Participación de JNK3 en los mecanismos de muerte neuronal e inflamación en procesos neurodegenerativos

[spa] La activación de JNK (c-Jun N-terminal Kinase) ha sido relacionada en modelos in vivo e in vitro con la neurodegeneración inducida por glutamato, ácido kaínico (KA) y privación neurotrófica. Además, la activación de la vía de JNK se ha descrito en enfermedades neurodegenerativas crónicas como la enfermedad de Alzheimer y la enfermedad de Parkinson. En mamíferos, se han identificado tres genes (Jnk1, Jnk2 y Jnk3) que codifican para distintas isoformas de JNK con diferente distribución tisular. Así, mientras que JNK1 y JNK2 están ampliamente distribuidas por los tejidos, JNK3 está básicamente localizada en el sistema nervioso central y, en menor medida, en corazón y testículo. La expresión de JNK3 específica de cerebro contribuye a que esta isoforma se presente como posible diana terapéutica en enfermedades neurodegenerativas. Además, diferentes estudios han evidenciado, que en ratones deficientes para JNK3 (Jnk3-/-), éstos demuestran neuroprotección y resistencia ante la excitotoxicidad del KA, ante la toxicidad del β-amiloide o en situaciones de hipoxia-isquemia. De acuerdo con esto, en la presente tesis se han estudiado los mecanismos moleculares y celulares responsables de la neuroprotección observada en ausencia de la isoforma JNK3, bajo la acción de diferentes estímulos neurotóxicos: i) el KA, como modelo experimental de epilepsia, y ii) el ácido 3-nitropropiónico (3NP), como modelo experimental de la enfermedad de Huntington. En primer lugar, se ha evidenciado que la falta de JNK3, además de reducir la muerte neuronal y la astrogliosis ante la acción del KA, modula la activación de otras MAPK, como ERK1/2 y p38. Sin embargo, la deleción de JNK3 no confiere neuroprotección ante la acción del 3NP, presentándose la vía de la calpaína/CDK5 como la responsable de la neuroprotección en este modelo experimental. En segundo lugar, se ha analizado la actividad transcripcional inducida por la ausencia de JNK3. Se ha observado una relación entre la falta de JNK3 y la activación de la vía de supervivencia de PI3K/AKT, mediante la regulación específica del gen Pik3cb. Además, esta relación no se ha detectado respecto a la ausencia de la isoforma JNK1. Por último, de acuerdo con los resultados obtenidos anteriormente se estudió comparativamente el efecto de la ausencia de JNK3 y JNK1 en el modelo del KA. Los análisis realizados de muerte neuronal, reactividad glial y expresión génica evidenciaron que la ausencia de JNK1, igual de lo que ocurría en ausencia de JNK3, mostraba neuroprotección frente a la muerte neuronal inducida por KA. En concordancia, se detectó una falta de inducción de los genes Fasl, Casp8 y Casp3 implicados en la vía extrínseca de la apoptosis tanto en ausencia de JNK3 como de JNK1. Por otro lado, la ausencia de JNK3 mostró una reducción de la reactividad astroglial y microglial inducida por KA, mientras que la ausencia de JNK1 manifestó una reducción de la reactividad astroglial. Sugiriendo que ambas isoformas divergen en las vías de actuación.[eng] The JNK pathway activation has been implicated in in vitro and in vivo models of neurodegeneration induced by glutamate, kainic acid (KA) and neurotrophic deprivation. Moreover, activation of the JNK pathway has been described in chronic neurodegenerative diseases. In mammals, there are three genes (Jnk1, Jnk2 and Jnk3) that encode different isoforms of JNK. Whereas JNK1 and JNK2 are widely distributed, JNK3 is mainly located in central nervous system and to a lesser extent in heart and testis. Specifically, JNK3 plays a crucial role in neuronal death and different studies have shown that the lack of the Jnk3 gene confers neuroprotection to kainic acid (KA), amyloid-β and hypoxia-ischemia situations. However, the specific mechanism involved in such neuroprotection has not yet been elucidated. The present thesis was undertaken in order to clarify the molecular and cellular mechanisms responsible for the neuroprotection observed in mice lacking Jnk3 in different neurodegeneration models: i) kainic acid epilepsy model and ii) 3-nitropropionic acid (3-NP) model of Huntington’s disease. Firstly, the results revealed that the lack of JNK3 protein attenuated the neuronal death induced by kainic acid and modulate the activation/inactivation of p38 and ERK1/2. Although the lack of JNK3 does not confer neuroprotection against 3-NP toxicity. Secondly, our results indicated that the activation of PI3K/AKT pathway in Jnk3 null mice was due to the increased of Pi3kcb transcription and this mechanism is specifically related to the lack of JNK3. Finally, according to the results obtained above, we comparatively analyzed the effect of the absence of JNK3 and JNK1 in KA model. Neuronal death, glial reactivity and gene expression analyses showed that the absence of JNK1, just as what detected in the absence of JNK3, showed neuroprotection against neuronal death induced by KA. Accordingly, a lack of induction of Fasl, Casp3 and Casp8 genes, involved in the extrinsic pathway of apoptosis, was detected in the absence of JNK3 and JNK1. Furthermore, the absence of JNK3 showed a reduction of microglial and astroglial reactivity, while the absence of JNK1 only showed a reduction of astroglial reactivity. Taking together, this data suggesting that both isoforms differ in the way of action

