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Jason King

Publications and source records attributed to Jason King.

4 recordsLinked to original sources
PubMed2006

Parasexual genetics using axenic cells.

Normally, vegetative Dictyostelium grow as haploid cells. Occasionally, two haploid cells fuse together during normal growth, forming a diploid cell containing both parental sets of chromosomes within a single nucleus. The diploid state is reasonably stable, and the growth, development, and general behavior of diploids are similar to their haploid parents. However, during normal growth of diploids, cells may spontaneously lose one copy of each chromosome at random and revert back to a haploid state containing a selection of chromosomes from both parents. This diploid cycle therefore allows nonsexual recombination between two different mutant strains. Diploid cells have multiple practical uses. They allow the generation of double and multiple knockouts, and are particularly useful for strains that are sick or difficult to generate using molecular genetics. They provide a means of manipulating genes that are lethal when disrupted in haploids. In diploids, it is possible to isolate heterozygous knockouts with no phenotype and then introduce a further mutant allele. These cells can then be segregated to yield haploid progeny with an effective gene replacement. Similarly, diploids made from different parent strains offer a means of examining the effects of different genetic backgrounds and overriding strain-specific phenotypes. A number of other uses are possible, making parasexual genetics potentially even more versatile.

Animals↗
PubMed2003

Parasexual genetics of Dictyostelium gene disruptions: identification of a ras pathway using diploids.

BACKGROUND: The relative ease of targeted gene disruption in the social amoeba Dictyostelium has stimulated its widespread use as an experimental organism for cell and developmental biology. However, the field has been hamstrung by the lack of techniques to recombine disrupted genes. RESULTS: We describe new techniques for parasexual fusion of strains in liquid medium, selection and maintenance of the resulting stable diploid strains, and segregation to make recombined haploids. We have used these techniques to isolate rasS/gefB double nulls. The phenotypes of these mutants are no more severe than either parent, with movement, phagocytosis and fluid-phase endocytosis affected to the same degree as in rasS or gefB single nulls. In addition, we have produced diploids from one AX2- and one AX3-derived parent, providing an axenic strain with fewer secondary phenotypes than has been previously available. CONCLUSIONS: The phenotype of the rasS/gefB double mutant suggests that the RasS and GefB proteins lie on the same linear pathway. In addition, axenic diploids and the techniques to generate, maintain and segregate them will be productive tools for future work on Dictyostelium. They will particularly facilitate generation of multiple mutants and manipulation of essential genes.

Animals↗
PubMed2002

Costs and benefits of different strategies to screen for cervical cancer in less-developed countries.

BACKGROUND: About 80% of cervical cancers occur in less-developed countries. This disproportionate burden of cervical cancer in such countries is due mainly to the lack of well-organized screening programs. Several cervical cancer screening strategies have been proposed as more cost-effective than cytology screening. We compared the costs and benefits of different strategies and their effectiveness in saving lives in a less-developed country. METHODS: We used a population-based simulation model to evaluate the incremental societal costs and benefits in Thailand of seven screening techniques, including visual inspection of the cervix after applying acetic acid (VIA), human papillomavirus (HPV) testing, Pap smear, and combinations of screening tests, and examined the discounted costs per year of life saved (LYS). RESULTS: Compared with no (i.e., not well-organized) screening, all strategies saved lives, at costs ranging from 121 US dollars to 6720 US dollars per LYS, and reduced mortality, by up to 58%. Comparing each strategy with the next least expensive alternative, VIA performed at 5-year intervals in women of ages 35-55 with immediate treatment if abnormalities are found was the least expensive option and saved the greatest number of lives, with a cost of 517 US dollars per LYS. HPV screening resulted in similar costs and benefits, if the test cost is 5 US dollars and if 90% of women undergo follow-up after an abnormal screen. Cytology (Pap smear) was a reasonable alternative if sensitivity exceeds 80% and if 90% of women undergo follow-up. Compared with no screening, use of a combination of Pap smear and HPV testing at 5-year intervals in women of ages 20-70 could achieve greater than 90% reduction in cervical cancer mortality at a cost of 1683 US dollars per LYS, and VIA could achieve 83% reduction at 524 US dollars per LYS. CONCLUSIONS: Well-organized screening programs can reduce cervical cancer mortality in less-developed countries at low costs. These cost-effectiveness data can enhance decision-making about optimal policies for a given setting.

Acetic Acid↗