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BACKGROUND: There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term. METHODS: Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation >14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database. RESULTS: Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p

Made available in DSpace on 2021-06-25T10:49:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A crop rotation system can reduce phytopathogen inoculum, and consequently reduce the incidence and severity of disease. Bean bacterial wilt is an important disease and several crops can act as inoculum sources for Curtobacterium flaccumfaciens pv. flaccumfaciens (Cff). The aim was to evaluate the influence of crop rotation systems on 10 common bean cultivars against bacterial wilt. Experiments were located in two different areas in Brazil (2012), cultivated under a no-tillage system and with a history of the disease. The evaluated rotation systems were black oat, wheat and fallow followed by common bean. After harvest, 10 dry bean cultivars were sown, together with a fallow area. Disease incidence and severity were assessed at 45, 60 and 80 days after sowing. Also evaluated were four agronomical parameters: pod numbers, grain numbers, total weight of grains per plant and weight of 100 grains. Epiphytic and endophytic colonization by Cff was evaluated in black oat and wheat, and in crop debris. The rotation systems significantly influenced the incidence and severity of bacterial wilt in common bean cultivars in both areas and negatively affected the four agronomic parameters. The cultivars BRS Campeiro, BRS Estilo, IPR Tuiuiú, IPR Tangará and IPR Campos Gerais presented low severity and incidence of the disease and higher productivity. Cff strains were recovered from black oat, wheat and crop debris. Our results reinforce the importance of planting non-Cff host crops in rotation systems with common bean, as well as planting cultivars with a level of resistance to bacterial wilt. Departamento de Proteção Vegetal Faculdade de Ciências Agronômicas (FCA) Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Avenida Universitária, 3780 Departamento de Proteção Vegetal Faculdade de Ciências Agronômicas (FCA) Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Avenida Universitária, 3780

Background Human immunodeficiency virus (HIV-1) infection is characterized by high viral replication and a decrease in CD4+ T cells (CD4+TC), resulting in AIDS, which can lead to death. In elite controllers and viremia controllers, viral replication is naturally controlled, with maintenance of CD4+TC levels without the use of antiretroviral therapy (ART). Methods The aim of the present study was to describe virological and immunological risk factors among HIV-1-infected individuals according to characteristics of progression to AIDS. The sample included 30 treatment-naive patients classified into three groups based on infection duration (> 6 years), CD4+TC count and viral load: (i) 2 elite controllers (ECs), (ii) 7 viremia controllers (VCs) and (iii) 21 nonviremia controllers (NVCs). Nested PCR was employed to amplify the virus genome, which was later sequenced using the Ion PGM platform for subtyping and analysis of immune escape mutations. Results Viral samples were classified as HIV-1 subtypes B and F. Greater selection pressure on mutations was observed in the group of viremia controllers, with a higher frequency of immunological escape mutations in the genes investigated, including two new mutations in gag. The viral sequences of viremia controllers and nonviremia controllers did not differ significantly regarding the presence of immune escape mutations. Conclusion The results suggest that progression to AIDS is not dependent on a single variable but rather on a set of characteristics and pressures exerted by virus biology and interactions with immunogenetic host factors.

Type B coxsackieviruses (CVB) are enteroviruses responsible for a common infectious myocarditis and pancreatitis. DCs and regulatory T cells (Tregs) are key players in controlling virus replication and regulating the immune response and tissue damage, respectively. However, the mechanisms underlying cellular migration to target tissues remain unclear. In the present study, we found that CVB5 infection induced CCL17 production and controlled the migration of CCR4+ DCs and CCR4+ Tregs to the pancreatic lymph nodes (pLN). CVB5 infection of CCR4−/− mice reduced the migration of the CD8α+ DC subset and reduced DC activation and production of IFN-β and IL-12. Consequently, CCR4−/− mice presented decreased IFN-γ-producing CD4+ and CD8+ T cells, an increased viral load and more severe pancreatitis. In addition, CCR4−/− mice had impaired Treg accumulation in pLN as well as increased T lymphocyte activation. Adoptive transfer of CCR4+ Tregs but not CCR4− Tregs was able to regulate T lymphocyte activation upon CVB5 infection. The present data reveal a previously unknown role for CCR4 in coordinating immune cell migration to CVB-infected tissues and in controlling subsequent pancreatitis. These new insights may contribute to the design of future therapies for acute and chronic infection of non-polio enteroviruses.

Chagas disease remains a serious public health concern with unsatisfactory treatment outcomes due to strain-specific drug resistance and various side effects. To identify new therapeutic drugs agai...

Human activities have enhanced environmental contamination by heavy metals such as mercury. One of the possible approaches to reducing mercury toxicity is chelation, with several plant compounds demonstrating this effect, such as gallic acid. The objective of this study was to evaluate the antioxidant, metal chelating and cytoprotective activity of gallic acid against the action of Mercury Chloride (HgCl2). Iron II and III chelation as well as antioxidant activity assays were performed using the DPPH (1,1-Diphenyl-1-picrylhydrazyl) method. The interaction between the metal and the phenolic compound was identified by infrared spectroscopy. The Minimum Inhibitory Concentration (MIC) was determined by microdilution. From these results, and using a sub-inhibitory concentration (64 μg mL−1 for bacterial and fungal assay respectively) of the phenolic compound, the Minimum Bactericidal (MBC) and Minimum Fungicide Concentration (MFC) were evaluated. Allelopathy and cytoprotection assays were performed using eukaryotic and prokaryotic models, with a protection of the fungi being observed. When using a plant model with a sub-allelopathic concentration (32 μg mL−1), the results demonstrated the cytoprotective effect of gallic acid against HgCl2, increasing the extension of caulicles and radicles as well as their dry mass. This protection may be associated with the chelating effect of gallic acid. These results demonstrate that natural products such as gallic acid may be used for toxic metal chelation allowing plant development in polluted environments thus retrieving land usage for crops or forestry initiatives.

Made available in DSpace on 2022-04-28T17:20:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 ConfederacAo da Agricultura e Pecuaria do Brasil (CNA) Empresa Brasileira de Pesquisa Agropecuaria (Embrapa) Instituto Capixaba de Pesquisa Assistencia Tecnica e ExtensAo Rural (Incaper) Introduction: The occurrence of Microtriatoma borbai in the state of Espirito Santo, Brazil is reported by the first time. Methods: A triatomine specimen collected in a hybrid eucalyptus crop in the municipality of Aracruz, Espirito Santo state was found to be a male M. borbai. Results: This finding expands the geographical distribution of M. borbai from four to five Brazilian states. It is the first report of M. borbai occurrence inside a eucalyptus crop. Conclusions: The occurrence of M. borbai in the state of Espirito Santo broadens the geographical distribution of this species in southeastern Brazil. Inst Oswaldo Cruz, Lab Diptera, Rio De Janeiro, RJ, Brazil Inst Capixaba Pesquisa Assistencia Tecn & Extensa, Vitoria, ES, Brazil Suzano SA, Unidade Aracruz, Aracruz, ES, Brazil Univ Sao Paulo, Fac Saude Publ, Lab Entomol Saude Publ, Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, Lab Parasitol, Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, Lab Parasitol, Araraquara, SP, Brazil

Malaltia de Chagas; Trypanosoma cruzi; Variabilitat genètica Chagas disease; Trypanosoma cruzi; Genetic variability Enfermedad de Chagas; Trypanosoma cruzi; Variabilidad genética Background: Trypanosoma cruzi has a high rate of biological and genetic variability, and its population structure is divided into seven distinct genetic groups (TcI-TcVI and Tcbat). Due to immigration, Chagas disease (ChD), caused by T. cruzi, has become a serious global health problem including in Europe. Therefore, the aim of this study was to evaluate the existence of genetic variability within discrete typing unit (DTU) TcV of T. cruzi in Bolivian patients with chronic ChD residing in Barcelona, Spain. Methods: The DNA was extracted from the peripheral blood of 27 patients infected with T. cruzi DTU TcV and the fragments of the genetic material were amplificated through the low stringency single primer-polymerase chain reaction (LSSP-PCR). The data generated after amplification were submitted to bioinformatics analysis. Results: Of the 27 patients evaluated in the study, 8/27 (29.6%) were male and 19/27 (70.4%) female, 17/27 (62.9%) were previously classified with the indeterminate clinical form of Chagas disease and 10/27 (37.1%) with Chagas cardiomyopathy. The LSSP-PCR detected 432 band fragments from 80 to 1,500 bp. The unweighted pair-group method analysis and principal coordinated analysis data demonstrated the existence of three distinct genetic groups with moderate-high rates of intraspecific genetic variability/diversity that had shared parasite's alleles in patients with the indeterminate and cardiomyopathy forms of ChD. Conclusions: This study demonstrated the existence of a moderate to high rate of intra-DTU TcV variability in T. cruzi. Certain alleles of the parasite were associated with the absence of clinical manifestations in patients harboring the indeterminate form of ChD. These results support the need to search for increasingly specific targets in the genome of T. cruzi to be correlated with its main biological properties and clinical features in patients with chronic ChD. This work was supported by São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2018/22093-4), São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2019/11943-0), São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2016/25403-9), and Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, PROSICS Barcelona, Spain.

