The oligomeric protein interference assay method for validation of antimalarial targets

The appearance of multi-drug resistant strains of malaria poses a major challenge to human health and validated drug targets are urgently required. To define a protein's function in vivo and thereby validate it as a drug target, highly specific tools are required that modify protein function with minimal cross-reactivity. While modern genetic approaches often offer the desired level of target specificity, applying these techniques is frequently challenging-particularly in the most dangerous malaria parasite, Plasmodium falciparum. Our hypothesis is that such challenges can be addressed by incorporating mutant proteins within oligomeric protein complexes of the target organism in vivo. The present study provides data to support our hypothesis by demonstrating that recombinant expression of mutant proteins within P. falciparum leverages the native protein oligomeric state to influence protein function in vivo, thereby providing a rapid validation of potential drug targets. Our data show that interference with aspartate metabolism in vivo leads to a significant hindrance in parasite survival and strongly suggest that enzymes integral to aspartate metabolism are promising targets for the discovery of novel antimalarials

A Linguística Textual na página do Facebook Vote LGBT

This research aims to identify the characteristics of textuality present in election campaign publications published on the Social Network Online Facebook, published by the page Vote Lesbians, Gays, Bisexuals e Transgender (Vote LGBT). As for the methodological procedures, the research has an exploratory character with a qualitative approach. The investigation collected data on publications on the page of the social organization Vote LGBT that took place between September 27 and November 15, 2020, during the period of municipal elections. The results presented the analysis of five photographs published by the Vote LGBT page, based on the characteristics of textuality (intentionality, acceptability, situationality, informativeness and intertextuality) that allowed visualizing the intention of the producer and the elements that composed the publications. As conclusions, the research presented that the publications seek to inform the receiver in order to make known, publicize, disseminate, invite the debate on the guidelines that surround the community and convince the voter to vote for the Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual, + (used to include other gender identities and sexual orientations that do not fit the cis-heteronormative pattern).Esta investigación tiene como objetivo identificar las características de la textualidad presente en las publicaciones de campaña electoral publicadas en la Red Social en Línea Facebook, publicadas por la página Vota Lesbianas, Gays, Bisexuales y Transgénero (Vota LGBT). En cuanto a los procedimientos metodológicos, la investigación tiene un carácter exploratorio con un enfoque cualitativo. La investigación recopiló datos sobre publicaciones en la página de la organización social Vota LGBT que se realizaron entre el 27 de septiembre y el 15 de noviembre de 2020, durante el periodo de elecciones municipales. Los resultados presentaron el análisis de cinco fotografías publicadas por la página Vota LGBT, a partir de las características de textualidad (intencionalidad, aceptabilidad, situacionalidad, informatividad e intertextualidad) que permitieron visualizar la intención del productor y los elementos que componían las publicaciones. Como conclusiones, la investigación presentó que las publicaciones buscan informar al receptor con el fin de dar a conocer, publicitar, difundir, invitar al debate sobre los lineamientos que envuelven a la comunidad y convencer al elector de votar por la comunidad Lesbiana, Gay, Bisexual, Transgénero, Queer, Intersex, Asexual, + (usado para incluir otras identidades de género y orientaciones sexuales que no encajan en el patrón cis-heteronormativo).Esta pesquisa tem como objetivo identificar as características de textualidade presentes nas publicações de campanhas eleitorais veiculadas na Rede Social Online Facebook, publicadas pela página Vote Lésbicas, Gays, Bissexuais e Transgênero (Vote LGBT). Quanto aos procedimentos metodológicos, a pesquisa possui caráter exploratório com abordagem qualitativa. A investigação coletou dados sobre as publicações na página da organização social Vote LGBT que ocorreram entre os dias 27 de setembro e 15 de novembro de 2020, durante o período das eleições municipais. Os resultados apresentaram as análises de cinco fotografias publicadas pela página Vote LGBT, a partir das características de textualidade (intencionalidade, aceitabilidade, situacionalidade, informatividade e intertextualidade) que permitiram visualizar a intenção do produtor e os elementos que compuseram as publicações. Como conclusões a pesquisa apresentou que as publicações buscam informar ao receptor no sentido de fazer conhecer, publicizar, disseminar, convidar ao debate sobre as pautas que circundam a comunidade e convencer o eleitor a votar nas candidaturas Lésbicas, Gays, Bissexuais, Transgênero, Queer, Intersexo, Assexual, + (usado para incluir outras identidades de gênero e orientações sexuais que não se encaixam no padrão cis-heteronormativo)

Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum

The de novo pyrimidine-biosynthesis pathway of Plasmodium falciparum is a promising target for antimalarial drug discovery. The parasite requires a supply of purines and pyrimidines for growth and proliferation and is unable to take up pyrimidines from the host. Direct (or indirect) inhibition of de novo pyrimidine biosynthesis via dihydroorotate dehydrogenase (PfDHODH), the fourth enzyme of the pathway, has already been shown to be lethal to the parasite. In the second step of the plasmodial pyrimidine-synthesis pathway, aspartate and carbamoyl phosphate are condensed to N-carbamoyl-l-aspartate and inorganic phosphate by aspartate transcarbamoylase (PfATC). In this paper, the 2.5 angstrom resolution crystal structure of PfATC is reported. The space group of the PfATC crystals was determined to be monoclinic P2(1), with unit-cell parameters a = 87.0, b = 103.8, c = 87.1 angstrom, alpha = 90.0, beta = 117.7, gamma = 90.0 degrees. The presented PfATC model shares a high degree of homology with the catalytic domain of Escherichia coli ATC. There is as yet no evidence of the existence of a regulatory domain in PfATC. Similarly to E. coli ATC, PfATC was modelled as a homotrimer in which each of the three active sites is formed at the oligomeric interface. Each active site comprises residues from two adjacent subunits in the trimer with a high degree of evolutional conservation. Here, the activity loss owing to mutagenesis of the key active-site residues is also described

Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases

Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, is a mitochondrial enzyme which catalyzes the transfer of sulfur in several molecular pathways. After its initial identification as a cyanide detoxification enzyme, it was found that its functions also include sulfur metabolism, modification of iron-sulfur clusters and the reduction of antioxidants glutathione and thioredoxin. TST deficiency was shown to be strongly related to the pathophysiology of metabolic diseases including diabetes and obesity. This review summarizes research related to the enzymatic properties and functions of TST, to then explore the association between the effects of TST on mitochondria and development of diseases such as diabetes and obesity

Notes on vocalizations of Brazilian amphibians IV: advertisement calls of 20 Atlantic Forest frog species

Bioacoustics is a powerful tool used for anuran species diagnoses, given that advertisement calls are signals related to specific recognition and mate attraction. Thus, call descriptions can support species taxonomy. In spite of that, call descriptions are lacking for many species, delaying advances in biodiversity research. Here, we describe the advertisement calls of 20 anuran species from the Brazilian Atlantic Forest. We accessed 50 digital recordings deposited in the Fonoteca Neotropical Jacques Vielliard. Acoustic analyses were carried out in the software Raven pro 1.5. We provide a general comparison of call structure among species inside taxonomic groups and genera. The vocalizations described here belong to poorly known species, which are representatives of six families: Brachycephalidae, Bufonidae, Ceratophryidae, Cycloramphidae, Hylidae, and Phyllomedusidae. Despite this, still there are 163 species of anurans from Atlantic Forest with calls not formally described. Our work represents an important step in providing data for a taxonomic perspective and improving the knowledge of the Atlantic Forest anuran diversity7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAIS - FAPEMIGFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP300896/2016-6; 438675/2016-9; 307091/2015-5; 302518/2013-4sem informaçãoAPQ-01796-15; RDP-00004-172013/21519-4; 2016/25358-3; 2013/50741-7; 2014/50342-8Grupo O Boticário de Proteção à Natureza: Proc. #085420101/A0001_2012. Instituto Mater Natura de Estudos Ambientais and Instituto Neotropical de Pesquisa e Conservaçã

Molecular detection of Mycobacterium bovis in cattle herds of the state of Pernambuco, Brazil

