Trade relations between the Mycenaean Greeks and the civilizations of the Eastern Mediterranean in the Late Bronze Age

The Mycenaean Greeks are often assumed to have been in contact with the civilizations of the Mediterranean throughout the Late Bronze Age. The extent of this contact however is not as clearly understood, and the archaeological evidence that has survived provides a sample of what must have exchanged hands. This thesis will examine the archaeological, textual and iconographic evidence from a number of sites and sources, from the Anatolian plains to the Kingdom of Egypt and major settlements in-between during the Late Bronze Age to examine what trade may have looked like for the Mycenaeans. Due to the extensive finds in some regions and a lack of evidence in others, this paper will also try to understand the relationship between the Mycenaeans and other cultures to determine whether a trade embargo was enacted on the Mycenaeans by the Central Anatolian Hittites during this period, or whether other factors contributed to the paucity of objects in Central Anatolia.

The Relationship Between Self-Awareness and Psychotic-Like Experiences

The psychosis phenotype is thought to exist on a continuum, such that the same symptoms experienced by individuals diagnosed with psychotic disorders can also manifest in the general population to a less severe degree. The subclinical psychotic-like experiences reported by healthy individuals share a number of risk factors with psychotic disorders and confer greater risk of developing a psychotic disorder. Thus, healthy individuals with psychotic-like experiences comprise a valid population in which to study the underlying mechanisms of clinically significant psychotic symptoms. In this thesis, we aimed to further our understanding of psychotic-like experiences and the individuals who report them. We explored the relationships between tasks measuring different aspects of self-awareness and self-reported psychotic-like experiences using data obtained from 30 university students. We found that greater sensitivity to the difference between one’s own voice and another person’s voice predicted fewer symptoms of persecutory ideation. Additionally, we found that greater tendency to misattribute one’s own voice to an external source predicted greater symptoms of persecutory ideation.

Calling for resistance: The political economy of Indian and Canadian call centre industries

Call centres have in the last three decades come to define the interaction between corporations, governments, and other institutions and their respective customers, citizens, and members. From telemarketing to tele-health services, to credit card assistance, and even emergency response systems, call centres function as a nexus mediating technologically enabled labour practices with the commodification of services. Because of the ubiquitous nature of the call centre in post-industrial capitalism, the banality of these interactions often overshadows the nature of work and labour in this now-global sector. Advances in telecommunication technologies and the globalization of management practices designed to oversee and maintain standardized labour processes have made call centre work an international phenomenon. Simultaneously, these developments have dislocated assumptions about the geographic and spatial seat of work in what is defined here as the new international division of knowledge labour. The offshoring and outsourcing of call centre employment, part of the larger information technology and information technology enabled services sectors, has become a growing practice amongst governments and corporations in their attempts at controlling costs. Leading offshore destinations for call centre work, such as Canada and India, emerged as prominent locations for call centre work for these reasons. While incredible advances in technology have permitted the use of distant and “offshore” labour forces, the grander reshaping of an international political economy of communications has allowed for the acceleration of these processes. New and established labour unions have responded to these changes in the global regimes of work by seeking to organize call centre workers. These efforts have been assisted by a range of forces, not least of which is the condition of work itself, but also attempts by global union federations to build a bridge between international unionism and local organizing campaigns in the Global South and Global North. Through an examination of trade union interventions in the call centre industries located in Canada and India, this dissertation contributes to research on post-industrial employment by using political economy as a juncture between development studies, critical communications, and labour studies.

Elucidation of the interactions between the transcription factor E2A and the transcriptional co-activator CBP/p300

E2A is a transcription factor that plays a particularly critical role in lymphopoiesis. The chromosomal translocation 1;19, disrupts the E2A gene and results in the expression of the fusion oncoprotein E2A-PBX1, which is implicated in acute lymphoblastic leukemia. Both E2A and E2A-PBX1 contain two activation domains, AD1 and AD2, which comprise conserved ΦxxΦΦ motifs where Φ denotes a hydrophobic amino acid. These domains function to recruit transcriptional co-activators and repressors, including the histone acetyl transferase CREB binding protein (CBP) and its paralog p300. The PCET motif within E2A AD1 interacts with the KIX domain of CBP/p300, the disruption of which abrogates the transcriptional activation by E2A and the transformative properties of E2A-PBX1. The generation of a peptide-based inhibitor targeting the PCET:KIX interaction would serve useful in further assessing the role of E2A and E2A-PBX1 in lymphopoiesis and leukemogenesis. An interaction between E2A AD2 and the KIX domain has also been recently identified, and the TAZ domains of CBP/p300 have been shown to interact with several transcription factors that contain ΦxxΦΦ motifs. Thus the design of an inhibitor of the E2A:CBP/p300 interaction requires the full complement of interactions between E2A and the various domains of CBP/p300 to be elucidated. Here, we have used nuclear magnetic resonance (NMR) spectroscopy to determine that AD2 interacts with KIX at the same site as PCET, which indicates that the E2A:KIX interaction can be disrupted by targeting a single binding site. Using an iterative synthetic peptide microarray approach, a peptide with the sequence DKELQDLLDFSLQY was derived from PCET to interact with KIX with higher affinity than the wild type sequence. This peptide now serves as a lead molecule for further development as an inhibitor of the E2A:CBP/p300 interaction. Fluorescence anisotropy, peptide microarray technology, and isothermal titration calorimetry were employed to characterize interactions between both TAZ domains of CBP/p300 and the PCET motif and AD2 of E2A. Alanine substitution of residues within PCET demonstrated that the ΦxxΦΦ motif is a key mediator of these interactions, analogous to the PCET:KIX interaction. These findings now inform future work to establish possible physiological roles for the E2A:TAZ1 and E2A:TAZ2 interactions.

