Houses, Secrets, and the Closet: Locating Masculinities from the Gothic Novel to Henry James

"Houses, Secrets, and the Closet" investigates the literary production of masculinities and their relation to secrets and sexualities in 18th and 19th century fiction. It focusses on close readings of Gothic fiction, Sensation Novels, and tales by Horace Walpole, Ann Radcliffe, William Godwin, Mary Elizabeth Braddon, Wilkie Collins, and Henry James. The study approaches these texts through the lens of domestic space, gender, knowledge, and power. This approach serves to investigate the cultural roots of the 'closet' - the male homosexual secret - which reveals a more general notion of male secrecy in modern society. The study thus contributes to a better understanding of the cultural history of masculinities and sexualities

Houses, Secrets, and the Closet

»Houses, Secrets, and the Closet« investigates the literary production of masculinities and their relation to secrets and sexualities in 18th and 19th century fiction. It focusses on close readings of Gothic fiction, Sensation Novels, and tales by Horace Walpole, Ann Radcliffe, William Godwin, Mary Elizabeth Braddon, Wilkie Collins, and Henry James. The study approaches these texts through the lens of domestic space, gender, knowledge, and power. This approach serves to investigate the cultural roots of the »closet« – the male homosexual secret – which reveals a more general notion of male secrecy in modern society. The study thus contributes to a better understanding of the cultural history of masculinities and sexualities

Ergebnisse nach modifizierter Norwood-Operation bei Patienten mit Linksherzhypoplasie-Varianten im Vergleich zum typischen Krankheitsbild

Während die Fehlbildungen des linken Herzens mit Hypoplasie der Mitralklappe, des linken Ventrikels, der Aortenklappe und des Aortenbogens als hypoplastisches Linksherzsyndrom (HLHS) bezeichnet werden, fasst man die anderen komplexen Herzfehler, die mit einer Hypoplasie des Aortenbogens bei verschiedener dominanter oder balancierter Ventrikelmorphologie einhergehen, als Non-HLHS zusammen. Diese Gruppe ist inhomogen und klein. Das Behandlungskonzept ist ebenfalls dreistufig wie beim klassischen hypoplastischen Linksherzsyndrom. In der vorliegenden Arbeit wurden die früh- und spätpostoperativen Verläufe und die jeweilige Letalität der Patientengruppe mit Non-HLHS (n = 26), die zwischen November 1993 und Juni 2006 im Kinderherzzentrum Kiel des Universitätsklinikums Schleswig-Holstein behandelt wurden, analysiert und mit einer Gruppe von Patienten mit HLHS (n = 157) verglichen. Alle Patientendaten wurden retrospektiv analysiert und anonymisiert ausgewertet. Das Follow-up erfolgte bis zum 31.12.2009. Das männliche Geschlecht überwog in allen Gruppen (76 % Non-HLHS/64,3 % HLHS). Zwischen den Gruppen der Non-HLHS-Patienten und der HLHS-Gruppe bestanden keine signifikanten Unterschiede bei der Geschlechtsverteilung, dem Geburtsgewicht, der Frühgeburtlichkeit und dem medianen Durchmesser der Aorta ascendens. 13 Kinder (50 %) in den drei Patientengruppen mit Non-HLHS und 21 Kinder mit HLHS (13,3 %) hatten zusätzliche extrakardiale Fehlbildungen. Dieser Unterschied zwischen beiden Gruppen war signifikant (50 % vs. 13,3 %; p ≤ 0,001). Alle Kinder mit Non-HLHS und alle Kinder mit HLHS erhielten eine modifizierte Norwood-Operation innerhalb der ersten Lebenstage bis -wochen. In der Non-HLHS-Gruppe gab es keine Hospitalletalität. In der HLHS-Gruppe verstarben dagegen 18 Kinder (11,5 %). Der Unterschied war nicht signifikant (p = 0,080). Der zweite und dritte Operationsschritt erfolgte je nach Ventrikelmorphologie entweder mit Hemi-Fontan- und späterer Fontan-Operation oder bei biventrikulärer Balance durch eine Rastelli-Operation. Im Langzeitverlauf verstarben insgesamt sechs Kinder aus allen drei Gruppen mit Non-HLHS. Dies entspricht einer Gesamtletalität von 23,1 %. Letztere war bei den Patienten mit dominantem rechtem Ventrikel signifikant höher als bei den Patienten mit balancierten Ventrikeln bzw. dominantem linkem Ventrikel (p = 0,015). Im Vergleich der Non-HLHS-Gesamtgruppe mit der Gruppe der HLHS-Patienten (31,6 %) zeigte sich kein signifikanter Unterschied (p = 0,192) in der Gesamtsterblichkeit. Die fehlende Hospitalletalität der Non-HLHS-Patienten ist im Vergleich zum Großteil der vorliegenden Literatur mit Sterblichkeitsangaben zwischen 17 und 25 % bemerkenswert und identisch mit der von Bradley (2002). Die im Langzeitverlauf verstorbenen Kinder hatten entweder zusätzliche extrakardiale Fehlbildungen, einen dominanten rechten Ventrikel oder es lagen Lungenvenenfehlmündungen vor. Tendenziell war das Langzeitüberleben in der Non-HLHS-Gruppe besser, besonders dann, wenn ein dominanter linker Ventrikel oder eine biventrikuläre Balance vorlag. Limitiert wurden unsere Ergebnisse durch die sehr kleinen Fallzahlen und individuellen Ausprägungen der komplexen Herzfehler der Non-HLHS-Gruppe

