A Family of Migrant Workers: Region and the Rise of Neoliberalism in the Fiction of Alistair MacLeod

Realism and regionalism are tightly coupled in critical analysis of Alistair MacLeod’s fiction, but Herb Wyile’s recent study Anne of Tim Hortons was the first to examine the ascendance of neoliberal ideologies and the effects of a globalized economy on the workers represented in his fiction. MacLeod’s novel No Great Mischief suggests that the underdevelopment of Atlantic Canada and migration of workers to other regions is a result of nineteenth- and twentieth-century economic and political changes. It traces the history of labour migration as embedded in the birth of neoliberalism, and MacLeod’s portrait of a migrant community acknowledges the effects of a longstanding history of economic globalization on workers from different corners of the world. No Great Mischief is visibly about clan, blood ties, race, and region, but its complex analogies create a kind of metaphorical family of migrant workers – a “family” that evokes the contours of, but is not identical with, the nation

"The animal out of the desert": The Nomadic Metaphysics of Michael Ondaatje’s In the Skin of a Lion

In In the Skin of a Lion, Michael Ondaatje explores mobile figures through the trope of nomadism. Linking a series of the novel's mobile figures together and suggesting their equivalence as nomadic migrants, Ondaatje dissolves the distinction between native and foreign workers. He thus attempts to resist the essentialist links between people and place that are prevalent in the arborescent metaphors of belonging that poststructuralists like Gilles Deleuze and Félix Guattari critique. Instead of what Liisa Malkki calls "sedentarist metaphysics," the novel subscribes to what Tim Cresswell refers to as "nomadic metaphysics" - an interest in the routes of travel and a concomitant dismissal of the fixity of rooted identity. Ondaatje's strategy of "nomadic metaphysics" obscures the material history of, and important differences among, specific migrations, routes, and/or patterns of mobility that his novel identifies. The novel seems to assert a citizenship that exceeds the nation-state and challenges the class hierarchies of liberal conceptions of citizenship; however, because of Ondaatje's use of patterns of equivalence, the cosmopolitan citizenship he gestures to is not realized

Intracellular application of an asparaginyl endopeptidase for producing recombinant head-to-tail cyclic proteins

Peptide backbone cyclization is commonly observed in nature and is increasingly applied to proteins and peptides to improve thermal and chemical stability and resistance to proteolytic enzymes and enhance biological activity. However, chemical synthesis of head-to-tail cyclic peptides and proteins is challenging, is often low yielding, and employs toxic and unsustainable reagents. Plant derived asparaginyl endopeptidases such as OaAEP1 have been employed to catalyze the head-to-tail cyclization of peptides in vitro, offering a safer and more sustainable alternative to chemical methods. However, while asparaginyl endopeptidases have been used in vitro and in native and transgenic plant species, they have never been used to generate recombinant cyclic proteins in live recombinant organisms outside of plants. Using dihydrofolate reductase as a proof of concept, we show that a truncated OaAEP1 variant C247A is functional in the Escherichia coli physiological environment and can therefore be coexpressed with a substrate protein to enable concomitant in situ cyclization. The bacterial system is ideal for cyclic protein production owing to the fast growth rate, durability, ease of use, and low cost. This streamlines cyclic protein production via a biocatalytic process with fast kinetics and minimal ligation scarring, while negating the need to purify the enzyme, substrate, and reaction mixtures individually. The resulting cyclic protein was characterized in vitro, demonstrating enhanced thermal stability compared to the corresponding linear protein without impacting enzyme activity. We anticipate this convenient method for generating cyclic peptides will have broad utility in a range of biochemical and chemical applications.</p

Capital Intraconversion' and Canadian Literary Prize Culture

This paper analyzes how the “particular symbolic fortunes” of Canada’s most widely recognized literary prize, the Scotiabank Giller Prize, undergo what James English calls “capital intraconversion”––how they are “culturally ‘laundered’” through their association with Frontier College, Canada’s longest-running adult literacy organization. While the Giller initially benefitted from fashioning itself as the private, industry-driven alternative to state-sponsored culture in Canada, increasing criticism of its corporate sponsorship has led, in the past decade, to a rebranding effort. This effort, I contend, seeks to benefit from two key terms––multiculturalism and literacy. Associated as the discourse of multiculturalism and the figure of the literate citizen are with the strong publics of the western, liberal-democratic nation-state, they possess a remarkable ability to accentuate the symbolic capital of Canada’s most widely recognized literary prize

Computational Competitive and Negative Design to Derive a Specific cJun Antagonist

Basic leucine zipper (bZIP) proteins reside at the end of cell-signaling cascades and function to modulate transcription of specific gene targets. bZIPs are recognized as important regulators of cellular processes such as cell growth, apoptosis, and cell differentiation. One such validated transcriptional regulator, activator protein-1, is typically comprised of heterodimers of Jun and Fos family members and is key in the progression and development of a number of different diseases. The best described component, cJun, is upregulated in a variety of diseases such as cancer, osteoporosis, and psoriasis. Toward our goal of inhibiting bZIP proteins implicated in disease pathways, we here describe the first use of a novel <i>in silico</i> peptide library screening platform that facilitates the derivation of sequences exhibiting a high affinity for cJun while disfavoring homodimer formation or formation of heterodimers with other closely related Fos sequences. In particular, using Fos as a template, we have computationally screened a peptide library of more than 60 million members and ranked hypothetical on/off target complexes according to predicted stability. This resulted in the identification of a sequence that bound cJun but displayed little homomeric stability or preference for cFos. The computationally selected sequence maintains an interaction stability similar to that of a previous experimentally derived cJun antagonist while providing much improved specificity. Our study provides new insight into the use of tandem <i>in silico</i> screening/<i>in vitro</i> validation and the ability to create a peptide that is capable of satisfying conflicting design requirements

Anionic lipid vesicles have differential effects on the aggregation of early onset-associated α-synuclein missense mutants

α-synuclein (αS) is the key component of synucleinopathies such as Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy. αS was first linked to PD through the identification of point mutations in the SNCA gene, causing single amino acid substitutions within αS and familial autosomal dominant forms of PD that profoundly accelerated disease onset by up to several decades. At least eight single-point mutations linked to familial PD (A30G/P, E46K, H50Q, G51D, and A53T/E/V) are located in proximity of the region preceding the non-β amyloid component (preNAC) region, strongly implicating its pathogenic role in αS-mediated cytotoxicity. Furthermore, lipids are known to be important for native αS function, where they play a key role in the regulation of synaptic vesicle docking to presynaptic membranes and dopamine transmission. However, the role of lipids in the function of mutant αS is unclear. Here, we studied αS aggregation properties of WT αS and five of the most predominant single-point missense mutants associated with early onset PD in the presence of anionic 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine lipid vesicles. Our results highlight significant differences between aggregation rates, the number of aggregates produced, and overall fibril morphologies of WT αS and the A30P, E46K, H50Q, G51D, and A53T missense mutants in the presence of lipid vesicles. These findings have important implications regarding the interplay between the lipids required for αS function and the individual point mutations known to accelerate PD and related diseases