In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

Stress and the brain: from adaptation to disease

There has been a surge of interest in the functional consequences of neurocognitive deficits in schizophrenia. The published literature in this area has doubled in the last few years. In this paper, we will attempt to confirm the conclusions from a previous review that certain neurocognitive domains (secondary verbal memory, immediate memory, executive functioning as measured by card sorting, and vigilance) are associated with functional outcome. In addition to surveying the number of replicated findings and tallying box scores of results, we will approach the review of the studies in a more thorough and empirical manner by applying a meta-analysis. Lastly, we will discuss what we see as a key limitation of this literature, specifically, the relatively narrow selection of predictor measures. This limitation has constrained identification of mediating variables that may explain the mechanisms for these relationships.

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Neurocognitive Deficits and Functional Outcome in Schizophrenia: Are We Measuring the “Right Stuff”?

A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.

A rating scale for drug-induced akathisia

We evolved muscarinic receptors in yeast to generate a family of G protein-coupled receptors (GPCRs) that are activated solely by a pharmacologically inert drug-like and bioavailable compound (clozapine-N-oxide) Subsequent screening in human cell lines facilitated the creation of a family of muscarinic acetylcholine GPCRs suitable for in vitro and in situ studies We subsequently created lines of telomerase-immortalized human pulmonary artery smooth muscle cells stably expressing all five family members and found that each one faithfully recapitulated the signaling phenotype of the parent receptor We also expressed a Gi-coupled designer receptor in hippocampal neurons (hM4D) and demonstrated its ability to induce membrane hyperpolarization and neuronal silencing We have thus devised a facile approach for designing families of GPCRs with engineered ligand specificities Such reverse-engineered GPCRs will prove to be powerful tools for selectively modulating signal-transduction pathways in vitro and in vivo

/pdf/evolving-the-lock-to-fit-the-key-to-create-a-family-of-g-1lys76mtgc.pdf

Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand

Objective. The clock-drawing test has achieved widespread clinical use in recent years as a cognitive screening instrument and a significant amount of literature relates to its psychometric properties and clinical utility. This review aims to synthesize the available evidence and assess the value of this screening test according to well-defined criteria.

Design. A Medline and Psycho-info literature search of all languages was done from 1983 to 1998 including manual cross-referencing of bibliographies. A brief summary of all original scoring systems is provided as well as a review of replication studies. Psychometric data including correlations with other cognitive tests were recorded. Qualitative aspects of the test are also described.

Results. Among published studies, the mean sensitivity (85%) and specificity (85%) of the clock-drawing test are impressive. Correlations with the Mini-Mental State Examination and other cognitive tests was high, generally greater than r = 0.5. High levels of inter-rater and test–re-test reliability and positive predictive value are recorded and despite significant variability in the scoring systems, all report similar psychometric properties. The clock test also shows a sensitivity to cognitive change with good predictive validity.

Conclusions. The clock-drawing test meets defined criteria for a cognitive screening instrument. It taps into a wide range of cognitive abilities including executive functions, is quick and easy to administer and score with excellent acceptability by subjects. Together with informant reports, the clock-drawing test is complementary to the widely used and validated Mini-Mental State Examination and should provide a significant advance in the early detection of dementia and in monitoring cognitive change. A simple scoring system with emphasis on the qualitative aspects of clock-drawing should maximize its utility. Copyright © 2000 John Wiley & Sons, Ltd.

Clock-drawing: is it the ideal cognitive screening test?

The major serogroups and distinct subgroups of spiroplasmas seem to represent distinct species. The scheme of classification into these groups was initially based on serologic properties and later supported by the results of studies of DNA-DNA homology and polyacrylamide-gel electrophoretic analyses of cellular proteins. Because separate subgroups within the same major serogroup cross-react in growth inhibition tests and other serologic tests, a taxonomic scheme is proposed which implies that certain major criteria for species differentiation within the genus Mycoplasma cannot be appropriately applied to the genus Spiroplasma without modification. Nevertheless, the grouping scheme and proposed speciation satisfy requirements for a species concept that is utilitarian and operational and consistent with recommendations by the International Committee on Systematic Bacteriology, Subcommittee on the Taxonomy of Mollicutes.

