Characterization of a genomic signature of pregnancy identified in the breast.

The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.

Crescimento e produção de primeiro ciclo da bananeira 'Prata Anã' (AAB) em sete espaçamentos

Este estudo teve por objetivo verificar o comportamento da bananeira (Musa spp.) 'Prata Anã' no primeiro ciclo de produção na localidade de Jaíba, MG, submetida a sete espaçamentos, com irrigação. Os tratamentos foram: triângulo: 2,7 m x 3,2 m (1.157 covas/ha) e 2,9 m x 3,4 m (1.014 covas/ha); fileira dupla em triângulo: 4,5 m x 2,0 m x 3,0 m (1.026 covas/ha) e 4,5 m x 2,0 m x 2,0 m (1.538 covas/ha); fileira dupla em retângulo: 4,5 m x 2,0 m x 3,5 m (879 covas/ha); e retângulo: 4,0 m x 2,0 m (1.250 covas/ha) e 3,0 m x 2,0 m (1.666 covas/ha). Os sistemas de espaçamento e as densidades populacionais testados não alteraram as taxas de crescimento das plantas nem suas características na época da colheita. Entretanto, as bananeiras plantadas em maiores densidades apresentaram maior produtividade, atingindo até 29,1 t/ha. As plantas apresentaram, em média, ciclo do plantio à colheita de 411 dias, ciclo do florescimento à colheita de 141 dias, e cachos com 17,7 kg, 9,1 pencas e 134 frutos. Para o primeiro ciclo de produção, o espaçamento mais apropriado foi de 3,0 m x 2,0 m, em retângulo, para a região de Jaíba.

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

Residence time, expansion toward the equator in the invaded range and native range size matter to climatic niche shifts in non-native species

Aim Identifying climatic niche shifts and their drivers is important to accurately predict the risk of biological invasions. The niches of non-native plants and birds have recently been assessed in large-scale multi-species studies, but such large-scale tests are lacking for non-native reptiles and amphibians (herpetofauna). Furthermore, little is known about the factors contributing to niche shifts when they occur. Based on the occurrence of 71 reptile and amphibian species, we compared native and non-native realized niches in 101 invaded ranges at a worldwide scale and identified the factors that affect niche shifts. Location The world except the Antarctic. Methods We assessed climatic niche dynamics in a gridded environmental space allowing the quantification of niche overlap and expansion into climatic conditions not colonized by the species in their native range. We analyzed the factors affecting niche shifts using a model averaging approach based on generalized linear mixed-effects models. Results Approximately 57% of the invaded ranges (51% for amphibians and 61% for reptiles) showed niche shifts (≥10% expansion in the realized climatic niche). Island endemics, species introduced to Oceania and invaded ranges outside the native biogeographic realm showed a higher proportion of niche shifts. Niche shifts were more likely for species that had smaller native range sizes, were introduced earlier into a new range or invaded areas located at lower latitudes than the native range. Main conclusions The proportion of niche shifts for non-native herpetofauna was higher than those for Holarctic non-native plants and European non-native birds. The 'climate matching hypothesis' should be used with caution for species shifting their niche because it could underestimate the risk of their establishment.

T cell receptor-ligand interactions: a conformational preequilibrium or an induced fit.

Kinetic parameters of T cell receptor (TCR) interactions with its ligand have been proposed to control T cell activation. Analysis of kinetic data obtained has so far produced conflicting insights; here, we offer a consideration of this problem. As a model system, association and dissociation of a soluble TCR (sT1) and its specific ligand, an azidobenzoic acid derivative of the peptide SYIPSAEK-(ABA)I (residues 252-260 from Plasmodium berghei circumsporozoite protein), bound to class I MHC H-2K(d)-encoded molecule (MHCp) were studied by surface plasmon resonance. The association time courses exhibited biphasic patterns. The fast and dominant phase was assigned to ligand association with the major fraction of TCR molecules, whereas the slow component was attributed to the presence of traces of TCR dimers. The association rate constant derived for the fast phase, assuming a reversible, single-step reaction mechanism, was relatively slow and markedly temperature-dependent, decreasing from 7.0 x 10(3) at 25 degrees C to 1.8 x 10(2) M(-1).s(-1) at 4 degrees C. Hence, it is suggested that these observed slow rate constants are the result of unresolved elementary steps of the process. Indeed, our analysis of the kinetic data shows that the time courses of TCR-MHCp interaction fit well to two different, yet closely related mechanisms, where an induced fit or a preequilibrium of two unbound TCR conformers are operational. These mechanisms may provide a rationale for the reported conformational flexibility of the TCR and its unusual ligand recognition properties, which combine high specificity with considerable crossreactivity.

[Venise. Basilica di San Marco]

Référence bibliographique : Weigert, 729

Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters.

Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (T(FH)) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed T(FH) markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Superação da dormência de cultivares de mirtileiro em ambiente protegido com cianamida hidrogenada e óleo mineral

O mirtileiro é uma frutífera de clima temperado que necessita de frio no outono/inverno. A insuficiência de frio pode provocar deficiente e desuniforme brotação e floração, com reflexos na produção. A pesquisa realizada na Universidade de Passo Fundo-RS, teve por objetivo estudar a superação da dormência de cultivares de mirtileiro (Georgiagem, Climax e Aliceblue) em ambiente protegido, tratadas em 25-07-2007 com cianamida hidrogenada (CH), nas doses de 0,52% e 1,04% (1% e 2% do produto comercial Dormex®), com a adição de 0,5% de óleo mineral (OM), comparando com plantas sem tratamento. As plantas encontravam-se no terceiro ciclo vegetativo e no primeiro de produção. O plantio foi realizado em 2005, no espaçamento de 0,7 m x 2,0 m, com irrigação por gotejamento. De acordo com os resultados obtidos, a aplicação no final de julho de CH + OM concentrou e uniformizou a floração e antecipou a brotação das cvs. Georgiagem e Clímax. A cianamida hidrogenada, nas concentrações de 0,52% e 1,04% (1% e 2% de Dormex®), combinado com 0,5% de óleo mineral, não teve efeito na porcentagem de brotação, mas reduziu a produção, evidenciando efeitos fitotóxicos.

Propagação de variedades de caramboleira por estaquia herbácea

Realizou-se o presente trabalho objetivando avaliar a propagação de três variedades de caramboleira por estaquia em função da dose de regulador de crescimento (ácido indolbutírico - AIB), empregada no tratamento das estacas. Foram utilizadas estacas herbáceas apicais, sendo o experimento conduzido em câmara de nebulização intermitente, localizada em condições de ripado (50% de luminosidade). As estacas das variedades B10, Hart e Golden Star receberam o tratamento com AIB, nas doses de 100; 200 e 400 mg.L-1 (imersäo lenta) e nas doses de 1.000, 3.000 e 5.000 mg.L-1 (imersäo rápida), mais tratamento-testemunha (0 mg.L-1 de AIB). As avaliações, 90 dias após a estaquia, foram quanto: porcentagens de sobrevivência, calejamento e enraizamento; número médio de raízes por estaca e comprimento médio das raízes (cm). O delineamento experimental foi o inteiramente casualizado, com quatro repetições por tratamento, compostas por 10 estacas, analisado em fatorial 3 x 7 (variedades x AIB). Conforme resultados obtidos neste trabalho, näo há necessidade do tratamento das estacas de caramboleira com regulador de crescimento (AIB). A variedade Golden Star mostrou melhores resultados, seguida pela Hart e B10.

Sanitary quality of edible bivalve mollusks in Southeastern Brazil using an UV based depuration system

The increase in seafood production, especially in mariculture worldwide, has brought out the need of continued monitoring of shellfish production areas in order to ensure safety to human consumption. The purpose of this research was to evaluate pathogenic protozoa, viruses and bacteria contamination in oysters before and after UV depuration procedure, in brackish waters at all stages of cultivation and treatment steps and to enumerate microbiological indicators of fecal contamination from production site up to depuration site in an oyster cooperative located at the Southeastern estuarine area of Brazil. Oysters and brackish water were collected monthly from September 2009 to November 2010. Four sampling sites were selected for enteropathogens analysis: site 1- oyster growth, site 2- catchment water (before UV depuration procedure), site 3 - filtration stage of water treatment (only for protozoa analysis) and site 4- oyster's depuration tank. Three microbiological indicators ! were examined at sites 1, 2 and 4. The following pathogenic microorganisms were searched: Giardia cysts, Cryptosporidium oocysts, Human Adenovirus (HAdV), Hepatitis A virus (HAV), Human Norovirus (HnoV) (genogroups I and II), JC strain Polyomavirus (JCPyV) and Salmonella sp. Analysis consisted of molecular detection (qPCR) for viruses (oysters and water samples); immunomagnetic separation followed by direct immunofluorescence assay for Cryptosporidium oocysts and Giardia cysts and also molecular detection (PCR) for the latter (oysters and water samples); commercial kit (Reveal-Neogee (R)) for Salmonella analysis (oysters). Giardia was the most prevalent pathogen in all sites where it was detected: 36.3%, 18.1%, 36.3% and 27.2% of water from sites 1, 2, 3 and 4 respectively; 36.3% of oysters from site 1 and 54.5% of depurated oysters were harboring Giardia cysts. The huge majority of contaminated samples were classified as Giardia duodenalis. HAdv was detected in water and o! ysters from growth site and HnoV GI in two batches of oysters ! (site 1) in huge concentrations (2.11 x 10(13), 3.10 x 10(12) gc/g). In depuration tank site, Salmonella sp., HAV (4.84 x 10(3)) and HnoV GII (7.97 x 10(14)) were detected once in different batches of oysters. Cryptosporidium spp. oocysts were present in 9.0% of water samples from site four. These results reflect the contamination of oysters even when UV depuration procedures are employed in this shellfish treatment plant. Moreover, the molecular comprehension of the sources of contamination is necessary to develop an efficient management strategy allied to shellfish treatment improvement to prevent foodborne illnesses. (C) 2011 Elsevier Ltd. All rights reserved.

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Reatividade Relativa em Solvólise Nucleofílica de Cloretos de Arilsulfenila, Arilcarbonila, Arilsulfonila, Arilmetila e de Arila

The experimental results for the 2-propanolysis of benzoyl, benzyl, benzene sulphenyl and benzene sulphonyl chlorides obtained by conductimetric technique were compared with estimates for chlorobenzene which is extremely unreactive as an electrophile. We thus obtained the following reactivity sequence: PhSCl>PhCOCl>PhSO2Cl>PhCH2 Cl>PhCl with rate-coefficiente ratios (in the same order): 9.5 x 10(4) : 1: 7.14 x 10-2 : 4.7 x 10-3 : about 10-26. We have discussed these results in specific terms and with the aid of general conclusions which stem from our own classification of electrophiles.