Relationship between abnormal maternal inflammation and insulin resistance during pregnancy

Abnormal maternal inflammation during pregnancy is linked to complications such as preeclampsia and fetal growth restriction. There is growing evidence that insulin resistance is also associated with a heightened inflammatory state, and is linked to pregnancy complications such as gestational diabetes. This study tested the hypothesis that abnormal inflammation during pregnancy is causally linked to elevations in blood glucose and insulin resistance. To induce a state of abnormal systemic inflammation, bacterial lipopolysaccharide (LPS) was administered to pregnant rats on gestational days (GD) 13.5-16.5. Dams treated with LPS exhibited an abnormal immune response characterized by an elevation in white blood cells, which was linked to reduced fetal weight and increased glucose levels over pregnancy. Abnormal inflammation is characterized by increased levels of circulating pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF) and interleukin-6, which contribute to insulin resistance by inhibiting the insulin signalling pathway. TNF in particular induces a serine phosphorylation (pSer307) of insulin receptor substrate 1 (IRS-1). In our model, insulin resistance was assessed by measuring the extent of pSer307 of IRS-1 and total IRS-1 expression in skeletal muscle, as well as changes in metabolic parameters and pancreas tissue morphology associated with insulin resistance. LPS-treated dams exhibited a significant reduction in IRS-1 expression, elevation in fasting glucose levels, and reduction in insulin sensitivity indices. There were also biologically relevant increases in fasting plasma insulin levels and insulin resistance indices, but not pSer307 of IRS-1 and pancreatic islet size. To determine whether inflammation plays a role in reducing insulin signalling and the other changes associated with LPS administration, etanercept, a TNF antagonist, was administered on GDs 13.5 and 15.5 prior to LPS injections. With the exception of IRS-1 expression, in rats treated with etanercept all of the measured parameters remained at the levels observed in saline controls, indicating a link between abnormal inflammation and insulin resistance. The results of this study support the practice of monitoring the inflammatory conditions of the mother prior to and during pregnancy, and support further investigation into the potential use of anti-inflammatory agents during pregnancy in women at risk of insulin resistance and gestational diabetes.

Differences in Abdominal and Liver Fat Accumulation Between Obesity-Matched Adults With and Without Type 2 Diabetes

Despite attempts to identify the mechanisms by which obesity leads to the development of Type 2 Diabetes (T2D), it remains unclear why some but not all adults with obesity develop T2D. Given the established associations between visceral adipose tissue (VAT) and liver fat with insulin resistance, we hypothesized that compared to age and obesity matched adults who were non-diabetic (NT2D), adults with T2D would have greater amounts of VAT and liver fat. The International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship with Cardiometabolic Risk/Intra-Abdominal Adiposity (INSPIRE ME IAA) aims to study the associations between VAT and liver fat and risk of developing T2D and cardiovascular disease. Four thousand, five hundred and four participants were initially recruited; from this, 2383 White and Asian adults were selected for this ancillary analysis. The NT2D and T2D groups were matched for age, body mass index (BMI) and waist circumference (WC). The T2D and NT2D groups were also compared to participants with either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT; IFG/IGT)). Abdominal adipose tissue was measured by computed tomography; liver fat was estimated using computed tomography-derived mean attenuation. Secondary analysis determined whether differences existed between NT2D and T2D groups in VAT and liver fat accumulation within selected BMI categories for Whites and Asians. We report across sex and race, T2D and IFG/IGT groups had elevated VAT and liver fat compared to the NT2D group (p<0.05). VAT was not different between IFG/IGT and T2D groups (p>0.05), however liver fat was greater in the T2D group compared to the IFG/IGT group in both Whites and Asians (p<0.05). Within each BMI category, the T2D group had elevated VAT and liver fat compared to the age and anthropometrically matched NT2D group in both Whites and Asians (p<0.05). With few exceptions, abdominal subcutaneous adipose tissue was not different in the T2D or IFG/IGT groups compared to the NT2D group independent of sex and race. Compared to age and obesity-matched adults who are NT2D, we observe that White and Asian adults with T2D, and those with IFG/IGT, present with greater levels of both VAT and liver fat.