Hepatocellular carcinoma (HCC) is quickly rising to become one of the deadliest cancers worldwide. Simultaneously inhibiting the Ras and NF-κB pathways in hepatocytes surprisingly causes liver tumorigenesis and circadian clock disruption in hepatocytes. However, it is unknown if there is clock crosstalk between hepatocytes and specific non-parenchymal cell populations. To study clock disruption in this HCC mouse model, I used single-cell RNA sequencing to characterize cell populations and study clock gene expression. My analysis revealed that compared to the wild type, the DKO model had a lower proportion of B cells, but a higher proportion of macrophages and neutrophils. I also found that circadian clock gene expression in non-parenchymal cells differ between cell populations. There appears to be higher expression of Dbp, Per1, and Per2 in stellate cells and cholangiocytes, Dbp in endothelial cells, Cry1 and Per1 in neutrophils, and Per1 in macrophages. To a lesser extent, clock gene expression in non-parenchymal cells also differs between wild type and DKO. Cell-cell interaction analysis revealed that in communication from hepatocytes to NPC populations, there were the addition of the Lgals9 - Ptprc and Lgals9 - Cd44 interactions in the DKO model. In communication from NPCs to hepatocytes, the DKO lacked the H2-K1 - Cd8a/Cd8b1 interaction, but had enhanced FN1 - Sdc4 interactions. These results suggest that hepatocytes may be communicating to specific NPC populations differently regarding the circadian clock, and further studies may help us uncover new mechanisms of clock crosstalk between hepatic cell types and their relation to liver tumorigenesis.

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It seems that transportation planners everywhere are looking for ways of reducing vehicle miles of travel (VMT) by automobile, even as citizens seem determined to drive more. The trend may be especially evident here in California where everyone seems to believe that use of cars is excessive, having conspired to foul the air, congest the highways, provoke traffic accidents, and erode the quality of people's lives. In response, a lot of creative remedies have been invented - schemes to entice travelers into carpools and public transit and schemes to induce them to stay home. 

ACCESS has been reporting on several of these, including the economists' pet formula for reducing VMT by pricing travel at closer to its true cost. Congestion pricing and parking pricing have been gaining considerable attention of late. So have proposals for raising gas taxes to levels that Europeans find tolerable. So have proposals for telecommuting. So have proposals for inter- and intra-metropolitan rail lines.

Despite huge reductions of noxious emissions from factories and cars, Southern California's air is still terrible. It's so bad that the state is requiring that two percent of new cars sold in 1998 be zero polluters and ten percent by 2003. Many researchers here have become preoccupied with teh foul air, and so are searching for ways of making cars less obnoxious and hence better servants.