Transmissão de valores morais entre gerações de famílias em condições de vulnerabilidade social e econômica

Introduction: this study analysed the transmission of values between generations in groups of people in unfavourable economic and social conditions. It was carried out with grandparents, their children, and their grandchildren who are residents of a peripheral neighbourhood of the capital of São Paulo and live in restricted economic conditions and under the daily impact of violence. The study sought to determine how the passage of values between generations is processed, in view of the exposure to conditions of deprivation to which these people are subjected, while they carry the obligation to ensure the minimum for their children but do not have the necessary resources. This raises the question of how it is possible to affirm a notion of right and wrong within this social framework. The theoretical basis of this study was psychoanalysis, using the concepts of Identification, Ego Ideal, Ideal Ego, Oedipus, and the dynamics underlying the insertion of the father in the Oedipal triad. Methods: interviews were conducted through group meetings to discuss issues related to morals. These discussions involved the three generational components of three families. Different arrangements were made that involved the same generational group in an initial meeting and, in another meeting, the mixture of different generations and different families responding to pre-established themes that involved moral dilemmas focused on the daily cultural and social life of these families. Results: the grandfathers were ambiguous because they have a reference to a law of morals transcending space and time. Parents, realising the ambiguity of these grandparents in relation to reality, reformulate these moral questions, basing their convictions on a law that is established within the contingencies of everyday life and, therefore, changeable. The adolescent grandchildren perceive this ambiguity in the parents and in their speech. Conclusion: There is greater identification of moral standards among grandchildren and grandparents than between children and parents. The interviewed parents were ambiguous in the way they act and speak, with the transgenerational reproduction model being more guided between grandchildren and grandparents than in the sequential temporal generational sequence.Introdução: analisou a passagem dos valores entre as gerações em grupos de pessoas em condições econômico e sociais desfavoráveis. O estudo foi realizado com avôs, seus filhos e netos, moradores de um bairro periférico da capital de São Paulo que vivem em condições econômicas restritas e sob o impacto cotidiano da violência. Buscou-se responder como se processa a passagem de valores entre as gerações, tendo em vista a exposição a condições de privação a que estas pessoas estão submetidas, ao mesmo tempo que carregam a obrigação de assegurar o mínimo aos seus filhos, mas não dispõem de recursos para isso. O que se configura então, é a pergunta de como é possível afirmar uma noção de certo e errado diante deste quadro social. A base de sustentação teórica foi a Psicanálise, resgatando os conceitos de Identificação, Ego Ideal, Ideal de Ego, Édipo e as dinâmicas subjacentes à inserção do pai na tríade edípica. Método: foram realizadas entrevistas por meio de encontros grupais de discussão de assuntos relacionados à moral. Estas discussões envolveram os três componentes geracionais de três famílias, em diferentes arranjos que envolviam o mesmo grupo geracional em um primeiro momento e em outro a mescla de diferentes gerações e diferentes famílias respondendo a temáticas pré-estabelecidas e que envolviam dilemas morais focados no cotidiano cultural e social destas famílias. Resultados: os avôs se mostraram ambíguos pois possuem uma referência de Lei, de moral, deslocada no espaço e no tempo; os pais percebendo a ambiguidade destes avôs em relação à realidade reformulam estas questões morais pautando suas convicções em uma Lei que se estabelece dentro das contingências do cotidiano e, portanto, mutável; os netos adolescentes percebem esta ambiguidade nos pais e nos seus discursos. Conclusão: há maior identificação de padrões morais entre netos e avôs do que entre filhos e pais. Os pais entrevistados se mostraram ambíguos na forma de agir e de discursar, sendo o modelo de reprodução transgeracional mais pautado entre netos e avôs do que na sequência geracional temporal sequencial

The Genome of Anopheles darlingi, the main neotropical malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vectorhuman and vectorparasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles- darlingi. © 2013 The Author(s)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A polyvalent hybrid protein elicits antibodies against the diverse allelic types of block 2 in Plasmodium falciparum merozoite surface protein 1.

Merozoite surface protein 1 (MSP1) of Plasmodium falciparum has been implicated as an important target of acquired immunity, and candidate components for a vaccine include polymorphic epitopes in the N-terminal polymorphic block 2 region. We designed a polyvalent hybrid recombinant protein incorporating sequences of the three major allelic types of block 2 together with a composite repeat sequence of one of the types and N-terminal flanking T cell epitopes, and compared this with a series of recombinant proteins containing modular sub-components and similarly expressed in Escherichia coli. Immunogenicity of the full polyvalent hybrid protein was tested in both mice and rabbits, and comparative immunogenicity studies of the sub-component modules were performed in mice. The full hybrid protein induced high titre antibodies against each of the major block 2 allelic types expressed as separate recombinant proteins and against a wide range of allelic types naturally expressed by a panel of diverse P. falciparum isolates, while the sub-component modules had partial antigenic coverage as expected. This encourages further development and evaluation of the full MSP1 block 2 polyvalent hybrid protein as a candidate blood-stage component of a malaria vaccine