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The continuing prevalence of a highly heritable and hypo-reproductive extreme tail of a human neurobehavioral quantitative diversity suggests the possibility that the reproductive majority retains the genetic mechanism for the extremes. From the perspective of stochastic epistasis, the effect of an epistatic modifier variant can randomly vary in both phenotypic value and effect direction among the careers depending on the genetic individuality, and the modifier careers are ubiquitous in the population distribution. The neutrality of the mean genetic effect in the careers warrants the survival of the variant under selection pressures. Functionally or metabolically related modifier variants make an epistatic network module and dozens of modules may be involved in the phenotype. To assess the significance of stochastic epistasis, a simplified module-based model was employed. The individual repertoire of the modifier variants in a module also participates in the genetic individuality which determines the genetic contribution of each modifier in the career. Because the entire contribution of a module to the phenotypic outcome is consequently unpredictable in the model, the module effect represents the total contribution of the related modifiers as a stochastic unit in the simulations. As a result, the intrinsic compatibility between distributional robustness and quantitative changeability could mathematically be simulated using the model. The artificial normal distribution shape in large-sized simulations was preserved in each generation even if the lowest fitness tail was un-reproductive. The robustness of normality beyond generations is analogous to the real situations of human complex diversity including neurodevelopmental conditions. The repeated regeneration of the un-reproductive extreme tail may be inevitable for the reproductive majority's competence to survive and change, suggesting implications of the extremes for others. Further model-simulations to illustrate how the fitness of extreme individuals can be low through generations may be warranted to increase the credibility of this stochastic epistasis model. [ABSTRACT FROM AUTHOR]

Copyright of Rigakuryoho Kagaku is the property of International Press Editing Center Incorporation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Rigakuryoho Kagaku is the property of International Press Editing Center Incorporation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Rigakuryoho Kagaku is the property of International Press Editing Center Incorporation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cetylpyridinium chloride (CPC) is used as a disinfectant in poultry processing plants in the United States due to its strong bactericidal effect on food poisoning bacteria such as Campylobacter jejuni/coli, pathogenic Escherichia coli, and Salmonella species. Although high-performance liquid chromatography (HPLC) methods for detecting CPC have been reported, the difficulties involved in the extraction and accurate detection of the residual agent from chicken meat containing proteins and fat have not been resolved. To develop a simple, rapid, stable, and accurate method for measurement of CPC residue in chicken meat by HPLC, a hydrophilic interaction chromatography (HILIC) column was adopted due to the high polarity of CPC. The residual CPC was extracted using a combination of mid-polarity sorbent and weak cation exchanger cartridge and a methacrylate-styrendivinyl benzene cartridge. The calibration curves were linear within the range 0.25–50 µg/mL CPC. This analytical method showed a correlation coefficient (r2) of 0.9997. Recoveries of CPC were between 83% and 89%, and the limit of quantitation was 0.125 µg/g. This proposed method is rapid, simple, and accurate. [ABSTRACT FROM AUTHOR]

The continuing prevalence of a highly heritable and hypo-reproductive extreme tail of a human neurobehavioral quantitative diversity suggests the reproductive majority retains the genetic mechanisms for extremes. From the perspective of stochastic epistasis, the effect of an epistatic modifier variant can randomly vary in both phenotypic value and effect direction among carriers depending on the genetic identity and the modifier carriers are ubiquitous in the population. The neutrality of the mean genetic effect in carriers ensures the survival of the variant under selection pressures. Functionally or metabolically related modifier variants make an epistatic network module and dozens of modules may be involved in the phenotype. To assess the significance of stochastic epistasis, a simplified module-based model was simulated. The individual repertoire of the modifier variants in a module also contributes in genetic identity, which determines the genetic contribution of each carrier modifier. Because the entire contribution of a module to phenotypic outcome is unpredictable in the model, the module effect represents the total contribution of related modifiers as a stochastic unit in simulations. As a result, the intrinsic compatibility between distributional robustness and quantitative changeability could mathematically be simulated using the model. The artificial normal distribution shape in large-sized simulations was preserved in each generation even if the lowest fitness tail was non-reproductive. The robustness of normality across generations is analogous to the real situation of complex human diversity, including neurodevelopmental conditions. The repeated regeneration of a non-reproductive extreme tail may be essential for survival and change of the reproductive majority, implying extremes for others. Further simulation to illustrate how the fitness of extreme individuals can be low across generations may be necessary to increase the plausibility of this stochastic epistasis model.

Antipsychotic drugs are classified as typical and atypical based on extrapyramidal effects. However, since the frontal cortex is one of the most important regions for antipsychotic actions, this study attempted to classify antipsychotic drugs based on gene expression in the frontal cortex. Chlorpromazine and thioridazine were selected as typical antipsychotics, and olanzapine and quetiapine as atypical antipsychotics. Since these drugs have similar chemical structures, the effect of the basic structure on gene expression can be eliminated. Cluster analysis of microarray experiments separated 4-drug-administered mice into chlorpromazine-quetiapine and thioridazine-olanzapine groups. This classification scheme is different from that which is based on criteria currently used to group the typical and atypical drugs and suggests that antipsychotic drugs can be further separated into multiple groups.

In order to clarify mechanisms underlying dopaminergic neuronal death in Parkinson's disease (PD), a gene expression profiling study was performed in a rodent model of PD. In this model, mice are intrastriatally injected with 6-hydroxydopamine (6-OHDA) and dopaminergic neurons in the substantia nigra (SN) gradually die by retrograde degeneration. The SN were removed 2 h, 24 h, or 14 days after 6-OHDA administration. Levels of mRNAs related to cell death or survival were quantified using adaptor-tagged competitive PCR (ATAC-PCR). The cyclin D1 gene showed an immediate increase in mRNA expression. After 24 h, when dopaminergic neurons were under intense degeneration, levels of caspase 8 mRNA and p53 apoptosis effecter related to pmp 22 (PERP) mRNA increased and, conversely, FAS mRNA decreased. After 14 days, when the degeneration was attenuated, levels of PERP mRNA and serum- and glucocorticoid-regulated kinase (SGK) mRNA still increased. SGK has a similarity to AKT, which is an important molecule involved in nerve growth factor signal transduction. AKT mRNA levels are low in dopaminergic neurons. These results suggest that an increase in cyclin D1 mRNA triggers dopaminergic neurons to enter an abnormal cell cycle, which leads to neuronal degeneration and cell death, possibly induced by PERP and caspase 8. In addition to cell death-related genes, several survival-related genes are activated. SGK might function as a key enzyme for the survival of dopaminergic neurons., (Copyright 2003 Wiley-Liss, Inc.)