A Novel G Protein-Coupled Receptor of Schistosoma mansoni (SmGPR-3) Is Activated by Dopamine and Is Widely Expressed in the Nervous System

Schistosomes have a well developed nervous system that coordinates virtually every activity of the parasite and therefore is considered to be a promising target for chemotherapeutic intervention. Neurotransmitter receptors, in particular those involved in neuromuscular control, are proven drug targets in other helminths but very few of these receptors have been identified in schistosomes and little is known about their roles in the biology of the worm. Here we describe a novel Schistosoma mansoni G protein-coupled receptor (named SmGPR-3) that was cloned, expressed heterologously and shown to be activated by dopamine, a well established neurotransmitter of the schistosome nervous system. SmGPR-3 belongs to a new clade of “orphan” amine-like receptors that exist in schistosomes but not the mammalian host. Further analysis of the recombinant protein showed that SmGPR-3 can also be activated by other catecholamines, including the dopamine metabolite, epinine, and it has an unusual antagonist profile when compared to mammalian receptors. Confocal immunofluorescence experiments using a specific peptide antibody showed that SmGPR-3 is abundantly expressed in the nervous system of schistosomes, particularly in the main nerve cords and the peripheral innervation of the body wall muscles. In addition, we show that dopamine, epinine and other dopaminergic agents have strong effects on the motility of larval schistosomes in culture. Together, the results suggest that SmGPR-3 is an important neuronal receptor and is probably involved in the control of motor activity in schistosomes. We have conducted a first analysis of the structure of SmGPR-3 by means of homology modeling and virtual ligand-docking simulations. This investigation has identified potentially important differences between SmGPR-3 and host dopamine receptors that could be exploited to develop new, parasite-selective anti-schistosomal drugs

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research

Managerialism and "infinite human resourcefulness" : a commentary upon the "therapeutic habitus", "derecognition of finitude" and the modern sense of self.

This paper examines new managerial discourses and practices in which the dialectic of labour is reconstructed as a series of acts of self-understanding, self-examination and "self-work", and through which the "self qua self" is constituted as the central object of management technologies. We interrogate concepts such as "excellence", "total quality", "performance", "knowledge", "play at work" and "wellness" in order to decipher the ways in which managerialism deploys what we term therapeutic habitus, and projects a new horizon of "human resourcefulness" as a store of unlimited potentialities. We invoke management's wider historical-cultural context to situate managerialism within the framework of modernity as a cultural epoch whose main characteristic is what we term "derecognition of finitude". It is the modern synthesis "with the "self" at the centre of its system of values" that provides the ground for current elaborations of subjectivity by managerialism. The paper examines how current vocabularies and practices in organisations use "work" to rearticulate discursively the human subject as an endless source of performativity by configuring work as the site of complex and continuous self-expression. Management itself thus acquires a new discursive outline: instead of appearing as an authoritarian instance forcing upon workers a series of limitations, it now presents itself as a therapeutic formula mediating self-expression by empowering individuals to work upon themselves to release their fully realised identity

Gnosis, science, and mysticism: A history of self-referential theory designs

In this paper, we understand we advent of a ''scientific spirit'' as a revival of Gnosticism, which proclaims the superiority of man over his creator and considers knowledge (gnosis) to be the key to salvation. Salvation is here understood as from of ''emancipation''. Empirically, toe see our interpretation confirmed in the tremendous influence of the Corpus Hermeticum and the Lurianic Cabala on all the Renaissance scientists. In the second part of this essay, we continue a line of research inaugurated by Ferdinand Christian Baur in the 19th century, and look for Gnostic outlooks in contemporary philosophy and social science. By reading Niklas Luhmann's systems theory as a modem version of Gnostic mysticism, we do not intend to dismiss the relevance of his work. For if Gnosticism defines ''modernity'', we should not be surprised to find a speculative Gnostic system among society's self-descriptions