Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The function of presenilin1 (PS1) in intra-membrane proteolysis is undisputed, as is its role in neurodegeneration in FAD, in contrast to its exact function in normal conditions. In this study, we analyzed synaptic plasticity and its underlying mechanisms biochemically in brain of mice with a neuron-specific deficiency in PS1 (PS1(n-/-)) and compared them to mice that expressed human mutant PS1[A246E] or wild-type PS1. PS1(n-/-) mice displayed a subtle impairment in Schaffer collateral hippocampal long-term potentiation (LTP) as opposed to normal LTP in wild-type PS1 mice, and a facilitated LTP in mutant PS1[A246E] mice. This finding correlated with, respectively, increased and reduced NMDA receptor responses in PS1[A246E] mice and PS1(n-/-) mice in hippocampal slices. Postsynaptically, levels of NR1/NR2B NMDA-receptor subunits and activated alpha-CaMKII were reduced in PS1(n-/-) mice, while increased in PS1[A246E] mice. In addition, PS1(n-/-) mice, displayed reduced paired pulse facilitation, increased synaptic fatigue and lower number of total and docked synaptic vesicles, implying a presynaptic function for wild-type presenilin1, unaffected by the mutation in PS1[A246E] mice. In contrast to the deficiency in PS1, mutant PS1 activated GSK-3beta by decreasing phosphorylation on Ser-9, which correlated with increased phosphorylation of protein tau at Ser-396-Ser-404 (PHF1/AD2 epitope). The synaptic functions of PS1, exerted on presynaptic vesicles and on postsynaptic NMDA-receptor activity, were concluded to be independent of alterations in GSK-3beta activity and phosphorylation of protein tau.
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PMID:Modulation of synaptic plasticity and Tau phosphorylation by wild-type and mutant presenilin1. 1722 48

The nondestructive evaluation of closed cracks is a challenging subject in ultrasonic testing. Recently, nonlinear ultrasonic phased array with fixed-voltage fundamental wave amplitude difference (fixed-voltage FAD) has been proposed as a practical approach. In this study, the maximum incident wave amplitude, which is one of the most critical parameters in closed-crack imaging, was investigated. First, a theoretical model was formulated to explicitly show the essence of the fundamental principle of FAD and the advantage of fixed-voltage FAD over different-voltage FAD. In experiments, the authors imaged a closed fatigue crack using a nonlinear ultrasonic phased array with fixed-voltage FAD while varying the incident wave amplitude. It was found that when the incident wave amplitude was sufficiently high, the nonlinear image visualized the closed crack tip, which could not be visualized in linear images. In addition, the incident-wave-amplitude dependence of the nonlinear responses was quantified. It was found that different parts within a single fatigue crack showed different nonlinear behaviors. This suggests that fixed-voltage FAD is useful not only for practical application of closed crack imaging but also for examining the nonlinear dynamics at various parts of closed cracks with a high spatial resolution.
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PMID:Nonlinear ultrasonic phased array with fixed-voltage fundamental wave amplitude difference for high-selectivity imaging of closed cracks. 3137 May 88