Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability.

Ketamine exposure can lead to selective neuroapoptosis in the developing brain. pShcA, the cellular adapter protein expressed selectively in immature neurons, is a known pro-apoptotic molecule that triggers neuroapoptosis when activated. Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg, six times at 2-hour intervals.

Value of sample size for computation of the Bayesian information criterion (BIC) in multilevel modeling.

The Bayesian information criterion (BIC) can be useful for model selection within multilevel-modeling studies. However, the formula for the BIC requires a value for sample size, which is unclear in multilevel models, since sample size is observed for at least two levels. In the present study, we used simulated data to evaluate the rate of false positives and the power when the level 1 sample size, the effective sample size, and the level 2 sample size were used as the sample size value, under various levels of sample size and intraclass correlation coefficient values.

A Bayesian analysis of quantal bioassay experiments incorporating historical controls via Bayes factors.

This paper addresses model-based Bayesian inference in the analysis of data arising from bioassay experiments. In such experiments, increasing doses of a chemical substance are given to treatment groups (usually rats or mice) for a fixed period of time (usually 2 years). The goal of such an experiment is to determine whether an increased dosage of the chemical is associated with increased probability of an adverse effect (usually presence of adenoma or carcinoma).

Bayesian Variable Selection on Model Spaces Constrained by Heredity Conditions.

This paper investigates Bayesian variable selection when there is a hierarchical dependence structure on the inclusion of predictors in the model. In particular, we study the type of dependence found in polynomial response surfaces of orders two and higher, whose model spaces are required to satisfy weak or strong heredity conditions. These conditions restrict the inclusion of higher-order terms depending upon the inclusion of lower-order parent terms.

Neonatal inhibition of Na-K-2Cl-cotransporter prevents ketamine induced spatial learning and memory impairments.

Prolonged ketamine exposure in neonates at anesthetic doses is known to cause long-term impairments of learning and memory. A current theoretical mechanism explains this phenomenon as being neuro-excitotoxicity mediated by compensatory upregulation of N-methyl-d-aspartate receptors (NMDARs), which then initiates widespread neuroapoptosis. Additionally, the excitatory behavior of GABAergic synaptic transmission mediated by GABA receptors (GABARs), occurring during the early neuronal development period, is proposed as contributing to the susceptibility of neonatal neurons to ketamine-induced injury.

An endogenous accelerator for viral gene expression confers a fitness advantage.

Many signaling circuits face a fundamental tradeoff between accelerating their response speed while maintaining final levels below a cytotoxic threshold. Here, we describe a transcriptional circuitry that dynamically converts signaling inputs into faster rates without amplifying final equilibrium levels. Using time-lapse microscopy, we find that transcriptional activators accelerate human cytomegalovirus (CMV) gene expression in single cells without amplifying steady-state expression levels, and this acceleration generates a significant replication advantage.

Human cytomegalovirus tegument protein pUL71 is required for efficient virion egress.

The human cytomegalovirus virion is composed of a DNA genome packaged in an icosahedral capsid, surrounded by a tegument of protein and RNA, all enclosed within a glycoprotein-studded envelope. Achieving this intricate virion architecture requires a coordinated process of assembly and egress. We show here that pUL71, a component of the virion tegument with a previously uncharacterized function, is required for the virus-induced reorganization of host cell membranes, which is necessary for efficient viral assembly and egress.

Contrasting evolutionary forces in the Arabidopsis thaliana floral developmental pathway.

The floral developmental pathway in Arabidopsis thaliana is composed of several interacting regulatory genes, including the inflorescence architecture gene TERMINAL FLOWER1 (TFL1), the floral meristem identity genes LEAFY (LFY), APETALA1 (AP1), and CAULIFLOWER (CAL), and the floral organ identity genes APETALA3 (AP3) and PISTILLATA (PI). Molecular population genetic analyses of these different genes indicate that the coding regions of AP3 and PI, as well as AP1 and CAL, share similar levels and patterns of nucleotide diversity. In contrast, the coding regions of TFL1 and LFY display a significant reduction in nucleotide variation, suggesting that these sequences have been subjected to a recent adaptive sweep.