Probing the role of the 37kDa/67kDa laminin receptor in amyloid beta mediated pathogenesis in alzheimer's disease

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2014.Alzheimer’s Disease (AD) is characterized by neurofibrillary tangles, senile plaques and neuronal loss. Although the mechanisms underlying Amyloid beta 42 (Aβ42) neurotoxicity have not been firmly established, it is proposed that the neuronal loss is elicited through associations with cell surface receptors. The cellular prion protein (PrPc) has been identified as an Aβ42 receptor and as a regulator of the amyloidogenic cleavage pathway. As Aβ42 shares common binding partners with the 37kDa/67kDa laminin receptor (LRP/LR), including PrPc, we investigated whether these proteins interact and assessed the pathological significance of this association. LRP/LR was found to co-localize with Aβ on the cell surface. The occurrence of FRET suggested that an interaction between LRP/LR and Aβ indeed exists at the cell surface. Furthermore, pull down assays and Aβ-specific ELISAs demonstrated that LRP/LR forms a physical association with endogenously shed Aβ, thereby verifying the physiological relevance of this association. Antibody blockade by IgG1-iS18 and shRNAmediated downregulation of LRP/LR significantly enhanced cell viability and proliferation and decreased apoptosis in cells co-treated with Aβ42 when compared to cells incubated with Aβ42 alone. In addition, antibody blockade and shRNA-mediated downregulation of LRP/LR significantly impeded Aβ42 internalization. These results suggest that LRP/LR acts as an internalization receptor for Aβ42 and may thereby contribute to the cytotoxicity of the neuropeptide by facilitating intracellular Aβ42 accumulation and aggregation - which has consequences for cell proliferation and may promote apoptosis. These findings recommend anti-LRP/LR specific antibodies and shRNAs as potential therapeutic tools for Alzheimer’s Disease treatment

Comportamento do consumidor na tomada de decisão para compras em pet shops da cidade de Porto Alegre/RS

O presente estudo objetivou compreender o processo de tomada de decisão de compra de produtos e serviços em Pet Shops da cidade de Porto Alegre/RS. A metodologia utilizada para a produção deste trabalho, caracterizou-se pela realização de uma pesquisa em duas etapas, a primeira qualitativa, através da realização de entrevistas em profundidade por meio de um roteiro semiestruturado aplicado em agosto de 2022 a 11 entrevistados, e a segunda, cuja amostra foi de 131 respondentes. Verificou-se que o consumidor tem por necessidade o bem-estar do animal, que ele busca as informações necessárias na internet, e que aceita as recomendações dos atendentes de Pet Shop para decidir entre as opções de produtos. E que a qualidade do produto é o atributo que os consumidores mais valorizam.The present study aimed to understand the decision-making process to purchase products and services in Pet Shops in the city of Porto Alegre/RS. The methodology used for the production of this work was characterized by carrying out a research in two stages, the first qualitative, through in-depth interviews through a semistructured script applied in August 2022 to 11 respondents, and the second, whose sample consisted of 131 respondents. It was found that the consumer has the animal's well-being as a necessity, that he seeks the necessary information on the internet, and that he accepts the recommendations of Pet Shop attendants to decide between the product options. And that product quality is the attribute that consumers value most

NA PERIFERIA DO SUCESSO: RÁDIO E MÚSICA POPULAR DE MASSA EM BELÉM NAS DÉCADAS DE 1940 E 1950

Este artigo trata da difusão musical promovida pelas rádios paraenses Clube e Marajoara em meados do século XX, como representativa de uma tendência local de hibridação cultural no campo da música. As emissoras sediadas em Belém, naquele período, estavam distantes dos centros dinâmicos da indústria cultural do país e do mecanismo midiático nacional de fabricação de cantores, conjuntos e ritmos musicais de sucesso. Porém, a interação local entre produtores de rádio, ouvintes e participantes de programas de auditório permitia a formação de um padrão local de consumo musical e a configuração de um star system, que combinava artistas locais, nacionais e estrangeiros

Chronic HIV-1 Infection Alters the Cellular Distribution of FcγRIIIa and the Functional Consequence of the FcγRIIIa-F158V Variant

Chronic HIV-infection modulates the expression of Fc gamma receptors (FcγRs) on immune cells and their antibody-dependent effector function capability. Given the increasingly recognized importance of antibody-dependent cellular cytotoxicity (ADCC) in HIV-specific immunity, we investigated the cellular distribution of FcγRIIIa on cytotoxic lymphocytes—natural killer cells and CD8+ T cells—and the effect of the FcγRIIIa-F158V variant on ADCC capacity in HIV-infected individuals (n = 23) and healthy controls (n = 23). Study participants were matched for F158V genotypes, carried two copies of the FCGR3A gene and were negative for FcγRIIb expression on NK cells. The distribution of CD56dimFcγRIIIabright and CD56negFcγRIIIabright NK cell subsets, but not FcγRIIIa surface expression, differed significantly between HIV-1 negative and HIV-1 positive donors. NK cell-mediated ADCC responses negatively correlated with the proportion of the immunoregulatory CD56brightFcγRIIIadim/neg cells and were lower in the HIV-1 positive group. Intriguingly, the FcγRIIIa-F158V variant differentially affected the NK-mediated ADCC responses for HIV-1 negative and HIV-1 positive donors. Healthy donors bearing at least one 158V allele had higher ADCC responses compared to those homozygous for the 158F allele (48.1 vs. 34.1%), whereas the opposite was observed for the HIV-infected group (26.4 vs. 34.6%), although not statistically significantly different. Furthermore, FcγRIIIa+CD8bright and FcγRIIIa+CD8dim T cell subsets were observed in both HIV-1 negative and HIV-1 positive donors, with median proportions that were significantly higher in HIV-1 positive donors compared to healthy controls (15.7 vs. 8.3%; P = 0.016 and 18.2 vs. 14.1%; P = 0.038, respectively). Using an HIV-1-specific GranToxiLux assay, we demonstrate that CD8+ T cells mediate ADCC through the delivery of granzyme B, which was overall lower compared to that of autologous NK cells. In conclusion, our findings demonstrate that in the presence of an HIV-1 infection, the cellular distribution of FcγRIIIa is altered and that the functional consequence of FcγRIIIa variant is affected. Importantly, it underscores the need to characterize FcγR expression, cellular distribution and functional consequences of FcγR genetic variants within a specific environment or disease state

Excitação ultravioleta em sistemas vítreos e cristalinos para aplicações em dispositivos ópticos

-Este projeto tem por objetivo o estudo dos processos ópticos chamados de conversão descendente de energia, nos quais energia luminosa Ultra Violeta pode ser convertida em visível e/ou infravermelha. Para tanto, propomos a expansão do alcance espectral da técnica de luminescência já disponível na UFJF, e que hoje opera na região do visível ao infravermelho, para incluir a região Ultra Violeta (UV) do espectro. Os sistemas de estudo propostos são materiais luminescentes com transições eletrônicas na região de 350 nm até 650 nm. Estas emissões podem ser originárias de níveis discretos de íons terras raras inseridos em sistemas vítreos ou amorfos, como também de transições entre a banda de condução e valência de semicondutores de gap largo. O interesse nessa região do espectro eletromagnético se dá em função da possibilidade de confecção de uma nova geração de dispositivos ópticos, como LEDs brancos, azuis e UV, lasers azuis e UV, displays planos RGB e lâmpadas fluorescentes sem mercúrio, nos quais o foco de estudo está centrado na obtenção de alta eficiência de conversão luminosa (e portanto baixa geração de calor)

Fluxos Turbulentos de Dióxido de Carbono Sobre o Reservatório da Usina Hidrelétrica de Itaipu – PR

Fluxos turbulentos de dióxido de carbono (CO2) foram medidos sobre o reservatório da usina hidrelétrica de Itaipu durante 13 dias de dezembro de 2012. Nessa campanha, notou-se que no período diurno os fluxos de CO2 eram controlados pela radiação solar incidente, sendo que se constatou fixação de  CO2 pelo reservatório durante o dia

Age at antiretroviral therapy initiation and cell-associated HIV-1 DNA levels in HIV-1-infected children

