16 research outputs found

    Rabaptin5 targets autophagy to damaged endosomes and Salmonella vacuoles via FIP200 and ATG16L1

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    Selective autophagy of damaged organelles is important to maintain cellular homeostasis. The mechanisms how autophagy selects specific targets is often poorly understood. Rabaptin5 was previously known as a major regulator of early endosome identity and maturation. Here, we identify two novel Rabaptin5 interactors: FIP200, a subunit of the ULK1 autophagy initiator complex, and ATG16L1, a central component of the E3-like enzyme in LC3 lipidation. Autophagy of early endosomes damaged by chloroquine or monensin treatment requires Rabaptin5 and particularly a short sequence motif that binds to the WD domain of ATG16L1. Rabaptin5 and its interaction with ATG16L1 further contributes to the autophagic elimination of Salmonella enterica early after infection, when it resides in phagosomes with early endosomal characteristics. Our results demonstrate a novel function of Rabaptin5 in quality control of early endosomes in the selective targeting of autophagy to damaged early endosomes and phagosomes

    Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation

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    Rab GTPases control membrane identity, fusion, and transport by interaction with effector proteins. Effectors that influence the activation/inactivation cycle of their own or other Rabs contribute to the timely conversion of Rab identities. Rab5 and its effector Rabaptin5 are generally considered the prime example for a positive feedback loop in which Rab5·GTP recruits Rabaptin5 complexed to Rabex5, the GDP/GTP exchange factor of Rab5, to early endosomes, thus maintaining the membrane's Rab5 identity. By deletion analysis, we found membrane recruitment of Rabaptin5 to require binding to Rab4 and Rabex5, but not Rab5. Deletion of either one of two Rab5 binding domains or silencing of Rab5 expression did not affect Rabaptin5 recruitment, but produced giant endosomes with early and late endosomal characteristics. The results contradict feedback activation of Rab5 and instead indicate that Rabaptin5 is recruited by Rabex5 recognizing ubiquitinated cargo and by Rab4 to activate Rab5 in a feed-forward manner

    Oficinas literĂĄrias: quando a palavra Ă© ofertada com excelĂȘncia pela escola

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    Discorrer acerca da leitura literĂĄria na escola nĂŁo constitui, a priori, nenhuma novidade. A questĂŁo que permeia o artigo a que nos propomos Ă© a de como a literatura comparada, em sua vertente de relação com outras artes, pode constituir um aporte teĂłrico-metodolĂłgico adequado ao letramento literĂĄrio, por meio da aplicação de oficinas literĂĄrias. O texto volta-se Ă  escola e aos anos finais do ensino fundamental, por compreender que Ă© na escola, e muitas vezes somente nela, que grande parte dos leitores tem contato com o texto literĂĄrio. AlĂ©m disso, cremos que um trabalho adequado nessa fase pode contribuir para um leitor que, nos anos subsequentes de escolarização – e mesmo depois dessa – seja capaz de ler o mundo que o cerca. O trabalho com a literatura infanto-juvenil, subsidiado pela pintura, pelo artesanato, pelas mĂ­dias digitais e por outros textos, busca, por meio da intertextualidade, uma aproximação do pequeno leitor com o universo literĂĄrio. Isso se dĂĄ ao promovermos a quebra do horizonte de expectativas do leitor e, em seguida, sua consequente expansĂŁo. Nossa proposta encontra ressonĂąncia em proposiçÔes como as de Magnani (1989), Candido (2011), Kleiman (2005); Cosson e Souza (2011), Cosson (2016), entre outras, e segue as diretrizes sugeridas por Mendoza Fillola (1994) para uma prĂĄtica comparatĂ­stica no ensino de literatura na escola.PALAVRAS-CHAVE: Literatura Comparada. Letramento LiterĂĄrio. EstĂ©tica da Recepção. Oficinas LiterĂĄrias

    A LEITURA LITERÁRIA NA ESCOLA: RESSIGNIFICAÇÕES DO PASSADO PELA LITERATURA HÍBRIDA INFANTIL DE HISTÓRIA E FICÇÃO

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    Este artĂ­culo propone un anĂĄlisis de la narrativa Barriga e Minhoca, Marinheiros de Cabral (2002) de AtĂ­lio Bari comparado a la Carta de Pero Vaz de Caminha (1500), comentĂĄrios de Leandro Garcia Rodrigues (2019). Discutimos posibles relaciones entre historia y literatura, convergencias y divergencias entre los discursos sobre el pasado presentes en la literatura hĂ­brida de historia y ficciĂłn infantil, basados en estudios de Cadermatori (1987), Coutinho (2003), Carvalhal (2006), Nitrini (2010), Candido (2011), Colomer (2017), Fleck (2017), Coelho (2020) sobre literatura comparada. Buscamos deconstruir, a partir de la ficciĂłn, las “verdades” del discurso oficial y alcanzar proceso de descolonizaciĂłn necesario.Neste artigo analisamos a narrativa Barriga e Minhoca, Marinheiros de Cabral (2002) de AtĂ­lio Bari em comparação Ă  Carta de Pero Vaz de Caminha (1500), comentĂĄrios de Leandro Garcia Rodrigues (2019). Discutimos as possĂ­veis relaçÔes entre histĂłria e literatura, convergĂȘncias e divergĂȘncias entre os discursos sobre o passado presentes na literatura hĂ­brida de histĂłria e ficção infantil, embasados nos estudos de Cadermatori (1987), Coutinho (2003), Carvalhal (2006), Nitrini (2010), Candido (2011), Colomer (2017), Fleck (2017), Coelho (2020) sobre literatura comparada. Buscamos desconstruir, a partir da ficção, as “verdades” impostas pelo discurso oficial e alcançar o processo de descolonização necessĂĄrio

    Secretion of Novel SEL1L Endogenous Variants Is Promoted by ER Stress/UPR via Endosomes and Shed Vesicles in Human Cancer Cells

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    We describe here two novel endogenous variants of the human endoplasmic reticulum (ER) cargo receptor SEL1LA, designated p38 and p28. Biochemical and RNA interference studies in tumorigenic and non-tumorigenic cells indicate that p38 and p28 are N-terminal, ER-anchorless and more stable relative to the canonical transmembrane SEL1LA. P38 is expressed and constitutively secreted, with increase after ER stress, in the KMS11 myeloma line and in the breast cancer lines MCF7 and SKBr3, but not in the non-tumorigenic breast epithelial MCF10A line. P28 is detected only in the poorly differentiated SKBr3 cell line, where it is secreted after ER stress. Consistently with the presence of p38 and p28 in culture media, morphological studies of SKBr3 and KMS11 cells detect N-terminal SEL1L immunolabeling in secretory/degradative compartments and extracellularly-released membrane vesicles. Our findings suggest that the two new SEL1L variants are engaged in endosomal trafficking and secretion via vesicles, which could contribute to relieve ER stress in tumorigenic cells. P38 and p28 could therefore be relevant as diagnostic markers and/or therapeutic targets in cancer

    2 nd Brazilian Consensus on Chagas Disease, 2015

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    Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

    A fresh look at the function of Rabaptin5 on endosomes

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    Rab GTPases act as organizers of protein networks defining identities and functions of organelles of the endocytic and secretory pathways. Various modes of coordination between different Rabs drive the timely maturation and conversion of membranes. Endosomal Rab5 has been known as the prime example for self-activation via a feedback loop recruiting Rabaptin5, which is complexed with the Rab5 exchange factor Rabex5, and couples to Rab4-GTP. Among other effectors, Rab5 also recruits the Mon1/SAND1-Ccz1 complex that both activates Rab7 and dissociates Rabex5 for Rab5-to-Rab7 conversion of early-to-late endosomes. A detailed deletion analysis now revealed 2 separate binding sites each for Rab4-GTP and Rab5-GTP and indicates a feedforward mechanism of Rab5 activation. Rabaptin5/Rabex5 is recruited to endosomal membranes positive for Rab4-GTP and ubiquitinated cargo (binding to the ubiquitin binding site of Rabex5). This mechanism also suggests additional criteria for Rab5 inactivation concomitant with increasing Rab7-GTP levels. The disappearance of ubiquitinated cargo upon ESCRT-mediated formation of intraluminal vesicles and inactivation of Rab4 may also contribute to loss of Rab5 activation. Rabaptin5/Rabex5 thus may integrate several cues of maturation to perform Rab conversion. Furthermore Rab5 binding to Rabaptin5 appears to prevent uncontrolled progression to late endosomes

    IntraokulÀre Blutung bei einer Ziege mit Thrombozytopenie und Karzinommetastase in der Iris

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    Im vorliegenden Fallbericht wird eine 10-jĂ€hrige weibliche Toggenburger-Ziege mit einer Adenokarzinommetastase in der Iris beschrieben. Zwei Wochen vor der Einlieferung wurde vom Besitzer erstmals ein Blepharospasmus am linken Auge beobachtet. Die vordere Augenkammer war zu drei Vierteln mit nicht geronnenem Blut gefĂŒllt und das Kammerwasser ĂŒber dem Blutspiegel war getrĂŒbt. Die Traubenkörner waren nur verschwommen zu erkennen. Alle ĂŒbrigen Augenabschnitte waren nicht einsehbar. Bei der Ultraschalluntersuchung zeigte sich eine Verdickung der Iris. Da der rechte Buglymphknoten deutlich vergrössert war, wurde er punktiert. Die zytologische Untersuchung des Punktats ergab fĂŒr eine Karzinommetastase typische Befunde. Der wichtigste Blutbefund war eine hochgradige Thrombozytopenie. Die Ziege wurde aufgrund der infausten Prognose euthanasiert und seziert. Der rechte Buglymphknoten, die Retropharyngeal-, Mediastinal, Leber- und Mesenteriallymphknoten sowie der Oesophagus und die Leber waren tumorös verĂ€ndert. Die Iris des linken Auges war verdickt und mit der Kornea verklebt. Die histologische Untersuchung der VerĂ€nderungen ergab ein Adenokarzinom. Die primĂ€re Tumorlokalisation konnte nicht eruiert werden
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