The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.

Le livre de messire Lancelot du Lac" : présentation matérielle et composition des manuscrits arthuriens de Jacques d'Armagnac (BNF fr. 117-120 et 113-116)

L'organisation des manuscrits arthuriens du cycle du Graal de Jacques d'Armagnac (BNF fr. 117-120 qu'il a hérité de son arrière-grand-père le duc Jean de Berry et dont il a fait retoucher les peintures et BNF fr. 113-116 qu'il a fait exécuter entre 1470 et 1475), leur agencement, leur illustration et leurs subdivisions sont un indice précieux de la conception et de la réception de ces compilations. Ils soulignent l'effort de constitution d'un ensemble romanesque cohérent centré sur la figure de Lancelot.

The 2010-2011 drought in the Horn of Africa in ECMWF reanalysis and seasonal forecast products

This study evaluates the use of European Centre for Medium-Range Weather Forecasts (ECMWF) products in monitoring and forecasting drought conditions during the recent 2010–2011 drought in the Horn of Africa (HoA). The region was affected by a precipitation deficit in both the October–December 2010 and March–May 2011 rainy seasons. These anomalies were captured by the ERA-Interim reanalysis (ERAI), despite its limitations in representing the March–May interannual variability. Soil moisture anomalies of ERAI also identified the onset of the drought condition early in October 2010 with a persistent drought still present in September 2011. This signal was also evident in normalized difference vegetation index (NDVI) remote sensing data. The precipitation deficit in October–December 2010 was associated with a strong La Niña event. The ECMWF seasonal forecasts for the October–December 2010 season predicted the La Niña event from June 2010 onwards. The forecasts also predicted a below-average October–December rainfall, from July 2010 onwards. The subsequent March–May rainfall anomaly was only captured by the new ECWMF seasonal forecast system in the forecasts starting in March 2011. Our analysis shows that a recent (since 1999) drying in the region during the March–May season is captured by the new ECMWF seasonal forecast system and is consistent with recently published results. The HoA region and its population are highly vulnerable to future droughts, thus global monitoring and forecasting of drought, such as that presented here, will become increasingly important in the future. Copyright © 2012 Royal Meteorological Society

AP-UV-MALDI mit flüssigen Matrizes: stabile Ionenausbeuten von mehrfach geladenen Peptid- und Proteinionen für die empfindliche Massenspektrometrie

In der biologischen Massenspektrometrie (MS) werden überwiegend zwei Ionisationstechniken für die Analyse von grçßeren Biomolekfürlen wie Polypeptiden eingesetzt. Dies sind die Nano-Elektrospray-Ionisation[1,2] (nanoESI) und die matrixunterstfürtzte Laserdesorption/-ionisation[3, 4] (MALDI). Beide Techniken werden als „sanft“ bezeichnet, weil sie die Desorption und Ionisation von intakten Analytmolekfürlen und damit ihre erfolgreiche massenspektrometrische Analyse erlauben. Einer der wichtigsten Unterschiede zwischen diesen beiden Ionisationstechniken liegt in ihrer F�higkeit, mehrfach geladene Ionen zu erzeugen. MALDI erzeugt typischerweise einfach geladene Peptidionen, w�hrend nano- ESI leicht mehrfach geladene Ionen produziert, sogar für Peptide mit einer Masse von weniger als 1000 Da. Die Erzeugung von hoch geladenen Ionen ist wünschenswert, da dies die Verwendung von Massenanalysatoren wie Ionenfallen (inkl. Orbitraps) und Hybrid-Quadrupolinstrumenten ermçglicht, die typischerweise nur einen begrenzten m/z- Bereich (<2000–4000) bieten. Hohe Ladungszust�nde ermçglichen auch die Aufnahme von informativeren Fragmentionenspektren, wenn Methoden wie die kollisionsinduzierte Dissoziation (CID), die Elektroneneinfang-Dissoziation (ECD) und die Elektronentransfer-Dissoziation (ETD) in Kombination mit der Tandem-MS (MS/MS) verwendet werden.