Background The latent viral reservoir is the major obstacle to achieving HIV remission and necessitates life-long antiretroviral therapy (ART) for HIV-infected individuals. Studies in adults and children have found that initiating ART soon after infection is associated with a reduction in the size of the HIV-1 reservoir. Here we quantified cell-associated HIV-1 DNA in early-treated but currently older HIV-infected children suppressed on ART. Methods The study participants comprised of a cohort of 146 early-treated children with HIV-1 RNA <50 copies/ml enrolled as part of a clinical trial in Johannesburg, South Africa. A stored buffy coat sample collected after a median 4.3 years on ART and where HIV-1 RNA was <50 copies/ml was tested for cell-associated HIV-1 DNA levels. An in-house, semi-nested real-time quantitative hydrolysis probe PCR assay to detect total HIV-1 subtype C proviral DNA was used. Children were followed prospectively for up to 3 years after this measurement to investigate subsequent HIV-1 RNA rebound/failure while remaining on ART. Age at ART initiation, HIV-1 RNA decline prior to HIV-1 DNA measurement and other factors were investigated. Results A gradient between age at ART initiation and later HIV-1 DNA levels was observed. When ART was started 50 copies/ml whilst on ART within 3 years after the DNA measurement was 2.07 (95% CI: 1.352–3.167) times greater if the HIV-1 DNA level was above the median of 55 copies/106 cells. Conclusions Cell-associated HIV-1 DNA levels measured after more than 4 years on ART were lower the younger the age of the child when ART was initiated. This marker of the size of the viral reservoir also predicted subsequent viral rebound/treatment failure while ART was sustained. The results provide additional evidence of the benefits of prompt diagnosis and early ART initiation in newborns and infants

Knock-down of the 37kDa/67kDa laminin receptor LRP/LR impedes telomerase activity.

Cancer has become a major problem worldwide due to its increasing incidence and mortality rates. Both the 37kDa/67kDa laminin receptor (LRP/LR) and telomerase are overexpressed in cancer cells. LRP/LR enhances the invasiveness of cancer cells thereby promoting metastasis, supporting angiogenesis and hampering apoptosis. An essential component of telomerase, hTERT is overexpressed in 85-90% of most cancers. hTERT expression and increased telomerase activity are associated with tumor progression. As LRP/LR and hTERT both play a role in cancer progression, we investigated a possible correlation between LRP/LR and telomerase. LRP/LR and hTERT co-localized in the perinuclear compartment of tumorigenic breast cancer (MDA-MB231) cells and non-tumorigenic human embryonic kidney (HEK293) cells. FLAG® Co-immunoprecipitation assays confirmed an interaction between LRP/LR and hTERT. In addition, flow cytometry revealed that both cell lines displayed high cell surface and intracellular LRP/LR and hTERT levels. Knock-down of LRP/LR by RNAi technology significantly reduced telomerase activity. These results suggest for the first time a novel function of LRP/LR in contributing to telomerase activity. siRNAs targeting LRP/LR may act as a potential alternative therapeutic tool for cancer treatment by (i) blocking metastasis (ii) promoting angiogenesis (iii) inducing apoptosis and (iv) impeding telomerase activity.This work was supported by the National Research Foundation, the Republic of South Africa.NCS201

Perceptions in the formation of graduates of residency in obstetric nursing: a described-exploratory study / As percepções na formação de egressos da residência em enfermagem obstétrica: estudo descrito-exploratório

Objetivo: compreender a percepção da formação de egressos da residência em enfermagem obstétrica. Método: pesquisa descritiva e exploratória, com abordagem qualitativa, com 14 egressos da residência em enfermagem obstétrica da Universidade Federal do Pará mediante de entrevista semiestruturada pelo aplicativo google meets, durante o período de outubro a dezembro de 2020. Os dados foram transcritos e submetidos à análise de conteúdo com auxílio do software ATLAS.ti 8.0. Resultados: a residência constitui pilar para trajetória profissional, com novos saberes e práticas para construção de competências profissionais, atuando em toda linha de cuidado do ciclo gravídico-puerperal. Mas, o modelo obstétrico centrado no médico e uma atuação volata mais para a burocracia, constituem com limitação da atuação dos egressos. Conclusão: a formação da residência possibilitou para os egressos o seu exercício com segurança, com os conhecimentos adquiridos, mas ainda necessita um amplo movimento para a garantia de sua prática.

Série de Williams adaptada associada ao treinamento resistido: análise do quadro da dor lombar em uma paciente idosa / Adapted Williams series associated with resistance training: analysis of low back pain in an elderly patient

O objetivo da pesquisa foi avaliar o grau de dor pela escala visual analógica (eva) antes e após a aplicação da série de williams adaptada (swa) aliada ao treinamento resistido (tr). A amostra foi constituída de uma paciente idosa de 83 anos, acometida de artrose e osteoporose lombar. O teste de eva foi realizado antes e após as 9 sessões. Com o tr houve diminuição no nível de dor