Human DCX blocking peptide

Neurite growth is an important process for the adult hippocampal neurogenesis which is regulated by a specific range of the intracellular free Ca2+ concentration ([Ca2+] i). Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable channel and activation of it causes an increase in [Ca2+] i. We recently reported that TRPV4 activation promotes the proliferation of stem cells in the adult hippocampal dentate gyrus (DG). The present study aimed to examine the effect of TRPV4 activation on the dendrite morphology of newborn neurons in the adult hippocampal DG. Here, we report that intracerebroventricular injection of the TRPV4 agonist GSK1016790A for 5 days (GSK1016790A-injected mice) reduced the number of doublecortin immunopositive (DCX+) cells and DCX+ fibers in the hippocampal DG, showing the impaired dendritic arborization of newborn neurons. The phosphorylated AMP-activated protein kinase (p-AMPK) protein level increased from 30 min to 2 h, and then decreased from 1 to 5 days after GSK1016790A injection. The phosphorylated protein kinase B (p-Akt) protein level decreased from 30 min to 5 days after GSK1016790A injection; this decrease was markedly attenuated by the AMPK antagonist compound C (CC), but not by the AMPK agonist AICAR. Moreover, the phosphorylated mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase (p70S6k) protein levels were decreased by GSK1016790A; these changes were sensitive to 740 Y-P and CC. The phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) at Y-216 was increased by GSK1016790A, and this change was accompanied by increased phosphorylation of microtubule-associated protein 2 (MAP2) and collapsin response mediator protein-2 (CRMP-2). These changes were markedly blocked by 740 Y-P and CC. Finally, GSK1016790A-induced decrease of DCX+ cells and DCX+ fibers was markedly attenuated by 740 Y-P and CC, but was unaffected by AICAR. We conclude that TRPV4 activation impairs the dendritic arborization of newborn neurons through increasing AMPK and inhibiting Akt to inhibit the mTOR-p70S6k pathway, activate GSK3 beta and thereby result in the inhibition of MAP2 and CRMP-2 function.

The LLC series resonant converter (SRC) is one of the most popular galvanically isolated dc-dc converters since it provides zero voltage switching (ZVS), reduces rms currents, and tightly couples the input and output voltages, when it is operated at (or below) the resonance frequency, and, therefore, acts as a dc transformer (DCX) without requiring closed-loop voltage control. Hence, this topology is of particular importance for the dc-dc converter stage of high power medium voltage to low voltage solid-state transformers (SSTs). This paper first highlights the limitations of passive and synchronous rectification (e.g., oscillations, current distortion, load-dependent voltage transfer ratio) for bridges employing semiconductors with large output capacitances. Afterward, a magnetizing current splitting ZVS (MCS-ZVS) modulation scheme, which allows an active sharing of the magnetizing current between the primary side and secondary side metal oxide semiconductor field effect transistor (MOSFET)-based bridges, is analyzed. It is shown that the ZVS mechanism is acting equivalent to a controller, allowing for a robust open-loop operation of the converter. The proposed modulation scheme features a load-independent voltage transfer ratio, load-independent ZVS for both bridges, and quasi-sinusoidal currents. Finally, the phase shift modulation scheme is experimentally verified for the SiC MOSFET-based dc-dc converter of a 25 kW ac-dc SST, which operates at 48 kHz between a 7 kV and a 400 V dc bus with an efficiency of 99.0%.