Fibroblast growth factor 10 regulates Meckel's cartilage formation during early mandibular morphogenesis in rats

AbstractFibroblast growth factors (FGF) are pluripotent growth factors that play pivotal roles in the development of various organs. During mandibular organogenesis, Meckel's cartilage, teeth, and mandibular bone differentiate under the control of various FGF. In the present study, we evaluated the role of FGF10 in rat mandibular chondrogenesis and morphogenesis using mandibular organ culture and mandibular cell micromass culture systems. The overexpression of Fgf10 induced by the electroporation of an FGF10 expression vector not only altered the size and shape of Meckel's cartilage, but also upregulated the expression of the cartilage characteristic genes Col2a1 and Sox9 in a mandibular organ culture system. Meckel's cartilage was deformed, and its size was increased when Fgf10 was overexpressed in the lateral area of the mandible. Meanwhile, no effect was found when Fgf10 was overexpressed in the medial portion. In the mandibular cell micromass culture, recombinant FGF10 treatment enhanced chondrogenic differentiation and endogenous ERK (extracellular signal-regulated kinase) phosphorylation in cells derived from the lateral area of the mandible. On the other hand, FGF10 did not have significant effects on mandibular cell proliferation. These results indicate that FGF10 regulates Meckel's cartilage formation during early mandibular morphogenesis by controlling the cell differentiation in the lateral area of the mandibular process in rats

Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2 expression inhibition independent of the Wnt/β-catenin signaling pathway

<p>Abstract</p> <p>Background</p> <p>Differentiation-inducing factor-1 (DIF-1) is a putative morphogen that induces cell differentiation in <it>Dictyostelium discoideum</it>. DIF-1 inhibits proliferation of various mammalian tumor cells by suppressing the canonical Wnt/β-catenin signaling pathway. To assess the potential of a novel cancer chemotherapy based on the pharmacological effect of DIF-1, we investigated whether DIF-1 exhibits anti-angiogenic effects <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>DIF-1 not only inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) by restricting cell cycle in the G₀/G₁phase and degrading cyclin D1, but also inhibited the ability of HUVECs to form capillaries and migrate. Moreover, DIF-1 suppressed VEGF- and cancer cell-induced neovascularization in Matrigel plugs injected subcutaneously to murine flank. Subsequently, we attempted to identify the mechanism behind the anti-angiogenic effects of DIF-1. We showed that DIF-1 strongly decreased vascular endothelial growth factor receptor-2 (VEGFR-2) expression in HUVECs by inhibiting the promoter activity of human VEGFR-2 gene, though it was not caused by inhibition of the Wnt/β-catenin signaling pathway.</p> <p>Conclusion</p> <p>These results suggested that DIF-1 inhibits angiogenesis both <it>in vitro </it>and <it>in vivo</it>, and reduction of VEGFR-2 expression is involved in the mechanism. A novel anti-cancer drug that inhibits neovascularization and tumor growth may be developed by successful elucidation of the target molecules for DIF-1 in the future.</p

Parabolic Jets from the Spinning Black Hole in M87

The M87 jet is extensively examined by utilizing general relativistic magnetohydrodynamic (GRMHD) simulations as well as the steady axisymmetric force-free electrodynamic (FFE) solution. Quasi-steady funnel jets are obtained in GRMHD simulations up to the scale of $\sim 100$ gravitational radius ($r_{\rm g}$) for various black hole (BH) spins. As is known, the funnel edge is approximately determined by the following equipartitions; i) the magnetic and rest-mass energy densities and ii) the gas and magnetic pressures. Our numerical results give an additional factor that they follow the outermost parabolic streamline of the FFE solution, which is anchored to the event horizon on the equatorial plane. We also identify the matter dominated, non-relativistic corona/wind play a dynamical role in shaping the funnel jet into the parabolic geometry. We confirm a quantitative overlap between the outermost parabolic streamline of the FFE jet and the edge of jet sheath in VLBI observations at $\sim 10^{1}$-$10^{5} \, r_{\rm g}$, suggesting that the M87 jet is likely powered by the spinning BH. Our GRMHD simulations also indicate a lateral stratification of the bulk acceleration (i.e., the spine-sheath structure) as well as an emergence of knotty superluminal features. The spin characterizes the location of the jet stagnation surface inside the funnel. We suggest that the limb-brightened feature could be associated with the nature of the BH-driven jet, if the Doppler beaming is a dominant factor. Our findings can be examined with (sub-)mm VLBI observations, giving a clue for the origin of the M87 jet.Comment: 29 pages, 23 figures, accepted for publication in Ap

Genetic Encoding of 3-Iodo-l-Tyrosine in Escherichia coli for Single-Wavelength Anomalous Dispersion Phasing in Protein Crystallography

SummaryWe developed an Escherichia coli cell-based system to generate proteins containing 3-iodo-l-tyrosine at desired sites, and we used this system for structure determination by single-wavelength anomalous dispersion (SAD) phasing with the strong iodine signal. Tyrosyl-tRNA synthetase from Methanocaldococcus jannaschii was engineered to specifically recognize 3-iodo-l-tyrosine. The 1.7 Å crystal structure of the engineered variant, iodoTyrRS-mj, bound with 3-iodo-l-tyrosine revealed the structural basis underlying the strict specificity for this nonnatural substrate; the iodine moiety makes van der Waals contacts with 5 residues at the binding pocket. E. coli cells expressing iodoTyrRS-mj and the suppressor tRNA were used to incorporate 3-iodo-l-tyrosine site specifically into the ribosomal protein N-acetyltransferase from Thermus thermophilus. The crystal structure of this enzyme with iodotyrosine was determined at 1.8 and 2.2 Å resolutions by SAD phasing at CuKα and CrKα wavelengths, respectively. The native structure, determined by molecular replacement, revealed no significant structural distortion caused by iodotyrosine incorporation

Asymmetric auxin distribution establishes a contrasting pattern of aerenchyma formation in the nodal roots of Zea nicaraguensis during gravistimulation

Auxin distribution is essential for determining root developmental patterns. The formation of lateral roots and constitutive aerenchyma, which is a gas space developed through cell death, is regulated by auxin in rice (Oryza sativa). However, it is unclear whether the involvement of auxin in constitutive aerenchyma formation is conserved in other species. In this study, we found that constitutive aerenchyma formation was regulated by auxin in the nodal roots of Zea nicaraguensis, a wild relative of maize (Zea mays ssp. mays) grown naturally on frequently flooded coastal plains. Subsequent gravistimulation (root rotation) experiments showed opposite patterns of aerenchyma and lateral root formation. Lateral root formation on the convex side of rotated roots is known to be stimulated by a transient increase in auxin level in the pericycle. We found that aerenchyma formation was accelerated in the cortex on the concave side of the rotated nodal roots of Z. nicaraguensis. A cortex-specific expression analysis of auxin-responsive genes suggested that the auxin level was higher on the concave side than on the convex side. These results suggest that asymmetric auxin distribution underlies the regulation of aerenchyma and lateral root formation in the nodal roots of Z. nicaraguensis. As aerenchyma reduces the respiratory cost of the roots, constitutive aerenchyma on the concave side of the nodal root may balance resource allocation, thereby contributing to the uptake of water and nutrients by newly formed lateral roots. Our study provides insights into auxin-dependent asymmetric root patterning such as that of gravistimulation and hydropatterning response

X-Ray and Near-Infrared Observations of GX 339-4 in the Low/Hard State with Suzaku and IRSF

X-ray and near-infrared ($J$-$H$-$K_{\rm s}$) observations of the Galactic black hole binary GX 339--4 in the low/hard state were performed with Suzaku and IRSF in 2009 March. The spectrum in the 0.5--300 keV band is dominated by thermal Comptonization of multicolor disk photons, with a small contribution from a direct disk component, indicating that the inner disk is almost fully covered by hot corona with an electron temperature of $\approx$175 keV. The Comptonizing corona has at least two optical depths, $\tau \approx 1,0.4$. Analysis of the iron-K line profile yields an inner disk radius of $(13.3^{+6.4}_{-6.0}) R_{\rm g}$ ($R_{\rm g}$ represents the gravitational radius $GM/c^2$), with the best-fit inclination angle of $\approx50^\circ$. This radius is consistent with that estimated from the continuum fit by assuming the conservation of photon numbers in Comptonization. Our results suggest that the standard disk of GX 339--4 is likely truncated before reaching the innermost stable circular orbit (for a non rotating black hole) in the low/hard state at $\sim$1% of the Eddington luminosity. The one-day averaged near-infrared light curves are found to be correlated with hard X-ray flux with $F_{\rm Ks} \propto F_{\rm X}^{0.45}$. The flatter near infrared $\nu F_{\nu}$ spectrum than the radio one suggests that the optically thin synchrotron radiation from the compact jets dominates the near-infrared flux. Based on a simple analysis, we estimate the magnetic field and size of the jet base to be $5\times10^4$ G and $6\times 10^8$ cm, respectively. The synchrotron self Compton component is estimated to be approximately 0.4% of the total X-ray flux.Comment: 17pages, 15 figures, accepted for publication in PASJ (Suzaku and MAXI Special Issue

Parabolic Jets from the Spinning Black Hole in M87

The M87 jet is extensively examined by utilizing general relativistic magnetohydrodynamic (GRMHD) simulations, as well as the steady axisymmetric force-free electrodynamic (FFE) solution. Quasi-steady funnel jets are obtained in GRMHD simulations up to the scale of ~100 gravitational radii (r(sub g)) for various black hole (BH) spins. As is known, the funnel edge is approximately determined by the following equipartitions: (i) the magnetic and rest-mass energy densities and (ii) the gas and magnetic pressures. Our numerical results give an additional factor that they follow the outermost parabolic streamline of the FFE solution, which is anchored to the event horizon on the equatorial plane. We also show that the matter-dominated, nonrelativistic corona/wind plays a dynamical role in shaping the funnel jet into the parabolic geometry. We confirm a quantitative overlap between the outermost parabolic streamline of the FFE jet and the edge of the jet sheath in very long baseline interferometry (VLBI) observations at ~(10(exp 1)10(exp 5))r(sub g), suggesting that the M87 jet is likely powered by the spinning BH. Our GRMHD simulations also indicate a lateral stratification of the bulk acceleration (i.e., the spine-sheath structure), as well as an emergence of knotty superluminal features. The spin characterizes the location of the jet stagnation surface inside the funnel. We suggest that the limb-brightened feature could be associated with the nature of the BH-driven jet, if the Doppler beaming is a dominant factor. Our findings can be examined with (sub)millimeter VLBI observations, giving a clue for the origin of the M87 jet