La cystocentèse chez le chat : enquête nationale auprès des vétérinaires praticiens et avis d’experts

La cystocentèse est considérée comme la méthode de référence pour collecter des urines chez le chat. Le but de cette étude était de réaliser une enquête afin d’évaluer cette pratique professionnelle parmi les vétérinaires praticiens français. Un questionnaire a choix multiple a été envoyé par courrier à l’ensemble des vétérinaires praticiens français (8198). Quarante-deux experts (travaillant dans l’enseignement, des laboratoires, dans l’industrie du pet-food ou des cliniques spécialisées) ont également été sondés dans le but de recueillir leur opinion sur la pratique de la cystocentèse par les vétérinaires praticiens. Le pourcentage de réponse des vétérinaires praticiens était de 27.2% et de 85.7% pour les experts. La fréquence de prélèvement d’urine par cystocentèse sur chat vigile était : jamais (30.7%), occasionnellement (42.4%), souvent (22.8%), toujours (2.8%), sans réponse (1.3%). La cystocentèse est considérée comme la méthode de référence pour le prélèvement d’urine par 67% des vétérinaires praticiens. Les indications de la cystocentèse pour les praticiens étaient : l’analyse d’urine (44.3%), la bactériologie (72.9%), et la décompression de la vessie (62.1%). La cystocentèse sans échographie était considérée comme très facile, facile, plutôt difficile, et très difficile par 12.3%, 48.2%, 25.6% et 2.5% des vétérinaires praticiens respectivement. En contraste, les experts considéraient que la cystocentèse était difficile ou très difficile pour l’ensemble des vétérinaires praticiens. 41.9% des praticiens seraient intéressés par une formation spécifique sur la cystocentèse. En conclusion, une formation sur la cystocentèse chez le chat est nécessaire. De plus, cette étude montre l’importance d’une enquête nationale pour évaluer les pratiques professionnelles

Enantioselectivity of human AMP, dTMP and UMP-CMP kinases

l-Nucleoside analogues such as lamivudine are active for treating viral infections. Like d-nucleosides, the biological activity of the l-enantiomers requires their stepwise phosphorylation by cellular or viral kinases to give the triphosphate. The enantioselectivity of NMP kinases has not been thoroughly studied, unlike that of deoxyribonucleoside kinases. We have therefore investigated the capacity of l-enantiomers of some natural (d)NMP to act as substrates for the recombinant forms of human uridylate-cytidylate kinase, thymidylate kinase and adenylate kinases 1 and 2. Both cytosolic and mitochondrial adenylate kinases were strictly enantioselective, as they phosphorylated only d-(d)AMP. l-dTMP was a substrate for thymidylate kinase, but with an efficiency 150-fold less than d-dTMP. Both l-dUMP and l-(d)CMP were phosphorylated by UMP-CMP kinase although much less efficiently than their natural counterparts. The stereopreference was conserved with the 2′-azido derivatives of dUMP and dUMP while, unexpectedly, the 2′-azido-d-dCMP was a 4-fold better substrate for UMP-CMP kinase than was CMP. Docking simulations showed that the small differences in the binding of d-(d)NMP to their respective kinases could account for the differences in interactions of the l-isomers with the enzymes. This in vitro information was then used to develop the in vivo activation pathway for l-dT

Molecular basis for the lack of enantioselectivity of human 3-phosphoglycerate kinase

Non-natural l-nucleoside analogues are increasingly used as therapeutic agents to treat cancer and viral infections. To be active, l-nucleosides need to be phosphorylated to their respective triphosphate metabolites. This stepwise phosphorylation relies on human enzymes capable of processing l-nucleoside enantiomers. We used crystallographic analysis to reveal the molecular basis for the low enantioselectivity and the broad specificity of human 3-phosphoglycerate kinase (hPGK), an enzyme responsible for the last step of phosphorylation of many nucleotide derivatives. Based on structures of hPGK in the absence of nucleotides, and bound to l and d forms of MgADP and MgCDP, we show that a non-specific hydrophobic clamp to the nucleotide base, as well as a water-filled cavity behind it, allows high flexibility in the interaction between PGK and the bases. This, combined with the dispensability of hydrogen bonds to the sugar moiety, and ionic interactions with the phosphate groups, results in the positioning of different nucleotides so to expose their diphosphate group in a position competent for catalysis. Since the third phosphorylation step is often rate limiting, our results are expected to alleviate in silico tailoring of l-type prodrugs to assure their efficient metabolic processing

