Biostratigraphic and palaeoenvironmental implications of the Middle Palaeolithic and Chatelperronian occupations of La Tour Fondue site in Chauriat (Puy-de-Dôme, France)

This article presents results of the excavations carried out in 2004 on part of the rock shelter of La Tour Fondue at Chauriat (fig. 1). The aim of this intervention was to specify the chronological and stratigraphic position of the human settlements, to characterize them at a cultural level and to establish the local palaeoenvironment. The sedimentary deposits were more than 3.20 m deep (fig. 5 to 7). They yielded a large quantity of micromammals associated with macrofauna. Studying these provided a bioclimatic and palaeoenvironmental framework that can be divided into five stages, starting at the end of Isotope Stage 5 and ending between Isotope Stages 3 and 2. The Middle Palaeolithic human occupations found in the upper levels occurred during a temperate episode with a cold tendency in Isotope Stage 5 (“Chauriat 1” Stage) and lasted until the “Chauriat 4” Stage at the end of Isotope Stage 3. For their lithic industries, Middle Palaeolithic people used tertiary flints found next to the shelter without considering their quality. These materials were used to obtain flakes in Levallois and discoid production modes. The upper levels contain Chatelperronian and unspecified Upper Palaeolithic occupations. The Chatelperronian took place in a climate correlated with an interstadial at the limit between Stages 3 and 2 (“Chauriat 5” Stage). Chatelperronian people were different than their predecessors in favouring better quality raw materials, found about twenty kilometres from the site. The industries of the upper levels aimed at producing straight and short blades blanks knapped with a soft stone hammer for the Chatelperronians, and long and curved blades blanks knapped with a soft organic hammer for the last occupiers of the shelter

Biostratigraphic and palaeoenvironmental implications of the Middle Palaeolithic and Chatelperronian occupations of La Tour Fondue site in Chauriat (Puy-de-Dôme, France)

This article presents results of the excavations carried out in 2004 on part of the rock shelter of La Tour Fondue at Chauriat (fig. 1). The aim of this intervention was to specify the chronological and stratigraphic position of the human settlements, to characterize them at a cultural level and to establish the local palaeoenvironment. The sedimentary deposits were more than 3.20 m deep (fig. 5 to 7). They yielded a large quantity of micromammals associated with macrofauna. Studying these provided a bioclimatic and palaeoenvironmental framework that can be divided into five stages, starting at the end of Isotope Stage 5 and ending between Isotope Stages 3 and 2. The Middle Palaeolithic human occupations found in the upper levels occurred during a temperate episode with a cold tendency in Isotope Stage 5 (“Chauriat 1” Stage) and lasted until the “Chauriat 4” Stage at the end of Isotope Stage 3. For their lithic industries, Middle Palaeolithic people used tertiary flints found next to the shelter without considering their quality. These materials were used to obtain flakes in Levallois and discoid production modes. The upper levels contain Chatelperronian and unspecified Upper Palaeolithic occupations. The Chatelperronian took place in a climate correlated with an interstadial at the limit between Stages 3 and 2 (“Chauriat 5” Stage). Chatelperronian people were different than their predecessors in favouring better quality raw materials, found about twenty kilometres from the site. The industries of the upper levels aimed at producing straight and short blades blanks knapped with a soft stone hammer for the Chatelperronians, and long and curved blades blanks knapped with a soft organic hammer for the last occupiers of the shelter

Chapitre 29. De la déclaration orale du témoin à sa restitution écrite par le commissaire et son clerc à Paris au xviiie siècle

Les témoins sont nécessaires à la justice d’Ancien Régime, qui n’a à sa disposition que peu de moyens scientifiques pour établir des preuves. Le flagrant délit étant rarissime et l’aveu toujours suspect, le témoignage est considéré comme la preuve la plus importante. L’information constitue donc, dans la plupart des affaires, l’élément fondamental de la procédure criminelle. Il est frappant de remarquer la qualité du niveau de la langue employée dans les dépositions, ainsi que la cohérence de..

