Early modern melancholia and present day depression: A comparative study of the female experience in dramatic and medical sources

This thesis examines the relationship between the early modern understanding of female melancholia and women’s depression today. Working with proto-medical treatises and Shakespearean drama from the early modern period (1580-1665), alongside contemporary diagnostic frameworks and psychosocial research (1960-2017), it investigates how female melancholics and depressed women speak to each other across the historical divide. Late sixteenth- and early seventeenth-century experiences of melancholia shed new light, in particular, on the neglected area of women’s experience of depression today. I interrogate the notion, prevalent in early modern literature and culture, that female melancholia is equated with weakness; and demonstrate how this assumption was explored and challenged on the early modern stage by William Shakespeare, John Fletcher, and George Wilkins. I argue that melancholia emerges in early modern drama as a potential site for identity and agency, and emphasise the importance of sympathetic recognition for sufferers in the past and the present. The terms ‘melancholia’ and ‘depression’ are only accessible to women under certain circumstances, however, and not all women are equally successful in eliciting a sympathetic response. In The Two Noble Kinsmen, women’s social class determines their degree of success in receiving sympathy, as I discuss through the sharp disparity between the grieving Queens and the greensick Jailer’s Daughter. In King John, royal position affects how much sympathy Queen Constance receives in her maternal grief. And in Pericles, a surprising relationship emerges between recognition, chastity and melancholia through the complex figure of Pericles’ daughter Marina. These three plays reveal important and counterintuitive links between early modern feminine selfhood and melancholia which, I argue, can illuminate in new ways the experience of female depression today. This thesis does not propose a seamless continuum from the early modern period to the present, but instead sets out to show how certain important cultural trends and assumptions are retained in more recent diagnostic and psychosocial studies. By exploring the narrative of these two periods together, in an open and interdisciplinary manner, my project seeks to improve our understanding of the way melancholic women were treated in the early modern period; and, in so doing, to reconsider the ways women experiencing depression are recognised and supported today

Characterization of inositol lipid metabolism in gut-associated Bacteroidetes

Inositol lipids are ubiquitous in eukaryotes and have finely tuned roles in cellular signalling and membrane homoeostasis. In Bacteria, however, inositol lipid production is relatively rare. Recently, the prominent human gut bacterium Bacteroides thetaiotaomicron (BT) was reported to produce inositol lipids and sphingolipids, but the pathways remain ambiguous and their prevalence unclear. Here, using genomic and biochemical approaches, we investigated the gene cluster for inositol lipid synthesis in BT using a previously undescribed strain with inducible control of sphingolipid synthesis. We characterized the biosynthetic pathway from myo-inositol-phosphate (MIP) synthesis to phosphoinositol dihydroceramide, determined the crystal structure of the recombinant BT MIP synthase enzyme and identified the phosphatase responsible for the conversion of bacterially-derived phosphatidylinositol phosphate (PIP-DAG) to phosphatidylinositol (PI-DAG). In vitro, loss of inositol lipid production altered BT capsule expression and antimicrobial peptide resistance. In vivo, loss of inositol lipids decreased bacterial fitness in a gnotobiotic mouse model. We identified a second putative, previously undescribed pathway for bacterial PI-DAG synthesis without a PIP-DAG intermediate, common in Prevotella. Our results indicate that inositol sphingolipid production is widespread in host-associated Bacteroidetes and has implications for symbiosis

Exile Vol. XXIX No. 2

Photo by John Taylor 2 Poem by Ezra Pound 3 Photo by James Lundy 4 Balanced Budget by August West 5 The Lighter by John Zarchen 6-7 Photo by Theodore Granberg 8 Uptown by Christopher B. Brougham 9 Photo by Jeff Russell 9 Heartstrings by Pete Waters 10 Spell by Eric Stevenson 10 Mums by Mandy Wilson 10 A New Day by Chad Hussey 11 Photo by Chad Hussey 12 Solitare by Gordon Black 13-14 Photo by James Lundy 15 A Grave Day-Dream by John Zarchen 16 Photo by James Lundy 17 Photo by Pauela Theodotou 18 Reconciliation by R. T. Hayashi 19 Michigan Rt. 37 by Ruth Wick 20 Shenango Valley by August West 20 Photo by James Lundy 21 Drawing by Adrienne Wehr 22 Ultraviolet Blues by Kathy Shelton 23 New Orleans & The Silky Black Seams Of My Stockings by Kate Reynolds 23 Refraction by Pam Houston 23-31 Photo by James Lundy 32 A Midsummer Night\u27s... by R. T. Hayashi 33 Couch sleeping by Eric Stevenson 33 Before We Could Build by Kim Kiefer 34 Photo by Chad Hussey 35 The Legend Of The Bear Mother by Amy Pence 36 Photo by James Lundy 37 Cover Drawing by Peter Brooke -title pag

Epigenetic and Genetic Influences on DNA Methylation Variation in Maize Populations

DNA methylation is a chromatin modification that is frequently associated with epigenetic regulation in plants and mammals. However, genetic changes such as transposon insertions can also lead to changes in DNA methylation. Genome-wide profiles of DNA methylation for 20 maize (Zea mays) inbred lines were used to discover differentially methylated regions (DMRs). The methylation level for each of these DMRs was also assayed in 31 additional maize or teosinte genotypes, resulting in the discovery of 1966 common DMRs and 1754 rare DMRs. Analysis of recombinant inbred lines provides evidence that the majority of DMRs are heritable. A local association scan found that nearly half of the DMRs with common variation are significantly associated with single nucleotide polymorphisms found within or near the DMR. Many of the DMRs that are significantly associated with local genetic variation are found near transposable elements that may contribute to the variation in DNA methylation. Analysis of gene expression in the same samples used for DNA methylation profiling identified over 300 genes with expression patterns that are significantly associated with DNA methylation variation. Collectively, our results suggest that DNA methylation variation is influenced by genetic and epigenetic changes that are often stably inherited and can influence the expression of nearby genes

Risk of Parkinson disease in carriers of parkin mutations : estimation using the kin-cohort method

Objective: To estimate the risk of Parkinson disease (PD) in individuals with mutations in the Parkin gene. Design: We assessed point mutations and exon deletions and duplications in the Parkin gene in 247 probands with PD (age at onset 50 years) and 104 control probands enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. For each first-degree relative, a consensus diagnosis of PD was established. The probability that each relative carried a mutation was estimated from the proband's Parkin carrier status using Mendelian principles and from the relationship of the relative to the proband. Setting: Tertiary care movement disorders center. Patients: Cases, controls, and their first-degree relatives were enrolled in the GEPD study. Main Outcome Measures: Estimated age-specific penetrance in first-degree relatives. Results: Parkin mutations were identified in 25 probands with PD (10.1%), 18 (72.0%) of whom were heterozygotes. One Parkin homozygote was reported in 2 siblings with PD. The cumulative incidence of PD to age 65 years in carrier relatives (age-specific penetrance) was estimated to be 7.0% (95% confidence interval, 0.4%-71.9%), compared with 1.7% (95% confidence interval, 0.8%-3.4%) in noncarrier relatives of the cases (P = .59) and 1.1% (95% confidence interval, 0.3%-3.4%) in relatives of the controls (compared with noncarrier relatives, P = .52). Conclusions: The cumulative risk of PD to age 65 years in a noncarrier relative of a case with an age at onset of 50 years or younger is not significantly greater than the general population risk among controls. Age-specific penetrance among Parkin carriers, in particular heterozygotes, deserves further study. Mutations in the Parkin gene (PARK2; GenBank AB009973) are associated primarily with early-onset Parkinson disease (PD), defined as age at onset (AAO) ranging from 45 years or younger to 55 years or younger, but have also been described in PD cases with an AAO older than 70 years. In PD cases with an AAO of 45 years or younger with a mode of inheritance consistent with autosomal recessive transmission, the frequency of Parkin mutations may be as high as 49%, whereas in cases without a family history of PD the range is 15% to 18%. Age at onset is inversely correlated with the frequency of Parkin mutations in both familial and sporadic cases. Several studies have compared the AAO of PD in heterozygous, compound heterozygous, and homozygous Parkin mutation carriers and found that heterozygous cases, both familial and sporadic, have an older AAO. Heterozygous Parkin mutation carriers are more frequently reported among sporadic than familial cases. Information on the risk of PD in individuals who carry Parkin mutations in either the homozygous, compound heterozygous, or heterozygous state (or penetrance) is essential for genetic counseling. The penetrance of Parkin mutations has only been reported for isolated families. Most of the previous study designs sampled PD cases based on family history of PD, which would bias penetrance estimates upwards. To obtain an unbiased estimate of risk, a population-based random sample would be desirable, but Parkin mutations are so rare in the population that such a sample would have to be extremely large to obtain sufficient precision in penetrance estimates. To obtain unbiased estimates of the risk of PD in Parkin carriers despite the low population frequency of Parkin mutations, we used a kin-cohort study design applied to participants in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. The kin-cohort design is highly efficient for estimating penetrance because the relatives' mutation status is not required for the analyses, thus reducing costs for genetic analysis

