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D’Arcy Thompson predicted a century ago that animal body shape is conditioned by gravity, but there has been no animal model to study how cellular forces are coordinated to generate body shapes that withstand gravity; the hirame medaka fish mutant, with pronounced body flattening, reveals how the hirame /YAP gene controls gravity-resisting cellular forces to produce complex 3D organs and body shapes. YAP protein gives tissue shape How is tissue tension controlled at the organismal level to maintain body shape and complex three-dimensional structures? Makoto Furutani-Seiki and colleagues describe a medaka fish mutant, hirame ( hir ), with a flattened body. They show that the phenotype is due to reduction of internal forces caused by the absence of YAP protein, part of the Hippo signalling pathway. This striking effect is linked to the control exerted by YAP on actomyosin-mediated tension through the regulation of the RhoGAP GTPase activating protein ARHGAP18. YAP also controls the 3D structure of human cell spheres in this manner in a human cell culture system. Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head 1 . Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force 2 , 3 . Although a century ago D’Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity 4 , there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish ( Oryzias latipes ) mutant, hirame ( hir ), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues.

Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when re-challenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype.

Medical herbs have been recognized till now as having different constituents that act on the human body. However, the fragrance of herbs is a complex mixture of odors, which makes it difficult to qualify or quantify the scent objectively on the human sense of smell. In this study, aromas of 15 medicinal herbs were recorded using an electronic nose FF-2A, and their characteristics were compared with aroma samples of wine such as Le Nez du Vin, to determine which wine aromas are similar to each medicinal herb. Thereafter, the aromas of the 15 herbs were standardized to create a reference axis for the aroma of each herb, and the similarity of tea herbs to the reference axis was examined. Additionally, the results were compared with those obtained by gas chromatography-mass spectrometry (GC-MS). In FF-2A, the measured scent is recorded as an absolute value. We succeeded in calculating the similarity of the scents of other herbs with the axes of the scent of each herb by standardizing their scents and creating new axis data. Conversely, although GC-MS is able to identify the components and concentrations of fragrances, an electronic nose can analyze fragrances in a way that is uncommon with GC-MS, such as comparison of similarities between fragrances.