Comparative Properties of Spiroplasmas and Emerging

本文通过对现代汉语助动词“会”的偏误分析, 考察了韩国学习者的偏误类型和特点, 并针对韩国学习者的情况提出了教学建议。通过分析前人研究, 考察了助动词“会”的传统用法和新增用法, 我们认为在教学语法中应该把“会”的语义功能分为“能力”, “信念”, “模式”, “承诺”等四类。通过分析韩国学习者的汉语病句, 发现偏误率按误加偏误, 误代偏误, 遗漏偏误顺序依次增大, 而且其偏误具有明显的特点。最后, 分析了造成韩国学习者“会”的偏误的原因, 发现主要是由于教学上的遗漏和误导, 还有母语干扰所致。另外, 根据偏误分析发现的问题, 我们建议在教材的编写和教学中, 应考虑韩语特点, 有必要对原有助动词“会”的表述做适当的改进和补充。 

The Semantic Function and Teaching Method of the Auxiliary Verb ‘Hui(会)’ in Mandarin Chinese: Based on the Error Analysis of Korean Learners

s | 79 Abstract Background: Group I metabotropic glutamate receptor (mGluR1 and mGluR5) allosteric modulators are currently being investigated as novel therapeutics for the treatment of neurodevelopmental disorders such as schizophrenia, autism, depression (Cleva and Olive, 2011). Recent evidence suggests that allosteric modulators have adverse pharmacological effects when bound to the monomeric, compared to the dimeric form of these receptors (El Moustaine et  al., 2012). Investigating the neurodevelopmental expression of dimeric and monomeric mGluR1 and mGluR5 may highlight possible implications for novel therapeutics at critical neurodevelopmental periods. Methods: Pregnant Sprague-Dawley rats were obtained at gestational day 14. Offspring were euthanised on postnatal day (PN) 12, 35 and 96 (n=6/group) coinciding with juvenile, adolescent and adult time points. Immunoblots were performed on prefrontal cortex (PFC) and hippocampal tissue under non-reducing conditions to measure dimeric and monomeric mGluR1 and mGluR5 proteins. Results: Dimeric mGluR1and mGluR5 was expressed in higher abundance than their monomeric forms. mGluR1 dimeric expression was lowest at PN12 in both the PFC and hippocampus; where it displayed an increase with age. Whilst monomeric mGluR1 expression was considerably lower, it showed a similar trend in the PFC, however, its expression remained constant in the hippocampus. In contrast, dimeric mGluR5 protein expression in the PFC peaked at PN12 and decreased throughout the neurodevelopmental time-points, however its expression in the hippocampus remained constant throughout. Interestingly, in both regions mGluR5 monomer was highly expressed at PN12, almost equal to dimeric expression and then declined to the lowest limits of detection at later time-points. Conclusion: The monomeric form of mGluR5 is relatively abundant during early post-natal development. Considering positive allosteric modulators exert an unregulated agonist effect when bound to the monomeric form of mGluRs, administration of these compounds during such a critical neurodevelopmental period, may cause seizures and neurotoxic effects, posing possible consequences for novel mGluR5 therapeutics.Background: Group I metabotropic glutamate receptor (mGluR1 and mGluR5) allosteric modulators are currently being investigated as novel therapeutics for the treatment of neurodevelopmental disorders such as schizophrenia, autism, depression (Cleva and Olive, 2011). Recent evidence suggests that allosteric modulators have adverse pharmacological effects when bound to the monomeric, compared to the dimeric form of these receptors (El Moustaine et  al., 2012). Investigating the neurodevelopmental expression of dimeric and monomeric mGluR1 and mGluR5 may highlight possible implications for novel therapeutics at critical neurodevelopmental periods. Methods: Pregnant Sprague-Dawley rats were obtained at gestational day 14. Offspring were euthanised on postnatal day (PN) 12, 35 and 96 (n=6/group) coinciding with juvenile, adolescent and adult time points. Immunoblots were performed on prefrontal cortex (PFC) and hippocampal tissue under non-reducing conditions to measure dimeric and monomeric mGluR1 and mGluR5 proteins. Results: Dimeric mGluR1and mGluR5 was expressed in higher abundance than their monomeric forms. mGluR1 dimeric expression was lowest at PN12 in both the PFC and hippocampus; where it displayed an increase with age. Whilst monomeric mGluR1 expression was considerably lower, it showed a similar trend in the PFC, however, its expression remained constant in the hippocampus. In contrast, dimeric mGluR5 protein expression in the PFC peaked at PN12 and decreased throughout the neurodevelopmental time-points, however its expression in the hippocampus remained constant throughout. Interestingly, in both regions mGluR5 monomer was highly expressed at PN12, almost equal to dimeric expression and then declined to the lowest limits of detection at later time-points. Conclusion: The monomeric form of mGluR5 is relatively abundant during early post-natal development. Considering positive allosteric modulators exert an unregulated agonist effect when bound to the monomeric form of mGluRs, administration of these compounds during such a critical neurodevelopmental period, may cause seizures and neurotoxic effects, posing possible consequences for novel mGluR5 therapeutics.

PM493. Interactions of tardive dyskinesia with cognitive function in patients with schizophrenia: worsening of working memory with clozapine treatment.

Myung A. Lee

Papers

Comparative Properties of Spiroplasmas and Emerging

The Semantic Function and Teaching Method of the Auxiliary Verb ‘Hui(会)’ in Mandarin Chinese: Based on the Error Analysis of Korean Learners

PM493. Interactions of tardive dyskinesia with cognitive function in patients with schizophrenia: worsening of working memory with clozapine treatment.