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The execution of a script often requires detecting and resolving conflict with a goal, particularly in nonroutine situations. To take the example of taking a bus daily to work, if someone’s usual bus is delayed and a bus for another destination comes first, the person must inhibit taking it and wait for the usual one. Young children can gradually acquire the ability to control the execution of scripts in such nonroutine situations, but few studies have explored the control process involved. In two experiments, we investigated the role of developments in the maintenance of hierarchical goal representations and in executive functions. We measured the ability to control the execution of scripts using a task in which children helped a doll select items to wear; clothing options were presented in an unexpected order in the nonroutine situations. The younger children (4-year-olds) could not flexibly control their execution of scripts in nonroutine situations, although they could exogenously detect and resolve conflict if they were prompted to maintain a subgoal. The older children (5-year-olds) endogenously controlled script execution based on a main goal, whereas subgoal maintenance led them to rigidly control their performance. In addition, children’s inhibition abilities were associated with their control of script execution. These findings indicate that the development of the control process underlying the execution of scripts in nonroutine situations is partially dependent on the ability to maintain hierarchical goal representations. [ABSTRACT FROM AUTHOR]

Background: Intestinal damage after ischemia followed by revascularization, referred to as “ischemia-reperfusion (I/R) injury,” is a devastating complication that can occur after acute superior mesenteric obstruction, or after both elective and emergent abdominal aortic surgery. Once an entire layer of intestine is involved in severe ischemia, the mortality rate reaches 90%; no effective medical treatment has been reported to date. Here, we demonstrate that a somatostatin analogue, octreotide, but not a free-radical scavenger, MCI-186, prevented death due to surgically induced intestinal I/R injury in rats. Methods: Superior mesenteric artery (SMA) of Male Sprague-Dawley rats, that received MCI-186 or octreotide, was surgically clamped, and then the clips were removed and SMA blood flow restored. Survival was assessed, and blood and small intestine were subjected to cell count, enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Results: Of interest, pretreatment with octreotide, but not with MCI-186, just before induced intestinal ischemia prompted the early expression of heme oxygenase-1 (HO-1) protein-associated accumulation of CD68-positive cells, a possible cellular source of HO-1. Inversely, the administration of tin protoporphyrin IX (SnPPN), a specific inhibitor of HO-1, completely abolished the therapeutic effects of octreotide, indicating that the favorable effects of octreotide against intestinal I/R injury is predominantly dependent on the early induction of HO-1. Conclusions: These results suggest that a somatostatin analogue may be useful in leading to an improvement of the prognosis of patients with intestinal I/R injury in the clinical setting. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hepatitis C virus (HCV) induces endoplasmic reticulum (ER) stress which, in turn, activates the unfolding protein response (UPR). UPR activates three distinct signalling pathways. Additionally, UPR induces autophagy (UPR-autophagy pathways). On the other hand, it has become clear that some positive-single-strand RNA viruses utilize autophagy. Some groups have used the siRNA silencing approach to show that autophagy is required for HCV RNA replication. However, the mechanism of induction of the UPR-autophagy pathways remain unclear in the cells with HCV. Method and results: we used a genome-length HCV RNA (strain O of genotype 1b) replication system (OR6) in hepatoma cells (HuH-7-derived OR6 cells). As control, we used OR6c cells from which the HCV genome had been removed by treatment with interferon-α. The UPR-autophagy pathways were activated to a greater degree in the OR6 cells as compared to the OR6c cells. Rapamycin, mTOR-independent autophagy inducer, activated HCV replication in the OR6 cells. On the other hand, HCV replication in the cells was inhibited by 3-methyladenine (3-MA), which is an inhibitor of autophagy. Salubrinal (Eukaryotic Initiation Factor 2(eIF2)-alpha phosphatase inhibitor), 3-ethoxy-5, 6-dibromosalicylaldehyde (X-box binding protein-1 (XBP-1) splicing inhibitor) and sp600125 (c-Jun N-terminal kinases (JNK) inhibitor) inhibited HCV replication and autophagy. Additionally, HCV replication and autophagy were inhibited more strongly by combination of these inhibitors. Conclusion: Our results suggest that UPR-autophagy pathways exert an influence on HCV replication. Therefore, control these pathways may serve as a novel therapeutic strategy against replication of HCV. [Copyright &y& Elsevier]