Antiovulatory antagonists of LHRH related to antide

We report 104 analogues of the potent antiovulatory antagonist of LHRH, N-Ac-D -Nal-D -Cpa-D -Pal-Ser-Lys(Nic)-D -Lys(Nic)-Leu-Ilys-Pro-D -Ala-NH₂, Antide. We replaced the Nic group in Antide with other acyl substituents to modulate size, hydrophilicity or basicity of the molecule, we also replaced th Lys residues with shorter basic amino acids, and made cyclic 5/6 analogues as well as position 5 or 6 dimers. We substituted Ilys⁸ with other alkyl groups and acyl derivatives. When injected in 0.1% DMSO in water in a typical antiovulatory (AO) assay, Antide gives six rats ovulating out of eight (6/8) at 2 μg, 4/8 at 4 μg, and the histamine release assay (HRA), ED₅₀ is >300 μg/ml; [Lys(N-Isobutyl)⁸]Antide gave 2/8 at 2 μg/rat; [Lys (8-Qis)⁵]Antide gave 1/8 at 1 μg, and 0/8 at 2 μg, and in the HRA ED₅₀, 22 μg/ml; [D -Lys(8-Qis)⁶]Antide gave 4/8 at 1 μg and 0/8 at 2 μg, and in the HRA, ED₅₀ was 27 μg/ml; [Lys(8-Qic)⁸] gave 5/8 at 1 μg, 1/8 at 2 μg/ [Lys(2-Pyc)⁵]Antide gave 5/8 at 1 μg and 0/8 at 2 μg, and in the HRA ED₅₀ was 116 μg/ml; [D -Lys (2-Pyc)⁶]Antide gave 3/8 at 1 μg, and in the HRA, ED₅₀ was 100 - >300 μg/ml; [Lys(2-Pyc)⁵,D -Lys(2-Pyc)⁶]Antide gave 2/8 at 1 μg. The substitutions of the Nic groups of Antide at Lys⁵ or D -Lys⁶ with 8-Qis or with 2-Pyc groups seem to give highly potent antiovulatory antagonists of LHRH and constitute significant new leads to generate potent antiovulatory compounds endowed with moderate or low histamine release.     

Influence of phosphorus loads and of some limnological processes on the purity of lake water

Various aspects of the relation between nutrient load-mainly phosphorus-and phytoplankton biomass, the influence of drainage from surrounding forest and land under agriculture, removal of phosphorus from lakes by sedimentation, internal loading and the role of biota, especially fish, are considered and commented upon.     

Some factors affecting the viability of mouse and cattle embryos frozen to −40°C before transfer to liquid nitrogen

A total of 1161 8- to 16-cell mouse embryos and 31 cattle early morulae and late blastocysts were frozen to ?40°C before transfer to liquid nitrogen. After thawing, mouse embryo viability was determined by in vitro development to the blastocyst stage and cattle embryo viability by both in vivo and in vitro development.Using glycerol as the cryoprotective agent, 88% of the mouse embryos developed to the blastocyst stage: thawing at 45 and 360° C/min gave the best results (88.8 and 84.8%, respectively). In another test with holding times at ?40°C of up to 60 min, about 70% of embryos developed to blastocysts with holding time 30–60 min.In cattle, 11 embryos frozen in DMSO and thawed at 360°C/min were transplanted to eight recipients. Four pregnancies (six fetuses) resulted. Thawing rates of 200 and 360°C/min resulted in the best in vitro development of cattle embryos.     

Hydrothermal vent myodocopid ostracods from the Eifelian (Middle Devonian) of southern Morocco

A monospecific assemblage of myodocopid ostracods has been found in the Middle Devonian of a unique hydrothermal vent system of Hamar Laghdad (eastern Anti-Atlas, southern Morocco), which developed over a submarine eruption of basaltic rocks. This fauna has been recovered from a neptunian dyke representing the sediment infill of an Eifelian venting fissure discovered in the central part of Hamar Laghdad. The assemblage consists of thousands of relatively large shells forming a coquina layer in which the valves are disarticulated, perfectly washed, well sorted and stacked into each other. Their orientation points to transport due to fluids migrating in the vent system. The ostracod specimens, on the base of the general outline, the presence of rostrum and rostral incisure is assigned to the order Myodocopida. The new genus and species Hamaroconcha kornickeri is proposed, most likely representing a new family. Its carapace morphology gives no clear clue to its mode of life; however, a relatively long rostral incisure may suggest that frontal appendages of this species were sufficient for active swimming. Therefore, a nectobenthic lifestyle is postulated for H. kornickeri nov. gen., nov. sp. Isotope data from the sediment infill provide evidence for the activity of hydrothermal fluids.     

Plasmon-waveguide resonance studies of ligand binding to integral proteins in membrane fragments derived from bacterial and mammalian cells

A procedure has been developed for directly depositing membrane fragments derived from bacterial cells (chromatophores from Rhodopseudomonas sphaeroides) and mammalian cells (μ-opioid receptor- and MC4 receptor-transfected human embryonic kidney (HEK) cells and rat trigeminal ganglion cells) on the silica surface of a plasmon-waveguide resonance (PWR) spectrometer. Binding of ligands (cytochrome c₂ for the chromatophores, the peptide agonists DAMGO and melanotan-II that are specific for the μ-opioid and MC4 receptors, and two nonpeptide agonists that are specific for the CB1 receptor) to these membrane fragments has been observed and characterized with high sensitivity using PWR spectral shifts. The K_D values obtained are in excellent agreement with conventional pharmacological assays and with prior PWR studies using purified receptors inserted into deposited lipid bilayer membranes. These studies provide a new tool for obtaining useful biological information about receptor-mediated processes in real biological membranes.