RNA systems biology: uniting functional discoveries and structural tools to understand global roles of RNAs

RNAs assume sophisticated structures that are active in myriad cellular processes. In this review, we highlight newly identified ribozymes, riboswitches, and small RNAs, some of which control the function of cellular metabolic and gene expression networks. We then examine recent developments in genome-wide RNA structure probing technologies that are yielding new insights into the structural landscape of the transcriptome. Finally, we discuss how these RNA ‘structomic’ methods can address emerging questions in RNA systems biology, from the mechanisms behind long non-coding RNAs to new bases for human diseases

T. brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes

Aims: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response. Methods and results: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release (Ca2+ waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10–15% increase of SERCA activity but reduced SR Ca2+ content, suggesting a concomitant increased SR-mediated Ca2+ leak. This conclusion was supported by data demonstrating that TbCatL increased Ca2+ wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events. Conclusion: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function

Postfledging Survival, Movements, and Dispersal of Ring Ouzels (Turdus torquatus)

We thank Invercauld Estate for cooperation with access to Glen Clunie. S. Redpath, J. Wilson, and S. Roos provided valuable comments on the manuscript. This study was funded by the Royal Society for the Protection of Birds, Scottish Natural Heritage, and the Cairngorms National Park Authority. J.L.L. was supported by the Natural Environment Research Council.Peer reviewedPublisher PD

Reviewing Directors' Business Judgements: Views from the Field

Directors take decisions that can have significant impacts on others, as illustrated by the global financial crisis and the collapse of Thomas Cook Group plc. Yet many academics argue that courts should not review or impose liability on directors for poor business judgements. These arguments often rely on untested empirical assumptions about directors’ behaviour and attitudes. Through semi‐structured interviews and focus groups, we explored the responses of directors, legal practitioners, company secretaries, and board headhunters to the prospect of judicial review of directors’ business judgements. Our findings challenge orthodox thinking: many directors supported some form of review and the impact of review may not be as great as the literature predicts, nor necessarily detrimental. The debate about whether courts should review directors’ business judgements should therefore move away from reliance on negative empirical assumptions about the impact of review, to clearly articulating, and engaging with, normative positions that underpin opposition to, and support for, review

The impact of long-term land leases on farm investment: Evidence from the Irish dairy sector

The European Union milk quota abolition in 2015 resulted in rapid dairy farm expansion across many Member States. Continued production growth requires both capital and herd investment with secure access to land resources being important for new and expanding farmers. As land sales and rental remain low in Ireland, tax incentives to encourage long-term land rental were increased in 2015. This paper assesses the influence of the length of land leases on dairy farm investment using farm-level data from 2015 to 2018 in the context of low levels of land sales and land rental, and liberal market regulations in Ireland. We find a positive association between lease lengths and both the probability and level of capital investment which is particularly important for farmers with a high portion of land rented in. We find that herd investment is not influenced by the duration of land leases. Our findings call for an extension of policies that encourage land rental on secure leases, especially for young farmers, to increase certainty and support growth in the industry