Identification of immunodominant epitopes of Schistosoma mansoni vaccine candidate antigens using human T cells

Paramyosin and Sm14 are two of the six antigens selected by the World Health Organization as candidates to compose a subunit vaccine against schistosomiasis. Both antigens are recognized by individuals naturally resistant to Schistosoma mansoni infection and induced protective immunity in the murine model. Three Sm14 epitopes and eleven paramyosin epitopes were selected by their ability to bind to different HLA-DR molecules using the TEPITOPE computer program, and these peptides were synthetically produced. The cellular recognition of Sm14 and paramyosin epitopes by peripheral blood mononuclear cells of individuals living in endemic area for schistosomiasis was tested by T cell proliferation assay. Among all Sm14 and paramyosin epitopes studied, Sm14-3 was preferentially recognized by individuals naturally resistant to S. mansoni infection while Para-5 was preferentially recognized by individuals resistant to reinfection. These two peptides represent promising antigens to be used in an experimental vaccine against schistosomiasis, since their preferential recognition by resistant individuals suggest their involvement in the induction of protective immunity

CXCR1 and SLC11A1 polymorphisms affect susceptibility to cutaneous leishmaniasis in Brazil: a case-control and family-based study.

BACKGROUND: L. braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. Wound healing neutrophil (PMN) and macrophage responses made following the bite of the vector sand fly contribute to disease progression in mice. To look at the interplay between PMN and macrophages in disease progression in humans we asked whether polymorphisms at genes that regulate their infiltration or function are associated with different clinical phenotypes. Specifically, CXCR1 (IL8RA) and CXCR2 (IL8RB) are receptors for chemokines that attract PMN to inflammatory sites. They lie 30-260 kb upstream of SLC11A1, a gene known primarily for its role in regulating macrophage activation, resistance to leishmaniasis, and wound healing responses in mice, but also known to be expressed in PMN, macrophages and dendritic cells. METHODS: Polymorphic variants at CXCR1, CXCR2 and SLC11A1 were analysed using Taqman or ABI fragment separation technologies in cases (60 CL; 60 ML), unrelated controls (n = 120), and multicase families (104 nuclear families; 88 ML, 250 CL cases) from Brazil. Logistic regression analysis, family-based association testing (FBAT) and haplotype analysis (TRANSMIT) were performed. RESULTS: Case-control analysis showed association between the common C allele (OR 2.38; 95% CI 1.23-4.57; P = 0.009) of CXCR1_rs2854386 and CL, supported by family-based (FBAT; Z score 2.002; P = 0.045) analysis (104 nuclear families; 88 ML, 250 CL cases). ML associated with the rarer G allele (Z score 1.999; P = 0.046). CL associated with a 3' insertion/deletion polymorphism at SLC11A1 (Z score 2.549; P = 0.011). CONCLUSIONS: The study supports roles for CXCR1 and SLC11A1 in the outcome of L. braziliensis infection in humans. Slc11a1 does not influence cutaneous lesion development following needle injection of Leishmania in mice, suggesting that its role here might relate to the action of PMN, macrophage and/or dendritic cells in the wound healing response to the sand fly bite. Together with the CXCR1 association, the data are consistent with hypotheses relating to the possible role of PMN in initiation of a lesion following the delivery of parasites via the sand fly bite. Association of ML with the rare derived G allele suggests that PMN also have an important positive role to play in preventing this form of the disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

MARKETING VERDE: PESQUISA SOBRE O CONHECIMENTO DAS PESSOAS ACERCA DE SEUS CONCEITOS

Introdução Marketing verde é uma tática utilizada pelas empresas no processo de vendas de produtos que são baseados nos benefícios do meio ambiente, é a ideia de criar um produto com a imagem ecologicamente consciente, para compreender o funcionando do Marketing Verde é preciso antes entender a importância do abandono dos velhos hábitos adotando atitudes ambientais, com a valorização do meio ambiente. As empresas buscam novas tendências para agregar valores em seus produtos a tática do Marketing Verde veio como um novo recurso para impulsionar o consumo de produtos e serviços ecologicamente corretos. Objetivos: Verificar através de um questionário sobre o conhecimentos das pessoas acerca do marketing verde. Material de métodos O estudo iniciou-se por meio de pesquisas bibliográficas, a fim de obter resposta sobre o assunto em questão. O método adotado da pesquisa é “quali-quantitativa” sendo realizada a aplicação de questionário (on-line). Os materiais utilizados foram livros de bibliotecas e sites acadêmicos disponibilizados na internet. Esta pesquisa foi aprovado pelo comitê de ética em pesquisa da Faculdade Patos de Minas (Parecer CAAE: 86626518.0.0000.8078) Resultados e discussão Questionou-se sobre a veracidade do Marketing Verde feito pelas empresas constatou-se nas respostas que 62% dos voluntários estão incertos da credibilidade do comprometimento ambiental proposto pelas empresas, sendo que, 16% acreditaram no não comprometimento da empresa e apenas 21% acreditam no comprometimento. Questionou-se sobre a crise ambiental 92% dos voluntários acreditam que existe uma crise ambiental instalada. Questionou-se o que voluntários fazem para melhorar a crise ambiental, 37% dizem que não tem feito nada, e 32% dizem consumir menos por conhecer os produtos e 16% responderam não ao questionamento. Os demais resultados não apresentam respostas pertinentes. Questionou-se aos voluntários, se eles se consideram consumistas, 43% alegam que as vezes são consumistas, 36% dizem que não e 18% afirmam que são consumistas. Questionou-se o que cada um deles tem feito para melhorar a qualidade ambiental do planeta, a maioria das pessoas disseram ter conhecimento que existe uma crise ambiental, mas mesmo assim disseram não contribuir para mudar essa realidade. Percebe-se a existência de muitas dúvidas em relação ao Marketing Verde

Associação de citocinas, incapacidade neurológica e duração da doença em pacientes com mielopatia associada ao HTLV-I/paraparesia espástica tropical (MAH/PET)

OBJECTIVE: To identify clinical and immunological markers associated with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD: 237 HTLV-I infected individuals were clinically assessed. They were classified according to the Expanded Disability Status Scale (EDSS) and Osame s Motor Disability Score (OMDS). Cytokine levels were determined in HTLV-I seropositive individuals. RESULTS: 37 patients had HAM/TSP. There was a correlation between the degrees of disability assessed by both scales. There was also a correlation between the duration of HAM/TSP and the severity of disability assessed by either EDSS or OMDS. Higher levels of IFN-g were detected in unstimulated peripheral blood mononuclear cells (PBMC) from HAM/TSP patients as compared with HTLV-I carriers. CONCLUSION: This study shows the validity of the neurological scales to classify the degree of neurological disability in HTLV-I carriers and suggests a progressive behavior of HAM/TSP. This study also shows that IFN-g in PBMC supernatants are markers of HAM/TSP. ________________________________________________________________________________________ RESUMO: OBEJETIVO: Identificar marcadores clínicos e imunológicos associados com a mielopatia associada ao HTLV-I/paraparesia espástica tropical (MAH/PET). MÉTODO: 237 indivíduos infectados pelo HTLV-I foram clinicamente avaliados. Eles foram classificados de acordo com a escala expandida do estado de incapacidade de Kurtzke (EDSS) e escala de incapacidade motora de Osame (OMDS). Níveis de citocinas foram determinados nos indivíduos. RESULTADOS: 37 pacientes tinham MAH/PET. Houve correlação entre os graus de incapacidade pelas escalas. Houve também correlação entre a duração da MAH/PET e o grau da incapacidade pelas escalas. Níveis elevados de IFN-g foram detectados em células mononucleares de sangue periférico (CMSP) não estimuladas de pacientes com MAH/PET quando comparados com indivíduos HTLV-I positivos assintomáticos. CONCLUSÃO: Os dados demonstram a validade das escalas neurológicas para classificar o grau de incapacidade neurológica em portadores do HTLV-I e sugerem o comportamento progressivo da MAH/PET. Este estudo também demonstra que os níveis de IFN-g em sobrenadante de CMSP são marcadores da MAH/PET

High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16

Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention.Funded by Grants # 2011/24035-2 and # 2012/23290-1, São Paulo Research Foundation (FAPESP

O que a nova forma de pagamento digital (Pix) altera na regulação brasileira e nos contratos com as instituições financeiras?

O presente artigo realiza uma análise aprofundada do método de pagamento Pix — introduzido pelo Banco Central do Brasil (BCB) no Sistema de Pagamentos Brasileiros no último semestre de 2020. O problema pelo qual o artigo se debruça é como o Pix irá impactar o Sistema de Regulação Brasileiro e nos contratos dos particulares com as Instituições Financeiras. O principal objetivo da pesquisa é analisar o papel regulatório do Estado e a sua relação, de caráter interventor, com o novo mecanismo de pagamento. Por meio de uma avaliação do regime de direito bancário, dos contratos de depósito e abertura de contas, o artigo também terá como objetivo descrever as transformações institucionais que a ferramenta propõe no âmbito do Sistema Financeiro Nacional (SFN). A pesquisa também tem como objetivo compreender o contexto tecnológico de inserção do modelo de pagamento, bem como o contrapor em relação aos demais mecanismos existentes de open banking. Ademais, trabalho também terá como objetivo investigar os impactos positivos e negativos do novo ecossistema de pagamentos instantâneos, avaliando a possibilidade de sistematização em uma estrutura centralizada, regulamentada e fiscalizada pelo BCB. A metodologia do artigo consistirá em um estudo das regulamentações do Banco Central acerca do tema, dos textos da literatura corrente, e das reportagens e notícias recentes sobre o modelo. A principal hipótese a ser analisada no texto é de que o Pix oferece mudanças significativas no Sistema Financeiro Nacional, modernizando o sistema de pagamentos e oferecendo diversas vantagens aos usuários, que vão possuir praticidade, rapidez e segurança nas suas transações financeiras. Finalmente, a conclusão deste artigo é de que o Pix não altera a modalidade de contrato entre particulares e Instituições Financeiras, mas impacta de forma significativa o modo de regulação dessas relações financeiras, pois, com a nova ferramenta, se mostra necessário apresentar mecanismos que trarão segurança aos usuários nas operações financeiras realizadas pelo Pix

Enhanced Leishmania braziliensis Infection Following Pre-Exposure to Sandfly Saliva

Parasites of the genus Leishmania cause a variety of diseases known as leishmaniasis, that are transmitted by bites of female sand flies that, during blood-feeding, inject humans with parasites and saliva. It was shown that, in mice, immunity to sand-fly saliva is able to protect against the development of leishmaniasis. We have investigated, in the present study, whether this finding extends the sand fly species Lutzomyia intermedia, which is responsible for transmission of Leishmania braziliensis, a parasite species able to cause destructive skin lesions that can be fatal if left untreated. We observed that mice injected with sand fly saliva develop a specific immune response against salivary proteins. Most importantly, however, this immune response was unable to protect mice against a challenge infection with L. braziliensis, indicating that exposure to this sand fly saliva is harmful to the host. Indeed, subjects with cutaneous leishmaniasis have a higher immune response against L. intermedia saliva. These findings indicate that the anti-saliva immune response to sand fly saliva plays an important role in the outcome of leishmaniasis caused by L. braziliensis, in both mice and humans, and emphasize possible hurdles in the development of vaccines based on sand fly saliva

BALB/c Mice Infected with Antimony Treatment Refractory Isolate of Leishmania braziliensis Present Severe Lesions due to IL-4 Production

Leishmaniasis is a neglected disease that affects more than 12 million people worldwide. In Brazil, the cutaneous disease is more prevalent with about 28,000 new cases reported each year, and L. braziliensis is the main causative agent. The interesting data about the infection with this parasite is the wide variety of clinical manifestations that ranges from single ulcerated lesions to mucocutaneous and disseminated disease. However, experimental models to study the infection with this parasite are difficult to develop due to high resistance of most mouse strains to the infection, and the mechanisms underlying the distinct manifestations remain poorly understood. Here, the authors use a mouse experimental model of infection with different L. braziliensis isolates, known to induce diseases with distinct severity in the human hosts, to elucidate immune mechanisms that may be involved in the different manifestations. They showed that distinct parasite isolates may modulate host response, and increased IL-4 production and Arg I expression was related to more severe disease, resulting in longer length of disease with larger lesions and reduced parasite clearance. These findings may be useful in the identification of immunological targets to control L. braziliensis infection and potential clinical markers of disease progression