69 research outputs found

    Statistically does Peer Assisted Learning make a difference on Engineering Degree Programme in the UK? HETL Scotland 2017

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    Black British minority ethnic (BME) students are nationally underachieving in comparison to their Ethnic Chinese and White peers, typically 16% graduate attainment gap in the UK. Previous research has suggested that attainment gap could be explained by BME students’; lack of sense of belonging; disengagement; typically commute from their family home to University; typically have part-time employment. However, peer assisted learning (PAL) has been shown to have a positive impact on addressing and resolving students’ alienation and disengagement. However, a question still remains regarding whether student perceptions hold up to statistical analysis of learning performance when scrutinised in comparison to similar cohorts without PAL interventions. This paper presents the results of a statistical study for two cohorts of students on engineering courses with a disproportionately high representation of BME students. The research method undertook a statistical analysis of student records for the two cohorts to ascertain any patterns of correlation between: PAL; student ethnicity; and student parental employment upon student academic performance; and placement attainment. Student family employment background has been shown to typically influence student engagement and retention on educational studies. The analysis of the results of the two cohorts indicate that PAL has no significant impact on the academic performance; however PAL has a positive impact upon the placement attainment for BME students and students with parents in non-managerial/professional employment. Previous research evaluation of peer assisted learning programmes have focused on quantitative study of students’ surveys and qualitative semi-structured research interviews with students on their student engagement and learning experience. Whereas this paper evaluates the intervention from a quantitative statistical analysis of the student records data approach to evaluate the impact of the peer assisted learning has on a cohort’s academic performance and placement attainment in comparison to different social categories (classifications). The results are compared with the results of another cohort with a similar student profile, but has no peer assisted learning intervention implementatio

    A merowr amongys hem: An examination of female piety in the late fourteenth- and early fifteenth-century Norwich (Margery Kempe, Julian of Norwich, England).

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    This thesis analyzes female piety in the late fourteenth- and early fifteenth-centuries (c. 1370-1430) in England focusing on the area around Norwich. Of particular interest, for the purpose of this study, was the piety of the laity in Norwich as expressed by the large number of hermits and anchorites in the area, as well as a community of religious lay women that resembled the Beguine movement on the Continent. In this area mystical writings, particularly by female authors appeared, and the Lollard movement, which accorded women spiritual authority, flourished. Norwich, in this period, functioned as a location in which many different religious movements appeared. In this sense, Norwich was not representative of the spiritual movements found in the rest of England. The extremes between the two social tensions, that of increased lay piety through mysticism and the fear generated by the Lollard heresy, can be examined through The Book of Margery Kempe and the Heresy Trials in the Diocese of Norwich, 1428-31 (Norman P. Tanner, editor). (Abstract shortened by UMI.) Source: Masters Abstracts International, Volume: 37-01, page: 0099. Adviser: Jacqueline Murray. Thesis (M.A.)--University of Windsor (Canada), 1997

    Differential phosphorylation determines the repressor and activator potencies of GLI1 proteins and their efficiency in modulating the HPV life cycle

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    The Sonic Hedgehog (Shh) signalling pathway plays multiple roles during embryonic development and under pathological conditions. Although the core components of the Shh pathway are conserved, the regulation of signal transduction varies significantly among species and cell types. Protein kinases Ulk3 and Pka are involved in the Shh pathway as modulators of the activities of Gli transcription factors, which are the nuclear mediators of the signal. Here, we investigate the regulation and activities of two GLI1 isoforms, full-length GLI1 (GLI1FL) and GLI1ΔN. The latter protein lacks the first 128 amino acids including the conserved phosphorylation cluster and the binding motif for SUFU, the key regulator of GLI activity. Both GLI1 isoforms are co-expressed in all human cell lines analysed and possess similar DNA binding activity. ULK3 potentiates the transcriptional activity of both GLI1 proteins, whereas PKA inhibits the activity of GLI1ΔN, but not GLI1FL. In addition to its well-established role as a transcriptional activator, GLI1FL acts as a repressor by inhibiting transcription from the early promoters of human papillomavirus type 18 (HPV18). Additionally, compared to GLI1ΔN, GLI1FL is a more potent suppressor of replication of several HPV types. Altogether, our data show that the N-terminal part of GLI1FL is crucial for the realization of its full potential as a transcriptional regulator

    The transcriptional profile of coronary arteritis in Kawasaki disease.

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    BACKGROUND: Kawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment. METHODS: Deep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD. RESULTS: T lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis. CONCLUSIONS: The immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies

    The transcriptional profile of coronary arteritis in Kawasaki disease

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    BackgroundKawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment.MethodsDeep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD.ResultsT lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis.ConclusionsThe immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies

    Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression

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    Publisher Copyright: © 2022 American Society for Clinical Investigation. All rights reserved.Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C-induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110α subunit or with smallmolecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C-induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling.Peer reviewe

    Soluble CD44 Interacts with Intermediate Filament Protein Vimentin on Endothelial Cell Surface

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    CD44 is a cell surface glycoprotein that functions as hyaluronan receptor. Mouse and human serum contain substantial amounts of soluble CD44, generated either by shedding or alternative splicing. During inflammation and in cancer patients serum levels of soluble CD44 are significantly increased. Experimentally, soluble CD44 overexpression blocks cancer cell adhesion to HA. We have previously found that recombinant CD44 hyaluronan binding domain (CD44HABD) and its non-HA-binding mutant inhibited tumor xenograft growth, angiogenesis, and endothelial cell proliferation. These data suggested an additional target other than HA for CD44HABD. By using non-HA-binding CD44HABD Arg41Ala, Arg78Ser, and Tyr79Ser-triple mutant (CD443MUT) we have identified intermediate filament protein vimentin as a novel interaction partner of CD44. We found that vimentin is expressed on the cell surface of human umbilical vein endothelial cells (HUVEC). Endogenous CD44 and vimentin coprecipitate from HUVECs, and when overexpressed in vimentin-negative MCF-7 cells. By using deletion mutants, we found that CD44HABD and CD443MUT bind vimentin N-terminal head domain. CD443MUT binds vimentin in solution with a Kd in range of 12–37 nM, and immobilised vimentin with Kd of 74 nM. CD443MUT binds to HUVEC and recombinant vimentin displaces CD443MUT from its binding sites. CD44HABD and CD443MUT were internalized by wild-type endothelial cells, but not by lung endothelial cells isolated from vimentin knock-out mice. Together, these data suggest that vimentin provides a specific binding site for soluble CD44 on endothelial cells
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