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.     

Stoneflies (Plecoptera) of the Black Hills of South Dakota and Wyoming, USA: distribution and zoogeographic affinities

The Black Hills of South Dakota and Wyoming are an insular mountain range completely surrounded by the Great Plains. The stonefly (Plecoptera) fauna of the Black Hills was surveyed and zoogeographic affinities examined. Twenty-seven species representing 22 genera and 6 families were found. Fifteen new state records for South Dakota and 2 for Wyoming are presented. Two species are removed from the South Dakota list. An analysis of the North American distribution of each species showed a strong relationship between the Black Hills and the Rocky Mountains, with much weaker relationships between the Black Hills and eastern and northern regions. Results of a logistic regression analysis comparing factors contributing to long-distance dispersal ability against presence/absence in the Black Hills were inconclusive. However, other evidence suggests that the Black Hills fauna is a result of expansion and subsequent vicariance of stonefly populations during Pleistocene climatic oscillations.     

Distribution of sculpins in the Clearwater River Basin, Idaho

The distributions of Cottus bairdi, C. rhotheus, and C. beldingi exhibited a highly significant positive degree of association. Conversely, the distribution of C. confusus exhibited a highly significant negative association with the distributional complex, C. bairdi, C. rhotheus, and C. beldingi. These species of sculpins can be grouped into two assemblages; one based on the distribution of C. confusus and the other based on the combined distributions of the other three species. The factor or factors limiting the downstream distribution of C. confusus or the upstream distribution of the other three species could not be positively identified. However, we hypothesize that competition between C. confusus and one or more members of the C. bairdi, C. rhotheus and C. beldingi complex is involved. In the area of overlapping distributions among C. bairdi, C. rhotheus, and C. bairdi we hypothesize that resource partitioning is occurring. However, the data did not allow evaluation of this hypothesis. &nbsp;&nbsp;     

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.     

Gene polymorphism in Netherton and common atopic disease.

Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420-->Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses.     

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.     

关于“阳光体育运动”实施效果的思考

采用文献资料法、访谈法、观察法对阳光体育运动实施过程中存在的问题进行反思,认为实施对象与直接执行者不在场,对象群体目的与决策者目标不一致,决策目标与实施方法、策略不协调,对不同年龄、地域、性别学生的实施要求与手段无差别,无经费支撑等是阳光体育运动难以为继的关键所在。