Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine

Reactive oxygen species (ROS) participate in numerous cell responses, including proliferation, DNA damage, and cell death. Based on these disparate activities, both promotion and inhibition of ROS have been proposed for cancer therapy. However, how the ROS response is determined is not clear. We examined the activities of ROS in a model of Apc deletion, where loss of the Wnt target gene Myc both rescues APC loss and prevents ROS accumulation. Following APC loss, Myc has been shown to up-regulate RAC1 to promote proliferative ROS through NADPH oxidase (NOX). However, APC loss also increased the expression of TIGAR, which functions to limit ROS. To explore this paradox, we used three-dimensional (3D) cultures and in vivo models to show that deletion of TIGAR increased ROS damage and inhibited proliferation. These responses were suppressed by limiting damaging ROS but enhanced by lowering proproliferative NOX-derived ROS. Despite having opposing effects on ROS levels, loss of TIGAR and RAC1 cooperated to suppress intestinal proliferation following APC loss. Our results indicate that the pro- and anti-proliferative effects of ROS can be independently modulated in the same cell, with two key targets in the Wnt pathway functioning to integrate the different ROS signals for optimal cell proliferation

A framework for the adoption and diffusion of Personal Learning Environments in commercial organisations: an exploratory study in the learning and development sector in the UK

This study presents an exploratory approach to identify the main factors of Personal Learning Environment (PLE) adoption and diffusion within commercial organisations. Utilising an inductive investigative approach via the use of Grounded Theory methodology, relevant adoption factors were identified and their resulting influence during various stages of the innovation diffusion process were proposed. Data was collected using semi-structured interviews followed by systematic analysis using a three-staged coding process. The results revealed 10 factors affecting the adoption of PLEs influencing the innovation diffusion process at various stages. Informed by the Technology Acceptance Model and Innovation Diffusion Theory, the proposed model could have important implications for key decision makers within commercial organisations, while adopting, rejecting and assimilating new technological innovations (e.g. PLE) for learning delivery

Zinc fingers 1 and 7 of yeast TFIIIA are essential for assembly of a functional transcription complex on the 5 S RNA gene

The binding of transcription factor (TF) IIIA to the internal control region of the 5 S RNA gene is the first step in the assembly of a DNA–TFIIIA–TFIIIC– TFIIIB transcription complex, which promotes accurate transcription by RNA polymerase III. With the use of mutations that are predicted to disrupt the folding of a zinc finger, we have examined the roles of zinc fingers 1 through 7 of yeast TFIIIA in the establishment of a functional transcription complex both in vitro and in vivo. Our data indicate that, in addition to their role in DNA binding, the first and seventh zinc fingers contribute other essential roles in the assembly of an active transcription complex. Alanine-scanning mutagenesis identified residues within zinc finger 1 that are not required for DNA binding but are required for incorporation of TFIIIC into the TFIIIA–DNA complex. Although disruption of zinc finger 2 or 3 had a deleterious effect on the activity of TFIIIA both in vitro and in vivo, we found that increasing the level of their in vivo expression allowed these mutant proteins to support cell viability. Disruption of zinc fingers 4, 5 or 6 had minimal effect on the DNA binding and TF activities of TFIIIA

Self-employment among the Armed Forces Community

The Institute for Employment Research at the University of Warwick, QinetiQ and X-Forces Enterprise were commissioned by Forces in Mind Trust to understand what more could be done to support the Armed Forces Community in pursuing self-employment and thereby help to maximise their chances of a successful and sustainable transition. This research seeks to fill the current gap in knowledge and contribute to policy-making and service delivery