Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21

In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ～5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.     

Home births in the UK, 1955 to 2006

This article presents data on trends in the percentage of maternities taking place at home in the UK. As well as the national trend, the article examines how home maternity levels vary according to mother's age, number of previous live births within marriage, country of birth, region, local authority and NHS Trust. Examination of trends and variations in home maternity levels provides a context for debates regarding factors that may influence where women give birth.     

Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris

Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these mutations are semidominant; heterozygotes show a very mild phenotype with incomplete penetrance. The mutations show a combined allele frequency of approximately 4% in populations of European ancestry, explaining the high incidence of ichthyosis vulgaris. Profilaggrin is the major protein of keratohyalin granules in the epidermis. During terminal differentiation, it is cleaved into multiple filaggrin peptides that aggregate keratin filaments. The resultant matrix is cross-linked to form a major component of the cornified cell envelope. We find that loss or reduction of this major structural protein leads to varying degrees of impaired keratinization.     

Orchid: A Cultural History

By now, the story of T. D. Lysenko's phantasmagoric career in the Soviet life sciences is widely familiar. While Lysenko's attempts to identify I. V. Michurin, the horticulturist, as the source of his own inductionist ideas about heredity are recognized as a gambit calculated to enhance his legitimacy, the real roots of those ideas are still shrouded in mystery. This paper suggests those roots may be found in a tradition in Russian biology that stretches back to the 1840s—a tradition inspired by the doctrines of Jean-Baptiste Lamarck and Etienne and Isidore Geoffroy Saint-Hilaire. The enthusiastic reception of those doctrines in Russia and of their practical application—acclimatization of exotic life forms—gave rise to the durable scientific preoccupation with transforming nature which now seems implicated in creating the context for Lysenko's successful bid to become an arbiter of the biological sciences.     

Characterization of tumor differentiation factor (TDF) and its receptor (TDF-R)

Tumor differentiation factor (TDF) is an under-investigated protein produced by the pituitary with no definitive function. TDF is secreted into the bloodstream and targets the breast and prostate, suggesting that it has an endocrine function. Initially, TDF was indirectly discovered based on the differentiation effect of alkaline pituitary extracts of the mammosomatotropic tumor MtTWlO on MTW9/PI rat mammary tumor cells. Years later, the cDNA clone responsible for this differentiation activity was isolated from a human pituitary cDNA library using expression cloning. The cDNA encoded a 108-amino-acid polypeptide that had differentiation activity on MCF7 breast cancer cells and on DU145 prostate cancer cells in vitro and in vivo. Recently, our group focused on identification of the TDF receptor (TDF-R). As potential TDF-R candidates, we identified the members of the Heat Shock 70-kDa family of proteins (HSP70) in both MCF7 and BT-549 human breast cancer cells (HBCC) and PC3, DU145, and LNCaP human prostate cancer cells (HPCC), but not in HeLa cells, NG108 neuroblastoma, or HDF-a and BLK CL.4 cells fibroblasts or fibroblast-like cells. Here we review the current advances on TDF, with particular focus on the structural investigation of its receptor and on its functional effects on breast and prostate cells.     

Wavelet-based Fuzzy Clustering of Time Series

Traditional procedures for clustering time series are based mostly on crisp hierarchical or partitioning methods. Given that the dynamics of a time series may change over time, a time series might display patterns that may enable it to belong to one cluster over one period while over another period, its pattern may be more consistent with those in another cluster. The traditional clustering procedures are unable to identify the changing patterns over time. However, clustering based on fuzzy logic will be able to detect the switching patterns from one time period to another thus enabling some time series to simultaneously belong to more than one cluster. In particular, this paper proposes a fuzzy approach to the clustering of time series based on their variances through wavelet decomposition. We will show that this approach will distinguish between time series with different patterns in variability as well identifying time series with switching patterns in variability.     

白族二爨碑文体与《文心雕龙》诔碑理论范式

爨氏是古代白族的大姓之一,东晋时期的<爨宝子碑>、刘宋时期的<爨龙颜碑>作为白族先民的碑刻文献,是魏晋南北朝时期白族文学的重要文本."二爨碑"的产生分别前于<文心雕龙>九十余年和四十余年,其体式与刘勰<文心雕龙>阐释的诔碑理论范式几乎偶合,为刘勰诔碑理论提供珍贵的历史文献实证,在白族古代文学发展史上具有上承后汉滇文化,下启唐代南诏文化的重要意义.     

Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis

Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10??, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10??, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10?3, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10?? (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10.