OpdA, a bacterial organophosphorus hydrolase, prevents lethality in rats after poisoning with highly toxic organophosphorus pesticides

Organophosphorus (OP) pesticides poison more than 3,000,000 people every year in the developing world, mostly through intentional self-poisoning. Advances in medical therapy for OP poisoning have lagged, and current treatment is not highly effective with mortality of up to 40% in even the most advanced Western medical facilities. Administration of a broadly active bacterial OP hydrolase to patients in order to hydrolyze OPs in circulation might allow current therapies to be more effective. The objective of this work was to evaluate the efficacy of a new recombinant bacterial OP hydrolase (OpdA), cloned from Agrobacterium radiobacter, in rat models of two chemically distinct but highly toxic and rapidly acting OP pesticides: dichlorvos and parathion. Without OpdA treatment, median time to death in rats poisoned with 3x LD(50) of dichlorvos or parathion was 6 min and 25.5 min, respectively. Administration of a single dose of OpdA immediately after dichlorvos resulted in 100% survival at 24h, with no additional antidotal therapy. After parathion poisoning, OpdA alone caused only a delay to death. However, an additional two doses of OpdA resulted in 62.5% survival at 24 h after parathion poisoning. In combination with pralidoxime therapy, a single dose of OpdA increased survival to 75% after parathion poisoning. Our results demonstrate that OpdA is able to improve survival after poisoning by two chemically distinct and highly toxic OP pesticides

We Are History: The Outlines of a Quasi-Substantive Philosophy of History

In times of a felt need to justify the value of the humanities, the need to revisit and re-establish the public relevance of the discipline of history cannot come as a surprise. On the following pages I will argue that this need is unappeasable by scholarly proposals. The much desired revitalization of historical writing lies instead in reconciling ourselves with the dual meaning of the word history, in exploring the necessary interconnection between history understood as the course of events and as historical writing. Despite the general tendency of the last decades to forbid philosophizing about history in the former sense (at least in departments of history and philosophy), I think that to a certain extent we already do so without succumbing to substantive thought. We already have the sprouts of a speculative although only quasi-substantive philosophy of history that nevertheless takes seriously the postwar criticism of the substantive enterprise. In this essay I will first try to outline this quasi-substantive philosophy of history that attests to the historical sensibility of our times; and second, I will try to outline its consequences regarding history as historical writing. Finally, in place of a conclusion I will suggest that historical writing is not as much a contribution to public agendas as it is the very arena in which public life is at stake

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Revisiting Contextualism in Political Theory: Putting Principles into Context

© 2017, Springer Nature B.V. In this article, we articulate and defend a contextual approach to political theory. According to what we shall call ‘iterative contextualism’, context has two important roles to play in determining what is required by justice. First, it is through the exploration and evaluation of multiple contexts that general principles are devised, revised and refined. Second, significant weight should be given to the norms to be found in specific contexts because the people affected by those norms strongly identify with them. Having said this, the application of general principles to particular contexts may still result in recommendations which deviate to some degree from the prevailing norms. In this case, we shall argue thatalthough justice requires something other than what local norms say, what is required is likely to be intimated by the relevant context. Thus, whilst considerations of identification act as significant constraints on iterative contextualists’ thinking, the idea of intimations provides them with an important resource