A panel of recombinant cell surface and secreted proteins identifies LdBPK_323600.1 as a serological marker of symptomatic infection.

Unlabelled: Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test.

Quasi-cyclical preferences in the ethics of Plato, Aristotle, and Kant.

Bermúdez describes the extensionality principle as being "almost unquestioned." This claim might come as a surprise to philosophers who work on agency and ethics. In Kantian deontological ethics and in Platonic or Aristotelian virtue ethics, our preferences for outcomes can be rationally affected by how those outcomes are framed in terms of maxims and character traits.

Systematic identification of genes encoding cell surface and secreted proteins that are essential for in vitro growth and infection in Leishmania donovani.

Leishmaniasis is an infectious disease caused by protozoan parasites belonging to the genus Leishmania for which there are no approved human vaccines. Infections localise to different tissues in a species-specific manner with the visceral form of the disease caused by Leishmania donovani and L. infantum being the most deadly in humans.

Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening.

Visceral leishmaniasis is an infectious parasitic disease caused by the protozoan parasites Leishmania donovani and Leishmania infantum. The drugs currently used to treat visceral leishmaniasis suffer from toxicity and the emergence of parasite resistance, and so a better solution would be the development of an effective subunit vaccine; however, no approved vaccine currently exists. The comparative testing of a large number of vaccine candidates requires a quantitative and reproducible experimental murine infection model, but the parameters that influence infection pathology have not been systematically determined.

Kantian indifference about moral reason.

The pessimistic arguments May challenges depend on an anti-Kantian philosophical assumption. That assumption is that what I call philosophical optimists about moral reason are also committed to empirical optimism, or what May calls "optimistic rationalism." I place May's book in the literature by explaining how that assumption is resisted by Christine Korsgaard, one of May's examples of a contemporary Kantian.

A role for trypanosomatid aldo-keto reductases in methylglyoxal, prostaglandin and isoprostane metabolism.

Trypanosomatid parasites are the infectious agents causing Chagas disease, visceral and cutaneous leishmaniasis and human African trypanosomiasis. Recent work of others has implicated an aldo-keto reductase (AKR) in the susceptibility and resistance of to benznidazole, a drug used to treat Chagas disease. Here, we show that AKR and homologues in the related parasites and do not reductively activate monocyclic (benznidazole, nifurtimox and fexinidazole) or bicyclic nitro-drugs such as PA-824.

Epistemic Authority and Genuine Ethical Controversies.

In 'Professional Hubris and its Consequences', Eric Vogelstein claims that 'that there are no good arguments in favor of professional organizations taking genuinely controversial positions on issues of professional ethics'. In this response, I defend two arguments in favour of organisations taking such positions: that their stance-taking may lead to better public policy, and that it may lead to better practice by medical professionals. If either of those defences succeeds, then Vogelstein's easy path to his conclusion - that professional organisations should not take such stances - is blocked.

Activation of Bicyclic Nitro-drugs by a Novel Nitroreductase (NTR2) in Leishmania.

Drug discovery pipelines for the "neglected diseases" are now heavily populated with nitroheterocyclic compounds. Recently, the bicyclic nitro-compounds (R)-PA-824, DNDI-VL-2098 and delamanid have been identified as potential candidates for the treatment of visceral leishmaniasis. Using a combination of quantitative proteomics and whole genome sequencing of susceptible and drug-resistant parasites we identified a putative NAD(P)H oxidase as the activating nitroreductase (NTR2).

The N-myristoylome of Trypanosoma cruzi.

Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas' disease. Here we have employed whole cell labelling with azidomyristic acid and click chemistry to identify N-myristoylated proteins in different life cycle stages of the parasite. Only minor differences in fluorescent-labelling were observed between the dividing forms (the insect epimastigote and mammalian amastigote stages) and the non-dividing trypomastigote stage.

A framework for assessing the ethics of doctors' strikes.

The first aim of this article is to offer a framework for constructive and rigorous discussions of the ethics of doctors' strikes, beginning with an in-principle distinction between the questions of how one should conduct oneself while working as a doctor and when and how one can suspend that work. The second is to explore how that framework applies to the contemporary British case of strikes by English junior doctors, with my suggestion being that those strikes do meet all of the criteria proposed. In closing, I gesture towards a further ethical dimension to strikes which is too often overlooked: namely, the responsibilities of employers and others not to misrepresent or demonise those doctors who are engaged in or considering taking industrial action.

Having hands and moral status: a reply to Curtis and Vehmas.

Curtis and Vehmas apply the form of Moore's 'Proof of an External World' to justify continuing to believe that all and only humans have full moral status in the absence of a plausible account of why. I note that the strategy is better suited for the sceptical problems Moore applies it to and suggest that resorting to it reflects too great a pessimism about the accounts available.

Biochemical and genetic characterization of Trypanosoma cruzi N-myristoyltransferase.

Co- and post-translational N-myristoylation is known to play a role in the correct subcellular localization of specific proteins in eukaryotes. The enzyme that catalyses this reaction, NMT (N-myristoyltransferase), has been pharmacologically validated as a drug target in the African trypanosome, Trypanosoma brucei. In the present study, we evaluate NMT as a potential drug target in Trypanosoma cruzi, the causative agent of Chagas' disease, using chemical and genetic approaches.

An improved method for surface immobilisation of RNA: application to small non-coding RNA-mRNA pairing.

Characterisation of RNA and its intermolecular interactions is increasing in importance as the inventory of known RNA functions continues to expand. RNA-RNA interactions are central to post-transcriptional gene regulation mechanisms in bacteria, and the interactions of bacterial small non-coding RNAs (sRNAs) with their mRNA targets are the subject of much current research. The technology of surface plasmon resonance (SPR) is an attractive approach to studying these interactions since it is highly sensitive, and allows interaction measurements to be recorded in real-time.