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61.
Intraspecific DNA divergence in Drosophila: a study on parthenogenetic D. mercatorum 总被引:1,自引:0,他引:1
Drosophila mercatorum is a species that can give rise to totally homozygous
parthenogenetic strains. Using the technique of DNA-DNA hybridization, we
have assessed the overall single-copy DNA differences among three
independently derived strains that represent three independent genomes.
Among strains, the average difference between homoduplex and heteroduplex
median melting temperatures is 1.3 degrees C. This represents greater than
or equal to 1.3% base-pair mismatch. Normalized percent of reassociation
indicates further genetic differences, probably reflecting
insertion/deletion differences and/or regions of the genome that are highly
variable. This overall intraspecific genetic variation is higher than
generally is thought to exist but is consistent with growing evidence of
extensive DNA diversity within species of invertebrates. High intraspecific
DNA variation may be correlated with rapid phyletic rates of evolution.
Because of this high level of variation, the technique of DNA-DNA
hybridization may be used to study intraspecific variation in invertebrates
but is limited in its usefulness for higher systematic studies.
相似文献
62.
Patrick R. Gentry Thomas M. Bridges Atin Lamsal Paige N. Vinson Emery Smith Peter Chase Peter S. Hodder Julie L. Engers Colleen M. Niswender J. Scott Daniels P. Jeffrey Conn Michael R. Wood Craig W. Lindsley 《Bioorganic & medicinal chemistry letters》2013,23(10):2996-3000
This Letter describes the further chemical optimization of the M5 PAM MLPCN probes ML129 and ML172. A multi-dimensional iterative parallel synthesis effort quickly explored isatin replacements and a number of southern heterobiaryl variations with no improvement over ML129 and ML172. An HTS campaign identified several weak M5 PAMs (M5 EC50 >10 μM) with a structurally related isatin core that possessed a southern phenethyl ether linkage. While SAR within the HTS series was very shallow and unable to be optimized, grafting the phenethyl ether linkage onto the ML129/ML172 cores led to the first sub-micromolar M5 PAM, ML326 (VU0467903), (human and rat M5 EC50s of 409 nM and 500 nM, respectively) with excellent mAChR selectivity (M1–M4 EC50s >30 μM) and a robust 20-fold leftward shift of the ACh CRC. 相似文献
63.
Niswender CM Willis BS Wallen A Sweet IR Jetton TL Thompson BR Wu C Lange AJ McKnight GS 《Genesis (New York, N.Y. : 2000)》2005,43(3):109-119
Using the cre-loxP recombination system, we generated a line of mice expressing a constitutively active catalytic subunit of Protein Kinase A (PKA) in a temporally and spatially regulated fashion. In the absence of cre recombinase the modified catalytic subunit allele is functionally silent, but after recombination the mutant allele is expressed, resulting in enhanced PKA effects at basal cAMP levels. Mice expressing the modified protein in hepatocytes using albumin-cre transgenics show defects in glucose homeostasis, glycogen storage, fructose 2,6-bisphosphate levels, and induction of glucokinase mRNA during feeding. Similar to animals lacking glucokinase in the liver (Postic et al.: J Biol Chem 274:305-315, 1999), these mice also have defects in glucose-stimulated insulin secretion, a hallmark of Type II diabetes. The widespread expression of PKA and the involvement of this kinase in a myriad of signaling pathways suggest that these animals will provide critical tools for the study of PKA function in vivo. 相似文献
64.
65.
The ovine corpus luteum is composed of two types of steroidogenic cells, which are referred to as small and large luteal cells. In this study, the size and number of steroidogenic cells were determined in corpora lutea collected on Days 4, 8, 12, and 16 of the estrous cycle. Corpora lutea were dissociated into single-cell suspensions that were stained for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity, a marker for steroidogenic cells. The size of 3 beta-HSD-positive cells was measured with a Zeiss Videoplan Image Analyzer. On Day 4, most of the 3 beta-HSD-positive cells were less than 18 microns in diameter, the median being 11.2 microns. By Day 8, the number of 3 beta-HSD-positive cells increased 3-fold, and the median diameter increased to 12.8 microns. Although the number of 3 beta-HSD-positive cells was reduced by approximately 50% on Day 16, the median size on Days 12 and 16 was 14.6 and 16.8 microns, respectively. The ratio of large (greater than 18 microns) to small (less than 18 microns) luteal cells was 0.11 +/- 0.03 on Day 4; the ratio increased linearly to 0.67 +/- 0.09 by Day 16. This increase between Days 4 and 12 was attributable to an overall increase in the size of the cells; the increase between Days 12 and 16, however, was due to a loss of small luteal cells. When the experiment was conducted near the end of the breeding season, before animals became anestrous, the median size of the luteal cells did not change at different times of the estrous cycle but remained constant throughout. These data suggest that development of the corpus luteum is associated with an increase in the size and number of steroidogenic luteal cells, and that luteolysis is associated with a preferential loss of small luteal cells. 相似文献
66.
Preparations of small and large steroidogenic cells from enzymatically dispersed ovine corpora lutea were utilized to study the in vitro effects of luteinizing hormone (LH) and prostaglandins (PG) E1, E2 and I2. Cells were allowed to attach to culture dishes overnight and were incubated with either LH (100 ng/ml), PGE1, PGE2, or PGI2 (250 ng/ml each). The secretion of progesterone by large cells was stimulated by all prostaglandins tested (P less than 0.05) while the moderate stimulation observed after LH treatment was attributable to contamination of the large cell population with small cells. Prostaglandins E1 and E2 had no effect on progesterone secretion by small cells, while LH was stimulatory at all times (0.5 to 4 hr) and PGI2 was stimulatory by 4 hr. Additional studies were conducted to determine if the effects of PGE2 upon steroidogenesis in large cells were correlated with stimulated activity of adenylate cyclase. In both plated and suspended cells PGE2 caused an increase (P less than 0.05) in the rate of progesterone secretion but had no effect upon the activity of adenylate cyclase or cAMP concentrations within cells or in the incubation media. Exposure of luteal cells to forskolin, a nonhormonal stimulator of adenylate cyclase, resulted in marked increases in all parameters of cyclase activity but had no effect on progesterone secretion. These data suggest that the actions of prostaglandins E1, E2 and I2 are directed primarily toward the large cells of the ovine corpus luteum and cast doubt upon the role of adenylate cyclase as the sole intermediary in regulation of progesterone secretion in this cell type. 相似文献
67.
68.
Bruce J. Melancon Michael S. Poslusney Patrick R. Gentry James C. Tarr Douglas J. Sheffler Margrith E. Mattmann Thomas M. Bridges Thomas J. Utley J. Scott Daniels Colleen M. Niswender P. Jeffrey Conn Craig W. Lindsley Michael R. Wood 《Bioorganic & medicinal chemistry letters》2013,23(2):412-416
This Letter describes the continued optimization of an MLPCN probe molecule (ML137) with a focused effort on the replacement/modification of the isatin moiety present in this highly selective M1 PAM. A diverse range of structures were validated as viable replacements for the isatin, many of which engendered sizeable improvements in their ability to enhance the potency and efficacy of acetylcholine when compared to ML137. Muscarinic receptor subtype selectivity for the M1 receptor was also maintained. 相似文献
69.
70.