Two widely expressed mammalian phosphatidylcholine (PC)-specific phospholipases D (PLD), PLD1 and PLD2, have been identified. Recombinantly expressed PLD2 has high basal activity and is insensitive to GTP-binding protein activators of PLD1 [Colley, W. C., et al. (1997) Curr. Biol. 7, 191-201]. To investigate the regulation of PLD2 we isolated PLD2, from mouse brain by immunoaffinity chromatography. The native and recombinant proteins have indistinguishable properties: PLD2 is potently activated by phosphoinositides with a vicinal 4,5-phosphate pair but is not stimulated by guanosine 5'-O-(3-thio triphosphate)-activated ADP-ribosylation factor-1, Rho family GTP-binding proteins, or protein kinases C-alpha, or -beta1. We used recombinant PLD2 in a reconstitution assay to search for regulators in cell and tissue extracts. Bovine brain contains a heat-stable protein factor that inhibits PLD2 activity in vitro. This factor was purified to homogeneity and identified as a mixture of alpha- and beta-synucleins by microsequencing and Western blotting. Recombinantly expressed alpha- and beta-synucleins inhibit PLD2 activity in vitro (K0.5 10 nM). Inhibition is not overcome by the protein or lipid activators of PLD1. Synucleins have been implicated in Parkinson's and Alzheimer's diseases. Our findings suggest that inhibition of PLD2 may be a function of synucleins. Modulation of PLD2 activity by synucleins may play a role in some aspects of the pathophysiologies that characterize these neurodegenerative diseases.
The health care system is composed of a mix of 2 community and 4 academics EDs in a major metropolitan area. Patient demographics, vital signs, laboratory results were extracted from our institutional COVID-19 Data Warehouse. Following the convention of qCSI variables, respiratory rate (breaths/min), pulse oximetry (%), and oxygen flow rate (L/ min) were used to calculate points between 0 to 12, with higher points associated with highly likelihood of respiratory decompensation within 24 hours.Results: 35,696 COVID-19 patients were admitted via the emergency department during the study period. The mean qCSI was 1.73 (SD 1.82) for non-ICU admissions (n¼34,647). The mean qCSI was 2.83 (SD 2.53) for ICU admission (n¼1,049). As of the time of submission, ED treat and release patients, as well as decompensation results are pending.Conclusions: In this validation study of qCSI using a large system cohort of COVID-19 patients, qCSI appears to correlate strongly with clinical triage for admission decision to regular floor vs. ICU level care. Further analysis is needed to identify 24-hour respiratory decompensation after regular floor admission.
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