Case-control study of the parkin gene in early-onset Parkinson disease

Background: Mutations in parkin are estimated to account for as much as 50% of familial Parkinson disease (PD) and 18% of sporadic PD. Single heterozygous mutations in parkin in both familial and sporadic cases may also increase susceptibility to PD. To our knowledge, all previous studies have been restricted to PD cases; this is the first study to systematically screen the parkin coding regions and exon deletions and duplications in controls. Objective: To determine the frequency and spectrum of parkin variants in early-onset PD cases (aged 50 years) and controls participating in a familial aggregation study. Patients and Methods: We sequenced the parkin gene in 101 cases and 105 controls. All cases and controls were also screened for exon deletions and duplications by semiquantitative multiplex polymerase chain reaction. Results: Thirteen (12.9% [95% confidence interval, 7%-21%]) of the 101 cases had a previously described parkin mutation: 1 was homozygous, 11 were heterozygous, and 1 was a compound heterozygote. The mutations Arg42Pro (exon 2) and Arg275Trp (exon 7) were recurrent. The previously reported synonymous substitution Leu261Leu (c.884A>G) was identified in 4 (3.9%) of 101 cases and 2 (2%) of 105 controls (P = .44). Excluding the synonymous substitution Leu261Leu (heterozygotes), 10 (9.9% [95% confidence interval, 4.6%-17.5%]) carried mutations. Conclusions: The frequency of mutations among cases that were not selected based on family history of PD is similar to what has previously been reported in sporadic PD. The similar frequency of Leu261Leu in cases and controls suggests it is a normal variant rather than a disease-associated mutation. We confirmed that heterozygous parkin mutations may increase susceptibility for early-onset PD

Multidisciplinary teams, and parents, negotiating common ground in shared-care of children with long-term conditions: A mixed methods study

Background: Limited negotiation around care decisions is believed to undermine collaborative working between parents of children with long-term conditions and professionals, but there is little evidence of how they actually negotiate their respective roles. Using chronic kidney disease as an exemplar this paper reports on a multi-method study of social interaction between multidisciplinary teams and parents as they shared clinical care. Methods. Phases 1 and 2: a telephone survey mapping multidisciplinary teams' parent-educative activities, and qualitative interviews with 112 professionals (Clinical-psychologists, Dietitians, Doctors, Nurses, Play-specialists, Pharmacists, Therapists and Social-workers) exploring their accounts of parent-teaching in the 12 British children's kidney units. Phase 3: six ethnographic case studies in two units involving observations of professional/parent interactions during shared-care, and individual interviews. We used an analytical framework based on concepts drawn from Communities of Practice and Activity Theory. Results: Professionals spoke of the challenge of explaining to each other how they are aware of parents' understanding of clinical knowledge, and described three patterns of parent-educative activity that were common across MDTs: Engaging parents in shared practice; Knowledge exchange and role negotiation, and Promoting common ground. Over time, professionals had developed a shared repertoire of tools to support their negotiations with parents that helped them accomplish common ground during the practice of shared-care. We observed mutual engagement between professionals and parents where a common understanding of the joint enterprise of clinical caring was negotiated. Conclusions: For professionals, making implicit knowledge explicit is important as it can provide them with a language through which to articulate more clearly to each other what is the basis of their intuition-based hunches about parents' support needs, and may help them to negotiate with parents and accelerate parents' learning about shared caring. Our methodology and results are potentially transferrable to shared management of other conditions. © 2013 Swallow et al.; licensee BioMed Central Ltd

Quantification of magnetosphere–ionosphere coupling timescales using mutual information : response of terrestrial radio emissions and ionospheric–magnetospheric currents

Auroral kilometric radiation (AKR) is a terrestrial radio emission excited by the same accelerated electrons which excite auroral emissions. Although it is well correlated with auroral and geomagnetic activity, the coupling timescales between AKR and different magnetospheric or ionospheric regions have yet to be determined. Estimation of these coupling timescales is non-trivial as a result of complex, non-linear processes which rarely occur in isolation. In this study, the mutual information between AKR intensity and different geomagnetic indices is used to assess the correlation between variables. Indices are shifted to different temporal lags relative to AKR intensity, and the lag at which the variables have the most shared information is found. This lag is interpreted as the coupling timescale. The AKR source region receives the effects of a shared driver before the auroral ionosphere. Conversely, the polar ionosphere reacts to a shared driver before the AKR source region. Bow shock interplanetary magnetic field BZ is excited about 1 h before AKR enhancements. This work provides quantitatively determined temporal context to the coupling timelines at Earth. The results suggest that there is a sequence of excitation following the onset of a shared driver: first, the polar ionosphere feels the effects, followed by the AKR source region and then the auroral ionosphere