Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 1: FHM1) is caused by mutations in Ca sub(V)2.1 (P/Q-type) Ca super(2+) channels. ...Knockin mice carrying a FHM1 mutation show increased neuronal P/Q-type current and facilitation of induction and propagation of cortical spreading depression (CSD), the phenomenon that underlies migraine aura and may activate migraine headache mechanisms. We studied cortical neurotransmission in neuronal microcultures and brain slices of FHM1 mice. We show gain of function of excitatory neurotransmission due to increased action-potential-evoked Ca super(2+) influx and increased probability of glutamate release at pyramidal cell synapses but unaltered inhibitory neurotransmission at fast-spiking interneuron synapses. Using an in vitro model of CSD, we show a causative link between enhanced glutamate release and CSD facilitation. The synapse-specific effect of FHM1 mutations points to disruption of excitation-inhibition balance and neuronal hyperactivity as the basis for episodic vulnerability to CSD ignition in migraine.
La grotte Tempiette, située sur le versant sud du Granier, en Chartreuse, correspond à une petite galerie horizontale longue de 7 m, au bout de laquelle s’ouvre un puits aux parois verticales, ...d’environ 3 m de diamètre et profond de 32 m. Cette grotte a fonctionné comme un piège naturel où sont tombés accidentellement de nombreux animaux, constituant ainsi un véritable ossuaire. Actuellement, 15 274 vestiges osseux ont été analysés. Les bouquetins (36 individus) et les chamois (16 individus) sont les plus abondants. Ont également été identifiés trois ours bruns, deux fouines, quatre belettes, trois hermines, un lièvre variable, plusieurs écureuils, un aigle royal, ainsi que de nombreux rongeurs et chauves-souris. Les bouquetins et les chamois semblent avoir été attirés dans la grotte par la présence de sel qui se formait au fond de la galerie, juste à l’aplomb du puits. Ce site a été fréquenté principalement pendant la bonne saison. Parmi tous les ossements recueillis dans la grotte Tempiette, aucun ne présente de traces résultant d’une activité anthropique ou de Carnivores. Sur le plan taphonomique, il s’agit d’un site qui a fonctionné strictement comme un aven-piège. Cependant près de la moitié des os longs sont brisés. Ils présentent des cassures en spirale, avec parfois des impacts de percussion (points d’écrasement, enfoncements, encoches) ou des stries. Ces stigmates rappellent beaucoup ceux que l’on peut observer sur des os animaux provenant de sites archéologiques en relation avec une exploitation des carcasses. La grotte Tempiette constitue un site paléontologique avec une importante accumulation d’ossements d’Ongulés de montagne. Il s’est formé dans des conditions environnementales comparables à celles des sites archéologiques proches. Il constitue un excellent référentiel taphonomique d’accumulation naturelle, en contexte de karst de montagne, qui permettra de mieux comprendre les accumulations osseuses dans les sites archéologiques alpins.
The Tempiette cave, on the south side of Granier in the Chartreuse mountains, is a small horizontal gallery, 7 m long, after the end of which is opened a vertical well, around 3 m in diameter and deep 32 m. This cave functioned as a natural trap where accidentally fell many animals, thus constituting a significant bone accumulation. Currently, 15 274 bone remains have been analyzed. Ibex (NISP = 36) and chamois (NISP = 16) are the most abundant. Three brown bears, two martens, four weasels, three stoats, one mountain hare, several red squirrels, one golden eagle, and many rodents and bats have also been identified. Ibex and chamois seem to have been misled by salt formation at the end of the gallery, directly above the well. This site was mainly frequented during the good season in the Late Glacial and early Holocene. Among all the bones found in the Tempiette cave, none has traces resulting from Carnivores or human activities. This site functioned strictly as a natural trap. However, almost half of the long bones are broken. They have spiral fractures, sometimes with percussion marks (crushing, punctures, notches) or striations and grooves. These traces look like what can be observed for animal bones in anthropogenic sites where there are exploitations of carcasses. Consequently, Tempiette cave constitutes a paleontological site that functioned as a natural trap, allowing significant bone accumulation. It was formed in environmental conditions similar to those of nearby archaeological sites. It could be an excellent taphonomic referential of natural accumulation that’s completely unique in karst mountain environment and would allow better understand of bone accumulations in alpine anthropogenic sites.
Nuclear power stations are designed to withstand substantial seismic activity and as such represent some of the most robust buildings in the world. However The Fukushima nuclear incident highlighted ...the potential vulnerability of nuclear power plants when multiple natural events of historic proportions happen simultaneously.
The study was designed to determine the time-course of cardiac troponin I (cTn-I) release in isolated and Langendorff-perfused rat hearts during hypoxia and reoxygenation (H/Reox), and after various ...durations of total ischemia and subsequent reperfusion (I/R). For this purpose, in H/Reox, cTn-I was measured with the conventional Access
® immunoassay (ng/ml) and a new immunoassay which operates at pg/ml, and compared with creatine kinase (CK), lactate dehydrogenase (LD) and cardiac troponin T (cTn-T). In I/R, cTn-I was compared with CK and LD. The anti-Tn-I mAbs used in cTn-I assays cross-react with cTn-I of the rat. A clear difference between time-courses and concentration levels of cTn-I in I/R and H/Reox models was found. In I/R, maximum release of cTn-I, CK and LD similarly occurred within minutes following reperfusion; however cTn-I did not return to baseline values. cTn-I levels were not linked to the duration of ischemia. In I/R, we were only able to detect small cTn-I concentrations. In H/Reox experiments, cTn-I, CK and LD increased time-dependently. We found higher cTn-I maximal peak levels detected with the Access
® immunoassay than with the new assay (median, 0.346 ng/ml per min/g dry wt vs 132 pg/ml per min/g dry wt). cTn-T maximal concentrations were lower than maximal cTn-I levels (median, 0.117 ng/ml per min/g dry wt). Time-courses of cTn-I release were roughly similar with both assays in the H/Reox model (
r=0.90). These data indicate that the cTn-I time-course is related to experimental model (I/R or H/Reox), but also likely depends on the sensitivity of cTn-I assays in such experimental conditions.
Spontaneous blood echogenicity in vein ultrasound images may be a marker for an increased erythrocyte aggregability, but a reliable quantitative evaluation method is a prerequisite for its use in ...clinical studies. We compared a simple scoring system of blood echogenicity intensity and pattern, with automatic image analysis.
157 femoral and popliteal vein digitized ultrasound sequences were reviewed by two independent observers who chose an image, delimited an area of interest (ROI), and graded blood echogenicity intensity and pattern, using a four class score. Each observer reviewed the images selected by the other, without and with ROI. The computer calculated first and second order parameters describing echo intensity and spatial organization.
Inter-observer reproducibility of subjective assessment was poor (Kappa<0.5), whereas the automatically calculated ROI average gray level intensity relatively to the whole image (tau(1)) effectively separated all grades of intensity. No parameter effectively separated patterns.
Tau(1) is a simple parameter for the in vivo evaluation of blood echogenicity intensity. It should be evaluated in standardized conditions for clinical hemorheology studies in correlation with in vitro erythrocyte aggregation measurements.
Few experimental studies report effects of direct contusion on cardiac enzyme release. Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of ...myocardial cell injury. This investigation was designed to determine and compare the acute effects of quantified magnitudes of blunt cardiac trauma upon release of cTnI and cTnT in comparison with creatine kinase (CK) and lactate dehydrogenase (LD).
In 24 rabbit hearts prepared on a standard Langendorff apparatus, myocardial contusion (MC) was produced by a single blow with a ball falling from a predefined height, delivered directly to the surface of the heart. Hearts were divided into control (n = 6) and various quantified impacts: 75 mJoules (mJ) (n = 6), 100 mJ (n = 6), 200 mJ (n = 6). Coronary effluent samples for cTnI, cTnT, CK, and LD were collected at baseline, immediately after MC and 5, 15, 30, 45, and 60 minutes after MC. At the end of experiment, histologic condition was evaluated.
The anti-cTnI and cTnT MAbs used in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rabbit. The time-courses of cTnI, cTnT, CK, and LD were monophasic in form. After MC, all parameters rose significantly compared with baseline and with control group. The maximal release occurred immediately after MC. The area under the cTnI curve and the maximal cTnI concentration were linked to the contusion energy when increased at 200 mJ. Maximal concentrations and areas under cTnT, CK, LD time activity curve were not linked to the contusion energy level and showed no between-energy group differences. The correlation found between maximal cTnI and maximal cTnT concentrations was 0.70 (p = 0.0001). Histologic examination showed cellular disruption and after the more severe impact, the extent of pathologic changes was more extensive.
After graded experimental MC, maximal cTnI concentration and area under cTnI curve increase with the power of impact kinetic energy. Levels of cTnI allow a much higher accuracy in detecting the extent of myocardial injury postMC in comparison with cTnT, CK, and LD in this experimental study. These results should be consistent with the more extensive cTnI release with more severe impact in patients with blunt chest trauma. Furthermore, because specificity and time-course of release, both cTnI and cTnT should have a role in the diagnosis and evaluation of such patients.
The analysis of the first plant genomes provided unexpected evidence for genome duplication events in species that had previously been considered as true diploids on the basis of their genetics. ...These polyploidization events may have had important consequences in plant evolution, in particular for species radiation and adaptation and for the modulation of functional capacities. Here we report a high-quality draft of the genome sequence of grapevine (Vitis vinifera) obtained from a highly homozygous genotype. The draft sequence of the grapevine genome is the fourth one produced so far for flowering plants, the second for a woody species and the first for a fruit crop (cultivated for both fruit and beverage). Grapevine was selected because of its important place in the cultural heritage of humanity beginning during the Neolithic period. Several large expansions of gene families with roles in aromatic features are observed. The grapevine genome has not undergone recent genome duplication, thus enabling the discovery of ancestral traits and features of the genetic organization of flowering plants. This analysis reveals the contribution of three ancestral genomes to the grapevine haploid content. This ancestral arrangement is common to many dicotyledonous plants but is absent from the genome of rice, which is a monocotyledon. Furthermore, we explain the chronology of previously described whole-genome duplication events in the evolution of flowering plants.
The analysis of the first plant genomes provided unexpected evidence for genome duplication events in species that had previously been considered as true diploids on the basis of their genetics. ...These polyploidization events may have had important consequences in plant evolution, in particular for species radiation and adaptation and for the modulation of functional capacities. Here we report a high-quality draft of the genome sequence of grapevine (Vitis vinifera) obtained from a highly homozygous genotype. The draft sequence of the grapevine genome is the fourth one produced so far for flowering plants, the second for a woody species and the first for a fruit crop (cultivated for both fruit and beverage). Grapevine was selected because of its important place in the cultural heritage of humanity beginning during the Neolithic period. Several large expansions of gene families with roles in aromatic features are observed. The grapevine genome has not undergone recent genome duplication, thus enabling the discovery of ancestral traits and features of the genetic organization of flowering plants. This analysis reveals the contribution of three ancestral genomes to the grapevine haploid content. This ancestral arrangement is common to many dicotyledonous plants but is absent from the genome of rice, which is a monocotyledon. Furthermore, we explain the chronology of previously described whole-genome duplication events in the evolution of flowering plants.
PDF
