\u27What Light. What Possibilities. What Hope. Revolutionary Millennialism in José Rivera\u27s Marisol

This thesis examines José Rivera’s 1992 play Marisol as an apocalyptic and millennial text. The play responds to the cultural climate of America at the end of the twenty-first century, presenting a social critique by playing on the nation’s widespread premillennial anxieties and anticipations. By paralleling the play with the Christian Apocalypse found in the book of Revelation, Rivera further plays with the audience’s expectations, but ultimately rewrites the millennial narrative to emphasize human agency over divine intervention. This is characteristic of revolutionary millenarian movements, which seek to recreate the world when faced with situations of extreme social distress. In the end, Rivera remains ambivalent to the legitimacy of violent revolution, but encourages the audience to determine their own methods of achieving change. Any theatrical production of Marisol must maintain this balance of millennial transformation and individual reflection. By subverting cultural expectations and fashioning new millennial narratives, Rivera creates a unique form of revolutionary millenarianism encouraging the audience to enact significant, human-driven social change

MUC1-C drives myeloid leukaemogenesis and resistance to treatment by a survivin-mediated mechanism

Acute myeloid leukaemia (AML) is an aggressive haematological malignancy with an unmet need for improved therapies. Responses to standard cytotoxic therapy in AML are often transient because of the emergence of chemotherapy-resistant disease. The MUC1-C oncoprotein governs critical pathways of tumorigenesis, including self-renewal and survival, and is aberrantly expressed in AML blasts and leukaemia stem cells (LSCs). However, a role for MUC1-C in linking leukaemogenesis and resistance to treatment has not been described. In this study, we demonstrate that MUC1-C overexpression is associated with increased leukaemia initiating capacity in an NSG mouse model. In concert with those results, MUC1-C silencing in multiple AML cell lines significantly reduced the establishment of AML in vivo. In addition, targeting MUC1-C with silencing or pharmacologic inhibition with GO-203 led to a decrease in active β-catenin levels and, in-turn, down-regulation of survivin, a critical mediator of leukaemia cell survival. Targeting MUC1-C was also associated with increased sensitivity of AML cells to Cytarabine (Ara-C) treatment by a survivin-dependent mechanism. Notably, low MUC1 and survivin gene expression were associated with better clinical outcomes in patients with AML. These findings emphasize the importance of MUC1-C to myeloid leukaemogenesis and resistance to treatment by driving survivin expression. Our findings also highlight the potential translational relevance of combining GO-203 with Ara-C for the treatment of patients with AML

Evolution of Mutational Robustness in an RNA Virus

Mutational (genetic) robustness is phenotypic constancy in the face of mutational changes to the genome. Robustness is critical to the understanding of evolution because phenotypically expressed genetic variation is the fuel of natural selection. Nonetheless, the evidence for adaptive evolution of mutational robustness in biological populations is controversial. Robustness should be selectively favored when mutation rates are high, a common feature of RNA viruses. However, selection for robustness may be relaxed under virus co-infection because complementation between virus genotypes can buffer mutational effects. We therefore hypothesized that selection for genetic robustness in viruses will be weakened with increasing frequency of co-infection. To test this idea, we used populations of RNA phage φ6 that were experimentally evolved at low and high levels of co-infection and subjected lineages of these viruses to mutation accumulation through population bottlenecking. The data demonstrate that viruses evolved under high co-infection show relatively greater mean magnitude and variance in the fitness changes generated by addition of random mutations, confirming our hypothesis that they experience weakened selection for robustness. Our study further suggests that co-infection of host cells may be advantageous to RNA viruses only in the short term. In addition, we observed higher mutation frequencies in the more robust viruses, indicating that evolution of robustness might foster less-accurate genome replication in RNA viruses

High glucose disrupts oligosaccharide recognition function via competitive inhibition : a potential mechanism for immune dysregulation in diabetes mellitus

Diabetic complications include infection and cardiovascular disease. Within the immune system, host-pathogen and regulatory host-host interactions operate through binding of oligosaccharides by C-type lectin. A number of C-type lectins recognise oligosaccharides rich in mannose and fucose – sugars with similar structures to glucose. This raises the possibility that high glucose conditions in diabetes affect protein-oligosaccharide interactions via competitive inhibition. Mannose binding lectin, soluble DC-SIGN & DC-SIGNR, and surfactant protein D, were tested for carbohydrate binding in the presence of glucose concentrations typical of diabetes, via surface plasmon resonance and affinity chromatography. Complement activation assays were performed in high glucose. DC-SIGN and DC-SIGNR expression in adipose tissues was examined via immunohistochemistry. High glucose inhibited C-type lectin binding to high-mannose glycoprotein and binding of DC-SIGN to fucosylated ligand (blood group B) was abrogated in high glucose. Complement activation via the lectin pathway was inhibited in high glucose and also in high trehalose - a nonreducing sugar with glucoside stereochemistry. DC-SIGN staining was seen on cells with DC morphology within omental and subcutaneous adipose tissues. We conclude that high glucose disrupts C-type lectin function, potentially illuminating new perspectives on susceptibility to infectious and inflammatory disease in diabetes. Mechanisms involve competitive inhibition of carbohydrate-binding within sets of defined proteins, in contrast to broadly indiscriminate, irreversible glycation of proteins

