Investigação de polimorfismos nos genes XRCC1, MTHFR e EGFR como possíveis marcadores de suscetibilidade ao câncer, na população de Belém-PA

Cancer is defined as a multifactorial disease resulting from complex interactions between extrinsic and intrinsic factors. Among the main intrinsic factors are the genetic and/or epigenetic alterations in genes involved with the carcinogenesis process. The identification and characterization of these genes may provide a better understanding of the molecular basis of cancer. Considering the importance of alterations in XRCC1, MRHFR and EGFR genes in various pro-carcinogenic pathways, it is extremely important to investigate the effects of functional polymorphisms in these genes and their molecular consequences in cancer susceptibility.The objective of this study was to identify possible associations between single nucleotide polymorphisms (SNPs) Arg194Trp (XRCC1) e Ala222Val (MTHFR) e Arg521Lys (EGFR) with the development of gastric and breast cancers in the population of Belém-PA, in a case-control study. Furthermore, the control of genomic ancestry was held to avoid spurious results arising from population substructuring in the groups investigated. Molecular analysis of SNPs was carried out by TaqMan. Statistical analyses were performed using the program SPSS v.20 and to estimate the interethnic admixture we used the program STRUCTURE v.2.2. Regarding polymorphisms Arg194Trp, Ala222Val we did not observe any significant association with susceptibility to breast and gastric tumors (P > 0.05).For the polymorphism Arg521Lys, in a first moment (univariate analysis), a significant effect for susceptibility to cancers investigated was found (P = 0.037). However, after genomic control for African and European ancestries, this result has proved to be spurious (P = 0.064). Regarding ancestries, our results showed a strong association of African ancestry with susceptibility to gastric and breast cancers (P = 0.010, OR = 76,723; 95% CI = 2.805 - 2098.230) whereas for European contribution a protective effect was found (P = 0.024, OR = 0071, 95% CI = 0.007-0.703). In conclusion, our study presented the evidence that the African and European genomic ancestries are important factors related to susceptibility to gastric and breast cancers. Regarding Arg521Ly polymorphism, further studies are necessary to confirm whether the association is indeed spurious.Câncer é definido como uma doença multifatorial, resultante de interações complexas entre fatores extrínsecos e intrínsecos. Dentre os principais fatores intrínsecos estão as alterações genéticas e/ou epigenéticas, em genes envolvidos no processo carcinogênico. A identificação e caracterização destes genes podem proporcionar uma melhor compreensão das bases moleculares da doença. Dada a importância de alterações nos genes XRCC1, MRHFR e EGFR em diversas vias pro-carcinogênicas, é de fundamental importância investigar os efeitos funcionais de polimorfismos moleculares nesses genes e suas consequências na suscetibilidade ao câncer. Assim, o objetivo deste estudo foi identificar possíveis associações entre os polimorfismos de nucleotídeo único (SNPs) Arg194Trp (XRCC1) e Ala222Val (MTHFR) e Arg521Lys (EGFR) com o desenvolvimento do câncer gástrico e mamário, na população de Belém-PA, em um estudo caso-controle. Além disso, o controle genômico da ancestralidade foi realizado pra evitar resultados e/ou interpretações espúrias decorrentes da subestruturação populacional entre os grupos investigados. A análise molecular dos SNPs foi realizada por TaqMan. As análises estatísticas foram realizadas através do programa SPSS v.20 e as relativas à subestruturação populacional pelo programa STRUCTURE v 2.2. Em relação aos polimorfismos Arg194Trp, Ala222Val não foi observada nenhuma associação significativa com a susceptibilidade aos tumores gástrico e mamário (P > 0,05). Para ao polimorfismo Arg521Lys, em um primeiro momento (análise univariada), um efeito significativo para a suscetibilidade aos cânceres investigados, foi encontrado (P = 0,037). Contudo, após o controle genômico pelas ancestralidades africana e europeia, esse resultado se revelou espúrio (P = 0,064). Em relação às ancestralidades, nossos resultados evidenciaram uma forte associação da ancestralidade africana com a suscetibilidade aos cânceres gástrico e mamário (P = 0,010; OR = 76,723; IC 95% = 2,805 – 2098,230) em quanto que para indivíduos com uma maior contribuição europeia, um efeito de proteção foi encontrado (P = 0,024; OR = 0,071; IC 95% = 0,007 – 0,703). Em conclusão, os resultados deste estudo apresentam evidencias de que as ancestralidades genômicas africana e europeia são importantes fatores relacionados à susceptibilidade as neoplasias gástrica e mamaria. Em relação ao polimorfismo Arg521Lys, estudos adicionais serão necessários para confirmar se a associação com a suscetibilidade ao câncer é realmente espúria

MicroRNA 320a and Membrane Antigens as Tools to Evaluate the Pathophysiology of Platelets Stored in Blood Banks

