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《Bioorganic & medicinal chemistry letters》2020,30(9):127071
New therapies for treating drug-resistant pneumococcal infections are urgently needed. The novel scaffold 6-hydroxy-4-oxo-1,2-dihydro-4H-quinoline was shown to have similar efficacies against all three different serotypes of S. pneumoniae, ATCC 49617™ (19F), ATCC BAA-1663™ (15B), and ATCC 700904™ (19A), in a resazurin-based high-throughput screen using the Korea Chemical Bank library. Further studies to identify a new lead with this scaffold, including tricyclic pyrrolo[3,2,1-ij]quinolone and pyrido[3,2,1-ij]quinolone derivatives, led to the identification of 6d, 7d and 12a. Compound 6d (IC50 = 0.92, 0.75, and 0.77 µM), 7d (IC50 = 0.57, 0.66, and 0.38 µM) and 12a (IC50 = 0.27, 1.03, and 0.62 µM) showed submicromolar IC50 values against 19F, 15B, and 19A, respectively, and thus serve as a starting point for further optimization. While some of compounds in this series exhibited acceptable pharmacokinetic profiles in preliminary in vivo rat experiments, the most active compound 12a showed poor solubility and high plasma protein binding. Our current research efforts are focused on optimizing compounds to improve physicochemical properties as well as potency. 相似文献
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Summary The ability of myogenic cells to migrate perpendicular to the long axis of freely autografted muscles was examined. Rat extensor digitorum longus muscles were divided, and one half was devitalized by repeated freezing in liquid nitrogen while the other half was kept viable in physiologic saline. The halves were reunited with sutures and grafted back into the original muscle bed. At intervals between 5 and 25 days the grafts were removed and examined histologically for the presence of myotubes within the devitalized region. Myotubes were first seen in the devitalized half 10 days postgrafting with the maximum number of myotubes observed after 12 to 15 days. These results indicate that myogenic cells are capable of migration perpendicular to the long axis of the muscle fibers in an autograft. 相似文献
4.
1 Introduction Molluscan species exhibit a range of morphologies associated with their particular function and habitat. The razor clam (Ensis siliqua) is a bivalve mollusc, usually found in fine sands, that burrows up to depths of 20 fathoms (~36 m)[1]. The species is found in several coastal regions of the British Isles, the Norwegian Sea, the Baltic south, the Iberian Peninsula, the Mediterranean and along the Atlantic coast of Morrocco[2]. The protec- tive outer shell, which is often … 相似文献
5.
An attempt was made to extend the area of distribution of a native population of brown trout Salmo trutta belonging to a Mediterranean lineage (ML), which has maintained itself in the Dranse d'Abondance, a fast-flowing alpine stream (Haute-Savoie, France), despite several decades of intensive restocking with brown trout derived from the Atlantic lineage (AL). This was done by releasing an ML component into the predominantly AL population still present on the Ugine, the main tributary of the Dranse d'Abondance. This strategy of rehabilitation restocking was tested using fluoro-marked juveniles produced from a captive breeding stock derived from the wild Dranse d'Abondance ML stock. Samples of 0+ year fish were collected over the period 1995–2003 in order to assess the impact of the restocking. Percentages of fluoro-marked otoliths revealed significant contributions of ML restocking in the 0+ year autumnal standing population, with levels ranging from 34·3 to 61·4%. The change in the genetic characteristics of the 0+ year population produced by natural recruitment was monitored by analysing the unmarked subjects. Frequencies observed at two microsatellite loci revealed a considerable rise (from 0 to 60%) in the level of Mediterranean alleles in the natural 0+ year population since the introduction of restocking using ML individuals. 相似文献
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T. Phanitchat C. Apiwathnasorn S. Sungvornyothin Y. Samung S. Dujardin J.‐P. Dujardin S. Sumruayphol 《Medical and veterinary entomology》2019,33(4):476-484
Wing geometry helps to identify mosquito species, even cryptic ones. On the other hand, temperature has a well‐known effect on insect metric properties. Can such effects blur the taxonomic signal embedded in the wing? Two strains of Aedes albopictus (laboratory and field strain) were examined under three different rearing temperatures (26, 30 and 33 °C) using landmark‐ and outline‐based morphometric approaches. The wings of each experimental line were compared with Aedes aegypti. Both approaches indicated similar associations between wing size and temperature. For the laboratory strain, the wing size significantly decreased as the temperature increased. For the field strain, the largest wings were observed at the intermediate temperature. The two morphometric approaches describing shape showed different sensibilities to temperature. For both strains and sexes, the landmark‐based approach disclosed significant wing shape changes with temperature changes. The outline‐based approach showed lesser effects, detecting significant changes only in laboratory females and in field males. Despite the size and shape changes induced by temperature, the two strains of Ae. albopictus were always distinguished from Ae. aegypti. The present study confirms the lability of size. However, it also suggests that, despite environmentally‐induced variation, the architecture of the wing still provides a strong taxonomic signal. 相似文献
7.
