Genome-wide association study reveals three susceptibility loci for common migraine in the general population

Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology.     

A new sceloporine lizard from Oaxaca, Mexico

Sceloporus megalepidurus halli, subsp. nov., is described from San Jos&eacute; Lachiguiri, Oaxaca, Mexico, from one adult male.     

Pocket gophers ( Thomomys talpoides ) in successional stages of spruce-fir forest in Idaho

This study examined (1) the relative abundance of the pocket gopher ( Thomomys talpoides ) in four successive stages (1&ndash;10, 11&ndash;39, 40&ndash;79, and 80+ years following disturbance) of spruce-fir forest; (2) the relationship between number of gopher sign (mounds and earth plugs) with gopher density; and (3) a method of sampling pocket gopher populations using a 500 by 4 m strip transect. The number of gopher mounds was significantly correlated with the number of earth plugs. Data were pooled and a categorical log linear analysis used to test for significant differences in pocket gopher sign between the four successive stages. The 1&ndash;10 and the 80+ -year-old sites had significantly more gopher sign than the 11&ndash;39 and the 40&ndash;79 year-old sites. No significant differences were found between the 11&ndash;39 and the 40&ndash;79-year-old sites, or between the 1&ndash;10 and the 80+ -year-old sites. The difference in population densities may be due to understory vegetation differences between the successional stages. There was a significant correlation between amount of gopher sign and gophers caught in each of the study sites. This indicates that counts of pocket gopher sign may be used to estimate pocket gopher density. The strip transect is recommended as the most appropriate method when sampling heterogeneous habitats or when there is cause to suspect gopher populations may be aggregated within the area rather than spaced randomly or regularly.     

Length of western tent caterpillar egg masses and diameter of their associated stems

Stems bearing egg masses of the western tent caterpillar ( Malacosoma californicum ), collected in Arizona and northern New Mexico during 1977&ndash;1980, had mean diameters between 2.9 and 4 mm. Mean lengths of the egg masses were consistently between 11 and 14 mm.     

Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia

The evolutionarily conserved SLX4 protein, a key regulator of nucleases, is critical for DNA damage response. SLX4 nuclease complexes mediate repair during replication and can also resolve Holliday junctions formed during homologous recombination. Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia. Btbd12-deficient animals are born at sub-Mendelian ratios, have greatly reduced fertility, are developmentally compromised and are prone to blood cytopenias. Btbd12(-/-) cells prematurely senesce, spontaneously accumulate damaged chromosomes and are particularly sensitive to DNA crosslinking agents. Genetic complementation reveals a crucial requirement for Btbd12 (also known as Slx4) to interact with the structure-specific endonuclease Xpf-Ercc1 to promote crosslink repair. The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway.     

The DNA sequence and analysis of human chromosome 13

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.     

A point mutation in the neu oncogene mimics ligand induction of receptor aggregation

The rat neu gene, which encodes a protein closely related to the epidermal growth factor receptor, is a proto-oncogene that can be converted into an oncogene by a point mutation. Both genes encode proteins with a relative molecular mass of 185,000 but the question of why the neu gene product, p185neu, is oncogenic, whereas the product of c-neu, p185c-neu, is not, remains unanswered. The proteins have several features common to the family of tyrosine kinase growth-factor receptors, including cysteine-rich external domains, a hydrophobic transmembrane region and a cytoplasmic tyrosine kinase domain. The oncogenic p185neu differs from p185c-neu by an amino-acid substitution in the transmembrane region of the glycoprotein: this replacement of valine by glutamic acid at position 664 induces increased intrinsic tyrosine kinase activity which is associated with transformation. Many glycoproteins with charged amino acids in the transmembrane region exist as multimeric complexes at the plasma membrane. We have therefore investigated the association state of both products of the neu gene and show that the oncoprotein p185neu is organized at the plasma membrane primarily in an aggregated form, but that p185c-neu is not. Induction of an aggregated state may mimic aspects of ligand-induced receptor aggregation resulting in enzymatic activation that leads to cellular transformation.     

Equilibrating metal-oxide cluster ensembles for oxidation reactions using oxygen in water.

Although many enzymes can readily and selectively use oxygen in water-the most familiar and attractive of all oxidants and solvents, respectively-the design of synthetic catalysts for selective water-based oxidation processes utilizing molecular oxygen remains a daunting task. Particularly problematic is the fact that oxidation of substrates by O2 involves radical chemistry, which is intrinsically non-selective and difficult to control. In addition, metallo-organic catalysts are inherently susceptible to degradation by oxygen-based radicals, while their transition-metal-ion active sites often react with water to give insoluble, and thus inactive, oxides or hydroxides. Furthermore, pH control is often required to avoid acid or base degradation of organic substrates or products. Unlike metallo-organic catalysts, polyoxometalate anions are oxidatively stable and are reversible oxidants for use with O2 (refs 8,9,10). Here we show how thermodynamically controlled self-assembly of an equilibrated ensemble of polyoxometalates, with the heteropolytungstate anion [AIVVW11O40]6- as its main component, imparts both stability in water and internal pH-management. Designed to operate at near-neutral pH, this system facilitates a two-step O2-based process for the selective delignification of wood (lignocellulose) fibres. By directly monitoring the central Al atom, we show that equilibration reactions typical of polyoxometalate anions keep the pH of the system near 7 during both process steps.