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade de S?o Paulo. Departamento de Patologia. Faculdade de Medicina. S?o Paulo, SP, Brazil. Funda??o Oncocentro de S?o Paulo. S?o Paulo, SP, Brazil. Faculdade de Medicina de S?o Jos? Do Rio Preto. S?o Paulo, SP, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal Do Cear?. Drug Research and Development Center. Laboratory of Pharmacogenetics. Fortaleza, CE, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Dengue virus causes dengue hemorrhagic fever (DHF) and has been associated to fatal cases worldwide. The liver is one of the most important target tissues in severe cases, due to its intense viral replication and metabolic role. microRNAs role during infection is crucial to understand the regulatory mechanisms of DENV infection and can help in diagnostic and anti-viral therapies development. We sequenced the miRNome of six fatal cases and compared to five controls, to characterize the human microRNAs expression profile in the liver tissue during DHF. Eight microRNAs were differentially expressed, including miR-126-5p, a regulatory molecule of endothelial cells, miR-122-5p, a liver specific homeostasis regulator, and miR-146a-5p, an interferon-regulator. Enrichment analysis with predicted target genes of microRNAs revealed regulatory pathways of apoptosis, involving MAPK, RAS, CDK and FAS. Immune response pathways were related to NF- kB, CC and CX families, IL and TLR. This is the first description of the human microRNA and isomicroRNA profile in liver tissues from DHF cases. The results demonstrated the association of miR-126-5p, miR-122-5p and miR-146a-5p with DHF liver pathogenesis, involving endothelial repair and vascular permeability regulation, control of homeostasis and expression of inflammatory cytokines.

Among the most economically significant agricultural crops, the species of the Brassicaceae family stand out as one of the most popular in human food. Cabbage leaf (Brassica oleracea var. acephala) is an essential ingredient in many regional dishes and is an excellent nutritional source for children, young and old. However, Brazilian production has been suffering from the incidence of pests and diseases that affect the crop, being the black rot of the cruciferous (BRC), the main cause of economic losses of its producers. Given this context, the objective is to build a theoretical framework by reviewing the literature on the agroecological management of BRC in cabbage leaf, based on the contribution of scientific knowledge to the preservation of agrobiodiversity in rural and traditional family communities. Entre los cultivos agrícolas de mayor importancia económica, la especie de la familia Brassicaceae se destaca como una de las más populares en la alimentación humana. La hoja de col (Brassica oleracea var. acephala) es un ingrediente esencial en muchos platos regionales y es una excelente fuente nutricional para niños, jóvenes y mayores. Sin embargo, la producción brasileña viene sufriendo la incidencia de plagas y enfermedades que afectan al cultivo, siendo la podredumbre negra de las crucíferas (PNC), la principal causa de pérdidas económicas de sus productores. Ante este contexto, el objetivo es construir un marco teórico mediante la revisión de la literatura sobre el manejo agroecológico de PNC en hoja de col, basado en el aporte del conocimiento científico a la preservación de la agrobiodiversidad en comunidades familiares rurales y tradicionales. Dentre as culturas agrícolas de maior expressividade econômica, as espécies da família Brassicaceae destacam-se como uma das mais populares na alimentação humana. A couve-manteiga (Brassica oleracea var. acephala) é um ingrediente essencial em diversos pratos regionais, sendo uma excelente fonte nutricional para crianças, jovens e idosos. Entretanto, a produção brasileira vem sofrendo com a incidência de pragas e doenças que acometem a lavoura, sendo a podridão negra das crucíferas (PNC), a principal causa de perdas econômicas de seus produtores. Diante deste contexto, objetiva-se a construção de um arcabouço teórico mediante revisão de literatura sobre o manejo fitotécnico e fitossanitário agroecológico de cultivares de couve comum, na premissa de agregar ao conhecimento científico ecológico na preservação da agrobiodiversidade em comunidades familiares rurais e tradicionais.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β cells. We show here that the protein NOD-like receptor family pyrin domain containing 1 (NLRP1) has a key role in the pathogenesis of mouse and human T1D. More specifically, downregulation of NLRP1 expression occurs during T helper 17 (Th17) differentiation, alongside greater expression of several molecules related to Th17 cell differentiation in a signal transducers and activators of transcription 3 (STAT3)-dependent pathway. These changes lead to a consequent increase in interleukin 17 (IL-17) production within the pancreas and higher incidence of diabetes in streptozotocin (STZ)-injected mice. Finally, in patients with T1D and a SNP (rs12150220) in NLRP1, there is a robust decrease in IL-17 levels in serum and in memory Th17 cells from peripheral blood mononuclear cells. Our results demonstrate that NLRP1 acts as a negative regulator of the Th17 cell polarization program, making it an interesting target for intervention during the early stages of T1D.

CAPES and Universidade Federal do Par? Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Programa de P?s-Gradua??o em Virologia. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias da Sa?de. Especializa??o em Hematologia e Imunologia. Bel?m, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias da Sa?de. Especializa??o em Hematologia e Imunologia. Bel?m, PA, Brasil. Universidade Federal do Par?. Faculdade de Forma??o e Desenvolvimento do Campo. Abaetetuba, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Tecnologia e Biomolecular. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. INTRODUCTION: Viral hepatitis is a major public health problem. It is necessary to understand the epidemic, verifying the combination of biological and demographic characteristics. METHODS: This is an analytical ecological and epidemiological study. Confirmed case data from the Notification Disease Information System (SINAN) were used. RESULTS: From 2009-2018, SINAN confirmed 404,003 viral hepatitis cases in Brazil, with 12.49%, 37.06%, and 48.28% cases of hepatitis A, B, and C, respectively. CONCLUSIONS: In Brazil, 4,296 deaths were associated with viral hepatitis, of which 36.66% were associated with acute hepatitis B. The proportional distribution of cases varied among the five Brazilian regions.

There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin

Mayaro virus (MAYV) is an emerging arbovirus of the Americas that may cause a debilitating arthritogenic disease. The biology of MAYV is not fully understood and largely inferred from related arthritogenic alphaviruses. Here, we present the structure of MAYV at 4.4 Å resolution, obtained from a preparation of mature, infective virions. MAYV presents typical alphavirus features and organization. Interactions between viral proteins that lead to particle formation are described together with a hydrophobic pocket formed between E1 and E2 spike proteins and conformational epitopes specific of MAYV. We also describe MAYV glycosylation residues in E1 and E2 that may affect MXRA8 host receptor binding, and a molecular “handshake” between MAYV spikes formed by N262 glycosylation in adjacent E2 proteins. The structure of MAYV is suggestive of structural and functional complexity among alphaviruses, which may be targeted for specificity or antiviral activity., Mayaro virus (MAYV) is an emerging arbovirus in Central and South America that is transmitted by mosquitoes and causes arthritogenic disease. Here, the authors present the 4.4 Å resolution cryo-EM structure of MAYV and describe specific features of the virus, which could be exploited for the design of MAYV-specific diagnostics and therapeutics.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the chronic phase of disease, while most infected people do not present symptoms, characterizing the asymptomatic form, some patients develop the cardiac form or chronic chagasic cardiomyopathy, which is considered the most severe manifestation of this disease. Considering that the activation of the PI3Kγ signaling pathway is essential for an efficient immune response against T. cruzi infection, we evaluated the PIK3CG C > T (rs1129293) polymorphism in exon 3 of this gene, which encodes the catalytic subunit of PI3Kγ. The PIK3CG CT and TT genotypes were found to be associated with an increased risk of developing the cardiac form of the disease rather than the asymptomatic or digestive forms. In conclusion, the presence of the T allele at single or double doses may differentiate the cardiac from other clinical manifestations of Chagas disease. This finding should help in further studies to evaluate the mechanisms underlying the differential association of PIK3CG in Chagas disease.

Background Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused approximately 2.1 million cases and >600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological, and viral genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. Methods Sera, cerebrospinal fluid (CSF), and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue virus (DENV), and Zika virus (ZIKV). Clinical, epidemiological, and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. Results Sixty-eight fatal cases had CHIKV infection confirmed by reverse-transcription quantitative polymerase chain reaction (52.9%), viral antigen (41.1%), and/or specific immunoglobulin M (63.2%). Co-detection of CHIKV with DENV was found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the subacute phase. Genetic analysis showed circulation of 2 CHIKV East-Central-South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. Conclusions The investigation of the largest cross-sectional cohort of CHIKV deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and nonrisk groups, including young adults., The introduction of the East-Central-South African genotype of Chikungunya virus (CHIKV) in Brazil caused neurological infections that led to death. The risk of death during acute and subacute CHIKV infection was higher in patients with diabetes.

The intestinal microbiome maintains a close relationship with the host immunity. This connection fosters a health state by direct and indirect mechanisms. Direct influences occur mainly through the production of short-chain fatty acids (SCFAs), gastrointestinal hormones and precursors of bioactive molecules. Indirect mechanisms comprise the crosstalk between bacterial products and the host's innate immune system. Conversely, intestinal dysbiosis is a condition found in a large number of chronic intestinal inflammatory diseases, such as ulcerative colitis and Crohn's disease, as well as in diseases associated with low-grade inflammation, such as obesity, type 1 and 2 diabetes mellitus and cardiovascular diseases. NOD-Like receptors (NLRs) are cytoplasmic receptors expressed by adaptive and innate immune cells that form a multiprotein complex, termed the inflammasome, responsible for the release of mature interleukin (IL)-1β and IL-18. NLRs are also involved in the recognition of bacterial components and production of antimicrobial molecules that shape the gut microbiota and maintain the intestinal homeostasis. Recent novel findings show that NLRs may act as positive or negative regulators of inflammation by modulating NF-κB activation. This mini-review presents current and updated evidence on the interplay between NLRs and gut microbiota and their dual role, contributing to progression or conferring protection, in diabetes and other inflammatory diseases.

We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

Leishmaniasis is a neglected infectious disease with clinical presentations ranging from asymptomatic or mild symptoms to chronic infection and eventual death. The mechanisms of disease susceptibility and pathology have been extensively studied, but there are no steadfast rules regarding leishmaniasis. A Th1 response is usually associated with infection control, while a predominant Th2 response is detrimental to the patient. In this scenario, the enzymes arginase and inducible nitric oxide synthase represent two possible pathways of immune response. While the former contributes to parasite replication, the latter is crucial for its control. In the present review, we collected study results that associate arginase expression in patients and in experimental models with disease susceptibility/chronicity and show some proposed mechanisms that explain the role of arginase in maintaining Leishmania infection, including polyamine and thiol synthesis, tissue-resident macrophage (TRM) proliferation and activation and T-cell suppression and exhaustion.

Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES), the Brazilian Research Council (CNPq) Edital Universal Grant 440722/2014-4 and Grant 302199/2014-4; Funda??o Amaz?nia Paraense de Amparo ? Pesquisa (FAPESPA), Grant Centro de Piscicultura do IFPA Campus Bragan?a and N?cleos Emergentes, Instituto Federal de Educa??o ci?ncia e Tecnologia do Par? (IFPA), Editais APIPA 2018 e 2019 . DD and CD were supported by Programa PROCAD AMAZ?NIA/CAPES 88887.310939/2018-00. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??o em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Universidade Federal Rural da Amaz?nia. Instituto Ci?ncias Agr?rias. Capit?o Po?o, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??o em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??o em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??o em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??o em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??o em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Universidade Federal do Oeste do Par?. Laborat?rio de Fisiologia Ambiental Aplicada. Oriximin?, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o, Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??o em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Microscopia Eletr?nica. Ananindeua, PA, Brasil. Fish use spatial cognition based on allocentric cues to navigate, but little is known about how environmental enrichment (EE) affects learning and memory in correlation with hematological changes or gene expression in the fish brain. Here we investigated these questions in Colossoma macropomum (Teleostei). Fish were housed for 192 days in either EE or in an impoverished environment (IE) aquarium. EE contained toys, natural plants, and a 12-h/day water stream for voluntary exercise, whereas IE had no toys, plants, or water stream. A third plus maze aquarium was used for spatial and object recognition tests. Compared with IE, the EE fish showed greater learning rates, body length, and body weight. After behavioral tests, whole brain tissue was taken, stored in RNA-later, and then homogenized for DNA sequencing after conversion of isolated RNA. To compare read mapping and gene expression profiles across libraries for neurotranscriptome differential expression, we mapped back RNA-seq reads to the C. macropomum de novo assembled transcriptome. The results showed significant differential behavior, cell counts and gene expression in EE and IE individuals. As compared with IE, we found a greater number of cells in the telencephalon of individuals maintained in EE but no significant difference in the tectum opticum, suggesting differential plasticity in these areas. A total of 107,669 transcripts were found that ultimately yielded 64 differentially expressed transcripts between IE and EE brains. Another group of adult fish growing in aquaculture conditions were either subjected to exercise using running water flow or maintained sedentary. Flow cytometry analysis of peripheral blood showed a significantly higher density of lymphocytes, and platelets but no significant differences in erythrocytes and granulocytes. Thus, under the influence of contrasting environments, our findings showed differential changes at the behavioral, cellular, and molecular levels. We propose that the differential expression of selected transcripts, number of telencephalic cell counts, learning and memory performance, and selective hematological cell changes may be part of Teleostei adaptive physiological responses triggered by EE visuospatial and somatomotor stimulation. Our findings suggest abundant differential gene expression changes depending on environment and provide a basis for exploring gene regulation mechanisms under EE in C. macropomum.

Chitin-binding proteins behave as storage and antifungal proteins in the seeds of Moringa oleifera. Moringa oleifera is a tropical multipurpose tree. Its seed constituents possess coagulant, bactericidal, fungicidal, and insecticidal properties. Some of these properties are attributed to a group of polypeptides denominated M. oleifera chitin-binding proteins (in short, Mo-CBPs). Within this group, Mo-CBP2, Mo-CBP3, and Mo-CBP4 were previously purified to homogeneity. They showed high amino acid similarity with the 2S albumin storage proteins. These proteins also presented antimicrobial activity against human pathogenic yeast and phytopathogenic fungi. In the present study, the localization and expression of genes that encode Mo-CBPs and the biosynthesis and degradation of the corresponding proteins during morphogenesis and maturation of M. oleifera seeds at 15, 30, 60, and 90 days after anthesis (DAA) and germination, respectively, were assessed. The Mo-CBP transcripts and corresponding proteins were not detected at 15 and 30 days after anthesis (DAA). However, they accumulated at the latter stages of seed maturation (60 and 90 DAA), reaching the maximum level at 60 DAA. The degradation kinetics of Mo-CBPs during seed germination by in situ immunolocalization revealed a reduction in the protein content 48 h after sowing (HAS). Moreover, Mo-CBPs isolated from seeds at 60 and 90 DAA prevented the spore germination of Fusarium spp. Taken together, these results suggest that Mo-CBPs play a dual role as storage and defense proteins in the seeds of M. oleifera.

Given its high-valued wood, the African mahogany (Khaya grandifoliola) has been envisaged as a renewable source of tropical hardwoods in Brazil. However, there are concerns about the hypothesized low diversity among the few K. grandifoliola germplasm sources introduced in the country. Using eight microsatellite markers, we evaluated the genetic diversity and divergence among 53 superior trees selected from three provenances of K. grandifoliola located in the state of Para. These populations are among the oldest plantations (>15 years) in Brazil and, therefore, the country's main seed sources. The average number of alleles per locus was 5.9, expected heterozygosity was moderate (^=0.56) and lower than the high observed heterozygosity (HO=0.74). Therefore, the intrapopulation fixation index was negative (f=-0.31) indicating the possibility that selection of superior trees might have favored heterozygous plants with heterosis. No genetic structure was observed between provenances. The genetic diversity observed within selected trees, with an effective population size (Ne) of 30.4, is comparable to that of natural populations of African and Brazilian mahoganies. Therefore, our results contradict the idea that the genetic diversity of K. grandifoliola introduced in Brazil is low and show that our germplasm can be exploited for breeding purposes.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major concerns in worldwide public health, and their pathophysiology involves immune cells activation, being macrophages one of the main players of both processes. It is suggested that metabolic pathways could contribute to macrophage modulation and phosphatidylinositol‑3 kinase (PI3K) pathway was shown to be activated in kidneys subjected to ischemia and reperfusion as well as unilateral ureteral obstruction (UUO). Although PI3K inhibition is mostly associated with anti-inflammatory response, its use in kidney injuries has been shown controversial results, which indicates the need for further studies. Our aim was to unveil the role of PI3Kγ in macrophage polarization and in kidney diseases development. We analyzed bone-marrow macrophages polarization from wild-type (WT) and PI3Kγ knockout (PI3K KO) animals. We observed increased expression of M1 (CD86, CCR7, iNOS, TNF, CXCL9, CXCL10, IL-12 and IL-23) and decreased of M2 (CD206, Arg-1, FIZZ1 and YM1) markers in the lack of PI3Kγ. And this modulation was accompanied by higher levels of inflammatory cytokines in PI3K KO M1 cells. PI3K KO mice had increased M1 in steady state kidneys, and no protection was observed in these mice after acute and chronic kidney insults. On the contrary, they presented higher levels of protein-to-creatinine ratio and Kim-1 expression and increased tubular injury. In conclusion, our findings demonstrated that the lack of PI3Kγ favors M1 macrophages polarization providing an inflammatory-prone environment, which does not prevent kidney diseases progression.

Made available in DSpace on 2022-04-29T08:27:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-07-20 Squamous cell carcinoma (SCC) is the second most common form of skin cancer and the mechanism(s) involved in the progression of this tumor are unknown. Increases in the expression of IL-33/ST2 axis components have been demonstrated to contribute to neoplastic transformation in several tumor models and interleukin-33 is correlated with poor prognosis of patients with squamous cell carcinoma of the tongue. Based on these observations, we sought to determine the role of the IL-33/ST2 pathway during the development of SCC. Our findings show that ST2- deficiency led to a marked decrease in the severity of skin lesions, suggesting that ST2 signaling contributed to tumor development. An analysis of tumor lesions in wild-type and ST2KO mice revealed that a lack of ST2 was associated with specific and significant reductions in the numbers of CD4+ T cells, CD8+ T cells, dendritic cells, and macrophages. In addition, NK cells that were isolated from ST2KO mice exhibited higher cytotoxic activity than cells isolated from wild-type mice. Notably, ST2 deficiency resulted in lower IFN-γ, TNF-α, IL-10, and IL-17 production in tumor samples. Our findings indicate that the IL-33/ST2 pathway contributes to the development of SCC by affecting leukocyte migration to tumor microenvironment and impairing NK cytotoxic activity. Department of Biological Sciences Bauru School of Dentistry University of São Paulo, Al. Dr. Octávio Pinheiro Brisolla Department of Microbiology and Immunology Institute of Biosciences of Botucatu São Paulo State University, R. Prof. Dr. Antônio Celso Wagner Zanin Department of Stomatology - Oral Pathology Bauru School of Dentistry University of São Paulo, Al. Dr. Octávio Pinheiro Brisolla Department of Biochemistry and Immunology School of Medicine of Ribeirão Preto University of São Paulo Department of Biomedical Sciences (Research Division of Immunology) and Medicine F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute Cedars-Sinai Medical Center Department of Medicine Division of Pulmonary and Critical Care Medicine Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center Department of Microbiology and Immunology Institute of Biosciences of Botucatu São Paulo State University, R. Prof. Dr. Antônio Celso Wagner Zanin

Recent evidence indicates that nonprofessional immune cells such as epithelial cells, endothelial cells, and fibroblasts also contribute to innate immunity via secretion of cytokines. Fibroblasts are the principal type of cell found in the periodontal connective tissues and they are involved in the immune response during periodontal disease. The role of fibroblasts in the recognition of pathogens via Toll-like receptors (TLRs) has been established; however, few studies have been conducted concerning the involvement of innate immune receptors in the recognition of Candida albicans by gingival fibroblast. In the current study, we investigate the functional activity of TLR2, cluster of differentiation 14 (CD14), and myeloid differentiation primary response gene 88 (MyD88) molecules in the recognition of C. albicans by gingival fibroblast. First, we identified that gingival fibroblasts expressed TLR2, TLR3, and TLR4. Our results showed that TLR agonists had no effect on these receptors’ expression by TLR2, MyD88, and CD14-deficient cells. Notably, C. albicans and a synthetic triacylated lipoprotein (Pam3CSK4) induced a remarkable increase of TLR3 expression on MyD88-deficient gingival fibroblasts. TLR4 expression levels were lower than TLR2 and TLR3 levels and remained unchanged after TLR agonist stimulation. Gingival fibroblasts presented morphological similarities; however, TLR2 deficiency on these cells leads to a lower proliferative response, whereas the deficiency on CD14 expression resulted in lower levels of type I collagen by these cells. In addition, the recognition of C. albicans by gingival fibroblasts had an effect on the secretion of cytokines and it was dependent on a specific recognition molecule. Specifically, tumor necrosis factor-α (TNF-α ) production after the recognition of C. albicans was dependent on MyD88, CD14, and TLR2 molecules, whereas the production of interleukin-1β (IL-1β ) and IL-13 was dependent on TLR2. These findings are the first to describe a role of gingival fibroblast in the recognition of C. albicans and the pathways involved in this process. An understanding of these pathways may lead to alternative treatments for patients with periodontal disease.

Background The analysis of modular gene co-expression networks is a well-established method commonly used for discovering the systems-level functionality of genes. In addition, these studies provide a basis for the discovery of clinically relevant molecular pathways underlying different diseases and conditions. Results In this paper, we present a fast and easy-to-use Bioconductor package named CEMiTool that unifies the discovery and the analysis of co-expression modules. Using the same real datasets, we demonstrate that CEMiTool outperforms existing tools, and provides unique results in a user-friendly html report with high quality graphs. Among its features, our tool evaluates whether modules contain genes that are over-represented by specific pathways or that are altered in a specific sample group, as well as it integrates transcriptomic data with interactome information, identifying the potential hubs on each network. We successfully applied CEMiTool to over 1000 transcriptome datasets, and to a new RNA-seq dataset of patients infected with Leishmania, revealing novel insights of the disease’s physiopathology. Conclusion The CEMiTool R package provides users with an easy-to-use method to automatically implement gene co-expression network analyses, obtain key information about the discovered gene modules using additional downstream analyses and retrieve publication-ready results via a high-quality interactive report. Electronic supplementary material The online version of this article (10.1186/s12859-018-2053-1) contains supplementary material, which is available to authorized users.

We acknowledge Funda??o Amaz?nia de Amparo a Estudos e Pesquisas do Par? (FAPESPA) for financially supporting (ICAAF 099/2014) our project. Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) also supported individual authors through Grant 311686/2015-0 (ECG). Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Tecnologia Biomolecular. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Tecnologia Biomolecular. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Exatas e Naturais. Laborat?rios de Investiga??o Sistem?tica em Biotecnologia e Biodiversidade Molecular. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Exatas e Naturais. Laborat?rios de Investiga??o Sistem?tica em Biotecnologia e Biodiversidade Molecular. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Tecnologia Biomolecular. Bel?m, PA, Brazil. Scytovirin is a lectin isolated from the cyanobacterium Scytonema varium that has shown activity against HIV, SARS coronavirus and Zaire Ebola virus. Its 95 amino acids are divided into two structural domains (SD), the first spanning amino acids 1?48 (SD1) and the second 49?95 (SD2). Interestingly, the domains are nearly identical but differ in their affinities for carbohydrates. With the aim of enhancing understanding of the binding properties of scytovirin, we performed molecular dynamics (MD) simulations of scytovirin complexed with Man4. We set up three systems: (i) Man4 bound to both domains (SD1+SD2) using the full-length protein; (ii) Man4 bound to an incomplete protein, containing only SD1 and (iii) Man4 bound to an incomplete protein containing only SD2. Contrary to other reports, binding free energy results suggest that Man4 can bind simultaneously to SD1 and SD2 binding regions, but SD1 individually has the best values of energy and the best affinity for Man4. Decomposition of the binding free energy showed that the residues that interact with Man4 were different in the three systems, suggesting that the binding mechanism of Man4 varies between full-length protein, SD1 and SD2. The results presented here may help to formulate strategies to use scytovirin and promote mutagenesis studies to improve the antiviral activity of scytovirin.

Turnera subulata L. is a plant that belongs to the Turneraceae family and is popularly known in Brazil as “Chanana”; it is used as an alternative medicine. Among all microorganisms, fungi are mostly associated with plants. The aim of this study is to isolate, identify and evaluate the antifungal and antioxidant activity of extracts of Phomopsis sp. isolated from T. subulata. From the leaf fragment obtained from T. subulata, the filamentous endophytic fungus Phomopsis sp was isolated. The fungal isolate had a higher growth in potato dextrose agar (PDA) and potato sucrose agar (PSA) culture medium, as well as in the presence of light. In the antagonism test of the endophytic Phomopsis sp. against human pathogens, there was inhibition zone against Escherichia coli, Staphylococcus aureus, Candida albicans, C. tropicalis and C. glabrata. Concerning the antioxidant activity, it was observed that the chloroform extract was more effective than hexane. On the other hand, all the extracts from the mycelium of Phomopsis sp. and its ethyl acetate extract from the cultured filtrate had low antimicrobial activity against strains of E. coli, S. aureus, C. albicans, C. tropicalis and C. glabrata. Therefore it was concluded that Phomopsis sp. may act as an endophyte of T. subulata. Extracts from Phomopsis sp. promoted inhibition zone of growth when tested against human pathogen. Its hexanic and chloroform extracts showed lower antioxidant activity. Key words: Biological control, endophytic fungus, secondary metabolites, filamentous fungus, fungal extract.

Sepsis is a life-threatening organ dysfunction caused by a deregulated host response to infection. This inappropriate response to micro-organism invasion is characterized by an overwhelmed systemic inflammatory response and cardiovascular collapse that culminate in high mortality and morbidity in critical care units. The occurrence of sepsis in diabetes mellitus (DM) patients has become more frequent, as the prevalence of DM has increased dramatically worldwide. These two important diseases represent a global public health concern and highlight the importance of increasing our knowledge of the key elements of the immune response related to both conditions. In this context, it is well established that the cells taking part in the innate and adaptive immune responses in diabetic patients have compromised function. These altered responses favor micro-organism growth, a process that contributes to sepsis progression. The present review provides an update on the characteristics of the immune system in diabetic and septic subjects. We also explore the beneficial effects of insulin on the immune response in a glycemic control-dependent and independent manner.

Background Trypanosoma cruzi has a high genetic and biological diversity and has been subdivided into seven genetic lineages, named TcI-TcVI and TcBat. DTUs TcI-TcII-TcV and TcVI are agents of ChD in different regions of Latin America. Due to population movements, the disease is an emergent global public health problem. Thus, the aim of this study was to quantify the parasitic load and identify the presence of T. cruzi DTUs in 101 Latin American immigrants with chronic ChD, residing in Barcelona, Spain. Methodology / Principal findings 5ml of peripheral blood were collected in guanidine/EDTA from each patient for DNA extraction, quantification of the parasitic load and genotyping. A great variation of the parasitic load of the patients was verified: from 0.001 to 22.2 T. cruzi DNA (fg) / Blood DNA (ng). In patients from Bolivia the parasitic load was 3.76±4.43 T. cruzi DNA (fg) / Blood DNA (ng) (mean ± SD), in patients of other countries was 0.95±1.38 T. cruzi DNA (fg) / Blood DNA (ng). No statistically significant difference was observed in the parasitic load between patients with the indeterminate and cardiac forms of ChD (p = 0,57). Parasite genotyping was performed by multilocus conventional PCR. In patients from Bolivia there was a nearly equal prevalence of DTUs TcV (27/77), TcII/TcV/TcVI (26/77), and TcII/TcVI (22/77). TcVI was detected in only 2 samples (2/77). A higher prevalence of TcII/TcVI (19/24) was verified in patients of other countries, with low prevalence of TcII/TcV/TcVI (4/24) and TcV (1/24). Conclusions/Significance In this study, low/medium parasitic load was found in all patients evaluated. Our data corroborate previous conclusions indicating that patients from the Bolivia, living in Spain, are predominantly infected by TcV, and TcVI DTUs. On the other hand, in Non-Bolivians patients TcII/TcVI predominated. Surprisingly, in our cohort of 101 patients no infection by TcI DTU was observed., Author summary Trypanosoma cruzi is divided in seven distinct genetic groups (TcI-TcVI) and TcBat. They can be related to several biological parameters, the main being resistance to specific treatment. Due to the intense migration movements, ChD has become a serious public health problem in Europe. Thus, the work has the important function of identifying the genetic variability of T. cruzi circulating in the European continent, in addition to assessing the parasitic burden present in 101 chronic chagasic patients, residing in Barcelona, Spain. We show differences in the predominance between the infecting DTUs among Bolivian (TcV) and non-Bolivian patients (TcII/TcVI). This is the first study to describe the presence of TcVI genotype in Europe. Although the level of parasite burden is low/medium, it is higher in patients from Bolivia when compared with patients of other countries. The low parasitic burden is a limitation factor for studies aimed at evaluating by qPCR the effects of treating this disease with the drugs available to date, Benznidazole and Nifurtimox, and for clinical trials of new drugs. The information generated in this study should impact planning of more effective public health interventions to improve the health of chagasic patients, control vertical transmission and treatment of ChD.

Schistosoma mansoni adaptive success is related to regulation of replication, transcription and translation inside and outside the intermediate and definitive host. We hypothesize that S. mansoni alters its epigenetic state in response to the mammalian host immune system, reprogramming gene expression and altering the number of eggs. In response, a change in the DNA methylation profile of hepatocytes could occurs, modulating the extent of hepatic granuloma. To investigate this hypothesis, we used the EBi3-/- murine (Mus musculus) model of S. mansoni infection and evaluated changes in new and maintenance DNA methylation profiles in the liver after 55 days of infection. We evaluated expression of epigenetic genes and genes linked to histone deubiquitination in male and female S. mansoni worms. Comparing TET expression with DNMT expression indicated that DNA demethylation exceeds methylation in knockout infected and uninfected mice and in wild-type infected and uninfected mice. S. mansoni infection provokes activation of demethylation in EBi3-/-I mice (knockout infected). EBi3-/-C (knockout uninfected) mice present intrinsically higher DNA methylation than WTC (control uninfected) mice. EBi3-/-I mice show decreased hepatic damage considering volume and reduced number of granulomas compared to WTI mice; the absence of IL27 and IL35 pathways decreases the Th1 response resulting in minor liver damage. S. mansoni males and females recovered from EBi3-/-I mice have reduced expression of a deubiquitinating enzyme gene, orthologs of which target histones and affect chromatin state. SmMBD and SmHDAC1 expression levels are downregulated in male and female parasites recovered from EBi3-/-, leading to epigenetic gene downregulation in S. mansoni. Changes to the immunological background thus induce epigenetic changes in hepatic tissues and alterations in S. mansoni gene expression, which attenuate liver symptoms in the acute phase of schistosomiasis., Author summary Schistosomiasis mansoni is a millennial disease and covers mainly tropical and economically disadvantaged regions. The disease mostly affects the liver, causing necrosis and fibrosis. Our study evaluated the effect of the immune system in modulating the oviposition of worms and the expression of genes mainly related to epigenetic regulation in worms. We also examined how methylation of liver DNA and the expression of related genes are influenced during Schistosoma mansoni infection depending on the type of immune response presented by the host. Our results revealed increased DNA demethylation during infection of EBi3-/- mice, while wild-type mice do not altered the methylation during infection. S. mansoni oviposition was decreased in infected EBi3-/- mice compared with wild-type mice, proving adaptation of the parasites to the type of host response. The livers of infected EBi3-/- mice presented less damage than those of wild-type mice, suggesting a protective hepatic effect conferred by the decrease in Th1 caused by IL27 and IL35 pathway knockout.

Type 2 diabetes (T2D) is a metabolic disease characterized by increased inflammation, NOD-like receptors (NLRs) activation and gut dysbiosis. Our research group has recently reported that intestinal Th17 response limits gut dysbiosis and LPS translocation to visceral adipose tissue (VAT), protecting against metabolic syndrome. However, whether NOD2 receptor contributes intestinal Th17 immunity, modulates dysbiosis-driven metabolic tissue inflammation, and obesity-induced T2D remain poorly understood. In this context, we observed that mice lacking NOD2 fed a high-fat diet (HFD) display severe obesity, exhibit greater adiposity, and more hepatic steatosis compared to HFD-fed wild-type (WT) mice. In addition, they develop increased hyperglycemia, worsening of glucose intolerance, and insulin resistance. Notably, the deficiency of NOD2 causes a deviation from M2 macrophage and regulatory T cells (Treg) to M1 macrophage and mast cells into VAT compared to WT mice fed HFD. An imbalance was also observed in Th17/Th1 cell populations, with reduced IL-17 and IL-22 gene expression in the mesenteric lymph nodes (MLNs) and ileum, respectively, of NOD2-deficient mice fed HFD. 16S rRNA sequencing indicates lower richness, alpha diversity, and a depletion of Allobaculum, Lactobacillus, and enrichment with Bacteroides genera in these mice compared to HFD-fed WT mice. These alterations were associated with disrupted tight-junctions expression, augmented serum LPS, and bacterial translocation into VAT. Overall, NOD2 activation is required for a protective Th17 over Th1 immunity in the gut, which seems to decrease gram-negative bacteria outgrowth in gut microbiota, attenuating the endotoxemia, metainflammation, and protecting against obesity-induced T2D.

Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??es em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Instituto Federal de Educa??o. Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o. Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o. Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o. Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o. Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o. Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Instituto Federal de Educa??o. Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??es em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Instituto Federal de Educa??o. Ci?ncia e Tecnologia do Par?. Laborat?rio de Biologia Molecular e Neuroecologia. Bragan?a, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??es em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Hospital Universit?rio Jo?o de Barros Barreto. Laborat?rio de Investiga??es em Neurodegenera??o e Infec??o. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Microscopia Eletr?nica. Bel?m, PA, Brasil. Astrocytes are essential for lipid neuronal metabolism in long-distance uninterrupted migratory flights, when glucose is not available as the main source of energy. We previously demonstrated in Calidris pusilla that after uninterrupted 5 days transatlantic flight, astrocytes shrink and reduce its number in the hippocampal formation. Here we shifted our attention to the wintering period and tested the hypothesis that hippocampal astrocyte morphology of A interpres will change as the wintering period progresses towards the premigration window. To that end we used Arenaria interpres, which also crosses the Atlantic Ocean and reaches the mangroves of the Amazon River estuary for wintering. Birds were captured in September/October (closer to the arrival in the coast of Bragan?a, Para, Brazil for wintering) and in April/May (closer to the departure towards the breeding sites) and had their brains processed for selective GFAP-astrocyte immunolabeling. Three-dimensional reconstructions of the immunostained astrocytes were performed and morphological classification was done based on hierarchical cluster and discriminant analysis of multimodal morphometric features. We found two morphological phenotypes of astrocytes in the newcomers which differentially increased its morphological complexities as wintering period progresses towards the pre-migration window. Taken together, our findings demonstrate that the long-distance non-stop flight and wintering period differentially affected the two astrocytes morphotypes, suggesting distinct physiological roles for these cells. We suggest that morphological changes during the wintering period, may be part of the adaptive plasticity of the local hippocampal circuits of A. interpres in preparation for the long journey back to their breeding sites in the north hemisphere.

Background: NLRP3 inflammasome activation in response to several signals, including mitochondrial DNA (mDNA), regulates inflammatory responses by caspase-1 activation and interleukin-1β (IL-1β) release. Circulating mDNA is linked to micro and macrovascular complications in diabetes. However, a role for mDNA in endothelial dysfunction is not clear. We tested the hypothesis that mDNA contributes to diabetes-associated endothelial dysfunction and vascular inflammation via NLRP3 activation. Methods: Vascular reactivity, reactive oxygen species (ROS) generation, calcium (Ca2+) influx and caspase-1 and IL-1β activation were determined in mesenteric resistance arteries from normoglicemic and streptozotocin-induced diabetic C57BL/6 and NLRP3 knockout (Nlrp3-/- ) mice. Endothelial cells and mesenteric arteries were stimulated with mDNA from control (cmDNA) and diabetic (dmDNA) mice. Results: Diabetes reduced endothelium-dependent vasodilation and increased vascular ROS generation and caspase-1 and IL-1β activation in C57BL/6, but not in Nlrp3-/- mice. Diabetes increased pancreatic cytosolic mDNA. dmDNA decreased endothelium-dependent vasodilation. In endothelial cells, dmDNA activated NLRP3 via mitochondrial ROS and Ca2+ influx. Patients with type 1 diabetes exhibited increased circulating mDNA as well as caspase-1 and IL-1β activation. Conclusion: dmDNA activates endothelial NLRP3 inflammasome by mechanisms that involve Ca2+ influx and mitochondrial ROS generation. NLRP3 deficiency prevents diabetes-associated vascular inflammatory damage and endothelial dysfunction. Our study highlights the importance of NLRP3 inflammasome in diabetes-associated vascular dysfunction, which is key to diabetic complications.

Evandro Chagas Institute, Federal University of Par?, Federal Institute of Education, Science and Technology of Par?, FAPESPA and CNPq. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Exatas e Naturais. Laborat?rio de Planejamento e Desenvolvimento de F?rmacos. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. Federal Institute of Education, Science and Technology of Par?. Tucuru?, PA, Brazil. Federal Institute of Education, Science and Technology of Par?. Tucuru?, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Exatas e Naturais. Laborat?rio de Planejamento e Desenvolvimento de F?rmacos. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. The envelope (E) protein is an important target for antibodies in favivirus. Literature reports that the mutation T198F, located at the domain I-II hinge of the E protein, regulates viral breathing and increases the accessibility of a distal cryptic epitope located on the fusion loop, having a direct impact in the neutralization of West Nile virus (WNV). Our study aimed to describe, using accelerated molecular dynamics simulations, the efects of the T198F mutation in the fexibility of the E protein of WNV and to elucidate the mechanism that regulates epitope accessibility. The simulation results revealed that the mutation favors the formation of alternative hydrogen bonds, hampering the bending movement between domains I and II. We hypothesized that this is the mechanism by which the T198F mutation, located at the middle of the protein, locks the distal cryptc epitope near a single preferred conformation, rendering it more prone to recognition by antibodies.

Monocytes play key roles in the maintenance of homeostasis and in the control of the infection. Monocytes are recruited from the bone marrow to inflammatory sites and are essential for antimicrobial activity to limit tissue damage and promote adaptive T cell responses. Here, we investigated the role of Nuclear Factor of Activated T cells 1 (NFAT1) in the regulation of Ly6Chi inflammatory monocyte recruitment to the CNS upon T. gondii infection. We show that NFAT-1-deficient monocytes are unable to migrate to the CNS of T. gondii-infected mice. Moreover, NFAT1-/- mice are highly susceptible to chronic T. gondii infection due to a failure to control parasite replication in the CNS. The inhibition of Ly6Chi inflammatory monocyte recruitment to the CNS severely blocked CXCL10 production and consequently the migration of IFN-γ-producing CD4+ T cells. Moreover, the transfer of Ly6Chi monocytes to infected NFAT1-/- mice favored CD4+ T cell migration to the CNS and resulted in the inhibition of parasite replication and host defense. Together, these results demonstrated for the first time the contribution of NFAT1 to the regulation of Ly6Chi monocyte recruitment to the CNS and to resistance during chronic T. gondii infection.

Summary The recognition of fungi by intracellular NOD-like receptors (NLRs) induces inflammasome assembly and activation. Although the NLRC4 inflammasome has been extensively studied in bacterial infections, its role during fungal infections is unclear. Paracoccidioidomycosis (PCM) is a pathogenic fungal disease caused by Paracoccidioides brasiliensis. Here, we show that NLRC4 confers susceptibility to experimental PCM by regulating NLRP3-dependent cytokine production and thus protective effector mechanisms. Early after infection, NLRC4 suppresses prostaglandin E2 production, and consequently reduces interleukin (IL)-1β release by macrophages and dendritic cells in the lungs. IL-1β is required to control fungal replication via induction of the nitric oxide synthase 2 (NOS2) pathway. At a later stage of the disease, NLRC4 impacts IL-18 release, dampening robust CD8+IFN-γ+ T cell responses and enhancing mortality of mice. These findings demonstrate that NLRC4 promotes disease by regulating the production of inflammatory cytokines and cellular responses that depend on the NLRP3 inflammasome activity., Graphical abstract, Highlights • NLRC4 promotes susceptibility to a highly pathogenic fungus. • NLRC4 regulates NLRP3 activity. • NLRC4 inhibits early NLRP3/IL-1β/NOS2/NO axis and promotes fungal replication. • NLRC4 dampens late IL-18 production, suppressing CD8+IFN-γ+ T cell responses., Immunology; Mycology

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis.

Made available in DSpace on 2018-12-11T16:42:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-08-01 Salmonella enterica serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid in chickens, a septicemic infection which results in high mortality rates. This disease causes high economic impact to the poultry industry worldwide because of the mortality or elimination of positive flocks to control bacterial dissemination. Live vaccines are used in the fields, however the characterization of immune mechanisms important for protection are being studied to improve the efficacy of vaccination schemes. In this study, we evaluated the immune response in brown layer-hens, vaccinated or not, during the most critical period of infection. Cellular and humoral immunity were extensively evaluated until 7 days post-infection (DPI), by flow cytometry and ELISA, respectively. Furthermore, we evaluated the expression of important pro-inflammatory cytokines after infection of bone marrow derived macrophages (BMDMs) with the live attenuated SG vaccine and with the wild SG strain. The results showed an increasing production of IgG and IgM during the first week post-infection, in vaccinated layer-hens, which was absent in unvaccinated birds. The population of CD8+CD44+ and CD4+CD44+ T cells in spleen and cecal tonsils constantly decreased in unvaccinated birds in comparison with vaccinated layers. The expression of IFN-γ and TNF-α in BMDMs was induced by both SG strains (attenuated and wild) at similar levels (p>0.05). Vaccination with live SG vaccine reduced systemic infection by challenge strain of SG and prevented the mortality rate of 85% that occurred in unvaccinated layer-hens during 30 dpi. Furthermore, the immunization enhanced the proliferation of effector CD4+ and CD8+ T cells after challenge. School of Agricultural and Veterinary Sciences São Paulo State University (UNESP), Jaboticabal Campus, SP Ribeirão Preto Medical School University of São Paulo (USP) College of Veterinary Medicine Cornell University School of Agricultural and Veterinary Sciences São Paulo State University (UNESP), Jaboticabal Campus, SP

