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- Fossat, P., et al.
(författare)
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Knockdown of L calcium channel subtypes : differential effects in neuropathic pain
- 2010
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 30:3, s. 1073-1085
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Forskningsöversikt (refereegranskat)abstract
- The maintenance of chronic pain states requires the regulation of gene expression, which relies on an influx of calcium. Calcium influx through neuronal L-type voltage-gated calcium channels (LTCs) plays a pivotal role in excitation-transcription coupling, but the involvement of LTCs in chronic pain remains unclear. We used a peptide nucleic acid (transportan 10-PNA conjugates)-based antisense strategy to investigate the role of the LTC subtypes Ca(V)1.2 and Ca(V)1.3 in long-term pain sensitization in a rat model of neuropathy (spinal nerve ligation). Our results demonstrate that specific knockdown of Ca(V)1.2 in the spinal dorsal horn reversed the neuropathy-associated mechanical hypersensitivity and the hyperexcitability and increased responsiveness of dorsal horn neurons. Intrathecal application of anti-Ca(V)1.2 siRNAs confirmed the preceding results. We also demonstrated an upregulation of Ca(V)1.2 mRNA and protein in neuropathic animals concomitant to specific Ca(V)1.2-dependent phosphorylation of the cAMP response element (CRE)-binding protein (CREB) transcription factor. Moreover, spinal nerve ligation animals showed enhanced transcription of the CREB/CRE-dependent gene COX-2 (cyclooxygenase 2), which also depends strictly on Ca(V)1.2 activation. We propose that L-type calcium channels in the spinal dorsal horn play an important role in pain processing, and that the maintenance of chronic neuropathic pain depends specifically on channels comprising Ca(V)1.2.
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| 2. |
- Tremblin, P., et al.
(författare)
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Site testing for submillimetre astronomy at Dome C, Antarctica
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 535:A112
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Over the past few years a major effort has been put into the exploration of potential sites for the deployment of submillimetre astronomical facilities. Amongst the most important sites are Dome C and Dome A on the Antarctic Plateau, and the Chajnantor area in Chile. In this context, we report on measurements of the sky opacity at 200 mu m over a period of three years at the French-Italian station, Concordia, at Dome C, Antarctica. We also present some solutions to the challenges of operating in the harsh polar environment.Methods. The 200-mu m atmospheric opacity was measured with a tipper. The forward atmospheric model MOLIERE (Microwave Observation LIne Estimation and REtrieval) was used to calculate the atmospheric transmission and to evaluate the precipitable water vapour content (PWV) from the observed sky opacity. These results have been compared with satellite measurements from the Infrared Atmospheric Sounding Interferometer (IASI) on Metop-A, with balloon humidity sondes and with results obtained by a ground-based microwave radiometer (HAMSTRAD). In addition, a series of experiments has been designed to study frost formation on surfaces, and the temporal and spatial evolution of thermal gradients in the low atmosphere.Results. Dome C offers exceptional conditions in terms of absolute atmospheric transmission and stability for submillimetre astronomy. Over the austral winter the PWV exhibits long periods during which it is stable and at a very low level (0.1 to 0.3 mm). Higher values (0.2 to 0.8 mm) of PWV are observed during the short summer period. Based on observations over three years, a transmission of around 50% at 350 mu m is achieved for 75% of the time. The 200-mu m window opens with a typical transmission of 10% to 15% for 25% of the time.Conclusions. Dome C is one of the best accessible sites on Earth for submillimetre astronomy. Observations at 350 or 450 mu m are possible all year round, and the 200-mu m window opens long enough and with a sufficient transparency to be useful. Although the polar environment severely constrains hardware design, a permanent observatory with appropriate technical capabilities is feasible. Because of the very good astronomical conditions, high angular resolution and time series (multi-year) observations at Dome C with a medium size single dish telescope would enable unique studies to be conducted, some of which are not otherwise feasible even from space.
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