Queen Elizabeth’s Leadership Abroad: The Netherlands in the 1570s

In 1576, after Edmund Grindal, archbishop of Canterbury, presumed to lecture Queen Elizabeth on the importance of preaching and on her duty to listen to such lectures, his influence diminished precipitously, and leadership of the established English church fell to Bishop Aylmer. Grindal’s friends on the queen’s Privy Council, “forward” Calvinists (or ultra-Protestants), were powerless to save him from the consequences of his indiscretion, which damaged the ultras’ other initiatives’ chances of success. This paper concerns one of those initiatives. From the late 1560s, they urged their queen “actively” to intervene in the Dutch wars. They collaborated with Calvinists on the Continent who befriended Prince William of Orange and who hoped to help him hold together a coalition of religiously reformed and Roman Catholic insurgents in the seventeen provinces of the Low Countries. The English ultra-Protestants would have their government send money, munitions, and men in arms to the Netherlands, to tip the balance against viceroys sent by King Philip II of Spain. Grindal’s setback undermined the English Calvinists’ efforts to form an Anglo-Dutch alliance which, they assumed, would boost the prospects for an international Protestant league. Yet Elizabeth did assist the Dutch as they wrestled with decisions forced on them by developments in the Netherlands during the 1570s, and she did so more consistently and more cleverly than many historians of Tudor diplomacy have thought. Two competing assessments determine the way questions are formulated in the study of the queen’s and regime’s Dutch diplomacy. The general consensus is that she was indecisive and inconsistent. Paul Hammer characterizes Elizabeth’s responses to the crises in the Low Countries as a “zigzag of different” (“even contradictory”) maneuvers. Wallace McCaffrey and R. B. Wernham agree that England’s “hesitations and gyrations” do not pass as coherent, creditable policy. Charles Wilson scolds Elizabeth for being timid and tepid--incapable of enthusiasm for “a great cause.” But David J.B. Trim’s striking counterthrust depicts the queen’s overtures to Netherlanders as part of her courageous – and “confessionally driven” – foreign policy; Trim replaces “hesitation” and “zigzag” with a coherent “Protestant programme of action prioritized by the Elizabethan government” with the aim of improving prospects for “Calvinist internationalism.” What follows is an alternative to all these characterizations, one that, as noted, finds evidence for greater consistency and coherence in Elizabeth’s leadership and less confessional “drive.” That she would have been uneasy around religious extremists ought not to astonish us; her father’s, step-brother’s, and step-sister’s reigns as well as the start of her own were disturbed by zealous subjects, who were bent on shoring up or dismantling the realm’s religious settlements

Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases

Anglo-Dutch translations of medical and scientific texts

In the seventeenth century the use of vernacular languages became more and more accepted in scientific publications and communications, and began to supplement the traditional language in this field, namely: Latin. The increase in the number of languages used in science and medicine was accompanied by a heightened need for translators. The close relationship between England and the Low Countries in the seventeenth century has led to a focus in the existing research on political and religious issues, and this has been reflected in the study of translations between English and Dutch. Yet one also finds in the fields of medicine and science an exchange of ideas through translation. The language skills of both Dutch and English men and women were often not sufficient to understand each other's language, which means that translations were vital. By considering the examples of how Thomas Browne's Religio medici was translated into Dutch, and how letters by Antoni van Leeuwenhoek and a publication by Jan Baptista van Helmont were translated into English, this essay examines the exchange of scientific and medical ideas across the Channel.Part of this article was written during a visiting fellowship in the Summer of 2016 at the Max Planck Institute for the History of Science in Berlin, and I would like to thank the MPIWG and the Global Knowledge Society Project for hosting me, as well as the Making Visible Project (Arts and Humanities Research Council, grant number AH/M001928/1) for providing me with support and the time to write

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Vaderland en vrijheid. Bewondering en twijfel

E.O.G. Haitsma Mulier, W.R.E. Velema, Vrijheid. Een geschiedenis van de vijftiende tot de twintigste eeuw N.C.F. van Sas, Vaderland. Een geschiedenis van de vijftiende eeuw tot 194