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Rama Jain Michelle Mathur Jiong Lan Abran Costales Gordana Atallah Savithri Ramurthy Sharadha Subramanian Lina Setti Paul Feucht Bob Warne Laura Doyle Stephen Basham Anne B. Jefferson Brent A. Appleton Mika Lindvall Cynthia M. Shafer 《Bioorganic & medicinal chemistry letters》2018,28(19):3197-3201
Utilizing the already described 3,4-bi-aryl pyridine series as a starting point, incorporation of a second ring system with a hydrogen bond donor and additional hydrophobic contacts yielded the azaindole series which exhibited potent, picomolar RSK2 inhibition and the most potent in vitro target modulation seen thus far for a RSK inhibitor. In the context of the more potent core, several changes at the phenol moiety were assessed to potentially find a tool molecule appropriate for in vivo evaluation. 相似文献
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Observations on habitat and behavior are reported for 10 of the 12 known species of the genus Hoplolatilus. These small (6 to 20 cm total length) fishes are widespread in the tropical Indo-Pacific and Red Sea. Adults live as stable monogamous pairs and each pair shares a burrow. They feed on plankton during the day and retreat into a burrow to escape disturbances and to retire for the night. Usually the burrow location is inconspicuous, but 3 of the deeper water species build elaborate rubble mounds, to over 3 m in diameter, around their burrows. We studied the shallowest (13 to 61 m depth) species, H. starcki, that does not build mounds, and compared it with the shallowest (51 to 73+ m) mound builder H. fronticinctus. Over 60 pairs of H. starcki were studied. Ten-min observations (N=237) on 14 pairs were analyzed by time of day for feeding rates, courtship behavior, and distances of pairs in relation to each other and their burrows. Over 20 pairs of H. fronticinctus were studied by divers and on video from a remotely operated vehicle. These data showed a high rate of moving rubble (96.0 h-1), an activity almost absent in non-mound builders (0.1 h-1). Observations are also reported for non-mound builders H. chlupatyi, H. cuniculus, H. luteus, H. marcosi, H. oreni, H. purpureus, H. sp. (an undescribed species), and the mound builder H. pohle. The results of a survey of 159 dive sites with suitable habitats to over 25 m depth (including 49 dive sites over 50 m) indicate an abundance of Hoplolatilus species in the southwest Pacific. In comparison, 41 survey dive sites (including 20 over 50 m) in the Red Sea resulted in an unexplained absence of Hoplolatilus species except in deep water (>60 m). Mound builder, H. geo, is known in the north Red Sea (depths 80-116 m). H. fronticinctus, newly reported here, was found in the south Red Sea (depths 70-73 m). We also report, for the first time, live sightings of the rare H. oreni and H. sp. living unpaired and without mounds below 60 m in the south Red Sea. The wide distribution of H. fronticinctus, like the related Malacanthus brevirostris, suggests a possible advantage to building mounds even though mounds reveal the location of burrows. Recent techniques to extend scuba depths should increase our knowledge of the distribution of Hoplolatilus species. 相似文献
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In a survey of 129 diabetic patients and 142 normal individuals, a significantly higher percentage of positive reactions in the fluorescent treponemal antibody-200 (FTA-200) test was found among diabetic patients than in the normal population. Absorption of all FTA-200-reactive sera with an extract of Reiter's treponeme eliminated most of the positive reactions in sera from diabetic patients, and three of the five positive reactions detected in sera from apparently normal subjects. On immunoelectrophoresis, precipitin bands developed most frequently between the Reiter sorbent and sera from diabetic patients positive in the FTA-200 test. Serum components responsible for FTA reactivity and precipitin reactions against the sorbent were resistant to treatment with mercaptoethanol, suggesting antibody of the IgG class. Cross-reacting antibodies produced in response to normal treponemal flora, and perhaps acquiring enhanced reactivity by means of nonspecific interacting substances in sera peculiar to the altered physiological state of diabetes, are suggested as possible causes of positive reactions of unabsorbed sera. No correlation could be made between age of the diabetic patient, treatment or duration of the disease, and FTA or precipitin reactivity of the patient's serum. 相似文献