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- Saliba-Gustafsson, P., et al.
(författare)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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- Galluzzi, L, et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Forskningsöversikt (refereegranskat)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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- Sagrado Garcia, I. C., et al.
(författare)
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Neutron production in neutron-induced reactions at 96 MeV on (56)Fe and (208)Pb
- 2011
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 84:4, s. 044619-
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Tidskriftsartikel (refereegranskat)abstract
- Double-differential cross sections for neutron production were measured in 96-MeV neutron-induced reactions at The Svedberg Laboratory in Uppsala, Sweden. Measurements for Fe and Pb targets were performed using two independent setups: DECOI-DEMON, time-of-flight telescope dedicated to the detection of emitted neutrons with energies between a few and 50 MeV and CLODIA-SCANDAL device devoted to measuring emitted neutrons with energies above 40 MeV. Double-differential cross sections were measured for an angular range between 15 and 98 deg and with low-energy thresholds (approximate to 2 MeV). Angular and energy distributions and total neutron emission cross sections have been obtained from those measurements. Results have been compared with predictions given by different models included in several transport codes (MCNPX, GEANT, TALYS, PHITS, and DYWAN) and with other experimental data (the EXFOR database).
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- Badiola, N, et al.
(författare)
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Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12.
- 2011
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Disturbance of calcium homeostasis and accumulation of misfolded proteins in the endoplasmic reticulum (ER) are considered contributory components of cell death after ischemia. However, the signal-transducing events that are activated by ER stress after cerebral ischemia are incompletely understood. In this study, we show that caspase-12 and the PERK and IRE pathways are activated following oxygen-glucose deprivation (OGD) of mixed cortical cultures or neonatal hypoxia-ischemia (HI). Activation of PERK led to a transient phosphorylation of eIF2α, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2α-directed phosphatase). Interestingly, the upregulation of ATF4 did not lead to an increase in the levels of CHOP. Additionally, IRE1 activation was mediated by the increase in the processed form of xbp1, which would be responsible for the observed expression of edem2 and the increased levels of the chaperones GRP78 and GRP94. We were also able to detect caspase-12 proteolysis after HI or OGD. Processing of procaspase-12 was mediated by NMDA receptor and calpain activation. Moreover, our data suggest that caspase-12 activation is independent of the unfolded protein response activated by ER stress.
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- Dangtip, S, et al.
(författare)
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A facility for measurements of nuclear cross sections for fast neutron cancer therapy
- 2000
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Ingår i: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 452:3, s. 484-504
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Tidskriftsartikel (refereegranskat)abstract
- A facility for measurements of neutron-induced double-differential light-ion production cross-sections, for application within. e.g.. fast neutron cancer therapy, is described. The central detection elements are three-detector telescopes consisting of two
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- Hangen, E, et al.
(författare)
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A brain-specific isoform of mitochondrial apoptosis-inducing factor: AIF2.
- 2010
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 17:7, s. 1155-66
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Tidskriftsartikel (refereegranskat)abstract
- Apoptosis-inducing factor (AIF) has important supportive as well as potentially lethal roles in neurons. Under normal physiological conditions, AIF is a vital redox-active mitochondrial enzyme, whereas in pathological situations, it translocates from mitochondria to the nuclei of injured neurons and mediates apoptotic chromatin condensation and cell death. In this study, we reveal the existence of a brain-specific isoform of AIF, AIF2, whose expression increases as neuronal precursor cells differentiate. AIF2 arises from the utilization of the alternative exon 2b, yet uses the same remaining 15 exons as the ubiquitous AIF1 isoform. AIF1 and AIF2 are similarly imported to mitochondria in which they anchor to the inner membrane facing the intermembrane space. However, the mitochondrial inner membrane sorting signal encoded in the exon 2b of AIF2 is more hydrophobic than that of AIF1, indicating a stronger membrane anchorage of AIF2 than AIF1. AIF2 is more difficult to be desorbed from mitochondria than AIF1 on exposure to non-ionic detergents or basic pH. Furthermore, AIF2 dimerizes with AIF1, thereby preventing its release from mitochondria. Conversely, it is conceivable that a neuron-specific AIF isoform, AIF2, may have been 'designed' to be retained in mitochondria and to minimize its potential neurotoxic activity.Cell Death and Differentiation advance online publication, 29 January 2010; doi:10.1038/cdd.2009.211.
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| 34. |
- Hildebrand, Angelica, et al.
(författare)
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Elastic Neutron Scattering at 96 MeV
- 2004
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Ingår i: Proc. Int. Conf. on Nuclear Data for Science and Technology.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 35. |
- Hildebrand, A, et al.
(författare)
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Elastic neutron scattering at 96 MeV
- 2005
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Ingår i: Proc. of the Int. Conf. on Nuclear Data for Science and Technology: Santa Fé, New Mexico, USA, September 26-October 1, 2004. ; , s. 853-
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Konferensbidrag (refereegranskat)
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- Maeda, Y., et al.
(författare)
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Differential cross section and analyzing power measurements for (n)over-right-arrowd elastic scattering at 248 MeV
- 2007
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 76:1, s. 014004-
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Tidskriftsartikel (refereegranskat)abstract
- The differential cross sections and vector analyzing powers for nd elastic scattering at E-n=248 MeV were measured for 10 degrees-180 degrees in the center-of-mass (c.m.) system. To cover the wide angular range, the experiments were performed separately by using two different setups for forward and backward angles. The data are compared with theoretical results based on Faddeev calculations with realistic nucleon-nucleon (NN) forces such as AV18, CD Bonn, and Nijmegen I and II, and their combinations with the three-nucleon forces (3NFs), such as Tucson-Melbourne 99 (TM99), Urbana IX, and the coupled-channel potential with Delta-isobar excitation. Large discrepancies are found between the experimental cross sections and theory with only 2N forces for theta(c.m.)>90 degrees. The inclusion of 3NFs brings the theoretical cross sections closer to the data but only partially explains this discrepancy. For the analyzing power, no significant improvement is found when 3NFs are included. Relativistic corrections are shown to be small for both the cross sections and the analyzing powers at this energy. For the cross sections, these effects are mostly seen in the very backward angles. Compared with the pd cross section data, quite significant differences are observed at all scattering angles that cannot be explained only by the Coulomb interaction, which is usually significant at small angles.
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| 38. |
- Murin, Y, et al.
(författare)
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SEE-Related Studies at CELSIUS
- 2005
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Ingår i: Proc. 6th Int. Conf. on Nuclear Physics at Storage Rings (STORI’05), Bonn. ; , s. 153-
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Konferensbidrag (refereegranskat)
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