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91.
The ATP-binding cassette transporter, ABCG2, has been identified as a gene of significance in the regulation of bovine lactation by a number of gene mapping studies yet its role in lactational physiology remains unclear. We have used the potent ABCG2 specific inhibitor, Ko143, to investigate role of ABCG2 in primary bovine mammary epithelial cell (BMEC) proliferation and differentiation. After incubation with Ko143, the proliferation rate of BMECs was reduced at 48 and 72 hours by up to 80% (P < 0.001), and the effect was dose-dependent (approximately 40% with 10 nM Ko143 and 80% with 20 nM Ko143). Morphological changes in BMEC mammosphere formation were not observed when co-incubated with Ko143. Our results suggested that ABCG2 plays a role in mammary epithelial cell proliferation and that functional polymorphisms in this gene may influence the cellular compartment of the mammary gland and potentially milk production. 相似文献
92.
Carolina V Morgante Patricia M Guimarães Andressa CQ Martins Ana CG Araújo Soraya CM Leal-Bertioli David J Bertioli Ana CM Brasileiro 《BMC research notes》2011,4(1):1-11
Background
Molecular genetic studies on rare tumour entities, such as bone tumours, often require the use of decalcified, formalin-fixed, paraffin-embedded tissue (dFFPE) samples. Regardless of which decalcification procedure is used, this introduces a vast breakdown of DNA that precludes the possibility of further molecular genetic testing. We set out to establish a robust protocol that would overcome these intrinsic hurdles for bone tumour research.Findings
The goal of our study was to establish a protocol, using a modified DNA isolation procedure and quality controls, to select decalcified samples suitable for array-CGH testing. Archival paraffin blocks were obtained from 9 different pathology departments throughout Europe, using different fixation, embedding and decalcification procedures, in order to preclude a bias for certain lab protocols. Isolated DNA samples were subjected to direct chemical labelling and enzymatic labelling systems and were hybridised on a high resolution oligonucleotide chip containing 44,000 reporter elements. Genomic alterations (gains and losses) were readily detected in most of the samples analysed. For example, both homozygous deletions of 0.6 Mb and high level of amplifications of 0.7 Mb were identified.Conclusions
We established a robust protocol for molecular genetic testing of dFFPE derived DNA, irrespective of fixation, decalcification or sample type used. This approach may greatly facilitate further genetic testing on rare tumour entities where archival decalcified, formalin fixed samples are the only source. 相似文献93.
Duncan CJ Sheehy SH Ewer KJ Douglas AD Collins KA Halstead FD Elias SC Lillie PJ Rausch K Aebig J Miura K Edwards NJ Poulton ID Hunt-Cooke A Porter DW Thompson FM Rowland R Draper SJ Gilbert SC Fay MP Long CA Zhu D Wu Y Martin LB Anderson CF Lawrie AM Hill AV Ellis RD 《PloS one》2011,6(7):e22271
Background
Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria.Methods
In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes.Results
A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = −0.93 [95% CI: −1.0, −0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = −0.93 [95% CI: −0.99, −0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5–9], control group median 9 days [range 7–9]).Conclusions
Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers.Trial Registration
ClinicalTrials.gov [] NCT00984763相似文献94.
Skylar R. Hopkins Jennie A. Wyderko Robert R. Sheehy Lisa K. Belden Jeremy M. Wojdak 《Ecology and evolution》2013,3(13):4427-4438
Predators of parasites have recently gained attention as important parts of food webs and ecosystems. In aquatic systems, many taxa consume free‐living stages of parasites, and can thus reduce parasite transmission to hosts. However, the importance of the functional and numerical responses of parasite predators to disease dynamics is not well understood. We collected host–parasite–predator cooccurrence data from the field, and then experimentally manipulated predator abundance, parasite abundance, and the presence of alternative prey to determine the consequences for parasite transmission. The parasite predator of interest was a ubiquitous symbiotic oligochaete of mollusks, Chaetogaster limnaei limnaei, which inhabits host shells and consumes larval trematode parasites. Predators exhibited a rapid numerical response, where predator populations increased or decreased by as much as 60% in just 5 days, depending on the parasite:predator ratio. Furthermore, snail infection decreased substantially with increasing parasite predator densities, where the highest predator densities reduced infection by up to 89%. Predators of parasites can play an important role in regulating parasite transmission, even when infection risk is high, and especially when predators can rapidly respond numerically to resource pulses. We suggest that these types of interactions might have cascading effects on entire disease systems, and emphasize the importance of considering disease dynamics at the community level. 相似文献
95.
Background
Genomic selection is an appealing method to select purebreds for crossbred performance. In the case of crossbred records, single nucleotide polymorphism (SNP) effects can be estimated using an additive model or a breed-specific allele model. In most studies, additive gene action is assumed. However, dominance is the likely genetic basis of heterosis. Advantages of incorporating dominance in genomic selection were investigated in a two-way crossbreeding program for a trait with different magnitudes of dominance. Training was carried out only once in the simulation.Results
When the dominance variance and heterosis were large and overdominance was present, a dominance model including both additive and dominance SNP effects gave substantially greater cumulative response to selection than the additive model. Extra response was the result of an increase in heterosis but at a cost of reduced purebred performance. When the dominance variance and heterosis were realistic but with overdominance, the advantage of the dominance model decreased but was still significant. When overdominance was absent, the dominance model was slightly favored over the additive model, but the difference in response between the models increased as the number of quantitative trait loci increased. This reveals the importance of exploiting dominance even in the absence of overdominance. When there was no dominance, response to selection for the dominance model was as high as for the additive model, indicating robustness of the dominance model. The breed-specific allele model was inferior to the dominance model in all cases and to the additive model except when the dominance variance and heterosis were large and with overdominance. However, the advantage of the dominance model over the breed-specific allele model may decrease as differences in linkage disequilibrium between the breeds increase. Retraining is expected to reduce the advantage of the dominance model over the alternatives, because in general, the advantage becomes important only after five or six generations post-training.Conclusion
Under dominance and without retraining, genomic selection based on the dominance model is superior to the additive model and the breed-specific allele model to maximize crossbred performance through purebred selection. 相似文献96.
97.
Mahdi Saatchi Mathew C McClure Stephanie D McKay Megan M Rolf JaeWoo Kim Jared E Decker Tasia M Taxis Richard H Chapple Holly R Ramey Sally L Northcutt Stewart Bauck Brent Woodward Jack CM Dekkers Rohan L Fernando Robert D Schnabel Dorian J Garrick Jeremy F Taylor 《遗传、选种与进化》2011,43(1):40
Background
Genomic selection is a recently developed technology that is beginning to revolutionize animal breeding. The objective of this study was to estimate marker effects to derive prediction equations for direct genomic values for 16 routinely recorded traits of American Angus beef cattle and quantify corresponding accuracies of prediction.Methods
Deregressed estimated breeding values were used as observations in a weighted analysis to derive direct genomic values for 3570 sires genotyped using the Illumina BovineSNP50 BeadChip. These bulls were clustered into five groups using K-means clustering on pedigree estimates of additive genetic relationships between animals, with the aim of increasing within-group and decreasing between-group relationships. All five combinations of four groups were used for model training, with cross-validation performed in the group not used in training. Bivariate animal models were used for each trait to estimate the genetic correlation between deregressed estimated breeding values and direct genomic values.Results
Accuracies of direct genomic values ranged from 0.22 to 0.69 for the studied traits, with an average of 0.44. Predictions were more accurate when animals within the validation group were more closely related to animals in the training set. When training and validation sets were formed by random allocation, the accuracies of direct genomic values ranged from 0.38 to 0.85, with an average of 0.65, reflecting the greater relationship between animals in training and validation. The accuracies of direct genomic values obtained from training on older animals and validating in younger animals were intermediate to the accuracies obtained from K-means clustering and random clustering for most traits. The genetic correlation between deregressed estimated breeding values and direct genomic values ranged from 0.15 to 0.80 for the traits studied.Conclusions
These results suggest that genomic estimates of genetic merit can be produced in beef cattle at a young age but the recurrent inclusion of genotyped sires in retraining analyses will be necessary to routinely produce for the industry the direct genomic values with the highest accuracy. 相似文献98.
Anna Wolc Chris Stricker Jesus Arango Petek Settar Janet E Fulton Neil P O'Sullivan Rudolf Preisinger David Habier Rohan Fernando Dorian J Garrick Susan J Lamont Jack CM Dekkers 《遗传、选种与进化》2011,43(1):5
Background
Genomic selection involves breeding value estimation of selection candidates based on high-density SNP genotypes. To quantify the potential benefit of genomic selection, accuracies of estimated breeding values (EBV) obtained with different methods using pedigree or high-density SNP genotypes were evaluated and compared in a commercial layer chicken breeding line.Methods
The following traits were analyzed: egg production, egg weight, egg color, shell strength, age at sexual maturity, body weight, albumen height, and yolk weight. Predictions appropriate for early or late selection were compared. A total of 2,708 birds were genotyped for 23,356 segregating SNP, including 1,563 females with records. Phenotypes on relatives without genotypes were incorporated in the analysis (in total 13,049 production records).The data were analyzed with a Reduced Animal Model using a relationship matrix based on pedigree data or on marker genotypes and with a Bayesian method using model averaging. Using a validation set that consisted of individuals from the generation following training, these methods were compared by correlating EBV with phenotypes corrected for fixed effects, selecting the top 30 individuals based on EBV and evaluating their mean phenotype, and by regressing phenotypes on EBV.Results
Using high-density SNP genotypes increased accuracies of EBV up to two-fold for selection at an early age and by up to 88% for selection at a later age. Accuracy increases at an early age can be mostly attributed to improved estimates of parental EBV for shell quality and egg production, while for other egg quality traits it is mostly due to improved estimates of Mendelian sampling effects. A relatively small number of markers was sufficient to explain most of the genetic variation for egg weight and body weight. 相似文献99.
100.
Christof J Majoor Marianne A van de Pol Pieter Willem Kamphuisen Joost CM Meijers Richard Molenkamp Katja C Wolthers Tom van der Poll Rienk Nieuwland Sebastian L Johnston Peter J Sterk Elisabeth HD Bel Rene Lutter Koenraad F van der Sluijs 《Respiratory research》2014,15(1):14