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.

The association of the Arabidopsis actin-related protein (ARP) 2/3 complex with cell membranes is linked to its assembly status but not its activation

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Unsteady shock motion on a NACA0012 aerofoil at low reduced frequencies

Using transonic blowdown windtunnel experiments, the 2D unsteady shock motion on a NACA0012 aerofoil is examined at various frequencies typical for helicopter blades in forward flight. The aerofoil is subjected to freestream velocities oscillating periodically between M = 0.66 and M = 0.77. Unsteady pressure traces and schlieren images are analyzed over a range of low reduced frequencies to provide information on shock location and strength throughout the cycle. Unsteady effects were noticeable even at very low reduced frequencies (down to O(0.01). However, through the range of frequencies investigated, and within experimental error, the unsteady shock location showed no discernible lag compared to the quasi-steady behaviour. On the other hand, significant variations were observed in shock strengths with the upstream running part of the cycle (decreasing Mach number) displaying considerably stronger shocks than during the accelerating part of the cycle. It could be shown that this variation in shock strength is primarily caused by the shock motion modifying the relative shock Mach number. As a result is was possible to use the quasi-steady results to predict the unsteady shock behaviour at the frequencies investigated here (below 0(0.1)).

Unsteady shock motion on a NACA0012 aerofoil at low reduced frequencies

Using transonic blowdown windtunnel experiments, the 2D unsteady shock motion on a NACA0012 aerofoil is examined at various frequencies typical for helicopter blades in forward flight. The aerofoil is subjected to freestream velocities oscillating periodically between M = 0.66 and M = 0.77. Unsteady pressure traces and schlieren images are analyzed over a range of low reduced frequencies to provide information on shock location and strength throughout the cycle. Unsteady effects were noticeable even at very low reduced frequencies (down to O(0.01). However, through the range of frequencies investigated, and within experimental error, the unsteady shock location showed no discernible lag compared to the quasi-steady behaviour. On the other hand, significant variations were observed in shock strengths with the upstream running part of the cycle (decreasing Mach number) displaying considerably stronger shocks than during the accelerating part of the cycle. It could be shown that this variation in shock strength is primarily caused by the shock motion modifying the relative shock Mach number. As a result is was possible to use the quasi-steady results to predict the unsteady shock behaviour at the frequencies investigated here (below 0(0.1)).

Bm-TFF2, a trefoil factor protein with platelet activation activity from frog Bombina maxima skin secretions

In mammals, trefoil factor family (TFF) proteins are involved in mucosal maintenance and repair, and they are also implicated in tumor suppression and cancer progression. A novel two domain TFF protein from frog Bombina maxima skin secretions (Bm-TFF2) has been purified and cloned. It activated human platelets in a dose-dependent manner and activation of integrin a(11b)beta(3) was involved. Aspirin and apyrase did not largely reduce platelet response to Bm-TFF2 (a 30% inhibition), indicating that the aggregation is not substantially dependent on ADP and thromboxane A2 autocrine feedback. Elimination of external Ca2+ with EGTA did not influence the platelet aggregation induced by Bm-TFF2, meanwhile a strong calcium signal (cytoplasmic Ca2+ release) was detected, suggesting that activation of phospholipase C (PLC) is involved. Subsequent immunoblotting revealed that, unlike in platelets activated by stejnulxin (a glycoprotein VI agonist), PLC gamma 2 was not phosphorylated in platelets activated by Bm-TFF2. FITC-labeled Bm-TFF2 bound to platelet membranes. Bm-TFF2 is the first TFF protein reported to possess human platelet activation activity. (c) 2005 Elsevier Inc. All rights reserved.