Liver genomic responses to ciguatoxin: evidence for activation of Phase I and Phase II detoxification pathways following an acute hypothermic response in mice

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (|fold change| ≥ 1.5 and p ≤ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice.

Dissecting Signaling Pathways That Govern Self-renewal of Rabbit Embryonic Stem Cells

The pluripotency and self-renewal of embryonic stem cells (ESC) are regulated by a variety of cytokines/growth factors with some species differences. We reported previously that rabbit ESC (rESC) are more similar to primate ESC than to mouse ESC. However,

Inhibitory plasticity balances excitation and inhibition in sensory pathways and memory networks

Cortical neurons receive balanced excitatory and inhibitory synaptic currents. Such a balance could be established and maintained in an experience-dependent manner by synaptic plasticity at inhibitory synapses. We show that this mechanism provides an explanation for the sparse firing patterns observed in response to natural stimuli and fits well with a recently observed interaction of excitatory and inhibitory receptive field plasticity. The introduction of inhibitory plasticity in suitable recurrent networks provides a homeostatic mechanism that leads to asynchronous irregular network states. Further, it can accommodate synaptic memories with activity patterns that become indiscernible from the background state but can be reactivated by external stimuli. Our results suggest an essential role of inhibitory plasticity in the formation and maintenance of functional cortical circuitry.

Core design options for high conversion BWRs operating in Th- 233U fuel cycle

Several options of fuel assembly design are investigated for a BWR core operating in a closed self-sustainable Th-233U fuel cycle. The designs rely on an axially heterogeneous fuel assembly structure consisting of a single axial fissile zone "sandwiched" between two fertile blanket zones, in order to improve fertile to fissile conversion ratio. The main objective of the study was to identify the most promising assembly design parameters, dimensions of fissile and fertile zones, for achieving net breeding of 233U. The design challenge, in this respect, is that the fuel breeding potential is at odds with axial power peaking and the core minimum critical power ratio (CPR), hence limiting the maximum achievable core power rating. Calculations were performed with the BGCore system, which consists of the MCNP code coupled with fuel depletion and thermo-hydraulic feedback modules. A single 3-dimensional fuel assembly having reflective radial boundaries was modeled applying simplified restrictions on the maximum centerline fuel temperature and the CPR. It was found that axially heterogeneous fuel assembly design with a single fissile zone can potentially achieve net breeding, while matching conventional BWR core power rating under certain restrictions to the core loading pattern design. © 2013 Elsevier B.V. All rights reserved.

BWR fuel design options for self-sustainable Th-233U fuel cycle

In this work, we investigate a number of fuel assembly design options for a BWR core operating in a closed self-sustainable Th-233U fuel cycle. The designs rely on axially heterogeneous fuel assembly structure in order to improve fertile to fissile conversion ratio. One of the main assumptions of the current study was to restrict the fuel assembly geometry to a single axial fissile zone "sandwiched" between two fertile blanket zones. The main objective was to study the effect of the most important design parameters, such as dimensions of fissile and fertile zones and average void fraction, on the net breeding of 233U. The main design challenge in this respect is that the fuel breeding potential is at odds with axial power peaking and therefore limits the maximum achievable core power rating. The calculations were performed with BGCore system, which consists of MCNP code coupled with fuel depletion and thermo-hydraulic feedback modules. A single 3-dimensional fuel assembly with reflective radial boundaries was modeled applying simplified restrictions on maximum central line fuel temperature and Critical Power Ratio. It was found that axially heterogeneous fuel assembly design with single fissile zone can potentially achieve net breeding. In this case however, the achievable core power density is roughly one third of the reference BWR core.

Neutronic optimization in high conversion Th-233U fuel assembly with simulated annealing

This paper reports on fuel design optimization of a PWR operating in a self sustainable Th-233U fuel cycle. Monte Carlo simulated annealing method was used in order to identify the fuel assembly configuration with the most attractive breeding performance. In previous studies, it was shown that breeding may be achieved by employing heterogeneous Seed-Blanket fuel geometry. The arrangement of seed and blanket pins within the assemblies may be determined by varying the designed parameters based on basic reactor physics phenomena which affect breeding. However, the amount of free parameters may still prove to be prohibitively large in order to systematically explore the design space for optimal solution. Therefore, the Monte Carlo annealing algorithm for neutronic optimization is applied in order to identify the most favorable design. The objective of simulated annealing optimization is to find a set of design parameters, which maximizes some given performance function (such as relative period of net breeding) under specified constraints (such as fuel cycle length). The first objective of the study was to demonstrate that the simulated annealing optimization algorithm will lead to the same fuel pins arrangement as was obtained in the previous studies which used only basic physics phenomena as guidance for optimization. In the second part of this work, the simulated annealing method was used to optimize fuel pins arrangement in much larger fuel assembly, where the basic physics intuition does not yield clearly optimal configuration. The simulated annealing method was found to be very efficient in selecting the optimal design in both cases. In the future, this method will be used for optimization of fuel assembly design with larger number of free parameters in order to determine the most favorable trade-off between the breeding performance and core average power density.