Submitted by Adagilson Silva ([email protected]) on 2017-09-01T12:35:29Z No. of bitstreams: 1 26897524 2016 cez-mol.oa.pdf: 466479 bytes, checksum: 72f2a61e564e72399e0dad54064bf1d4 (MD5)Approved for entry into archive by Adagilson Silva ([email protected]) on 2017-09-01T12:42:28Z (GMT) No. of bitstreams: 1 26897524 2016 cez-mol.oa.pdf: 466479 bytes, checksum: 72f2a61e564e72399e0dad54064bf1d4 (MD5)Made available in DSpace on 2017-09-01T12:42:28Z (GMT). No. of bitstreams: 1 26897524 2016 cez-mol.oa.pdf: 466479 bytes, checksum: 72f2a61e564e72399e0dad54064bf1d4 (MD5) Previous issue date: 2016-02-20Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, BrasilThe present study aimed to direct detect Mycobacterium bovis in milk (n = 401) and blood (n = 401) samples collected from 401 dairy cows of 20 properties located in the state of Pernambuco, Brazil, by real-time quantitative PCR (qPCR) targeting the region of difference 4 (RD4). Risk factors possibly associated with bovine tuberculosis (BTB) were also evaluated

Association Between miR-148a and DNA Methylation Profile in Individuals Exposed to Lead (Pb)

2018/24643-1 (São Paulo Research Foundation, FAPESP, Brazil), by the National Council for Scientific and Technological Development (Brazil) and by grant UID-BIM-00009-2020 (Foundation for Science and Technology, FCT, Portugal).Experimental and epidemiologic studies have shown that lead (Pb) is able to induce epigenetic modifications, such as changes in DNA methylation profiles, in chromatin remodeling, as well as the expression of non-coding RNAs (ncRNAs). However, very little is known about the interactions between microRNAs (miRNAs) expression and DNA methylation status in individuals exposed to the metal. The aim of the present study was to investigate the impact of hsa-miR-148a expression on DNA methylation status, in 85 workers exposed to Pb. Blood and plasma lead levels (BLL and PLL, respectively) were determined by ICP-MS; expression of the miRNA-148a was quantified by RT-qPCR (TaqMan assay) and assessment of the global DNA methylation profile (by measurement of 5-methylcytosine; % 5-mC) was performed by ELISA. An inverse association was seen between miR-148a and % 5-mC DNA, as a function of BLL and PLL (β = −3.7; p = 0.071 and β = −4.1; p = 0.049, respectively) adjusted for age, BMI, smoking, and alcohol consumption. Taken together, our study provides further evidence concerning the interactions between DNA methylation profile and miR-148a, in individuals exposed to Pb.publishersversionpublishe

Um estudo da prevalência e da caracterização da mortalidade em crianças e adolescentes por leucemia no Brasil

This article aims to characterize the prevalence of mortality from leukemia in children and adolescents in Brazil. It is an epidemiological study, of the ecological type, whose area analysis units were the regions of Brazil. Data from this study were of the secondary type, obtained through the Department of Informatics of the Unified Health System (DATASUS), from the Mortality Information System (SIM). For the investigation, children and adolescents, aged between zero and nineteen years old, with deaths in the period from 2017 to 2021, whose leukemia was the underlying cause mentioned in the Death Certificate by means of codes according to the tenth International Classification, were chosen. of Diseases. It is concluded that leukemia is the main cause of death in children and adolescents and the subtype Acute Lymphoid Leukemia represented by the ICD-91 is the most common among the cases of deaths notified in the Brazilian regions.  Este artigo tem por objetivo caracterizar a prevalência da mortalidade por leucemias em crianças e adolescentes no Brasil. Trata-se de um estudo epidemiológico, do tipo ecológico, cujas unidades de análise de área foram as regiões do Brasil. Os dados desse estudo foram do tipo secundário, obtidos através do Departamento de Informática do Sistema Único de Saúde (DATASUS), provenientes do Sistema de Informação sobre Mortalidade (SIM). Para investigação elegeu-se, crianças e adolescentes, com faixa etária entre zero e dezenove anos, com óbitos no período de 2017 a 2021, cujo, a leucemia foi a causa básica mencionada na Declaração de Óbito por meios de códigos conforme a décima Classificação Internacional de Doenças. Conclui-se que a leucemia é a principal causa de morte em crianças e adolescentes e o subtipo Leucemia Linfoide Aguda representada pelo CID-91 é o mais comum entre os casos de óbitos notificados nas regiões brasileiras