A British man was killed and five other people were injured after several heavy branches fell from a tree onto a crowd during a music festival in the south of France was cancelled after the branches fell late afternoon on Friday (June 7) The festival was due to take place in the les jardins de l’Évêché next to the historic Saint Alain de Lavaur Cathedral The branches fell onto an area where around 15 people were awaiting the start of the festival Most of them had time to jump out of the way one of whom - a 54-year-old British man who reportedly lived in Ariège - severely The Red Cross immediately scrambled to reach the injured people under the debris Read more: Family may have to move as cannot uproot ‘dangerous’ tree in France  “I was under the tree,” festival goer Robert Mosniertold local newspaper Le Tarn Libre The people sitting in front of me were not so lucky.  “We rushed to get them free from the leaves but the two branches were really heavy and we needed several people to lift them.”  “I have expressed our profound compassion to the family in this difficult time I hope that all the injured people recover quickly from this terrible tragedy,” he told Le Tarn Libre “Never has such a dramatic event happened in our town.” The mayor said that the tree’s branches had been cut back only several months ago “The accident was impossible to foresee - the branches that fell were green and nothing indicated that they could fall,” he added The group compared two popular EV models and considered six specialist EV offers The prefectural ban is set to remain in place until at least December 31 The geographical spread of Canadian nationals follows a similar pattern to Americans This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page France - Mark Cavendish nearly lost a shoe in the final stretch but kept his cool to win a rainy 11th stage of the Tour de France in a mass sprint Wednesday easily beating Andre Greipel of Germany at the line to seize the leading sprinter's green jersey French rider Thomas Voeckler kept the race leader's yellow jersey after the 104.1-mile trek from Blaye-les-Mines to Lavaur Cavendish made the most of the last stage designed for sprinters before the race reaches the Pyrenees to claim his 18th stage win at the Tour It's the most beautiful jersey in the world," said Cavendish who got an assist from HTC-Highroad teammate Mark Renshaw Cavendish's efforts were almost ruined toward the end when he hit the front wheel of Frenchman Romain Feillu's bike "There were 10 of us close together and my shoe banged into his front wheel," Cavendish said "My foot technically came out of the shoe - I had to reach down and slide the ratchet and redo it with 600 meters to go I was lucky there were no swerves in the peloton who took the green jersey from Philippe Gilbert of Belgium Despite his impressive tally of stage wins at the Grande Boucle the coveted sprint champion's jersey has so far eluded the 26-year-old Cavendish 11 points behind Alessandro Petacchi of Italy and second by 10 points to two-time sprint champion Thor Hushovd in 2009 Cavendish pulled out before the Alpine stages in 2008 to conserve energy for the Olympics Voeckler said he was expecting to lose his yellow jersey during today's 12th stage which takes the riders on the first of a three-day trek across the Pyrenees with a punishing 131-mile ride over the legendary col du Tourmalet and finishing on top of Luz-Ardiden The stage is likely to be a key moment of the race a 6.15-mile ascent with an average gradient of 7.5 percent With their minds already on the big mountain battle to come three-time champion Alberto Contador and his rivals stayed comfortably in the pack and didn't take any risks who has been hampered by crashes this year trails Cadel Evans of Australia and Andy Schleck of Luxembourg by 1:41 and 1:30 which might be more united than Contador's one," Voeckler said and his teammates are doing an amazing job for him." The stage came alive after 8 miles when six breakaway riders - Ruben Perez Moreno Lars Boom and Andriy Grivko - pulled away under a light rain The bunch started the chase before the intermediate sprint halfway through the stage where Cavendish took seventh place ahead of Rojas HTC-Highroad manager Bob Stapleton said intermediate sprints tired out Cavendish this year after race organizers changed the rules There is only one intermediate sprint in each stage with 20 points available to the rider who wins - as opposed to six points in previous years when there were more intermediate sprints Metrics details a synthetic glutamate analog that provokes an increase in ambient glutamate through the blockade of glutamate uptake and the stimulation of its release In summary, present data demonstrate that the noble gas xenon has the ability to provide protection and to exert trophic or restorative effects for AD vulnerable neurons (Figure 1). Noticeably, some of the effects of xenon were improved by the AD medication memantine. Altogether, these observations are an indication that the noble gas may have potential utility for AD treatment. Simplified scheme describing the effects of xenon on cortical neurons and basal forebrain cholinergic neurons (a) Protective effects of xenon (Xe) in cortical cultures treated with PDC to generate sustained Xenon (75%) afforded robust but partial protection in this experimental setting This effect was improved by a co-treatment with the noncompetitive NMDA receptor antagonist memantine (MEM) at a concentration that had no protective effect in itself (low MEM) This suggests that xenon and MEM acted cooperatively to promote neuronal survival virtually all cortical neurons were rescued Note that a similar response profile was observed when MEM was replaced with the NMDA receptor antagonist (b) Xenon also stimulated cholinergic traits and promoted the morphological differentiation of cholinergic neurons in basal forebrain septal cultures Banks P et al Anesthesiology 2010; 112: 614–622 Winkler DA et al Pharmacol Ther 2016; 160: 44–64 Liu LT et al J Phys Chem B 2010; 114: 9010–9016 Vaarmann A et al Cell Death Dis 2013; 4: e455 Talantova M et al Proc Natl Acad Sci USA 2013; 110: E2518–E2527 McShane R et al Cochrane Database Syst Rev 2006: CD003154 Lavaur J et al Cell Death Discov 2016; 2: 16018 Andrade-Moraes CH et al Brain 2013; 136: 3738–3752 Strada O et al Proc Natl Acad Sci USA 1992; 89: 9549–9553 Liu X et al J Neurophysiol 2008; 99: 2443–2455 Download references The research leading to these results was supported by program Investissements d’Avenir (ANR-10-IAIHU-06) and Translational Research Infrastructure for Biotherapies in Neurosciences (ANR-11-INBS-0011-NeurATRIS) This study was funded by a grant from Air Liquide Santé International We gratefully acknowledge the operational support of David Akbar from the CELIS cell culture core facility and the contribution of Air Liquide staff members Institut National de la Santé et de la Recherche Médicale Institut du Cerveau et de la Moelle épinière DLN is recipient of a CIFRE fellowship co-funded by Association Nationale de la Recherche et de la Technologie (ANRT) and Air Liquide Healthcare The remaining authors declare no conflict of interest Reprints and permissions Download citation DOI: https://doi.org/10.1038/cddis.2016.86 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Cavendish gives Greipel a gorilla hug (Image credit: Bettini Photo)Andre Greipel (Omega Pharma-Lotto) was over the moon with his stage win(Image credit: Bettini Photo)The André Greipel-Mark Cavendish duel has been a fascinating subplot to this year’s Tour de France not least because the bitterness that marked the pair’s time together at Highroad appears to have been tempered since Greipel’s departure from the team last winter Cavendish gracious after defeat by Greipel Greipel not looking for revenge after sprint success "We tried again today and the team did a great job," Greipel told reporters huddled around the Omega Pharma-Lotto team bus in Lavaur after the finish He singled out Jurgen Roelandts for particular praise for his efforts in leading him out but complained at what he perceived to be the careless sprinting of Feillu in the finale but I had some problems with Feillu," Greipel said because it was the first time that Jurgen and I found each other in the sprint." Greipel accused Feillu of switching wheels several times in the breathless run-in to Lavaur and showing little consideration for the safety of his fellow sprinters The German was particularly aggrieved by Feillu’s attempts to latch onto Roedlandt’s wheel in the final kilometre "Romain Feillu did a crazy sprint and he just didn’t care," Greipel claimed "He needs to choose a wheel but he changes wheel every 50 metres It’s pretty dangerous when somebody in the bunch is going crazy to get the right spot." and insisted to Sporza that he had done nothing wrong in the final throes of the day’s stage "I jumped on to Roedlandt’s wheel because if you have nobody to lead you out in the sprint you have to jump from wheel to wheel," Feillu said who has been struggled with tendinitis in this Tour subsequently revealed that he is on the point of abandoning the race ahead of its entry into the Pyrenees if anything it’s getting worse and worse," Feillu told rmc.fr I’m leaving the Tour with some placings but without winning I’ve simply been missing a bit of luck Knight was known as the "Dog Listener." Tour de France 2011 stage 11 photo gallery by Graham Watson>> Mark Cavendish moved into the green jersey for the first time in the Tour de France since the 2009 race after picking up his third stage victory of this year's edition in Lavaur this afternoon. Cav started the day off in third place in the standings, but having taken nine points in the intermediate sprint he then added another 45 to his tally after picking up his 18th Tour stage victory. Yesterday's winner Andre Greipel beat Tyler Farrar into second, with Cav's green jersey rivals Jose Rojas finishing in seventh, while overnight leader Philippe Gilbert did not contest the sprint finish. Speaking afterwards, Cav said: "I just went. I said I'd kick and when I kick normally I get a gap. Acceleration is the strongest part of my sprint.... I hit, and I got the gap." The Brit last wore the green jersey on stage 12 of the 2009 Tour, before losing it to Thor Hushovd, who kept it to the end of the race. Thomas Voeckler (Europcar) remains in the yellow jersey, although he is expected to lose that tomorrow on the way to Luz-Ardiden. The latest race content, interviews, features, reviews and expert buying guides, direct to your inbox! A crash free and quiet dayThe peloton was reduced to 177 riders this morning after John Gadret (Ag2r-La Mondiale) failed to take the start in Blaye-les-Mines, citing fatigue from the Giro d'Italia, in which he finished fourth overall. A six-man breakaway - consisting of Ruben Perez (Euskaltel), Lars Boom (Rabobank), Andriy Grivko (Astana), Mickael Delage (FDJ), Tristan Valentin (Cofidis) and Jimmy Engoulvent (Saur-Sojasun) - escaped early on in the stage, although like yesterday's breakaway, the peloton wanted to keep control of affairs and never let their advantage balloon out of control. Delage took the maximum points on offer at the sprint in Gaillac, but notably Cavendish beat Rojas, Greipel and Gilbert to win the bunch gallop for seventh, thus adding nine points to his tally. This meant that, provided Cav won the stage, he could take the green jersey if Rojas finished third or lower, and Gilbert couldn't place in the top seven at the finish. Their escapees' advantage came down as slowly as it went up, and their chances of staying away were bolstered by a downpour that struck within the final 30km. Despite the heavy rain, which continued after the finish, no crashes were reported throughout the stage. Responding to the inclement weather, initially the pace in the peloton decreased, and going into the final 10km the six leaders, who continued to work cohesively, had a gap of over a minute. The bunch failed to make any inroads into their lead between the 8 and 7km to go mark, although the break were hovering at 14s with 5km remaining. At that point, Boom - one of the strongest time trialists in the race - attacked, and none of his breakaway companions were able to follow his explosive move. The remnants of the group were reeled in with 3km to go, before Boom was caught