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Jonas G. Barlind Linda K. Buckett Sharon G. Crosby Öjvind Davidsson Hans Emtenäs Anne Ertan Ulrik Jurva Malin Lemurell Pablo Morentin Gutierrez Karolina Nilsson Gavin O’Mahony Annika U. Petersson Alma Redzic Fredrik Wågberg Zhong-Qing Yuan 《Bioorganic & medicinal chemistry letters》2013,23(9):2721-2726
[Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to na?ve, p <0.01) in plasma triacylglycerol (TAG) concentration. 相似文献
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Michael P. Crosby 《Journal of experimental marine biology and ecology》1985,93(3):273-283
Utilization of the organic components of senescent Spartina alterniflora Loisel detritus by the grass shrimp, Palaemonetes pugio Holthuis, was investigated in laboratory feeding studies. A 14C-dimethyl sulfate labeling procedure was utilized to label the sterilized detritus. The formed covalent bond is stable to autoclaving, freezing and extremes of pH. An ingestion rate of 2.0 × 10?4CS·h?1 was determined for P. pugio. Estimates for rate of incorporation, gross growth efficiency, and total biomass incorporated are presented. An inverse relationship was demonstrated between shrimp size and rates of ingestion and incorporation. 相似文献
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The susceptibility of sheep oocytes to temperature changes during maturation in vitro was tested by reducing the incubation temperature to 20 degrees C at various stages of meiosis. Cooling induced chromosomal abnormalities including disorganized metaphase plates and multipolar spindles in 28-54% of oocytes cooled at all stages of meiosis from germinal vesicle breakdown (GVBD) to metaphase II. The time of GVBD (8-11 h after the start of culture) was the most sensitive to cooling, whereas fewest abnormalities were found in oocytes cooled in late metaphase I (16-19 h). In addition to the chromosomal abnormalities, unusual vesicles appeared in the cytoplasm of oocytes cooled at 8-11 h and 12-15 h. No abnormalities in protein synthesis were detected by one-dimensional SDS gel electrophoresis. The consequences of the abnormalities for the developmental potential of the cooled oocytes were tested by transfer to recipient ewes and fertilization in vivo. After 12 days of development only 6% and 11% oocytes cooled at 12-15 h and 20-23 h respectively had developed to expanded blastocysts, compared with 44% of control oocytes. The results demonstrated that maturing sheep oocytes are very sensitive to a drop in temperature. 相似文献
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The cardiac actin locus (Actc-1) is not on mouse chromosome 17 but is linked to beta 2-microglobulin on chromosome 2 总被引:1,自引:0,他引:1
A restriction fragment variant and recombinant inbred strains were used to show that the cardiac actin locus (Actc-1) is closely linked to beta 2-microglobulin (B2m) and several other loci on chromosome 2 of the mouse. Close linkage of Actc-1 and B2m in both man and mouse provides another example of a chromosomal segment that has been conserved since the divergence of the lineages leading to these two species. 相似文献
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Structure of the cel-3 gene from Fibrobacter succinogenes S85 and characteristics of the encoded gene product, endoglucanase 3. 总被引:18,自引:8,他引:10 下载免费PDF全文
M J McGavin C W Forsberg B Crosby A W Bell D Dignard D Y Thomas 《Journal of bacteriology》1989,171(10):5587-5595
The cel-3 gene cloned from Fibrobacter succinogenes into Escherichia coli coded for the enzyme EG3, which exhibited both endoglucanase and cellobiosidase activities. The gene had an open reading frame of 1,974 base pairs, coding for a protein of 73.4 kilodaltons (kDa). However, the enzyme purified from the osmotic shock fluid of E. coli was 43 kDa. The amino terminus of the 43-kDa protein matched amino acid residue 266 of the protein coded for by the open reading frame, indicating proteolysis in E. coli. In addition to the 43-kDa protein, Western immunoblotting revealed a 94-kDa membranous form of the enzyme in E. coli and a single protein of 118 kDa in F. succinogenes. Thus, the purified protein appears to be a proteolytic degradation product of a native protein which was 94 kDa in E. coli and 118 kDa in F. succinogenes. The discrepancy between the molecular weight expected on the basis of the DNA sequence and the in vivo form may be due to anomalous migration during electrophoresis, to glycosylation of the native enzyme, or to fatty acyl substitution at the N terminus. One of two putative signal peptide cleavage sites bore a strong resemblance to known lipoprotein leader sequences. The purified 43-kDa peptide exhibited a high Km (53 mg/ml) for carboxymethyl cellulose but a low Km (3 to 4 mg/ml) for lichenan and barley beta-glucan. The enzyme hydrolyzed amorphous cellulose, and cellobiose and cellotriose were the major products of hydrolysis. Cellotriose, but not cellobiose, was cleaved by the enzyme. EG3 exhibited significant amino acid sequence homology with endoglucanase CelC from Clostridium thermocellum, and as with both CelA and CelC of C. thermocellum, it had a putative active site which could be aligned with the active site of hen egg white lysozyme at the highly conserved amino acid residues Asn-44 and Asp-52. 相似文献