During cell division, precise and regulated distribution of cellular material between daughter cells is a critical step and is governed by complex biochemical and biophysical mechanisms. To achieve this, membraneless organelles and condensates often require complete disassembly during mitosis. The biophysical principles governing the disassembly of condensates remain poorly understood. Here, we used a physical biology approach to study how physical and material properties of the nucleolus, a prominent nuclear membraneless organelle in eukaryotic cells, change during mitosis and across different scales. We found that nucleolus disassembly proceeds continuously through two distinct phases with a slow and reversible preparatory phase followed by a rapid irreversible phase that was concurrent with the nuclear envelope breakdown. We measured microscopic properties of nucleolar material including effective diffusion rates and binding affinities as well as key macroscopic properties of surface tension and bending rigidity. By incorporating these measurements into the framework of critical phenomena, we found evidence that near mitosis surface tension displays a power-law behavior as a function of biochemically modulated interaction strength. This two-step disassembly mechanism maintains structural and functional stability of nucleolus while enabling its rapid and efficient disassembly in response to cell cycle cues.
To investigate the effect of phenylhexyl isothiocyanate (PHI) on histone acetylation and apoptosis in hepatocellular carcinoma cell line (SMMC-7721) in vitro.The viability of SMMC-7721 cells was determined by trypan blue exclusion. Apoptotic cells were assessed by TUNEL assay. The proteins of Bcl-2, Procaspase-9, Procaspase-8, Procaspase-3, caspase-9, caspase-3, histone acetylated H3 and H4 were detected by Western blot.Compared with the vehicle control, PHI at 5, 10, 20, 40 and 80 µmol/L reduced the cell viability of SMMC-7721 cells in a concentration-dependent manner. PHI induced apoptosis in SMMC-7721 cells. An increased amount of apoptotic cells was detected after 7 hours exposure to PHI at 10, 20, and 40 µmol/L, 6.9% ± 2.4%, 17.5% ± 4.2% and 54.5% ± 5.4%, respectively, while that of the vehicle control was 4.5% ± 2.3% (P < 0.05). Along with the prolongation of time and increase of dose, the expressions of bcl-2, procaspase-9, procaspase-3 were decreased, that of caspase-9 and caspase-3 was increased. In contrast, alteration of procaspase-8 was not significant at those concentrations. PHI accumulated acetylated histone H3 and H4. After 3 hours exposure to PHI at 10, 20 and 40 µmol/L, the level of histone acetylated H3 was 1.87-, 2.43-, 3.67-fold increased and histone acetylated H4 was 1.29-, 1.45-, and 2.25-fold increased, compared with that of the vehicle control. The protein of histone acetylated H3 and H4 was significantly accumulated after 7 hours exposure.PHI is a new histone deacetylation inhibitor. It may induce accumulation of histone acetylation H3 and H4, inhibit cell growth and induce apoptosis in SMMC-7721 cells via the mitochondrial pathway.
To investigate the effects of PHI on histone acetylation and methylation in hepatocellular carcinoma line SMMC-7721 cells.Apoptosis was measured by TUNNEL assay. Histone methylation and acetylation were detected by Western blot.PHI inhibited cells growth and induced apoptosis. PHI treatment resulted in increased acetylation of histone H3 and H4 , elevated level of histone H3 lysine 4 methylation, and decreased level of histone H3 lysine 9 methylation.PHI can modulate both histone acetylation and methylation, which could remodel chromatin structure. PHI may be a novel anticancer drug.
ABSTRACT We have previously shown that the Drosophila Ste20 kinase encoded by misshapen (msn) is an essential gene in Drosophila development. msn function is required to activate the Drosophila c-Jun N-terminal kinase (JNK), basket (Bsk), to promote dorsal closure of the Drosophila embryo. Later in development, msn expression is required in photoreceptors in order for their axons to project normally. A mammalian homolog of msn, the NCK-interacting kinase (NIK) (recently renamed to mitogen-activated protein kinase kinase kinase kinase 4; Map4k4), has been shown to activate JNK and to bind the SH3 domains of the SH2/SH3 adapter NCK. To determine whether NIK also plays an essential role in mammalian development, we created mice deficient in NIK by homologous recombination at the Nik gene. Nik−/− mice die postgastrulation between embryonic day (E) 9.5 and E10.5. The most striking phenotype in Nik−/− embryos is the failure of mesodermal and endodermal cells that arise from the anterior end of the primitive streak (PS) to migrate to their correct location. As a result Nik−/− embryos fail to develop somites or a hindgut and are truncated posteriorly. Interestingly, chimeric analysis demonstrated that NIK has a cell nonautonomous function in stimulating migration of presomitic mesodermal cells away from the PS and a second cell autonomous function in stimulating the differentiation of presomitic mesoderm into dermomyotome. These findings indicate that despite the large number of Ste20 kinases in mammalian cells, members of this family play essential nonredundant function in regulating specific signaling pathways. In addition, these studies provide evidence that the signaling pathways regulated by these kinases are diverse and not limited to the activation of JNK because mesodermal and somite development are not perturbed in JNK1-, and JNK2-deficient mice.
Densities and viscosities of the binary mixtures of cyclopropanecarboxylic acid with methanol, ethanol, propan-1-ol, and butan-1-ol have been measured at different temperatures (298.15, 308.15, 318.15, 328.15, and 338.15) K and atmospheric pressure over the whole range of compositions. The excess molar volumes were calculated from the experimental data and correlated by the Redlich−Kister polynomial equation. McAllister's three-body and four-body interaction models are also used to correlate the kinematic viscosities of these binary mixtures.
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