Ilha de cáries às moscas : percursos da atuação entre ilhas, cacos, buracos, caminhos & encruzilhadas.

Trabalho de Conclusão de Curso (graduação)—Universidade de Brasília, Instituto de Artes, Departamento de Artes Cênicas, 2021

O museu como espaço social: o caso do Museu De Arte Moderna Aloísio Magalhães no centro expandido continental do Recife / The museum as a social space: the case of the Aloísio Magalhães Museum Of Modern Art in the expanded continental center of Recife

A cidade é uma rede de vias, espaços livres e espaços edificados, cujas relações são de fundamental para compreender as cidades. No âmbito dos espaços edificados, este estudo enfoca o museu de arte na cidade contemporânea, tendo como objeto específico o Museu de Arte Moderna Aloísio Magalhães (MAMAM), situado no Recife. A teoria da arquitetura pode ser estudada a partir de suas causas (determinações ambientais, políticas, ideológicas etc.), como uma variável dependente, ou de se seus efeitos, isto é, através de seus impactos diretos nos usuários (funcionais, econômicos, sociológicos, bioclimáticos etc.), portanto, como variável independente. A presente metodologia fundamenta-se neste segundo grupo, especificamente, no campo da sintaxe espacial, enquanto teoria e ferramenta analítica da arquitetura, cuja investigação-chave é em que medida a arquitetura e o urbanismo interferem nas relações sociais (HILLIER e HANSON,1984: 2003). O enfoque da pesquisa é a análise morfológica dos leiautes espaciais do MAMAM, antes e pós reforma sofrida na década de 1990.  Possuindo um rico acervo permanente e exposições temporárias, defende-se que o museu tenha tanto um papel pedagógico como de transmissor de experiência espacial e social. Para que fosse empreendida a análise sintática dos espaços, primeiro, levantaram-se as plantas baixas do museu nos dois momentos em questão, para, depois, serem elaborados mapas convexos e grafos justificados  visando a averiguação dos tipos de espaços conforme categorizados por Hillier (1996). Posteriormente, foram realizados mapas de visibilidade, juntamente com simulações de agentes autômatos para investigar padrões de deslocamento nos espaços. Além disso, foram feitas observações e rastreamento de visitantes in loco. Após a análise dos dados, observou-se que a reforma ocorrida não parece ter tido um impacto relevante na integração visual dos ambientes, se comparada à configuração original, e, de acordo com as simulações de agentes autômatos, novos percursos mostram uma nítida distinção no deslocamento de visitantes, o que se deve a uma partição espacial mais complexa do que no leiaute anterior à reforma. Entende-se que os resultados apresentados são importantes por revelar informações valiosas ao entendimento do espaço estudado, estimulando desdobramentos futuros da pesquisa no campo da sintaxe espacial, que visem a produção de espaços expositivos mais positivos em relação ao seu potencial, tanto como espaço social, como caráter pedagógico-cultural

Projeto recriar-se: Artes plásticas: Desenhar e pintar para lá do que se vê

info:eu-repo/semantics/publishedVersio

Desafios para a conquista do direito à moradia digna no assentamento Ilha

This booklet has been prepared from the actions for the university extension project entitled "Housing and Environment: building dialogue on urbanization of the settlement Ilha”. The study was conducted in a community located on the south end of the city of Almirante Tamandaré, among Barigui and Tanguá rivers. This project was conducted by a group of professors and students of the Federal University of Technology - Paraná (UTFPR), Campus Curitiba. The main objective was to investigate ways of intervention in housing and urbanization of the settlement Ilha, for the regularization of their properties. However, throughout the project, the group found that regularization of this settlement was not possible, in view of the risk of flooding on site. Therefore, this booklet provides information about the area and the rivers in their surroundings, on the positive aspects of living there, brings the story of some struggles of residents for better living conditions, as well as suggestions of funding sources for facilitating a possible relocation of existing families.Esta cartilha foi elaborada durante as ações do projeto de extensão universitária, intitulado “Moradia e Meio Ambiente: a construção do diálogo na urbanização do assentamento Ilha”. O trabalho foi realizado numa comunidade localizada na extremidade sul do município de Almirante Tamandaré, entre os rios Barigui e Tanguá. A execução deste projeto teve a participação de um grupo de professores e estudantes da Universidade Tecnológica Federal do Paraná (UTFPR), Câmpus Curitiba. O objetivo principal foi investigar formas de intervenção nas condições de moradia e urbanização da Ilha, visando sua regularização fundiária. Porém, ao longo do projeto, o grupo constatou que essa regularização não era possível, tendo em vista os riscos de enchentes no local. Portanto, esta cartilha apresenta informações sobre a área e os rios no seu entorno, sobre os aspectos positivos de se viver no local, traz o relato de lutas dos moradores por melhores condições de vida, além de sugestões de fontes de financiamento para viabilizar um possível reassentamento das famílias existentes atualmente

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

Background: Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods: Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results: Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions: In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications

Osteopatia hipertrófica secundária a osteossarcoma condroblástico extraesquelético em um cão

