Religion, anti-slavery, and identity: Irish Presbyterians, the United States, and transatlantic evangelicalism, c. 1820-1914

Scholars have devoted much attention to the causes and consequences of Presbyterian emigration from Ulster to the thirteen colonies before 1776. This article moves beyond the eighteenth century to examine the continued religious links between Presbyterians in Ireland and the United States in the nineteenth century. It begins with an examination of the influence of evangelicalism on both sides of the Atlantic and how this promoted unity in denominational identity, missionary activity to convert Catholics, and revivalist religion during the first half of the century. Though Irish Presbyterians had great affection for their American co-religionists, they were not uncritical, and significant tensions did develop over slavery. The article then examines the religious character of Scotch-Irish or Ulster-Scots identity in the late nineteenth century, which was articulated in response to the alleged demoralising influence of large-scale Irish immigration during and after the Famine of the 1840s, the so-called Romanisation of Catholicism, and the threat of Home Rule in Ireland. The importance of identity politics should not obscure religious developments, and the article ends with a consideration of the origins and character of fundamentalism, perhaps one of the most important cultural connections between Protestants in Northern Ireland and the United States in the twentieth century.

Antibiotic and anti-inflammatory therapies for cystic fibrosis

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.

The community trigger for anti-social behaviour: protecting victims or raising unrealistic expectations?

In October 2014, a statutory remedy for victims of anti-social behaviour became available called the community trigger. It affords complainants a right to request a review of their case if they consider that the response from local agencies has been inadequate. The Government has hailed the reform as “putting victims first”. This article first explores the context behind this reform. This includes a number of high profile cases involving the deaths of complainants after systematic failures led to prolonged exposure to anti-social behaviour. The article then examines the provisions and how they are likely to operate in practice. It argues that whilst much will depend upon implementation, the community trigger has the potential to improve the level of service offered to vulnerable complainants without necessarily impacting adversely on the rights of alleged perpetrators. As such, the community trigger may provide a model from which other areas of the criminal justice system may draw.

Catholicism and Fascism in Interwar Ireland

The interwar era saw the collapse of liberal democracy and the rise of anti-democratic authoritarian movements and states throughout much of Europe. Parliamentary or liberal democracy proved especially vulnerable in countries with large Catholic populations and ‘successor states’ – those states that achieved independence following the Great War. Despite meeting both criteria, the democratic structures of the Irish Free State – established in 1922 following a revolutionary struggle against British rule – proved remarkably resilient: indeed, it was arguably the only successor state to remain fully democratic by 1939 This outcome appears all the more striking given the formation of the state amidst a civil war, a form of conflict that frequently prevented the successful emergence of democracy. This is an article about the dog that didn’t bark: why did the kind of authoritarian political movements that flourished in many other parts of interwar Europe attract negligible support in the Irish Free State, and what does this have to tell us about the relationship between Catholicism and authoritarian politics? It begins by surveying the Irish Catholic Church’s attitudes to far-right politics in Continental Europe, and assessing how ‘official’ Catholic attitudes shaped popular perceptions of fascism and clerical authoritarianism within Ireland. It then explores the extent to which Ireland’s only significant fascistic movement – the Blueshirts – was influenced by, and sought to exploit, Catholicism. It concludes by questioning whether the immense influence of the Catholic Church and Catholic values within Irish political culture and society facilitated or hindered the cause of authoritarian politics in Ireland.

Zein-Based Nanoparticles Improve the Oral Bioavailability of Resveratrol and Its Anti-inflammatory Effects in a Mouse Model of Endotoxic Shock

Resveratrol offers pleiotropic health benefits including a reported ability to inhibit lipopolysaccharide (LPS)-induced cytokine production. The aim of this work was to prepare, characterize and evaluate a resveratrol nanoparticulate formulation based on zein. For this purpose, the oral bioavailability of the encapsulated polyphenol as well as its anti-inflammatory effects in a mouse model of endotoxic shock was studied. The resveratrol-loaded nanoparticles displayed a mean size of 307±3 nm, with a negative zeta potential (-51.1±1.55 mV), and a polyphenol loading of 80.2±3.26 μg/mg. In vitro, the release of resveratrol from the nanoparticles was found to be pH independent and adjusted well to the Peppas-Sahlin kinetic model, suggesting a mechanism based on the combination of diffusion and erosion of the nanoparticle matrix. Pharmacokinetic studies demonstrated that zein-based nanoparticles provided high and prolonged plasma levels of the polyphenol for at least 48 h. The oral bioavailability of resveratrol when administered in these nanoparticles increased up to 50% (19.2-fold higher than for the control solution of the polyphenol). Furthermore, nanoparticles administered daily for 7 days at 15 mg/kg, were able to diminish the endotoxic symptoms induced in mice by the intraperitoneal administration of LPS (i.e., hypothermia, piloerection and stillness). In addition, serum TNF-α levels were slightly lower (approximately 15%) than those observed in the control.

An unbiased genetic screen reveals the polygenic nature of the influenza virus anti-interferon response

UNLABELLED: Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space.

IMPORTANCE: In natural virus infections, the production of interferons leads to an antiviral state in cells that effectively limits virus replication. The interferon response places considerable selection pressure on viruses, and they have evolved a variety of ways to evade it. Although the influenza virus NS1 protein is a powerful interferon antagonist, the contributions of other viral genes to interferon evasion have not been well characterized. Here, we examined the effects of alleviating the selection pressure exerted by interferon by serially passaging influenza viruses in cells unable to respond to interferon. Viruses that grew to high titers had mutations at many normally conserved positions in nearly all genes and were not restricted to the NS1 gene. Our results demonstrate that influenza viruses have fine-tuned their entire genomes to evade the interferon response, and by removing interferon-mediated constraints, viruses can mutate at genome positions normally restricted by the interferon response.