with 2km remaining. However, the hard work in bringing the race back together had meant Cavendish only had loyal servant Mark Renshaw for support. Luckily, HTC-Highroad were able to benefit from the work done by Garmin-Cervélo, who were trying to set Farrar up for his second stage win in the Tour. Cavendish clipped Romain Feillu on the run-in, forcing the Brit to adjust his shoes, but ultimately once the race for the line began, nothing was going to stop Cavendish. Tour de France 2011, stage 11 - Blaye les Mines-Lavaur, 167.5km 1. Mark Cavendish (GB) HTC-Highroad in 3-46-07 10. William Bonnet (Fra) FDJ all same time 1. Thomas Voeckler (Fra) Europcar in 42-06-32 2. Luis-Leon Sanchez (Spa) Rabobank at 1-49 4. Frank Schleck (Lux) Leopard-Trek at 2-29 5. Andy Schleck (Lux) Leopard-Trek at 2-37 7. Peter Velits (Slo) HTC-Highroad at 2-28 8. Andreas Kloden (Ger) Radioshack at 2-43 9. Philippe Gilbert (Bel) Omega Pharma-Lotto at 2-55 10. Jakob Fuglsang (Den) Leopard-Trek at 3-08 Mark Cavendish wins his third stage and puts himself in the green jersey Tour de France 2011: Cycling Weekly's coverage index Greipel's first Tour stage win 'extra special' Greipel takes first win over Cav since HTC split Voeckler living the yellow jersey dream again Schlecks within striking distance of Tour's race lead Tour bans motorcyclist after Sorensen's crash Cavendish's race for the Tour green jersey Cavendish surprises with Tour stage win and press conference Tour de France 2011: Teams, riders, start list Stage 10: Greipel beats Cavendish in Tour stage 10 sprint Stage nine: Sanchez conquers day of crashes and climbs Stage eight: Costa wins first mountain stage of 2011 Tour Stage seven: Cavendish wins but Wiggins crashes out of Tour Stage six: Boasson Hagen takes Sky's first Tour de France win Stage four: Evans edges out Contador on the Mur-de-Bretagne Stage three: Farrar sprints to first Tour victory in Redon Stage two: Garmin win team time trial to put Hushovd in yellow Stage one: Gilbert blasts to victory as Tour gets off to spectacular start Video: Erik Zabel's role as Cavendish's sprint advisor Video: The ride of Philippe Gilbert at the Tour de France Stage eight photo gallery by Graham Watson Stage seven photo gallery by Graham Watson Stage three photo gallery by Graham Watson Tour de France 2011 team time trial training photo gallery by Andy Jones Tour de France 2011 team presentation by Andy Jones Tour de France 2011 team press conferences by Andy Jones Tour de France 2011 team presentation by Graham Watson Tour de France 2011 LIVE: CW's text coverage schedule Tour de France 2011: Archive articles1999 Tour de France stage two: Passage du Gois causes chaos British Eurosport Tour de France 2011 TV schedule Tour de France: The jerseys, what they are and what they mean Brits in the Tours: From Robinson to Wiggins Tour de France 2010: Cycling Weekly's coverage index Thank you for reading 20 articles this month* Join now for unlimited access Enjoy your first month for just £1 / $1 / €1 *Read 5 free articles per month without a subscription Try first month for just £1 / $1 / €1 Cycling Weekly and its team of expert journalists brings cyclists in-depth reviews extensive coverage of both professional and domestic racing as well as fitness advice and 'brew a cuppa and put your feet up' features Cycling Weekly serves its audience across a range of platforms from good old-fashioned print to online journalism Metrics details Noble gases such as xenon and argon have been reported to provide neuroprotection against acute brain ischemic/anoxic injuries we wished to evaluate the protective potential of these two gases under conditions relevant to the pathogenesis of chronic neurodegenerative disorders we established cultures of neurons typically affected in Alzheimer's disease (AD) pathology cortical neurons and basal forebrain cholinergic neurons and exposed them to L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) to generate sustained PDC caused a progressive loss of cortical neurons which was prevented substantially when xenon replaced nitrogen in the cell culture atmosphere Xenon acted downstream of the inhibitory and stimulatory effects elicited by PDC on glutamate uptake and efflux Neuroprotection by xenon was mimicked by two noncompetitive antagonists of NMDA glutamate receptors Each of them potentiated xenon-mediated neuroprotection when used at concentrations providing suboptimal rescue to cortical neurons but most surprisingly The survival-promoting effects of xenon persisted when NMDA was used instead of PDC to trigger neuronal death indicating that NMDA receptor antagonism was probably accountable for xenon’s effects An excess of glycine failed to reverse xenon neuroprotection thus excluding a competitive interaction of xenon with the glycine-binding site of NMDA receptors antioxidants such as Trolox and N-acetylcysteine reduced PDC-induced neuronal death but xenon itself lacked free radical-scavenging activity Cholinergic neurons were also rescued efficaciously by xenon in basal forebrain cultures xenon stimulated cholinergic traits and promoted the morphological differentiation of cholinergic neurons in these cultures Memantine reproduced some of these neurotrophic effects we demonstrate for the first time that xenon may have a therapeutic potential in AD We demonstrate for the first time that xenon can provide partial but sustained protection to cortical neurons undergoing neurodegeneration through mild excitotoxic stress These protective effects were mimicked and amplified by two noncompetitive NMDA glutamate receptor antagonists Xenon also provided robust protection to PDC-treated cholinergic neurons in septal cultures but quite unexpectedly it also exerted potent neurotrophic effects on these neurons Xenon but not argon is protective against neuronal death induced by PDC in cortical cultures (a) Survival rate of cortical neurons (MAP-2+ cells) in cultures exposed or not to PDC (3–100 μM) for 4 days under an atmosphere containing 75% N2 **P<0.01,***P<0.001 relative to cultures receiving a same concentration of PDC under N2 atmosphere (b) Survival of cortical neurons exposed to 30 μM PDC for 1 or 4 days in an atmosphere