Base-excision repair of oxidative DNA damage

Maintaining the chemical integrity of DNA in the face of assault by oxidizing agents is a constant challenge for living organisms. Base-excision repair has an important role in preventing mutations associated with a common product of oxidative damage to DNA, 8-oxoguanine. Recent structural studies have shown that 8-oxoguanine DNA glycosylases use an intricate series of steps to locate and excise 8-oxoguanine lesions efficiently against a high background of undamaged bases. The importance of preventing mutations associated with 8-oxoguanine is shown by a direct association between defects in the DNA glycosylase MUTYH and colorectal cancer. The properties of other guanine oxidation products and the associated DNA glycosylases that remove them are now also being revealed.     

Vernier templating and synthesis of a 12-porphyrin nano-ring

Templates are widely used to arrange molecular components so they can be covalently linked into complex molecules that are not readily accessible by classical synthetic methods. Nature uses sophisticated templates such as the ribosome, whereas chemists use simple ions or small molecules. But as we tackle the synthesis of larger targets, we require larger templates-which themselves become synthetically challenging. Here we show that Vernier complexes can solve this problem: if the number of binding sites on the template, n(T), is not a multiple of the number of binding sites on the molecular building blocks, n(B), then small templates can direct the assembly of relatively large Vernier complexes where the number of binding sites in the product, n(P), is the lowest common multiple of n(B) and n(T) (refs 8, 9). We illustrate the value of this concept for the covalent synthesis of challenging targets by using a simple six-site template to direct the synthesis of a 12-porphyrin nano-ring with a diameter of 4.7?nm, thus establishing Vernier templating as a powerful new strategy for the synthesis of large monodisperse macromolecules.     

Forecasting Ability of a Periodic Component Extracted from Large‐Cap Index Time Series

We develop a method to extract periodic variations in a time series that are hidden in large non‐periodic and stochastic variations. This method relies on folding the time series many times and allows direct visualization of a hidden periodic component without resorting to any fitting procedure. Applying this method to several large‐cap stock time series in Europe, Japan and the USA yields a component with periodicity of 1 year. Out‐of‐sample tests on these large‐cap time series indicate that this periodic component is able to forecast long‐term (decade) behavior for large‐cap time series. Copyright © 2016 John Wiley & Sons, Ltd.     

Phospholipase C-induced neural tube defects in the mouse embryo

Summary Mouse embryo neurulae were exposed in vitro to phospholipase C to examine the role of carbohydrate-rich extracellular material (ECM) during neurulation. Exposure of embryos to this agent for 12 h resulted in failure of closure of the neural tube. Ultrastructural examination revealed an absence of ECM from regions of the neural tube which failed to close.This study was supported by a grant from the National Fund for Research into Crippling Diseases.     

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.