Using a surface forces apparatus, we have investigated the adhesive and lubrication forces of mica surfaces separated by a molecularly thin, subnanometer film of a high-molecular-weight (2.3 MDa) anionic polysaccharide from the algae Porphyridium sp. adsorbed from aqueous solution. The adhesion and friction forces of the confined biopolymer were monitored as a function of time, shearing distance, and driving velocity under a large range of compressive loads (pressures). Although the thickness of the dilute polysaccharide was <1 nm, the friction was low (coefficient of friction = 0.015), and no wear was ever observed even at a pressure of 110 atm over 3 decades of velocity, so long as the shearing distances were less than twice the contact diameter. Atomic force microscopy in solution shows that the biopolymer is able to adsorb to the mica surface but remains mobile and easily dragged upon shearing. The adhesion (adsorption) of this polysaccharide even to negatively charged surfaces, its stable low friction, its robustness (high-load carrying capacity and good wear protection), and the weak (logarithmic) dependence of the friction force on the sliding velocity make this class of polyelectrolytes excellent candidates for use in water-based lubricant fluids and as potential additives to synovial fluid in joints and other biolubricating fluids. The physical reasons for the remarkable tribological properties of the ultrathin polysaccharide monolayer are discussed and appear to be quite different from those of other polyelectrolytes and proteins that act as thick "polymer brush" layers.

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c Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. Y es-associated protein (YAP) is a key transcriptional coactivator of the Hippo signaling pathway that plays pivotal roles in stem/progenitor cell proliferation and organ size control (1-11). YAP has also been shown to be a candidate oncogene in the development and progression of multiple human cancers (12-14). The activity of YAP is negatively regulated by its upstream kinase cascade (MstI/2, Sav1, Lats1/2, and Mob1), which leads to the phosphorylation and subsequent degradation of YAP and its paralog TAZ. Inhibition of Hippo signaling relieves YAP and TAZ, which can then translocate into the nucleus. In the nucleus, YAP or TAZ associates with TEAD or other transcription factors to activate the transcription of its target genes (15-18). Conventional knockout of Yap in mice causes early embryonic lethality due to defects in yolk sac vasculogenesis (19). Overexpression of YAP results in enlarged organ size in Drosophila and in mice with profound cell proliferation and inhibition of apoptosis (1,2,7,11, 20). In addition, YAP also plays a critical role in maintaining mouse embryonic stem cell pluripotency and regulating tissue-specific progenitor cells (21).Although the core components of the Hippo pathway are highly conserved between Drosophila and mammalian systems, the transcriptional outputs differ greatly depending on when and where the pathway is deployed. For example, overexpression of YAP in the mouse small intestine leads to Notch-dependent hyperplasia and loss of terminally differentiated cell types but does not appreciably increase the overall size of the organ (1). In Drosophila, the YAP ortholog Yki induces the expression of cycE, diap1, and bantam microRNA (11, 22). In mammalian cells, YAP induces ...