Ferretti G., Gabriele F. and Palmas C. 1981. Development of human and mouse strain of Hymenolepis nana in mice. International Journal for Parasitology11: 425–430. An Hymenolepis nana strain isolated from human faeces was transferred in the mouse. At first, the q ratio (the number of parasites to the number of eggs used) was very low. After 10 passages adaptation was complete: when mice of different age and strain (CD1 and BDF1) were infected with eggs of the above strain and eggs of 2 different murine strains, no differences emerged in the q ratio or in the parasite mean dry weight. Survival also appeared the same in the 3 parasite strains, however, human and murine strains live for a shorter time in BDF1 than in CD1 mice. Discussion bears on the hypothesis that the difficulties that emerge during the first passages may be connected to the adult and not to the larval phase. 相似文献
8.
Developmental Patterns of Catechol-O-Methyltransferase in Genetically Different Rat Strains: Enzymatic and Immunochemical Studies 总被引:4,自引:4,他引:0
D. J. Goldstein R. M. Weinshilboum J. H. Dunnette C. R. Creveling 《Journal of neurochemistry》1980,34(1):153-162
Abstract: Catechol- O -methyltransferase (COMT) activity in the liver and kidneys of adult Fischer-344 (F-344) rats is only half of that in the same organs of Wistar-Furth (W-F) rats. The trait of low COMT activity in these animals is inherited in an autosomal recessive fashion. A comprehensive study of patterns of change in COMT activity during growth and development was performed to determine whether "temporal gene" effects might play a role in the inherited differences in enzyme activity present in adult animals. The COMT activity expressed per mg protein in liver and kidneys of newborn F-344 rats is only 50–60% of that in the same organs of W-F animals. The liver and the kidneys of newborn rats of both strains have COMT activity an order of magnitude higher than those in brain, heart, or blood. In addition, in both strains there are much larger increases in liver and kidney COMT activities during growth and development (5–10 fold) than in blood, brain, or heart (one- to twofold). Immunotitration with antibodies against rat COMT demonstrates that differences in immunoreactive COMT parallel differences in COMT activity, both between strains and within strains during growth and development. However, when the temporal patterns of change in enzyme activities in the liver and the kidneys of the two strains of rat are compared at multiple times during growth and development, no differences in the patterns are present. These results make it unlikely that temporal gene effects can explain the inherited differences in COMT activity in liver and kidneys of F-344 and W-F rats. 相似文献
9.
Certain structures, associated with the flagellum, and which had hitherto been described as appearing occasionally in some species of trypanosomes, were found very frequently in epimastigote forms of strain F of Trypanosoma cruzi: (a) a group of tubular elements in an electron-dense mass enclosed within a swelling of the flagellar membrane as the flagellum emerges from its reservoir; (b) an expansion of the flagellar membrane at the point of the above swelling, which in cross-sections appears as a ring; and (c) an electron dense band in the body of the organism alongside the border of the flagellar pocket. The possible significance of these structures and the fact that so far they have been found only in one strain of T. cruzi are discussed. 相似文献
10.