Anticoccidial riboflavine antagonists

Summary 4 types of riboflavine antagonists have broad-spectrum activity in poultry coccidiosis. 5-Deazariboflavine is most effective. 10-Benzyl analogs of riboflavine control intestinal species of coccidia.     

Common sequence variants on 20q11.22 confer melanoma susceptibility

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.     

An evaluation of HapMap sample size and tagging SNP performance in large-scale empirical and simulated data sets

A substantial investment has been made in the generation of large public resources designed to enable the identification of tag SNP sets, but data establishing the adequacy of the sample sizes used are limited. Using large-scale empirical and simulated data sets, we found that the sample sizes used in the HapMap project are sufficient to capture common variation, but that performance declines substantially for variants with minor allele frequencies of <5%.     

Atomism and ‘subtlety’ in Francis Bacon's philosophy

Francis Bacon's reflections on atomism have generally been misunderstood because they have never been systematically studied in relation to the speculative chemical philosophy which he developed in the interval between about 1592 and his death in 1626. This philosophy, in many respects unknown to historians until quite recently, was the only body of positive science which Bacon ever accepted. The speculative philosophy was, on the whole, chemical and non-mechanical, and consequently not consistent with atomist doctrines. In fact, Bacon never at any time accepted the principal atomist tenets. It is therefore necessary to explain why he was interested in atomism at all. Of the several reasons for his interest one (hitherto unrecognised) is especially important—namely, his belief that the speculative and atomic philosophies had affinities. In particular, he believed that of all the ancient philosophies atomism alone approached the ideals associated with the key notion of ‘subtlety’—ideals represented in their highest form (as he imagined) in the speculative philosophy.     

Phenotypic consequences of 1,000 generations of selection at elevated CO2 in a green alga

Estimates of the effect of increasing atmospheric CO2 concentrations on future global plant production rely on the physiological response of individual plants or plant communities when exposed to high CO2 (refs 1-6). Plant populations may adapt to the changing atmosphere, however, such that the evolved plant communities of the next century are likely to be genetically different from contemporary communities. The properties of these future communities are unknown, introducing a bias of unknown sign and magnitude into projections of global carbon pool dynamics. Here we report a long-term selection experiment to investigate the phenotypic consequences of selection for growth at elevated CO2 concentrations. After about 1,000 generations, selection lines of the unicellular green alga Chlamydomonas failed to evolve specific adaptation to a CO2 concentration of 1,050 parts per million. Some lines, however, evolved a syndrome involving high rates of photosynthesis and respiration, combined with higher chlorophyll content and reduced cell size. These lines also grew poorly at ambient concentrations of CO2. We tentatively attribute this outcome to the accumulation of conditionally neutral mutations in genes affecting the carbon concentration mechanism.     

BluB cannibalizes flavin to form the lower ligand of vitamin B12

Vitamin B12 (cobalamin) is among the largest known non-polymeric natural products, and the only vitamin synthesized exclusively by microorganisms. The biosynthesis of the lower ligand of vitamin B(12), 5,6-dimethylbenzimidazole (DMB), is poorly understood. Recently, we discovered that a Sinorhizobium meliloti gene, bluB, is necessary for DMB biosynthesis. Here we show that BluB triggers the unprecedented fragmentation and contraction of the bound flavin mononucleotide cofactor and cleavage of the ribityl tail to form DMB and D-erythrose 4-phosphate. Our structural analysis shows that BluB resembles an NAD(P)H-flavin oxidoreductase, except that its unusually tight binding pocket accommodates flavin mononucleotide but not NAD(P)H. We characterize crystallographically an early intermediate along the reaction coordinate, revealing molecular oxygen poised over reduced flavin. Thus, BluB isolates and directs reduced flavin to activate molecular oxygen for its own cannibalization. This investigation of the biosynthesis of DMB provides clarification of an aspect of vitamin B12 that was otherwise incomplete, and may contribute to a better understanding of vitamin B12-related disease.