August Weismann's theory of the germ-plasm and the problem of unconceived alternatives

I have argued elsewhere that scientific realism is most significantly challenged neither by traditional arguments from underdetermination of theories by the evidence, nor by the traditional pessimistic induction, but by a rather different historical pattern: our repeated failure to conceive of alternatives to extant scientific theories, even when those alternatives were both (1) well-confirmed by the evidence available at the time and (2) sufficiently scientifically serious as to be later embraced by actual scientific communities. Here I use August Weismann's defense of his influential germ-plasm theory of inheritance to support my claim that this pattern characterizes the history of theoretical scientific investigation generally. Weismann believed that the germ-plasm must become disintegrated into its constituent elements over the course of development, I argue, only because he failed to conceive of any possible alternative mechanism of ontogenetic differentiation. This and other features of the germ-plasm theory, I suggest, reflect a still more fundamental failure to imagine that the germ-plasm might be a productive rather than expendable resource for the cell. Weismann's case provides impressive support for the problem of unconceived alternatives while rendering its challenge to scientific realism deeper and sharper in a number of important ways.     

Genetic linkage analysis of prostate cancer families to Xq27-28

OBJECTIVES: A recent linkage analysis of 360 families at high risk for prostate cancer identified the q27-28 region on chromosome X as the potential location of a gene involved in prostate cancer susceptibility. Here we report on linkage analysis at this putative HPCX locus in an independent set of 186 prostate cancer families participating in the Prostate Cancer Genetic Research Study (PROGRESS). METHODS: DNA samples from these families were genotyped at 8 polymorphic markers spanning 14.3 cM of the HPCX region. RESULTS: Two-point parametric analysis of the total data set resulted in positive lod scores at only two markers, DXS984 and DXS1193, with scores of 0.628 at a recombination fraction (theta) of 0.36 and 0.012 at theta = 0.48, respectively. The stratification of pedigrees according to the assumed mode of transmission increased the evidence of linkage at DXS984 in 81 families with no evidence of male-to-male transmission (lod = 1.062 at theta = 0.28). CONCLUSIONS: Although this analysis did not show statistically significant evidence for the linkage of prostate cancer susceptibility to Xq27-28, the results are consistent with a small percentage of families being linked to this region. The analysis further highlights difficulties in replicating linkage results in an etiologically heterogeneous, complexly inherited disease.     

Impact of feed processing and mixed ruminal culture on the fate of recombinant EPSP synthase and endogenous canola plant DNA

The impact of feed processing and in vitro ruminal cultures on the persistence of recombinant and canola-specific endogenous DNA was studied using various canola substrates (whole seed, cracked seed, meal and diet). For both, parental and genetically modified substrates, ribulose-1,5-bisphosphate carboxylase/oxygenase gene was amplifiable up to varying time points. Persistence of recombinant DNA, encoding 5-enolpyruvylshikimate-3-phosphate synthase (1,363 bp) was detected up to 8 h for meal and 4 h for mixed diet. Upon processing of canola, DNA large enough to contain intact plant genes remains. In an in vitro environment, plant DNA was rapidly degraded upon its release into rumen fluid.     

Nitric oxide protects thymocytes from gamma-irradiation-induced apoptosis in correlation with inhibition of p53 upregulation and mitochondrial damage

Apoptosis plays a crucial role in clonal deletion in the thymus, and NO has been shown to prevent apoptosis in some cell types. Therefore, we examined the effect of NO on gamma-irradiation-induced thymocyte apoptosis. Treatment of 5 Gy gamma-irradiated thymocytes with 1 mM SNAP reduced cell death from 78 to 49% after 8 h incubation (spontaneous cell death in medium control cells was 26%). Coincubation with ZVAD blocked both the spontaneous cell death and the cell death induced by SNAP or gamma-irradiation. The gamma-irradiation-induced increase in caspase 3 and 6 activities was inhibited in the presence of SNAP. The increase in cytosolic cytochrome c as well as the decrease in mitochondrial membrane potential after gamma-irradiation was inhibited in the presence of SNAP. SNAP treatment also decreased the p53 upregulation in gamma-irradiated cells. In summary, we found that NO exerts a protective effect on mouse thymocyte apoptosis induced by gamma-irradiation. The mechanism of this protective effect may involve inhibition of p53 upregulation and reduction in mitochondrial damage, with subsequent inhibition of downstream caspase activation.