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at ribbon sites in retinal bipolar cells, and find that, although ribbon synapses deliver and prime vesicles faster than most conventional synapses, both vesicle absence and vesicle priming contribute to the long recovery from paired-pulse depression.Maps of the synapses made and neurotransmitters released by all neurons in model systems, such as Caenorhabditis elegans have left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit of C. elegans as a model, we mapped which cells express each of the 26 neurotransmitter GPCRs of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. Receptor knockouts reveal few egg-laying defects under standard laboratory conditions, suggesting that the receptors function redundantly or regulate egg-laying only in specific conditions; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for understanding GPCR signaling in other neural circuits.SIGNIFICANCE STATEMENT Neurotransmitters signal through GPCRs to modulate activity of neurons, and changes in such signaling can underlie conditions such as depression and Parkinson's disease. To determine how neurotransmitter GPCRs together help regulate function of a neural circuit, we analyzed the simple egg-laying circuit in the model organism C. elegans We identified all the cells that express every neurotransmitter GPCR and genetically analyzed how each GPCR affects the behavior the circuit produces. We found that many neurotransmitter GPCRs are expressed in each neuron, that neurons also appear to use these receptors to communicate with other cell types, and that GPCRs appear to often act redundantly or only under specific conditions to regulate circuit function.The subthalamic nucleus (STN) plays a key role in the control of voluntary movements and basal ganglia disorders, such as Parkinson's disease and hemiballismus. The STN receives glutamatergic inputs directly from the cerebral cortex via the cortico-STN hyperdirect pathway and GABAergic inputs from the external segment of the globus pallidus (GPe) via the cortico-striato-GPe-STN indirect pathway. The STN then drives the internal segment of the globus pallidus, which is the output nucleus of the basal ganglia. Thus, clarifying how STN neuronal activity is controlled by the two inputs is crucial. Cortical stimulation evokes early excitation and late excitation in STN neurons, intervened by a short gap. Here, to examine the origin of each component of this biphasic response, we recorded neuronal activity in the STN, combined with electrical stimulation of the motor cortices and local drug application in two male monkeys (Macaca fuscata) in the awake state. Local application of glutamate receptor antagonists, a mis and therapy targeting the STN. Lesions or application of high-frequency stimulation in the STN ameliorates parkinsonian symptoms. These procedures could affect all components in the STN, such as afferent inputs through the hyperdirect and indirect pathways, and STN neuronal activity. If we can understand which component is most affected by such procedures, we may be able to identify more effective manipulation targets or methods to treat Parkinson's disease. To examine violent crime in relation to sleep and explore pathways, including psychological distress, safety perceptions and perceived police presence, that may account for associations. In 2018, 515 predominantly Black American (94%) adults (Pittsburgh, Pennsylvania, USA) provided survey data actigraphy-assessed sleep duration and wakefulness after sleep onset (WASO). https://www.selleckchem.com/products/pt2399.html We estimated pathways from violent crime (2016-2018) to sleep through psychological distress, perceptions of safety and perceived adequacy of police presence. WASO was most strongly associated with violent crimes that were within 1/10 mile of the participant's home and within the month preceding the interview. Violent crimes were associated with lower perceived safety (β=-0.13 (0.03), p<0.001) and greater WASO (β=5.96 (2.80), p=0.03). We observed no indirect associations between crime and either WASO or sleep duration through any of the tested mediators. Crime was not associated with sleep duration. We demonstrated that more proximal and more recent violent crimes were associated with reduced perceived safety and worse WASO. Differential exposure to violent crime among Black Americans may contribute to health disparities by reducing residents' perceived safety and sleep health. We demonstrated that more proximal and more recent violent crimes were associated with reduced perceived safety and worse WASO. Differential exposure to violent crime among Black Americans may contribute to health disparities by reducing residents' perceived safety and sleep health.The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread quickly across the globe, creating unique and pressing challenges for today's physicians. Although this virus disproportionately affects adults, initial SARS-CoV-2 infection can present a significant disease burden for the pediatric population. A review of the literature yields descriptive studies in pediatric patients; however, no evidence-based or evidence-informed guidelines for the diagnosis and treatment of the hospitalized pediatric patient have been published in peer-reviewed journals. The authors, working at a quaternary care children's hospital in the national epicenter of the SARS-CoV-2 pandemic, found an urgent need to create a unified, multidisciplinary, evidence-informed set of guidelines for the diagnosis and management of coronavirus disease 2019 in children. In this article, the authors describe our institutional practices for the hospitalized pediatric patient with confirmed or suspected initial SARS-CoV-2 infection.
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