Influence of environmental changes on degradation of chiral pollutants in soils.

Numerous anthropogenic chemicals of environmental concern--including some phenoxy acid herbicides, organophosphorus insecticides, polychlorinated biphenyls, phthalates, freon substitutes and some DDT derivatives--are chiral. Their potential biological effects, such as toxicity, mutagenicity, carcinogenicity, and endocrine disrupter activity, are generally enantiomer-selective, and different enantiomers are preferentially degraded (transformed) by micro-organisms in various environments. Here we use field and laboratory experiments to demonstrate that environmental changes in soils can alter these preferences, and to suggest that the preferences shift owing to different groups of related microbial genotypes being activated by different environmental changes. In Brazilian soils, almost all pasture samples preferentially transformed the non-herbicidal enantiomer of dichlorprop ((RS)-2-(2,4-dichlorophenoxy)propionic acid), while most forest samples either transformed the herbicidal enantiomer more readily or as rapidly as the non-herbicidal enantiomer. Organic nutrient enrichments shifted enantioselectivity for methyl dichlorprop ((RS)-methyl 2-(2,4-dichlorophenoxy)propionic acid) strongly towards preferentially removing the non-herbicidal enantiomer in soils from Brazil and North America, potentially increasing phytotoxicity of its residues relative to that of the racemate. Assessments of the risks chemical pollutants pose to public health and the environment need to take into account the chiral selectivity of microbial transformation processes and their alteration by environmental changes, especially for pesticides as up to 25 per cent are chiral.     

Functional improvement of dystrophic muscle by myostatin blockade

Mice and cattle with mutations in the myostatin (GDF8) gene show a marked increase in body weight and muscle mass, indicating that this new member of the TGF-beta superfamily is a negative regulator of skeletal muscle growth. Inhibition of the myostatin gene product is predicted to increase muscle mass and improve the disease phenotype in a variety of primary and secondary myopathies. We tested the ability of inhibition of myostatin in vivo to ameliorate the dystrophic phenotype in the mdx mouse model of Duchenne muscular dystrophy (DMD). Blockade of endogenous myostatin by using intraperitoneal injections of blocking antibodies for three months resulted in an increase in body weight, muscle mass, muscle size and absolute muscle strength in mdx mouse muscle along with a significant decrease in muscle degeneration and concentrations of serum creatine kinase. The functional improvement of dystrophic muscle by myostatin blockade provides a novel, pharmacological strategy for treatment of diseases associated with muscle wasting such as DMD, and circumvents the major problems associated with conventional gene therapy in these disorders.     

Multiple regions within 8q24 independently affect risk for prostate cancer

After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.