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41.
42.
A genome scan reveals QTL for growth, fatness, leanness and meat quality in a Duroc-Pietrain resource population 总被引:3,自引:0,他引:3
Liu G Jennen DG Tholen E Juengst H Kleinwächter T Hölker M Tesfaye D Un G Schreinemachers HJ Murani E Ponsuksili S Kim JJ Schellander K Wimmers K 《Animal genetics》2007,38(3):241-252
We performed a genome-wide QTL scan for production traits in a line cross between Duroc and Pietrain breeds of pigs, which included 585 F(2) progeny produced from 31 full-sib families genotyped with 106 informative microsatellites. A linkage map covering all 18 autosomes and spanning 1987 Kosambi cM was constructed. Thirty-five phenotypic traits including body weight, growth, carcass composition and meat quality traits were analysed using least square regression interval mapping. Twenty-four QTL exceeded the genome-wide significance threshold, while 47 QTL reached the suggestive threshold. These QTL were located at 28 genomic regions on 16 autosomal chromosomes and QTL in 11 regions were significant at the genome-wide level. A QTL affecting pH value in loin was detected on SSC1 between marker-interval S0312-S0113 with strong statistical support (P < 3.0 x 10(-14)); this QTL was also associated with meat colour and conductivity. QTL for carcass composition and average daily gain was also found on SSC1, suggesting multiple QTL. Seventeen genomic segments had only a single QTL that reached at least suggestive significance. Forty QTL exhibited additive inheritance whereas 31 QTL showed (over-) dominance effects. Two QTL for trait backfat thickness were detected on SSC2; a significant paternal effect was found for a QTL in the IGF2 region while another QTL in the middle of SSC2 showed Mendelian expression. 相似文献
43.
Biftu T Feng D Qian X Liang GB Kieczykowski G Eiermann G He H Leiting B Lyons K Petrov A Sinha-Roy R Zhang B Scapin G Patel S Gao YD Singh S Wu J Zhang X Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2007,17(1):49-52
Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin. 相似文献
44.
Modeling assisted rational design of novel, potent, and selective pyrrolopyrimidine DPP-4 inhibitors
Gao YD Feng D Sheridan RP Scapin G Patel SB Wu JK Zhang X Sinha-Roy R Thornberry NA Weber AE Biftu T 《Bioorganic & medicinal chemistry letters》2007,17(14):3877-3879
Molecular modeling was used to improve potency of the cyclohexylamine series. In addition, a 3-D QSAR method was used to gain insight for reducing off-target DPP-8/9 activities. Compounds 3, 4, and 5 were synthesized and found to be potent DPP-4 inhibitors, in particular 4 and 5 are designed to be highly selective against off-target DASH enzymes while maintaining potency on DPP-4. 相似文献
45.
Liang GB Qian X Feng D Fisher M Brown CM Gurnett A Leavitt PS Liberator PA Misura AS Tamas T Schmatz DM Wyvratt M Biftu T 《Bioorganic & medicinal chemistry letters》2007,17(13):3558-3561
Diaryl imidazo[1,2-a]pyridine derivatives, such as 6a and 7i, have been synthesized and found to be potent inhibitors of parasite PKG activity. The most potent compounds are the 7-isopropylaminomethyl analog 6a and 2-isopropylamino analog 7i. These compounds are also fully active in in vivo assay as anticoccidial agents at 25 ppm in feed. 相似文献
46.
Biftu T Scapin G Singh S Feng D Becker JW Eiermann G He H Lyons K Patel S Petrov A Sinha-Roy R Zhang B Wu J Zhang X Doss GA Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2007,17(12):3384-3387
Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile. 相似文献
47.
Heme is synthesized from glycine and succinyl CoA by eight heme synthesis enzymes. Although genetic defects in any of these enzymes are known to cause severe human blood diseases, their developmental expression in mammals is unknown. In this paper, we report two zebrafish heme synthesis enzymes, uroporphyrinogen III synthase (UROS) and protoporphyrinogen oxidase (PPO) that are well conserved in comparison to their human counterparts. Both UROS and PPO formed pairs of bilateral stripes in the lateral plate mesoderm at the 15-somite stage. At 24 h post-fertilization (hpf), UROS and PPO were predominantly expressed in the intermediate cell mass (ICM) that is the major site of primitive hematopoiesis. The expression of UROS and PPO was drastically suppressed in the bloodless mutants cloche and vlad tepes/gata 1 from 15-somite to 24hpf stages, indicating that both cloche and vlad tepes/gata 1 are required for the induction and maintenance of UROS and PPO expression in the ICM. 相似文献
48.
Association of the FADS2 gene with omega-6 and omega-3 PUFA Concentration in the egg yolk of Japanese quail 总被引:1,自引:0,他引:1
Khang NT Jennen DG Tholen E Tesfaye D Mennicken L Hoelker M Schellander K Ponsuksili S Murani E Wimmers K 《Animal biotechnology》2007,18(3):189-201
This study focused on the association of polymorphisms of the FADS2 gene with fatty acid profiles in egg yolk of eight Japanese quail lines selected for high and low omega-6:omega-3 PUFA ratio (h2 = 0.36-0.38). For the identification of polymorphisms within the FADS2 gene 1350 bp of cDNA sequence were obtained encoding 404 amino acids. Five synonymous SNPs were found by comparative sequencing of animals of the high and low lines. These SNPs were genotyped by single base extension on 160 Japanese quail. The association analysis, comprising analysis of variance and family based association test (FBAT), revealed significant effects of SNP3 and SNP4 genotypes on the egg yolk fatty acid profiles, especially the omega-6 and omega-3 PUFAs (P < 0.05). No effects of the other SNPs were found - indicating that these are not in linkage disequilibrium with the causal polymorphism. The results of this study promote FADS2 as a functional candidate gene for traits related to omega-6 and omega-3 PUFA concentration in the egg yolk. 相似文献
49.
50.
Barciszewska AM Murawa D Gawronska I Murawa P Nowak S Barciszewska MZ 《IUBMB life》2007,59(12):765-770
5-methylcytosine (m(5)C) can be used as a sensitive marker of progress of the tumor formation induced by the oxidative damage reactions. We have analyzed the amount of m(5)C in DNA of patients with breast and colon cancers. Two dimensional thin layer chromatography (TLC) has been used to monitor 5-methylcytosine level in DNA extracted from cancer tissues. The level of methylation of cytosine at C-5 position in DNA from breast cancer patients correlates well with the malignancy of tumors. Interestingly higher amount of m(5)C in DNA for the breast cancer patients treated with different chemotherapeutics was observed. It suggests an activation of DNA methyltransferase as well as a genomic suppression of the DNA repair genes expression. These differences clearly reflect the health condition of patients and support the global analysis of m(5)C in DNA as a good marker for diagnosis of neoplasia in clinical practice. 相似文献