Genome-wide association study identifies eight loci associated with blood pressure.

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

A rotação de cultura reduz a matocompetição e aumenta o teor de clorofila e a produtividade do arroz

A rotação de culturas é uma prática importante em sistemas agrícolas sustentáveis pelos efeitos benéficos tanto na fertilidade do solo como na redução da matocompetição, entre outros. Este trabalho foi conduzido no campo experimental da UEMA, em São Luís, MA. Avaliou-se o efeito da rotação de culturas na incidência de plantas invasoras, nos teores de clorofila e na produtividade do arroz (Oryza sativa L. cv. Guarani). Cultivou-se o arroz com e sem adubação nitrogenada, bem como em rotação com caupi (Vigna unguiculata (L.) Walp.), crotalária (Crotalaria paulina Schrank) e mucuna (Mucuna aterrima Piper & Tracy). No primeiro ciclo a cobertura morta das leguminosas, deixada sobre o solo para a safra seguinte, foi máxima na crotalária, intermediária na mucuna e mínima no caupi. No segundo ciclo, cultivado em plantio direto sem uso de herbicidas, a rotação com mucuna e crotalária reduziu a biomassa, a cobertura e a densidade das invasoras. O teor de clorofila foi maior na rotação com crotalária do que na testemunha. A produtividade do arroz foi maior na rotação com crotalária e mucuna do que no arroz em cultivo sucessivo com ou sem N. Concluiu-se que a rotação do arroz com leguminosas aumenta a produtividade do arroz e reduz a matocompetição.

Comportamento de espécies de adubos verdes em diferentes épocas de semeadura e espaçamentos na região dos Cerrados

Com o objetivo de avaliar o crescimento e desenvolvimento de leguminosas utilizadas como adubos verdes, instalaram-se três ensaios, em três épocas de semeadura e dois espaçamentos na região dos Cerrados, durante o ano agrícola de 1991/1992, na área experimental da Embrapa-Centro Nacional de Pesquisa do Solo (CNPS), em Senador Canedo, GO. As espécies avaliadas foram Crotalaria juncea L., mucuna-preta (Mucuna aterrima (Piper & Tracy) Merr.), guandu cv. Kaki (Cajanus cajan (L.) Millsp.) e Crotalaria ochroleuca G. Don. O delineamento experimental utilizado, dentro de cada época, foi o de blocos ao acaso com parcelas subdivididas, com três repetições. Os resultados indicaram que C. juncea e C. cajan apresentaram as maiores produções de fitomassa seca. O atraso da semeadura, em relação ao início da estação chuvosa, reduziu os rendimentos de fitomassas verde e seca produzidos pelas leguminosas, exceto pela mucuna-preta. Os espaçamentos de 0,5 m e 0,4 m não influenciaram o período para o florescimento e as produções de fitomassas verde e seca.

The influence of tobacco consumption on the relationship between schizotypy and hemispheric asymmetry.

Tobacco use is positively associated with severity of symptoms along the schizophrenia spectrum. Accordingly it could be argued that neuropsychological performance, formerly thought to be modulated by schizotypy, is actually modulated by drug use or an interaction of drug use and schizotypy. We tested whether habitual cigarette smokers as compared to non-smokers would show a neuropsychological profile similar to that observed along the schizophrenia spectrum and, if so, whether smoking status or nicotine dependence would be more significant modulators of behavior than schizotypy. Because hemispheric dominance has been found to be attenuated along the schizophrenia spectrum, 40 right-handed male students (20 non-smokers) performed lateralized left- (lexical decisions) and right- (facial decision task) hemisphere dominant tasks. All individuals completed self-report measures of schizotypy and nicotine dependence. Schizotypy predicted laterality in addition to smoking status: While positive schizotypy (Unusual Experiences) was unrelated to hemispheric performance, Cognitive Disorganization predicted reduced left hemisphere dominant language functions. These latter findings suggest that Cognitive Disorganization should be regarded separately as a potentially important mediator of thought disorganization and language processing. Additionally, increasing nicotine dependence among smokers predicted a right hemisphere shift of function in both tasks that supports the role of the right hemisphere in compulsive/impulsive behavior.

Treatment implications of the emerging molecular classification system for melanoma.

