Analysis of the collapsibility of the upper airway in a spectrum of sleep-disordered breathing: a modelling approach

Using a simplified model of the upper airways with two independent collapsible elements (nostrils and hypo-pharynx), we calculated the cross-sectional area of these two elements, taking into account pressure drops. We experimentally measured flow and pressure in the fossa and hypo-pharynx in various syndromes. This allowed us to compare the behaviour of the area supplied by our model with the aerodynamic resistance that is often used to analyse upper airway flow limitation events. We showed that nostril and hypo-pharyngeal areas are better correlated than the resistance values and thus concluded that the pressure divided by the square of the flow is a better parameter for analysing flow limitation in upper airways than resistance. Owing to its simplicity, our model is able to supply the area of the collapsible element in real time, which is impossible with more sophisticated models.     

Insight into the chiral recognition of warfarin enantiomers by epichlorhydrin/beta-cyclodextrin polymer-based supports: determination of stoichiometry and stability of warfarin/beta-cyclodextrin polymer complexes

The complexation of warfarin (W) enantiomers by a hydrosoluble high-molecular-weight beta-cyclodextrin/epichlohydrin polymer (EP/beta-CD polymer) was studied using HPLC with a mobile phase of methanol/0.1 M Na acetate/acetic acid (pH 4) at 22 degrees C. It was found that the complexes (W/beta-CD unit) have a 1:1 stoichiometry. The stability constants of the complex involving each enantiomer and the polymer beta-CD units were determined in the mobile phase, and the highest stability of the complex (S-warfarin/beta-CD unit) was observed. From the chromatographic separations of warfarin enantiomers on different beta-CD or its derivative supports, we have deduced the role of the simultaneous presence of several glyceryl (-O-CH(2)-CHOH-CH(2)-O-) and dihydroxypropyl (-O-CH(2)-CHOH-CH(2)OH) groups on one beta-CD ring in promoting the chiral recognition of warfarin enantiomers.     

Structural features of two distinct molecular complexes of copper(II) cationic porphyrin and deoxyribonucleotides

The associations of the water-soluble cationic copper(II)-5,10,15,20-meso-tetrakis(4-N-methylpyridyl) porphyrin (CuP) with d(pT)9 oligothymidylate and its building blocks deoxythymidine (dT) and deoxythymidine 5'-monophosphate (dTMP) were investigated by spectrophotometric titration [absorption, nanosecond transient resonance Raman (ns-RR) and picosecond time-resolved resonance Raman (ps-TR3) spectroscopies] to elucidate the structural requirements for the CuP exciplex formation in molecular complexes with unchained mononucleotides. In the d(pT)9 a factor analysis and global fit of the CuP absorption spectra revealed the formation of a single spectral species attributable to a 1 : 1 CuP. d(pT)9 complex throughout a wide range of d(pT)9/CuP ratios (0-10). Using ps-TR3 spectroscopy, the CuP. d(pT)9 complex was shown to be fully responsible for exciplex formation. In contrast, CuP mixed with dTMP ([dTMP]/[CuP] < 3000) yielded two spectroscopically distinct types of molecular complexes with 1 : 1 (CuP. dTMP) and 1 : 2 (CuP. (dTMP)2) (or even higher for [dTMP]/[CuP] > 3000) stoichiometry, the latter being spectroscopically identical to the CuP. d(pT)9 and providing a microenvironment favorable for exciplex formation to the same extent as the oligothymidylate. On the other hand, the 1 : 1 CuP. dTMP complex (prevailing for [dTMP]/[CuP] < 100) yielded no exciplex features. Similar behavior was observed for the CuP complexed with dT. To explain the difference in the ability of the CuP. dTMP and CuP. (dTMP)2 species to form the exciplex, two types of molecular complexes were suggested and discussed, differing in the orientation of the thymine planes with respect to the porphyrin macrocycle.     

Local survival after fire in Mediterranean shrublands: combining capture-recapture data over several bird species

Post-disturbance survival is a key factor in the onset of secondary successions. Here we analyse capture-recapture data from two before/after disturbance studies to estimate the effect of fire on local bird survival. Analyses of six bird species at two Mediterranean shrubland sites were combined using a meta-analysis approach. Two warblers, Sylvia undata and S. melanocephala, were studied at one site altered by prescribed burning, and five passerines (Luscinia megarhynchos, Turdus merula, Parus major, P. caeruleus and S. melanocephala) at one site disturbed by wildfire. Based on the combined analysis, annual survival probability significantly decreased from 0.49 to 0.18 (i.e. a 64% decline) after the fire. Our results further suggest a trend for a higher decrease in annual survival associated with wildfire (–72%, from 0.51 to 0.14) than with prescribed burning (–35%, from 0.41 to 0.27), although this should be properly tested with a specific experimental design. In S. undata, a decline in survival in the long-term cannot account for the drop in density observed the first spring after fire. We suggest that a decrease in recruitment rate and an increase in the proportion of non-breeders immediately after the fire may contribute more strongly to the decline in the breeding population. Our results tend to support the idea that bird populations may respond to moderate disturbances with noticeable time lags, because of individual site tenacity.     

Characterization of a radish introgression carrying the Ogura fertility restorer gene Rfo in rapeseed,using the Arabidopsis genome sequence and radish genetic mapping

The radish Rfo gene restores male fertility in radish or rapeseed plants carrying Ogura cytoplasmic male-sterility. This system was first discovered in radish and was transferred to rapeseed for the production of F1 hybrid seeds. We aimed to identify the region of the Arabidopsis genome syntenic to the Rfo locus and to characterize the radish introgression in restored rapeseed. We used two methods: amplified consensus genetic markers (ACGMs) in restored rapeseed plants and construction of a precise genetic map around the Rfo gene in a segregating radish population. The use of ACGMs made it possible to detect radish orthologs of Arabidopsis genes in the restored rapeseed genome. We identified radish genes, linked to Rfo in rapeseed and whose orthologs in Arabidopsis are carried by chromosomes 1, 4 and 5. This indicates several breaks in colinearity between radish and Arabidopsis genomes in this region. We determined the positions of markers relative to each other and to the Rfo gene, using the progeny of a rapeseed plant with unstable meiotic transmission of the radish introgression. This enabled us to produce a schematic diagram of the radish introgression in rapeseed. Markers which could be mapped both on radish and restored rapeseed indicate that at least 50 cM of the radish genome is integrated in restored rapeseed. Using markers closely linked to the Rfo gene in rapeseed and radish, we identified a contig spanning six bacterial artificial chromosome (BAC) clones on Arabidopsis chromosome 1, which is likely to carry the orthologous Rfo gene.Electronic Supplementary Material Supplementary material is available in the online version of this article at Communicated by H. C. BeckerS. Giancola and S. Marhadour contributed equally to this work     

Which future for the French Pyrenean brown bear (Ursus arctos) population? An approach using stage-structured deterministic and stochastic models

The Pyrenean brown bear (Ursus arctos) population is considered as one of the most seriously threatened with extinction in Western Europe. To assess its viability and possible needs of augmentation, we develop deterministic and stochastic stage-structured demographic models. The deterministic model reveals that a bear population cannot have a high annual growth rate and is particularly sensitive to breeder survival. High demographic parameters appear to be crucial to population persistence, especially for a small population that remains vulnerable to demographic and environmental stochasticities. The Pyrenean population cannot therefore be considered as viable. Successful conservation strategies for this population would require releasing more bears in both sub-populations in the near future.     

Structure-activity relationships of human urotensin II and related analogues on rat aortic ring contraction

The sequence of human urotensin II (UII) has been recently established as H-Glu-Thr-Pro-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH, and it has been reported that UII is the most potent mammalian vasoconstrictor peptide identified so far. A series of UII analogues was synthesized, and the contractile activity of each compound was studied in vitro using de-endothelialised rat aortic rings. Replacement of each amino acid by an L-alanine or by a D-isomer showed that the N- and C-terminal residues flanking the cyclic region of the amidated peptide were relatively tolerant to substitution. Conversely, replacement of any residue of the cyclic region significantly reduced the contractile activity of the molecule. The octapeptide UII(4-11) was 4 times more potent than UII, indicating that the C-terminal region of the molecule possesses full biological activity. Alanine or D-isomer substitutions in UII(4-11) or in UII(4-11)-NH2, respectively, showed a good correlation with the results obtained for UII-NH2. Disulfide bridge disruption or replacement of the cysteine residues by their D-enantiomers markedly reduced the vasoconstrictor effect of UII and its analogues. In contrast, acetylation of the N-terminal residue of UII and UII-NH2 enhanced the potency of the peptide. Finally, monoiodination of the Tyr6 residue in UII(4-11) increased by 5 fold the potency of the peptide in the aortic ring bioassay. This structure-activity relationship study should provide useful information for the rational design of selective and potent UII receptor agonists and antagonists.     

Synthesis and cytotoxic evaluation of novel thiazolocarbazoles. Part III

Novel thiazolocarbazole derivatives have been synthesized via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor activity of these polyheterocyclic compounds was studied.     

Synthesis of 5-substituted-2,3-dihydro-1,4-benzoxathiins: biological evaluation as melatonin receptors ligands

The synthesis of benzoxathiins bearing a retroamide function is described from 8-hydroxythiochroman, the key step involving the synthesis of the benzoxathiin ring through a sulfonium salt. These new melatonin analogues were evaluated on human receptors MT1 and MT2 and have a similar affinity to that of melatonin itself.     

Potential inhibitors of angiogenesis. Part I: 3-(imidazol-4(5)-ylmethylene)indolin-2-ones

The synthesis and pharmacological evaluation of new 3-(imidazol-4(5)-ylmethylene)indolin-2-ones, analogues of SU-5416, are reported. The final compounds 20-51 were obtained by Knoevenagel coupling between the substituted indolin-2-ones 1-15 and either the formylimidazole derivatives 16-18 or 2-formyl-3,5-dimethylpyrrole 19. Methylation at the nitrogen atom of the indolin-2-one and/or imidazole moities was carried out in the presence of the couple NaH/DMF. A Mannich reaction afforded the 1-dimethylaminomethyl derivatives 43 and 48. The antiangiogenic activity of these compounds was evaluated in a three dimensional in vitro rat aortic ring assay. In this test, compound 20 induced a decrease of angiogenesis comparable to that observed with SU-5416; the vascular density indexes at 1 microM were 30 +/- 18 and 22 +/- 4% of control, respectively. The compounds were also evaluated, in an independent manner, as inhibitors of the human EGF-receptor tyrosine kinase activity. As expected, only minor activities were observed with four compounds, out of thirty-one, exerting inhibitory effects in the range of 40-55% at 10 microM concentration.