High-Throughput Screening Platform To Identify Inhibitors of Protein Synthesis with Potential for the Treatment of Malaria

Artemisinin-based combination therapies have been crucial in driving down the global burden of malaria, the world’s largest parasitic killer. However, their efficacy is now threatened by the emergence of resistance in Southeast Asia and sub-Saharan Africa. Thus, there is a pressing need to develop new antimalarials with diverse mechanisms of action. One area of Plasmodium metabolism that has recently proven rich in exploitable antimalarial targets is protein synthesis, with a compound targeting elongation factor 2 now in clinical development and inhibitors of several aminoacyl-tRNA synthetases in lead optimization. Given the promise of these components of translation as viable drug targets, we rationalized that an assay containing all functional components of translation would be a valuable tool for antimalarial screening and drug discovery. Here, we report the development and validation of an assay platform that enables specific inhibitors of Plasmodium falciparum translation (PfIVT) to be identified. The primary assay in this platform monitors the translation of a luciferase reporter in a P. falciparum lysate-based expression system. Hits identified in this primary assay are assessed in a counterscreen assay that enables false positives that directly interfere with the luciferase to be triaged. The remaining hit compounds are then assessed in an equivalent human IVT assay. This platform of assays was used to screen MMV’s Pandemic and Pathogen Box libraries, identifying several selective inhibitors of protein synthesis. We believe this new high-throughput screening platform has the potential to greatly expedite the discovery of antimalarials that act via this highly desirable mechanism of action

In search of phylogenetic congruence between molecular and morphological data in bryozoans with extreme adult skeletal heteromorphy

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Markovian evolution of quantum coherence under symmetric dynamics

Both conservation laws and practical restrictions impose symmetry constraints on the dynamics of open quantum systems. In the case of time-translation symmetry, which arises naturally in many physically relevant scenarios, the quantum coherence between energy eigenstates becomes a valuable resource for quantum information processing. In this work we identify the minimum amount of decoherence compatible with this symmetry for a given population dynamics. This yields a generalisation to higher-dimensional systems of the relation T2 2T1 for qubit decoherence and relaxation times. It also enables us to witness and assess the role of non-Markovianity as a resource for coherence preservation and transfer. Moreover, we discuss the relationship between ergodicity and the ability of Markovian dynamics to indenitely sustain a superposition of diferent energy states. Finally, we establish a formal connection between the resource-theoretic and the master equation approaches to thermodynamics, with the former being a non-Markovian generalisation of the latter. Our work thus brings the abstract study of quantum coherence as a resource towards the realm of actual physical applications

Clinical supervision for clinical psychology students in Uganda: an initial qualitative exploration

Background Burn out in clinical psychologists working in low income countries has been reported. Clinical supervisory structures do not yet exist in Uganda. A way to decrease levels of burn out and increase quality of care for people with mental illness is through clinical supervision. The aim of this study was to explore the initial experiences of supervision for clinical psychology students in Uganda to ascertain whether or not clinical supervision is culturally appropriate, and what aspects of supervision had been helpful and unhelpful. Methods A qualitative design with thematic analysis was utilized. A focus group was held with 12 second year clinical psychology students to ask their experiences of receiving supervision. Results Data analysis created five themes. Firstly, the negative emotions that resulted from the training processed were discussed, and how supervision helped and did not help the students to manage these. Secondly, the students voiced that supervision helped them to learn through observational experiences, co-therapist roles and parallel processes within the supervisory relationship. Thirdly, supervision had taught the clinical psychology students their role as a clinical psychology student, how to act within the Ugandan mental health system and skills to conduct therapy. Fourthly, suggestions for the future of supervision were given, with the students requesting for it to start earlier in the training, for supervisors who can meet with the students on a regular basis to be selected and for the training the students receive at university to match the skills required on their placements, with a request for more practical techniques rather than theory. The final theme related to left over miscellaneous data, such as the students agreeing with each other. Conclusions The students stated that supervision was helpful overall, implying that clinical supervision is culturally appropriate for clinical psychology students in Uganda. Suggestions for future supervision were given. In order to decrease high levels of staff burn out in the mental health systems in Uganda, supervisory structures with an emphasis on self care need to be established

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability

Ancient DNA Suggests Dwarf and ‘Giant’ Emu Are Conspecific

) is unclear. King Island Emu were mainly distinguished by their much smaller size and a reported darker colour compared to modern Emu. oxidase subunit I (COI) region (1,544 bp), as well as a region of the melanocortin 1 receptor gene (57 bp) were sequenced using a multiplex PCR approach. The results show that haplotypes for King Island Emu fall within the diversity of modern Emu.These data show the close relationship of these emu when compared to other congeneric bird species and indicate that the King Island and modern Emu share a recent common ancestor. King Island emu possibly underwent insular dwarfism as a result of phenotypic plasticity. The close relationship between the King Island and the modern Emu suggests it is most appropriate that the former should be considered a subspecies of the latter. Although both taxa show a close genetic relationship they differ drastically in size. This study also suggests that rates of morphological and neutral molecular evolution are decoupled