Molecular basis for the lack of enantioselectivity of human 3-phosphoglycerate kinase

Non-natural l-nucleoside analogues are increasingly used as therapeutic agents to treat cancer and viral infections. To be active, l-nucleosides need to be phosphorylated to their respective triphosphate metabolites. This stepwise phosphorylation relies on human enzymes capable of processing l-nucleoside enantiomers. We used crystallographic analysis to reveal the molecular basis for the low enantioselectivity and the broad specificity of human 3-phosphoglycerate kinase (hPGK), an enzyme responsible for the last step of phosphorylation of many nucleotide derivatives. Based on structures of hPGK in the absence of nucleotides, and bound to l and d forms of MgADP and MgCDP, we show that a non-specific hydrophobic clamp to the nucleotide base, as well as a water-filled cavity behind it, allows high flexibility in the interaction between PGK and the bases. This, combined with the dispensability of hydrogen bonds to the sugar moiety, and ionic interactions with the phosphate groups, results in the positioning of different nucleotides so to expose their diphosphate group in a position competent for catalysis. Since the third phosphorylation step is often rate limiting, our results are expected to alleviate in silico tailoring of l-type prodrugs to assure their efficient metabolic processing

Observations of the dispersion characteristics and meridional sea level structure of equatorial waves in the Pacific Ocean

Author Posting. © American Meteorological Society, 2008. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 38 (2008): 1669-1689, doi:10.1175/2007JPO3890.1.Spectral techniques applied to altimetry data are used to examine the dispersion relation and meridional sea level structure of wavelike variability with periods of about 20 to 200 days in the equatorial Pacific Ocean. Zonal wavenumber–frequency power spectra of sea surface height, when averaged over about 7°S–7°N, exhibit spectral peaks near the theoretical dispersion curves of first baroclinic-mode equatorial Kelvin and Rossby waves. There are distinct, statistically significant ridges of power near the first and second meridional-mode Rossby wave dispersion curves. Sea level variability near the theoretical Kelvin wave and first meridional-mode Rossby wave dispersion curves is dominantly (but not perfectly) symmetric about the equator, while variability near the theoretical second meridional-mode Rossby wave dispersion curve is dominantly antisymmetric. These results are qualitatively consistent with expectations from classical or shear-modified theories of equatorial waves. The meridional structures of these modes resemble the meridional modes of equatorial wave theory, but there are some robust features of the meridional profiles that were not anticipated. The meridional sea level structure in the intraseasonal Kelvin wave band closely resembles the theoretically expected Gaussian profile, but sea level variability coherent with that at the equator is detected as far away as 11.75°S, possibly as a result of the forced nature of these Kelvin waves. Both first and second meridional-mode Rossby waves have larger amplitude in the Northern Hemisphere. The meridional sea level structure of tropical instability waves closely resembles that predicted by Lyman et al. using a model linearized about a realistic equatorial zonal current system.This work was supported in part by the NOAA Climate Prediction Program for the Americas (Grant NA17RJ1223)

Barotropic Rossby waves radiating from tropical instability waves in the Pacific Ocean

Author Posting. © American Meteorological Society, 2011. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 41 (2011): 1160–1181, doi:10.1175/2011JPO4547.1.Tropical instability waves are triggered by instabilities of the equatorial current systems, and their sea level signal, with peak amplitude near 5°N, is one of the most prominent features of the dynamic topography of the tropics. Cross-spectral analysis of satellite altimetry observations shows that there is sea level variability in the Pacific Ocean as far north as Hawaii (i.e., 20°N) that is coherent with the sea level variability near 5°N associated with tropical instability waves. Within the uncertainty of the analysis, this off-equatorial variability obeys the dispersion relation for nondivergent, barotropic Rossby waves over a fairly broad range of periods (26–38 days) and zonal wavelengths (9°–23° of longitude) that are associated with tropical instability waves. The dispersion relation and observed wave properties further suggest that the waves are carrying energy away from the instabilities toward the North Pacific subtropical gyre, which, together with the observed coherence of the sea level signal of the barotropic waves with that of the tropical instability waves, suggests that the barotropic Rossby waves are being radiated from the tropical instability waves. The poleward transport of kinetic energy and westward momentum by these barotropic Rossby waves may influence the circulation in the subtropics.Funding for this research came from WHOI’s TropicalResearch Initiative, the Charles D. Hollister Fund for Assistant Scientist Support, the John E. and Anne W. Sawyer Endowed Fund in Special Support of Scientific Staff, and Grant OCE-0845150 from the National Science Foundation

Structural Insights into the Inhibition of Cytosolic 5′-Nucleotidase II (cN-II) by Ribonucleoside 5′-Monophosphate Analogues

Cytosolic 5′-nucleotidase II (cN-II) regulates the intracellular nucleotide pools within the cell by catalyzing the dephosphorylation of 6-hydroxypurine nucleoside 5′-monophosphates. Beside this physiological function, high level of cN-II expression is correlated with abnormal patient outcome when treated with cytotoxic nucleoside analogues. To identify its specific role in the resistance phenomenon observed during cancer therapy, we screened a particular class of chemical compounds, namely ribonucleoside phosphonates to predict them as potential cN-II inhibitors. These compounds incorporate a chemically and enzymatically stable phosphorus-carbon linkage instead of a regular phosphoester bond. Amongst them, six compounds were predicted as better ligands than the natural substrate of cN-II, inosine 5′-monophosphate (IMP). The study of purine and pyrimidine containing analogues and the introduction of chemical modifications within the phosphonate chain has allowed us to define general rules governing the theoretical affinity of such ligands. The binding strength of these compounds was scrutinized in silico and explained by an impressive number of van der Waals contacts, highlighting the decisive role of three cN-II residues that are Phe 157, His 209 and Tyr 210. Docking predictions were confirmed by experimental measurements of the nucleotidase activity in the presence of the three best available phosphonate analogues. These compounds were shown to induce a total inhibition of the cN-II activity at 2 mM. Altogether, this study emphasizes the importance of the non-hydrolysable phosphonate bond in the design of new competitive cN-II inhibitors and the crucial hydrophobic stacking promoted by three protein residues

Note à propos de la Communication de M. Fabry

Périgaud . Note à propos de la Communication de M. Fabry . In: Bulletin astronomique, tome 12, 1895. pp. 152-153

Le mariage mixte comme indicateur social de l'adaptation : le mariage franco-arménien [Mixed marriage as a social indicator of adaptation : French-Armenian marriage]

The definition of mixed marriages must be divorced from collective feeling to be of scien¬ tific value. Research will then no longer be focused upon a social and concrete fact but upon a phenomenon which subjacent laws will participate in explaining. After having postulated that the notion of mixed marriages no longer corresponds to a condensed heterogeneity, which is socially intolerable, but to a scattered homogeneity, a typology, designed to be experimentally validated, will be elaborated. The concept of adapta¬ tion and the notion of entropy will be employed at a theoretical level in order to show that mixed marriages are the result of complex processes tending to homogenize populations who are from different cultures but who live in permanent contact. According to a first approximation, the experimental results would demonstrate that mixed unions, as a social phenomenon, obey in part an adaptation process and are in conflict with the entropy of a cultural system which develops amidst a minority group whose original culture differs from that of the neighbouring society.Périgaud Jacques. Le mariage mixte comme indicateur social de l'adaptation : le mariage franco-arménien [Mixed marriage as a social indicator of adaptation : French-Armenian marriage]. In: Ethnies, volume 4, 1974. Les mariages mixtes. pp. 41-54

Gélion Towne. — Astronomie, Astrophysique, Géodésie, Topographie et Photogrammétrie pratique, avec méthodes d’observation et exemples numériques. — Texte accompagné de 91 figures et d’un planisphère céleste, etc. 2 volumes, Dijon, 1896. Paris, librairie Bertaux

Périgaud . Gélion Towne. — Astronomie, Astrophysique, Géodésie, Topographie et Photogrammétrie pratique, avec méthodes d’observation et exemples numériques. — Texte accompagné de 91 figures et d’un planisphère céleste, etc. 2 volumes, Dijon, 1896. Paris, librairie Bertaux. In: Bulletin astronomique, tome 13, 1896. pp. 223-225