DNA-mediated gene transfer as an indicator of DNA damage and its repair by recipient cells

AbstractPreparations of plasmid containing the thymidine kinase gene (pHSV106) were treated with the alkylating agents methyl methanesulphonate or N-methyl-N-nitrosourea prior to transfection into thymidine kinase-deficient mouse L-cells using the DNA-calcium phosphate co-precipitation technique. Relative to transfection with unmodified plasmid, a reduced transformation efficiency was observed using alkylation-damaged plasmid, N-methyl-N-nitrosourea causing the greatest inhibition. Treatment of recipient cells with arabinosyl cytosine or dideoxythymidine during the expression period following transfection by the ‘damaged’ plasmid reduced transformation efficiency, suggesting that DNA repair 4–6 h post-transfection was required for gene expression

Digestion of Repair Sites in Rat Liver DNA by Endogenous Nucleases

The proportion of sheared rat liver DNA recovered from benzoylated DEAE-cellulose in the final stage following stepwise elution with NaCl and caffeine solutions was dependent upon the DNA isolation procedure. An increase in the proportion of DNA containing single stranded regions, consequent upon delay or addition of Mg2+ prior to phenol extraction, suggested nuclease mediated degradation. Administration of methyl methanesulphonate to rats resulted in a consistent proportional increase in the caffeine-eluted fraction. The results of caffeine gradient elution of control and alkylated DNA from benzoylated DEAE-cellulose were consistent with repair-associated single stranded regions being substrates for endogenous single strand-specific exonucleases

Radiation pions in two-nucleon effective field theory

For interactions involving two or more nucleons it is useful to divide pions into three classes: potential, radiation, and soft. The momentum threshold for the production of radiation pions is $Q_r = \sqrt{M_N m_\pi}$. We show that radiation pions can be included systematically with a power counting in $Q_r$. The leading order radiation pion graphs which contribute to NN scattering are evaluated in the PDS and OS renormalization schemes and are found to give a small contribution. The power counting for soft pion contributions is also discussed.Comment: 21 pages, 3 figs, journal versio

Chiral Extrapolation: An Analogy with Effective Field Theory

We draw an analogy between the chiral extrapolation of lattice QCD calculations from large to small quark masses and the interpolation between the large mass (weak field) and small mass (strong field) limits of the Euler--Heisenberg QED effective action. In the latter case, where the exact answer is known, a simple extrapolation of a form analogous to those proposed for the QCD applications is shown to be surprisingly accurate over the entire parameter range.Comment: 6 pp, revtex, 3 figs; minor changes -- version to appear in PL

Slim Epistemology with a Thick Skin

The distinction between ‘thick’ and ‘thin’ value concepts, and its importance to ethical theory, has been an active topic in recent meta-ethics. This paper defends three claims regarding the parallel issue about thick and thin epistemic concepts. (1) Analogy with ethics offers no straightforward way to establish a good, clear distinction between thick and thin epistemic concepts. (2) Assuming there is such a distinction, there are no semantic grounds for assigning thick epistemic concepts priority over the thin. (3) Nor does the structure of substantive epistemological theory establish that thick epistemic concepts enjoy systematic theoretical priority over the thin. In sum, a good case has yet to be made for any radical theoretical turn to thicker epistemology

Cardiovascular disease risk profile and microvascular complications of diabetes: comparison of Indigenous cohorts with diabetes in Australia and Canada

<p>Abstract</p> <p>Background</p> <p>Indigenous populations of Australia and Canada experience disproportionately high rates of chronic disease. Our goal was to compare cardiovascular (CVD) risk profile and diabetes complications from three recent comprehensive studies of diabetes complications in different Indigenous populations in Australia and Canada.</p> <p>Methods</p> <p>We compared participants from three recent studies: remote Indigenous Australians (2002-2003, n = 37 known diabetes), urban Indigenous Australians (2003-2005, n = 99 known diabetes), and remote Aboriginal Canadians (2001-2002, n = 188 known diabetes).</p> <p>Results</p> <p>The three groups were similar for HbA1c, systolic BP, diabetes duration. Although leaner by body-mass-index criteria, remote Indigenous Australians displayed a more adverse CVD risk profile with respect to: waist-hip-ratio (1.03, 0.99, 0.94, remote Indigenous Australians, urban Indigenous Australians, remote Canadians, p < 0.001); HDL-cholesterol (0.82, 0.96, 1.17 mmol/L, p < 0.001); urine albumin-creatinine-ratio (10.3, 2.4, 4.5 mg/mmol); and C-reactive protein. With respect to diabetes complications, microalbuminuria (50%, 25%, 41%, p = 0.001) was more common among both remote groups than urban Indigenous Australians, but there were no differences for peripheral neuropathy, retinopathy or peripheral vascular disease.</p> <p>Conclusions</p> <p>Although there are many similarities in diabetes phenotype in Indigenous populations, this comparison demonstrates that CVD risk profiles and diabetes complications may differ among groups. Irrespective, management and intervention strategies are required from a young age in Indigenous populations and need to be designed in consultation with communities and tailored to community and individual needs.</p

