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Sökning: WFRF:(Käll Anna)

  • Resultat 1-10 av 28
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  • Schober, Florian A., et al. (författare)
  • The one-carbon pool controls mitochondrial energy metabolism via complex I and iron-sulfur clusters
  • 2021
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Induction of the one-carbon cycle is an early hallmark of mitochondrial dysfunction and cancer metabolism. Vital intermediary steps are localized to mitochondria, but it remains unclear how one-carbon availability connects to mitochondrial function. Here, we show that the one-carbon metabolite and methyl group donor S-adenosylmethionine (SAM) is pivotal for energy metabolism. A gradual decline in mitochondrial SAM (mitoSAM) causes hierarchical defects in fly and mouse, comprising loss of mitoSAM-dependent metabolites and impaired assembly of the oxidative phosphorylation system. Complex I stability and iron-sulfur cluster biosynthesis are directly controlled by mitoSAM levels, while other protein targets are predominantly methylated outside of the organelle before import. The mitoSAM pool follows its cytosolic production, establishing mitochondria as responsive receivers of one-carbon units. Thus, we demonstrate that cellular methylation potential is required for energy metabolism, with direct relevance for pathophysiology, aging, and cancer.
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3.
  • Andersson, Gerhard, et al. (författare)
  • Free choice of treatment content, support on demand and supervision in internet-delivered CBT for adults with depression : A randomized factorial design trial
  • 2023
  • Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 162
  • Tidskriftsartikel (refereegranskat)abstract
    • Even if much is known regarding the effects of internet-delivered cognitive behaviour therapy (ICBT) for depression there are several topics that have not been studied. In this factorial design trial with 197 participants we investigated if clients in ICBT could select treatment modules themselves based on a selection of 15 tailored treatment modules developed for use in ICBT for depression. We contrasted this against clinician-tailored module selection. We also investigated if support on demand (initiated by the client) could work as well as scheduled support. Finally, we tested if clients that were mentioned in supervision would improve more than clients not mentioned (with the exception of acute cases). The treatment period lasted for 10 weeks, and we measured effects at post-treatment and two-year follow-up. Measures of depression and secondary outcomes were collected at pre-treatment, post-treatment and two-year follow-up. Overall, within-group effects were large across con-ditions (e.g., d = 1.73 on the BDI-II). We also found a small but significant difference in favour of self-tailored treatment over clinician-tailored (d = 0.26). Within-group effects for the secondary measures were all moderate to large including a test of knowledge about CBT. The other two contrasts "support on demand" and "supervision" yielded mostly non-significant differences, with the exception of a larger dropout rate in the support on demand condition. There were few negative effects (2.2%). Effects were largely maintained at a two-year follow-up. We conclude that clients can choose treatment modules and that support on demand may work. The role of su-pervision is not yet clear as advice can be transferred across clients.
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  • Ahrén, Maria, et al. (författare)
  • Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
  • 2010
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
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8.
  • Bodvard, Kristofer, 1981, et al. (författare)
  • The Yeast Transcription Factor Crz1 Is Activated by Light in a Ca2+/Calcineurin-Dependent and PKA-Independent Manner
  • 2013
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Light in the visible range can be stressful to non-photosynthetic organisms. The yeast Saccharomyces cerevisiae has earlier been reported to respond to blue light via activation of the stress-regulated transcription factor Msn2p. Environmental changes also induce activation of calcineurin, a Ca2+/calmodulin dependent phosphatase, which in turn controls gene transcription by dephosphorylating the transcription factor Crz1p. We investigated the connection between cellular stress caused by blue light and Ca2+ signalling in yeast by monitoring the nuclear localization dynamics of Crz1p, Msn2p and Msn4p. The three proteins exhibit distinctly different stress responses in relation to light exposure. Msn2p, and to a lesser degree Msn4p, oscillate rapidly between the nucleus and the cytoplasm in an apparently stochastic fashion. Crz1p, in contrast, displays a rapid and permanent nuclear localization induced by illumination, which triggers Crz1p-dependent transcription of its target gene CMK2. Moreover, increased extracellular Ca2+ levels stimulates the light-induced responses of all three transcription factors, e. g. Crz1p localizes much quicker to the nucleus and a larger fraction of cells exhibits permanent Msn2p nuclear localization at higher Ca2+ concentration. Studies in mutants lacking Ca2+ transporters indicate that influx of extracellular Ca2+ is crucial for the initial stages of light-induced Crz1p nuclear localization, while mobilization of intracellular Ca2+ stores appears necessary for a sustained response. Importantly, we found that Crz1p nuclear localization is dependent on calcineurin and the carrier protein Nmd5p, while not being affected by increased protein kinase A activity (PKA), which strongly inhibits light-induced nuclear localization of Msn2/4p. We conclude that the two central signalling pathways, cAMP-PKA-Msn2/4 and Ca2+-calcineurin-Crz1, are both activated by blue light illumination.
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9.
  • Casini, Michele, et al. (författare)
  • Hypoxic areas, density-dependence and food limitation drive the body condition of a heavily exploited marine fish predator
  • 2016
  • Ingår i: Royal Society Open Science. - : The Royal Society. - 2054-5703. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Investigating the factors regulating fish condition is crucial in ecology and the management of exploited fish populations. The body condition of cod (Gadus morhua) in the Baltic Sea has dramatically decreased during the past two decades, with large implications for the fishery relying on this resource. Here, we statistically investigated the potential drivers of the Baltic cod condition during the past 40 years using newly compiled fishery-independent biological data and hydrological observations. We evidenced a combination of different factors operating before and after the ecological regime shift that occurred in the Baltic Sea in the early 1990s. The changes in cod condition related to feeding opportunities, driven either by density-dependence or food limitation, along the whole period investigated and to the fivefold increase in the extent of hypoxic areas in the most recent 20 years. Hypoxic areas can act on cod condition through different mechanisms related directly to species physiology, or indirectly to behaviour and trophic interactions. Our analyses found statistical evidence for an effect of the hypoxia-induced habitat compression on cod condition possibly operating via crowding and density-dependent processes. These results furnish novel insights into the population dynamics of Baltic Sea cod that can aid the management of this currently threatened population.
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10.
  • Engström, Maria, et al. (författare)
  • High Proton Relaxivity for Gadolinium Oxide Nanoparticles
  • 2006
  • Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 19:4, s. 180-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The objective of the present study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm) Gd2O3 nanocrystals.Materials and methods: Gd2O3 nanocrystals were synthesized by a colloidal method and capped with diethylene glycol (DEG). The oxidation state of Gd2O3 was confirmed by X-ray photoelectron spectroscopy. Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements were performed in aqueous solutions and cell culture medium (RPMI).Results: Results showed a considerable relaxivity increase for the Gd2O3–DEG particles compared to Gd-DTPA. Both T 1 and T 2 relaxivities in the presence of Gd2O3–DEG particles were approximately twice the corresponding values for Gd–DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low concentrations was predicted for the nanoparticle solutions, using experimental data to simulate a T1-weighted spin echo sequence.Conclusion: The study indicates the possibility of obtaining at least doubled relaxivity compared to Gd–DTPA using Gd2O3–DEG nanocrystals as contrast agent. The high T 1 relaxation rate at low concentrations of Gd2O3 nanoparticles is very promising for future studies of contrast agents based on gadolinium-containing nanocrystals.
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