As these studies attempt to exploit the intensity information contained in the MS/MS spectra, a critical step required for a meaningful comparison of this information between MS/MS spectra is peak intensity normalization. We here describe a procedure for quantifying the efficiency of different published normalization methods in terms of the quartile coefficient of dispersion (qcod) statistic.
The quartile coefficient of dispersion is applied to measure the dispersion of the peak intensities between redundant MS/MS spectra, allowing the quantification of the differences in computed peak intensity reproducibility between the different normalization methods. We demonstrate that our results are independent of the data set used in the evaluation procedure, allowing us to provide generic guidance on the choice of normalization method to apply in a certain MS/MS pipeline application.”
“It S3I-201 mw PD0332991 cost is postulated that disruptions of glutamatergic signalling may underlie the pathophysiology of psychosis and schizophrenia. A strong body of evidence indicates that antagonism of the N-methyl-d-aspartate receptor (NMDAR) leads to similar molecular, cellular, cognitive and behavioural changes in rodents and/or humans to those that have been identified to occur in psychosis. One of the main
loci of change appears to comprise the hippocampus, raising the question as to whether changes in hippocampal glutamatergic transmission may drive changes in GABAergic and dopaminergic-mediated signalling in schizophreniform diseases. NMDAR antagonists such as MK801, PCP and ketamine all elicit similar psychosis-related effects, with MK801 inducing the most potent psychotomimetic PF-6463922 supplier reactions.
Treatment with MK801 is associated with a loss of hippocampal synaptic plasticity, hippocampusdependent learning and cognitive deficits. These findings have raised the question as to whether targeting the NMDA receptors or its modulators could prove an effective strategy in treatment of psychosis and schizophrenia. Specifically, the otherwise untreatable negative and cognitive symptoms of schizophrenia currently comprise the highest research priority. A single injection with MK801 has been used to emulate first-episode psychosis in animals. This treatment induces both psychosis-related acute effects but interestingly also persisting consequences, which might be more sensitive as indicators of drug efficacy. Here, we review the current status of the field with regard to the MK801 animal model of firstepisode psychosis and its relevance for the glutamate hypothesis of schizophrenia. Furthermore, we argue that synaptic plasticity may be a better assay for assessing novel schizophrenia therapeutics than behavioural evaluation.
This article is part of the Special Issue entitled ‘Glutamate Receptor-Dependent Synaptic Plasticity’. (C) 2013 Elsevier Ltd.