Hidden in the Middle : Culture, Value and Reward in Bioinformatics

Bioinformatics - the so-called shotgun marriage between biology and computer science - is an interdiscipline. Despite interdisciplinarity being seen as a virtue, for having the capacity to solve complex problems and foster innovation, it has the potential to place projects and people in anomalous categories. For example, valorised 'outputs' in academia are often defined and rewarded by discipline. Bioinformatics, as an interdisciplinary bricolage, incorporates experts from various disciplinary cultures with their own distinct ways of working. Perceived problems of interdisciplinarity include difficulties of making explicit knowledge that is practical, theoretical, or cognitive. But successful interdisciplinary research also depends on an understanding of disciplinary cultures and value systems, often only tacitly understood by members of the communities in question. In bioinformatics, the 'parent' disciplines have different value systems; for example, what is considered worthwhile research by computer scientists can be thought of as trivial by biologists, and vice versa. This paper concentrates on the problems of reward and recognition described by scientists working in academic bioinformatics in the United Kingdom. We highlight problems that are a consequence of its cross-cultural make-up, recognising that the mismatches in knowledge in this borderland take place not just at the level of the practical, theoretical, or epistemological, but also at the cultural level too. The trend in big, interdisciplinary science is towards multiple authors on a single paper; in bioinformatics this has created hybrid or fractional scientists who find they are being positioned not just in-between established disciplines but also in-between as middle authors or, worse still, left off papers altogether

Corporate reputation past and future: a review and integration of existing literature and a framework for future research

The concept of corporate reputation is steadily growing in interest among management researchers and practitioners. In this article, we trace key milestones in the development of reputation literature over the past six decades to suggest important research gaps as well as to provide contextual background for a subsequent integration of approaches and future outlook. In particular we explore the need for better categorised outcomes; a wider range of causes; and a deeper understanding of contingencies and moderators to advance the field beyond its current state while also taking account of developments in the macro business environment. The article concludes by presenting a novel reputation framework that integrates insights from reputation theory and studies, outlines gaps in knowledge and offers directions for future research

The Mitochondrial BK Channel as a Novel Therapeutic Target During Renal Cold Storage and Transplantation: Its Role as a Mitochondrial-Protective Factor

Last year ~34% of donor kidneys were discarded due in part to injury that occurs during cold storage (CS), leading to a high mortality of patients waiting for transplantation. Deceased donor kidneys exposed to CS are five-fold more likely to fail than those from living donors (without CS). Thus, there is a critical need to investigate mechanisms involved with CS-induced renal injury, which will help advance the development of novel therapeutic interventions to improve transplant outcomes. Our laboratory and others have shown that CS ‘alone’ induces renal mitochondrial dysfunction and oxidative injury. However, the extent of injury when CS is combined with transplantation (CS+Tx) as well as the identity of specific mitochondrial targets remain elusive. Exploring these questions was the primary goal of this dissertation project. First, using a novel rat renal transplant model, we demonstrated that even short-term (4h) CS exacerbates mitochondrial and renal injury after Tx compared to Tx alone (without CS). Next, we speculated that the mitochondrial large-conductance Ca2+-activated K+ channel (mitoBK) was a potential therapeutic target since its activation has been shown to be mitochondrial-protective during warm ischemic injury. The hypothesis to be tested is CS-induced mitochondrial ROS impair mitoBK channel function, which contributes to renal and mitochondrial injury. Addition of BK activators during CS protects against mitochondrial and renal injury following transplantation. Using our rat renal cell line (NRK), we identified, for the first time, the presence of an active mitoBK channel. Cells exposed to CS followed by rewarming (CS+RW) significantly reduced mitoBK function. Excitingly, addition of the specific BK activator, NS11021 (1 μM), during CS restored mitoBK function and mitigated CS+RW-induced mitochondrial and cell injury. Finally, using our preclinical rat model of CS+Tx, NS11021 (3 μM) partially mitigated mitochondrial dysfunction and cell injury, but not renal dysfunction. Overall, these studies support our hypothesis and identify the mitoBK channel as a promising pharmacotherapeutic target for preventing CS-induced mitochondrial injury and renal injury. Future studies are warranted to better characterize mitoBK’s mitochondrial-protective role and to optimize this therapeutic approach, which is a clinically attractive strategy that avoids systemic drug exposure in the transplant recipient

Tocotrienols Provide Radioprotection to Multiple Organ Systems through Complementary Mechanisms of Antioxidant and Signaling Effects

Tocotrienols have powerful radioprotective properties in multiple organ systems and are promising candidates for development as clinically effective radiation countermeasures. To facilitate their development as clinical radiation countermeasures, it is crucial to understand the mechanisms behind their powerful multi-organ radioprotective properties. In this context, their antioxidant effects are recognized for directly preventing oxidative damage to cellular biomolecules from ionizing radiation. However, there is a growing body of evidence indicating that the radioprotective mechanism of action for tocotrienols extends beyond their antioxidant properties. This raises a new pharmacological paradigm that tocotrienols are uniquely efficacious radioprotectors due to a synergistic combination of antioxidant and other signaling effects. In this review, we have covered the wide range of multi-organ radioprotective effects observed for tocotrienols and the mechanisms underlying it. These radioprotective effects for tocotrienols can be characterized as (1) direct cytoprotective effects, characteristic of the classic antioxidant properties, and (2) other effects that modulate a wide array of critical signaling factors involved in radiation injury