Laughter at Auschwitz: George Tabori’s “Theater der Peinlichkeit” and “Vergangenheitsbewältigung” in Post-War Germany

For his premiere of The Cannibals at the Berliner Schiller Theater in December of 1969, George Tabori had an escape car waiting just in case the German audience reacted poorly to his play. Not only was he bringing the first Holocaust play set at a concentration camp to the German stage, but it was extremely comedic in nature. Tabori’s Holocaust play was funny. This had never been done before, especially not by a Hungarian Jew who had lost most of his family in the Holocaust. No one knew how the German audience, especially the non-Jewish audience, would react. Tabori wanted to be prepared. He needn’t have been. The audience responded with standing ovations. The critics were surprised. The American audience had received The Cannibals mildly. More importantly, a German audience had never reacted with such enthusiasm to a Holocaust play. What had George Tabori done to the Berlin audience? Two of his later comedic Holocaust plays, My Mother\u27s Courage, which premiered in Munich in 1979, and Mein Kampf, which premiered in Vienna in 1987, caused similar reactions. As a third generation German-American born and raised in Berlin, I can’t help but wonder what happened at the Schiller Theater that night in December 1969. Tabori’s “Theater der Peinlichkeit,”[1] as it is called nowadays, roused something in the Berlin audience that hadn’t been heard in a long time. I suspect it was laughter. Laughter about something the Germans hadn’t ever been able to laugh about. They were laughing during a play about the Holocaust. I don’t believe it. In this paper I will to argue that their laughter was a vehicle for something else. Their laughter was a first breath. The German audience was breathing for the first time in a long time. It was alive again. It was responding viscerally and veraciously to something that it had been failing to address. I want to argue that Tabori’s “Theater der Peinlichkeit” broke pre-conceived Holocaust-theater taboos by utilizing comedy as a theatrical device. He reinforced this upheaval of taboos by upsetting the victim-perpetrator relationships, confusing the audience’s expectations about feelings such as guilt and shame, and breaking down the fourth wall in his work. With his plays Mein Kampf, My Mother\u27s Courage, and The Cannibals, Tabori brought into existence for German theater-goers a new kind of “Vergangenheitsbewältigung,” or process of dealing with ones past

Using epigenomic studies in monozygotic twins to improve our understanding of cancer

Cancer is a set of diseases that exhibit not only genetic mutations but also a profoundly distorted epigenetic landscape. Over the last two decades, great advances have been made in identifying these alterations and their importance in the initiation and progression of cancer. Epigenetic changes can be seen from the very early stages in tumorigenesis and dysregulation of the epigenome has an increasingly acknowledged pathogenic role. Epigenomic twin studies have great potential to contribute to our understanding of complex diseases, such as cancer. This is because the use of monozygotic twins discordant for cancer enables epigenetic variation analysis without the confounding influence of the constitutive genetic background, age or cohort effects. It therefore allows the identification of susceptibility loci that may be sensitive to modification by the environment. These studies into cancer etiology will potentially lead to robust epigenetic markers for the detection and risk assessment of cance

Reversing microcrystalline tests: an analytical approach to recycling of microcrystals from drugs of abuse

A combined analysis of microcrystalline tests followed by LC-MS or GC-MS analysis is described. Microcrystalline tests are shown to be non-destructive as addition products formed were easily dissociated after the application of an appropriate solvent. Subsequent analysis of the sample was done to quantify the recovery of the drug. Examples were performed using the date rape drug γ-hydroxybutyrate (GHB) and the synthetic opioid methadone

Patterns of High-Dose and Long-Term Proton Pump Inhibitor Use: A Cross-Sectional Study in Six South Australian Residential Aged Care Services

Aim: While proton pump inhibitors (PPIs) are generally considered safe and well tolerated, frail older people who take PPIs long term may be susceptible to adverse events. This study characterized PPI use and determined factors associated with high-dose use among older adults in residential aged care services (RACSs).Methods: A cross-sectional study of 383 residents of six South Australian RACSs within the same organization was conducted. Clinical, diagnostic, and medication data were collected by study nurses. The proportions of residents who took a PPI for > 8 weeks and without documented indications were calculated. Factors associated with high-dose PPI use compared to standard/low doses were identified using age- and sex-adjusted logistic regression models.Results: 196 (51%) residents received a PPI, with 45 (23%) prescribed a high dose. Overall, 173 (88%) PPI users had documented clinical indications or received medications that can increase bleeding risk. Three-quarters of PPI users with gastroesophageal reflux disease or dyspepsia had received a PPI for > 8 weeks. High-dose PPI use was associated with increasing medication regimen complexity [odds ratio (OR) 1.02; 95% confidence interval (CI) 1.01–1.04 per one-point increase in Medication Regimen Complexity Index score] and a greater number of medications prescribed for regular use (OR 1.11; 95% CI 1.01–1.21 per additional medication).Conclusions: Half of all residents received a PPI, of whom the majority had documented clinical indications or received medications that may increase bleeding risk. There remains an opportunity to review the continuing need for treatment and consider “step-down” approaches for high-dose PPI users.</p

Identification of African swine fever virus-like elements in the soft tick genome provides insights into the virus’ evolution