containing 75% N2 or 75% Xe ***P<0.001 relative to control cultures maintained under N2 atmosphere and ###P<0.001 relative to age-matched PDC-treated cultures under N2 atmosphere (c) Fluorescence digitized images illustrating the neuroprotective effects provided by a gas atmosphere containing 75% Xe (versus 75% N2) in cortical cultures exposed for 1 or 4 days to 30 μM of PDC we aimed to further characterize the neuroprotective effects of xenon Role of NMDA glutamate receptors in xenon-mediated neuroprotection (a) Survival rate of cortical neurons exposed to PDC (30 μM) for 4 days and treated concurrently or not with the NMDA receptor blocker memantine (MEM 10 μM) or the amino acid glycine (1 mM) under a gas atmosphere containing 75% N2 Some cultures treated with PDC were also placed under a gas atmosphere containing 75% Xe and treated with or without glycine ***P<0.001 relative to control cultures under N2 atmosphere and ###P<0.001 relative to PDC-treated cultures under N2 atmosphere (b) Survival of cortical neurons exposed to NMDA (100 μM) for 4 days under 75% N2 and the impact of a treatment with memantine (10 μM) or 75% Xe ***P<0.001 relative to control cultures maintained under N2 atmosphere and ###P<0.001 relative to PDC-treated cultures under N2 atmosphere (c) Survival of cortical neurons exposed to PDC (30μM) for 4 days in the presence or not of various concentrations of memantine (0.1; 1; 10 μM) or ketamine (0.01; 0.1; 1 μM) under gas atmospheres containing either 75% N2 or 75% Xe ***P<0.001 relative to control cultures under N2 atmosphere ###P<0.001 relative to PDC-treated cultures under N2 atmosphere; §§P<0.01 §§§P<0.001 relative to PDC-treated cultures maintained under 75% Xe and PDC-treated cultures maintained under 75% N2 with a same concentration of memantine (d) Fluorescence digitized images showing the impact that treatments with xenon alone or xenon+memantine (0.1; 10 μM) exert on the survival of cortical cultures exposed to PDC No cooperative effects were observed with a concentration of 1 μM ketamine that was already optimally protective in itself Impact of xenon on the uptake and release of [3H]-D-aspartate in cortical cultures exposed to PDC (a) [3H]-D-aspartate uptake measured in cortical cultures exposed acutely or not to PDC (30 μM) under an atmosphere containing 75% N2 or 75% Xe in the presence or not of memantine (10 μM) (b) [3H]-D-aspartate released in cortical cultures exposed or not to PDC (30 μM) in an atmosphere containing 75% N2 or 75% Xe Impact of an atmosphere containing 75% Xe on [3H]-D-aspartate release evoked by a depolarizing treatment with 4-aminopyridine (4-AP; 2.5 mM) and bicuculline (Bic; 50 μM) ***P<0.001 relative to control cultures maintained under N2 atmosphere Using cortical cultures initially pre-loaded with [3H]-D-aspartate, we found that PDC (30 μM) stimulated the release of the tritiated neurotransmitter, which suggests that neuroprotection by xenon could potentially result from a reduction of PDC-evoked glutamate release. Xenon failed, however, to reduce the efflux of [3H]-D-aspartate upon PDC exposure (Figure 3b) memantine did not interfere significantly with the release of [3H]-D-aspartate after PDC treatment the depolarizing treatment enhanced [3H]-D-aspartate efflux but xenon failed to interfere with this process which signifies that the noble gas had no significant impact on presynaptic glutamatergic release Xenon prevents a death mechanism that implicates oxidative stress (a) Survival of cortical neurons in cultures exposed or not to PDC (30 μM) for 4 days and treated or not concomitantly with Trolox (10 μM) or NAC (30 μM) under an atmosphere containing 75% N2 Comparison with cultures receiving the same concentration of PDC under an atmosphere containing 75% Xe ***P<0.001 relative to control cultures maintained under 75% N2 and #P<0.05 ###P<0.001 relative to PDC-treated cultures maintained under 75% N2 (b) DPPH radical scavenging assay comparing the antioxidant potential of Trolox (10 μM) NAC (30 μM) and memantine (10 μM) under 75% N2 to that of an atmosphere containing 75% xenon ***P<0.001 relative to controls maintained under 75% N2 Xenon exerts both neurotrophic and neuroprotective effects for cholinergic neurons in septal cultures (a) Left panel: Size of ChAT+ cell bodies in septal cultures exposed or not for 4 days to memantine (MEM; 10 μM) under a gas atmosphere containing 75% N2 or 75% Xe Right panel: ChAT fluorescence intensity in ChAT+ cell bodies exposed or not for 4 days to memantine (MEM; 10 μM) under a gas atmosphere containing 75% N2 or 75% Xe (n=25 randomly chosen neurons per condition) *** P<0.001 relative to control cultures maintained under 75% N2 and §P<0.05 relative to cultures maintained under 75% Xe and to cultures maintained under 75% N2 in the presence of memantine (b) Fluorescence digitized images presented under an inverted format to illustrate the impact of the same treatments as in (a) onto cholinergic neurons (c) Number of ChAT+ neurons in septal cultures maintained for 4 days under a gas atmosphere containing 75% N2 or 75% Xe and treated or not with PDC (30 μM) in the presence or the absence of memantine (10 μM) *** P<0.001 relative to control cultures maintained under 75% N2; ###P<0.001 relative to PDC-treated cultures maintained under 75% N2 and §§P<0.01 relative to PDC-treated cultures maintained in 75% Xe and PDC-treated cultures maintained in 75% N2 in the presence of memantine (d) Fluorescence digitized images showing the impact of the same treatments as in (c) onto cholinergic neurons Scale bars: 25 μm and 50 μm in (b) and (d) When septal cultures were exposed to 30 μM PDC between 12 and 16 DIV only 26% of ChAT+ neurons survived compared with control cultures maintained under a standard nitrogen atmosphere the survival rate of ChAT+ neurons was increased by more than threefold The increase in ChAT+ neuron survival was less important with memantine (10 μM) when xenon and memantine treatments were combined under PDC exposure the number of cholinergic neurons exceeded that found in control cultures We demonstrate for the first time that the noble gas xenon can provide partial but sustained protection to AD vulnerable neurons (i.e. cortical neurons and septal cholinergic neurons) that undergo degeneration though chronic low-level excitotoxic stress The protective effect of xenon was not reproduced with the other noble gas argon We established that xenon interferes with a death pathway in which NMDA receptors and reactive oxygen species intervene crucially xenon exerted cooperative neuroprotection with two noncompetitive NMDA receptor channel antagonists When evaluating the impact of xenon in septal cultures we found that the noble gas was not only robustly neuroprotective for cholinergic neurons but that it also exerted potent trophic effects on them This set of data clearly indicates that xenon is unlikely to afford protection by interfering with a presynaptic mechanism linked to the uptake or release of glutamate Still consistent with the view that xenon operated via an antagonistic effect on NMDA receptors the noble gas remained strongly protective when NMDA the prototypical agonist of NMDA receptors was used instead of PDC to induce cortical cell death The use of the cell-free DPPH assay revealed that xenon does not behave as an antioxidant in comparison with Trolox and NAC used as reference molecules one may assume that xenon prevented the propagation of oxidative stress-mediated damage through its capacity to limit NMDA receptor overstimulation xenon also provided robust protection to cholinergic neurons exposed to PDC The noble gas was proportionally more efficacious to rescue cholinergic neurons than the bulk population of neurons that undergoes neurodegeneration in septal cultures (not shown) or in cortical cultures This suggests that the trophic effects of xenon also occurred in PDC-treated septal cultures despite ongoing neurodegenerative changes which was less effective than xenon in increasing the number of ChAT+ neurons in control cultures was also comparatively less efficacious than the noble gas to protect cholinergic neurons against PDC exposure our data demonstrate that the noble gas xenon exerts robust protective effects for cortical neurons and subcortical cholinergic neurons that are preferentially vulnerable in AD Besides exerting true neuroprotective effects xenon can also operate as a potent trophic factor for cholinergic neurons Although any extrapolation from our in vitro work to a pathologic situation must be regarded as speculative our data raise the intriguing possibility that xenon may have the potential to halt neurodegenerative events associated with the progression of the AD pathology The non-metabolizable analog of L-glutamate PDC the preferential agonist of NMDA receptors NMDA and the NMDA receptor antagonist memantine were all purchased from Tocris Biotechne (Lille the non-selective K+ channel blocker 4-aminopyridine Trolox and the DPPH free radical were from Sigma–Aldrich (Saint-Quentin Fallavier handled and taken care of in accordance with recommendations of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH Publication no revised 1996) and the European Union Council Directives (86/609/CEE) Experimental procedures were authorized by the ethical committee on animal experiments Charles Darwin n°5 48-well multi-dish plates containing cultured cells were disposed above a metallic base plate receiving atop of it a Plexiglas incubation chamber The two pieces were then screwed together to produce an air-tight seal Humidification of the chamber was achieved by disposing a multi-dish plate wherein culture wells filled with distilled water were placed directly in contact with the inside atmosphere the pre-defined gas mixture comprising 20% O2 5% CO2 and 75% of the test gas was injected at a flow rate of ~10 l/min into the incubation chamber with the inlet and outlet valves open When the CO2 concentration measured at the outlet with a gas analyzer reached 5% the injection was stopped and the chamber was sealed by turning off the inlet and outlet valves The incubation chamber was then placed in a conventional incubator at 37 °C for incubation times indicated in the manuscript We generally used pre-defined gas mixtures provided by Air Liquide (France) controlled gas atmospheres were also delivered to incubation chambers using a gas mixing system (GasMix France) supplied by tanks filled by individual pure gases (Air Liquide) fixed with 4% formaldehyde in Dulbecco’s phosphate-buffered saline (PBS) were washed twice with PBS before an incubation step at 4 °C for 48–96 h with primary antibodies diluted in PBS containing 0.2% Triton X-100 to improve cell membrane permeability #M2320; Sigma–Aldrich) diluted 1/200 was used as the pan-neuronal marker and a goat anti-ChAT affinity purified antibody diluted 1/100 (#AB144P; Merck Millipore Detection of primary antibodies was performed with an Alexa Fluor-555 conjugate of an anti-mouse IgG antibody (1/500) or an Alexa Fluor-555 conjugate of an anti-goat antibody (1/1000) both obtained from Life Technologies (Saint Aubin The survival of all neurons regardless of their neurotransmitter phenotype was monitored by counting MAP-2+ cells fluorescent images of cultured cells were acquired with an Eclipse TE-2000 inverted fluorescent microscope (Nikon France) equipped with an ORCA-ER digital camera (Hamamatsu Photonics France) operated with the HCI software (Hamamatsu Corp. 10 digitized images randomly acquired with a ×10 objective were taken for cell counting using the image processing program Image J Counting of ChAT+ neurons was performed on digitized images acquired with a ×10 objective mounted onto an Arrayscan XTi automated workstation equipped with the HCS Studio Software (Thermofisher Scientific Mosaic reconstruction of partially overlapping digitized images allowed the counting of ChAT+ neurons over >60% of the surface area of each culture well To estimate the impact that test treatments could have on the maturation of cholinergic neurons digitized images of ChAT+ neurons were taken randomly with the Nikon Eclipse TE-2000 microscope using a ×40 objective and identical acquisition parameters Images were used to quantify the surface area and the fluorescence intensity of positive cell bodies using the MCID analysis software (InterFocus Imaging Ltd Specific ChAT fluorescence