Some Results on Mean Square Error for Factor Score Prediction

Abstract

The cyclo-octapdepsipeptide anthelmintic emodepside exerts a profound paralysis on parasitic and free-living nematodes. The neuromuscular junction is a significant determinant of this effect. Pharmacological and electrophysiological analyses in the parasitic nematode Ascaris suum have resolved that emodepside elicits a hyperpolarisation of body wall muscle, which is dependent on extracellular calcium and the efflux of potassium ions. The molecular basis for emodepside's action has been investigated in forward genetic screens in the free-living nematode Caenorhabditis elegans. Two screens for emodepside resistance, totalling 20,000 genomes, identified several mutants of slo-1, which encodes a calcium-activated potassium channel homologous to mammalian BK channels. Slo-1 null mutants are more than 1000-fold less sensitive to emodepside than wild-type C. elegans and tissue-specific expression studies show emodepside acts on SLO-1 in neurons regulating feeding and motility as well as acting on SLO-1 in body wall muscle. These genetic data, combined with physiological measurements in C. elegans and the earlier physiological analyses on A. suum, define a pivotal role for SLO-1 in the mode of action of emodepside. Additional signalling pathways have emerged as determinants of emodepside's mode of action through biochemical and hypothesis-driven approaches. Mutant analyses of these pathways suggest a modulatory role for each of them in emodepside's mode of action; however, they impart much more modest changes in the sensitivity to emodepside than mutations in slo-1. Taken together these studies identify SLO-1 as the major determinant of emodepside's anthelmintic activity. Structural information on the BK channels has advanced significantly in the last 2 years. Therefore, we rationalise this possibility by suggesting a model that speculates on the nature of the emodepside pharmacophore within the calcium-activated potassium channels.Keywords Cyclo-octadepsipeptide Á C. elegans Á Ascaris suum Á Anthelmintic Á BK channel Receptors and effectors for emodepsideEmodepside is a semi-synthetic derivative of the cyclooctadepsipeptide PF1022A, a secondary metabolite of the fungus Rosellinia spp. PF1022. It is effective against a wide-range of parasitic nematodes and has anthelminticresistance breaking properties suggesting a novel mode of action, for review see (Krucken et al. 2012). A key aspect of its efficacy is its ability to interfere with neuromuscular transmission in parasitic nematodes, an effect that was shown to be both calcium-and potassium dependent . It also inhibits neuromuscular function in the free-living nematode C. elegans, disrupting feeding, egg-laying and motility ). The inhibition of motility leads to complete paralysis and is consistent with dysfunction at the neuromuscular junction. Observation of the flaccid paralysis triggered by

Necessary Conditions for Mean Square Convergence of the Best Linear Factor Predictor

“…This generalizes the convergence in mean square by Krijnen (2006), who obtained his results under the assumption that the error variances are bounded and bounded away from zero. Under the latter assumption, Conditions 1 and 2 are equivalent (Krijnen, 2006), a result which cannot be generalized to the Heywood case. Condition 2 is necessary and sufficient, by Theorem 1, for the existence of a unique true factor (Krijnen, 2004).…”

“…Condition 2 generalizes the necessary and sufficient condition for mean square convergence of factor predictors by Krijnen (2006), who obtained his result under the assumption that all error variances are bounded and bounded away from zero. Under this assumption it is without loss of generality to take equal to zero.…”

“…A necessary and sufficient condition is given in the Heywood case with respect to (confirmatory) factor analysis. This condition generalizes that of Krijnen (2006) and performs better than a signal-to-noise type of condition (Schneeweiss & Mathes, 1995). …”

“…In case all error variances are bounded away from zero, several of these are equivalent and a necessary condition for mean square convergence of the best linear factor predictor is known (Krijnen, 2006). However, prediction theory of factor scores is not complete for the Heywood (1931) case, where some of the error variances are zero.…”

Neuroglobin immunoreactivity in the human cochlea

“…Neuroglobin (Ngb) is a tissue globin mainly expressed in the central and peripheral nervous systems of mammals with a potential role in regulating oxidative stress pathways (Burmester et al, 2000; Greenberg et al, 2008, Reuss et al, 2015). In the mouse cerebral cortex, Ngb expression is upregulated by neuronal hypoxia in vitro and by focal cerebral ischemia in vivo (Sun et al, 2001).…”