L'évolution des gastéropodes lacustres et la paléoéologie des diatomées dans le Néogène de Kos (Dodécanèse,Grèce)

Evolutionary lineages of several limnic gastropod genera (Viviparus, Melanopsis, Theodoxus) from the Neogene of Kos island (Dodecanese, Greece) are described and interpreted. The attempt is made to analyse the paleoecological development of a limnic sedimentary basin in the eastern portion of Kos by means of Diatoms. Obviously, there is no relation between the chemical parameters of the water of the former lake and the morphological development of the gastropods. The lineages of Viviparus brevis, Theodoxus doricus and Melanopsis gorceixi are suggested to be caused by phyletic transformations and not by changing environmental conditions. It is, thus, possible to establish a local biostratigraphy based on subspecies, and moreover, a more regional one based on longer ranging species.     

Structures of complexes of rhizopuspepsin with pepstatin and other statine-containing inhibitors.

The three-dimensional structures of the complexes of the aspartic proteinase from Rhizopus chinensis (Rhizopuspepsin, EC 3.4.23.6) with pepstatin and two pepstatin-like peptide inhibitors of renin have been determined by X-ray diffraction methods and refined by restrained least-squares procedures. The inhibitors adopt an extended conformation and lie in the deep groove located between the two domains of the enzyme. Inhibitor binding is accompanied by a conformational change at the "flap," a beta-hairpin loop region, that projects over the binding cleft and closes down over the inhibitor, excluding water molecules from the vicinity of the scissile bond. The hydroxyl group of the central statyl residue of the inhibitors replaces the water molecule found between the two active aspartates, Asp-35 and Asp-218, in the native structure. The refined structures provide additional data to define the specific subsites of the enzyme and also show a system of hydrogen bonding to the inhibitor backbone similar to that observed for a reduced inhibitor.     

The Sleep-inducing Lipid Oleamide Deconvolutes Gap Junction Communication and Calcium Wave Transmission in Glial Cells

Oleamide is a sleep-inducing lipid originally isolated from the cerebrospinal fluid of sleep-deprived cats. Oleamide was found to potently and selectively inactivate gap junction–mediated communication between rat glial cells. In contrast, oleamide had no effect on mechanically stimulated calcium wave transmission in this same cell type. Other chemical compounds traditionally used as inhibitors of gap junctional communication, like heptanol and 18β-glycyrrhetinic acid, blocked not only gap junctional communication but also intercellular calcium signaling. Given the central role for intercellular small molecule and electrical signaling in central nervous system function, oleamide- induced inactivation of glial cell gap junction channels may serve to regulate communication between brain cells, and in doing so, may influence higher order neuronal events like sleep induction.     

Synthesis of appropriately functionalized vancomycin CD and DE ring systems

Synthesis of appropriately and fully functionalized 16-membered CD and DE ring systems of vancomycin is detailed.     

Design, synthesis, and biological evaluation of 10-methanesulfonyl-DDACTHF, 10-methanesulfonyl-5-DACTHF, and 10-methylthio-DDACTHF as potent inhibitors of GAR Tfase and the de novo purine biosynthetic pathway

The synthesis and evaluation of 10-methanesulfonyl-DDACTHF (1), 10-methanesulfonyl-5-DACTHF (2), and 10-methylthio-DDACTHF (3) as potential inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) are reported. The compounds 10-methanesulfonyl-DDACTHF (1, K(i) = 0.23 microM), 10-methanesulfonyl-5-DACTHF (2, K(i) = 0.58 microM), and 10-methylthio-DDACTHF (3, K(i) = 0.25 microM) were found to be selective and potent inhibitors of recombinant human GAR Tfase. Of these, 3 exhibited exceptionally potent, purine sensitive growth inhibition activity (3, IC50 = 100 nM) against the CCRF-CEM cell line being 3-fold more potent than Lometrexol and 30-fold more potent than the parent, unsubstituted DDACTHF, whereas 1 and 2 exhibited more modest growth inhibition activity (1, IC50 = 1.0 microM and 2, IC50 = 2.0 microM).     

