Maxillary sinus variation in hybrid macaques: implications for the genetic basis of craniofacial pneumatization

There has been a long‐standing debate regarding the diversification of paranasal sinuses, namely pneumatized spaces in the face. Functional adaptation and structural constraints have generally been suggested to explain sinus diversification in vertebrates. Here we investigated variation in the maxillary sinus and the external facial cranium in hybrid Taiwanese–Japanese macaques to estimate the genetic basis of phenotypic differences. The Taiwanese macaques have a large sinus, whereas the Japanese macaques have a small sinus; they are also significantly different in their external craniofacial morphology. Variations in the hybrids' external craniofacial morphology can be mostly explained by a simple additive model. In contrast, their sinus morphology significantly deviates from the value expected under this additive model, wherein most hybrids have a large sinus, similar to that in Taiwanese macaques, regardless of the degree of hybridization. When the whole structure is considered, a novel phenotype can be seen in the hybrids. Our results suggest that the sinus and face are independent of each other, both genetically and developmentally, and that the small sinus is mainly caused by intrinsic genetic factors, rather than being structurally constrained by the craniofacial architecture. Such genetic factors may have contributed to the enigmatic diversity of craniofacial pneumatization. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 115 , 333–347.     

Enhanced Expression of Integrin αvβ3 Induced by TGF-β Is Required for the Enhancing Effect of Fibroblast Growth Factor 1 (FGF1) in TGF-β-Induced Epithelial-Mesenchymal Transition (EMT) in Mammary Epithelial Cells

Epithelial-to-mesenchymal transition (EMT) plays a critical role in cancer metastasis, and is regulated by growth factors such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGF) secreted from the stromal and tumor cells. However, the role of growth factors in EMT has not been fully established. Several integrins are upregulated by TGF-β1 during EMT. Integrins are involved in growth factor signaling through integrin-growth factor receptor crosstalk. We previously reported that FGF1 directly binds to integrin αvβ3 and the interaction was required for FGF1 functions such as cell proliferation and migration. We studied the role of αvβ3 induced by TGF-β on TGF-β-induced EMT. Here, we describe that FGF1 augmented EMT induced by TGF-β1 in MCF10A and MCF12A mammary epithelial cells. TGF-β1 markedly amplified integrin αvβ3 and FGFR1 (but not FGFR2). We studied if the enhancing effect of FGF1 on TGF-β1-induced EMT requires enhanced levels of both integrin αvβ3 expression and FGFR1. Knockdown of β3 suppressed the enhancement by FGF1 of TGF-β1-induced EMT in MCF10A cells. Antagonists to FGFR suppressed the enhancing effect of FGF1 on EMT. Integrin-binding defective FGF1 mutant did not augment TGF-β1-induced EMT in MCF10A cells. These findings suggest that enhanced integrin αvβ3 expression in addition to enhanced FGFR1 expression is critical for FGF1 to augment TGF-β1-induced EMT in mammary epithelial cells.     

CFAP53 regulates mammalian cilia-type motility patterns through differential localization and recruitment of axonemal dynein components

Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia of Cfap53 mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia of Cfap53^-/- mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types.     

Design,synthesis, inhibitory activity,and binding mode study of novel DNA methyltransferase 1 inhibitors

To identify novel non-nucleoside DNA methyltransferase (DNMT) inhibitors, we designed and synthesized a series of maleimide derivatives. Among this series, compounds 5–8 were found to be more potent DNMT1 inhibitors than RG108, a DNMT1 inhibitor reported previously by Siedlecki et al. The binding mode analysis of compound 5 is also reported.     

Phagocytosis and resorption during the reassembly of dissociated embryonic cells of sea urchins.

Time-lapse and electron microscopic observations were made on both epithelial and mesenchymal cells during the reassembly of embryos from dissociated cells of Strongylocentrotus purpuratus. In epithelial cells, where lysosomes are produced through the fusion of saccules formed from Golgi bodies, both phagocytosis of cell debris and resorption of differentiated cell structures were observed. In these cells, the lysosomes migrate and fuse with both autosomes and phagosomes. On the other hand, in the mesenchyme cells, where lysosomes are produced through the direct enlargement of the Golgi body's cisterna, neither phagocytosis nor resorption was observed. The migration of the lysosomes to the epithelial cell margins is the first indication of a re-establishment of cellular polarity after dissociation.     

Early induction of interleukin-5 and peripheral eosinophilia in acute pneumonia in Japanese children infected by pandemic 2009 influenza A in the Tokyo area

A novel influenza A (2009 H1N1) virus has led to a worldwide pandemic. A significant number of patients with pneumonia have been reported, although its pathogenesis remains to be elucidated. To determine its pathogenesis, we evaluated serum interleukin (IL)-5 and peripheral eosinophil counts in patients with acute pneumonia caused by the 2009 H1N1 virus. During the period from October to December 2009, 40 patients with laboratory-confirmed 2009 H1N1 pneumonia were under investigation. Their mean age at presentation was 6.8 years. The most characteristic finding was the early development of hypoxemic respiratory distress in the first 24 hr after the onset of fever. Bronchial mucous plugs included eosinophils in addition to neutrophils, even in patients without allergies. Serum IL-5 levels were elevated in 20 out of 24 patients (83%) whose samples were obtained in the first 24 hr after the onset of fever (26.5 ± 20.1 pg/mL), independent of the presence of underlying allergies. In contrast, induction of IL-5 was not documented in sera from eight patients with laboratory-confirmed 2009 H1N1 virus who developed neurological complications, but without lower respiratory infection (2.1 ± 0.7 pg/mL, P < 0.001 vs acute pneumonia). Peripheral eosinophilia was characteristic in acute pneumonia, but not in patients without a lower respiratory infection. There was a marked difference in the induction of IL-5 in 2009 H1N1 patients who developed acute pneumonia, compared with those without a lower respiratory infection. IL-5 may play a role in the early phase of acute pneumonia caused by the 2009 H1N1 virus in Japanese children.