Extending the Prym map to toroidal compactifications of the moduli space of abelian varieties

The main purpose of this paper is to present a conceptual approach to understanding the extension of the Prym map from the space of admissible double covers of stable curves to different toroidal compactifications of the moduli space of principally polarized abelian varieties. By separating the combinatorial problems from the geometric aspects we can reduce this to the computation of certain monodromy cones. In this way we not only shed new light on the extension results of Alexeev, Birkenhake, Hulek, and Vologodsky for the second Voronoi toroidal compactification, but we also apply this to other toroidal compactifications, in particular the perfect cone compactification, for which we obtain a combinatorial characterization of the indeterminacy locus, as well as a geometric description up to codimension six, and an explicit toroidal resolution of the Prym map up to codimension four.Comment: 53 pages, AMS LaTeX, Appendix by Mathieu Dutour Sikiric, minor revisions, to appear in JEM

Extending the Prym map to toroidal compactifications of the moduli space of abelian varieties (with an appendix by Mathieu Dutour Sikiric)

The main purpose of this paper is to present a conceptual approach to understanding the extension of the Prym map from the space of admissible double covers of stable curves to different toroidal compactifications of the moduli space of principally polarized abelian varieties. By separating the combinatorial problems from the geometric aspects we can reduce this to the computation of certain monodromy cones. In this way we not only shed new light on the extension results of Alexeev, Birkenhake, Hulek, and Vologodsky for the second Voronoi toroidal compactification, but we also apply this to other toroidal compactifications, in particular the perfect cone compactification, for which we obtain a combinatorial characterization of the indeterminacy locus, as well as a geometric description up to codimension six, and an explicit toroidal resolution of the Prym map up to codimension four. © 2017 European Mathematical Society

The Role of IL-15 Deficiency in the Pathogenesis of Virus-Induced Asthma Exacerbations

Rhinovirus infections are the major cause of asthma exacerbations. We hypothesised that IL-15, a cytokine implicated in innate and acquired antiviral immunity, may be deficient in asthma and important in the pathogenesis of asthma exacerbations. We investigated regulation of IL-15 induction by rhinovirus in human macrophages in vitro, IL-15 levels in bronchoalveolar lavage (BAL) fluid and IL-15 induction by rhinovirus in BAL macrophages from asthmatic and control subjects, and related these to outcomes of infection in vivo. Rhinovirus induced IL-15 in macrophages was replication-, NF-κB- and α/β interferon-dependent. BAL macrophage IL-15 induction by rhinovirus was impaired in asthmatics and inversely related to lower respiratory symptom severity during experimental rhinovirus infection. IL-15 levels in BAL fluid were also decreased in asthmatics and inversely related with airway hyperresponsiveness and with virus load during in vivo rhinovirus infection. Deficient IL-15 production in asthma may be important in the pathogenesis of asthma exacerbations

Viruses exacerbating chronic pulmonary disease: the role of immune modulation

Chronic pulmonary diseases are a major cause of morbidity and mortality and their impact is expected to increase in the future. Respiratory viruses are the most common cause of acute respiratory infections and it is increasingly recognized that respiratory viruses are a major cause of acute exacerbations of chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. There is now increasing evidence that the host response to virus infection is dysregulated in these diseases and a better understanding of the mechanisms of abnormal immune responses has the potential to lead to the development of new therapies for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in chronic pulmonary diseases and discuss avenues for future research and therapeutic implications

Toll-Like Receptor 3 Is Induced by and Mediates Antiviral Activity against Rhinovirus Infection of Human Bronchial Epithelial Cells

Rhinoviruses (RV) are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. Toll-like receptors (TLRs) are a conserved family of receptors that recognize and respond to a variety of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA, an important intermediate of many viral life cycles (including RV). The importance of TLR3 in host responses to virus infection is not known. Using BEAS-2B (a human bronchial epithelial cell-line), we demonstrated that RV replication increased the expression of TLR3 mRNA and TLR3 protein on the cell surface. We observed that blocking TLR3 led to a decrease in interleukin-6, CXCL8, and CCL5 in response to poly(IC) but an increase following RV infection. Finally, we demonstrated that TLR3 mediated the antiviral response. This study demonstrates an important functional requirement for TLR3 in the host response against live virus infection and indicates that poly(IC) is not always a good model for studying the biology of live virus infection