Molecular dynamics simulations were used to model the response of several double-stranded dodecamers to gradually increasing tension applied to the opposing 3′ ends of the two polynucleotide strands. At forces between 0.80 and 1.45 nN, depending on sequence, the strands separated completely. The separation force for one of the dodecamers studied has been measured and is close to that seen in the simulation. Before strand separation, at forces between 0.065 and 0.090 nN, again depending on sequence, there was an abrupt extension and transition to a novel ladder structure in which bases of one strand were stacked on those of the other strand. Sudden extensions have been observed in very long DNA molecules at forces similar to those seen in the simulations. After the abrupt extension but before strand separation, the ladder structure became more regular, and the phosphate backbones became more linear. Throughout the entire molecular extension, most hydrogen-bonded base pairs remained intact.
Variants in 2 genes were associated with early-onset MI: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. The identification of these variants could improve understanding of disease mechanisms and suggest novel drug targets.
Noncardioembolic stroke and coronary heart disease (CHD) may share genetic predispositions. We tested the hypothesis that genetic variants which are associated with risk of CHD would also be associated with risk of noncardioembolic stroke in 562 cases from the Vienna Stroke Registry and 815 controls. We selected 6 gene variants that had been consistently associated with risk of CHD in 3 studies, including the Atherosclerosis Risk in Communities study, and found that 4 of these gene variants were also associated with risk of noncardioembolic stroke. The odds ratios for noncardioembolic stroke were 1.31 (90% CI 1.07–1.60) for rs3900940 in MYH15, 1.24 (90% CI 1.01–1.5) for rs20455 in KIF6, 1.21 (90% CI 0.99–1.49) for rs1010 in VAMP8, and 1.20 (90% CI 0.95–1.50) for rs10757274 on chromosome 9p21.
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