B --> pi and B --> K transitions in partially quenched chiral perturbation theory

We study the properties of the B-->pi and B-->K transition form factors in partially quenched QCD by using the approach of partially quenched chiral perturbation theory combined with the static heavy quark limit. We show that the form factors change almost linearly when varying the value of the sea quark mass, whereas the dependence on the valence quark mass contains both the standard and chirally divergent (quenched) logarithms. A simple strategy for the chiral extrapolations in the lattice studies with Nsea=2 is suggested. It consists of the linear extrapolations from the realistically accessible quark masses, first in the sea and then in the valence quark mass. From the present approach, we estimate the uncertainty induced by such extrapolations to be within 5%.Comment: Published versio

Assessing the association of the HNF1A G319S variant with C-reactive protein in Aboriginal Canadians: a population-based epidemiological study

<p>Abstract</p> <p>Background</p> <p>C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased risk of developing cardiovascular disease. Common variants of the hepatocyte nuclear factor 1A (<it>HNF1A) </it>gene encoding HNF-1α have been associated with plasma CRP in predominantly European Caucasian samples. <it>HNF1A </it>might therefore have an impact on vascular disease and diabetes risk that is mediated by CRP. In an Aboriginal Canadian population, a private polymorphism, <it>HNF1A </it>G319S, was associated with increased prevalence of type 2 diabetes. However, it has not been investigated whether this association is mediated by CRP. We aimed to investigate whether CRP was mediating the association between <it>HNF1A </it>G319S and type 2 diabetes in an Aboriginal Canadian population with a high prevalence of diabetes.</p> <p>Methods</p> <p>A total of 718 individuals who participated in a diabetes prevalence and risk factor survey were included in the current analysis. Participants were genotyped for <it>HNF1A </it>G319S. Fasting plasma samples were analyzed for CRP. Fasting plasma glucose and a 75-g oral glucose tolerance test were obtained to determine type 2 diabetes.</p> <p>Results</p> <p>The prevalence rate of type 2 diabetes was 17.4% (125/718) using the 1999 World Health Organization definition and was higher among S319 allele carriers compared to G/G homozygotes (p < 0.0001). Among participants without type 2 diabetes, CRP levels were higher among G/G homozygotes (1.64 [95% confidence interval 1.35-2.00] mg/l) than in S319 carriers (1.26 [1.04-1.54] mg/l) (p = 0.009) after adjustment for age, sex, 2-h post-load glucose, waist circumference, and serum amyloid A. CRP levels were elevated among those with diabetes after similar adjustment (4.39 [95% confidence interval 3.09-6.23] and 4.44 [3.13-6.30] mg/L, respectively), and no significant difference in CRP was observed between S319 carriers and non-carriers (p = 0.95).</p> <p>Conclusions</p> <p>CRP levels were lower in S319 allele carriers of the <it>HNF1A </it>gene compared to non-carriers among individuals without diabetes, but this difference was not present among those with diabetes, who uniformly had elevated CRP levels. Therefore, while <it>HNF1A </it>appears to influence CRP concentrations in the non-diabetic state, chronic elevation of CRP is unlikely mediating the association between the <it>HNF1A </it>polymorphism and the high prevalence of type 2 diabetes in this Aboriginal population.</p

An estimate of the flavour singlet contributions to the hyperfine splitting in charmonium

We explore the splitting between flavour singlet and non-singlet mesons in charmonium. This has implications for the hyperfine splitting in charmonium