176 research outputs found

    Business and social entrepreneurs in the UK : gender, context and commitment

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    Objectives: What sort of people become social entrepreneurs, and in what way do they differ from business entrepreneurs? This question is important for policy because there has been a shift from direct to indirect delivery of many public services, requiring a professional approach to social enterprise. Yet we know little about who sets up social enterprises. Prior work: Much prior work on social entrepreneurs has been based on small and convenience samples, and this is true in the United Kingdom as elsewhere. An exception is work based on annual UK Global Entrepreneurship monitor (GEM) surveys (e.g. Levie et al., 2006). Approach: Defining and distinguishing business from social entrepreneurs is problematic. However, inclusion of items that measured the relative importance of economic, social and environmental goals in the 2009 UK GEM survey enables us to compare business and social entrepreneurs based on two different definitions: activity-based (setting up or running a new business or any kind of social, voluntary or community activity, venture or initiative) and goals-based (setting up or running a new organisation which has mainly economic goals versus mainly social goals). We use logistic multivariate regression techniques to identify differences between business and social entrepreneurs in demographic characteristics, effort, aspiration, use of resources, industry choice, location and organisational structure, identified from a representative sample of 30,000 adults interviewed in the United Kingdom in 2009. Results: The results show that the odds of an early-stage entrepreneur being a social rather than a business entrepreneur are reduced if they are male, from an ethnic minority, if they work 10 hours or more per week on the venture, and if they ever worked in their parents business, while they are increased if they have higher levels of education and if they are a settled in-migrant to their area. Implications: These results suggest that a high proportion of social enterprise founders are part-time founders. This could be a cause for concern for policy-makers keen to shift delivery of professional services from the public sector to a professional third sector. Future surveys could test if there is a hand-over of control from founders to full-time managers as social enterprises mature. Value: To our knowledge, this is the first time that large representative samples of business and social entrepreneurs have been compared using multivariate analysis. This type of research complements case-based research, enabling hypotheses raised by qualitative research to be tested on representative samples of a population

    Upper primary school students’ scientific and socio-scientific thinking: A case study investigating epistemic challenges in year-six inquiry science lessons

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    Science education in schools has moved from the learning of scientific facts to investigating the impact that science has on students’ lives; providing students with an understanding of how they relate to, and affect, their environment. This shift is evident in many countries’ curricula (e.g. Australian National Curriculum). One example of this is the requirement for students to consider issues related to ‘sustainability’; to consider scientific facts and to consider themselves as both part of the problem and part of the solution. Socio-scientific issues are ill-structured; that is, they may have many viable alternative solutions and it can be difficult to know when a satisfactory solution has been reached. Solving socio-scientific problems involves the use of knowledge learnt in different contexts, including scientific knowledge and experiential knowledge. This study seeks to gain a better understanding of how and when year 6 primary school students (aged 10 to 12 years) activate prior knowledge while considering sustainability issues. The study sought to vary the context in which students were set sustainability problems. Using a ‘knowledge in pieces’ theoretical framework, which attunes to changes in context, the study investigates conditions that may promote appropriate knowledge activations. Based on a case study methodology, the research employs epistemic interviewing techniques coupled with close participant observations to gain a better, more nuanced understanding of the processes involved when year-six primary school students consider issues about sustainability. The thesis reports on three empirical episodes during which different aspects of context were varied; the problem context, the knowledge context and the physical context. Data was analysed using inductive thematic analysis and the results were considered alongside existing pedagogical approaches. The results showed that the variation of all three contextual elements led to variations in the manner in which the students solved the sustainability problems. It was observed that epistemic prompts helped the participants to make progress towards viable solutions. These epistemic prompts came from the facilitator of learning, from other students, and from the activities in which the students were engaged. When embarking on a learning program that involves socio-scientific issues, facilitators of learning can benefit from recognising that the nature of these issues will require students to integrate both taught knowledge and everyday experiences. Students may activate conflicting knowledge resources that lead to confusing results. It is at these points that epistemic challenges (challenging the students to consider their knowledge and to justify that knowledge) can prove beneficial in helping the students sort out their own solutions to these complex issues

    Translation controlled

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    A report of the meeting 'Translational Control', Cold Spring Harbor, USA, 3-7 September 2008

    Dynamic cycling of eIF2 through a large eIF2B-containing cytoplasmic body: implications for translation control

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    The eukaryotic translation initiation factor 2B (eIF2B) provides a fundamental controlled point in the pathway of protein synthesis. eIF2B is the heteropentameric guanine nucleotide exchange factor that converts eIF2, from an inactive guanosine diphosphate–bound complex to eIF2-guanosine triphosphate. This reaction is controlled in response to a variety of cellular stresses to allow the rapid reprogramming of cellular gene expression. Here we demonstrate that in contrast to other translation initiation factors, eIF2B and eIF2 colocalize to a specific cytoplasmic locus. The dynamic nature of this locus is revealed through fluorescence recovery after photobleaching analysis. Indeed eIF2 shuttles into these foci whereas eIF2B remains largely resident. Three different strategies to decrease the guanine nucleotide exchange function of eIF2B all inhibit eIF2 shuttling into the foci. These results implicate a defined cytoplasmic center of eIF2B in the exchange of guanine nucleotides on the eIF2 translation initiation factor. A focused core of eIF2B guanine nucleotide exchange might allow either greater activity or control of this elementary conserved step in the translation pathway

    These - Are - The Breaks : A Roundtable Discussion on Teaching the Post-Soul Aesthetic

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    We met at Duke University - mid-summer, in the mid Atlantic, at mid-campus - to talk about teaching courses that focused on the post-soul aesthetic. We met outside the John Hope Franklin Center, and soon enough we five youngish black professors were walking a hallway towards a conference room near the African and African American Studies program. Not at all surprisingly, the walls of the hallway were lined with framed photographs of the esteemed John Hope Franklin at various stages throughout his long and storied career. For me, given the topic I was about to raise among these professional colleagues, walking that hallway was something like running a gauntlet: Franklin\u27s career is one of continued, sustained Negro uplift, as the photomontage of him documents. The post-soul aesthetic, on the other hand, critiques and questions certain black assumptions and traditions, and most professors who teach the art and literature of this post-civil rights movement aesthetic must, to apprehend the course material, assume a peculiar, if not precarious, pedagogical stance in the classroom, one that respects careers like Dr. Franklin\u27s, but also constructively interrogates - and sometimes explodes - the very presumptions and precepts on which such a career stands

    Cellular eIF2B subunit localisation: implications for the integrated stress response and its control by small molecule drugs

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    eIF2 is a G protein critical for translation. It is tightly regulated in the integrated stress response (ISR) via phosphorylation of eIF2α and the subsequent control of eIF2B, a multisubunit guanine nucleotide exchange factor (GEF). Through studying the localisation of eIF2B subunits we identified cytoplasmic eIF2B bodies in mammalian cells. We highlight a relationship between body size and the eIF2B subunits localising to them; larger bodies contain all subunits and smaller bodies contain predominantly catalytic subunits. eIF2 localises to eIF2B bodies and shuttles within these bodies in a manner which correlates with eIF2B activity. Upon stress eIF2α-P localises predominately to larger bodies and results in a decreased shuttling of eIF2. Interestingly drugs which inhibit the ISR can rescue eIF2 shuttling in a manner correlating to levels of eIF2α-P. In contrast, smaller bodies show increased eIF2 shuttling in response to stress, which is accompanied by the localisation of eIF2Bδ to these bodies, suggesting the formation of a novel trimeric complex of eIF2B. This response is mimicked by ISR inhibiting drugs, providing insight into their potential mechanism of action. This study provides evidence that the composition and function of mammalian eIF2B bodies is regulated by the ISR and drugs which control it

    Stress-dependent relocalization of translationally primed mRNPs to cytoplasmic granules that are kinetically and spatially distinct from P-bodies

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    Cytoplasmic RNA granules serve key functions in the control of messenger RNA (mRNA) fate in eukaryotic cells. For instance, in yeast, severe stress induces mRNA relocalization to sites of degradation or storage called processing bodies (P-bodies). In this study, we show that the translation repression associated with glucose starvation causes the key translational mediators of mRNA recognition, eIF4E, eIF4G, and Pab1p, to resediment away from ribosomal fractions. These mediators then accumulate in P-bodies and in previously unrecognized cytoplasmic bodies, which we define as EGP-bodies. Our kinetic studies highlight the fundamental difference between EGP- and P-bodies and reflect the complex dynamics surrounding reconfiguration of the mRNA pool under stress conditions. An absence of key mRNA decay factors from EGP-bodies points toward an mRNA storage function for these bodies. Overall, this study highlights new potential control points in both the regulation of mRNA fate and the global control of translation initiation

    Constitutively-stressed yeast strains are high-yielding for recombinant Fps1:implications for the translational regulation of an aquaporin

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    Background: We previously selected four strains of Saccharomyces cerevisiae for their ability to produce the aquaporin Fps1 in sufficient yield for further study. Yields from the yeast strains spt3Δ, srb5Δ, gcn5Δ and yTHCBMS1 (supplemented with 0.5 μg/mL doxycycline) that had been transformed with an expression plasmid containing 249 base pairs of 5′ untranslated region (UTR) in addition to the primary FPS1 open reading frame (ORF) were 10–80 times higher than yields from wild-type cells expressing the same plasmid. One of the strains increased recombinant yields of the G protein-coupled receptor adenosine receptor 2a (A2aR) and soluble green fluorescent protein (GFP). The specific molecular mechanisms underpinning a high-yielding Fps1 phenotype remained incompletely described. Results: Polysome profiling experiments were used to analyze the translational state of spt3Δ, srb5Δ, gcn5Δ and yTHCBMS1 (supplemented with 0.5 μg/mL doxycycline); all but gcn5Δ were found to exhibit a clear block in translation initiation. Four additional strains with known initiation blocks (rpl31aΔ, rpl22aΔ, ssf1Δ and nop1Δ) also improved the yield of recombinant Fps1 compared to wild-type. Expression of the eukaryotic transcriptional activator GCN4 was increased in spt3Δ, srb5Δ, gcn5Δ and yTHCBMS1 (supplemented with 0.5 μg/mL doxycycline); these four strains also exhibited constitutive phosphorylation of the eukaryotic initiation factor, eIF2α. Both responses are indicative of a constitutively-stressed phenotype. Investigation of the 5′UTR of FPS1 in the expression construct revealed two untranslated ORFs (uORF1 and uORF2) upstream of the primary ORF. Deletion of either uORF1 or uORF1 and uORF2 further improved recombinant yields in our four strains; the highest yields of the uORF deletions were obtained from wild-type cells. Frame-shifting the stop codon of the native uORF (uORF2) so that it extended into the FPS1 ORF did not substantially alter Fps1 yields in spt3Δ or wild-type cells, suggesting that high-yielding strains are able to bypass 5′uORFs in the FPS1 gene via leaky scanning, which is a known stress-response mechanism. Yields of recombinant A2aR, GFP and horseradish peroxidase could be improved in one or more of the yeast strains suggesting that a stressed phenotype may also be important in high-yielding cell factories. Conclusions: Regulation of Fps1 levels in yeast by translational control may be functionally important; the presence of a native uORF (uORF2) may be required to maintain low levels of Fps1 under normal conditions, but higher levels as part of a stress response. Constitutively-stressed yeast strains may be useful high-yielding microbial cell factories for recombinant protein production

    Functional diversification of Argonautes in nematodes:an expanding universe

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    In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism
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