6,371 research outputs found

    Biological functions of CDK5 and potential CDK5 targeted clinical treatments.

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    Cyclin dependent kinases are proline-directed serine/threonine protein kinases that are traditionally activated upon association with a regulatory subunit. For most CDKs, activation by a cyclin occurs through association and phosphorylation of the CDK\u27s T-loop. CDK5 is unusual because it is not typically activated upon binding with a cyclin and does not require T-loop phosphorylation for activation, even though it has high amino acid sequence homology with other CDKs. While it was previously thought that CDK5 only interacted with p35 or p39 and their cleaved counterparts, Recent evidence suggests that CDK5 can interact with certain cylins, amongst other proteins, which modulate CDK5 activity levels. This review discusses recent findings of molecular interactions that regulate CDK5 activity and CDK5 associated pathways that are implicated in various diseases. Also covered herein is the growing body of evidence for CDK5 in contributing to the onset and progression of tumorigenesis

    Building bridges: enhancing mentoring skills, knowledge and practice through an online course

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    This paper outlines the rationale for an open online course for teachers, Enhance your Mentoring Skills, aimed at addressing the UK National Mentor Standards (2016), and describes how this was put into practice. The professional needs of school-based mentors and how these were met in the design for learning are examined alongside a consideration of the efficacy of the curriculum and associated pedagogy of the course. Drawing on the evaluations of 73 teachers who have completed the course in 2017 and their contributions to individual and communal learning activities the paper develops an impression of mentoring practice that represents mentors’ theories-in-use. Teachers’ accounts of the value of the course suggest considerable effect on their levels of confidence and some evidence of impact on their mentoring practice. However, findings also indicate that participants’ understandings of their mentoring role lacks a clearly defined model for mentoring relationships and that mentors welcome greater opportunity to reflect on their practice and to share this with others discursively. The paper discusses the extent to which the course offers a bridge between mentors’ wishes and intentions and how they are realised in practice. Recommendations for future iterations of the course are made, with proposals to develop this case study further, as an instrumental form of theory building (Stake, 1995), in order to better understand how mentors understand and develop their practice

    Nfix expression critically modulates early B lymphopoiesis and myelopoiesis

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    The commitment of stem and progenitor cells toward specific hematopoietic lineages is tightly controlled by a number of transcription factors that regulate differentiation programs via the expression of lineage restricting genes. Nuclear factor one (NFI) transcription factors are important in regulating hematopoiesis and here we report an important physiological role of NFIX in B- and myeloid lineage commitment and differentiation. We demonstrate that NFIX acts as a regulator of lineage specification in the haematopoietic system and the expression of Nfix was transcriptionally downregulated as B cells commit and differentiate, whilst maintained in myeloid progenitor cells. Ectopic Nfix expression in vivo blocked early B cell development stage, coincident with the stage of its downregulation. Furthermore, loss of Nfix resulted in the perturbation of myeloid and lymphoid cell differentiation, and a skewing of gene expression involved in lineage fate determination. Nfix was able to promote myeloid differentiation of total bone marrow cells under B cell specific culture conditions but not when expressed in the hematopoietic stem cell (HSPC), consistent with its role in HSPC survival. The lineage choice determined by Nfix correlated with transcriptional changes in a number of genes, such as E2A, C/EBP, and Id genes. These data highlight a novel and critical role for NFIX transcription factor in hematopoiesis and in lineage specification

    Discounted cash flow and business valuation in a nineteenth century merger: A note

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    In 1889 the Shelton Iron, Steel and Coal Company Limited was incorporated to take over the assets and business activities of two existing companies. To guide the contracting parties in negotiating a price to be paid for the properties belonging to the Shelton Collieries and Ironworks an independent valuation was arranged by Deloitte, Dever, Griffiths & Co., later appointed auditors of the new company. The article comprises an appraisal of the valuation exercise, which is an early example of the use of a discounted cash flow technique to provide relevant information for a capital investment decision
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