Tyrosine phosphorylation regulates multiple cell signaling pathways and functionally modulates a number of ion channels and receptors. Neurotransmitter transporters, which act to clear transmitter from the synaptic cleft, are regulated by multiple second messenger pathways that exert their effects, at least in part, by causing a redistribution of the transporter protein to or from the cell surface. To test the hypothesis that tyrosine phosphorylation affects transporter function and to determine its mechanism of action, we examined the regulation of the rat brain ␥-aminobutyric acid (GABA) transporter GAT1 expressed endogenously in hippocampal neurons and expressed heterologously in Chinese hamster ovary cells. Inhibitors of tyrosine kinases decreased GABA uptake; inhibitors of tyrosine phosphatases increased GABA uptake. The decrease in uptake seen with tyrosine kinase inhibitors was correlated with a decrease in tyrosine phosphorylation of GAT1 and resulted in a redistribution of the transporter from the cell surface to intracellular locations. A mutant GAT1 construct that was refractory to tyrosine phosphorylation could not be regulated by tyrosine kinase inhibitors. Activators of protein kinase C, which are known to cause a redistribution of GAT1 from the cell surface, were additive to the effects of tyrosine kinase inhibitors suggesting that multiple signaling pathways control transporter redistribution. Application of brain-derived neurotrophic factor, which activates receptor tyrosine kinases, up-regulated GAT1 function suggesting one potential trigger for the cellular regulation of GAT1 signaling by tyrosine phosphorylation. These data support the hypothesis that transporter expression and function is controlled by the interplay of multiple cell signaling cascades. ␥-Aminobutyric acid (GABA)1 is the predominant inhibitory neurotransmitter in the central nervous system and plays a pivotal role in the balance between neuronal excitation and inhibition. The time course of neurotransmitter in the synaptic cleft is one determinant of synaptic transmission, and its removal from the cleft via specific transporters provides an efficient mechanism for termination of signaling. GABA transporters (GATs) are located on the plasma membrane of neurons and glia (1) and function to remove GABA through co-transport of ions down their electrochemical gradient (2). Demonstration of a physiological role for GABA transporters comes from experiments involving specific GABA uptake inhibitors; these inhibitors affect both GABA A and GABA B receptor-mediated synaptic signaling (3-5). GABA transporters also play a pathophysiological role in temporal lobe epilepsy (6) and are the targets of pharmacological interventions in epilepsy (7). An important property of GABA transporters, and neurotransmitter transporters in general, is their ability to be functionally regulated by a wide variety of signaling cascades (for review, see Refs. 8 and 9). Functional modulation occurs in part through second messengers such as kinases, phosphatas...
Nursing administrators should develop and/or evaluate policies regarding patient care providers with visible tattoos and/or body piercings.
Background: Nursing governance and effects on nurserelated outcomes are not well studied. Methods: Associations were evaluated using average IPNG scores from 2170 RNs and nurse-sensitive indicators (NSIs) and patient and RN satisfaction outcomes (n = 205 study units, 20 hospitals, 4 countries). Results: International units had better IPNG shared governance scores (113.5; US = 100.6; P < 0.001), and outcomes outperforming unit benchmarks (6 of 15, 40.0%; US = 2 of 15, 13.3%). Shared governance significantly outperformed traditional governance for 5 of 20 (25.0%) US outcomes (patient satisfaction = 1, RN satisfaction = 4) and for 3 of 11 (27.3%) international (patient satisfaction = 1, RN satisfaction = 2).Internationally, self-governance significantly outperformed traditional governance and shared governance for 5 of 12 (41.7%) outcomes (NSI = 2, patient satisfaction = 3). Conclusions: Shared governance is a strategy that can be considered by nurse leaders for improving select outcomes.
Evidence suggests that interventions such as quiet time and closingdoors don't help ICU staff achieve WHO or EPA sound-level goals.
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