy as the AFM state. Using simple scaling arguments of the droplet model, we derive a scaling form for the ac susceptibility data of a 2D SG, which our experimental data follow fairly well. Due to simplifications in this 2D case, the proposed scaling form only contains two unknown variables, ψν and τ0. Hence, the logarithmic growth law of the SG correlation predicted by the droplet model is convincingly evidenced by the scaling of our experimental data. The origin and nature of this 2D SG state are also discussed.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Simonsson, Ulrika S.H., et al.
(författare)
-
In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin
- 2006
-
Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 36:9, s. 647-653
-
Tidskriftsartikel (refereegranskat)abstract
- Backround Artemisinin (a sesquiterpene lactone endoperoxide) has become important in multi-drug treatment of malaria. There is evidence that artemisinin induces drug metabolism which could result in drug-drug interactions. The objective of this study was to characterize the inductive properties of artemisinin on drug-metabolizing cytochrome P450 (CYP450) enzymes. Materials and methods The possibility of artemisinin to induce CYP450 was studied in artemisinin-treated (orally for four days) and vehicle-treated rats using reverse transcriptase polymerase chain reaction (RT-PCR). The effect on enzymatic activities in mouse microsomes from multiple artemisinin administration (intraperitonally) to mice were also studied as well as the effect on the expression in mouse primary hepatocytes and HEK293 cells. Results Increased CYP2B1 mRNA levels in rats could be seen after artemisinin treatment as well as a weak but reproducible increase in the intensity of CYP1A2. Administration of artemisinin to mice up-regulated hepatic CYP2B10-dependent, and to a lesser extent, CYP2A5-dependent enzyme activities. In primary hepatocyte culture, artemisinin significantly increased the CYP2B10 mRNA levels whereas the CYP2A5 mRNA levels were increased to a lesser extent. No significant changes were seen in the levels of other CYP enzymes. Artemisinin was an activator of constitutive androstane receptor (CAR) but not pregnane X receptor (PXR) in HEK293 cells. Conclusions The results demonstrate that the drug exerts its effects on drug metabolism via the CAR receptor that results in up-regulation of genes such as the Cyp2b. The weaker up-regulation of CYP2A5 might also be CAR-dependent or alternatively, a consequence of artemisinin toxicity. The results of this study are of importance when predicting potential drug-drug interactions in multi-drug therapies with artemisinin.
|
|
| 24. |
- Söderberg, Malin, et al.
(författare)
-
Identification of a regulatory cis-element within the 3 '-untranslated region of the murine inducible nitric oxide synthase (NOS) mRNA : interaction with heterogeneous nuclear ribonucleoproteins I and L and role in the NOS gene expression
- 2007
-
Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 44:4, s. 434-442
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the role of heterogeneous nuclear ribonucleoprotein I (hnRNPI) and hnRNPL in the regulation of the murine inducible nitric,oxide synthase (iNOS) gene during inflammation. Treatment of mice with lipopolysaccharide (LPS)/D-galactosamine, or of RAW 264.7 cells with LPS/interferon-gamma (IFN-gamma), strongly increased iNOS expression while reducing hnRNPI levels and complex formation between hnRNPI/hnRNPL and the 3'-untranslated region (3'-UTR) of iNOS mRNA. Introduction of the iNOS 3'-UTR to a luciferase reporter gene reduced its expression in RAW 264.7 cells. However, when hnRNPI and hnRNPL binding sites were deleted, luciferase expression was recovered. LPS/IFN-gamma increased the luciferase activity of the full-length 3'-UTR construct compared to control, while its effects on the deletion constructs were modest. The results indicate that LPS/IFN-gamma induce iNOS through a mechanism involving hnRNPI and hnRNPL binding to iNOS 3'-UTR. Our data suggest that iNOS mRNA degradation is promoted upon binding of hnRNPI and hnRNPL to a destabilizing region within its 3'-UTR, while inflammatory stimuli causing dissociation of the mRNA-protein complex, yield a more stable transcript. This appears to be particularly significant during extended inflammatory stimuli, resulting in sustained nitric oxide production. The critical event launching this process appears to be the degradation of hnRNPI.
|
|
| 25. |
- Söderberg, Malin, 1974-
(författare)
-
Post-Transcriptional Regulation of the Murine Inducible Nitric Oxide Synthase Gene
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Large amounts of nitric oxide (NO) are produced by the inducible nitric oxide synthase (iNOS) upon inflammatory stimuli. NO is a multifaceted molecule, which may have beneficial effects as an antimicrobial agent in the immune defense, or cytotoxic effects in chronic inflammations, manifested as e.g. arthritis and asthma. Understanding the mode of regulation of the iNOS gene is a prerequisite for developing intervention strategies in various pathological conditions where detrimental effects of NO need to be prevented.Transcriptional processes of the iNOS gene regulation are well described, while post-transcriptional events have not been studied in detail. The aim of the present thesis was to investigate post-transcriptional regulatory mechanisms involving the 3’untranslated region (UTR) of the murine iNOS mRNA.Inflammation-dependent RNA-protein interactions with the iNOS mRNA 3’UTR were characterized by RNA gel shift analysis and UV cross-linking. Trans-acting factors interacting with the 3’UTR were detected in mouse liver and macrophages and identified as heterogeneous nuclear ribonucleoproteins (hnRNP) I and L. Western blot revealed that reduced hnRNPI levels are responsible for the decreased interaction of hnRNPI with iNOS 3’UTR upon induction in inflammatory conditions. This decrease was reversed by the glucocorticoid dexamethasone, concomitant with decreased iNOS mRNA levels and stability. Introduction of the iNOS 3’UTR into a luciferase reporter gene reduced its expression in macrophages. Upon deletions of the binding sites for hnRNPI and hnRNPL, the luciferase expression was recovered. In addition, inflammatory stimuli increased the luciferase activity of the construct with the full-length 3’UTR, while only weak effects of the stimuli were seen on the deletion constructs.In conclusion, the results suggest that binding of hnRNPI and hnRNPL to the iNOS mRNA 3’UTR promotes degradation of the transcript. Induction of iNOS by inflammatory stimuli dissociates the RNA-protein complex, yielding a more stable mRNA. In addition, post-transcriptional down-regulation of the iNOS gene by the anti-inflammatory glucocorticoid dexamethasone, seems to involve hnRNPI.
|
|
