Habitat et mode de vie des chasseurs paléolithiques de la Caune de l'Arago (600 000-400 000 ans)

Several human occupations have been identified within the deposits of the Caune de l’Arago Cave site, dated from 700 000 years to 100 000 years old. The exceptional wealth of these archeological levels provides an opportunity for the study of different types of habitat and behavioral patterns of Paleolithic hunters between 600 000 and 400 000 years ago. Results from preliminary studies, carried out over the last 30 years on these archeological levels, allow for the proposition of a typology for cave habitats during the Middle Pleistocene in the south of France. In fact, four types of habitat were identified and defined. They have been described according to different characteristics such as, the thickness of the archeological accumulation, the animal species represented, the season during which the animals were hunted, the state of conservation of the fossils discovered, the morpho-technological and typological characteristics of the lithics, the categories of raw materials used and the territory exploited by the hominids inhabiting the cave, as defined by the raw materials represented. The four habitation types defined are: the long duration habitat, where the cave was used as a home base; the temporary seasonal habitat, in which case the cave served as a secondary campsite; the hunting stopover and the bivouac, during which the cave was used as a refuge for short term stays. Behavioral patterns appear to be directly related to the type of habitat and oriented towards a principal activity: hunting. The activities performed by the inhabitants of the cave seem to be more diversified during prolonged or seasonal occupations, whereas they appear to be reduced or very specialised during brief stays. Generally, The characteristics studied show that the Caune de l’Arago Cave site had multiple uses over time for Anteneandertalian family groups and hunters who left traces of their activities, allowing us to better understand their lifestyle.     

Proprotein convertase activation of aggrecanases in cartilage in situ

Proteolytic degradation of the major cartilage macromolecules, aggrecan and type II collagen, is a key pathological event in osteoarthritis (OA). ADAMTS-4 and ADAMTS-5, the primary aggrecanases capable of cartilage aggrecan cleavage, are synthesized as latent enzymes and require prodomain removal for activity. The N-termini of the mature proteases suggest that activation involves a proprotein convertase, but the specific family member responsible for aggrecanase activation in cartilage in situ has not been identified. Here we describe purification of a proprotein convertase activity from human OA cartilage. Through biochemical characterization and the use of siRNA, PACE4 was identified as a proprotein convertase responsible for activation of aggrecanases in osteoarthritic and cytokine-stimulated cartilage. Posttranslational activation of ADAMTS-4 and ADAMTS-5 was observed in the extracellular milieu of cartilage, resulting in aggrecan degradation. These findings suggest that PACE4 represents a novel target for the development of OA therapeutics.     

Increased formation of pyridinoline cross-links due to higher telopeptide lysyl hydroxylase levels is a general fibrotic phenomenon.

Fibrosis is characterized by an excessive accumulation of collagen which contains increased levels of pyridinoline cross-links. The occurrence of pyridinolines in the matrix is an important criterion in assessing the irreversibility of fibrosis, which suggests that collagen containing pyridinoline cross-links significantly contributes to the unwanted collagen accumulation. Pyridinoline cross-links are derived from hydroxylated lysine residues located within the collagen telopeptides (hydroxyallysine pathway). Here, we have investigated whether the increase in hydroxyallysine-derived cross-links in fibrotic conditions can be ascribed to an increased expression of one of the lysyl hydroxylases (LH1, LH2 with its splice variants LH2a and LH2b, or LH3) and/or to an increased expression of lysyl oxidase (LOX). In fibroblast cultures of hypertrophic scars, keloid and palmar fascia of Dupuytren's patients, as well as in activated hepatic stellate cells, increased levels of LH2b mRNA expression were observed. Only minor amounts of LH2a were present. In addition, no consistent increase in the mRNA expression levels of LH1, LH3 and LOX could be detected, suggesting that LH2b is responsible for the overhydroxylation of the collagen telopeptides and the concomitant formation of pyridinolines as found in the collagen matrix deposited in long-term cultures by the same fibrotic cells. This is consistent with our previous observation that LH2b is a telopeptide lysyl hydroxylase. We conclude that the increased expression of LH2b, leading to the increased formation of pyridinoline cross-links, is present in a wide variety of fibrotic disorders and thus represents a general fibrotic phenomenon.     

Endoplasmic reticulum-associated degradation of glycoproteins bearing Man5GlcNAc2 and Man9GlcNAc2 species in the MI8-5 CHO cell line.

Endoplasmic reticulum-associated degradation of newly synthesized glycoproteins has been demonstrated previously using various mammalian cell lines. Depending on the cell type, glycoproteins bearing Man9 glycans and glycoproteins bearing Man5 glycans can be efficiently degraded. A wide variety of variables can lead to defective synthesis of lipid-linked oligosaccharides and, therefore, in mammalian cells, species derived from Man9GlcNAc2 or Man5GlcNAc2 are often recovered on newly synthesized glycoproteins. The degradation of glycoproteins bearing these two species has not been studied. We used a Chinese hamster ovary cell line lacking Glc-P-Dol-dependent glucosyltransferase I to generate various proportions of Man5GlcNAc2 and Man9GlcNAc2 on newly synthesized glycoproteins. By studying the structure of the soluble oligomannosides produced by degradation of these glycoproteins, we demonstrated the presence of a higher proportion of soluble oligomannosides originating from truncated glycans, showing that glycoproteins bearing Man5GlcNAc2 glycans are degraded preferentially.     

Euxinocythere (Ostracoda, Cytheridae, Leptocytherinae) du Miocène supérieur du Bassin de Turiec (Slovaquie) : taxonomie et paléoécologie

Eight new species of the family Cytheridae have been identified in the Upper Miocene deposits of the Turiec Basin (Slovakia), a small isolated intermountain depression. Six species are new - Euxinocythere aphroditae, E. delicata, E. lactea, E. minuscula, E. quadricostata, E. satyrica - and two are kept in open nomenclature. Their attribution to the genus Euxinocythere is based on arrangement of the hinge elements and of anterior marginal zone. This genus is known from brackish ostracod assemblages of the Paratethys and the Eastern Mediterranean while the species from the Turiec Basin are associated to fresh-water assemblages. The Euxinocythere have been found in littoral as well in deep limnic environment.     

Markers of vascular endothelial cell damage and P. falciparum malaria: association between levels of both sE-selectin and thrombomodulin, and cytokines, hemoglobin and clinical presentation

We investigated associations between markers of damage of vascular endothelial cells (MDVECs) and plasma cytokine levels, hemoglobin level and temperature in individuals with acute uncomplicated malaria, as well as healthy controls, using enzyme linked immunosorbent assay (ELISA) for the presence of soluble endothelial cell adhesion molecule-1 (sE-selectin), circulating granule membrane protein-140 (sP-selectin), circulating thrombomodulin (TM), circulating von Willebrand factor (VWf), interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Significant differences were observed between falciparum malaria patients and the healthy people in term of levels of both sE-selectin and TM. The serum levels of sP-selectin and VWf were comparable between the two groups. The levels of both sE-Selectin and TM correlated positively with temperature, levels of IFN-gamma and levels of TNF-alpha; and negatively with hemoglobin levels. Trends of positive correlations were observed between level of sP-selectin or VWf and temperature. Furthermore, sE-selectin levels correlated with vomiting. These data suggest that sE-selectin and TM might be useful markers of endothelium activation in in vivo studies. Moreover, our results highlight the use of both sE-selctin and TM as markers of anemia.     

Synthesis and biological evaluation of new donepezil-like Thiaindanones as AChE inhibitors

Pharmacomodulations of previously reported thiaindanones related to donepezil were achieved with the aim to enhance their AChE inhibitory activity. Condensation of the cyclopentane carbonyl group into hydrazone or cyanolefine derivatives, as well as its hydrogenation and the subsequent substitution of the resulting hydroxyl group led to new 2-(4-benzylpiperazin-1-yl)-N-(1,3-dibromo-6-hydroxy-5,6-dihydro-4H-cyclopenta[c]thien-4-yl) acetamides. The in vitro evaluation of this new series, according to the method of Ellman, shows however that it conserved only partially the biological activity. The best compound remains the alcohol 11 (IC(50) = 0.40 microM, against 0.02 microM for donepezil).     

Recent advances in tRNA mitochondrial import

In many eukaryotes, tRNA import from the cytosol into mitochondria is essential for mitochondrial biogenesis and, consequently, for cell viability. Recent work has begun to unravel the molecular mechanisms involved in tRNA transport in yeast, trypanosomatids and plants. The mechanisms of tRNA targeting to, and translocation through, the double mitochondrial membrane in addition to how selectivity and regulation of these processes are achieved are the main questions that have been addressed. The characterization of both direct and co-import mechanisms involving distinct protein-import factors is in agreement with a polyphyletic origin of tRNA import. Moreover, our increased understanding of the tRNA-import pathway has been exploited recently to rescue dysfunctions associated with mitochondrial tRNA mutations.     

Drench treatments for management of larval Japanese beetle (Coleoptera: Scarabaeidae) in field-grown balled and burlapped nursery plants

Insecticide drenches were applied to postharvest field-grown nursery plants harvested as 60-cm-diameter balled and burlapped (B&B) root balls for controlling third instars of Japanese beetle, Popillia japonica Newman (Coleoptera: Scarabaeidae). Bifenthrin, chlorpyrifos, lambda-cyhalothrin, and thiamethoxam were drench-applied in fall and spring tests at volumes of runoff (1X; approximately equal 2.57 liters per drench per root ball) or twice runoff (2X). Tests also examined consecutive drenches (two, four, or six) and B&B rotation between drenches. Fall-applied drenches did not meet the Domestic Japanese Beetle Harmonization Plan (DJHP) standards of < or =1 grub and ranged from 0 to 90% control. However, most fall-applied drenches significantly reduced grub numbers relative to the untreated root balls. Spring-applied drenches were more effective than fall drenches: chlorpyrifos treatments gave 94-100% control, whereas other spring-applied treatments were less consistent, including thiamethoxam (83-100% control) and bifenthrin (61-100% control). Lambda-cyhalothrin was not effective. A higher drench volume (2X) did not significantly improve treatment efficacy; however, grub numbers decreased as the number of drenches increased for fall-applied chlorpyrifos and thiamethoxam and spring-applied bifenthrin. Rotation of root balls significantly reduced grub numbers compared with nonrotated treatments for fall-applied chlorpyrifos (six drenches) and bifenthrin (two or six drenches), but these treatments did not meet DJHP standards. The study indicates chlorpyrifos, bifenthrin, and thiamethoxam drenches can control Japanese beetle in the spring and may provide a new postharvest option to certify B&B plants for Japanese beetle.