Kate Lowe

CLEC-2 is required for development and maintenance of lymph nodes.

The importance of CLEC-2, a natural ligand/receptor for Gp38/Podoplanin, in the formation of the lymphatic vasculature has recently been demonstrated. As the development and maintenance of lymph nodes (LNs) is dependent on the formation of the lymphatic vasculature and the differentiation of Gp38/Podoplanin(+) stromal cells, we investigated the role of CLEC-2 in lymphoneogenesis and LN homeostasis. Using constitutive Clec1b(-/-) mice, we showed that while CLEC-2 was not necessary for initiation of the LN anlage, it was required at late stages of development. Constitutive deletion of CLEC-2 induced a profound defect in lymphatic endothelial cell proliferation, resulting in lack of LNs at birth. In contrast, conditional deletion of CLEC-2 in the megakaryocyte/platelet lineage in Clec1b(fl/fl)PF4-Cre mice led to the development of blood-filled LNs and fibrosis, in absence of a proliferative defect of the lymphatic endothelial compartment. This phenotype was also observed in chimeric mice reconstituted with Clec1b(fl/fl)PF4-Cre bone marrow, indicating that CLEC-2 expression in platelets was required for LN integrity. We demonstrated that LNs of Clec1b(fl/fl)PF4-Cre mice are able to sustain primary immune responses but show a defect in immune cell recirculation after repeated immunizations, thus suggesting CLEC-2 as target in chronic immune response.

Crime, Society and the Law in Renaissance Italy

Preface List of contributors 1. Writing the history of crime in the Italian Renaissance Trevor Dean and Kate Lowe 2. Criminal justice in mid fifteenth-century Bologna Trevor Dean 3. The judicial system in Florence in the fourteenth and fifteenth centuries Andrea Zorzi 4. The incidence of crime in Sicily in the mid fifteenth century: the evidence from composition records Alan Ryder 5. Theology, nature and the law: sexual sin and sexual crime in Italy from the fourteenth to the seventeenth century Nicholas Davidson 6. Practical problems in the enforcement of Italian sumptuary law, 1200-1500 Catherine Kovesi Killerby 7. The prince, the judges and the law: Cosimo I and sexual violence, 1558 Elena Fasano Guarini 8. Intervention by church and state in marriage disputes in sixteenth- and seventeenth-century Florence Daniela Lombardi 9. The writer and the man: real crimes and mitigating circumstances: Il caso Cellini Paolo Rossi 10. The political crime of conspiracy in fifteenth- and sixteenth-century Rome Kate Lowe 11. Fighting or flyting?: verbal duelling in mid sixteenth-century Italy Donald Weinstein 12. Banditry and lawlessness on the Venetian terraferma in the later cinquecento Peter Laven 13. Mihi vindictam: aristocratic clans and rural communities in a feud in Friuli in the late fifteenth and early sixteenth centuries Furio Bianco.

‘REPRESENTING’ AFRICA: AMBASSADORS AND PRINCES FROM CHRISTIAN AFRICA TO RENAISSANCE ITALY AND PORTUGAL, 1402–1608

During the fifteenth and sixteenth centuries, a number of sub-Saharan envoys and ambassadors from Christian countries, predominantly Ethiopia and the Congo, were sent to Portugal and Italy. This essay shows how cultural assumptions on both sides complicated their task of ‘representing’ Africa. These African ambassadors and princes represented the interests of their rulers or their countries in a variety of ways, from forging personal relationships with the king or pope, to providing knowledge of the African continent and African societies, to acquiring knowledge of European languages and behaviours, to negotiating about war, to petitioning for religious or technological help, to carrying out fact-finding missions. But Renaissance preconceptions of Africa and Africans, reinforced by the slave trade, and Renaissance and papal assumptions about diplomatic interaction, ensured that the encounters remained unsatisfactory, as this cultural history of diplomacy makes clear. The focus of the essay is on religious and cultural exchange and the ceremonial culture of embassies.

Platelet adhesion to podoplanin under flow is mediated by the receptor CLEC-2 and stabilised by Src/Syk-dependent platelet signalling

Summary Platelet-specific deletion of CLEC-2, which signals through Src and Syk kinases, or global deletion of its ligand podoplanin results in blood-filled lymphatics during mouse development. Platelet-specific Syk deficiency phenocopies this defect, indicating that platelet activation is required for lymphatic development. In the present study, we investigated whether CLEC-2-podoplanin interactions could support platelet arrest from blood flow and whether platelet signalling is required for stable platelet adhesion to lymphatic endothelial cells (LECs) and recombinant podoplanin under flow. Perfusion of human or mouse blood over human LEC monolayers led to platelet adhesion and aggregation. Following αIIbβ3 blockade, individual platelets still adhered. Platelet binding occurred at venous but not arterial shear rates. There was no adhesion using CLEC-2-deficient blood or to vascular endothelial cells (which lack podoplanin). Perfusion of human blood over human Fc-podoplanin (hFcPDPN) in the presence of monoclonal antibody IV.3 to block FcγRIIA receptors led to platelet arrest at similar shear rates to those used on LECs. Src and Syk inhibitors significantly reduced global adhesion of human or mouse platelets to LECs and hFcPDPN. A similar result was seen using Syk-deficient mouse platelets. Reduced platelet adhesion was due to a decrease in the stability of binding. In conclusion, our data reveal that CLEC-2 is an adhesive receptor that supports platelet arrest to podoplanin under venous shear. Src/Syk-dependent signalling stabilises platelet adhesion to podoplanin, providing a possible molecular mechanism contributing to the lymphatic defects of Syk-deficient mice.

Platelets in Lymph Vessel Development and Integrity

Blood platelets have recently been proposed to play a critical role in the development and repair of the lymphatic system. The platelet C-type lectin receptor CLEC-2 and its ligand, the transmembrane protein Podoplanin, which is expressed at high levels on lymphatic endothelial cells (LECs), are required to prevent mixing of the blood and lymphatic vasculatures during mid-gestation. A similar defect is seen in mice deficient in the tyrosine kinase Syk, which plays a vital role in mediating platelet activation by CLEC-2. Furthermore, blood-lymphatic mixing is also present in mice with platelet-/megakaryocyte-specific deletions of CLEC-2 and Syk, suggesting that the phenotype is platelet in origin. The molecular basis of this effect is not known, but it is independent of the major platelet receptors that support hemostasis, including integrin αIIbβ3 (GPIIb-IIIa). Radiation chimeric mice reconstituted with CLEC-2-deficient or Syk-deficient bone marrow exhibit blood-lymphatic mixing in the intestines, illustrating a role for platelets in repair and growth of the lymphatic system. In this review, we describe the events that led to the identification of this novel role of platelets and discuss possible molecular mechanisms and the physiological and pathophysiological significance.

Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse

There is no therapeutic intervention proven to prevent acute respiratory distress syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes that occur during ARDS; however, the mechanisms remain elusive. The platelet receptor CLEC-2 has been shown to regulate vascular integrity at sites of acute inflammation. Therefore the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS. Platelet-specific CLEC-2-deficient, as well as alveolar epithelial type I cell (AECI)-specific or hematopoietic-specific podoplanin deficient, mice were established using cre-loxP strategies. Combining these with intratracheal (IT) instillations of lipopolysaccharide (LPS), we demonstrate that arterial oxygen saturation decline in response to IT-LPS in platelet-specific CLEC-2-deficient mice is significantly augmented. An increase in bronchoalveolar lavage (BAL) neutrophils and protein was also observed 48 h post-IT-LPS, with significant increases in pro-inflammatory chemokines detected in BAL of platelet-specific CLEC-2-deficient animals. Deletion of podoplanin from hematopoietic cells but not AECIs also reduces lung function and increases pro-inflammatory chemokine expression following IT-LPS. Furthermore, we demonstrate that following IT-LPS, platelets are present in BAL in aggregates with neutrophils, which allows for CLEC-2 interaction with podoplanin expressed on BAL inflammatory alveolar macrophages. Taken together, these data suggest that the platelet CLEC-2-podoplanin signaling axis regulates the severity of lung inflammation in mice and is a possible novel target for therapeutic intervention in patients at risk of developing ARDS.

Cultural links between Portugal and Italy in the Renaissance

Introduction. Kate Lowe: Understanding Cultural Exchange between Portugal and Italy in the Renaissance. Social and Institutional Relations. D. S. Chambers: Venetian Perceptions of Portugal c.1500. Giuseppe Bertini: The Marriage of Alessandro Farnese and D. Maria of Portugal in 1565: Court Life in Lisbon and Parma. A. D. Wright: The Interaction of the Portuguese and Italian Churches in the Counter-Reformation. Art and Literature. J. B. Bury: The Italian Contribution to Sixteenth-Century Portuguese Architecture, Military and Civil. Dalila Rodrigues: Italian Influences on Portuguese Painting in the First Half of the Sixteenth Century. Sandra Sider: Manneristic Style in Portuguese and Italian Compass Roses on Manuscript Portolan Charts. Jeremy Lawrence: Medieval Portuguese Literature and the Questione della lingua. T. F. Earle: Sa de Mirandas Roman Comedy. Patronage and Collecting. Albinia de la Mare: Notes on Portuguese Patrons of the Florentine Book Trade in the Fifteenth Century. Eric Apfelstadt: Bishop and Pawn: New Documents for the Chapel of the Cardinal of Portugal at S. Miniato al Monte, Florence. Kate Lowe: Rainha D. Leonor of Portugals Patronage in Renaissance Florence and Cultural Exchange. Sylvie Deswarte-Rosa: The Portuguese in Rome and the Palazzo dei Tribunali. Annemarie Jordan: Portuguese Royal Collecting after 1521: The Choice between Flanders and Italy. Bibliography

Elections of Abbesses and Notions of Identity in Fifteenth- and Sixteenth-Century Italy, with Special Reference to Venice

Ceremonies of election to abbess were occasions of great display. Election to this highest of offices was the defining moment of a successful nuns life, and thereafter self-identity became crucial. This article examines an anatomy of an election of 1509 by a nun from San Zaccaria in Venice; the illustrated chronicle of Santa Maria delle Vergini in Venice dated 1523, written by an anonymous nun; and the visual representation (in a range of media) of various abbesses from Florence, Pavia, and Venice. Success in election conferred the possibility of personality and consequently legitimated personalized representation.

Visible Lives: Black Gondoliers and Other Black Africans in Renaissance Venice*

This article contributes to the study of the early sub-Saharan African diaspora in Europe by analyzing both visual and documentary evidence relating to black gondoliers in Renaissance Venice. Gondolas and gondoliers were iconic features in fifteenth-century Venice, yet most gondoliers were not Venetian. Although black Africans were highly visible in a predominantly white society, naming practices and linguistic usages rendered them virtually invisible in the documentary sources. It is now possible not only to investigate representations of black gondoliers in paintings, but also to identify black gondoliers in the lists of gondoliers’ associations and in criminal records. Slavery was an accepted institution in late medieval Italy, and nearly all black Africans arrived in Venice as slaves, yet usually ended their lives free. Being a gondolier gave a few black Africans a niche occupation that allowed them to manage their transition to freedom, and to integrate successfully into Venetian society.

Africa in the News in Renaissance Italy: News Extracts from Portugal about Western Africa Circulating in Northern and Central Italy in the 1480s and 1490s

Abstract This article addresses issues surrounding news of Western Africa, from Senegambia to the Congo, coming via Lisbon to the Northern Italian courts and Florence during the reign of King João II of Portugal (1481–95), who developed a policy of exploration and alliance along the African coast. It examines this news from a variety of standpoints, paying attention to both transmission and content, and relates the key concepts of newsworthiness and news stories to Renaissance news from Africa in order to gauge Italian perceptions about the worth or value of Africa. The article analyses in detail excerpts from four quasi-private letters (published here as an appendix) sent to correspondents in Italy in the 1480s and 1490s, giving news of previously unknown parts of Western Africa or previously unknown Africans.