Book Review

Bessie Smith: A Poet’s Biography of a Blues Legend. By Jackie Kay. New York: Vintage. 2021. Pp. 224. Price $16.95 (Paperback). ISBN 13: 978-0593314271

Doing it for the kids?: The discursive construction of the teenager and teenage sexuality in E4’s Skins

The teen series is often regarded by television scholars as an inherently American genre. Indeed, the genre is marked by US constructs, such as the cheerleader, jock, homecoming dance and prom and, in turn, teen television scholarship has focused almost exclusively on US texts. However, more recent years have seen the emergence of British teen drama series, most notably Skins (E4, 2007-), which has been so successful that it has spawned an (albeit short-lived) US version which aired on MTV. In an attempt to redress the dearth of academic study of British teen dramas, this article explores Skins in more detail. Journalistic discourse on the programme has frequently emphasised the series' nihilism in contrast to the didacticism that characterises its US generic counterparts, which the series' creators justify by claims for its authenticity. This article moves beyond the authentic/inauthentic debate to explore instead the discursive construction of the teenager and teenage sexuality in the specific context of broadcasting in the UK. Thus, after situating Skins in relation to the history of youth programming in Britain and, specifically, on Channel 4, the article will explore issue-led storylines involving teenage sexuality in more detail. It will argue that despite the programme's nihilistic ethos, Skins is underpinned by more conservative ideologies, particularly regarding the depiction of gender and sexuality. In turn, this ambivalence makes it difficult to discern the programme's ideological stance on sexual issues

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

Cell-cell adhesion proteins in melanocytic pilomatrix carcinoma

Tumors of the matrix of rigid structures include matrical tumors of the hairs, nails, and teeth. These tumors share similar phenotypical and signaling features. Although benign matrical hair tumors are among the most common of these tumors, hair matrix tumors containing pigmented melanocytes are very rare. The malignant variant called melanocytic pilomatrix carcinoma contains benign colonizing dendritic melanocytes admixed with the carcinomatous follicular matrical cells

Developing the specifications of an Open Angle Glaucoma screening intervention in the United Kingdom : a Delphi approach

PMID: 23216983 [PubMed - indexed for MEDLINE] PMCID: PMC3563574 Free PMC Article Acknowledgements We thank all the glaucoma specialists who took part in the Delphi process. We thank the Glaucoma screening Platform Study advisory panel including R Bativala, D Crabb, D Garway-Heath, M Griffiths, R Hitchings; S McPherson, A Tuulonen, A Viswanathan, H Waterman, R Wormald, D Wright for their guidance and contribution to the Delphi process and Luke Vale and Rodolfo Hernandez for their advice on development of the Delphi questionnaires. This paper was developed from the first phase of a project funded by the MRC (project reference G0701759) Developing the intervention & outcome components of a proposed randomized controlled trial of screening for open angle glaucoma. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates. The views expressed in this report are those of the authors and not necessarily those of the funders.Peer reviewedPublisher PD

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Refining associations between TAS2R38 diplotypes and the 6-n-propylthiouracil (PROP) taste test: findings from the Avon Longitudinal Study of Parents and Children

<p>Abstract</p> <p>Background</p> <p>Previous investigations have highlighted the importance of genetic variation in the determination of bitter tasting ability, however have left unaddressed questions as to within group variation in tasting ability or the possibility of genetic prescription of intermediate tasting ability. Our aim was to examine the relationships between bitter tasting ability and variation at the <it>TAS2R38 </it>locus and to assess the role of psychosocial factors in explaining residual, within group, variation in tasting ability.</p> <p>Results</p> <p>In a large sample of children from the Avon Longitudinal Study of Parents and Children, we confirmed an association between bitter compound tasting ability and <it>TAS2R38 </it>variation and found evidence of a genetic association with intermediate tasting ability. Antisocial behaviour, social class and depression showed no consistent relationship with the distribution of taste test scores.</p> <p>Conclusion</p> <p>Factors which could influence a child's chosen taste score, extra to taste receptor variation, appeared not to show relationships with test score. Observed spread in the distribution of the taste test scores <it>within </it>hypothesised taster groups, is likely to be, or at least in part, due to physiological differentiation regulated by other genetic contributors. Results confirm relationships between genetic variation and bitter compound tasting ability in a large sample, and suggest that <it>TAS2R38 </it>variation may also be associated with intermediate tasting ability.</p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN