Potential novel candidate polymorphisms identified in genome-wide association study for breast cancer susceptibility

Previous genome-wide association studies (GWAS) have shown several risk alleles to be associated with breast cancer. However, the variants identified so far contribute to only a small proportion of disease risk. The objective of our GWAS was to identify additional novel breast cancer susceptibility variants and to replicate these findings in an independent cohort. We performed a two-stage association study in a cohort of 3,064 women from Alberta, Canada. In Stage I, we interrogated 906,600 single nucleotide polymorphisms (SNPs) on Affymetrix SNP 6.0 arrays using 348 breast cancer cases and 348 controls. We used single-locus association tests to determine statistical significance for the observed differences in allele frequencies between cases and controls. In Stage II, we attempted to replicate 35 significant markers identified in Stage I in an independent study of 1,153 cases and 1,215 controls. Genotyping of Stage II samples was done using Sequenom Mass-ARRAY iPlex platform. Six loci from four different gene regions (chromosomes 4, 5, 16 and 19) showed statistically significant differences between cases and controls in both Stage I and Stage II testing, and also in joint analysis. The identified variants were from EDNRA, ROPN1L, C16orf61 and ZNF577 gene regions. The presented joint analyses from the two-stage study design were not significant after genome-wide correction. The SNPs identified in this study may serve as potential candidate loci for breast cancer risk in a further replication study in Stage III from Alberta population or independent validation in Caucasian cohorts elsewhere.     

A multivariate,osteological approach to Towa culture history

Eleven cranial measurements on 14 archeological populations from the American Southwest support the archeologically derived reconstruction of Towa population movements. The supposed (linguistic) relationship between Pecos and the Towa speaking villages is questioned.     

18S rRNA data indicate that Aschelminthes are polyphyletic in origin and consist of at least three distinct clades

The Aschelminthes is a collection of at least eight animal phyla, historically grouped together because the absence of a true body cavity was perceived as a pseudocoelom. Analyses of 18S rRNA sequences from six Aschelminth phyla (including four previously unpublished sequences) support polyphyly for the Aschelminthes. At least three distinct groups of Aschelminthes were detected: the Priapulida among the protostomes, the Rotifera-Acanthocephala as a sister group to the protostomes, and the Nematoda as a basal group to the triploblastic Eumetazoa.      

Unstable dynamics of a periodically driven oscillator in the presence of noise

Two qualitatively different unstable dynamical behaviours are shown to arise from the application of a periodic input to a simple mathematical model of an oscillator in the presence of noise. Rhythms similar to quasiperiodic dynamics may arise when there is a low amplitude periodic input, while with high amplitude inputs, patterns with irregular skipped or intercalated beats are found. These two qualitatively different types of unstable dynamics are similar to those observed in the respiratory activity of mechanically ventilated cats. A number of numerical simulations are performed to illustrate the quantitative properties of the two unstable patterns and to show how the quantitative properties can be compared with experimental data.     

Heat shock protein synthesis and thermotolerance in Salmonella typhimurium

The resistance of stationary phase Salmonella typhimurium to heating at 55 degrees C was greater in cells grown in nutritionally rich than in minimal media, but in all media tested resistance was enhanced by exposing cells to a primary heat shock at 48 degrees C. Chloramphenicol reduced the acquisition of thermotolerance in all media but did not completely prevent it in any. The onset of thermotolerance was accompanied by increased synthesis of major heat shock proteins of molecular weight about 83, 72, 64 and 25 kDa. When cells were shifted from 48 degrees C to 37 degrees C, however, thermotolerance was rapidly lost with no corresponding decrease in the levels of these proteins. There is thus no direct relationship between thermotolerance and the cellular content of the major heat shock proteins. One minor protein of molecular weight about 34 kDa disappeared rapidly following a temperature down-shift. Its presence in the cell was thus correlated with the thermotolerant state.     

The relationship between the base composition of bacterial DNA and its intracellular melting temperature as determined by differential scanning calorimetry

The correlation between the melting temperature of intracellular DNA, determined by differential scanning calorimetry (DSC) of whole bacteria, and its guanine + cytosine (G + C) content, was examined for 58 species of bacteria. Samples of vegetative cells were heated in a Perkin-Elmer DSC-2C at 10 degrees C min-1 from 5 to 130 degrees C, cooled to 5 degrees C and then re-heated as before. Literature values for the mole fraction of G + C, XGC, were linearly related to the temperature, Tmax, at which the reversible peak, pr, observed on the second heating run was at a maximum, via the equation XGC = (Tmax -73.8)/41.0. This equation accounted for 91.9% of the variance in XGC with 95% confidence limits of +/- 7.3%, approximately 1.6 times the corresponding uncertainty (+/- 4.5%) quoted by De Ley (Journal of Bacteriology 101, 738-754, 1970) for estimates based on the spectroscopically determined melting temperature of purified DNA. Random errors of measurement of Tmax did not greatly limit the precision of the prediction and it was concluded that factors additional to base composition affected the temperature of DNA melting within the bacterial cell. Displacement of Tmax values from the fitted line was particularly noticeable in Campylobacter, Corynebacterium and Bacterionema species and part of the residual variation appeared to be species specific, possibly caused by differences in intracellular solute concentration.