"Eu mato": The Linguistic and Religious Rewriting of the Tupí under Portuguese Missionary Rule (1555-1630)

Abstract: This paper investigates the relationship between Portuguese missionary grammars, imperial-indigenous relations, and Tupí resistance between 1555 and 1630. Focusing on José de Anchieta’s popular grammar Arte de gramática de língua mais usada na costa do brasil (1555) and Luís Figueira’s Arte da Língua Brasílica (1621), it argues that the shifting focuses of these texts represent the values of the Jesuit order and the interests of Portugal in the New World. Portuguese missionaries moved from an earlier emphasis on trade and Christian conversion with an exclusively oral culture toward a more aggressive and insidious campaign for cultural and linguistic erasure in the region. While previous scholarship has examined changes in Tupí phonemes, morphemes, and syntax between the grammars, this study instead investigates the historical changes pertinent between these texts, their constructed relationships between Portuguese and Tupí, and shifts in their lexical emphases. Keywords: colonial translation; grammars; Jesuit missionaries; cultural erasure; Tupí-GuaraníResumen: En este artículo se investiga la relación entre las gramáticas de los misioneros portugueses, las relaciones imperiales-indígenas y la resistencia de los tupíes entre 1555 y 1630. Tomando como objeto de estudio la gramática popular de José de Anchieta, Arte de gramática de língua mais usada na costa do brasil (1555), y el Arte da Língua Brasílica (1621) de Luís Figueira, se argumenta que los focos cambiantes de estos textos representan los valores de la orden de los jesuitas y los intereses de Portugal en el Nuevo Mundo. Los misioneros portugueses pasaron del énfasis inicial en el comercio y la conversión al cristianismo con un enfoque exclusivamente oral hacia una campaña más agresiva e insidiosa dirigida a la erradicación lingüística y cultural en la región. Si bien en obras académicas anteriores se han abordado los cambios en los fonemas, morfemas y la sintaxis tupí entre las gramáticas, el presente estudio investiga los cambios históricos pertinentes entre estos textos, sus relaciones construidas entre los portugueses y los tupíes, y los giros en sus énfasis léxicos. Palabras clave: traducción colonial; gramáticas; misioneros jesuitas; erradicación cultural; tupí-guaraníRésumé : Dans cet article, l’auteure analyse la relation entre les grammaires des missionnaires portugais, les relations empire-autochtones et la résistance des Tupis entre 1555 et 1630. L’étude est axée sur la célèbre grammaire de José de Anchieta, Arte de gramática de língua mais usada na costa do brasil (1555) et celle de Luís Figueira, Arte da Língua Brasílica (1621). Il ressort que les priorités changeantes de ces textes représentent les valeurs de l’ordre des Jésuites et les intérêts du Portugal au nouveau monde. Effectivement, les missionnaires portugais ont évolué : ils ont d’abord mis l’accent sur le commerce et la conversion chrétienne avec une culture orale exclusivement, puis ont adopté une campagne plus agressive et insidieuse d’anéantissement culturel et linguistique dans la région. Si ce sont les changements au niveau des phonèmes, des morphèmes et de la syntaxe de la langue tupi d’une grammaire à l’autre qui étaient sujet d’étude, ce travail s’attarde, lui, sur les changements historiques pertinents entre les ouvrages, la relation construite entre les Portugais et les Tupis et les changements au niveau des emphases lexicales. Mots clés : traduction coloniale; grammaires; missionnaires jésuites; anéantissement culturel; Tupi-GuaraniResumo: Este trabalho investiga a relação entre as gramáticas dos missionários  portugueses, as relações entre o império e o povo indígena e a resistência tupi entre 1555 e 1630. Tomando a conhecida gramática de José de Anchieta, Arte de gramática de língua mais usada na costa do brasil (1555) e a Arte da Língua Brasílica (1621), de Luís Figueira,  argumentamos que os enfoques cambiantes desses textos representam os valores da Ordem Jesuíta e os interesses de Portugal no Novo Mundo. A ênfase inicial dos missionários portugueses no comércio e conversão cristã, com uma cultura totalmente oral tomou mais tarde a forma de uma campanha mais agressiva e insidiosa de apagamento cultural e linguístico da região. Estudos anteriores  analisaram mudanças nos fonemas, morfemas e sintaxe do Tupi entre as gramáticas, ao passo que este estudo se propõe a investigar as mudanças históricas pertinentes entre esses textos, as relações construídas entre o português e o Tupi, bem como as mudanças de ênfase lexical. Palavras-chave: tradução colonial; gramáticas; missionários jesuítas; apagamento cultural; Tupi-Guaran

Lymph node-derived donor encephalitogenic CD4+ T cells in C57BL/6 mice adoptive transfer experimental autoimmune encephalomyelitis highly express GM-CSF and T-bet

Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model for the human demyelinating inflammatory disorder of the central nervous system (CNS), multiple sclerosis (MS). Induction of EAE by adoptive transfer allows studying the role of the donor T lymphocyte in disease pathogenesis. It has been challenging to reliably induce adoptive transfer EAE in C57BL/6 (H-2b) mice. The goal of this study was to develop a reproducible and high yield protocol for adoptive transfer EAE in C57BL/6 mice. A step-wise experimental approach permitted us to develop a protocol that resulted in a consistent relatively high disease incidence of ~70% in recipient mice. Donor mice were immunized with myelin oligodendrocyte glycoprotein (MOG)p35-55 in complete Freund's adjuvant (CFA) followed by pertussis toxin (PT). Only lymph node cells (LNC) isolated at day 12 post immunization, and restimulated in vitro for 72 hours with 10 μg/mL of MOGp35-55 and 0.5 ng/mL of interleukin-12 (IL-12) were able to transfer disease. The ability of LNC to transfer disease was associated with the presence of inflammatory infiltrates in the CNS at day 12. Interferon gamma (IFNγ) was produced at comparable levels in cell cultures prepared from mice at both day 6 and day 12 post immunization. By contrast, there was a trend towards a negative association between IL-17 and disease susceptibility in our EAE model. The amount of GM-CSF secreted was significantly increased in the culture supernatants from cells collected at day 12 post immunization versus those collected at day 6 post-immunization. Activated CD4+ T cells present in the day 12 LNC cultures maintained expression of the transcription factor T-bet, which has been shown to regulate the expression of the IL-23 receptor. Also, there was an increased prevalence of MOGp35-55-specific CD4+ T cells in day 12 LNC after in vitro re-stimulation. In summary, encephalitogenic LNC that adoptively transfer EAE in C57BL/6 mice were not characterized by a single biomarker in our study, but by a composite of inflammatory markers. Our data further suggest that GM-CSF expression by CD4+ T cells regulated by IL-23 contributes to their encephalitogenicity in our EAE model

PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease

Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS). Minocycline, a potent inhibitor of matrix metalloproteinase (MMP)-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG) minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs), we determined that PEG minocycline-liposome preparations stabilized with CaCl(2) are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS

Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling

The primary biological function of the endogenous cellular prion protein has remained unclear. We investigated its biological function in the generation of cellular immune responses using cellular prion protein gene-specific small interfering ribonucleic acid in vivo and in vitro. Our results were confirmed by blocking cellular prion protein with monovalent antibodies and by using cellular prion protein-deficient and -transgenic mice. In vivo prion protein gene-small interfering ribonucleic acid treatment effects were of limited duration, restricted to secondary lymphoid organs and resulted in a 70% reduction of cellular prion protein expression in leukocytes. Disruption of cellular prion protein signalling augmented antigen-specific activation and proliferation, and enhanced T cell receptor signalling, resulting in zeta-chain-associated protein-70 phosphorylation and nuclear factor of activated T cells/activator protein 1 transcriptional activity. In vivo prion protein gene-small interfering ribonucleic acid treatment promoted T cell differentiation towards pro-inflammatory phenotypes and increased survival of antigen-specific T cells. Cellular prion protein silencing with small interfering ribonucleic acid also resulted in the worsening of actively induced and adoptively transferred experimental autoimmune encephalomyelitis. Finally, treatment of myelin basic protein1–11 T cell receptor transgenic mice with prion protein gene-small interfering ribonucleic acid resulted in spontaneous experimental autoimmune encephalomyelitis. Thus, central nervous system autoimmune disease was modulated at all stages of disease: the generation of the T cell effector response, the elicitation of T effector function and the perpetuation of cellular immune responses. Our findings indicate that cellular prion protein regulates T cell receptor-mediated T cell activation, differentiation and survival. Defects in autoimmunity are restricted to the immune system and not the central nervous system. Our data identify cellular prion protein as a regulator of cellular immunological homoeostasis and suggest cellular prion protein as a novel potential target for therapeutic immunomodulation

The Impact of Product-Country Image and Marketing Efforts on Retailer-Perceived Brand Equity. An Empirical Analysis

Although both product-country images (PCI) and firm assets such as brand equity have been extensively studied in separate contexts, we know very little about the combined performance effects of these two important constructs in international research. Extant research has investigated brand equity primarily from a consumer perspective, but rarely from the point of view of a retailer. Retailers represent the ultimate participants in the value chain selling the product to consumers. They have the ability to significantly influence consumers' evaluations and purchase decisions. Based upon existing literature documenting the contributions of PCI and marketing activities on brand equity, this study extends these findings by investigating their effects on retailer-perceived brand equity (RPBE) and ultimate brand profitability performance. Results indicate that both marketing activities and PCI affect retailer-perceived brand equity with PCI also strongly and positively influencing brand profitability performance. © 2009 New York University

Experimental Infection of NOD/SCID Mice Reconstituted with Human CD34(+) Cells with Epstein-Barr Virus

Epstein-Barr virus (EBV)-induced lymphoproliferative disease is an important complication in the context of immune deficiency. Impaired T-cell immunity allows the outgrowth of transformed cells with the subsequent production of predominantly B-cell lymphomas. Currently there is no in vivo model that can adequately recapitulate EBV infection and its association with B-cell lymphomas. NOD/SCID mice engrafted with human CD34(+) cells and reconstituted mainly with human B lymphocytes may serve as a useful xenograft model to study EBV infection and pathogenesis. We therefore infected reconstituted mice with EBV. High levels of viral DNA were detected in the peripheral blood of all infected mice. All infected mice lost weight and showed decreased activity levels. Infected mice presented large visible tumors in multiple organs, most prominently in the spleen. These tumors stained positive for human CD79a, CD20, CD30, and EBV-encoded RNAs and were light chain restricted. Their characterization is consistent with that of large cell immunoblastic lymphoma. In addition, tumor cells expressed EBNA1, LMP1, and LMP2a mRNAs, which is consistent with a type II latency program. EBV(+) lymphoblastoid cell lines expressing human CD45, CD19, CD21, CD23, CD5, and CD30 were readily established from the bone marrow and spleens of infected animals. Finally, we also demonstrate that infection with an enhanced green fluorescent protein (EGFP)-tagged virus can be monitored by the detection of infected EGFP(+) cells and EGFP(+) tumors. These data demonstrate that NOD/SCID mice that are reconstituted with human CD34(+) cells are susceptible to infection by EBV and accurately recapitulate important aspects of EBV pathogenesis