Functional Diversity of the Schistosoma mansoni Tyrosine Kinases

Schistosoma mansoni, one of the causative agents of schistosomiasis, has a complex life cycle infecting over 200 million people worldwide. Such a successful and prolific parasite life cycle has been shown to be dependent on the adaptive interaction between the parasite and hosts. Tyrosine kinases (TKs) play a key role in signaling pathways as demonstrated by a large body of experimental work in eukaryotes. Furthermore, comparative genomics have allowed the identification of TK homologs and provided insights into the functional role of TKs in several biological systems. Finally, TK structural biology has provided a rational basis for obtaining selective inhibitors directed to the treatment of human diseases. This paper covers the important aspects of the phospho-tyrosine signaling network in S. mansoni, Caenorhabditis elegans, and humans, the main process of functional diversification of TKs, that is, protein-domain shuffling, and also discusses TKs as targets for the development of new anti-schistosome drugs

Vitamin D3 as adjuvant in the treatment of type 2 diabetes mellitus: modulation of genomic and biochemical instability

Erratum in - Corrigendum: Vitamin D3 as adjuvant in the treatment of type 2 diabetes mellitus: modulation of genomic and biochemical instability. Fagundes GE, Macan TP, Rohr P, Damiani AP, Da Rocha FR, Pereira M, Longaretti LM, Vilela TC, Ceretta LB, Mendes C, Silveira PCL, Teixeira JPF, de Andrade VM. Mutagenesis. 2019 May 29;34(2):215. doi: 10.1093/mutage/gez006.Type 2 diabetes mellitus has undergone a worldwide growth in incidence in the world and has now acquired epidemic status. There is a strong link between type 2 diabetes and vitamin D deficiency. Because vitamin D has beneficial effects on glucose homeostasis, the aim of this study was to evaluate the influence of vitamin D3 supplementation on the modulation of glycaemic control and other metabolic effects, as well as modulation of genomic instability in patients with type 2 diabetes. We evaluated 75 patients with type 2 diabetes, registered in the Integrated Clinics of the University of Southern Santa Catarina. Participants received 4000 IU of vitamin D3 (25(OH)D) supplementation daily for 8 weeks. Blood samples were collected at the beginning and at the end of the supplementation, and 4 weeks after the end of supplementation. The glycidic and lipid profiles [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein and triglycerides], oxidative stress, DNA damage and 25(OH)D levels were evaluated. Vitamin D3 supplementation for 8 weeks showed enough to significantly increase blood levels of 25(OH)D. A significant difference in lipid profile was observed only in non-HDL cholesterol. Significant changes were observed in glucose homeostasis (fasting glucose and serum insulin) and, in addition, a reduction in the parameters of oxidative stress and DNA damage. There was a significant reduction in the values of 25(OH)D 4 weeks after the end of the supplementation, but levels still remained above baseline. Use of vitamin D supplementation can be an ally in the health modulation of patients with type 2 diabetes mellitusThis work was supported by grants from Conselho Nacional de Pesquisa e Desenvolvimento (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) and Programa de Pós-Graduação em Ciências da Saúde/ Universidade do Extremo Sul Catarinense.info:eu-repo/semantics/publishedVersio

Assembléias de Formicidae da serapilheira como bioindicadores da conservação de remanescentes de Mata Atlântica no extremo sul do Estado da Bahia

In the extreme south of Bahia State, the Atlantic rainforest has been strongly affected by anthropogenic actions for a long time. Ants are seen as good biological indicators because of their abundance and sensitivity to changes of environmental conditions, thus allowing the evaluation of environmental impacts. The purpose of this study was to evaluate the environmental quality in four Atlantic Forest remnants through the study of Formicidae assemblages. Four reserves sampled during the experiment were: the school of agriculture EMARC (CEPLAC) in Teixeira de Freitas; Vista Alegre Farm in Alcobaça; FIBRASA Farm in Itamarajú; and Riacho das Pedras Farm in Prado. In each area, 50 units of one square meter of litter were sampled at intervals of 50m and 100m of the border using “Winkler” traps. The most frequent ants in EMARC reserve were: Wasmannia auropunctata (60%) and Solenopsis sp.1 (58%); in FIBRASA farm: W. auropunctata (64%) and Solenopsis sp.1 (46%); in Riacho das Pedras farm: Pyramica eggersi (80%) and Solenopsis sp.1 (64%); in Vista Alegre farm: Pheidole sp.1 (34%), Hypoponera sp.8 (32%) and Pyramica denticulata (24%). The highest value of diversity index (Shannon-Weaver) was observed in FIBRASA farm (3.41), followed by Riacho das Pedras farm (3.31), Vista Alegre farm (3.00), and EMARC reserve (2.33). The largest number of species was observed in FIBRASA and in Riacho das Pedras farms (55 species), followed by Vista Alegre (33) and EMARC (22). The area with the highest estimated diversity is the FIBRASA farm, while the reserve of EMARC had the lowest estimate. There were correlations between the level of human impact, the species found and generic richness, as well as with other ecological variables. All the studied areas had a high occurrence of species typical of degraded lands, showing that urgent conservation measures are needed to the increasingly more rare remnants of forest in the extreme South Bahia State.No extremo sul do Estado da Bahia, a Mata Atlântica tem sido fortemente afetada pelas atividades humanas. As formigas são vistas como indicadores biológicos confiáveis por serem sensíveis às mudanças das condições do ambiente, permitindo uma avaliação do impacto ambiental. O objetivo do presente estudo foi de avaliar a qualidade ambiental em quatro remanescentes de Mata Atlântica através de uma análise da estrutura das assembléias de Formicidae. As quatro reservas estudadas, todas situadas naquela região, foram: reserva da escola agrícola EMARC, Município de Teixeira de Freitas; Fazenda Vista Alegre, Alcobaça; Fazenda FIBRASA, Itamarajú e Fazenda Riacho das Pedras, Prado. Em cada área, foram amostrados 50 pontos de um metro quadrado de serapilheira, com o auxílio de armadilhas de tipo “Winkler”. O maior número de espécies observado foi na Fazenda FIBRASA (55 espécies) e na Fazenda Riacho das Pedras, seguidas pela Fazenda Vista Alegre (33) e a reserva da EMARC (22). A área de maior diversidade de espécies esperada (estimador Chao2) é também a da Fazenda FIBRASA, enquanto a área da EMARC foi também a de menor diversidade esperada. As espécies mais freqüentes na reserva da EMARC foram Wasmannia auropunctata (60% das amostras) e Solenopsis sp1 (58%); na Fazenda FIBRASA, W. auropunctata (64%) e Solenopsis sp.1 (46%); na Fazenda Riacho das Pedras, Pyramica eggersi (80%) e Solenopsis sp.1 (64%); na Fazenda Vista Alegre, Pheidole sp.1 (34%), Hypoponera sp.8 (32%) e Pyramica denticulata (24%). Existem correlações entre o nível de impacto humano e as riquezas específica e genérica, assim como com outras variáveis ecológicas, nas áreas estudadas. Todas essas apresentaram uma ocorrência elevada de espécies típicas de ambientes degradados, como é o caso de W. auropunctata, mostrando a urgência que existe numa política de conservação mais efetiva dos cada vez mais raros remanescentes do extremo sul do Estado da Bahia

Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer

Background: Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and -4 are highly expressed, but PAR-3 shows low expression and unclear functions. Methods: Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGF beta monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. Results: We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and -4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGF beta in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. Conclusions: Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells.Associacao Beneficente de Coleta de Sangue (Colsan)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Univ Fed Sao Paulo, Dept Gynecol, BR-04024002 Sao Paulo, SP, BrazilCOLSAN, Charitable Assoc Blood Collect, BR-04080006 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biophys, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biochem, BR-04024002 Sao Paulo, SP, BrazilAntonio Prudente Fdn, AC Camargo Canc Ctr, AC Camargo Hosp Biobank, Dept Pathol, BR-01509010 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Cellular Gynecol Lab, Dept Gynecol, Rua Napoleao Barros 608, BR-04024002 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Gynecol, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biophys, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biochem, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Cellular Gynecol Lab, Dept Gynecol, Rua Napoleao Barros 608, BR-04024002 Sao Paulo, BrazilFAPESP: 2012/19780-3FAPESP: 2012/19851-8FAPESP: 2009/53766-5Web of Scienc

Genomics and epidemiology for gastric adenocarcinomas (GE4GAC): a Brazilian initiative to study gastric cancer

Abstract Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings