Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition

We identified the specific role of vaccinia-related kinase 1 (VRK1) in the progression of hepatocellular carcinoma (HCC) and evaluated its therapeutic and prognostic potential. VRK1 levels were significantly higher in HCC cell lines than a normal hepatic cell line, and were higher in HCC than non-tumor tissue. VRK1 knockdown inhibited the proliferation of SK-Hep1, SH-J1 and Hep3B cells; moreover, depletion of VRK1 suppressed HCC tumor growth in vivo. We also showed that VRK1 knockdown increased the number of G1 arrested cells by decreasing cyclin D1 and p-Rb while upregulating p21 and p27, and that VRK1 depletion downregulated phosphorylation of CREB, a transcription factor regulating CCND1. Additionally, we found that luteolin, a VRK1 inhibitor, suppressed HCC growth in vitro and in vivo, and that the aberrant VRK1 expression correlated with poor prognostic features of HCC. High levels of VRK1 were associated with shorter overall and disease-free survival and higher recurrence rates. Taken together, our findings suggest VRK1 may act as a tumor promoter by controlling the level of cell cycle regulators associated with G1/S transition and could potentially serve as a therapeutic target and/or prognostic biomarker for HCC.1110Ysciescopu

Information flow between stock indices

Using transfer entropy, we observed the strength and direction of information flow between stock indices. We uncovered that the biggest source of information flow is America. In contrast, the Asia/Pacific region the biggest is receives the most information. According to the minimum spanning tree, the GSPC is located at the focal point of the information source for world stock markets

Experimental investigation of the 30S(α, p) thermonuclear reaction in x-ray bursts

We performed the first measurement of 30 S+α resonant elastic scattering to experimentally examine the 30 S(α, p) stellar reaction rate in type I x-ray bursts. These bursts are the most frequent thermonuclear explosions in the galaxy, resulting from thermonuclear runaway on the surface of accreting neutron star binaries. The 30 S(α, p) reaction plays a critical role in burst models, yet very little is known about the compound nucleus 34 Ar at these energies nor the reaction rate itself. We performed a measurement of alpha elastic scattering with a radioactive beam of 30 S to experimentally probe the entrance channel. Utilizing a gaseous active target system and silicon detector array, we extracted the excitation function from 1.8 to 5.5 MeV near 160° in the center-of-mass frame. The experimental data were analyzed with an R -Matrix calculation, and we discovered several new resonances and extracted their quantum properties (resonance energy, width, spin, and parity). Finally, we calculated the narrow resonant thermonuclear reaction rate of 30 S(α, p) for these new resonances

Quasinormal modes from potentials surrounding the charged dilaton black hole

We clarify the purely imaginary quasinormal frequencies of a massless scalar perturbation on the 3D charged-dilaton black holes. This case is quite interesting because the potential-step appears outside the event horizon similar to the case of the electromagnetic perturbations on the large Schwarzschild-AdS black holes. It turns out that the potential-step type provides the purely imaginary quasinormal frequencies, while the potential-barrier type gives the complex quasinormal modes.Comment: 19 pages, 8 figure

Alkyl Glycosides from the Flowers of Magnolia obovata

Abstract The flowers of Magnolia obovata were extracted with aqueous MeOH and fractionated into EtOAc, n-BuOH, and H 2 O fractination. Three alkyl glycosides were isolated from the EtOAc fraction through repeated silica gel and ODS column chromatography. The structures were identified to be 2-methylbutan-1-ol-β-Dgalacto-pyranoside (1), 2-methylbutan-1-ol-β-D-glucopyranoside (2), and 2-methylpropan-1-ol-β-D-glucopyranoside (3) on the basis of spectroscopic analyses such as fast atom bombardment mass spectrometry, infrared spectroscopy, 1D nuclear magnetic resonance (NMR) ( 1 H and 13 C-NMR), and 2D NMR (gCOSY, gHSQC, and gHMBC). These compounds were isolated for the first time from the flower of M. obovata in this study

Bond operator theory of doped antiferromagnets: from Mott insulators with bond-centered charge order, to superconductors with nodal fermions

The ground states and excitations of two-dimensional insulating and doped Mott insulators are described by a bond operator formalism. While the method represents the degrees of freedom of an arbitrary antiferromagnet exactly, it is especially suited to systems in which there is a natural pairing of sites into bonds, as in states with spontaneous or explicit spin-Peierls order (or bond-centered charge order). In the undoped insulator, as discussed previously, we obtain both paramagnetic and magnetically-ordered states. We describe the evolution of superconducting order in the ground state with increasing doping--at low doping, the superconductivity is weak, can co-exist with magnetic order, and there are no gapless spin 1/2 fermionic excitations; at high doping, the magnetic order is absent and we obtain a BCS d-wave superconductor with gapless spin 1/2, nodal fermions. We present the critical theory describing the onset of these nodal fermionic excitations. We discuss the evolution of the spin spectrum, and obtain regimes where a spin 1 exciton contributes a sharp resonance in the dynamic spin susceptiblity. We also discuss the experimental consequences of low-energy, dynamically fluctuating, spin-Peierls order in an isotropic CuO_2 plane--we compute consequences for the damping and dispersion of an optical phonon involving primarily the O ions, and compare the results with recent neutron scattering measurements of phonon spectra.Comment: 16 pages + 14 pages of appendices, 18 figures; (v3) expanded discussion of theory and experimental implications; (v4) Removed some introductory review discussion and moved it to cond-mat/010823

Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene

Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state

NovelRPL13Variants and Variable Clinical Expressivity in a Human Ribosomopathy With Spondyloepimetaphyseal Dysplasia

Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of disorders with variable growth failure and skeletal impairments affecting the spine and long bone epiphyses and metaphyses. Here we report on four unrelated families with SEMD in which we identified two monoallelic missense variants and one monoallelic splice site variant inRPL13, encoding the ribosomal protein eL13. In two out of four families, we observed autosomal dominant inheritance with incomplete penetrance and variable clinical expressivity; the phenotypes of the mutation-positive subjects ranged from normal height with or without hip dysplasia to severe SEMD with severe short stature and marked skeletal dysplasia.In vitrostudies on patient-derived dermal fibroblasts harboringRPL13missense mutations demonstrated normal eL13 expression, with proper subcellular localization but reduced colocalization with eL28 (p<0.001). Cellular functional defects in fibroblasts from mutation-positive subjects indicated a significant increase in the ratio of 60S subunits to 80S ribosomes (p= 0.007) and attenuated global translation (p= 0.017). In line with the human phenotype, ourrpl13mutant zebrafish model, generated by CRISPR-Cas9 editing, showed cartilage deformities at embryonic and juvenile stages. These findings extend the genetic spectrum ofRPL13mutations causing this novel human ribosomopathy with variable skeletal features. Our study underscores for the first time incomplete penetrance and broad phenotypic variability in SEMD-RPL13 type and confirms impaired ribosomal function. Furthermore, the newly generatedrpl13mutant zebrafish model corroborates the role of eL13 in skeletogenesis. (c) 2020 The Authors.Journal of Bone and Mineral Researchpublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..Peer reviewe