Unraveling the role of ectopic thymic tissue in patients undergoing thymectomy for myasthenia gravis

Extended thymectomy has been considered the goal of surgery for myasthenia gravis (MG) mainly due to the existence of ectopic thymic tissue. Recently, ectopic thymic tissue has attracted increasing attention in patients with MG following thymectomy. However, the specific role of ectopic thymic tissue in patients with MG is still under debate. A systematic search of the literature was performed on PubMed and Medline according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) statement. Studies evaluating the rate of ectopic thymic tissue in patients with MG with or without thymoma were included. Extraction was performed for all eligible studies and the rate of ectopic thymic tissue at common locations was calculated. Eighteen out of fifty-nine studies were eligible for inclusion, of which ten studies reported the common locations of ectopic thymic tissue in mediastinal fat. Of these ten studies, the presence of ectopic thymic tissue was investigated in different anatomical locations in 882 patients, of whom, 509 patients (58%) have at least one positive location with the most common ones being anterior mediastinal fat, pericardiophrenic angles, aortopulmonary window, cervical region (pretracheal fat) and lateral to phrenic nerves. On the other hand, nine studies analyzed the influence of the presence of ectopic thymic tissue on the clinical outcomes of MG patients. Of these, six found that the presence of ectopic thymic tissue in MG patients is a significant predictor of poor outcome after thymectomy, however, the other three did not find a significance. Altogether, ectopic thymic tissue is likely to present in more than a half of patients undergoing thymectomy for MG. Besides, MG patients who have ectopic thymic tissue after thymectomy do not seem to have as good outcome as those who have not

Human Dermis Harbors Distinct Mesenchymal Stromal Cell Subsets

Multipotent mesenchymal stromal cells (MSCs) are found in a variety of adult tissues including human dermis. These MSCs are morphologically similar to bone marrow–derived MSCs, but are of unclear phenotype. To shed light on the characteristics of human dermal MSCs, this study was designed to identify and isolate dermal MSCs by a specific marker expression profile, and subsequently rate their mesenchymal differentiation potential. Immunohistochemical staining showed that MSC markers CD73/CD90/CD105, as well as CD271 and SSEA-4, are expressed on dermal cells in situ. Flow cytometric analysis revealed a phenotype similar to bone marrow–derived MSCs. Human dermal cells isolated by plastic adherence had a lower differentiation capacity as compared with bone marrow–derived MSCs. To distinguish dermal MSCs from differentiated fibroblasts, we immunoselected CD271+ and SSEA-4+ cells from adherent dermal cells and investigated their mesenchymal differentiation capacity. This revealed that cells with increased adipogenic, osteogenic, and chondrogenic potential were enriched in the dermal CD271+ population. The differentiation potential of dermal SSEA-4+ cells, in contrast, appeared to be limited to adipogenesis. These results indicate that specific cell populations with variable mesenchymal differentiation potential can be isolated from human dermis. Moreover, we identified three different subsets of dermal mesenchymal progenitor cells

The HIV protease inhibitor saquinavir inhibits HMGB1 driven inflammation by targeting the interaction of cathepsin V with TLR4/MyD88

Extracellular HMGB1 (disulfide form), via activation of Toll-Like-Receptor (TLR4)-dependent signaling, is a strong driver of pathologic inflammation in both acute and chronic conditions. Identification of selective inhibitors of HMGB1-TLR4 signaling could offer novel therapies that selectively target proximal endogenous activators of inflammation. A cell-based screening strategy led us to identify first generation HIV-protease inhibitors (PI) as potential inhibitors of HMGB1-TLR4 driven cytokine production. Here we report, that the first-generation HIV-PI saquinavir (SQV), as well as a newly identified mammalian protease inhibitor STO33438 (334), potently block disulfide HMGB1 induced TLR4 activation, as assayed by the production of TNF-alpha by human monocyte-derived macrophages (THP-1). We further report on the identification of mammalian cathepsin V, a protease, as a novel target of these inhibitors. Cellular as well as recombinant protein studies show that the mechanism of action involves a direct interaction between cathepsin V with TLR4 and its adaptor protein MyD88. Treatment with SQV, 334, or the known cathepsin inhibitor SID26681509 (SID) significantly improved survival in murine models of sepsis and reduced liver damage following warm liver I/R, models both characterized by strong HMGB1-TLR4 driven pathology. The current study demonstrates a novel role for cathepsin V in TLR4 signaling and implicates cathepsin V as a novel target for first-generation HIV-PI compounds. The identification of cathepsin V as a target to block HMGB1-TLR4 driven inflammation could allow for a rapid transition of the discovery from the bench to the bedside

Differential Expression of PD-L1 during Cell Cycle Progression of Head and Neck Squamous Cell Carcinoma

The expression of PD-L1 by tumor cells is mainly associated with its immunosuppressive effect. In fact, PD-1/PD-L1 immune checkpoint inhibitors demonstrated remarkable effects in advanced cancer patients including HNSCC. In this context, irradiation is currently being investigated as a synergistic treatment modality to immunotherapy. However, the majority of HNSCC patients still show little improvement or even hyperprogression. Interestingly, there is increasing evidence for additional cell-intrinsic functions of PD-L1 in tumor cells. In previous studies, we showed that PD-L1 has a strong influence on proliferation, migration, invasion, and survival after irradiation. We demonstrated that cellular expression and localization of PD-L1 differed depending on sensitivity to irradiation. Here, we show that PD-L1 is also differentially expressed during cell cycle progression of HNSCC. Furthermore, cellular localization of PD-L1 also changes depending on a particular cell cycle phase. Moreover, distinct observations occurred depending on the general differentiation status. Overall, the function of PD-L1 cannot be generalized. Rather, it depends on the differentiation status and microenvironment. PD-L1 expression and localization are variable, depending on different factors. These findings may provide insight into why differential response to PD-1/PD-L1 antibody therapy can occur. Detailed understanding of cell-intrinsic PD-L1 functions will further allow antibody-based immunotherapy to be optimized

The stories we tell: uncanny encounters in Mr Straw’s house

During my first visit to Mr Straw’s House, a National Trust Property in the North of England, I was intrigued by the discrepancies between the narrative framework provided by the National Trust – its exclusions, silences and invisibilities – and the far more complex stories the house seemed to tantalisingly hint at. As a scholar I am drawn to certain sites and affectively engage with them and yet I usually keep silent about my investment which informs not only my interest but also how I read these heritage sites. My aim here is not primarily to interrogate my own investment, but to ask how productive it is, what it enables me to see and to describe and where its limits are. This case study explores a particular tourist attraction from the perspective of storytelling and asks what narratives can be constructed around, and generated through, the spatial-emotional dimensions of this heritage site. I am interested in the hold sites have over people, why and how they provoke imaginative and empathic investment that generates a network of stories and triggers processes of unravelling which have the potential to transform silences and unmetabolised affect into empathy and emotional thought

Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Maintaining the integrity of sperm DNA is vital to reproduction and male fertility. Sperm contain a number of molecules and pathways for the repair of base excision, base mismatches and DNA strand breaks. The presence of Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues has recently been shown in male germ cells, specifically during stage VII of spermatogenesis. High PARP expression has been reported in mature spermatozoa and in proven fertile men. Whenever there are strand breaks in sperm DNA due to oxidative stress, chromatin remodeling or cell death, PARP is activated. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Therefore, cleaved PARP (cPARP) may be considered a marker of apoptosis. The presence of higher levels of cPARP in sperm of infertile men adds a new proof for the correlation between apoptosis and male infertility. This review describes the possible biological significance of PARP in mammalian cells with the focus on male reproduction. The review elaborates on the role played by PARP during spermatogenesis, sperm maturation in ejaculated spermatozoa and the potential role of PARP as new marker of sperm damage. PARP could provide new strategies to preserve fertility in cancer patients subjected to genotoxic stresses and may be a key to better male reproductive health