Sex wars and (trans) gender panics : identity and body politics in contemporary UK feminism

This article considers how sex and gender – as conceptual categories and as a lived experience – are subject to contestation and renegotiation in the contemporary UK. Exploring gendered shifts through the lenses of identity and embodiment, the article captures key moments where certainties have been undone within feminist and transgender thought and activism. Yet such fissures resound with calls for a return to traditional understandings of the sexed body. The article pays particular attention to debates within feminism around transgender issues, and sketches out a climate of transgender moral panic whereby conservative thinkers and some feminist activists are joining forces with the aim of resurrecting gender binaries

Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains

Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA + strains caused significantly more cellular damage than pfoA − strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA + C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies

Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth

The gut microbiota's function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tumor progression in multiple BrCa mouse models. Metagenomics highlights the common loss of several bacterial species following antibiotic administration. One such bacteria, Faecalibaculum rodentium, rescued this increased tumor growth. Single-cell transcriptomics identified an increased number of cells with a stromal signature in tumors, and subsequent histology revealed an increased abundance of mast cells in the tumor stromal regions. We show that administration of a mast cell stabilizer, cromolyn, rescues increased tumor growth in antibiotic treated animals but has no influence on tumors from control cohorts. These findings highlight that BrCa-microbiota interactions are different from other cancers studied to date and suggest new research avenues for therapy development

Reciprocal interactions between the gut microbiome and mammary tissue mast cells promote metastatic dissemination of HR+ breast tumors

Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, before breast tumor initiation, enhances early dissemination of hormone receptor–positive (HR+) mammary tumor cells. Here, we sought to determine whether cellular changes occurring in normal mammary tissues, before tumor initiation and in response to dysbiosis, enhanced dissemination of HR+ tumors. Commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in normal, non–tumor-bearing mammary tissues, a phenotypic change that persisted after tumor implantation. Pharmacological and adoptive transfer approaches demonstrated that profibrogenic mammary tissue mast cells from dysbiotic animals were sufficient to enhance dissemination of HR+ tumor cells. Using archival HR+ patient samples, we determined that enhanced collagen levels in tumor-adjacent mammary tissue positively correlated with mast cell abundance and HR+ breast cancer recurrence. Together, these data demonstrate that mast cells programmed by commensal dysbiosis activate mammary tissue fibroblasts and orchestrate early dissemination of HR+ breast tumors

Altered Microenvironment Promotes Progression of Preinvasive Breast Cancer: Myoepithelial Expression of v 6 Integrin in DCIS Identifies High-risk Patients and Predicts Recurrence

PURPOSE: This study investigated the functional and clinical significance of integrin ?v?6 up-regulation in myoepithelial cells of ductal carcinoma in-situ (DCIS).EXPERIMENTAL DESIGN: Archival samples of DCIS and DCIS with associated invasion (n=532) were analysed for expression of ?v?6 by immunohistochemistry, and ability to predict recurrence and progression assessed in an independent, unique cohort of DCIS cases with long term follow up. Primary myoepithelial cells and myoepithelial cell lines, with and without ?v?6 expression, were used to measure the effect of ?v?6 on growth and invasion of tumor cell lines in vitro, and in a xenograft mouse model. Involvement of TGF? signaling was established using MLEC assay and antibody inhibition, and expression and activation of matrix-metalloproteinase (MMP)-9 established by RT-PCR and zymography.RESULTS: Expression of ?v?6 is significantly associated with progression to invasive cancer (p<0.006) and with recurrence over a median follow-up of 114 months in a series of matched DCIS cases treated with local excision. We show that expression of ?v?6 drives myoepithelial cells to promote tumor cell invasion in vitro and enhances mammary tumor growth in vivo. The tumor promoting effect of ?v?6-positive myoepithelial cells is dependent on TGF?-driven up-regulation of MMP9, and can be abrogated by inhibiting this pathway.CONCLUSION: These findings indicate that altered myoepithelial cells in DCIS predict disease progression and recurrence, and demonstrate that up-regulation of ?v?6 on myoepithelial cells generates a tumor-promoter function through TGF? up-regulation of MMP-9. These data suggest expression of ?v?6 may be used to stratify patients with DCIS

Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains.

Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA+ strains caused significantly more cellular damage than pfoA- strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA+ C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies