Optimizing purebred selection for crossbred performance using QTL with different degrees of dominance

A method was developed to optimize simultaneous selection for a quantitative trait with a known QTL within a male and a female line to maximize crossbred performance from a two-way cross. Strategies to maximize cumulative discounted response in crossbred performance over ten generations were derived by optimizing weights in an index of a QTL and phenotype. Strategies were compared to selection on purebred phenotype. Extra responses were limited for QTL with additive and partial dominance effects, but substantial for QTL with over-dominance, for which optimal QTL selection resulted in differential selection in male and female lines to increase the frequency of heterozygotes and polygenic responses. For over-dominant QTL, maximization of crossbred performance one generation at a time resulted in similar responses as optimization across all generations and simultaneous optimal selection in a male and female line resulted in greater response than optimal selection within a single line without crossbreeding. Results show that strategic use of information on over-dominant QTL can enhance crossbred performance without crossbred testing.     

Mutations induced by ionizing radiation in a plasmid replicated in human cells. I. Similar, nonrandom distribution of mutations in unirradiated and X-irradiated DNA

The Escherichia coli supF gene encoding the suppressor tyrosine tRNA in a human shuttle plasmid, pZ189, was used as a target for molecular analysis of X-ray-induced mutations in human lymphoblastoid cells. Following replication of the in vitro-irradiated plasmid in human cells, the mutant supF-containing molecules were cloned by phenotypic screening in E. coli and the nature of the mutations was determined by direct sequencing of the tRNA gene. At 160 Gy the mutant frequency was 13 times (0.39%) that observed in unirradiated controls (0.031%). When control plasmid was replicated directly in E. coli, the mutant frequency was 16 times less than that of the plasmid passaged through the human cells. The distribution of mutations was highly nonrandom and remarkably similar in both irradiated and control DNAs. The majority of the mutations were transitions involving G.C pairs and occurred selectively at most 5'-TC (3'-AG) sequences. These mutations at C's were preferentially distributed in the nontranscribed strand. We propose that mutations in the control plasmid result from oxidative damages that occur during and/or after its incorporation into human cells and that these damages are similar to those induced by ionizing radiation. The hot spots for mutations suggest that the proximate nucleotide sequence and the overall conformation of the target DNA are important in the production and/or processing of these damages during repair and replication.     

Effect of nutrition improvement project on morbidity from infectious diseases in preschool children in Vietnam: comparison with control commune.

OBJECTIVE: To evaluate the effect of a nutrition improvement project based on home garden production and nutrition education on morbidity from acute respiratory infection and diarrhoeal disease in preschool children. DESIGN: The morbidity survey comprised five data collections undertaken by trained interviewers to ascertain the incidence and severity of respiratory infections and the incidence of diarrhoeal disease in children in two communes. SETTING: A project commune and a control commune in Vietnam. SUBJECTS: Preschool children to 6 years of age living in the project commune Khai Xuan (average 469 children) and the control commune Ching Cong (average 251 children). MAIN OUTCOME MEASURES: Differences between the two communes over time in the incidence and severity of respiratory infections and the incidence of diarrhoeal disease. RESULTS: In Khai Xuan there was a significant reduction (P < 0.0001) in the incidence of respiratory infections (from 49.5% to 11.2%) and diarrhoeal infections (18.3% to 5.1%); the incidence of pneumonia and severe pneumonia was also significantly reduced (P < 0.0001). In Ching Cong there was no significant change in the incidence and severity of respiratory disease nor in the incidence of diarrhoeal disease. CONCLUSIONS: These findings emphasise the successful health outcome of a nutrition project based on household food production and nutrition education and the value of evaluating nutrition projects by reference to measurable health outcomes.     

D- and L-lactate catabolism to CO2 in rat tissues

The current study was initiated in order to compare the rates of oxidative catabolism of D- and L-lactate in various rat tissues. Uniformly labeled D- or L-[14C]lactate was incubated at 37 degrees C in a closed system with tissue homogenates in Krebs-Ringer phosphate buffer. Evolved 14CO2 was trapped in a center well containing a fluted filter paper saturated with strong base and the radioactivity determined. The ratio of L-lactate to D-lactate oxidation was greatest in brain, followed by kidney, heart, and liver. In liver the rate of oxidation of D-lactate exceeded that of L-lactate, in heart the rates were not significantly different and in the other two tissues L-lactate was oxidized more rapidly than D-lactate. These results indicate that the rate of D-lactate catabolism is considerable and is relatively greater than had been reported previously.     

Human T lymphocyte differentiation antigens: effects of blood sample storage on Leu antibody binding

Current studies of human T lymphocytes and their subsets often use quantitative immunofluorescence analysis with monoclonal antibodies against cell surface antigens. With storage of whole blood or separated mononuclear cells for more than a few hours we have found marked changes in lymphocyte analysis using a fluorescence activated cell sorter (FACS). Experiments were done to determine if these lymphocyte changes were influenced by storage temperature and if lymphocytes could be made more stable by addition of culture media RPMI 1640 to whole blood. Optimal conditions found for blood storage were with with addition of 50% RPMI 1640 and with samples held at room temperature (22 degrees C). With these storage conditions, delay on FACS analysis up to 24 hours did not result in spurious results. When blood samples are collected in places remote from the laboratory or when batch analysis of serially collected samples is desirable, excessive storage times should be avoided.     

The repair of large DNA adducts in mammalian cells.

This paper describes experiments involving the measurement of DNA damage and repair after treatment with 4-nitroquinoline 1-oxide (4NQO) or aflatoxin B1 (AFB1) epoxide in a number of mammalian cell cultures primarily associated with defects in the excision repair of UV-induced DNA damage. The results with transformed derivatives of XP cells belonging to different complementation groups showed that the extent of repair of 4NQO adducts at the N2 or C8 of guanosine did not correlate to the extent of repair reported by others after UV-irradiation. An examination of 4NQO repair in rodent UV-sensitive cell lines from different ERCC groups indicated that again there was little correlation between the extent of 4NQO and UV repair. However, regardless of complementation group those mutants that were defective in the repair of pyrimidine dimers and 6,4-photoproducts did exhibit a reduced ability to repair the 4NQO N2 guanosine adduct, whereas those mutants defective in pyrimidine dimer repair alone were able to repair this lesion as normal. In all of these cell lines there was a normal capacity to repair the 4NQO C8 guanosine adduct. Less extensive experiments involving AFB1 epoxide showed an XPC-transformed cell line was able to repair 40% of lesions after 6 h, whereas only 20% of repair is seen after UV. The rodent mutant V-C4 which belongs to the same ionising radiation group as irs2, was partially defective in repairing AFB1-induced damage. These experiments highlight the fact that although there are many commonalities between the repair of UV damages and lesions classed as large DNA adducts differences clearly exist, the most striking example here being the repair of the C8 guanosine 4NQO adduct which rarely correlates with a defect in UV repair.