The Low-Molecular-Weight Ligands of the Gonadotropin Receptors as the New Generation of the Regulators of the Reproductive Functions and Steroidogenesis

In clinic, the luteinizing (LH) and follicle-stimulating (FSH) hormones and human chorionic gonadotropin (hCG) are used to treat reproductive dysfunctions and in assisted reproductive technology. They are the αβ-heterodimeric complexes and specifically bind to ectodomain of G protein-coupled LH and FSH receptors. This leads to activation of many signaling cascades; some of which are responsible for steroidogenesis, folliculogenesis, and spermatogenesis, while the others, such as β-arrestin pathways, trigger the downregulation of gonadotropin receptors. A low selectivity of the intracellular signaling of gonadotropins and a large number of their isoforms are the main causes of undesirable effects of gonadotropins, limiting their clinical applications. Unlike gonadotropins, the low-molecular-weight (LMW) ligands interact with an allosteric site located in the transmembrane domain of the LH and FSH receptors and selectively activate the certain signaling pathway, preventing a number of side effects of gonadotropins. The LMW ligands are characterized by activity of the full and inverse agonists and neutral antagonists, as well as the positive and negative modulators, and they have the in vivo activity, including when administered orally. This review focuses on the advances in the development of LMW allosteric ligands of the LH and FSH receptors and the prospects for their use in reproductive medicine

ПОЗДНЕГОЛОЦЕНОВОЕ ОСАДКОНАКОПЛЕНИЕ В АКТИВНЫХ ГЕОЛОГИЧЕСКИХ СТРУКТУРАХ ЧУКОТСКОГО МОРЯ

The article presents the detailed analysis results considering bottom sediments from the Chukchi Sea. Two core samples, b16 and НС–8 were taken from the northern Herald Canyon 150 km northeast from NE Wrangel Island. Core b16 has been studied in more detail. According to the 210Pb measurements, the recent sedimentation rate amounts to 0.9 mm/y–1 at the sampling point. In the bottom layer of the core sample, the minimum concentrations of biogenic components (SiO2bio, Corg, Ntot, and Br) and the increased concentrations of cold-water diatom species Thalassiosira antarctica may result from low biological productivity during the Maunder Minimum. A correlation with recent global warming (11–22 years) is shown by the increased concentrations of SiO2bio, Corg, Ntot, and Br and the decreased values of magnetic susceptibility and X-ray density in the top layer (1–2 cm) of the same core sample. The results of our geochemical and diatom analysis support the available literature data and confirm that the Late Holocene sedimentation in the Chukchi Sea takes place in the zone wherein the water transits from the Pacific to the Arctic Ocean.Представлены результаты комплексного исследования вещественного состава донных осадков, вскрытых двумя кернами в северной части каньона Геральд Чукотского моря. Одна из полученных колонок была выбрана для более детального исследования. Скорость современного осадконакопления в точке отбора этого керна, измеренная по 210Pb, составляет 0.9 мм/год. Минимальные концентрации биогенных компонентов (SiO2биог., Сорг., Nобщ., Br) и увеличение содержаний холодноводного вида диатомей Thalassiosira antarctica в нижнем слое колонки, вероятно, объясняются низкой биологической продуктивностью во время минимума Маундера. Повышенные концентрации SiO2биог, Сорг, Nобщ, Br, пониженные значения магнитной восприимчивости и рентгеновской плотности в самом верхнем интервале разреза (до 1–2 см) соответствуют последним 11–22 годам глобального потепления климата. Результаты геохимического и диатомового анализов подтверждают имеющиеся в литературе данные о том, что позднеголоценовая седиментация в Чукотском море происходит в зоне транзита тихоокеанских вод в Северный Ледовитый океан

LATE HOLOCENE SEDIMENTATION IN ACTIVE GEOLOGICAL STRUCTURES OF THE CHUKCHI SEA

The article presents the detailed analysis results considering bottom sediments from the Chukchi Sea. Two core samples, b16 and НС–8 were taken from the northern Herald Canyon 150 km northeast from NE Wrangel Island. Core b16 has been studied in more detail. According to the 210Pb measurements, the recent sedimentation rate amounts to 0.9 mm/y–1 at the sampling point. In the bottom layer of the core sample, the minimum concentrations of biogenic components (SiO2bio, Corg, Ntot, and Br) and the increased concentrations of cold-water diatom species Thalassiosira antarctica may result from low biological productivity during the Maunder Minimum. A correlation with recent global warming (11–22 years) is shown by the increased concentrations of SiO2bio, Corg, Ntot, and Br and the decreased values of magnetic susceptibility and X-ray density in the top layer (1–2 cm) of the same core sample. The results of our geochemical and diatom analysis support the available literature data and confirm that the Late Holocene sedimentation in the Chukchi Sea takes place in the zone wherein the water transits from the Pacific to the Arctic Ocean

Gold-Catalyzed Hydrohydrazidation of Terminal Alkynes

Facile gold-catalyzed hydrohydrazidation of alkynes with various hydrazides R²CONHNH₂ (R = Alk or Ar; including those with an additional nucleophilic moiety) in the presence of Ph₃PAuNTf₂ (6 mol %) leading to a wide range of substituted keto-<i>N</i>-acylhydrazones (18 examples) in excellent to good yields (99–66%) is reported. This novel metal-catalyzed coupling proceeds under mild conditions (chlorobenzene, 60 °C), exhibits high functional group tolerance, and is insensitive to the electronic and steric effects of the substituents in the reactants