AMPA receptor (AMPAR) surface expression in the nucleus accumbens (NAc) is enhanced after withdrawal from repeated cocaine exposure. However, it is unclear whether this contributes to the expression of locomotor sensitization and whether similar changes can be observed in other striatal regions. Here we examined the relationship between AMPAR surface expression in the NAc and locomotor sensitization. We also examined AMPAR distribution in the dorsolateral striatum (DS) and NMDA receptor (NMDAR) distribution in the NAc and DS. Trends but no significant changes in NMDAR distribution were found in the NAc after withdrawal. No changes were observed in the DS. AMPAR surface expression was increased in the NAc 15 days after the last exposure to cocaine, but decreased in the DS. Re-exposure to cocaine on withdrawal day 14 decreased AMPAR surface expression in the NAc 24 h, but not 30 min, after challenge, but increased it in the DS 24 h and 30 min after challenge. Locomotor sensitization was evaluated at times associated with increased or decreased AMPAR surface expression in the NAc. The magnitude of sensitization did not vary with changes in the level of AMPAR surface expression, nor was it significantly reduced by decreasing AMPAR transmission via intra-NAc infusion of CNQX prior to cocaine challenge. Based on our results, and other findings, we suggest that the expression of sensitization has no clear relationship to altered AMPAR surface expression in NAc although the latter may play a role in the enhanced pursuit and self-administration of drugs observed in sensitized rats.

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Inactivation of the Rb tumor suppressor can lead to increased cell proliferation or cell death depending on specific cellular context. Therefore, identification of the interacting pathways that modulate the effect of Rb loss will provide novel insights into the roles of Rb in cancer development and promote new therapeutic strategies. Here, we identify a novel synthetic lethal interaction between Rb inactivation and deregulated Wg/Wnt signaling through unbiased genetic screens. We show that a weak allele of axin, which deregulates Wg signaling and increases cell proliferation without obvious effects on cell fate specification, significantly alters metabolic gene expression, causes hypersensitivity to metabolic stress induced by fasting, and induces synergistic apoptosis with mutation of fly Rb ortholog, rbf. Furthermore, hyperactivation of Wg signaling by other components of the Wg pathway also induces synergistic apoptosis with rbf. We show that hyperactivated Wg signaling significantly increases TORC1 activity and induces excessive energy stress with rbf mutation. Inhibition of TORC1 activity significantly suppressed synergistic cell death induced by hyperactivated Wg signaling and rbf inactivation, which is correlated with decreased energy stress and decreased induction of apoptotic regulator expression. Finally the synthetic lethality between Rb and deregulated Wnt signaling is conserved in mammalian cells and that inactivation of Rb and APC induces synergistic cell death through a similar mechanism. These results suggest that elevated TORC1 activity and metabolic stress underpin the evolutionarily conserved synthetic lethal interaction between hyperactivated Wnt signaling and inactivated Rb tumor suppressor.

This study analyzed the effects of ecological factors on secondary metabolites of Scutellaria baicalensis using two sources: 92 individual roots of S. baicalensis from all over China, and secondary metabolites, medicinal materials and inorganic element contents obtained from the testing of 92 S. baicalensis rhizosphere soil samples. The study used environmental data from the Genuine Medicinal Material Spatial Analysis Database. Most of the chemical constituents of S. baicalensis were negatively correlated to latitude and positively correlated to temperature; generally, the contents of 21 chemical constituents were higher at low latitudes than that at high latitudes. By gradual regression analysis, it was found that the content of baicalin in S. baicalensis was negatively correlated to latitude and generally the content of inorganic elements in soil was excessively high (excluding Mg and Ca), which has a negative effect on the accumulation of chemical constituents in S. baicalensis. Based on the cluster analysis of 21 constituents, S. baicalensis from different places of origin was divided into two groups, and S. baicalensis was not genuine only in a specific small region. Within the zone from Chifeng, Inner Mongolia to Taibai, Shaanxi is suitable for accumulation of secondary metabolites of S. baicalensis and such a zone represents a suitable distribution and potential genuine producing area. Scutellaria baicalensis, ecological factors, geoherbs, Daodi-herbs, geographical variation Citation:Guo L P, Wang S, Zhang J, et al. Huáng qín (Chinese: 黄芩) is originally from Scutellaria baicalensis. Its dried root is popular in traditional Chinese medicine. It works as an anti-inflammatory, antioxidant, and anti-allergen, and it is often used to treat fevers, coughs, allergic rhinitis, and wheezing [11]. Scutellaria baicalensis is widely distributed in Northeast China, North China, Central China and Southwest China, and is common in extensive areas north of the Yangtze River [12]. Research has demonstrated that variation in the quality of S. baicalensis is mainly due to environmental factors [13]. In our earlier study, 92 individual roots of S. baicalensis and the 92 corresponding rhizosphere soil samples were taken from all over China; the secondary metabolites in roots of S. baicalensis and inorganic elements in roots and rhizosphere soil were tested. Based on the data of these secondary metabolites and inorganic elements, massive environmental data from the Spatial Analysis Database of Geoherbs are used to investigate the influence of ecological factors on the accumulation of secondary metabolites and their comprehensive effect, which may provide guidance for high-quality cultivation of S. baicalensis.

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