“Happiest Delineation:” Literature, Reading Habits, and Characterization in Austen’s Northanger Abbey

In response to the strictly gendered society of Regency England, Jane Austen’s 1817 Gothic parody novel Northanger Abbey offers insight to the nuances of gender disparities. As such, the use of a gendered and historical critical approach throughout the project allows for a more comprehensive view of the societal expectations and taboos of 18th-century reading

"Half Savage and Hardy, and Free": The Failure of Feminine Identity in Wuthering Heights

Over the last half-century, much of the scholarly discourse concerning Wuthering Heights has considered Catherine Earnshaw’s struggle for belonging in the social order, using a transgressive mode of gender criticism to push against the constraints of traditional femininity found in both the space of Brontë’s world and within the norms of the eighteenth and nineteenth centuries at large. Using Lacanian theoretical analysis, however, I argue that Brontë’s novel effects an uncanny interpretation of womanhood, placing Catherine between two impossible, failed identities. The first, beginning in childhood, is rooted in an Imaginary form of identification with Heathcliff, who acts as the image with whom she identifies. The second emerges through her participation in the Symbolic order as a socially recognized wife, mother, and upper-class lady. Unable to find satisfaction in the self-mediation necessitated by these Imaginary and Symbolic identities, she lacks any identity at all. Instead, it is only in death that Catherine attains true freedom from the agony of identification. By tracing this search for a fully realized sense of self throughout her life, I endeavor to illustrate how Lacan’s theory offers a framework for understanding Catherine’s inner conflict, revealing the fundamental futility of searching for oneself in an external object or system

Epigenome-wide association studies of prenatal maternal mental health and infant epigenetic profiles: a systematic review

Abstract Prenatal stress and poor maternal mental health are associated with adverse offspring outcomes; however, the biological mechanisms are unknown. Epigenetic modification has linked maternal health with offspring development. Epigenome-wide association studies (EWAS) have examined offspring DNA methylation profiles for association with prenatal maternal mental health to elucidate mechanisms of these complex relationships. The objective of this study is to provide a comprehensive, systematic review of EWASs of infant epigenetic profiles and prenatal maternal anxiety, depression, or depression treatment. We conducted a systematic literature search following PRISMA guidelines for EWAS studies between prenatal maternal mental health and infant epigenetics through May 22, 2023. Of 645 identified articles, 20 fulfilled inclusion criteria. We assessed replication of CpG sites among studies, conducted gene enrichment analysis, and evaluated the articles for quality and risk of bias. We found one repeated CpG site among the maternal depression studies; however, nine pairs of overlapping differentially methylatd regions were reported in at least two maternal depression studies. Gene enrichment analysis found significant pathways for maternal depression but not for any other maternal mental health category. We found evidence that these EWAS present a medium to high risk of bias. Exposure to prenatal maternal depression and anxiety or treatment for such was not consistently associated with epigenetic changes in infants in this systematic review and meta-analysis. Small sample size, potential bias due to exposure misclassification and statistical challenges are critical to address in future efforts to explore epigenetic modification as a potential mechanism by which prenatal exposure to maternal mental health disorders leads to adverse infant outcomes

Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control

Protein misfolding is linked to a wide array of human disorders, including Alzheimer’s disease, Parkinson’s disease and type II diabetes1,2. Protective cellular protein quality control (PQC) mechanisms have evolved to selectively recognize misfolded proteins and limit their toxic effects3,4,5,6,7,8,9, thus contributing to the maintenance of the proteome (proteostasis). Here we examine how molecular chaperones and the ubiquitin–proteasome system cooperate to recognize and promote the clearance of soluble misfolded proteins. Using a panel of PQC substrates with distinct characteristics and localizations, we define distinct chaperone and ubiquitination circuitries that execute quality control in the cytoplasm and nucleus. In the cytoplasm, proteasomal degradation of misfolded proteins requires tagging with mixed lysine 48 (K48)- and lysine 11 (K11)-linked ubiquitin chains. A distinct combination of E3 ubiquitin ligases and specific chaperones is required to achieve each type of linkage-specific ubiquitination. In the nucleus, however, proteasomal degradation of misfolded proteins requires only K48-linked ubiquitin chains, and is thus independent of K11-specific ligases and chaperones. The distinct ubiquitin codes for nuclear and cytoplasmic PQC appear to be linked to the function of the ubiquilin protein Dsk2, which is specifically required to clear nuclear misfolded proteins. Our work defines the principles of cytoplasmic and nuclear PQC as distinct, involving combinatorial recognition by defined sets of cooperating chaperones and E3 ligases. A better understanding of how these organelle-specific PQC requirements implement proteome integrity has implications for our understanding of diseases linked to impaired protein clearance and proteostasis dysfunction