Background:Patient’s Global Assessment of Disease Activity (PtGA) and Physician’s Global Assessment of Disease Activity (PhGA) are assessed as part of commonly used measures of disease activity in RA.1Both are important measures in treat-to-target strategies in Rheumatoid Arthritis (RA), but often provide discordant results.2,3This can provide an erroneous assessment of disease activity in patients under Biologic treatment and mislead treatment decisions, namely switches.Objectives:To assess differences and determinants of PtGA and PhGA in RA patients under biologic treatment.Methods:Cross-sectional study, including 46 patients with RA diagnosed according to the ACR/EULAR criteria, under biologic treatment, consecutively evaluated in day-care unit. Participants completed patient-reported outcomes (PROs), including PtGA, and sociodemographic characteristics. Physicians collected comorbidities and parameters of inflammatory activity (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) and completed PhGA and disease activity score 28 with ESR (DAS28). SPSS was used for statistical analysis and significance level was defined as 2-sided pResults:Clinical and laboratory characteristics of patients are shown in table 1. PtGA and PhGA were significantly different (36.1±27.6 mmvs8.7±14.2 mm, p< 0.001) and a positive discordance (PtGA>PhGA, more than 25mm in visual analogue scale [VAS]) was found in 54.3% of cases.PtGA had a correlation with PROs (Pain VAS, 36-Item Short Form Health Survey [SF-36], Health Assessment Questionnaire [HAQ], Functional Assessment of Chronic Illness Therapy [FACIT], EuroQol [EQ5D] and Hospital Anxiety and Depression Scale [HADS]), CRP, tender and swollen joint counts and an association with comorbidities like fibromyalgia or osteoarthritis (OA). No association was found between PtGA and age, sex, education level, profession, employment status, extra-articular manifestations, positivity of rheumatoid factor, ESR, years of disease evolution or number of biologic treatments. In multivariable analyse including SF-36, CRP, tender joints count and OA (R2adjusted= 0.672), the main predictors of PtGA were lower SF36, concomitant OA and higher CRP level.PhGA had a correlation with PtGA, pain VAS, CRP, tender and swollen joints. No association was found between PhGA and patient or physician age, patient or physician sex, extra-articular manifestations, positivity of rheumatoid factor, ESR level, years of disease evolution or number of biologic treatments. In multivariable analysis including ESR, tender and swollen joints count and CRP (R2adjusted= .800), the main predictors of PhGA were swollen joint count and higher CRP level.Conclusion:This study showed the variability implied on global assessment of RA activity. Overall PtGA is based on function and also in subjective and emotional experience of pain, whereas the PhGA is based on more objective measures, more related to disease activity.References:[1]Kanekoa Y. et al, Determinants of Patient’s Global Assessment of Disease Activity and Physician’s Global Assessment of Disease Activity in patients with rheumatoid arthritis: A post hoc analysis of overall and Japanese results from phase 3 clinical trials.Modern Rheumatology2018; 28(6):960–967[2]Furu M. et al. Discordance and accordance between patient’s and physician’s assessments in rheumatoid arthritis.Scand J Rheumatol.2014; 43(4):291-5.Ann Rheum Dis. 2016 Sep;75(9):1661-6. doi: 10.1136/annrheumdis-2015-208251. Epub 2015 Oct 22.[3]Portier A. et al, Patient-perceived flares in rheumatoid arthritis: A sub-analysis of the STRASS treatment tapering strategy trial.Joint Bone Spine. 2017; 84(5):577-581Disclosure of Interests:None declared

Universidad Nacional. Facultad de Ciencias Medicas. Instituto de Virologia Dr J. M. Vanella. Ciudad Universit?ria, CO, Argentina. University of S?o Paulo. Ribeir?o Preto Medical School. Virology Research Center. Ribeir?o Preto, SP, Brazil. Universidad Nacional. Facultad de Ciencias Medicas. Instituto de Virologia Dr J. M. Vanella. Ciudad Universit?ria, CO, Argentina. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidad Nacional. Facultad de Ciencias Medicas. Instituto de Virologia Dr J. M. Vanella. Ciudad Universit?ria, CO, Argentina. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidad Nacional. Facultad de Ciencias Medicas. Instituto de Virologia Dr J. M. Vanella. Ciudad Universit?ria, CO, Argentina. During 2013, in Argentina, three new isolates of serogroup Bunyamwera virus (genus Orthobunyavirus, family Peribunyaviridae) were recovered from two horses with encephalitis, and from an aborted equine fetus. In the present study, we report the complete genome sequence, genetic characterization, and phylogenetic analysis of three new strains isolated in Argentina to clarifying their relationship within the Bunyamwera serogroup virus and to investigate the evolutionary history of viruses with segmented genomes.

Sound evidence supports a role for interleukin‐17 (IL‐17) ‐producing γδ T cells and IL‐17‐producing helper T (Th17) cells in intestinal homeostasis, especially in intestinal barrier integrity. In the present study, we aimed to evaluate the role of IL‐17 cytokine in the regulation of intestinal immunity and obesity‐induced metabolic syndrome (MetS) in an experimental murine model. C57BL/6 wild‐type (WT) mice and mice lacking the IL‐17 cytokine receptor (IL‐17RA(−/−)) were fed either a control diet (CD) or a high‐fat diet (HFD) for 9 weeks. Our data demonstrate that IL‐17RA(−/−) mice are protected against obesity, but develop hyperglycemia, hyperinsulinemia and insulin resistance. In parallel, HFD‐fed IL‐17RA(−/−) mice display intense inflammation in the ileum compared with WT mice on the HFD. IL‐17RA(−/−) mice fed the HFD exhibit impaired neutrophil migration to the intestinal mucosa and reduced gene expression of the CXCL‐1 chemokine and CXCR‐2 receptor in the ileum. Interestingly, the populations of neutrophils (CD11b(+) Ly6G(+)) and anti‐inflammatory macrophages (CD11b(+) CX3CR1(+)) are increased in the mesenteric lymph nodes of these mice. IL‐17RA(−/−) mice on the HFD also display increased commensal bacterial translocation into the bloodstream and elevated lipopolysaccharide (LPS) levels in the visceral adipose tissue (VAT). Metagenomic analysis of bacterial 16S gene revealed increased Proteobacteria and Bacteroidetes phyla, the main representatives of Gram‐negative bacteria, and reduced Akkermansia muciniphila in the fecal samples of IL‐17RA(−/−) mice fed the HFD. Together, these data indicate that the IL‐17/IL‐17R axis drives intestinal neutrophil migration, limits gut dysbiosis and attenuates LPS translocation to VAT, resulting in protection to MetS.

The application of medicinal plants are the most important biotechnological alternative in the treatment of numerous diseases, especially in developing countries, such as Brazil. Among them, we specified some specimens of the genus Cnidoscolus used as phytotherapies, with healing properties, analgesic, anti-inflammatory, antibiotic and diuretic, anticancer, among others. Such effects are possibly associated with the presence of terpenoids, alkaloids, coumarins, flavonoids phenolic compounds, among others. Thus, the objective of this work was to evaluate in the literature the studies on the phytochemical, ethnopharmacological and biotechnological applications of this genus, from 1998 to 2017. Among the sixty-one studies reported in this review, ten species are popularly utilized to pharmacological and/or biotechnological applications. Cnidoscolus aconitifolius and Cnidoscolus chayamansa are the most cited species, which were also supported by either animal or cellular investigations indicating some beneficial pharmacological actions like antioxidant, anti-inflammatory and potential cytotoxic activity. The plant parts of this genus under study are important as sources for the isolation and identification of bioactive molecules with biotechnological applications, among the many diseases treated with this phytotherapy. Given these verdicts, ethnopharmacological approaches are significant systematic tools in the determination of plant species that exhibit medicinal and nutritional purposes. The results presented here should further stimulate the development of validation studies to ensure the safe and effective use of these plant species.

Chagas disease is caused by infection with the protozoan Trypanosoma cruzi (T. cruzi) and is an important cause of severe inflammatory heart disease. However, the mechanisms driving Chagas disease cardiomyopathy have not been completely elucidated. Here, we show that the canonical PI3Kγ pathway is upregulated in both human chagasic hearts and hearts of acutely infected mice. PI3Kγ-deficient mice and mutant mice carrying catalytically inactive PI3Kγ are more susceptible to T. cruzi infection. The canonical PI3Kγ signaling in myeloid cells is essential to restrict T. cruzi heart parasitism and ultimately to avoid myocarditis, heart damage, and death of mice. Furthermore, high PIK3CG expression correlates with low parasitism in human Chagas’ hearts. In conclusion, these results indicate an essential role of the canonical PI3Kγ signaling pathway in the control of T. cruzi infection, providing further insight into the molecular mechanisms involved in the pathophysiology of chagasic heart disease., Trypanosoma cruzi infection causes Chagas disease, but mechanisms underlying pathogenesis are unclear. Here, Silva et al. show that canonical PI3Kγ signaling in myeloid cells restricts T. cruzi infection in mice and that high PIK3CG expression correlates with low parasite levels in human Chagas’ hearts.

Polymorphism of the calcium-sensing receptor gene (CaSR or CaR) has been associated with an increased risk for breast cancer. This receptor plays an important role in calcium homeostasis, and has also been detected in several tissues that are unrelated to calcium metabolism, such as the skin, brain, and breast. The calcium-sensing receptor on cellular level, it regulates cell differentiation, proliferation, cell death, and gene expression. In breast cancer cells, CaSR seems to stimulate secretion of the parathyroid hormone-related protein (PTHrP), which stimulates cellular proliferation. Likewise, some studies have supported not only an association between calcium receptor gene polymorphism and breast cancer risk, but also a higher aggressiveness and unfavorable outcomes in breast cancer, which led us to make a survey in Pubmed on the subject in the last 10 years. Thus, in the literature there is a paucity of studies on the subject and the aim of this review was to show the role of calcium-sensing receptor and its association with breast cancer risk.

Mutations in NOD2 predisposes to Inflammatory Bowel Diseases. Therefore, we evaluated the role of this innate receptor in the modulation of immunity in face of host microbiota changes. NOD2-/- mice presented higher susceptibility to experimental colitis than WT, with increased CD4 and CD8 T lymphocytes in the spleen. NOD2 deficiency also led to reduced Th17-related cytokines in the colon, with overall augmented IFN-γ in the gut and spleen. Nonetheless, there was increased frequency of CD4+IL-4+ cells in the mesenteric lymph nodes besides elevated CTLA-4 and FoxP3 regulatory markers in the spleen of NOD2-/- mice, although it did not result in more efficient control of gut inflammation. Indeed, these animals also had augmented IL-1β and IL-5 in the peritoneum, indicating that this receptor may be important to control bacteria translocation too. Microbiota exchanging between cohoused WT and NOD2-/- mice led to colitis worsening in the absence of the receptor, while antibiotic therapy in WT mice abrogated this effect. Then, not only the genetic mutation confers increased susceptibility to inflammation, but it is also influenced by the microbiota harbored by the host. Finally, NOD2-/- mice are more prone to intestinal inflammation due to deregulated immune response and increased susceptibility to colitogenic bacteria.

Made available in DSpace on 2018-11-26T15:47:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-03-01 Breast cancer is a disease of unknown etiology, whose major risk factors are genetic alterations. Polymorphism of the calcium-sensing receptor (CaSR) has been a focus of some recent studies, due to a probable association with breast cancer risk and tumor aggressiveness. A relationship between polymorphic rs17251221 variant of the CaSR gene, and allele G (considered a gain-of-function mutation) and breast cancer risk has been stressed, despite the paucity of studies found in the literature. The present study involved 137 women (69 women with breast cancer-case; and 68 controls without breast cancer) who had 3 ml of peripheral blood drawn for DNA study. Genomic DNA was extracted from leukocytes by genotyping technique with real-time polymerase chain reaction. The AG genotype (rs17251221) was present in 13 women (18.84%) from the case group and in 8 (11.76%) women from the control group (p = 0.3434), while the GG genotype (rs17251221) did not occur in any group. In contrast, no statistically significant difference was observed between the AG genotype of variant rs17251221 in premenopausal case and control women (p = 0.71). There was also no statistically significant difference between postmenopausal case and control patients (p = 0.6851). In the current study, CaSR gene polymorphism of SNP variant rs17251221 did not show any statistically significant association with breast cancer, in both premenopausal and postmenopausal women. Univ Fed Piaui, Postgaduate Program Hlth & Sci, BR-64049550 Teresina, Brazil Univ Fed Piaui, Postgrad Program Northeast Network Biotechnol REN, BR-64049550 Teresina, Brazil Univ Fed Piaui, Natan Portella Hosp, Dept Mol Biol, BR-64001450 Teresina, Brazil State Univ Sao Paulo, Dept Stat, BR-03178200 Sao Paulo, Brazil Univ Fed Sao Paulo, Dept Mastol, BR-04023900 Sao Paulo, Brazil State Univ Sao Paulo, Dept Stat, BR-03178200 Sao Paulo, Brazil

To analyze the participation of the enzyme 5-lipoxygenase (5-LO) in skin repair, WT wounds were compared to those in 5-LO deficient mice (5-LO-/-), which presented faster closure and reduced inflammatory infiltrate in the skin, together with increased CD4 regulatory T cells markers in the draining lymph nodes. The 5-LO-/- wounds also had diminished TNF-α, CCL11, CCL7, CCL2, CXCL9, CCR1 and CXCR2 mRNA expression in the lesions, besides differential extracellular matrix remodeling. Furthermore, when cysteinyl leukotriene (cysLT) and leukotriene (LTB4) receptors were antagonized in WT mice, there was a remarkable reduction in TNF-α expression and faster skin healing, similarly to the findings in 5-LO-/- animals. Finally, our results suggested that 5-LO products, in special cysLT and LTB4, underline skin inflammation that follows skin injury and their neutralization may be an important strategy to improve cutaneous healing.

Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each year and can induce chagasic megacolon. Little is known about how serotonin (5-HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters T. cruzi infection in the colon.Forty-eight paraffin-embedded samples from normal colon and chagasic megacolon were histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout (KO) mice and c-KitIn both humans and experimental mouse models, the serotonergic system was activated by T. cruzi infection (p 0.05). While treating Tph1KO mice with 5-HT did not significantly increase parasitemia in the colon (p 0.05), rescuing its synthesis promoted trypanosomiasis (p 0.01). T. cruzi-related 5-HT release (p 0.05) seemed not only to increase inflammatory signaling, but also to enlarge the pericryptal macrophage and mast cell populations (p 0.01). Knocking out mast cells reduced trypanosomiasis (p 0.01), although it did not further alter the neuroendocrine cell number and Tph1 expression (p 0.05). Further experimentation revealed that pharmacologically inhibiting mast cell activity reduced colonic infection (p 0.01). A similar finding was achieved when 5-HT synthesis was blocked in c-KitWe show that mast cells may modulate the T. cruzi-related increase of 5-HT synthesis in the intestinal colon.

Funda??o Amaz?nia Paraense de Amparo ? Pesquisa. Grant Number: ICAAF 099/2014 Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico. Grant Number: 311686/2015?0 Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Tecnologia Biomolecular. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Tecnologia Biomolecular. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Tecnologia Biomolecular. Bel?m, PA, Brazil. ? Universidade Federal do Par?. Instituto de Ci?ncias Naturais. Laborat?rios de Investiga??o Sistem?tica em Biotecnologia e Biodiversidade Molecular. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Tecnologia Biomolecular. Bel?m, PA, Brazil. Lectins are proteins of nonimmune origin, which are capable of recognizing and binding to glycoconjugate moieties. Some of them can block the interaction of viral glycoproteins to the host cell receptors acting as antiviral agents. Although cyanobacterial lectins have presented broad biotechnological potential, little research has been directed to Amazonian Cyanobacterial diversity. In order to identify new antiviral lectins, we performed genomic analysis in seven cyanobacterial strains from Cole??o Amaz?nica de Cianobact?rias e Microalgas (CACIAM). We found 75 unique CDS presenting one or more lectin domains. Since almost all were annotated as hypothetical proteins, we used homology modeling and molecular dynamics simulations to evaluate the structural and functional properties of three CDS that were more similar to known antiviral lectins. Nostoc sp. CACIAM 19 as well as Tolypothrix sp. CACIAM 22 strains presented cyanovirin?N homologues whose function was confirmed by binding free energy calculations. Asn, Glu, Thr, Lys, Leu, and Gly, which were described as binding residues for cyanovirin, were also observed on those structures. As for other known cyanovirins, those residues in both our models also made favorable interactions with dimannose. Finally, Alkalinema sp. CACIAM 70d presented one CDS, which was identified as a seven?bladed beta?propeller structure with binding sites predicted for sialic acid and N?acetylglucosamine. Despite its singular structure, our analysis suggested this molecule as a new putative antiviral lectin. Overall, the identification and the characterization of new lectins and their homologues are a promising area in antiviral research, and Amazonian cyanobacteria present biotechnological potential to be explored in this regard.