intensity was corrected by subtracting background intensity levels for each treatment condition All results were expressed in percent of control values the culture medium was removed and the cultures were allowed to recover for 5 min at 37 °C in PBS supplemented with 5 mM glucose before further processing The uptake was initiated by the addition of 1 μl of [2,3-3H]-D-aspartate (13 Ci/mmol; Perkin Elmer USA) to culture wells exposed or not to different test treatments in the presence of gas atmospheres enriched or not with xenon the cultures were washed twice with cold PBS to remove the tritiated amino acid in excess and the radioactivity accumulated intracellularly was recovered by scrapping off cells in distilled water Samples were then assessed by liquid scintillation spectrometry The release of [2,3-3H]-D-aspartate was carried out in cultures that were pre-loaded for 30 min with the tritiated amino acid washed twice with PBS and then exposed to various test treatments in the presence of gas atmospheres enriched or not with xenon The fraction of radioactivity recovered in the incubation medium during the next 30 min was collected for assessment by liquid scintillation spectrometry 225 μl of a DPPH ethanol solution (0.025 mg/ml) were distributed into individual wells of a Nunc 96-well microplate The volume was then completed to 250 μl by addition of the test compounds diluted in ethanol or by ethanol Blanks contained 250 μl of pure ethanol instead of DPPH The microplate shaken vigorously during 10 s was then allowed to stand for 1 h in the dark at room temperature under atmospheres containing either 75% nitrogen or 75% xenon This was followed by measurement of the absorbance at 517 nm using a Spectramax M4 multiplate reader (Molecular Devices Blank values obtained by replacing DPPH with pure ethanol were subtracted from test samples Data expressed as means±S.E.M were analyzed using the SigmaPlot 12.5 software (Systat Software Inc Multiple comparisons against a single reference group were made by one-way ANOVA with Dunnett’s test post hoc analysis When all pairwise comparisons were required one-way ANOVA was followed by the Student-Newman-Keuls post hoc test Xenon consumption during general surgery: a retrospective observational study Xenon preconditioning protects against renal ischemic-reperfusion injury via HIF-1α activation Pretreatment with xenon protected immature rabbit heart from ischaemia/reperfusion injury by opening of the mitoKATP channel offering long-term functional and histopathologic neuroprotection after neonatal hypoxia/ischemia Xenon augmented hypothermia reduces early lactate/N-acetylaspartate and cell death in perinatal asphyxia Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor mediates xenon neuroprotection against hypoxia-ischemia Reduction of ischemic brain damage by nitrous oxide and xenon J Cereb Blood Flow Metab 2003; 23: 1168–1173 Xenon and sevoflurane protect against brain injury in a neonatal asphyxia model Cooling combined with immediate or delayed xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia J Cereb Blood Flow Metab 2009; 29: 707–714 Morphological evidence that xenon neuroprotects against N-methyl-DL-aspartic acid-induced damage in the rat arcuate nucleus: a time-dependent study Effects of xenon on ischemic spinal cord injury in rabbits: a comparison with propofol Xenon improves neurologic outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury Neuroprotection against traumatic brain injury by xenon is mediated by inhibition at the N-methyl-D-aspartate receptor glycine site Argon: systematic review on neuro- and organoprotective properties of an "inert" gas Ex vivo and in vivo neuroprotection induced by argon when given after an excitotoxic or ischemic insult Neuroprotective effects of argon in an in vivo model of transient middle cerebral artery occlusion in rats Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats Neuronal preconditioning by inhalational anesthetics: evidence for the role of plasmalemmal adenosine triphosphate-sensitive potassium channels Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon Identification of two mutations (F758W and F758Y) in the N-methyl-D-aspartate receptor glycine-binding site that selectively prevent competitive inhibition 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neurons by depolarizing concentrations of K+ requires concurrent inactivation of NMDA or AMPA/kainate receptors Download references The research leading to these results was supported by program Investissements d’Avenir [ANR-10-IAIHU-06] and Translational Research Infrastructure for Biotherapies in Neurosciences [ANR-11-INBS-0011-NeurATRIS] We thank Géraldine Farjot for helpful comments on the manuscript We are grateful to Matthieu Chalopin for coordinating operational aspects of the project and to François Gilles for his expertise with gas delivery systems We also wish to acknowledge the valuable assistance of David Akbar from the CELIS cell culture core facility regarding fluorescence microscopy analysis Air Liquide Santé International Medical R&D Paris DLN is recipient of a CIFRE fellowship (2014/0589) co-funded by Association Nationale de la Recherche et de la Technologie (ANRT) and Air Liquide Santé International Download citation DOI: https://doi.org/10.1038/cddiscovery.2016.18 Please enable JS and disable any ad blocker Turn autoplay off Turn autoplay on Please activate cookies in order to turn autoplay off A comparatively short jaunt around Southern France begins in Blaye-les-Mines a picturesque town situated on the banks of the river Tarn which numbers the Cathedral of Saint Cecilia the Toulouse-Lautrec Museum and a "painfully beautiful" giant crater (the legacy of a a once-thriving open coal mining industry) among its tourist attractions a small medieval town which stands on the left bank of the Agout it boasts a monument erected in memory of Dame Giraude de Laurac who was thrown down a well and stoned to death during the wars of the Albigenses in 1211 "More lumpy roads through the Tarn but not as grim as the day before," writes Guardian cycling correspondent Will Fotheringham in our indispensable interactive guide to the Tour de France "The sprinters and their teams will be eyeing this one It's short and should be fast and controlled and Cavendish will be the favourite." Although magnanimous in defeat after being overtaken by his former team-mate André Greipel in yesterday's closing metres Mark Cavendish is certain to be pumped for revenge in a stage that represents one of very few remaining chances of glory for the Manxman in this year's Tour Video: View highlights of yesterday's stage above Mark Cavendish @markcavendish: "Just took the surgical dressing of my saddle sore #aaaarrrrrgggggghhhhhh Maybe shaving just my legs isn't enough." Mark Cavendish @markcavendish: "Had dinner with warriors I call my teammates Incredible how they stay upbeat after riding so hard all day & I don't finish the job #legends" Greipel rode it perfect & got speed by running up on me" The gizmo above is our link to Citizenside whose goal is "to create the largest online community of amateur and independent reporters where everyone can share their vision of the news by uploading photos and videos for fellow reporters to see." In short it's lots of photographs from the Tour de France so feel free to explore by scrolling through using the arrow keys Thomas Voeckler (France/Europcar) 42hr 06min 32sec 2 Luis Leon Sanchez (Spain/Rabobank) +1min 49sec 3 Cadel Evans (Australia/BMC Racing) +2min 26sec4 Fraenk Schleck (Luxembourg/Leopard) +2min 29sec 5 Andy Schleck (Luxembourg/Leopard) +2min 37sec 6 Tony Martin (Germany/HTC-Highroad) +2min 38sec7 Andreas Kloeden (Germany/RadioShack) +2min 43sec 9 Philippe Gilbert (Belgium/Omega Pharma - Lotto) +2min 55sec 10 Jakob Fuglsang (Denmark/Leopard) +3min 08sec Full standings ... Stage 11 so far: With 79 kilometres down and 88 to go a group of six riders has broken clear of the peloton and opened a gap of 3min 18sec Tristan Valentin (COF) and Jimmy Engoulvent (SAU) the peloton is being pushed along by a tailwind and the intermediate sprint is looming 2.10pm: The escape party pass get their knees pumping for the intermediate sprint 2.11pm: "Not sure I can remember a day in the Tour when the three main jersey holders honoured their jerseys as much as yesterday with the maillot jaune and vert attacking together on the last climb and the maillot a pois fighting through injury," writes Graham Fulcher who is somehow able to see the screen of his computer monitor despite having gone all misty-eyed "Hoogerland will definitely lose the polka dot jersey on Thursday and Vockler will lose yellow in the Pyrenees However Greipel's win yesterday could really compromise Gilbert's chances of keeping the green jersey as well Despite what they said yesterday there has clearly been tension in the Omega team between Gilbert sprinting for points and Greipel for the win Had Greipel lost to Cavendish again yesterday Gilbert would have had justification for asking for the strategy to be switched solely to him When (as I expect) Cavendish takes the stage today the gap between he Rojas and Gilbert could narrow significantly The question will then be how many points does Cavendish lose to the others on intermediate sprints in mountain stages." Today's Tour de France coverage has gone from late to farcical - due to having to field a phone call I managed to miss the bunch as they completed the intermediate sprint I'm fairly certain I saw yesterday's stage-winner Andre Greipel flash past the line first of the green jersey contenders How the green jersey contenders fared in the intermediate sprint: 7th: Cavendish (nine points) In other news: AG2R La Mondiale rider John Cadret failed to sign on for the race today He was the first man to be shelled out the back of the peloton on the final climb yesterday and has not been riding well the gap between the six-man breakaway group and the peloton is 3min 16sec It will be astonishing if this stage isn't decided by a bunch sprint finish @fmk_RoI: "@BGlendenning How bout some news from back of peloton 2day? Last chance 4 lanterne rouge contenders 2 buffer up b4 mtns " Infostrada Sports @Infostrada2012 "Cavendish claims green jersey if he wins today's #TdF stage and if Gilbert does not finish in Top 5 and Rojas does not finish in Top 2." The good news is that my knee was fine this morning when I woke up but it was fine all day and I had no problems I think my easier-than-normal rest day on Monday paid dividends today I would have done almost three hours' riding but the pain in my knee meant I turned back after 20 minutes and spent most of the day in bed reading my book and actually resting About a half an hour before the start today it started lashing hailstones We all dived for the cover of the team bus and were busy changing our sunglasses to clear lenses and putting on rain jackets when Maxime Bouet said he still had to go and sign on some of the big riders would just sit on their buses until the last minute if it was raining and ride off without the crowd having the opportunity to see them in the flesh signing on before the start Article continues ... Omega Pharma-Lotto rider Andre Greipel is now back on more mundane duty at his team car stocking up on water bottles for his team-mates It's always interesting to see how many bidons a rider can stuff down his shirt before heading back to the peloton to hand them out; somebody once told me the riders have an ongoing competition to see who can carry the most and the record is 16 Last year this site was designated a Unesco World Heritage Site." He looked pretty clean over the last week-and-a-half." the gap between the six-man breakaway and the peloton is coming down - it's currently 2min 37sec 3pm: Nothing to do with cycling department: News Corporation has withdrawn its bid for BSkyB there are only some many reeled-in breakaways that a man can watch Tomorrow we'll finally get a chance to see who's in good form and to see the pack being reduced to a dozen riders with everyone going off the back Have a feeling my fellow Evans will struggle and that Andy Schleck should take a big stride towards his first TDF tomorrow." 3.04pm: "Stefan Schumacher 'der Rad-Schumi' also 'looked pretty clean' during his disastrous Beijing Olympics bang to rights for Pantani-esque amounts of doping which he subsequently denied (think he even still does) with a really irritating 'lawyering' of his language," writes David Hindle as several Guardian lawyers with shotguns surround my desk and stare gimlet-eyed down the barrels daring me to divulge any more of the content of David's email 3.10pm: It's raining quite heavily as the six-man breakaway continue on their way to Lavaur with just 1min 38sec between them and the peleton 3.18pm: "I can't get Eurosport over here in Jersey (the new one) so I'm curious how AC Jimbo is doing as presenter of the Tour?" asks Alex Langlois "Handing out sledgehammer puns like a domestique delivering bottles I'd love a break from the Phil N'Paul show every now and then." Well it's funny you should ask. The Eurosport I watch at home has coverage, interspersed with footage of my podcasting colleague James Richardson broadcasting from a studio with a burly German expert and a bloke with a mullet but the Eurosport I watch here in the office just has the coverage because I haven't seen much of AC Jimbo this year I can tell you he got both Nicolas Roche's name and that of the newspaper he writes a column in wrong in the space of one sentence on Sunday 3.23pm: The escape party of Perez Moreno (EUS) Tristan Valentin (COF) and Jimmy Engoulvent (SAU) are going about their business well working excellently together to keep the gap between themselves and the peloton at a fairly steady 1min 25sec with 27km to go 3.25pm: "Have to agree with James Evans," writes Matthew Lysaght I fancy Evans to make light work of Schleck (A) - he just seems to want it a little more this year as if he knows it's his last real chance to win it Cav today - and then he shall be transferred out of my Fantasy Tour team." How fickle you are - I bet he won't be transferred out of Page 3 stunnah Peta Todd's Fantasy Tour team Peta Todd @petatodd: "Well today is a bit different at work.. 3.34pm: Rabobank's Dutch rider Lars Boon pushes the breakaway group down a descent through driving rain Sean Kelly points out that they're about to turn into a headwind which should put a stop to their gallop The gap stands at 1min 16sec with a little over 19 kilometres to go If the breakaway can make it to the 10km To Go banner with the same gap one of them would have a good chance of winning David Harmon reckons they've a 50-50 chance of making it Lampre and HTC-Highroad are all putting men on the front of the peloton the breakaway group are 49 seconds clear - that gap is getting smaller and smaller the peloton drives on through torrential rain with a couple of HTC-Highroad riders putting the hammer down The six riders in the breakaway are continuing to work well together - they could conceivably get away with this if they can delay the inevitable end-of-stage cat-and-mouse games for as long as possible 3.44pm: The peloton is strung out in a long line with the entire HTC-Highroad team leading from the front "Speaking of getting names wrong Barry," writes my smug podcasting chum James Richardson from his plush Eurosport studio "That might be Magnus Backstedt you're referring to 3.47pm: Just 9.4 kilometres to go and the gap between breakaway group and peloton is is down to 30 seconds which almost certainly won't be enough for one of the half-dozen escapees to prevail 3.50pm: "Your commentary is getting as banal as something out of NOTW," writes Anna Corrall "I couldn't care less about Peta Todd; it may be nice to actually get some commentary on the cycling rather than her daily routine." Cheers Anna it's always nice to hear from people who take the Tour de France so seriously they rely on written online reports from websites not hugely renowned for their Tour de France overage for their updates 3.54pm: I'd tell you whether or not it's still hammering down with rain in France but Anna Corrall probably isn't interested in hearing bland pleasantries about the weather All she wants to hear is that some men on bkes are cycling fast Lars Boom makes a break for it and puts a few seconds between himself and his fellow escapees 3.57pm: The riders in the peloton catch up with five of the six escapees and have Lars Boom in their sights but eventually gives up the ghost upon realising the jig is up Garmin and HTC-Highroad get their respective trains doing the locomotion as their riders cycle on in formation A couple of the HTC riders have already hollered "enough" Closing stages: Mark Cavendish takes the stage by more than a bike-length after another excellent lead-out from Mark Renshaw It looked as if he might have shot his bolt too early but it turned out to be a textbook finish when Andre Greipel was unable to pass him despite having got on his wheel That win puts Cavendish in the green jersey 4.04pm: To celebrate Mark Cavendish's 18th stage win on the Tour the TV director cuts to a helicopter shot of a nice French chateau Anna Corrall would be unimpressed with that kind of frippery; they could be showing some cyclists .. Mark Cavendish compliments Andre Greipel on a "technically perfect" sprint-finish yesterday thanks his team-mates for another fine job of work and then explains that he won today by just "going for it after he got such a good lead-out" He also explains that accidental contact he made with Romain Feillu 500 metres from the line meant that his shoe came undone and he had to lean over to tighten it ahead of his stage-winning finish Upon being informed that he's ridden himself into the green jersey he looks genuinely surprised and delighted 4.11pm: "Enough about the cycling Barry," writes Luke Remsbury "There's been no Peta Todd update now since 3.34pm Has the pull-along trolley launched a break Peta Todd @petatodd: "Mid-transformation ..." I can confirm that she is happy with the obligatory donkey/cow shots but only if they last for under 5 seconds," writes Gareth Jones "She did make a comment about the quad-bikes-for-bicycle-wheels shot earlier on in the Tour as not being particularly green Yellow jersey: Thomas Voeckler (Team Europcar) 45hr 52min 39secGreen jersey: Mark Cavendish (HTC-Highroad) 251 pointsPolka dot jersey: Johnny Hoogerland (Vacansoleil-DCM) 22 pointsWhite jersey: Robert Gesink (Rabobank) 45hr 56min 40sec Full standings ...