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

Malus domestica: A review on nutritional features, chemical composition, traditional and medicinal value

Fruit-derived bioactive substances have been spotlighted as a regulator against various diseases due to their fewer side effects compared to chemical drugs. Among the most frequently consumed fruits, apple is a rich source of nutritional molecules and contains high levels of bioactive compounds. The main structural classes of apple constituents include polyphenols, polysaccharides (pectin), phytosterols, and pentacyclic triterpenes. Also, vitamins and trace elements complete the nutritional features of apple fruit. There is now considerable scientific evidence that these bioactive substances present in apple and peel have the potential to improve human health, for example contributing to preventing cardiovascular disease, diabetes, inflammation, and cancer. This review will focus on the current knowledge of bioactive substances in apple and their medicinal value for human health

Managerialism, the therapeutic habitus and the self in contemporary organising.

Over the last two decades, managerialism (Enteman, 1993) has become consolidated on multiple fronts. As a formula of governance, it has elaborated various vocabularies: the `audit society' (Power, 1997, 2007) has become entrenched in all types of organizations; surveillance methods (Lyon, 2001) have become increasingly dispersed and insidious; and — alongside —`new' concepts of subjectivity and the`self' are used to frame more intense regimes of self-discipline or what Tipton (1984) called `self-work'. These moves have been captured by Heelas (2002), Thrift (1997) and others in the term `soft capitalism'. In this article, we reflect upon this phenomenon by analysing some examples: `culture', `performativity', `knowledge' and `wellness'. Although they belong to a group often described as `fads' and `fashions' and dismissed as managerial `mumbo-jumbo', we suggest that their proliferation indicates a more stable cultural tendency of management discourses to capture subjectivity in its general agenda. We attempt to offer an historical-cultural interpretation from which this range of managerial concepts might be viewed. Our argument suggests that they have a certain cultural coherence that can be perhaps better glimpsed within a wider historical context. As a particular way in which managerialism frames its logic, analysing `soft capitalism' historically offers a reasonable basis for understanding the strength of its hard disciplinary edge as a regime of governance