Cellular and serological responses to vaccination in chronic kidney disease

Chronic kidney disease (CKD) and haemodialysis (HD) are associated with an increased risk of hepatitis B infection due to exposure to the virus during haemodialysis, in conjunction with impaired seroconversion to hepatitis B vaccination (HBV). Studies examining augmented vaccine schedules to enhance seroconversion have so far been inconclusive. Furthermore, the cellular defects responsible for impaired vaccine immunity observed in CKD and HD have not yet been identified. This project studied serological and cellular responses to HBV in CKD and HD to identify defects in vaccine-induced cellular responses that could account for impaired seroconversion and clarify the effects of an augmented vaccine dose schedule. These results were compared with responses to seasonal influenza vaccination. There was a clear benefit in rates and magnitude of seroconversion after an augmented 40mcg HBV dose schedule in CKD. This permitted comparison of responders and non-responders. Serological non-responders with CKD exhibited a reduction in CXCR3+CCR6- CXCR5+ memory T cells at baseline. Seasonal influenza vaccine elicited a plasmablast (PB) response in both healthy controls and CKD, but HBV elicited a poor plasmablast response in both groups. Both vaccinations induced activation of the CXCR3+CCR6- subset of circulating T follicular helper cells (cTFH) in healthy controls, and but this response was impaired in CKD after HBV, even with the augmented 40mcg HBV dose schedule, and appears not to be reversed by haemodialysis. Despite this, some patients receiving haemodialysis generate detectable post-vaccination HBsAb, and this correlates with activation within the CXCR3+CCR6- cTFH compartment. We concluded that cellular responses to seasonal influenza vaccine are preserved in CKD and haemodialysis. However, CKD confers a specific defect in cTFH activation that contributes to the impaired seroconversion to HBV, and this defect persists despite renal replacement therapy with haemodialysis

REESTRUTURAÇÃO PRODUTIVA E IMPACTOS NA FORMAÇÃO EM SERVIÇO SOCIAL

RESUMO A discussão acerca das transformações no mundo do trabalho, no debate contemporâneo, e suas implicações com o Serviço Social serão abordadas neste texto, tomando com forma de desenho quatro eixos de discussão: a) as transformações em si como reflexo das transformações da acumulação capitalista centrada no capitalismo financeiro; b) os reflexos dessas transformações no mundo do trabalho e em particular na prática do Serviço Social; c) os reflexos dessa transformação apontado nas diferentes expressões da Questão Social e a insistência de alguns teóricos de enquandrar a Questão Social no manto de uma Nova Questão Social; e, por fim, na indicação do papel do serviço social a partir de propostas de formação diferenciada (formação presencial e a distância)

Structure and in Situ Stress Analysis of the Tazhong Uplift, NW China: Implications for Fault Reactivation

The Tarim Basin in northwest China is an intracratonic, poly-phase basin with a subsurface structure that records a protracted tectonic history associated with crustal accretion and amalgamation. Currently, the basin is bounded by actively deforming mountain belts but displays little evidence of active deformation within the basin. Here, detailed interpretation of 3D seismic reflection data and analysis of drilling-induced deformation in deep boreholes (e.g. borehole breakouts) are used to resolve uncertainties about the timing and distribution of past deformation, the effect of pre-existing structures on subsequent deformation, and the current in situ stress state in the Tazhong Uplift of the Central Tarim Basin. The geometry and kinematics of Ordovician thrust faults and folds, Silurian-Permian strike-slip faults, and Triassic igneous bodies and normal faults, along with stratigraphic relationships, suggest that creation of new faults, and reactivation of pre-existing faults occurred during tectonic events in the Paleozoic and Early Mesozoic; however, no evidence of faulting is observed in Late Mesozoic or Cenozoic strata in the Tazhong Uplift. The current in situ stress should favor extensional and strike-slip tectonics with maximum horizontal compression directed NE, which contrasts with past stress states in the basin inferred from Paleozoic and Mesozoic structures. In situ differential stress magnitude in the Tazhong Uplift (ranging from 94 to 170 MPa) is insufficient to reactivate the most optimally-oriented faults in the Central Tarim Basin, even though the basin is bounded by the active Tian Shan and Kunlun Shan thrust belts to the north- and south-west, and the left-lateral strike-slip Altyn Tagh fault to the south, all associated with the ongoing Himalayan-Tibetan orogeny. The low differential stress may be understood if the basin-bounding faults (particularly the Altyn Tagh fault) operate at low absolute shear stress, similar to continental transform faults such as the San Andreas fault, CA

Synthesis of 2,4,6-triamino-1,3,5- trinitrobenzene

The 2,4,6-triamino-1,3,5-trinitrobenzene (TATB) is perhaps the most thermostable and insensitive explosive known. Its low sensibility to shock makes it suitable for military and civil applications. TATB application is done either alone or in combination with another high energetic material. This study aimed at reporting the review about many processes to produce TATB and the problems associated with them, as well as suggest techniques like Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC), which can be useful in the characterization of this energetic compound

The contribution of the European UNESCO Global Geoparks for the 2030 Agenda for Sustainable Development – a study based on several data sources

With the approval of the International Geoscience and Geoparks Programme (IGGP) by UNESCO, in November 2015, the new designation ‘UNESCO Global Geoparks’ (UGGps) was created. Based on a holistic approach, and in a sense of territorial ownership of its inhabitants, where the creation of local companies and innovative local products is added, these territories aim at a true sustainable regional development. In this context, this research was developed in the framework of the 2030 Agenda for Sustainable Development (SD) seeking to understand whether and how the UGGps contribute to this universal endeavor. To this end, this study was based on a selection of 33 UGGps, located in 22 European countries, and based on four sources: the Progress Reports (PRs) presented during the biennium 2015-2016, the abstracts presented in two Geoparks conferences (Rokua, 2015, and English Riviera, 2016), a questionnaire fulfilled by the managers of the selected UGGps (2017), and interviews to elements of the staff and local inhabitants and stakeholders of the Marble Arch Caves UGGp (2019). This methodology allowed obtaining data from 91 ‘PRs’, 95 abstracts, 22 questionnaires, and five interviews. Taking into account the UGGp concept, the five pillars of the 2030 Agenda – People, Planet, Prosperity, Peace, and Partnership –, together with the 17 Sustainable Development Goals (SDGs), and the ‘Top Ten Focus Areas’ defined by the IGGP, this study was focused on trying to answer three research questions: 1) How do the European UGGps effectively contribute to the achievement of the 17 SDGs of the 2030 Agenda? And if so, do they contribute far more than the ‘Eight SDGs’ selected by the IGGP?; 2) How can these contributions be accounted for, in a qualitative approach? ; 3) How can some of these contributions be used as examples of good practices, demonstrating the real impact in the achievement of some of the 17 SDGs, within the scope of UNESCO’s strategies, in this field?. From the analysis of the obtained data, it was possible to achieve the main objectives of this study and to arrive at a positive answer to the posed research questions. Consequently, it was possible to demonstrate that the UGGps, directly or indirectly in their activities, contribute to the 17 SDGs. It was also feasible to prove that UGGps contribute effectively far more than the selected ‘Eight SDGs’. With the applied methodology, it was possible to identify the strengths, weaknesses, opportunities, and threats that UGGps currently face, concerning the SDGs and, in this context, a proposal for a new model of an 'Annual Progress Report’ was prepared for the UGGps, contemplating this reality. This study also sheds new light on the effective involvement of local communities in these territories and the need to adapt to new challenges, (e.g. pandemic COVID-19). Therefore, it is expected that this research may open new paths and generate innovative ideas for scientific projects related to the contribution of the UGGps to the achievement of the 17 SDGs of the 2030 Agenda, allowing to contribute to future actions and strategic plans developed by the management structures of the UGGps.Com a aprovação do Programa Internacional de Geociências e Geoparques (IGGP) pela UNESCO, em novembro de 2015, foi criada a nova designação ‘Geoparques Mundiais da UNESCO (UGGps). Assentes numa abordagem holística, e num sentido de pertença territorial dos seus habitantes, onde se acrescenta a criação de empresas locais e de produtos locais inovadores, estes