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21.
Ayres KL 《Genetica》2000,108(2):137-143
A two-locus match probability is presented that incorporates the effects of within-subpopulation inbreeding (consanguinity)
in addition to population subdivision. The usual practice of calculating multi-locus match probabilities as the product of
single-locus probabilities assumes independence between loci. There are a number of population genetics phenomena that can
violate this assumption: in addition to consanguinity, which increases homozygosity at all loci simultaneously, gametic disequilibrium
will introduce dependence into DNA profiles. However, in forensics the latter problem is usually addressed in part by the
careful choice of unlinked loci. Hence, as is conventional, we assume gametic equilibrium here, and focus instead on between-locus
dependence due to consanguinity. The resulting match probability formulae are an extension of existing methods in the literature,
and are shown to be more conservative than these methods in the case of double homozygote matches. For two-locus profiles
involving one or more heterozygous genotypes, results are similar to, or smaller than, the existing approaches.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
22.
G. W. Tinney P. E. Hatcher P. G. Ayres N. D. Paul J. B. Whittaker 《Entomologia Experimentalis et Applicata》1998,88(2):137-145
The effects of sublethal doses of deltamethrin and propoxur, applied topically at LD10, LD30 and LD50 on German cockroaches, were studied by reciprocal crossing. Male and female longevities decreased curvilinearly with increasing sublethal doses of deltamethrin, and decreased linearly with increasing sublethal doses of propoxur. Fecundity of females treated with deltamethrin and propoxur was reduced with increasing sublethal doses of both insecticides. Oothecal production, oothecal hatchability and nymphal production also declined with increasing doses of deltamethrin and propoxur. Preoviposition and incubation periods were not affected by sublethal doses of deltamethrin and propoxur, although some significant differences were observed at certain oothecal numbers. Two-way analysis of variance indicated that only treated females showed an effect on oothecal production while oothecal hatch and nymphal production were governed by both treated females and males. Insecticide susceptibility tests on the progeny of parents treated with sublethal doses demonstrated that these doses did not increase insecticidal tolerance in the F1 generation. 相似文献
23.
Tyler JW Robinson Melody Pai Jeff C Liu Frederick Vizeacoumar Thomas Sun Sean E Egan Alessandro Datti Jing Huang Eldad Zacksenhaus 《Cell cycle (Georgetown, Tex.)》2013,12(18):3013-3024
Triple-negative breast cancer (TNBC) represents an aggressive subtype, for which radiation and chemotherapy are the only options. Here we describe the identification of disulfiram, an FDA-approved drug used to treat alcoholism, as well as the related compound thiram, as the most potent growth inhibitors following high-throughput screens of 3185 compounds against multiple TNBC cell lines. The average IC50 for disulfiram was ~300 nM. Drug affinity responsive target stability (DARTS) analysis identified IQ motif-containing factors IQGAP1 and MYH9 as direct binding targets of disulfiram. Indeed, knockdown of these factors reduced, though did not completely abolish, cell growth. Combination treatment with 4 different drugs commonly used to treat TNBC revealed that disulfiram synergizes most effectively with doxorubicin to inhibit cell growth of TNBC cells. Disulfiram and doxorubicin cooperated to induce cell death as well as cellular senescence, and targeted the ESA+/CD24-/low/CD44+ cancer stem cell population. Our results suggest that disulfiram may be repurposed to treat TNBC in combination with doxorubicin. 相似文献
24.
Fife MS Gutierrez A Ogilvie EM Stock CJ Samuel JM Thomson W Mack LF Lewis CM Woo P 《Arthritis research & therapy》2006,8(5):R148-5
Juvenile idiopathic arthritis (JIA) is the most common cause of chronic childhood disability and encompasses a number of disease
subgroups. In this study we have focused on systemic JIA (sJIA), which accounts for approximately 11% of UK JIA cases. This
study reports the investigation of three members of the IL10 gene family as candidate susceptibility loci in children with
sJIA. DNA from 473 unaffected controls and 172 patients with sJIA was genotyped for a single nucleotide polymorphism (SNP)
in IL19 and IL20 and two SNPs in IL10. We examined evidence for association of the four SNPs by single marker and haplotype
analysis. Significant differences in allele frequency were observed between cases and controls, for both IL10-1082 (p = 0.031)
and IL20-468 (p = 0.028). Furthermore, examination of the haplotypes of IL10-1082 and IL20-468 revealed greater evidence for
association (global p = 0.0006). This study demonstrates a significant increased prevalence of the low expressing IL10-1082
genotype in patients with sJIA. In addition, we show a separate association with an IL20 polymorphism, and the IL10-1082A/IL20-468T
haplotype. The two marker 'A-T' haplotype confers an odds ratio of 2.24 for sJIA. This positive association suggests an important
role for these cytokines in sJIA pathogenesis. 相似文献
25.
Evaluation of TFAM and FABP4 gene polymorphisms in three lines of Nellore cattle selected for growth
Ayres DR Souza FR Mercadante ME Fonseca LF Tonhati H Cyrillo JN Bonilha SF Albuquerque LG 《Genetics and molecular research : GMR》2010,9(4):2050-2059
We analyzed the polymorphisms TFAM HaeIII, TFAM MboI and FABP4 MspA1I in three Nellore lines selected for growth in order to evaluate how selection affects the frequencies of these polymorphisms and evaluate their association with growth and carcass traits in Zebu cattle. Birth, weaning and yearling weights, rump height, longissimus muscle area, backfat thickness, and rump fat thickness were analyzed. The sample was constituted of animals from two lines selected for yearling weight (NeS and NeT), and a control line (NeC), established in 1980, at the S?o Paulo Instituto de Zootecnia. Two hundred and seventy-two heifers were genotyped for TFAM gene SNPs, and 325 heifers were genotyped for the FABP4 SNP. High frequencies were observed for the alleles A (TFAM HaeIII), C (TFAM MboI) and C (FABP4 MspA1I). Significant differences in allele frequencies between NeS and NeT were observed for the TFAM HaeIII, and between the line NeT and lines NeC and NeS for the FABP4 MspA1I SNP. Five haplotypes were observed for the two polymorphisms in the TFAM gene, haplotype AACC being the most frequent. None of the markers separately or according to haplotype was significantly associated with the growth and carcass traits. The low frequencies of alleles that are associated with high marbling scores and thick subcutaneous fat in taurine breeds might explain the low means for these traits in Nellore cattle. 相似文献
26.
Hall RJ Hastings A Ayres DR 《Proceedings. Biological sciences / The Royal Society》2006,273(1592):1385-1389
The emergence of hybrids between native and introduced species is an increasingly widespread problem which can alter entire ecosystems. We present a general model for the hybridization of two plant species to investigate the conditions under which hybrid invasions can occur, and the ecological and genetic consequences of such hybridizations. We find that parental compatibility and fecundity are important determinants of whether (and at what rate) hybrid genotypes emerge. Enhanced hybrid fitness traits affect both the population's genetic structure and total rate of increase, with rapid selection for the fittest genotype. Conversely, if different genotypes maximize different life-history characteristics, the ensuing population can be genetically very variable. The model provides a novel approach to evaluate the contributions of population dynamic and genetic processes in the study of hybrid invasions. 相似文献
27.
28.
An example of the evolution of the interacting behaviours of parents and progeny is studied using iterative equations linking the frequencies of the gametes produced by the progeny to the frequencies of the gametes in the parental generation. This population genetics approach shows that a model in which both behaviours are determined by a single locus can lead to a stable equilibrium in which the two behaviours continue to segregate. A model in which the behaviours are determined by genes at two separate loci leads eventually to fixation of the alleles at both loci but this can take many generations of selection. Models of the type described in this paper will be needed to understand the evolution of complex behaviour when genomic or experimental information is available about the genetic determinants of behaviour and the selective values of different genomes. 相似文献
29.
Xiao SH Farrelly E Anzola J Crawford D Jiao X Liu J Ayres M Li S Huang L Sharma R Kayser F Wesche H Young SW 《Analytical biochemistry》2007,367(2):179-189
Several drugs inhibiting protein kinases have been launched successfully, demonstrating the attractiveness of protein kinases as therapeutic targets. Functional genomics research within both academia and industry has led to the identification of many more kinases as potential drug targets. Although a number of well-known formats are used for measuring protein kinase activity, some less well-characterized protein kinases identified through functional genomics present particular challenges for existing assay formats when there is limited knowledge of the endogenous substrates or activation mechanisms for these novel kinase targets. This is especially the case when a very sensitive assay is required to differentiate often highly potent inhibitors developed by late-stage medicinal chemistry programs. ACK1 is a non-receptor tyrosine kinase that has been shown to be involved in tumorigenesis and metastasis. Here we describe the development of an extremely sensitive high-throughput assay for ACK1 capable of detecting 240 fmol per well of the kinase reaction product employing a BV-tag-based electrochemiluminescence assay. This assay is universally applicable to protein tyrosine kinases using a BV-tag-labeled monoclonal antibody against phosphotyrosine. Furthermore, this assay can be extended to the evaluation of Ser/Thr kinases in those cases where an antibody recognizing the phospho-product is available. 相似文献
30.
Kan Chen Wanlu Cao Juan Li Dave Sprengers Pratika Y Hernanda Xiangdong Kong Luc JW van der Laan Kwan Man Jaap Kwekkeboom Herold J Metselaar Maikel P Peppelenbosch Qiuwei Pan 《Molecular medicine (Cambridge, Mass.)》2015,21(1):792-802
As uncontrolled cell proliferation requires nucleotide biosynthesis, inhibiting enzymes that mediate nucleotide biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which cancer cells evade the effect of nucleotide biosynthesis restriction is urgently needed. Here we explored the notion that intrinsic differences in cancer cell cycle velocity are important in the resistance toward inhibition of inosine monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). In short-term experiments, MPA treatment of fast-growing cancer cells effectively elicited G0/G1 arrest and provoked apoptosis, thus inhibiting cell proliferation and colony formation. Forced expression of a mutated IMPDH2, lacking a binding site for MPA but retaining enzymatic activity, resulted in complete resistance of cancer cells to MPA. In nude mice subcutaneously engrafted with HeLa cells, MPA moderately delayed tumor formation by inhibiting cell proliferation and inducing apoptosis. Importantly, we developed a lentiviral vector–based Tet-on label-retaining system that enables to identify, isolate and functionally characterize slow-cycling or so-called label-retaining cells (LRCs) in vitro and in vivo. We surprisingly found the presence of LRCs in fast-growing tumors. LRCs were superior in colony formation, tumor initiation and resistance to MPA as compared with fast-cycling cells. Thus, the slow-cycling compartment of cancer seems predominantly responsible for resistance to MPA. 相似文献