The role of cytochrome c in caspase activation in Drosophila melanogaster cells

The release of cytochrome c from mitochondria is necessary for the formation of the Apaf-1 apoptosome and subsequent activation of caspase-9 in mammalian cells. However, the role of cytochrome c in caspase activation in Drosophila cells is not well understood. We demonstrate here that cytochrome c remains associated with mitochondria during apoptosis of Drosophila cells and that the initiator caspase DRONC and effector caspase DRICE are activated after various death stimuli without any significant release of cytochrome c in the cytosol. Ectopic expression of the proapoptotic Bcl-2 protein, DEBCL, also fails to show any cytochrome c release from mitochondria. A significant proportion of cellular DRONC and DRICE appears to localize near mitochondria, suggesting that an apoptosome may form in the vicinity of mitochondria in the absence of cytochrome c release. In vitro, DRONC was recruited to a >700-kD complex, similar to the mammalian apoptosome in cell extracts supplemented with cytochrome c and dATP. These results suggest that caspase activation in insects follows a more primitive mechanism that may be the precursor to the caspase activation pathways in mammals

The COVID-safe university is an opportunity to end the default ableism of academia

Universities and academic institutions are making radical changes in an attempt to make their spaces and practices COVID-safe. In this post, Dr Stuart Read, Dr Anne Parfitt and Dr Tanvir Bush, put forward that this restructuring of academia presents a clear and present opportunity to expand inclusivity in academia and to redress the ableism currently present in academic life

How do we know that our research is ‘inclusive’?

COVID-19 has led to new ways of working which have transformed research practices. This has created opportunities for research cultures to be more inclusive and accessible- especially to those for whom the university is a barrier. However, post-pandemic, research cultures also need to change. In this post, Stuart Read, Anne Parfitt and Tanvir Bush outline three provocations that researchers can ask as part of an inclusive research practice

Prediction and control under uncertainty: Outcomes in angel investing

The article of record as published may be found at http://dx.doi.org/10.1016/j.jbusvent.2007.11.004Venture investing plays an important role in entrepreneurship not only because financial resources are important to new ventures, but also because early investors help shape the ventures' managerial and strategic destiny. In this study of 121 angel investors who had made 1038 new venture investments, we empirically investigate angel investors' differential use of predictive versus non-predictive control strategies. We show how the use of these strategies affects the outcomes of angel investors. Results show that angels who emphasize prediction make significantly larger venture investments, while those who emphasize nonpredictive control experience a reduction in investment failures without a reduction in their number of successes

Dilemmas of stigma, support seeking, and identity performance in physical disability: A social identity approach

Physically disabled people belong to a stigmatised group that is subject to negative societal stereotypes of incompetence and dependency on others. In order to maintain a positive sense of self, as well as receive needed support from others, physically disabled people need to continually navigate the stigma associated with disability. In so doing, they may face a number of dilemmas about how to express their disabled identity to others. The core argument of this thesis is that managing these identity dilemmas can have implications for support-seeking behaviour, as well as individual health and well-being. To develop this argument, this thesis aimed: first, to investigate the way in which physically disabled people experience their identity; second, to explore the role of stigma in shaping the experience and expression of identity among disabled individuals; and third, to elaborate a model of identity performance to describe how physically disabled people enact their identities in ways that navigate the twin concerns of stigma and accessing needed support. Before presenting a series of studies designed to address these aims, Chapters 1 through 3 explore the existing literature and develop the rationale for the present work. Chapter 1 presents a substantive review of previous research into stigma and physical disability. This review includes studies of general attitudes about disability and toward disabled individuals from the perspective of the non-disabled, and studies documenting the experience of stigmatisation from the perspective of disabled individuals themselves. Chapter 2 presents the social identity approach as a general framework for understanding identity in the context of stigma, and for theorising links between these processes and individual outcomes in terms of health and well-being. This chapter extends the basic social identity approach by incorporating recent thinking about identity performance, and considers the applicability of this to the disability context. Chapters 4 through 6 present the empirical work undertaken as part of this thesis. Chapter 4 provides a qualitative investigation of the ways in which people with cerebral palsy experience stigmatisation when accessing support. These experiences demonstrate individual awareness of stigma in support-seeking contexts and that this awareness is associated with felt pressures to perform one’s disabled identity in specific ways. In particular, respondents reported a tension between needing to be seen as sufficiently disabled in order to qualify for others’ support, but also the need to downplay feelings of difference from non-disabled people when accessing this support. Chapter 5 explores this tension further via a series of three connected quantitative studies. Using self-report data, these studies assessed how the salience of stigma as an issue (Study 2), and the salience of specific stigmatising audiences (healthcare providers, the general public, educators and employers; Studies 3 and 4) might promote changes in how physically disabled people enact their selves, and the implications of this for subjective feelings of health and well-being, and willingness to engage in support-seeking behaviour. The key finding from these studies is that the salience of specific audiences (but not the issues to which these connect) can activate expectations of stigma in the form of negative meta-stereotypes, and that these activated stereotypes shape the form and consequences of individual identity expressions. Healthcare providers were associated with especially negative stereotypes about disabled people, and these stereotypes undermined individual health and well-being as well as willingness to engage with support. Consistent with our identity-based analysis of these processes, individual differences in identification were found to play a role in modifying responses to these salient audiences and the meta-stereotypes these audiences activated in Studies 3 and 4. Finally, Chapter 6 presents a further qualitative investigation designed to build on the insights of the previous four studies. Specifically, Study 5 delves deeper into physically disabled people’s experiences of stigma when interacting with healthcare providers, educators and employers, the behavioural pressures they felt when doing so, and the strategies they engaged to deal with those pressures. When interacting with healthcare providers, participants discussed concerns about their deservingness for care potentially being questioned, and so sought to perform their identity in ways that demonstrated their legitimacy or need for support. When interacting with educators and employers, participants were instead concerned about being devalued in terms of their competence, and so sought to demonstrate their identity in ways that amplified their capabilities. However, in enacting these performances, participants noted the possible negative implications these behaviours had for how they personally viewed themselves (and wanted to be viewed by others). In this sense, Study 5 demonstrated that disabled people face dilemmas in negotiating demands from their audience, while also attempting to maintain a positive view of their self. In the concluding Chapter 7, a final discussion is completed in which the results from the five studies are reviewed and integrated, and the theoretical and practical contributions this work are noted.ESR