Implications biostratigraphiques et paléoenvironnementales des occupations du Paléolithique moyen et du Châtelperronien du site de La Tour Fondue à Chauriat (Puy-de-Dôme, France)

International audienceThis work presents the results of the excavation carried out in 2004 on part of the shelter of La Tour Fondue at Chauriat (fig. 1). The aim of this intervention was to specify the chronological and stratigraphic position of the human settlements, to characterize them at a cultural level and to establish the local paleoenvironment. The sedimentary deposits were more than 3.20 m high (fig. 5 to 7). The lower set (levels 5 to 3b) yielded Mousterian industry and fauna. The upper set yielded Chatelperronian industry and fauna (level 3a) and some lithic artefacts which belong to an unidentified Upper Paleolithic settlement (level 2). The paleontological studies demonstrated the essentially anthropological character of the bones remains in the shelter, the carnivores playing only a minor role. Horse remains are dominant in the fauna followed by Bos or Bison and Reindeer (tab. 6 to 14).The large quantity of micromammals collected during the excavation allowed determining a bioclimatic paleoenvironment, largely confirmed by the study of the macro-fauna (fig. 8). The Mousterian activities constituting the lower set took place during a temperate episode with a cold tendency in OIS 5 (« Chauriat 1 » stage). The environment was quite dry and the landscape sharply opened, with some restricted woody areas which declined during the following climatic deterioration (« Chauriat 2 » stage), correlated to OIS 4. During the following stage, dry and correlated to the end of OIS 3 (« Chauriat 3 » stage), the forest almost completely disappeared around the site. The conditions became milder again during the following stage which, from its beginning, corresponded to the end of the Mousterian (« Chauriat 4 » stage). The forest increased again with more humidity. This stage, situated at the end of OIS 3, corresponds very certainly to Les Cottés Interstadial. The evolution of the biozone corresponded to the climatic instability which followed the interstadial. The climate became drier and the forest increased again during the following stage, correlated with an interstadial at the limit between OIS 3 and OIS 2 (« Chauriat 5 » stage). The Chatelperronian took place during this last phase (33 402554 BP (Wk-17109)) at the base of level 2 and the top of level 3a. As it is the case in several sites such as « La grotte du Renne » in Arcy-sur-Cure, the Chatelperronian is found at the end of Les Cottés Interstadial (Girard et al. 1990 ; Pelegrin 1995).The Mousterian lithic industry shows an homogeneity which is certainly attributable to the small size of the series. The behavioural differences are clearer when we compare the Mousterian with the Chatelperronian and with the last Palaeolithic level. From the point of view of raw materials, Mousterian people used flint situated near the shelter without questioning its qualities. Châtelperronian people worried about this more and their territory of acquisition was about twenty kilometers around the site. It is also the case of the last occupants of the shelter who imported material from the Berry region. The Mousterian industry was using Levallois and discoïdal debitages to obtain flakes which are essentially retouched in scrapers (fig. 11 and 12). Chatelperronian people used soft stone to produce rectilinear and short blades and retouched different types of tools (fig. 13 to 16). The last inhabitants of the shelter used organic soft hammers to obtain long and curved blades (fig. 17).Ce travail présente les résultats de l’opération de terrain réalisée en 2004 sur une partie de l’abri-sous-roche de la Tour Fondue à Chauriat. Les objectifs de cette intervention ponctuelle (ravivage de coupe) étaient de préciser la position chronologique et stratigraphique des occupations humaines, de les caractériser sur un plan culturel et d’établir le cadre paléoenvironnemental dans lequel elles se sont développées. Les dépôts sédimentaires qui se développent sur plus de 3,20 m ont livré une grande quantité de micromammifères associés à de la macrofaune. Le cadre bioclimatique et paléoenvironnemental obtenu grâce à leur étude se divise en 5 phases, couvrant la fin du stade isotopique 5 jusqu’à la limite entre les stades isotopiques 3 et 2. Les occupations humaines du Paléolithique moyen constituant l’ensemble inférieur se mettent en place au cours d’un épisode tempéré à tendance froide du stade isotopique 5 (phase « Chauriat 1 ») et perdurent jusqu’à la phase « Chauriat 4 », située à la fin du stade isotopique 3. Du point de vue des industries lithiques, les hommes du Paléolithique moyen utilisent des silex tertiaires situés à proximité de l’abri sans tenir compte de leur qualité. Ces matériaux sont destinés à produire des éclats selon des modes de production Levallois et discoïde. L’ensemble supérieur regroupe les vestiges d’une occupation châtelperronienne et paléolithique supérieur indéterminée. Le Châtelperronien se développe dans un climat corrélé à un interstade marquant la limite entre les stades 3 et 2 (phase « Chauriat 5 »). Les Châtelperroniens marquent leurs différences par rapport à leurs prédécesseurs en privilégiant des matériaux de meilleure qualité, situés à une vingtaine de kilomètres autour du site. Les industries de cet ensemble supérieur sont orientées vers la production de supports laminaires rectilignes et courts, détachés à la pierre tendre dans le cas du Châtelperronien, longs et courbes, débités au percuteur tendre organique pour les derniers occupants de l’abri

Disrupting D1-NMDA or D2-NMDA receptor heteromerization prevents cocaine’s rewarding effects but preserves natural reward processing

International audienc

ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is a high-risk subtype of acute lymphoblastic leukemia (ALL) with gradually improved survival through introduction of intensified chemotherapy. However, therapy-resistant or refractory T-ALL remains a major clinical challenge. Here, we evaluated B-cell lymphoma (BCL)-2 inhibition by the BH3 mimetic ABT-199 as a new therapeutic strategy in humanT-ALL. The T-ALL cell line LOUCY, which shows a transcriptional program related to immature T-ALL, exhibited high in vitro and in vivo sensitivity for ABT-199 in correspondence with high levels of BCL-2. In addition, ABT-199 showed synergistic therapeutic effects with different chemotherapeutic agents including doxorubicin, L-asparaginase, and dexamethasone. Furthermore, in vitro analysis of primary patient samples indicated that some immature, TLX3-orHOXA-positive primary T-ALLs are highly sensitive to BCL-2 inhibition, whereas TAL1 driven tumors mostly showed poor ABT-199 responses. Because BCL-2 shows high expression in early T-cell precursors and gradually decreases during normal T-cell differentiation, differences in ABT-199 sensitivity could partially be mediated by distinct stages of differentiation arrest between different molecular genetic subtypes of human T-ALL. In conclusion, our study highlights BCL-2 as an attractive molecular target in specific subtypes of human T-ALL that could be exploited by ABT-199

Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (rs). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (rs −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population

Distress in parents of children with first-onset steroid-sensitive nephrotic syndrome

Background Steroid-sensitive nephrotic syndrome (SSNS) is associated with a relapsing-remitting course that can be stressful for parents. As little is known of parental distress at the first onset of SSNS, this study aims to describe parental distress and everyday problems in mothers and fathers of a child with newly diagnosed SSNS participating in a randomized controlled trial of levamisole added to corticosteroids. Methods To assess distress, the Distress Thermometer for Parents (DT-P) was used, which includes questions on distress (thermometer score 0-10, >= 4 "clinical distress") and presence of everyday problems in six domains: practical, social, emotional, physical, cognitive, and parenting. The DT-P was completed 4 weeks after the onset of SSNS. Total sum and individual items of everyday problems were compared with reference data from mothers and fathers of the Dutch general population. Results There was no difference in clinically elevated parental distress between SSNS mothers (n = 37) and fathers (n = 25) and reference parents. Compared to reference fathers, fathers of a child with SSNS scored significantly higher on emotional problems (P = 0.030), while mothers experienced more parenting problems (P = 0.002). Regression analyses showed that lower parental age and having a girl with SSNS were significantly associated with more practical problems and higher distress thermometer scores, respectively. Conclusions Four weeks after onset, SSNS mothers and fathers experience equal distress as reference parents. However, both parents endorsed significantly more everyday problems. Therefore, monitoring parental distress, even in the first weeks of the disease, could contribute to timely interventions and prevent worsening of problems. Clinical trial registry Dutch Trial Register (https://onderzoekmetmensen.nl/en/trial/27331)