Background: hypertrophic osteopathy is a periosteum disturb characterized by diffuse new bone formation which leads to significant thickening and deformity of members. Secondary in nature, it usually follows large pulmonary lesions such as abscesses and neoplasms. Extraskeletal osteosarcomas are rare and extremely malignant mesenchymal neoplasms. They comprise approximately 1% of all domestic animals’ osteosarcomas and develop in the absence of a primary bone lesion. The aim of this paper was to describe a case of hypertrophic osteopathy, involving joints and upper limbs bones including ilium, secondary to a mediastinal chondroblastic osteosarcoma with pulmonary metastasis.Case: A 10-year-old spayed female mixed breed dog, weighing 9 kg, was presented with painful limbs, lameness, hind limbs swelling and a four-month history of weight loss. Radiographic examination revealed bilateral and asymmetric periosteal reactions on diaphyseal and/or epiphyseal areas of all proximal phalanges; metacarpal, metatarsal, carpal and tarsal bones; radius; ulna; tibia; fibula; humerus; femur and right ilium. An increased soft tissue radiopacity was noted on the lateral side of the right knee joint. Thoracic radiographies and ultrasonography suggested the presence of a 5-cm neoplasm or abscess in the left caudal lung lobe. At necropsy, the lobe showed a firm and solid, oval white mass measuring 5.2 x 2.9 cm. Another mass was found in the caudal mediastinum, near the diaphragm, with same color and more irregular aspect, measuring 3.3 cm of diameter. Intense periosteal new-bone formation was seen in the entire length of the four limbs bones, characterized by thickening of the bone surface and formation of irregular trabeculae perpendicular to the cortex. Significant swelling and thickening of the joint capsule was noted in the right knee. There was no microbial growth on aerobic or anaerobic cultures from the masses samples sent to culture. Histopathological examination showed areas of chondroid differentiation, osteoidtissue formation and cell morphology suggestive of chondroblastic osteosarcoma in mediastinal region, with invasion and involvement of the diaphragm and lungs. The analyzed bone fragment had large foci of tissue compaction, peritrabecular bleeding and mineralization of osteoid tissue, permeated by plasma cells and typical lymphocytes.Discussion: Although hypertrophic osteopathy is often characterized as a disease which affects the diaphysis of distal long bones, this case presented a proximal progression of the disease. There was an unusual involvement of joints and ilium, which reinforces the importance of radiographic evaluation of these regions. Further studies on the pathogenesis of the syndrome are required, as its exact mechanisms remain obscure. It is suggested that the term hypertrophic osteoarthropathy should not be consider a misnomer since joint involvement is not exclusive of human form of the disease. Mediastinal masses are important cause of hypertrophic osteopathy. However, this is the first paper the authors are aware of that reports the occurrence of hypertrophic osteopathy secondary to mediastinal osteosarcoma. Finally, although rare, extra skeletal osteosarcoma should be considered in the differential diagnosis of intrathoracic masses in dogs with hypertrophic osteopathy. Timely diagnosis of hypertrophic osteopathy, whose signs of lameness and painful limbs draw the owner’s attention, may favor the diagnosis of severe concomitant diseases

Wild dogs at stake: deforestation threatens the only Amazon endemic canid, the short-eared dog (Atelocynus microtis)

The persistent high deforestation rate and fragmentation of the Amazon forests are the main threats to their biodiversity. To anticipate and mitigate these threats, it is important to understand and predict how species respond to the rapidly changing landscape. The short-eared dog Atelocynus microtis is the only Amazon-endemic canid and one of the most understudied wild dogs worldwide. We investigated short-eared dog habitat associations on two spatial scales. First, we used the largest record database ever compiled for short-eared dogs in combination with species distribution models to map species habitat suitability, estimate its distribution range and predict shifts in species distribution in response to predicted deforestation across the entire Amazon (regional scale). Second, we used systematic camera trap surveys and occupancy models to investigate how forest cover and forest fragmentation affect the space use of this species in the Southern Brazilian Amazon (local scale). Species distribution models suggested that the short-eared dog potentially occurs over an extensive and continuous area, through most of the Amazon region south of the Amazon River. However, approximately 30% of the short-eared dog's current distribution is expected to be lost or suffer sharp declines in habitat suitability by 2027 (within three generations) due to forest loss. This proportion might reach 40% of the species distribution in unprotected areas and exceed 60% in some interfluves (i.e. portions of land separated by large rivers) of the Amazon basin. Our local-scale analysis indicated that the presence of forest positively affected short-eared dog space use, while the density of forest edges had a negative effect. Beyond shedding light on the ecology of the short-eared dog and refining its distribution range, our results stress that forest loss poses a serious threat to the conservation of the species in a short time frame. Hence, we propose a re-assessment of the short-eared dog's current IUCN Red List status (Near Threatened) based on findings presented here. Our study exemplifies how data can be integrated across sources and modelling procedures to improve our knowledge of relatively understudied species

Fundamentos sensoriais da arquitetura

Resumo simples produzido pelos alunos da Faculdade Araguaia no ano de 2018, em parceria com os professores, e aprovado pela Coordenação de cada curso