Effectual versus predictive logics in entrepreneurial decision-making: Differences between experts and novices

The article of record as published may be found at http://dx.doi.org/10.1016/j.jbusvent.2008.02.002In support of theory, this study demonstrates that entrepreneurial experts frame decisions using an “effectual” logic (identify more potential markets, focus more on building the venture as a whole, pay less attention to predictive information, worry more about making do with resources on hand to invest only what they could afford to lose, and emphasize stitching together networks of partnerships); while novices use a “predictive frame” and tend to “go by the textbook.”We asked 27 expert entrepreneurs and 37MBAstudents to think aloud continuously as they solved typical decision-making problems in creating a new venture. Transcriptions were analyzed using methods from cognitive science. Results showed that expert entrepreneurs framed problems in a dramatically different way than MBA students

Along-Strike Growth of the Ostler Fault, New Zealand: Consequences for Drainage Deflection above Active Thrust

Rarely are geologic records available to constrain the spatial and temporal evolution of thrust‐fault growth as slip accumulates during repeated earthquake events. Here, we utilize multiple generations of dated and deformed fluvial terraces to explore two key aspects of the along‐strike kinematic development of the Ostler fault zone in southern New Zealand over the past ∼100 k.y.: accumulation of fault slip through space and time and fixed‐length thrust growth that results in patterns of drainage diversion suggestive of laterally propagating faults. Along the Ostler fault, surface deformation patterns revealed by topographic surveying of terrace profiles in nine transverse drainages define systematic variations in fault geometry and suggest deformation over both listric and planar thrust ramps. Kinematic modeling of folded terrace profiles and \u3e100 fault‐scarp surveys along major fault sections reveals remarkably similar slip distributions for multiple successions of geomorphic surfaces spanning ∼100 k.y. Spatially abrupt and temporally sustained displacement gradients across zones of fault section overlap suggest that either persistent barriers to fault propagation or interference between overlapping faults dominate the interactions of fault tips from the scale of individual scarps to the entire fault zone. Deformed terrace surfaces dated using optically stimulated luminescence and cosmogenic radionuclides indicate steady, maximum rates of fault slip of ∼1.9 mm/yr during the Late Quaternary. Slip data synthesized along the central Ostler fault zone imply that displacement accumulated at approximately constant fault lengths over the past ∼100 k.y. A northward temporal progression of abandoned wind gaps along this section thus reflects lateral tilting in response to amplification of displacement, rather than simple fault lengthening or lateral propagation. Oscillations of climate at ∼104‐yr time scales modulate the formation and incision of geomorphic surfaces during successive glacial stages. Superimposed on apparently steadier rates of fault slip, such climate‐dependent surfaces contribute to a pattern of progressive drainage deflection along the central Ostler fault zone that is largely independent of fault propagation

Uranium Migration in Crystalline Rocks

The mechanisms controlling the migration of uranium in crystalline rocks such as granites or granodiorites are insufficiently well understood to arrive at a quantitatively defensible safety case for deep disposal of radioactive waste. To help further our knowledge of the relevant processes, a controlled column experiment was undertaken using a disc of metallic (depleted) uranium as a source and granodiorite samples from a former candidate disposal site for spent uranium fuel, Sievi in Finland, as the host medium. The experiment ran for approximately 500 days. This report summarises efforts made to simulate the uranium migration observed during the experiment. The model was developed from blind predictions to an inverse model that attempted to reproduce the measured effluent data. In the absence of independently derived kinetic data for uranium precipitation and dissolution it is difficult to arrive at a truly unique solution. Nevertheless, the exercise has been instructive in highlighting the principal areas of uncertainty and the pit falls that await those seeking to represent far more complex hydrogeochemical systems than that investigated here.JRC.F.7-Energy systems evaluatio

Entrepreneurial talent and venture performance: A meta-analytic investigation of SMEs

AbstractAs the broad link between small and medium-sized firm activity and key policy goals such as employment or economic growth has become generally accepted, the conversation has focused on a more nuanced understanding of the entrepreneurial engines of economic activity. A significant body of research looking at antecedents to venture performance has identified that entrepreneurial talent variables account for meaningful differences in venture performance and that significant heterogeneity exists across performance measures. These are important issues for institutions and policy makers seeking to achieve specific economic goals (e.g., survival or growth of ventures, employment or revenue). Using meta-analysis, we integrate this work to view connections between aspects of entrepreneurial talent and different performance outcomes. Our investigation includes 50,045 firms (K of 183 studies) and summarizes 1002 observations of small and medium-sized firms. Analysis of these data yields an unexpectedly weak connection between education and performance. Furthermore, growth, scale (number of employees) and sales outcomes are significantly related to planning skills, while profit and other financial and qualitative measures are strongly connected with the network surrounding the firm founders. Moreover, we observe that entrepreneurial talent is more relevant in developing economies