Three-Dimensional Lattice Boltzmann Simulation of Two-Phase Flow Containing a Deformable Body with a Viscoelastic Membrane

First published in Communications in Commun. Comput. Phys. in No. 5, 9 (2011), published by Global Science PressThe lattice Boltzmann method (LBM) with an elastic model is applied to the simulation of two-phase flows containing a deformable body with a viscoelastic membrane. The numerical method is based on the LBM for incompressible two-phase fluid flows with the same density. The body has an internal fluid covered by a viscoelastic membrane of a finite thickness. An elastic model is introduced to the LBM in order to determine the elastic forces acting on the viscoelastic membrane of the body. In the present method, we take account of changes in surface area of the membrane and in total volume of the body as well as shear deformation of the membrane. By using this method, we calculate two problems, the behavior of an initially spherical body under shear flow and the motion of a body with initially spherical or biconcave discoidal shape in square pipe flow. Calculated deformations of the body (the Taylor shape parameter) for various shear rates are in good agreement with other numerical results. Moreover, tank-treading motion, which is a characteristic motion of viscoelastic bodies in shear flows, is simulated by the present method.ArticleCommunications in Computational Physics. 9(5):1397-1413 (2011)journal articl

Lattice Boltzmann simulation of nucleate pool boiling in saturated liquid

First published in Communications in Commun. Comput. Phys. in No. 5, 9 (2011), published by Global Science PressA thermal lattice Boltzmann method (LBM) for two-phase fluid flows in nucleate pool boiling process is proposed. In the present method, a new function for heat transfer is introduced to the isothermal LBM for two-phase immiscible fluids with large density differences. The calculated temperature is substituted into the pressure tensor, which is used for the calculation of an order parameter representing two phases so that bubbles can be formed by nucleate boiling. By using this method, two-dimensional simulations of nucleate pool boiling by a heat source on a solid wall are carried out with the boundary condition for a constant heat flux. The flow characteristics and temperature distribution in the nucleate pool boiling process are obtained. It is seen that a bubble nucleation is formed at first and then the bubble grows and leaves the wall, finally going up with deformation by the buoyant effect. In addition, the effects of the gravity and the surface wettability on the bubble diameter at departure are numerically investigated. The calculated results are in qualitative agreement with other theoretical predictions with available experimental data.ArticleCommunications in Computational Physics. 9(5):1347-1361 (2011)journal articl

Molecular Dynamics Simulation of Diffusion Behavior in Liquid Sn and Pb

This study aimed to clarify the effect of a unique structure with a "shoulder,"which represents a hump on the high wave vector side of the first peak of static structure factor, in liquid Sn (liq-Sn) on the self-diffusion behavior through molecular dynamics (MD) simulation. The MD simulations of liq-Sn at 573 K and liquid Pb (liq-Pb) at 773 K were performed for comparison. The former and latter were selected as element with and without shoulder structure and reliable self-diffusion coefficients in liquid have been measured in both elements. The calculated self-diffusion coefficients of liq-Sn and liq-Pb were reproduced as the same order of magnitude with the referred reliable data of diffusion coefficients, which were obtained by experiments on the ground. The microscopic diffusion behavior of liq-Sn is unlike that of the hard-sphere model because the atoms become sluggish in the range that corresponds to the shoulder appearing in the pair distribution function of liq-Sn as well as in the structure factor of liq-Sn based on the local atomic configurations and time-series analyses of individual atoms. Therefore, the velocity autocorrelation function (VACF) converges to zero more rapidly than that of liq-Pb, and it is reproduced by the hard-sphere model. However, the macroscopic diffusion behavior of liq-Sn expressed by the self-diffusion coefficient is the same as that of the hard-sphere model with the non-correlation of the VACF in the long time

Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling

The metabolic processes of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3 signalling are involved in cell migration. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a PI(4,5)P2-binding protein, regulates cancer cell migration. PRIP overexpression in MCF-7 and BT-549 human breast cancer cells inhibited cell migration in vitro and metastasis development in vivo. Overexpression of the PRIP pleckstrin homology domain, a PI(4,5)P2 binding motif, in MCF-7 cells caused significant suppression of cell migration. Consistent with these results, in comparison with wild-type cells, Prip-deficient mouse embryonic fibroblasts exhibited increased cell migration, and this was significantly attenuated upon transfection with a siRNA targeting p110α, a catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI(3,4,5)P3 production was decreased in Prip-overexpressing MCF-7 and BT-549 cells. PI3K binding to PI(4,5)P2 was significantly inhibited by recombinant PRIP in vitro, and thus the activity of PI3K was downregulated. Collectively, PRIP regulates the production of PI(3,4,5)P3 from PI(4,5)P2 by PI3K, and the suppressor activity of PRIP in PI(4,5)P2 metabolism regulates the tumour migration, suggesting PRIP as a promising target for protection against metastatic progression.This work was supported by grants from JSPS KAKENHI Grant Numbers JP15K20372, JP17K11644, JP16K11503

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

Phenotypes of pain behavior in phospholipase C-related but catalytically inactive protein type 1 knockout mice

Phospholipase C-related inactive protein (PRIP) plays important roles in trafficking to the plasma membrane of GABAA receptor, which is involved in the dominant inhibitory neurotransmission in the spinal cord and plays an important role in nociceptive transmission. However, the role of PRIP in pain sensation remains unknown. In this study, we investigated the phenotypes of pain behaviors in PRIP type 1 knockout (PRIP-1 -/- ) mice. The mutant mice showed hyperalgesic responses in the second phase of the formalin test and the von Frey test as compared with those in wild-type mice. In situ hybridization studies of GABAA receptors revealed significantly decreased expression of γ2 subunit mRNA in the dorsal and ventral horns of the spinal cord in PRIP-1 -/- mice, but no difference in α1 subunit mRNA expression. β2 subunit mRNA expression was significantly higher in PRIP-1 -/- mice than in wild-type mice in all areas of the spinal cord. On the other hand, the slow decay time constant for the spontaneous inhibitory current was significantly increased by treatment with diazepam in wild-type mice, but not in PRIP-1 -/- mice. These results suggest that PRIP-1 -/- mice exhibit the changes of the function and subunits expression of GABAA receptor in the spinal cord, which may be responsible for abnormal pain sensation in these mice

Two regulatory steps of ER-stress sensor Ire1 involving its cluster formation and interaction with unfolded proteins

Chaperone protein BiP binds to Ire1 and dissociates in response to endoplasmic reticulum (ER) stress. However, it remains unclear how the signal transducer Ire1 senses ER stress and is subsequently activated. The crystal structure of the core stress-sensing region (CSSR) of yeast Ire1 luminal domain led to the controversial suggestion that the molecule can bind to unfolded proteins. We demonstrate that, upon ER stress, Ire1 clusters and actually interacts with unfolded proteins. Ire1 mutations that affect these phenomena reveal that Ire1 is activated via two steps, both of which are ER stress regulated, albeit in different ways. In the first step, BiP dissociation from Ire1 leads to its cluster formation. In the second step, direct interaction of unfolded proteins with the CSSR orients the cytosolic effector domains of clustered Ire1 molecules

Massively parallel single-cell genomics of microbiomes in rice paddies

世界初のイネ根圏微生物叢の網羅的1細胞ゲノム解析に成功 --コメ生産現場が抱える問題のデータベース化に向けて--. 京都大学プレスリリース. 2022-11-09.Plant growth-promoting microbes (PGPMs) have attracted increasing attention because they may be useful in increasing crop yield in a low-input and sustainable manner to ensure food security. Previous studies have attempted to understand the principles underlying the rhizosphere ecology and interactions between plants and PGPMs using ribosomal RNA sequencing, metagenomic sequencing, and genome-resolved metagenomics; however, these approaches do not provide comprehensive genomic information for individual species and do not facilitate detailed analyses of plant–microbe interactions. In the present study, we developed a pipeline to analyze the genomic diversity of the rice rhizosphere microbiome at single-cell resolution. We isolated microbial cells from paddy soil and determined their genomic sequences by using massively parallel whole-genome amplification in microfluidic-generated gel capsules. We successfully obtained 3, 237 single-amplified genomes in a single experiment, and these genomic sequences provided insights into microbial functions in the paddy ecosystem. Our approach offers a promising platform for gaining novel insights into the roles of microbes in the rice rhizomicrobiome and to develop microbial technologies for improved and sustainable rice production

Effects of beta-adrenergic blocking agents on specific binding of [3H]D-Ala2-Met5-enkephalinamide and [3H]naloxone.

To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated.</p

In-Stent Yellow Plaque at 1 Year After Implantation Is Associated With Future Event of Very Late Stent Failure The DESNOTE Study (Detect the Event of Very late Stent Failure From the Drug-Eluting Stent Not Well Covered by Neointima Determined by Angioscopy)

AbstractObjectivesThis study examined whether coronary angioscopy-verified in-stent yellow plaque at 1 year after drug-eluting stent (DES) implantation is associated with future event of very late stent failure (VLSF).BackgroundAtherosclerosis detected as yellow plaque by angioscopy has been associated with future events of acute coronary syndrome. Development of in-stent neoatherosclerosis is a probable mechanism of VLSF.MethodsThis study included 360 consecutive patients who received successful angioscopic examination at 1 year after implantation of a DES. They were clinically followed up for VLSF defined as cardiac death, acute myocardial infarction or unstable angina, or need for revascularization associated with the stent site.ResultsThe follow-up interval was 1,558 ± 890 days (4.3 ± 2.4 years). The incidence of VLSF was significantly higher in the patients with yellow plaque than in those without (8.1% vs. 1.6%; log rank p = 0.02). Multivariable analysis revealed the presence of yellow plaque (hazard ratio [HR]: 5.38; p = 0.02) and absence of statin therapy (HR: 3.25; p = 0.02) as risks of VLSF.ConclusionsIn-stent atherosclerosis evaluated by yellow plaque at 1 year after the implantation of DES and the absence of statin therapy were risks of VLSF. The underlying mechanism of VLSF appeared to be the progression of atherosclerosis as demonstrated by the yellow plaque