Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

AVALIAÇÃO DA TRANSLOCAÇÃO T(14;18) MBR EM INDIVÍDUOS EXPOSTOS A BAIXAS DOSES DE RADIAÇÃO DE 137CsCl EM GOIÂNIA, GOIÁS, BRASIL

Made available in DSpace on 2016-08-10T10:38:27Z (GMT). No. of bitstreams: 1 Hugo Freire Nunes.pdf: 9223555 bytes, checksum: 727e689aec4609cbe403ed62b05a1443 (MD5) Previous issue date: 2011-02-11Healthy radio-exposed individuals, who received low levels of Cesium-137 radiation, during the accident that happened in Goiania, in 1987 and their familiars were tested for the detection of t(14;18) rearranged B cells in peripheral blood, using a high sensitive real-time quantitative PCR method. Also were tested a control group comprised of healthy non exposed age matched men. The chromosomal translocation t(14;18)(q32;q21) is characteristic of Follicular Lymphoma and it is a frequent abnormality in other types of non-Hodgkin lymphoma. This translocation leads to constitutive activation of the BCL2 oncogene by the enhancers of the immunoglobulin heavy chain loco. T(14;18) translocation constitute the genetic hallmark and early initiating event of Follicular Lymphoma. In healthy individuals, the same translocation may also be found in a small fraction of peripheral blood lymphocytes and positive cells might serve as an indicator for environmental exposure to carcinogens and possibly correlate with the cumulative risk of developing t(14;18)-positive non-Hodgkin lymphoma. Eight healthy radio-exposed, five relatives including three children, and four not exposed healthy men were tested for the detection of this translocation. Only one unexposed individual from the control group was positive for the chromosomal translocation, healthy radio-exposed individuals presented lower levels of cells bearing the BCL-2/JH rearrangement when compared to the levels of the patients with Follicular Lymphoma before treatment, however, test more cells would be required to confirm the total absence of circulating cells bearing the rearrangement BCL2/JH.Indivíduos radioexpostos saudáveis que receberam acidentalmente baixas doses de radiação ionizante de Césio -137 no acidente ocorrido em Goiânia em 1987 e familiares, foram testados neste trabalho para a presença de células B em sangue periférico apresentando a translocação t(14;18) MBR. Da mesma maneira foram testados voluntários sem histórico de exposição à radiação ionizante, componentes de um grupo controle. Foi utilizado um método de PCR quantitativo em tempo real muito sensível. A translocação cromossômica t(14;18)(q31; q21) é característica de Linfomas Foliculares e é uma anormalidade freqüente em outros Linfomas não Hodgkin. Esta translocação acarreta em uma ativação constitutiva do oncogene BCL2 por uma região do gene de imunoglobulina de cadeia pesada. A ocorrência da translocação é considerada um evento marcante e inicial para o desenvolvimento de Linfoma Folicular. Em indivíduos saudáveis a mesma translocação pode ser encontrada em pequenas frações dentre os linfócitos de sangue periférico. As células translocadas são importantes referências para exposição ambiental à carcinógenos e possivelmente podem ser correlacionadas ao risco acumulativo de desenvolvimento de Linfoma não Hodgkin t(14;18) positivo. Oito radio expostos, cinco familiares e quatro voluntários não expostos foram testados para a detecção desta translocação cromossômica. Não foram encontras células t(14;18) MBR nos radioexpostos e familiares. Apenas um indivíduo não exposto pertencente ao grupo controle apresentou o rearranjo BCL2/JH, assim foi possível determinar com o estudo que os radioexpostos e familiares não apresentam freqüência da célula B t(14;18) similares das encontradas em média no sangue periférico de indivíduos com Linfoma Folicular antes do tratamento segundo outros estudos, entretanto apenas testando maiores quantidades de DNA de cada indivíduo será possível determinar abstenção total de células portando o rearranjo BCL2/J

Influence of different concentrations of plasticizer diethyl phthalate (DEP) on toxicity of Lactuca sativa seeds, Artemia salina and Zebrafish

Like other phthalates, diethyl phthalate (DEP) is considered as a contaminant of emerging concern (CEC) due to its ease in migrating from a package to water and food, and hence contaminate consumers, being metabolized and excreted in the urine. Its presence has a negative impact on aquatic ecosystems, especially with respect to disruption of the endocrine system and to reproductive disorders in humans. It mainly enters water bodies via sewage effluents from effluent treatment plants, due to its incomplete or inefficient removal. The objective of this work was to evaluate the toxicity of DEP at different trophic levels and to analyze data on the incidence and concentration of DEP according to its solubility. The concentrations ranged from 12.5 mg L−1 to 500 mg L−1 considering the response for toxicity at each trophic level and to determine the lethal concentration in 50% of the following organisms (LC50) (in mg L−1): Lactuca sativa seeds, Artemia salina Leach nauplii and Zebrafish embryo larval stage (Danio rerio), being 41,057.58 after 120 h; 401.77 after 48 h; and 470 after 96 h of exposure, respectively. As expected, higher organisms were more affected even at low concentrations, which shows the anthropological contribution of CECs to water bodies