Fewer non‐native insects in freshwater than in terrestrial habitats across continents

Aim Biological invasions are a major threat to biodiversity in aquatic and terrestrial habitats. Insects represent an important group of species in freshwater and terrestrial habitats, and they constitute a large proportion of non-native species. However, while many non-native insects are known from terrestrial ecosystems, they appear to be less represented in freshwater habitats. Comparisons between freshwater and terrestrial habitats of invader richness relative to native species richness are scarce, which hinders syntheses of invasion processes. Here, we used data from three regions on different continents to determine whether non-native insects are indeed under-represented in freshwater compared with terrestrial assemblages. Location Europe, North America, New Zealand. Methods We compiled a comprehensive inventory of native and non-native insect species established in freshwater and terrestrial habitats of the three study regions. We then contrasted the richness of non-native and native species among freshwater and terrestrial insects for all insect orders in each region. Using binomial regression, we analysed the proportions of non-native species in freshwater and terrestrial habitats. Marine insect species were excluded from our analysis, and insects in low-salinity brackish water were considered as freshwater insects. Results In most insect orders living in freshwater, non-native species were under-represented, while they were over-represented in a number of terrestrial orders. This pattern occurred in purely aquatic orders and in orders with both freshwater and terrestrial species. Overall, the proportion of non-native species was significantly lower in freshwater than in terrestrial species. Main conclusions Despite the numerical and ecological importance of insects among all non-native species, non-native insect species are surprisingly rare in freshwater habitats. This is consistent across the three investigated regions. We review hypotheses concerning species traits and invasion pathways that are most likely to explain these patterns. Our findings contribute to a growing appreciation of drivers and impacts of biological invasions

“I am afraid of being treated badly if I show it”: A cross-sectional study of healthcare accessibility and Autism Health Passports among UK Autistic adults

Background: Autistic people are more likely to experience stigma, communication barriers and anxiety during healthcare. Autism Health Passports (AHPs) are a communication tool that aim to provide information about healthcare needs in a standardised way. They are recommended in research and policy to improve healthcare quality. Aim: To explore views and experiences of AHPs among Autistic people from the UK who have been pregnant. Methods: We developed an online survey using a combination of open and closed questions focused on healthcare impairments and views and experiences of AHPs. Data were anlaysed using descriptive statistics, Kruskal-Wallis tests, and content analysis. Findings: Of 193 Autistic respondents (54% diagnosed, 22% undergoing diagnosis and 24% self-identifying), over 80% reported anxiety and masking during healthcare always or most of the time. Some significant differences were identified in healthcare (in)accessibility by diagnostic status. Only 4% of participants knew a lot about AHPs, with 1.5% of participants using one at least half of the time. Almost three quarters of respondents had not previously seen an AHP. Open text responses indicated that the biggest barrier to using an AHP was a belief that health professionals would discriminate against Autistic patients. Additional barriers included staff lack of familiarity with AHPs and respondents expecting a negative response to producing an AHP. Conclusions: Our findings suggest that AHPs are not reducing health inequalities for Autistic adults who have been pregnant. Alternative solutions are needed to reduce health inequalities for Autistic people

Diversity, fragmentation, and connectivity across the UK amphibian and reptile data management landscape

Large-scale biodiversity monitoring remains a challenge in science and policy. ‘Biodiversity Observation Networks’ provide an integrated infrastructure for monitoring biodiversity through timely discovery, access, and re-use of data, but their establishment relies on an in-depth understanding of existing monitoring effort. We performed a scoping review and network analysis to assess the scope of available data on amphibians and reptiles in the UK and catalogue the mobilisation of information across the data landscape, thereby highlighting existing gaps. The monitoring portfolio has grown rapidly in recent decades, with over three times as many data sources than there are amphibian and reptile species in the UK now available. We identified 45 active sources of ‘FAIR’ (‘Findable’, ‘Accessible’, ‘Interoperable’ and ‘Reusable’) data. The taxonomic, geographic and temporal coverage of datasets appears largely uneven and no single source is currently suitable for producing robust multispecies assessments on large scales. A dynamic and patchy exchange of data occurs between different recording projects, recording communities and digital data platforms. The National Biodiversity Network Atlas is a highly connected source but the scope of its data (re-)use is potentially limited by insufficient accompanying metadata. The emerging complexity and fragmented nature of this dynamic data landscape is likely to grow without a concerted effort to integrate existing activities. The factors driving this complexity extend beyond the UK and to other facets of biodiversity. We recommend integration and greater stakeholder collaboration behind a coordinated infrastructure for data collection, storage and analysis, capable of delivering comprehensive assessments for large-scalecbiodiversity monitorin

Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics.

OBJECTIVE:To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia. STUDY DESIGN:Included were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS:Twenty-five serum biomarkers along with maternal age <34 years and poverty status identified >80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing). CONCLUSION:Together with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia

Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth