These results demonstrate the antiproliferative activity of the guava leaf
extract which is at least in part caused by inhibition of the catalytic activity of PGHS isoforms. (C) 2009 Elsevier Ltd. All rights reserved.”
“Endosomal protein sorting governs the fate of many physiologically important proteins involved in a panoply VE-821 nmr of cellular functions. Recent discoveries have revealed a vital role for endosomally localised branched actin patches in facilitating protein sorting. The formation of the actin patches has been shown to require the function of the WASH complex – the major endosomal actin polymerisation-promoting complex – which stimulates the activity of the ubiquitously expressed Arp2/3 complex. Another key component of the endosomal protein-sorting machinery is the retromer complex. Studies now show that retromer mediates
the recruitment of the WASH complex and its regulators to endosomes. In this review, recent progress in understanding the role of the WASH complex along with retromer in endosomal protein sorting is discussed.”
“Fragile X syndrome is a neurodevelopmental condition caused by the transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. The Fmr1 knockout (KO) mouse exhibits age-dependent deficits in long term potentiation (LTP) at association (ASSN) synapses in anterior piriform cortex (APC). To investigate the mechanisms for this, whole-cell voltage-clamp recordings of ASSN stimulation-evoked synaptic currents were made in APC of slices from adult Fmr1-KO and wild-type Sclareol (WT) mice, using MRT67307 in vivo the competitive N-methyl-D-aspartate (NMDA) receptor antagonist, CPP, to distinguish currents mediated by NMDA and AMPA receptors. NMDA/AMPA current ratios were lower in Fmr1-KO mice than in WT mice, at ages ranging from 3-18 months. Since amplitude
and frequency of miniature excitatory postsynaptic currents (mEPSCs) mediated by AMPA receptors were no different in Fmr1-KO and WT mice at these ages, the results suggest that NMDA receptor-mediated currents are selectively reduced in Fmr1-KO mice. Analyses of voltage-dependence and decay kinetics of NMDA receptor-mediated currents did not reveal differences between Fmr1-KO and WT mice, suggesting that reduced NMDA currents in Fmr1-KO mice are due to fewer synaptic receptors rather than differences in receptor subunit composition. Reduced NMDA receptor signaling may help to explain the LTP deficit seen at APC ASSN synapses in Fmr1-KO mice at 6-18 months of age, but does not explain normal LTP at these synapses in mice 3-6 months old. Evoked currents and mEPSCs were also examined in senescent Fmr1-KO and WT mice at 24-28 months of age. NMDA/AMPA ratios were similar in senescent WT and Fmr1-KO mice, due to a decrease in the ratio in the WT mice, without significant change in AMPA receptor-mediated mEPSCs. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.