Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission
and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and R428 GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity’ by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. Neuropsychopharmacology (2013) 38, 729-742; doi:10.1038/npp.2012.246;
published online 30 January 2013″
“The family see more Endornaviridae selleck products infects diverse hosts, including plants, fungi, and oomycetes. Here we report for the first time the assembly of bell pepper endornavirus by next-generation sequencing of viral small RNA. Such a population of small RNA indicates the activation of the viral immunity silencing machinery by this cryptic virus, which probably encodes a novel silencing suppressor.”
“Studies with animal models in vivo as well as with animal and human tumor cells in vitro suggest that specific fatty acids could reduce
breast tumorigenesis. The most striking dietary fatty acid studies in animal models that show promise for reduction of breast cancer risk in humans are with conjugated linoleic acids (CIA) and n-3 fatty acids. Although a number of mechanisms have been proposed, the specific target of those fatty acids is not yet known. We sought to determine whether the effects of those fatty acids on terminally differentiated tumor cell seen could be due to alteration of breast cancer stem cells. The isomers, cis9, trans11-CLA and trans10, cis12-CLA, and the n-3 fatty acids, docosahexaenoic and eicosapentaenoic, reduced the proliferation of, and had increased toxicity towards, mammary tumor initiating cells.