In vitro and in vivo effects of SerpinA1 on the modulation of Transthyretin proteolysis

Transthyretin (TTR) proteolysis has been recognized as a complementary mechanism contributing to transthyretin-related amyloidosis (ATTR amyloidosis). Accordingly, amyloid deposits can be composed mainly of full-length TTR or contain a mixture of both cleaved and full-length TTR, particularly in the heart. The fragmentation pattern at Lys48 suggests the involvement of a serine protease, such as plasmin. The most common TTR variant, TTR V30M, is susceptible to plasmin-mediated proteolysis, and the presence of TTR fragments facilitates TTR amyloidogenesis. Recent studies revealed that the serine protease inhibitor, SerpinA1, was differentially expressed in hepatocyte-like cells (HLCs) from ATTR patients. In this work, we evaluated the effects of SerpinA1 on in vitro and in vivo modulation of TTR V30M proteolysis, aggregation, and deposition. We found that plasmin-mediated TTR proteolysis and aggregation are partially inhibited by SerpinA1. Furthermore, in vivo downregulation of SerpinA1 increased TTR levels in mice plasma and deposition in the cardiac tissue of older animals. The presence of TTR fragments was observed in the heart of young and old mice but not in other tissues following SerpinA1 knockdown. Increased proteolytic activity, particularly plasmin activity, was detected in mice plasmas. Overall, our results indicate that SerpinA1 modulates TTR proteolysis and aggregation in vitro and in vivo.This research was funded by COMPETE 2020 of PT2020 through the European Regional Development Fund (ERDF), “NETDIAMOND—New Targets in DIAstolic heart failure: from coMOrbidities to persoNalizeD medicine” project financed by the European Structural and Investment Funds (ESIF), through the Programa Operacional Regional (POCI-01-0145-FEDER-016385) and HEALTHUNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological, and infectious diseases, NORTE- 01-0145-FEDER-000039. FB was supported by FCT—Fundação para a Ciência e Tecnologia/MEC— Ministério da Educação e Ciência with a PhD fellowship (SFRH/BD/123674/2016)

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined

New directions in corpus-based translation studies

Corpus-based translation studies has become a major paradigm and research methodology and has investigated a wide variety of topics in the last two decades. The contributions to this volume add to the range of corpus-based studies by providing examples of some less explored applications of corpus analysis methods to translation research. They show that the area keeps evolving as it constantly opens up to different frameworks and approaches, from appraisal theory to process-oriented analysis, and encompasses multiple translation settings, including (indirect) literary translation, machine(-assisted) translation and the practical work of professional legal translators. The studies included in the volume also expand the range of application of corpus applications in terms of the tools used to accomplish the research tasks outlined