Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.

The Resurgence of Gaelic power in Ireland and Scotland and its wider impact, c.1350-1513

Over the course of the later Middle Ages nearly half the landmass of the British Isles fell under the control of a handful of Gaelic dynasties in Ireland and Scotland. The impact of this profound geopolitical recasting of much of the Atlantic Archipelago has however, received very little scholarly attention. Instead, historians have tended to view events within this expanding Gaelic world, or Gàidhealtachd, as peripheral to the political development of the British Isles and the course of Anglo-Scottish relations during the later Medieval period. Drawing upon a comprehensive range of sources from Ireland, Scotland, and England, as well as significant archival research, this thesis challenges the concept of the so-called 'Celtic fringe' and illustrates how developments within the Gàidhealtachd impacted upon the course of 'British' politics during the period c.1350-1513. The thesis centres on an examination of how two competing Gaelic alliance systems came to dominate much of the Gàidhealtachd from the late fourteenth century through to the early 1500s. The first of these alliance blocs was controlled chiefly by the O'Neills of Tyrone, the O'Briens of Thomond, and MacDonalds of the Hebrides; in the other network the O'Donnells of Tyrconnell, the Burkes of Mayo and the Campbells of Argyll held sway. By tracing the interconnectivity of the lordships in each respective network, the thesis investigates how these alliance systems became a durable force not only within the Gàidhealtachd but also on the broader 'British' stage. The thesis is structured in a manner that makes the intricate, lineage-based world of the Gàidhealtachd more accessible. Each chapter shifts between the various regions of the Gaelic world and examines how developments in one region impacted upon corresponding territory. Ultimately, this provides historians with a new model for exploring what has previously been a majorly neglected area of Irish and British history.

An archaeology of female monasticism in medieval Ireland

This thesis considers the archaeological evidence for female monasticism in medieval Ireland, with a particular emphasis on the later medieval period. Female monasticism has been considered from an archaeological perspective in several countries, most notably Britain, but has yet to be considered in any detail in Ireland. The study aims to bring together all the currently available evidence on female monasticism and consider it through an engendered archaeological approach. The data gathering for this research has been deliberately wide, and where gaps have been identified in the Irish evidence, comparative material from elsewhere has been considered. Nunneries should not be expected to conform to what has become the male monastic template of a claustrally-planned monastery. The research conducted shows a distinct and varied archaeology and architecture for medieval nunneries in Ireland which suggests that a claustral plan was not considered an essential part of a nunnery scheme. Nunneries provided an enclosed environment where women, for a variety of motives could become brides of Christ. Through the performance and celebration of the daily Divine Office, the Mass and seasonal liturgy, spaces used by the nunnery community were negotiated and transformed into a sacred Paradise on earth. However, rather than being isolated in the landscape nunneries in later medieval Ireland were located either within or close to walled towns, larger unenclosed settlements and settlement clusters and would have been well known throughout their hinterlands. This research concludes that nunneries were an intrinsic part of the medieval monastic landscape in Ireland and an essential component of patrons’ portfolios of patronage, at a particularly local level, and where they interacted closely with their local community.