Our research group, through the analysis of miRNomes in platelet concentrates (PCs) stored in blood banks, identified and validated the miR-127 and miR-320a miRNAs as biomarkers of platelet storage lesions (PSLs) in PCs. In order to validate the miRNAs 127 and 320a methodologically, as PSL biomarkers in a large number of PC bags, we also evaluated important immunological markers involved in the platelet activation/aggregation process—the CD62P receptor (P-selectin), the surface glycoproteins (GP) IIb/IIIa, and the purinergic P2Y12 receptor—via flow cytometry. The miRNAs miR-127 and miR-320a were quantified by real-time quantitative PCR (RT-qPCR). To carry out this study, 500 collection tubes were used at the upper edge of the PC bags containing platelets. Each tube was divided into seven equal parts (totaling 3500 samples) for platelet analysis from 7 different storage days, where the 1st day represents the high-quality control, and the 7th day corresponds to the low-quality control of the platelets. After analyzing all parameters during storage days, it was concluded that the relative quantification of miR-320a below 0.50 and the CD62P receptor below 27.92% are reliable indicators of the absence of storage lesions in blood banks. We believe that the values found in the expression of the CD62P receptor legitimize the use of the miR-320a and miR-127 miRNAs to build a kit capable of accurately measuring whether the stored platelets are suitable for transfusion

Detection of Sepsis in Platelets Using MicroRNAs and Membrane Antigens

The present study proposes to legitimize in sepsis a characteristic found in platelets that suffer storage lesions in blood banks, which is the increased expression of miRNA miR-320a in relation to miR-127. Under physiologically normal conditions, an inverse relationship is observed. The aim of this study was to verify whether the analysis of miR-320a and miR-127 expression in platelets could detect a decrease in their viability and function due to the presence of pathogens in the blood of patients hospitalized in the Intensive Care Unit. We also investigated the expression of membrane antigens sensitive to platelet activation. Of the 200 patients analyzed, only those who developed sepsis (140) were found to have a higher relative quantity of miR-320a than that of miR-127. This characteristic and the increased expression of membrane antigens P2Y12, CD62P, CD41, and CD61 showed a significant association (p < 0.01) with all types of sepsis evaluated in this study. Additionally, 40% of patients hospitalized for sepsis had negative results for the first cultures. We conclude that analysis of miR-127 and miR-320a expression combined with membrane antigens evaluation, in association with the available clinical and diagnostic parameters, are important tools to detect the onset of sepsis

Prevalence, incidence and residual risk of transfusion-transmitted HBV infection before and after the implementation of HBV-NAT in northern Brazil.

BACKGROUND:Nucleic acid testing (NAT) for virus detection during blood screening has helped to prevent transfusion-transmitted infections worldwide. In northern Brazil, NAT was implemented in 2012 for HIV and HCV and more recently, in January 2015, the screening for HBV was included and currently used concomitant with serological tests (HBsAg and anti-HBc). This study aims to evaluate the prevalence and the incidence of HBV infection among voluntary blood donors at ten regional blood centers of HEMOPA Foundation in Pará state and to compare the residual risk of transfusion-transmitted HBV infection before and after the Brazilian HBV-NAT implementation. METHODS:The prevalence (restricted to first time donors- FT) and seroconversion rate (restricted to repeat donors- RP) of HBV were calculated based on rates of confirmed positive samples. Residual risk was based on the incidence and window period (WP) model described by Schreiber and coauthors. Logistic and Poisson regression were used in the statistical analysis by SPSS v20.0. A p value <0.05 was considered statistically significant. RESULTS:HBV prevalence in the periods before and after the implementation of HBV-NAT were 247 and 251 per 100,000 donations, respectively. Seroconversion rates were 114 and 122 per 100,000 donations in the two periods, respectively. The residual risk (RR) for HBV decreased significantly in the posterior period to the HBV-NAT implementation, when compared to RR before implementation, with a reduction of 1:144,92 to 1:294,11 donations (p <0,001). CONCLUSIONS:The RR to HBV decreased after the implementation of HBV-NAT, increasing significantly the transfusional security in the North region of Brazil at HEMOPA Foundation

Estudos agrários: a complexidade do rural contemporâneo

Esta obra reúne trabalhos de pesquisadores de três universidades públicas brasileiras apresentados durante o I Colóquio de Pesquisas do Núcleo de Estudos Agrários da Unesp de Rio Claro, realizado em outubro de 2010. Organizada por Darlene Aparecida de Oliveira Ferreira, Enéas Rente Ferreira e Adriano Corrêa Maia, pretende compreender a realidade agrária brasileira contemporânea a partir de suas principais características, considerando o passado e o presente. A obra mostra que a diversidade espacial é umas das marcas importantes do sistema, com o mundo rural organizado distintamente em contextos regionais e atrelando culturas a áreas específicas. Por isso, os trabalhos tratam também de contextos espaciais historicamente construídos, dos quais emergem novos atores sociais ou se consolidam os detentores de estruturas passadas. As pesquisas identificam principalmente as características e as tendências da geografia agrária no Brasil do início do século XXI, os processos, como produção e migração, os usos modernos do espaço agrícola (como o turismo rural) e o papel atual das pequenas propriedades na agricultura brasileira

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved