Oxaliplatin is widely used as a key drug in the treatment of colorectal cancer. However, its administration is associated with the dose-limiting adverse effect, peripheral neuropathy. Platinum accumulation in the dorsal root ganglion (DRG) is the major mechanism responsible for oxaliplatin-induced neuropathy. Some drug transporters have been identified as platinum complex transporters in kidney or tumor cells, but not yet in DRG. In the present study, we investigated oxaliplatin transporters and their contribution to peripheral neuropathy. We identified 12 platinum transporters expressed in DRG with real-time PCR, and their transiently overexpressing cells were established. After exposure to oxaliplatin, the accumulation of platinum in these overexpressing cells was evaluated using a coupled plasma mass spectrometer. Octn1/2-and Mate1-expressing cells showed the intracellular accumulation of oxaliplatin. In an animal study, peripheral neuropathy developed after the administration of oxaliplatin (4 mg/kg, intravenously, twice a week) to siRNA-injected rats (0.5 nmol, intrathecally, once a week) was demonstrated with the von Frey test. The knockdown of Octn1 in DRG ameliorated peripheral neuropathy, and decreased platinum accumulation in DRG, whereas the knockdown of Octn2 did not. Mate1 siRNA-injected rats developed more severe neuropathy than control rats. These results indicate that Octn1 and Mate1 are involved in platinum accumulation at DRG and oxaliplatininduced peripheral neuropathy.
Thraustochytrids are marine single-cell protists that produce large amounts of PUFAs, such as DHA. They accumulate PUFAs in lipid droplets (LDs), mainly as constituent(s) of triacylglycerol (TG). We identified a novel protein in the LD fraction of F26-b using 2D-difference gel electrophoresis. The protein clustered with orthologs of thraustochytrids; however, the cluster was evolutionally different from known PAT family proteins or plant LD protein; thus, we named it thraustochytrid-specific LD protein 1 (TLDP1). TLDP1 surrounded LDs when expressed as a GFP-tagged form. Disruption of the gene decreased the content of TG and number of LDs per cell; however, irregular and unusually large LDs were generated in -deficient mutants. Although the level of TG synthesis was unchanged by the disruption of, the level of TG degradation was higher in -deficient mutants than in the WT. These phenotypic abnormalities in-deficient mutants were restored by the expression of These results indicate that TLDP1 is a thraustochytrid-specific LD protein and regulates the TG accumulation and LD morphology in F26-b.
This study focuses on media multitasking (MM) tendency while accounting for the heterogeneity of the store visits and purchase behaviors of media multitaskers. We employed a latent class model to identify several consumer segments and investigate the effect of behavioral traits on segment membership. Based on the results, we identified three segments and labeled them Apathetic, E-shopper, and E-buyer segments. Apathetic consumers show no interest in MM, store visits, and online purchases. The E-shopper segment records the highest MM, store visit probability, and low transaction rate, while the E-buyers exhibit the opposite behavior pattern. Furthermore, the results revealed that people who frequently use the Internet or television and watch more news programs are more likely to belong to the “E-shopper” segment. We also observed that people in the “E-buyer” segment are less probable to zap and watch variety shows more frequently. These findings are helpful for marketers to understand their customers better and devise more efficient marketing strategies.
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