Writing a Novel with Roma Primary School Children: Tensions in Disrupting Aetonormativity

Story Makers Press (SMP) is a University-based publisher which co-constructs stories with under-represented groups of children in order to diversify representation in children’s literature and disrupt the way adult perceptions of normality pattern children’s literature (aetonormativity). In this paper we analyse six drama and creative writing workshops run by SMP with Czech and Slovak Roma children from an inner city primary school in the north of England to co-construct a story about climate change. Our analysis identifies how in developing the story, the children were often reluctant to draw upon their funds of knowledge relating to their Roma backgrounds, instead Westernising their protagonists and settings. We also explore how the children disrupt aetonormativity by interweaving magical elements into realistic narrative about climate change in order to establish a genre of magical realism. Finally, we identify how this genre of magical realism is problematic when considering stereotypical depictions of Roma characters in children’s literature and how changes were made to our story in light of a critical race theory reading of the first draft. As well as helping SMP to refine its processes, this analysis suggests that minority groups such as Roma need to be able to draw upon more literary representations of Roma in order to shape their creative outputs and that the curriculum needs to focus on developing children’s critical responses to the representation of minority ethnic groups in children’s literature

Tree Nuts Anaphylaxis in Preschool Age Children

Summary: Introduction. The incidence of food-induced anaphylaxis (FIA) is increasing in young children. Although the commonest culprits are cow's milk and egg, FIA to tree nuts (TNs) have been increasing. Objective. Characterization of children referred to our allergy department due to TNs-induced anaphylaxis (TNs-FIA) during preschool age. Materials and methods. We have retrospectively included 25 children with clinical history of preschool TNs-FIA, proven by allergological work-up. TNs sensitization was assessed by skin prick tests and/or specific IgE. Results. The mean age of the first anaphylactic episode was 3.1±1.2 years. The majority (92%) had an allergic disease (52% asthma). The implicated TNs were cashew (11 children), walnut (8), pine nut (5), hazelnut (2) and almond (1). The reaction occurred after the first known ingestion in 68%. In 92%, symptoms appeared within 30 minutes after exposure. The most frequent clinical symptoms were mucocutaneous (96%), respiratory (80%) and gastrointestinal (52%). Twenty-one children were admitted to the emergency department, although only 48% were treated with epinephrine. An underneath IgE-mediated mechanism was proven in all cases. Immunologic cross-reactivity with other TNs was identified in 84%, and with peanut in 36%. Overall, in our center, TNs-FIA represents 18% of all causes of FIA. Conclusions. In preschool age children with TNs-FIA, cashew and walnut were the commonest implicated nuts. Most reactions occurred briefly after exposure to minimal amounts of TNs, demonstrating the high potency of these allergens. About one-third also had peanut sensitization. Potentially life-threatening TNs allergy can occur early in childhood and adequate management should be undertaken.publishersversionpublishe

KAT2A complexes ATAC and SAGA play unique roles in cell maintenance and identity in hematopoiesis and leukemia

Author notes: *E.F. and S.W. contributed equally to this study. ChIP-seq and A-seq data have been deposited in GEO (accession numbers GSE128902 and GSE128512). Send data sharing requests via e-mail to the corresponding author. The full-text version of this article contains a data supplement.Copyright © 2021 The Authors. Epigenetic histone modifiers are key regulators of cell fate decisions in normal and malignant hematopoiesis. Their enzymatic activities are of particular significance as putative therapeutic targets in leukemia. In contrast, less is known about the contextual role in which those enzymatic activities are exercised, and specifically, how different macromolecular complexes configure the same enzymatic activity with distinct molecular and cellular consequences. We focus on KAT2A, a lysine acetyltransferase responsible for Histone 3 Lysine 9 acetylation, which we recently identified as a dependence in Acute Myeloid Leukemia stem cells, and that participates in 2 distinct macromolecular complexes: Ada Two- A-Containing (ATAC) and Spt-Ada-Gcn5-Acetyltransferase (SAGA). Through analysis of human cord blood hematopoietic stem cells and progenitors, and of myeloid leukemia cells, we identify unique respective contributions of the ATAC complex to regulation of biosynthetic activity in undifferentiated self-renewing cells, and of the SAGA complex to stabilisation or correct progression of cell type-specific programs with putative preservation of cell identity. Cell type and stage-specific dependencies on ATAC and SAGA-regulated programs explain multi-level KAT2A requirements in leukemia and in erythroid lineage specification and development. Importantly, they set a paradigm against which lineage specification and identity can be explored across developmental stem cell systems.Rosetrees Trust PhD Studentship; Kendall Leukaemia Fund Intermediate Fellowship (KKL888); Leuka John Goldman Fellowship for Future Science (2017); Wellcome Trust/University of Cambridge ISSF Grant; Lady Tata Memorial Trust PhD Studentship; Trinity Henry Barlow Trust Studentship; NIH RO1 grant (1R01GM131626-01); Agence Nationale de la Recherche (ANR) Program grants (AAPG2019 PICen, PRCI AAPG2019 EpiCAST, ANR-10-LABX-0030-INRT, frame program Investissements d’Avenir ANR-10IDEX-0002-02); Brunel University

Oxacillin sensitization of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius by antisense peptide nucleic acids in vitro

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Antibiotic resistance genes can be targeted by antisense agents, which can reduce their expression and thus restore cellular susceptibility to existing antibiotics. Antisense inhibitors can be gene and pathogen specific, or designed to inhibit a group of bacteria having conserved sequences within resistance genes. Here, we aimed to develop antisense peptide nucleic acids (PNAs) that could be used to effectively restore susceptibility to β-lactams in methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP). RESULTS: Antisense PNAs specific for conserved regions of the mobilisable gene mecA, and the growth essential gene, ftsZ, were designed. Clinical MRSA and MRSP strains of high oxacillin resistance were treated with PNAs and assayed for reduction in colony forming units on oxacillin plates, reduction in target gene mRNA levels, and cell size. Anti-mecA PNA at 7.5 and 2.5 μM reduced mecA mRNA in MRSA and MRSP (p < 0.05). At these PNA concentrations, 66 % of MRSA and 92 % of MRSP cells were killed by oxacillin (p < 0.01). Anti-ftsZ PNA at 7.5 and 2.5 μM reduced ftsZ mRNA in MRSA and MRSP, respectively (p ≤ 0.05). At these PNA concentrations, 86 % of MRSA cells and 95 % of MRSP cells were killed by oxacillin (p < 0.05). Anti-ftsZ PNAs resulted in swelling of bacterial cells. Scrambled PNA controls did not affect MRSA but sensitized MRSP moderately to oxacillin without affecting mRNA levels. CONCLUSIONS: The antisense PNAs effects observed provide in vitro proof of concept that this approach can be used to reverse β-lactam resistance in staphylococci. Further studies are warranted as clinical treatment alternatives are needed.Peer reviewedFinal Published versio

Youths are less susceptible to exercise-induced muscle damage than adults; a systematic review with meta-analysis

Purpose; This meta-analysis aimed to 1) provide a comparison of peak changes in indirect markers of EIMD in youths versus adults and 2) determine if the involved limb moderated this effect. Method; Studies were eligible for inclusion if they 1) provided a human youth versus adult comparison, 2) provided data on muscle strength, soreness or creatine kinase (CK) markers beyond ≥ 24 hours, 3) did not provide a recovery treatment. Effect sizes (ES) were presented alongside 95% confidence intervals. Results; EIMD exhibited larger effects on adults than in youths for muscle strength (ES=-2.01; P0.05). As such, the between-group effects for muscle soreness (ES=-2.10 versus -1.03; P<0.05) were greater in the upper- than lower-limb. Conclusion; The magnitude of EIMD in youths is substantially less than their adult counterparts, and this effect is greater in upper- than lower-limbs for muscle soreness. These findings help guide practitioners who may be concerned about the potential impact of EIMD when training youth athletes

Youths are less susceptible to exercise-induced muscle damage than adults:a systematic review with meta-analysis

Purpose: This meta-analysis aimed to (1) provide a comparison of peak changes in indirect markers of exercise-induced muscle damage (EIMD) in youths versus adults and (2) determine if the involved limb moderated this effect. Method: Studies were eligible for inclusion if they (1) provided a human youth versus adult comparison; (2) provided data on muscle strength, soreness, or creatine kinase markers beyond ≥24 hours; and (3) did not provide a recovery treatment. Effect sizes (ES) were presented alongside 95% confidence intervals. Results: EIMD exhibited larger effects on adults than in youths for muscle strength (ES = −2.01; P &lt; .001), muscle soreness (ES = −1.52; P &lt; .001), and creatine kinase (ES = −1.98; P &lt; .001). The random effects meta-regression indicated that the effects of upper- and lower-limb exercise in youths and adults were significant for muscle soreness (coefficient estimate = 1.11; P &lt; .001) but not for muscle strength or creatine kinase (P &gt; .05). As such, the between-group effects for muscle soreness (ES = −2.10 vs −1.03; P &lt; .05) were greater in the upper than lower limbs. Conclusion: The magnitude of EIMD in youths is substantially less than in their adult counterparts, and this effect is greater in upper than lower limbs for muscle soreness. These findings help guide practitioners who may be concerned about the potential impact of EIMD when training youth athletes

RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen responsible for significant human morbidity and mortality. Post-transcriptional regulation by small RNAs (sRNAs) has emerged as an important mechanism for controlling virulence. However, the functionality of the majority of sRNAs during infection is unknown. To address this, we performed UV cross-linking, ligation, and sequencing of hybrids (CLASH) in MRSA to identify sRNA-RNA interactions under conditions that mimic the host environment. Using a double-stranded endoribonuclease III as bait, we uncovered hundreds of novel sRNA-RNA pairs. Strikingly, our results suggest that the production of small membrane-permeabilizing toxins is under extensive sRNA-mediated regulation and that their expression is intimately connected to metabolism. Additionally, we also uncover an sRNA sponging interaction between RsaE and RsaI. Taken together, we present a comprehensive analysis of sRNA-target interactions in MRSA and provide details on how these contribute to the control of virulence in response to changes in metabolism