territórios visam um verdadeiro desenvolvimento regional sustentável. Neste contexto, esta investigação foi centrada nos propósitos da Agenda 2030 para o Desenvolvimento Sustentável, procurando compreender se e como os UGGps contribuem para esse esforço universal. Para tal, este estudo baseou-se numa seleção de 33 UGGps, localizados em 22 países europeus, e com base em quatro fontes: os Relatórios de Atividades (PRs) relativos ao biénio 2015-2016, os resumos apresentados em duas conferências de Geoparques (Rokua, 2015 e English Riviera, 2016), um questionário preenchido pelos gestores dos UGGps selecionados (2017) e um conjunto de entrevistas realizadas a elementos da equipa, habitantes locais e parceiros do Marble Arch Caves UGGp (2019). Esta metodologia permitiu obter dados de 91 ‘PRs’, 95 resumos, 22 questionários e cinco entrevistas. Tendo em consideração o conceito de ‘Geoparque’, os cinco pilares da Agenda 2030 - Pessoas, Planeta, Prosperidade, Paz e Parcerias -, conjuntamente com os 17 Objetivos de Desenvolvimento Sustentável (ODS) e as 'Dez Principais Áreas de Foco' definidas pelo IGGP, este estudo focou-se em procurar responder a três questões de investigação: 1) Como é que os UGGps europeus contribuem efetivamente para a concretização dos 17 ODS da Agenda 2030? Em caso afirmativo, se estes contribuem para mais do que os 'Oito ODS' selecionados pelo IGGP?; 2) Como é que algumas dessas contribuições podem ser contabilizadas, tendo por base uma abordagem qualitativa?; 3) Como é que algumas dessas contribuições podem ser usadas como exemplos de boas práticas, demonstrando o real impacto na concretização de alguns dos 17 ODS, no âmbito das estratégias definidas pela UNESCO neste domínio?. A partir da análise dos dados obtidos foi possível atingir os principais objetivos deste estudo, e chegar a uma resposta positiva às questões de investigação colocadas. Consequentemente, foi exequível demonstrar que os UGGps, direta ou indiretamente nas suas atividades, contribuem para os 17 ODS. Foi também viável provar que os UGGps contribuem efetivamente para mais do que os 'Oito ODS'. Com a metodologia aplicada, foi possível identificar os pontos fortes, os pontos fracos, as oportunidades e as ameaças que os UGGps enfrentam atualmente, no que se refere aos ODS e, neste contexto, foi elaborada uma proposta para um novo modelo de ‘Relatório Anual de Atividades’ para os UGGps, contemplando esta realidade. Este estudo traz ainda uma nova luz sobre o efetivo envolvimento das comunidades locais nesses territórios e a necessidade de adaptação a novos desafios, (e.g. pandemia COVID-19). Espera-se que esta investigação possa abrir novos caminhos e gerar ideias inovadoras para projetos científicos relacionados com a contribuição dos UGGps para a consecução dos 17 ODS da Agenda 2030, permitindo contribuir para ações futuras e planos estratégicos desenvolvidos pelas estruturas de gestão dos UGGps

DNA polymerase proofreading: active site switching catalyzed by the bacteriophage T4 DNA polymerase

DNA polymerases achieve high-fidelity DNA replication in part by checking the accuracy of each nucleotide that is incorporated and, if a mistake is made, the incorrect nucleotide is removed before further primer extension takes place. In order to proofread, the primer-end must be separated from the template strand and transferred from the polymerase to the exonuclease active center where the excision reaction takes place; then the trimmed primer-end is returned to the polymerase active center. Thus, proofreading requires polymerase-to-exonuclease and exonuclease-to-polymerase active site switching. We have used a fluorescence assay that uses differences in the fluorescence intensity of 2-aminopurine (2AP) to measure the rates of active site switching for the bacteriophage T4 DNA polymerase. There are three findings: (i) the rate of return of the trimmed primer-end from the exonuclease to the polymerase active center is rapid, >500 s−1; (ii) T4 DNA polymerase can remove two incorrect nucleotides under single turnover conditions, which includes presumed exonuclease-to-polymerase and polymerase-to-exonuclease active site switching steps and (iii) proofreading reactions that initiate in the polymerase active center are not intrinsically processive

Genetic and humoral autoimmunity markers of type 1 diabetes: from theory to practice

O diabetes melito tipo 1 auto-imune (DM1A) resulta da destruição auto-imune seletiva das células-beta pancreáticas produtoras de insulina. O principal determinante genético de suscetibilidade para o DM1A está em genes do complexo principal de histocompatibilidade, no cromossomo 6p211.3 (locus IDDM1), responsável por 40% ou mais da agregação familiar dessa doença. O maior risco é conferido pelo genótipo do antígeno leucocitário humano HLA-DR3-DQA1* 0501-DQB1*0201/DR4-DQA1*0301-QB1*0302, e o haplótipo HLA-DR15-DQA1* 0102-DQB1*0602 é associado à proteção. Três outros loci relacionados à predisposição a DM1A são o número variável de freqüências repetidas (VNTR) do gene da insulina (IDDM2), que confere 10% da suscetibilidade genética, o antígeno-4 associado ao linfócito T citotóxico (CTLA-4) e o protein tyrosine phosphatasis nonreceptor-type 22 (PTPN22). Muitos outros genes suspeitos de predispor à auto-imunidade estão sendo investigados. O DM1A é freqüentemente associado com doença auto-imune tiroidiana, doença celíaca, doença de Addison e várias outras doenças auto-imunes, caracterizadas por auto-anticorpos órgãos-específicos, relacionados aos mesmos determinantes genéticos. Esses anticorpos são úteis na detecção de auto-imunidade órgão-específica antes do aparecimento da doença clínica, prevenindo comorbidades.Type 1 A diabetes mellitus (T1AD) results from the autoimmune destruction of the insulin producing pancreatic beta-cells. The largest contribution to genetic susceptibility comes from several genes located in the major histocompatibility complex on chromosome 6p21.3 (IDDM1 locus), accounting for at least 40% of the family aggregation of this disease. The highest-risk human leukocyte antigen HLA genotype for T1AD is DR3-DQA1*0501-DQB1*0201/DR4-DQA1*0301-DQB1*0302, whereas -DR15-DQA1*0102-DQB1*0602 haplotype is associated with dominant protection. Three other T1D loci associated with predisposition are the Variable Number for Tandem Repeats (VNTR) near the insulin gene (IDDM2), which accounts to 10% of genetic susceptibility, the Cytotoxic T-Lymphocyte-associated Antigen (CTLA-4)(IDDM 12) and the Protein Tyrosine Phosphatasis Nonreceptor-type 22 (PTPN22). Many other gene suspected to predispose to autoimmunity have been investigated. T1AD is frequently associated with autoimmune thyroid disease, celiac disase, Addison´s disease and many other autoimmune diseases, characterized by organ-specific autoantibodies and related to the same genetic background. Using these autoantibodies, organ specific autoimmunity may be detected before the development of clinical disease preventing significant morbidity

Dropping out of the Chemistry course at the University of Brasilia : students reasons to leave the course

Neste trabalho o escopo do estudo foi o da evasão do aluno do curso de Química da Universidade de Brasília, porém, com o objetivo de conhecer as razões que levaram os alunos, que ingressaram por vestibular, a saírem do curso antes da sua conclusão.This study aimed the investigation of the reasons that led undergraduate students of the Chemistry course at Universidade de Brasília to abandon the course before its conclusion. From the former students’ point of view, the reasons that led them to leave the course were related to aspects of their academic life prior to university entrance, expectations which failed to be met by the course, the intricate nature of the academic system, personal and social experiences. Abandonment is a consequence of the problems he encounters during the course and takes on a connotation of protest, more than of failure