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Lock, R.

Publications and source records attributed to Lock, R..

2 recordsLinked to original sources

Advances in the Design and Functionality of a Compact Multi-Reflecting Time-of-Flight Mass Spectrometer

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSRationaleC_ST_ABSHigh-resolution mass spectrometry is routinely used for the analysis of complex samples in pharmaceutical, environmental, and omics related studies. Such applications demand instrumentation to be capable of combining sub-ppm mass accuracy, high resolving power, rapid full m/z range acquisition, over a wide dynamic range. MethodsAchieving the above requirements places constraints on analyzer design and performance. Multi-reflecting time-of-flight (MRT) based analyzers have previously been reported as a means of significantly extending the effective flight path in compact TOF designs. Here, further instrument and functionality advances in a compact MRT mass spectrometer design are described. ResultsThe impact of these enhancements was assessed for targeted and non-targeted omics applications, examining the impact of acquisition speed on resolving power, dynamic range including limits of quantitation, and quantitative precision. ConclusionThe results obtained characterize the performance of the enhanced design features of a compact MRT mass spectrometer. Operation at elevated acquisition rates up to 200 Hz was observed without loss in resolving power, isotopic ratio accuracy, or quantitative precision.

biochemistry↗

STK25 inhibits PKA signaling by phosphorylating PRKAR1A

In the heart, Protein Kinase A (PKA) is critical for activating calcium handling and sarcomeric proteins in response to beta adrenergic stimulation leading to increased myocardial contractility and performance. The catalytic activity of PKA is tightly regulated by regulatory subunits which inhibit the catalytic subunit until released by cAMP binding. Phosphorylation of Type II regulatory subunits promotes PKA activation, however the role of phosphorylation in Type I regulatory subunits remain uncertain. Here we utilized human induced pluripotent stem cell cardiomyocytes (iPSC-CM) to identify STK25 as a kinase of the Type Ia regulatory subunit PRKAR1A. Phosphorylation of PRKAR1A led to inhibition of PKA kinase activity and increased binding to the catalytic subunit in the presence of cAMP. Stk25 knockout in mice diminished Prkar1a phosphorylation, increased Pka activity and augmented contractile response to beta adrenergic stimulation. Together, these data support STK25 as a negative regulator of PKA signaling through phosphorylation of PRKAR1A.

physiology↗