The Transcriptional Repressor TupA in Aspergillus niger Is Involved in Controlling Gene Expression Related to Cell Wall Biosynthesis, Development, and Nitrogen Source Availability.

The Tup1-Cyc8 (Ssn6) complex is a well characterized and conserved general transcriptional repressor complex in eukaryotic cells. Here, we report the identification of the Tup1 (TupA) homolog in the filamentous fungus Aspergillus niger in a genetic screen for mutants with a constitutive expression of the agsA gene. The agsA gene encodes a putative alpha-glucan synthase, which is induced in response to cell wall stress in A. niger. Apart from the constitutive expression of agsA, the selected mutant was also found to produce an unknown pigment at high temperatures. Complementation analysis with a genomic library showed that the tupA gene could complement the phenotypes of the mutant. Screening of a collection of 240 mutants with constitutive expression of agsA identified sixteen additional pigment-secreting mutants, which were all mutated in the tupA gene. The phenotypes of the tupA mutants were very similar to the phenotypes of a tupA deletion strain. Further analysis of the tupA-17 mutant and the DeltatupA mutant revealed that TupA is also required for normal growth and morphogenesis. The production of the pigment at 37 degrees C is nitrogen source-dependent and repressed by ammonium. Genome-wide expression analysis of the tupA mutant during exponential growth revealed derepression of a large group of diverse genes, including genes related to development and cell wall biosynthesis, and also protease-encoding genes that are normally repressed by ammonium. Comparison of the transcriptome of up-regulated genes in the tupA mutant showed limited overlap with the transcriptome of caspofungin-induced cell wall stress-related genes, suggesting that TupA is not a general suppressor of cell wall stress-induced genes. We propose that TupA is an important repressor of genes related to development and nitrogen metabolism

Renaissance women: Brigid Brophy, Mary McCarthy and the public intellectual

Unashamedly intellectual, idiosyncratic, and often contrarian, Mary McCarthy and Brigid Brophy stood out amongst late twentieth century female writers not only as public intellectuals, but for the way their writing and social commentary cut against the grain on pivotal issues of progress, freedom, and aesthetic form, exposing and often satirising the hypocrisy of their male contemporaries. From the mid-twentieth-century onwards, on both sides of the Atlantic, the public intellectual took on a prominent and sharply defined role; Brophy and McCarthy developed complementary, dissident positions that provided a counter-model to the mainstream liberalism of such male intellectuals, opening an alternative space for female writers in the late twentieth- and early twenty-first-century. By unpacking their shared aesthetic practices and values, including the influence of a cultural Catholicism and an intense investment in the Italian Renaissance, this essay uncovers their role in establishing an alternative model of public intellectual that continues to influence the status of female writers and thinkers

Teju Cole and Ralph Ellison’s aesthetics of invisibility

Considering ‘invisibility’ as both subject matter and aestheticizing mode of experience, this essay uses the case studies of two American novels - Teju Cole’s Open City (2011) and Ralph Ellison’s Invisible Man (1952) - to explore how a culturally specific, racially charged, subject is mapped outwards to occupy a broader aesthetic realm

Co-creation, contexts, and complexity: a case study concerning blended learning

This case study reports on the value of engaging students as partners in research carried out concerning module redesign, specifically the development of blended learning activities for a first-year module in linguistics. It should be noted that the focus of this report is on the partnership approach to researching, not the material redesign itself. The approach taken involves recognising universities as complex systems, and so need to be researched incorporating the voices of all stakeholders. It supplies an exploration of the reasons for choosing this partnership approach; it gives a description of how this partnership was maintained (relating both to ethical issues and to practicalities); and summarises the guidance and lessons learnt to be shared with others to encourage them to consider such partnerships

Cohort Profile : Pregnancy And Childhood Epigenetics (PACE) Consortium

Peer reviewe

DNA Methylation in Newborns and Maternal Smoking in Pregnancy:Genome-wide Consortium Meta-analysis

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value &lt;2.2 x 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.</p