The effects of bone and pore volume fraction on the mechanical properties of PMMA/bone biopsies extracted from augmented vertebrae

Vertebroplasty forms a porous PMMA/bone composite which was shown to be weaker and less stiff than pure PMMA. It is not known what determines the mechanical properties of such composites in detail. This study investigated the effects of bone volume fraction (BV/TV), cement porosity (PV/(TV-BV), PV…pore volume) and cement stiffness. Nine human vertebral bodies were augmented with either standard or low-modulus PMMA cement and scanned with a HR-pQCT system before and after augmentation. Fourteen cylindrical PMMA/bone biopsies were extracted from the augmented region, scanned with a micro-CT system and tested in compression until failure. Micro-finite element (FE) models of the complete biopsies, of the trabecular bone alone as well as of the porous cement alone were generated from CT images to gain more insight into the role of bone and pores. PV/(TV-BV) and experimental moduli of standard/low-modulus cement (R(2)=0.91/0.98) as well as PV/(TV-BV) and yield stresses (R(2)=0.92/0.83) were highly correlated. No correlation between BV/TV (ranging from 0.057 to 0.138) and elastic moduli was observed (R(2)< 0.05). Interestingly, the micro-FE models of the porous cement alone reproduced the experimental elastic moduli of the standard/low-modulus cement biopsies (R(2)=0.75/0.76) more accurately than the models with bone (R(2)=0.58/0.31). In conclusion, the mechanical properties of the biopsies were mainly determined by the cement porosity and the cement material properties. The study showed that bone tissue inside the biopsies was mechanically "switched off" such that load was carried essentially by the porous PMMA.     

Oviposition response of the moth Lobesia botrana to sensory cues from a host plant

The grapevine moth Lobesia botrana is a generalist insect herbivore and grapevine is one of its hosts. Previous studies have shown that insects use their olfactory abilities to locate hosts from a distance; whereas contact chemoreception mediates the stimulation of oviposition after landing. Little is known about the role of olfaction and its interactions with contact chemoreception and vision once the insect lands on the plant. Plant volatile compounds can be sensed by host-searching insects located some distance from the plant and insects sense both volatile and nonvolatile cues after landing on a plant. In the present study, we investigated the effects of these volatile and nonvolatile cues on the oviposition behavior of L. botrana. A behavioral bioassay with choice was developed in which insects were offered each sensory cue either alone or in combination with one or 2 other cues. Females were allowed to choose between a device with the stimulus and a blank device. Results were evaluated in terms of 2 parameters: quantity of eggs laid (egg counts) and preference for the stimulus (ODI: oviposition discrimination index). Our results suggest that olfaction significantly affects egg quantity and that there is significant synergism between olfaction and vision, in terms of their combined effect on egg quantity. In terms of preference (ODI), our results did not show a significant preference for any single cue; the highest ODI was measured for the full-cue stimulus (olfaction, vision, and contact). For ODI, a significant interaction was observed between olfaction and vision and a nearly significant interaction was observed between the olfactory and contact cues. The results are discussed in relation to the effects of plant sensory cues on the oviposition behavior of L. botrana.     

Multidrug resistance reversal activity of key ningalin analogues

Key analogue derivatives of the ningalins, potent multidrug resistance (MDR) reversal compounds, were examined resulting in the discovery of a potent MDR reversal agent that hypersensitizes P-gp resistant tumor cell lines to front-line conventional therapeutic agents.     

Cytokine receptor dimerization and activation: prospects for small molecule agonists

Ligand-induced dimerization of cell surface receptors has emerged as a general mechanism for the initiation of signal transduction. A number of therapeutically important receptor families are believed to be activated by this process. Recently available structural information, particularly for the erythropoietin receptor, has provided insight into the mechanism of receptor activation. These findings have also revealed important constraints on the nature of receptor-agonist complexes. The prospects of discovering small-molecule mimetics of such receptor agonists are discussed, including strategies which have led to the identification of a small number of peptide and non-peptide cytokine mimetics.