Novel imidazole-based histamine H3 antagonists

A novel series of imidazole containing histamine H₃ receptor ligands were investigated and found to be potent functional antagonists. After improving the stability of these molecules towards liver microsomes, these compounds were found to have no appreciable affinity for CYP P450s. Subsequent in vivo experiments showed significant brain uptake of (4-chloro-phenyl)-[2-(1-isopropyl-piperidin-4-ylmethoxy)-3-methyl-3H-imidazol-4-yl]-methanone 22.     

A new genus and nine new species of Eugnomini (Coleoptera,Curculionidae) from New Caledonia

The genus Rasilinus gen. n. is described (type species Rasilinus tchambicus sp. n.). Nine new species: Rasilinus bicolor sp. n., Rasilinus bifurcatus sp. n., Rasilinus bimaculatus sp. n., Rasilinus grandidens sp. n., Rasilinus longulus sp. n., Rasilinus subgemellus sp. n., Rasilinus subnodulus sp. n., Rasilinus tchambicus sp. n., Rasilinus virgatus sp. n. are described from New Caledonia. Illustrations of the external morphology, male and female terminalia, dorsal habitus colour photographs of the adults, key to species and distribution map of the new genus Rasilinus are provided.     

Spectral properties and bio-activity of copper(II) clofibriates, part III: crystal structure of Cu(clofibriate)2(2-pyridylmethanol)2, Cu(clofibriate)2(4-pyridylmethanol)2(H2O) dihydrate, and Cu2(clofibriate)4(N,N-diethylnicotinamide)2

New copper(II) clofibriates (clof, {2-(4-chlorophenoxy)-2-methylpropionic or 2-(4-chlorophenoxy)isobutyric acid}) of composition Cu(clof)₂L₂ (where L=2-pyridylmethanol (2-pymeth) (1), N-methylnicotinamide (Menia) (4), N,N-diethylnicotinamide (Et₂nia) (5), isonicotinamide (isonia) (7) or methyl-3-pyridylcarbamate (mpc) (8)), [Cu(clof)₂(4-pymeth)₂(H₂O)] · 2H₂O (4-pymeth=4-pyridylmethanol) (2 · 2H₂O) and Cu(clof)₂L (where L=4-pymeth (3) or Et₂nia (6)) have been prepared and spectroscopically characterized. All the Cu(clof)₂L₂ compounds seem to possess distorted octahedral copper(II) stereochemistry with differing tetragonal distortions. An X-ray analysis of 1 was carried out and it featured a tetragonal-bipyramidal geometry around the copper(II) atom. X-ray analysis of 2 · 2H₂O featured a square-pyramidal geometry around copper(II) atom. Both the Cu(clof)₂L compounds seem to consist of a binuclear unit of tetracarboxylate type bridging. An X-ray analysis of 6 revealed typical binuclear paddle-wheel type structure, consisting of two copper(II) atoms in square-pyramidal geometry bridged by four carboxylate anions in the xy-plane. All complexes under study were characterized by EPR and electronic spectroscopy. The antimicrobial effects have been tested on various strains of bacteria, yeasts and filamentous fungi.     

Excitation of a magnetospheric MHD cavity by Kelvin-Helmholtz instability

The Kelvin-Helmholtz instability is investigated analytically by using a one-dimensional nonuniform model of the Earth’s magnetosphere and the adjacent solar wind region. Its properties are shown to be essentially governed by the presence of an MHD cavity that arises in the magnetosphere because of the non-uniformity of the latter and also because of the jump in the parameters of the medium at the magnetopause (the outer boundary of the magnetosphere). System oscillations constitute a discrete spectrum of eigenmodes, which are determined by the wave vector k _t along the tangential discontinuity and also by the mode number n = 0, 1, 2, …, playing the role of the wavenumber along a coordinate normal to the magnetopause. Analytic expressions are obtained for the frequency and instability growth rate of each eigenmode and for the functions describing its spatial structure. All these quantities depend parametrically on the solar wind velocity V _W , or more precisely, on the Doppler frequency shift ω _W = k _t · V _W . For each eigenmode, there is a lower instability threshold depending on the parameter ω _W and a sharp maximum in the growth rate at the eigenfrequency of the magnetospheric cavity. For ω _W values below the threshold, the properties of an eigenmode are highly sensitive to the type of solar wind nonuniformity. Three cases are considered: a uniform solar wind and solar winds in which the speed of sound increases or decreases away from the magnetopause.     

Diffusion and diffusion-osmosis models of the transfer of charged molecules across biological barriers

Mathematical models of the transfer of large enough charged molecules (macroions) have been constructed on the basis of the classical equations of electromigration diffusion (Helmholtz-Smoluchowski, Goldman, and Goldman-Hodgkin-Katz). It is shown that ion transfer in placental barriers (mimicking lipid-protein membrane barriers) and in muscle barriers proceeds by different mechanisms. In placental barriers, the electromigration diffusion takes place through lipid-protein channels formed by conformational alteration of phospholipid and protein molecules, with diffusion coefficients D = (2.6–3.6) × 10⁻⁸ cm²/s. The transfer in muscle barriers is due to migration via charged interfibrillar channels with negative diffusion activation energy (explained by changes in the structure of muscle fibers and expenditures of thermal energy for the displacement of Cl⁻ from channel walls), and D = (6.0–10.0) × 10⁻⁶ cm²/s.     

Extreme rapid warming yields high functional survivals of vitrified 8-cell mouse embryos even when suspended in a half-strength vitrification solution and cooled at moderate rates to −196 °C

To cryopreserve cells, it is essential to avoid intracellular ice formation during cooling and warming. One way to do so is to subject them to procedures that convert cell water into a non-crystalline glass. Current belief is that to achieve this vitrification, cells must be suspended in very high concentrations of glass-inducing solutes (i.e., ?6 molal) and cooled at very high rates (i.e., ?1000 °C/min). We report here that both these beliefs are incorrect with respect to the vitrification of 8-cell mouse embryos. In this study, precompaction 8-cell embryos were vitrified in several dilutions of EAFS10/10 using various cooling rates and warming rates. Survival was based on morphology, osmotic functionality, and on the ability to develop to expanded blastocysts. With a warming rate of 117,500 °C/min, the percentages of embryos vitrified in 1×, 0.75×, and 0.5× EAFS that developed to blastocysts were 93%, 92%, and 83%, respectively. And the percentages of morphological survivors that developed to expanded blastocysts were 100%, 92%, and 97%, respectively. Even when the solute concentration of the EAFS was reduced to 33% of normal, we obtained 40% functional survival of these 8-cell embryos.     

In vivo replication of the hamster polyomavirus genome and generation of specific deletions in the process of lymphomagenesis.

Hamster polyomavirus (HaPV) causes lymphomas when injected into newborn hamsters. These tumors are virus-free but accumulate large amounts of deleted extrachromosomal viral genomes. In order to identify the major sites of virus replication in animals, we have monitored the HaPV DNA present in different organs at various times after injection. The data demonstrate that viral replication preferentially occurs in lymphoid organs. Lymphoma-associated viral genomes display specific deletions. PCR analysis shows that such viral genomes are the only variants detectable in infected animals, suggesting that they are generated by a specific cellular mechanism. We have tested the possible role of the lymphoid cell-specific V(D)J recombination activity in the generation of these specific variants. Our results indicate that this mechanism is not solely responsible for the viral genome rearrangement, if involved at all.