| 1. |
- Blumel, Edda, et al.
(författare)
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Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
- 2019
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Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.
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| 2. |
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| 3. |
- Gluud, Maria, et al.
(författare)
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MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas
- 2020
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:5
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Forskningsöversikt (refereegranskat)abstract
- Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.
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| 4. |
- Kjær, Kasper S., et al.
(författare)
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Finding intersections between electronic excited state potential energy surfaces with simultaneous ultrafast X-ray scattering and spectroscopy
- 2019
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 10:22, s. 5749-5760
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Tidskriftsartikel (refereegranskat)abstract
- Light-driven molecular reactions are dictated by the excited state potential energy landscape, depending critically on the location of conical intersections and intersystem crossing points between potential surfaces where non-adiabatic effects govern transition probabilities between distinct electronic states. While ultrafast studies have provided significant insight into electronic excited state reaction dynamics, experimental approaches for identifying and characterizing intersections and seams between electronic states remain highly system dependent. Here we show that for 3d transition metal systems simultaneously recorded X-ray diffuse scattering and X-ray emission spectroscopy at sub-70 femtosecond time-resolution provide a solid experimental foundation for determining the mechanistic details of excited state reactions. In modeling the mechanistic information retrieved from such experiments, it becomes possible to identify the dominant trajectory followed during the excited state cascade and to determine the relevant loci of intersections between states. We illustrate our approach by explicitly mapping parts of the potential energy landscape dictating the light driven low-to-high spin-state transition (spin crossover) of [Fe(2,2′-bipyridine)3]2+, where the strongly coupled nuclear and electronic dynamics have been a source of interest and controversy. We anticipate that simultaneous X-ray diffuse scattering and X-ray emission spectroscopy will provide a valuable approach for mapping the reactive trajectories of light-triggered molecular systems involving 3d transition metals.
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| 5. |
- Kjær, Kasper S., et al.
(författare)
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Solvent control of charge transfer excited state relaxation pathways in [Fe(2,2′-bipyridine)(CN)4]2-
- 2018
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 20:6, s. 4238-4249
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Tidskriftsartikel (refereegranskat)abstract
- The excited state dynamics of solvated [Fe(bpy)(CN)4]2-, where bpy = 2,2′-bipyridine, show significant sensitivity to the solvent Lewis acidity. Using a combination of optical absorption and X-ray emission transient spectroscopies, we have previously shown that the metal to ligand charge transfer (MLCT) excited state of [Fe(bpy)(CN)4]2- has a 19 picosecond lifetime and no discernable contribution from metal centered (MC) states in weak Lewis acid solvents, such as dimethyl sulfoxide and acetonitrile.1,2 In the present work, we use the same combination of spectroscopic techniques to measure the MLCT excited state relaxation dynamics of [Fe(bpy)(CN)4]2- in water, a strong Lewis acid solvent. The charge-transfer excited state is now found to decay in less than 100 femtoseconds, forming a quasi-stable metal centered excited state with a 13 picosecond lifetime. We find that this MC excited state has triplet (3MC) character, unlike other reported six-coordinate Fe(ii)-centered coordination compounds, which form MC quintet (5MC) states. The solvent dependent changes in excited state non-radiative relaxation for [Fe(bpy)(CN)4]2- allows us to infer the influence of the solvent on the electronic structure of the complex. Furthermore, the robust characterization of the dynamics and optical spectral signatures of the isolated 3MC intermediate provides a strong foundation for identifying 3MC intermediates in the electronic excited state relaxation mechanisms of similar Fe-centered systems being developed for solar applications.
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| 6. |
- Kunnus, Kristjan, et al.
(författare)
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Vibrational wavepacket dynamics in Fe carbene photosensitizer determined with femtosecond X-ray emission and scattering
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The non-equilibrium dynamics of electrons and nuclei govern the function of photoactive materials. Disentangling these dynamics remains a critical goal for understanding photoactive materials. Here we investigate the photoinduced dynamics of the [Fe(bmip)2]2+ photosensitizer, where bmip = 2,6-bis(3-methyl-imidazole-1-ylidine)-pyridine, with simultaneous femtosecond-resolution Fe Kα and Kβ X-ray emission spectroscopy (XES) and X-ray solution scattering (XSS). This measurement shows temporal oscillations in the XES and XSS difference signals with the same 278 fs period oscillation. These oscillations originate from an Fe-ligand stretching vibrational wavepacket on a triplet metal-centered (3MC) excited state surface. This 3MC state is populated with a 110 fs time constant by 40% of the excited molecules while the rest relax to a 3MLCT excited state. The sensitivity of the Kα XES to molecular structure results from a 0.7% average Fe-ligand bond length shift between the 1 s and 2p core-ionized states surfaces.
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| 7. |
- Leshchev, Denis, et al.
(författare)
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Tracking the picosecond deactivation dynamics of a photoexcited iron carbene complex by time-resolved X-ray scattering
- 2018
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 9:2, s. 405-414
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Tidskriftsartikel (refereegranskat)abstract
- Recent years have seen the development of new iron-centered N-heterocyclic carbene (NHC) complexes for solar energy applications. Compared to typical ligand systems, the NHC ligands provide Fe complexes with longer-lived metal-to-ligand charge transfer (MLCT) states. This increased lifetime is ascribed to strong ligand field splitting provided by the NHC ligands that raises the energy levels of the metal centered (MC) states and therefore reduces the deactivation efficiency of MLCT states. Among currently known NHC systems, [Fe(btbip)2]2+ (btbip = 2,6-bis(3-tert-butyl-imidazol-1-ylidene)pyridine) is a unique complex as it exhibits a short-lived MC state with a lifetime on the scale of a few hundreds of picoseconds. Hence, this complex allows for a detailed investigation, using 100 ps X-ray pulses from a synchrotron, of strong ligand field effects on the intermediate MC state in an NHC complex. Here, we use time-resolved wide angle X-ray scattering (TRWAXS) aided by density functional theory (DFT) to investigate the molecular structure, energetics and lifetime of the high-energy MC state in the Fe-NHC complex [Fe(btbip)2]2+ after excitation to the MLCT manifold. We identify it as a 260 ps metal-centered quintet (5MC) state, and we refine the molecular structure of the excited-state complex verifying the DFT results. Using information about the hydrodynamic state of the solvent, we also determine, for the first time, the energy of the 5MC state as 0.75 ± 0.15 eV. Our results demonstrate that due to the increased ligand field strength caused by NHC ligands, upon transition from the ground state to the 5MC state, the metal to ligand bonds extend by unusually large values: by 0.29 Å in the axial and 0.21 Å in the equatorial direction. These results imply that the transition in the photochemical properties from typical Fe complexes to novel NHC compounds is manifested not only in the destabilization of the MC states, but also in structural distortion of these states.
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| 8. |
- Lövblad, Gun, et al.
(författare)
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The deposition of base cations in the Nordic countries
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Base cation deposition from the atmosphere provides, together with weathering, ions for neutralising acidity and, after sufficient reductions of acidifying deposition, a source for replenishing lost base cation pools. In the integrated assessment modelling to support the strategies of pollution abatement, a need for base cation data over Europe has been expressed. Data are needed by the scientists working with acidification effects and recovery of ecosystems. A study has been made on a procedure for mapping base cation deposition over the Nordic countries, with an additional aim of recommendations for base cation mapping on a European scale. The mapping over the Nordic countries was made using the data assimilation part of the MATCH model, run with a resolution of 11x11 km. The mapping was based on monitoring data for concentrations of base cations in air and precipitation in the Nordic and surrounding countries.The influence of base cation deposition in the calculation of critical loads and their exceedance as well as for the dynamic modelling of recovery processes was analysed and base cation deposition was found to be of significant importance. For dynamic modelling, the influence of base cation deposition is less important when using models, which are calibrated with monitoring data. However, in prognoses for the future, it is still very with accurate estimates of the base cation deposition. The procedure for mapping base cation deposition proposed in this project represents an improvement with respect to many previous mapping exercises, because it includes both wet and dry estimates of base cation deposition, and because it handles the decreasing sea salt gradients from the coast towards inland. It is recommended in the report to use the experiences from this Nordic mapping activitiy to initiate a process to compile necessary monitoring and emission data in order to carry out a mapping procedure of base cation deposition at European level.
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| 9. |
- Persson, Anders, et al.
(författare)
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Samfundet som konstant, samfundet som variabel - retfærdiggørelse af læring som magtproblem (e-bok)
- 2013
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Ingår i: Læring - en status (e-bok). - 8779553583 ; , s. 57-82
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Bokkapitel (refereegranskat)abstract
- I antologibidraget visas att lärande, eller kanske snarare deltagande i olika former av utbildning, rättfärdigas på olika sätt beroende på om de som utbildas är barn eller vuxna. Rättfärdigandet sker genom retoriska konstruktioner av samhället som närmast kan ses som motsatser: barnens skolgång rättfärdigas genom att samhället konstrueras som en, åtminstone värdemässig, konstant; vuxnas deltagande i utbildning rättfärdigas å andra sidan genom att samhället konstrueras som en variabel i ständig och omvälvande förändring. Vad ska vi då ha en sådan kunskap om rättfärdigande av utbildning till? Framförallt kan den kunskapen användas i en kritisk reflektion över den idag ymniga utbildningsretoriken.
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| 10. |
- Persson, Anders, et al.
(författare)
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Samfundet som konstant, samfundet som variabel - retfärdiggörelse af läring som magtproblem
- 2005
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Ingår i: Läring - en status. - 8779553583 ; , s. 57-82
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Bokkapitel (refereegranskat)abstract
- I antologibidraget visas att lärande, eller kanske snarare deltagande i olika former av utbildning, rättfärdigas på olika sätt beroende på om de som utbildas är barn eller vuxna. Rättfärdigandet sker genom retoriska konstruktioner av samhället som närmast kan ses som motsatser: barnens skolgång rättfärdigas genom att samhället konstrueras som en, åtminstone värdemässig, konstant; vuxnas deltagande i utbildning rättfärdigas å andra sidan genom att samhället konstrueras som en variabel i ständig och omvälvande förändring. Vad ska vi då ha en sådan kunskap om rättfärdigande av utbildning till? Framförallt kan den kunskapen användas i en kritisk reflektion över den idag ymniga utbildningsretoriken.
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| 11. |
- Tatsuno, Hideyuki, et al.
(författare)
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Hot Branching Dynamics in a Light-Harvesting Iron Carbene Complex Revealed by Ultrafast X-ray Emission Spectroscopy
- 2020
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Ingår i: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:1, s. 364-372
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Tidskriftsartikel (refereegranskat)abstract
- Iron N-heterocyclic carbene (NHC) complexes have received a great deal of attention recently because of their growing potential as light sensitizers or photocatalysts. We present a sub-ps X-ray spectroscopy study of an FeIINHC complex that identifies and quantifies the states involved in the deactivation cascade after light absorption. Excited molecules relax back to the ground state along two pathways: After population of a hot 3MLCT state, from the initially excited 1MLCT state, 30 % of the molecules undergo ultrafast (150 fs) relaxation to the 3MC state, in competition with vibrational relaxation and cooling to the relaxed 3MLCT state. The relaxed 3MLCT state then decays much more slowly (7.6 ps) to the 3MC state. The 3MC state is rapidly (2.2 ps) deactivated to the ground state. The 5MC state is not involved in the deactivation pathway. The ultrafast partial deactivation of the 3MLCT state constitutes a loss channel from the point of view of photochemical efficiency and highlights the necessity to screen transition-metal complexes for similar ultrafast decays to optimize photochemical performance.
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| 12. |
- Watanabe, Takeshi, et al.
(författare)
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Nocebo response in dentistry : A systematic review and meta-analysis of adverse events in analgesic trials of third molar removal
- 2023
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 50:4, s. 332-342
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Forskningsöversikt (refereegranskat)abstract
- BackgroundThe nocebo response refers to the phenomenon where non-specific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Non-specific factors are also likely to influence AE occurrence following administration of active pharmacological treatments. ObjectiveThis meta-analysis aimed to estimate the nocebo response in dentistry by assessing the AEs prevalence in placebo- and active arms of randomised controlled trials (RCTs) assessing analgesic treatment following third molar (M3) surgery. MethodsA systematic search was performed in PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies had to report the number of patients experiencing at least one drug-related AE (patients with AE >= 1) separately for the active and placebo arms. The proportion of patients with AE >= 1 and drug-related dropouts were pooled, and risk differences (RDs) between patients in the placebo- and active arm were calculated. ResultsIn 50 independent RCTs of 47 identified articles, the pooled rates of patients with AE >= 1 were 22.8% in the placebo arm and 20.6% in the active arm. The pooled rates of drug-related dropout were 0.24% in the placebo arm and 0.08% in the active arm. There were no significant RDs in patients with AE >= 1 and drug-related dropouts. ConclusionThese results show that patients in the placebo arm reported AEs to the same extent as patients receiving active treatment, suggesting that most AEs in analgesic medication following M3 surgery may be attributed to the nocebo phenomenon.
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