BACKGROUND: African swine fever virus (ASFV) is a most devastating pathogen affecting swine. In 2007, ASFV was introduced into Eastern Europe where it continuously circulates and recently reached Western Europe and Asia, leading to a socio-economic crisis of global proportion. In Africa, where ASFV was first described in 1921, it is transmitted between warthogs and soft ticks of the genus Ornithodoros in a so-called sylvatic cycle. However, analyses into this virus’ evolution are aggravated by the absence of any closely related viruses. Even ancient endogenous viral elements, viral sequences integrated into a host’s genome many thousand years ago that have proven extremely valuable to analyse virus evolution, remain to be identified. Therefore, the evolution of ASFV, the only known DNA virus transmitted by arthropods, remains a mystery. - RESULTS: For the identification of ASFV-like sequences, we sequenced DNA from different recent Ornithodoros tick species, e.g. O. moubata and O. porcinus, O. moubata tick cells and also 100-year-old O. moubata and O. porcinus ticks using high-throughput sequencing. We used BLAST analyses for the identification of ASFV-like sequences and further analysed the data through phylogenetic reconstruction and molecular clock analyses. In addition, we performed tick infection experiments as well as additional small RNA sequencing of O. moubata and O. porcinus soft ticks. - CONCLUSION: Here, we show that soft ticks of the Ornithodoros moubata group, the natural arthropod vector of ASFV, harbour African swine fever virus-like integrated (ASFLI) elements corresponding to up to 10% (over 20 kb) of the ASFV genome. Through orthologous dating and molecular clock analyses, we provide data suggesting that integration could have occurred over 1.47 million years ago. Furthermore, we provide data showing ASFLI-element specific siRNA and piRNA in ticks and tick cells allowing for speculations on a possible role of ASFLI-elements in RNA interference-based protection against ASFV in ticks. We suggest that these elements, shaped through many years of co-evolution, could be part of an evolutionary virus-vector ‘arms race’, a finding that has not only high impact on our understanding of the co-evolution of viruses with their hosts but also provides a glimpse into the evolution of ASFV.Background Results - Evidence of ASFLI-elements in the O. moubata tick cell genome - Phylogenetic analysis shows ASFLI-elements are close relatives of ASFV sequences - ASFLI-elements are present in recently sampled O.moubata, O. porcinus and approx. 100-year-old O.moubata and O. porcinus field-collected ticks from Africa - Phylogenetic reconstruction using full-length mitochondrial genomes of soft ticks reveals a possible integration of an ASFLI-element might have occurred over 1.46–1.47 million years ago (mya) - Molecular clock analyses using ASFLI-elements from different Ornithodoros species provide an estimate for a time to the most recent common ancestor consistent with orthologous dating - Ornithodoros tick species and tick cell lines show differences in the infectability with various ASFV genotype isolates - RNA sequencing demonstrates ASFLI-element-specific mRNA—small-interfering and piwi-interacting RNAs in tick cells - The reconstructed ASFLI-A104R protein is highly similar to its ASFV homologue but is not expressed in tick cell lines Discussion Conclusion Methods - Virus strains - Tick rearing, tick infection and tick cell cultures - Nucleic acid extraction - Oligonucleotide design - PCR - qPCR - RT-qPCR - Sanger sequencing - Next-generation sequencing - Amplicon sequencing for assembly validation - Data analysis - Phylogenetic analysis - Clock rate estimates and Bayesian time-scaled trees - Protein expression and purification in E. coli and rabbit immunisation - Transfection - SDS-PAGE and immunoblotting - Statistical analysi

第831回千葉医学会例会・第15回千葉大学放射線医学教室例会

Figure S2. All a-DMRs within (1) genomic location. Top: a-DMRs (purple), gene, DHS clusters, transcription factor ChIP-seq, ChromHMM segmentation, combined segmentation and conservation; and (2) scatterplot: x-axis = Age, y-axis = Normalised methylation. (PDF 34909 kb

Single and repeated moderate consumption of native or dealcoholized red wine show different effects on antioxidant parameters in blood and DNA strand breaks in peripheral leukocytes in healthy volunteers: a randomized controlled trial [ISRCTN68505294]

BACKGROUND: Red wine (RW) is rich in antioxidant polyphenols that might protect from oxidative stress related diseases, such as cardiovascular disease and cancer. Antioxidant effects after single ingestion of RW or dealcoholized RW (DRW) have been observed in several studies, but results after regular consumption are contradictory. Thus, we examined if single or repeated consumption of moderate amounts of RW or DRW exert antioxidant activity in vivo. METHODS: Total phenolic content and concentration of other antioxidants in plasma/serum, total antioxidant capacity (TEAC) in plasma as well as DNA strand breaks in peripheral leukocytes were measured in healthy non-smokers A) before, 90 and 360 min after ingestion of one glass of RW, DRW or water; B) before and after consumption of one glass of RW or DRW daily for 6 weeks. DNA strand breaks (SB) were determined by single cell gel electrophoresis (Comet Assay) in untreated cells and after induction of oxidative stress ex vivo with H(2)O(2 )(300 μM, 20 min). RESULTS: Both RW and DRW transiently increased total phenolic content in plasma after single consumption, but only RW lead to a sustained increase if consumed regularly. Plasma antioxidant capacity was not affected by single or regular consumption of RW or DRW. Effects of RW and DRW on DNA SB were conflicting. DNA strand breaks in untreated cells increased after a single dose of RW and DRW, whereas H(2)O(2 )induced SB were reduced after DRW. In contrast, regular RW consumption reduced SB in untreated cells but did not affect H(2)O(2 )induced SB. CONCLUSION: The results suggest that consumption of both RW and DRW leads to an accumulation of phenolic compounds in plasma without increasing plasma antioxidant capacity. Red wine and DRW seem to affect the occurrence of DNA strand breaks, but this cannot be referred to antioxidant effects

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes