Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite with potent neurotrophic activity. Proteomics indicate that LK interacts with collapsin response mediator protein-2 (CRMP2/DPYSL2/UNC-33), a brain-enriched protein that was shown to regulate cytoskeletal remodeling, neuronal morphology, and synaptic function. To elucidate further the molecular interplay and biological action of LK and UNC-33, we began examining the nervous system of Caenorhabditis elegans nematodes in which both LK concentrations and UNC-33 protein were manipulated. To this end, a cell-permeable LK-ester (LKE) was administered to developing C. elegans engineered to express yellow fluorescent protein (YFP) in cholinergic neurons (strain RM3128) or green fluorescent protein (GFP) in GABAergic neurons (strain CZ1200), and neural morphology was assessed. Fluorescent imaging analyses show that LKE exposure to wild-type animals induced neural commissure outgrowth, crossing over, and bundling in both neurites from GABAergic and cholinergic motor neurons. Additionally, when unc-33(e204) hypomorph mutant nematodes (D389N substitution mutants) were exposed to LKE, both the neuroanatomical defects of incomplete dorsoventral neural commissures and the ventral nerve cord gaps were partially rescued. In contrast, LKE did not rescue ventral nerve cord gaps found in unc-33(mn407) null mutant. Together these data suggest possible functions for LK as a regulator of neuritic elongation, corroborate roles for UNC-33/CRMP2 in the mechanism of LKE activity, and suggest the potential of LKE as a therapeutic molecule for neurological diseases involving CRMP2 dysfunction.
The coherent control of cooperative spontaneous emission from two identical non-overlapping three-level atoms in the V-configuration located within a photonic band gap (PBG) material with two resonant frequencies near the upper band edge of the PBG and confined to a region small in comparison to their radiation wavelengths but still greater than their atomic sizes is investigated. The dependencies of cooperative effects in which a photon emitted by one atom is reabsorbed by the other atom on the inter-atomic separation, on the initial state of the two-atom system, on the strength of the driving control laser field, and on the detuning of the atomic resonant frequencies from the upper band edge frequency is analyzed so as to identify the conditions for which these cooperative effects are enhanced or inhibited. Cooperative effects between atoms are shown to be influenced more by the PBG than by the nature of the atomic transitions involved. Excited state populations as well as coherences between excited levels are expressed in terms of timedependent amplitudes which are shown to satisfy coupled integro-differential equations for which analytic solutions are derived under special conditions. Unlike for the case of one atom in a PBG where the fractional non-zero steady state populations on the excited levels as well as the coherence between the excited levels are constants independent of time, in the case of two atoms in PBG these quantities continuously oscillate as a manifestation of beating due to the continuous exchange between the two atoms of the photon trapped by the PBG. The values of these quantities as well as the amplitudes and frequencies of their oscillations depend of the parameters of the system, providing different ways of manipulating the system. The general formalism presented here is shown to recapture the special results of investigations of similar systems in free space when the non-Markovian memory kernels of the PBG are replaced by delta function dependent Markovian memory kernels.
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