A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Quantum oscillations of the critical current and high-field superconducting proximity in ballistic graphene

Graphene-based Josephson junctions provide a novel platform for studying the proximity effect due to graphene's unique electronic spectrum and the possibility to tune junction properties by gate voltage. Here we describe graphene junctions with a mean free path of several micrometres, low contact resistance and large supercurrents. Such devices exhibit pronounced Fabry-P\'erot oscillations not only in the normal-state resistance but also in the critical current. The proximity effect is mostly suppressed in magnetic fields below 10mT, showing the conventional Fraunhofer pattern. Unexpectedly, some proximity survives even in fields higher than 1 T. Superconducting states randomly appear and disappear as a function of field and carrier concentration, and each of them exhibits a supercurrent carrying capacity close to the universal quantum limit. We attribute the high-field Josephson effect to mesoscopic Andreev states that persist near graphene edges. Our work reveals new proximity regimes that can be controlled by quantum confinement and cyclotron motion

Impact of PGL-I Seropositivity on the Protective Effect of BCG Vaccination among Leprosy Contacts: A Cohort Study

Although leprosy has become a neglected disease, it is an important cause of disability, and 250,000 new cases are still diagnosed worldwide every year. The current study was carried out in Brazil, where almost 40,000 new cases of leprosy are diagnosed every year. The study targeted contacts of leprosy patients, who are at the highest risk of contracting the disease. We studied 2,135 contacts who were diagnosed at the Leprosy Outpatient Clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, RJ, Brazil, between 1987 and 2007. The presence of antibodies against a specific Mycobacterium leprae antigen (PGL-I) at the first examination and BCG vaccination status were evaluated. PGL-I-positive contacts had a higher risk of developing leprosy than PGL-I-negative contacts. Among the former, vaccinated contacts were at higher risk than unvaccinated contacts. Our results indicate that contact examination combined with PGL-I testing and BCG vaccination appears to justify the targeting of PGL-I-positive individuals for enhanced surveillance. Furthermore, it is highly recommended that PGL-I-positive contacts and contacts with a high familial bacterial index (i.e., the sum of results from index and co-prevalent cases), regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis

The intergenerational association between parents' problem gambling and impulsivity-hyperactivity/inattention behaviors in children

Despite the well-established association between problem gambling and ADHD core categories of impulsivity-hyperactivity and inattention, the link between parents’ problem gambling and impulsivity-hyperactivity/inattention (IH/I) behaviors in children has not been investigated. This study investigated the association between parents’ problem gambling and children’s IH/I behaviors while controlling for potential confounding variables. A population-based prospective cohort followed-up from kindergarten to age 30, the Quebec Longitudinal Study of Kindergarten Children (QLSKC), provided data over three generations. Among 1358 participants at age 30, parents with a child aged 1 year or older (N=468; Mean age=4.65 years; SD=2.70) were selected. Generalized Linear Models included measures of grandparents’ and parents’ problem gambling, parents’ IH/I behaviors in childhood, and a host of risk factors and comorbidities to predict IH/I in children. Intergenerational bivariate associations were observed between grandparents’ problem gambling, parents’ IH/I in childhood and problem gambling at age 30, and between parents’ IH/I, problem gambling, and children’s IH/I behaviors. Parents’ problem gambling predicted children’s IH/I behaviors above and beyond the effects of covariates such as family and socioeconomic characteristics, alcohol and drug use, depression symptoms and parents’ gambling involvement. Parents’ IH/I behaviors in childhood also predicted children’s IH/I and had a moderating, enhancing effect on parents’ problem gambling association with their offspring’s IH/I behaviors. Problem gambling is a characteristic of parents’ mental health that is distinctively associated with children’s IH/I behaviors, above and beyond parents’ own history of IH/I and of typically related addictive, psychopathological or socioeconomic risk factors and comorbidities

Nucleo-cytoplasmic transport of proteins and RNA in plants

Merkle T. Nucleo-cytoplasmic transport of proteins and RNA in plants. Plant Cell Reports. 2011;30(2):153-176.Transport of macromolecules between the nucleus and the cytoplasm is an essential necessity in eukaryotic cells, since the nuclear envelope separates transcription from translation. In the past few years, an increasing number of components of the plant nuclear transport machinery have been characterised. This progress, although far from being completed, confirmed that the general characteristics of nuclear transport are conserved between plants and other organisms. However, plant-specific components were also identified. Interestingly, several mutants in genes encoding components of the plant nuclear transport machinery were investigated, revealing differential sensitivity of plant-specific pathways to impaired nuclear transport. These findings attracted attention towards plant-specific cargoes that are transported over the nuclear envelope, unravelling connections between nuclear transport and components of signalling and developmental pathways. The current state of research in plants is summarised in comparison to yeast and vertebrate systems, and special emphasis is given to plant nuclear transport mutants

Positividade sorológica antiPGL-I em contatos domiciliares e peridomiciliares de hanseníase em área urbana Seropositivity with anti-PGL-I of household and neighbours contacts of leprosy patients in an urban area

FUNDAMENTOS: Pesquisas atuais buscam avaliar a prevalência de pessoas infectadas pelo M. leprae, bem como o valor preditivo dos testes utilizados, em meio aos quais está a sorologia, que detecta anticorpos contra um antígeno específico da parede do Mycobacterium leprae, o glicolipídio fenólico (PGL-I). OBJETIVOS: Conhecer a taxa de infecção em contatos intra e peridomiciliares, e a relação de soropositividade com sexo, idade e grupo multibacilar/paucibacilar. MATERIAIS E MÉTODOS: Inquérito soroepidemiológico em contatos domiciliares e peridomiciliares dos casos notificados como hanseníase entre 1998 e 2002, no segundo distrito do Município de Duque de Caxias, RJ, utilizando o teste sorológico rápido de fluxo lateral ou ML Flow. RESULTADOS: Em 390 domicílios de casos de hanseníase foram identificados 2.130 contatos, e submetidos à sorologia 1.866 (12,4% de perda). A soropositividade foi de 15,7% (292/1.866), sendo 15,8% no domicílio e 15,6% no peridomicílio. Também não houve diferença na relação entre soropositividade e sexo e em maiores e menores de 15 anos. Observou-se diferença significativa na soropositividade de contatos de casos de hanseníase MB (67,5%), duas vezes maior do que a dos casos de PB (32,5%). DISCUSSÃO / CONCLUSÃO: Nas condições de moradia da periferia urbana de área endêmica devem ser submetidos igualmente à vigilância epidemiológica os contatos domiciliares e peridomiciliares.<br>BACKGROUND: Actually many studies have been made to evaluate the predictive value of tests that identify patients infected by Mycobacterium leprae. Among then, the serology that determinates the presence o M. leprae specific antibody. OBJECTIVES: To know the infections tax among households and direct neighbours contacts, establish soropositivity relationship according to sex, household/ neighbour, age and classification of leprosy of the index case (paucibacillary x multibacillary). PATIENTS AND METHODS: seroepidemiological study covering all the household and neighbours of leprosy patients diagnosticated from 1998 to 2002, in the second district of Duque de Caxias, Rio de Janeiro, using fast ML-Flow. RESULTS: A total of 2.130 contacts were identified in 390 domiciles of leprosy patients. Of the 2130 contacts, 1866 were submmited to serology (12.4% lost). Seroprevalence was 15,7%(292/1866); 15.8% household and 15.6% neighbour. The relationship of seropositivity with sex and age (>15 >15 years old) did not shown any statistic difference. But it was seen among contacts of MB index cases ( 67,5%) 2 times higher than contacts of PB cases (32,5%). DISCUSSION / CONCLUSION: In highly endemic areas for leprosy, situated at peripheral metropoliten cities not only household contacts of the index case, but also people living in the close vicinity were more likely to harbour antibodies against M. leprae. Through measuring the serological status of contacts and using a broader definition for them, higher risk groups can be more specifically identified