| 1. |
- Davison, Lucy J, et al.
(författare)
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Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:2, s. 322-333
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Tidskriftsartikel (refereegranskat)abstract
- The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.
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| 2. |
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| 3. |
- Huaraca Huasco, Walter, et al.
(författare)
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Fine root dynamics across pantropical rainforest ecosystems
- 2021
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 27:15, s. 3657-3680
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Tidskriftsartikel (refereegranskat)abstract
- Fine roots constitute a significant component of the net primary productivity (NPP) of forest ecosystems but are much less studied than aboveground NPP. Comparisons across sites and regions are also hampered by inconsistent methodologies, especially in tropical areas. Here, we present a novel dataset of fine root biomass, productivity, residence time, and allocation in tropical old-growth rainforest sites worldwide, measured using consistent methods, and examine how these variables are related to consistently determined soil and climatic characteristics. Our pantropical dataset spans intensive monitoring plots in lowland (wet, semi-deciduous, and deciduous) and montane tropical forests in South America, Africa, and Southeast Asia (n = 47). Large spatial variation in fine root dynamics was observed across montane and lowland forest types. In lowland forests, we found a strong positive linear relationship between fine root productivity and sand content, this relationship was even stronger when we considered the fractional allocation of total NPP to fine roots, demonstrating that understanding allocation adds explanatory power to understanding fine root productivity and total NPP. Fine root residence time was a function of multiple factors: soil sand content, soil pH, and maximum water deficit, with longest residence times in acidic, sandy, and water-stressed soils. In tropical montane forests, on the other hand, a different set of relationships prevailed, highlighting the very different nature of montane and lowland forest biomes. Root productivity was a strong positive linear function of mean annual temperature, root residence time was a strong positive function of soil nitrogen content in montane forests, and lastly decreasing soil P content increased allocation of productivity to fine roots. In contrast to the lowlands, environmental conditions were a better predictor for fine root productivity than for fractional allocation of total NPP to fine roots, suggesting that root productivity is a particularly strong driver of NPP allocation in tropical mountain regions.
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| 4. |
- Humphries, Matthew P., et al.
(författare)
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A case-matched gender comparison transcriptomic screen identifies eIF4E and eIF5 as potential prognostic markers in male breast cancer
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 23:10, s. 2575-2583
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor. Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77, 1.12-2.8 and P = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed (P = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P = 0.016; HR = 2.38 (1.18-4.8), eIF5 P = 0.022; HR = 2.55 (1.14-5.7); coexpression P = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival. Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.
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| 5. |
- Jeffery, Lucy
(författare)
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An Interview with Tim Parkinson
- 2020
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Ingår i: Journal of Beckett Studies. - : Edinburgh University Press. - 0309-5207 .- 1759-7811. ; 29:2, s. 249-260
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Jeffery, Lucy
(författare)
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‘An Old Hullo Out of the Dark’ : Radio Echoes between Samuel Beckett and Harold Pinter
- 2020
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Ingår i: Historical Journal of Film, Radio and Television. - : Informa UK Limited. - 0143-9685 .- 1465-3451. ; 40:3, s. 516-532
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Tidskriftsartikel (refereegranskat)abstract
- Radio provided Samuel Beckett and Harold Pinter with new ways of experimenting with voice, silence, and absence. As they maximised radio’s potential to explore the ephemerality of language and non-linear narratives, the works they created were concerned with the medium itself. On radio, Beckett’s silences and Pinter’s pauses create a heightened sense of uncertainty and ambiguity. Their medium-conscious works also provided them with a platform through which they could experiment with their shared frustration with the inaccuracies of language. The article explores Pinter’s interest in Beckett’s work by drawing on Pinter’s letters to Richard Seaver, Patrick Magee, and Mick Goldstein from the Harold Pinter Archive. It then shows how Pinter’s own work is intermedial in its experimentation with new technologies such as radio. By pointing to examples within Pinter’s Landscape (1968) that speak to moments in Beckett’s Embers (1959), the parallels between these writers in their use of radio are identified. Finally, the article suggests that Pinter’s work is not merely derivative of Beckett’s but demonstrates how the radio drama of both writers is underwritten by an intermedial creative process.
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| 7. |
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| 8. |
- Jeffery, Lucy
(författare)
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Ezra Pound and Constantin Brancusi : sculptural form and the struggle to "make it cohere"
- 2020
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Ingår i: Word and Image. - : Informa UK Limited. - 0266-6286 .- 1943-2178. ; 36:3, s. 237-247
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Tidskriftsartikel (refereegranskat)abstract
- This article takes an interdisciplinary approach in order to show the artistic importance of the friendship between Ezra Pound and Constantin Brancusi. It refers to key moments in Pound’s late cantos that evidence his development of a specifically sculptural aesthetic technique. With reference to Pound’s critical writings on the visual arts as well as to his allusions to sculpture and the process of direct carving throughout The Cantos, Pound’s and Brancusi’s work is seen as exemplary of experiments in poetic and sculptural form during the first half of the twentieth century. More specifically, Pound’s invocation of ‘no slither’ and his reference to Brancusi’s Bird in Space (1924, etc.) in Canto CXVII are read as being connected to his struggle to ‘make it cohere’. While Harriet Zinnes and Rebecca Beasley have both analysed Pound’s work in relation to the visual arts, this article sees his interest in the work of Brancusi as something that not only influences the shape of his late cantos, but also is intrinsic to his fraught creative process and sculptural aesthetic.
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| 9. |
- Jeffery, Lucy, et al.
(författare)
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Introduction
- 2022
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Ingår i: Green Letters. Studies in Ecocriticism. - : Informa UK Limited. - 1468-8417 .- 2168-1414. ; 26:3, s. 203-209
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Jeffery, Lucy
(författare)
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Magda Szabó : Finding Home in the Homeland in Post-1956 Hungary
- 2020
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Ingår i: SIC - Journal of Literature, Culture and Literary Translation. - : University of Zadar. - 1847-7755. ; 11:3, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- In Iza’s Ballad, Magda Szabó writes about the lives of two doctors who meet and fall in love at university. “Don’t get too involved with politics,” experienced Antal warns a seemingly ingénue Iza. To which she responds: “Politics will be my life as long as I live.” In this brief encounter, Szabó connects the predominant themes of her oeuvre: politics and life, or, to be more specific, Communism and the domestic. In its analysis of Iza’s Ballad (1963), Katalin Street (1969), and The Door (1987), this article illustrates how Szabó’s descriptions of the domestic convey the impact of Hungary’s troubled political history on the concept of the home/homeland. The article illustrates the ways in which Szabó contrasts the relatively comfortable years of Goulash Communism with the hardship endured during WWII, under Rákosi, and during the 1956 Revolution, to convey the lasting effects of the Soviet occupation on the notion of home.
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