Melanoma is an aggressive disease with few standard treatment options. The conventional classification system for this disease is based on histological growth patterns, with division into four subtypes: superficial spreading, lentigo maligna, nodular, and acral lentiginous. Major limitations of this classification system are absence of prognostic importance and little correlation with treatment outcomes. Recent preclinical and clinical findings support the notion that melanoma is not one malignant disorder but rather a family of distinct molecular diseases. Incorporation of genetic signatures into the conventional histopathological classification of melanoma has great implications for development of new and effective treatments. Genes of the mitogen-associated protein kinase (MAPK) pathway harbour alterations sometimes identified in people with melanoma. The mutation Val600Glu in the BRAF oncogene (designated BRAF(V600E)) has been associated with sensitivity in vitro and in vivo to agents that inhibit BRAF(V600E) or MEK (a kinase in the MAPK pathway). Melanomas arising from mucosal, acral, chronically sun-damaged surfaces sometimes have oncogenic mutations in KIT, against which several inhibitors have shown clinical efficacy. Some uveal melanomas have activating mutations in GNAQ and GNA11, rendering them potentially susceptible to MEK inhibition. These findings suggest that prospective genotyping of patients with melanoma should be used increasingly as we work to develop new and effective treatments for this disease.

Cultivar de soja BRS 205

A BRS 205, cultivar de soja de ciclo semiprecoce, obtida do cruzamento [BR-16(2) x Ocepar 8] x Tracy-M, é indicada para o Rio Grande do Sul, em semeaduras de novembro. Possui crescimento determinado, plantas de flor branca, pubescência marrom, porte baixo e grãos de hilo preto. Tem resistência ao cancro-da-haste (Diaporthe phaseolorum f. sp. meridionalis), à podridão-parda-da-haste (Phialophora gregata), à mancha-olho-de-rã (Cercospora sojina) e à pústula bacteriana (Xanthomonas axonopodis pv. glycines). É moderadamente resistente ao oídio (Microsphaera diffusa). O rendimento médio de grãos foi 6% e 11% superior ao das cultivares RS 7-Jacuí e BR-16, respectivamente.

Nutrientes minerais na biomassa da parte aérea em culturas de cobertura de solo

O objetivo deste trabalho foi estimar as quantidades de nutrientes reciclados por cinco espécies vegetais utilizadas como culturas de cobertura do solo e que podem retornar ao solo pela mineralização da biomassa. Foram coletadas de vários experimentos amostras da matéria verde de aveia-preta (Avena strigosa Schreb), mucu-napreta (Stizolobium aterrimum Piper & Tracy), guandu (Cajanus cajan (L.) Millsp), tremoço (Lupinus albus L. e L. angustifolius L.) e ervilhaca (Vicia sativa L.). Foi estimado o rendimento de matéria seca e determinados os teores de N, P, K, Ca, Mg, Mn, Zn, Cu, e, a partir dessas concentrações, foram calculadas a média observada, a média estimada e o intervalo de confiança a 95% para cada nutriente dentro de cada classe de rendimento de matéria seca, em cada espécie vegetal. Os dados foram tabulados dentro de intervalos de classe de rendimento de matéria seca e apresentadas as quantidades estimadas de nutrientes minerais. Foram ajustadas equações para estimar as quantidades desses nutrientes. A aveia-preta e a ervilhaca reciclam grande quantidade de K, e a ervilhaca, a mucu-napreta, o tremoço e o guandu reciclam grande quantidade de N. Todas as espécies reciclam quantidades apreciáveis de Ca, Mg e micronutrientes, porém baixas quantidades de P. A rotação de culturas é um meio de implementar com sucesso o aumento das áreas de lavoura em semeadura direta.

Formation of virus-like clusters is an intrinsic property of the tumor necrosis factor family member BAFF (B cell activating factor).

The oligomeric state of BAFF (B cell activing factor), a tumor necrosis factor (TNF) family cytokine that plays a critical role in B cell development and survival, has been the subject of recent debate. Myc-tagged BAFF starting at residue Gln136 was previously reported to crystallize as trimers at pH 4.5, whereas a histidine-tagged construct of BAFF, starting at residue Ala134, formed a virus-like cluster containing 60 monomers when crystallized at pH 9.0. The formation of the BAFF 60-mer was pH dependent, requiring pH >or= 7.0. More recently, 60-mer formation was suggested to be artificially induced by the histidine tag, and it was proposed that BAFF, like all other TNF family members, is trimeric. We report here that a construct of BAFF with no amino-terminal tag (Ala134-BAFF) can form a 60-mer in solution. Using size exclusion chromatography and static light scattering to monitor trimer to 60-mer ratios in BAFF preparations, we find that 60-mer formation is pH-dependent and requires histidine 218 within the DE loop of BAFF. Biacore measurements established that the affinity of Ala134-BAFF for the BAFF receptor BAFFR/BR3 is similar to that of myc-Gln136-BAFF, which is exclusively trimeric in solution. However, Ala134-BAFF is more efficacious than myc-Gln136-BAFF in inducing B cell proliferation in vitro. We additionally show that BAFF that is processed and secreted by 293T cells transfected with full-length BAFF, or by a histiocytic lymphoma cell line (U937) that expresses BAFF endogenously, forms a pH-dependent 60-mer in solution. Our results indicate that the formation of the 60-mer in solution by the BAFF extracellular domain is an intrinsic property of the protein, and therefore that this more active form of BAFF may be physiologically relevant.

Randomized trial of a computerized coronary heart disease risk assessment tool in HIV-infected patients receiving combination antiretroviral therapy.

BACKGROUND: Exposure to combination antiretroviral therapy (cART) can lead to important metabolic changes and increased risk of coronary heart disease (CHD). Computerized clinical decision support systems have been advocated to improve the management of patients at risk for CHD but it is unclear whether such systems reduce patients' risk for CHD. METHODS: We conducted a cluster trial within the Swiss HIV Cohort Study (SHCS) of HIV-infected patients, aged 18 years or older, not pregnant and receiving cART for >3 months. We randomized 165 physicians to either guidelines for CHD risk factor management alone or guidelines plus CHD risk profiles. Risk profiles included the Framingham risk score, CHD drug prescriptions and CHD events based on biannual assessments, and were continuously updated by the SHCS data centre and integrated into patient charts by study nurses. Outcome measures were total cholesterol, systolic and diastolic blood pressure and Framingham risk score. RESULTS: A total of 3,266 patients (80% of those eligible) had a final assessment of the primary outcome at least 12 months after the start of the trial. Mean (95% confidence interval) patient differences where physicians received CHD risk profiles and guidelines, rather than guidelines alone, were total cholesterol -0.02 mmol/l (-0.09-0.06), systolic blood pressure -0.4 mmHg (-1.6-0.8), diastolic blood pressure -0.4 mmHg (-1.5-0.7) and Framingham 10-year risk score -0.2% (-0.5-0.1). CONCLUSIONS: Systemic computerized routine provision of CHD risk profiles in addition to guidelines does not significantly improve risk factors for CHD in patients on cART.

Sistemas de preparo do solo, plantas de cobertura e produtividade da cultura da mandioca

O objetivo deste trabalho foi avaliar os efeitos do uso de plantas de cobertura e de sistemas de preparo do solo, no desenvolvimento e na produtividade da cultura da mandioca (Manihot esculenta Crantz). O trabalho foi conduzido em Argissolo Vermelho, sob sistema convencional de preparo do solo, e em cultivo mínimo sobre palhada de mucuna-cinza (Stizolobium cinereum Piper & Tracy), sorgo granífero [Sorghum bicolor (L.) Moench] e milheto [Pennisetum americanum (L.) K. Schum.]. Aos dezoito meses após o plantio da mandioca, foram avaliados: altura de plantas, produção de massa de matéria seca da parte aérea, número de raízes tuberosas, produtividade, percentagem de matéria seca e de amido nas raízes tuberosas e índice de colheita. Observou-se que o sistema convencional de preparo do solo pode ser substituído, na cultura da mandioca, pela prática do cultivo mínimo, associada ao uso de coberturas vegetais, por promover incrementos significativos na produtividade da cultura, especialmente, quando se utiliza o milheto como planta de cobertura. O uso de plantas de cobertura no pré-cultivo de mandioca, em sistema de preparo mínimo do solo, representa uma alternativa eficiente para um melhor manejo dessa cultura.

Type I IFN controls chikungunya virus via its action on nonhematopoietic cells.

Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. As viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type I interferon (IFN) in CHIKV pathogenesis. Based on human studies and mouse experimentation, we show that CHIKV does not directly stimulate type I IFN production in immune cells. Instead, infected nonhematopoietic cells sense viral RNA in a Cardif-dependent manner and participate in the control of infection through their production of type I IFNs. Although the Cardif signaling pathway contributes to the immune response, we also find evidence for a MyD88-dependent sensor that is critical for preventing viral dissemination. Moreover, we demonstrate that IFN-alpha/beta receptor (IFNAR) expression is required in the periphery but not on immune cells, as IFNAR(-/-)-->WT bone marrow chimeras are capable of clearing the infection, whereas WT-->IFNAR(-/-) chimeras succumb. This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV.

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

BACKGROUND: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD. OBJECTIVE: We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD. DESIGN: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10(-8)) were tested for association with CAD in 31,400 cases and 92,927 controls. RESULTS: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 Ã- 10(-9)), SLC17A3 (1.0 Ã- 10(-8)), GTPB10 (1.7 Ã- 10(-8)), CUBN (7.5 Ã- 10(-10)), HNF1A (1.2 Ã- 10(-12)), and FUT2 (6.6 Ã- 10(-9)), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-μmol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 Ã- 10(-36)). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49). CONCLUSIONS: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD.