Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization

The molecular mechanisms of how primordial adherens junctions (AJs) evolve into spatially separated belt-like AJs and tight junctions (TJs) during epithelial polarization are not well understood. Previously, we reported the establishment of ZO-1/ZO-2–deficient cultured epithelial cells (1[ko]/2[kd] cells), which lacked TJs completely. In the present study, we found that the formation of belt-like AJs was significantly delayed in 1(ko)/2(kd) cells during epithelial polarization. The activation of Rac1 upon primordial AJ formation is severely impaired in 1(ko)/2(kd) cells. Our data indicate that ZO-1 plays crucial roles not only in TJ formation, but also in the conversion from “fibroblastic” AJs to belt-like “polarized epithelial” AJs through Rac1 activation. Furthermore, to examine whether ZO-1 itself mediate belt-like AJ and TJ formation, respectively, we performed a mutational analysis of ZO-1. The requirement for ZO-1 differs between belt-like AJ and TJ formation. We propose that ZO-1 is directly involved in the establishment of two distinct junctional domains, belt-like AJs and TJs, during epithelial polarization

Evolution of Very Massive Population III Stars with Mass Accretion from Pre-Main Sequence to Collapse

We calculate the evolution of zero-metallicity Population III (Pop III) stars whose mass grows from the initial mass of $\sim 1M_{\odot}$ by accreting the surrounding gases. Our calculations cover a whole evolutionary stages from the pre-main sequence, via various nuclear burning stages, through the final core collapse or pair-creation instability phases. We adopt the following stellar mass-dependent accretion rates which are derived from cosmological simulations of early structure formation based on the low mass dark matter halos at redshifts $z \sim 20$: (1) the accretion rates for the first generation (Pop III.1) stars and (2) the rates for zero-metallicity but the second generation (Pop III.2) stars which are affected by radiation from the Pop III.1 stars. For comparison, we also study the evolution with the mass-dependent accretion rates which are affected by radiatibe feedback. We show that the final mass of Pop III.1 stars can be as large as $\sim 1000M_{\odot}$, beyond the mass range ($140 - 300M_{\odot}$) for the pair-instability supernovae. Such massive stars undergo core-collapse to form intermediate-mass black holes, which may be the seeds for merger trees to supermassive black holes. On the other hand, Pop III.2 stars become less massive (\lsim 40 - 60M_{\odot}), being in the mass range of ordinary iron core-collapse stars. Such stars explode and eject heavy elements to contribute to chemical enrichment of the early universe as observed in the abundance patterns of extremely metal-poor stars in the Galactic halo.Comment: 24 pages, 11 figures (15 figure files

Mixed germ cell tumor infiltrating the pineal gland without elevated tumor markers: illustrative case

BACKGROUND: Tumors in the pineal region consist of various histological types, and correct diagnosis from biopsy specimens is sometimes difficult. The authors report the case of a patient with a mixed germ cell tumor infiltrating into the pineal gland despite showing no elevation of tumor markers. OBSERVATIONS: An 18-year-old man complained of headache and nausea and showed disturbance of consciousness. Magnetic resonance imaging showed hydrocephalus associated with a cystic pineal tumor. The patient underwent tumor biopsy followed by endoscopic third ventriculostomy for hydrocephalus in a local hospital. A pineocytoma was diagnosed, and the patient was referred to the authors' hospital for treatment. Concentrations of placental alkaline phosphatase, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin in cerebrospinal fluid were not elevated. However, the authors' review of the tumor specimen revealed some immature cells infiltrating the pineal gland. These cells were positive for AFP, Sal-like protein 4, and octamer-binding transcription factor 3/4; and the diagnosis was changed to mixed germ cell tumor. Chemoradiotherapy was initiated, followed by surgical removal of the residual tumor. LESSONS: Careful examination of all tumor specimens and immunohistochemical analyses are important for accurate diagnosis of pineal tumors

Core-Collapse Very Massive Stars: Evolution, Explosion, and Nucleosynthesis of Population III 500 -- 1000 M⊙M_{\odot} Stars

We calculate evolution, collapse, explosion, and nucleosynthesis of Population III very-massive stars with 500$M_{\odot}$ and 1000$M_{\odot}$. Presupernova evolution is calculated in spherical symmetry. Collapse and explosion are calculated by a two-dimensional code, based on the bipolar jet models. We compare the results of nucleosynthesis with the abundance patterns of intracluster matter, hot gases in M82, and extremely metal-poor stars in the Galactic halo. It was found that both 500$M_{\odot}$ and 1000$M_{\odot}$ models enter the region of pair-instability but continue to undergo core collapse. In the presupernova stage, silicon burning regions occupy a large fraction, more than 20% of the total mass. For moderately aspherical explosions, the patterns of nucleosynthesis match the observational data of both intracluster medium and M82. Our results suggest that explosions of Population III core-collapse very-massive stars contribute significantly to the chemical evolution of gases in clusters of galaxies. For Galactic halo stars, our [O/Fe] ratios are smaller than the observational abundances. However, our proposed scenario is naturally consistent with this outcome. The final black hole masses are $\sim 230M_{\odot}$ and $\sim 500M_{\odot}$ for the $500M_{\odot}$ and 1000$M_{\odot}$ models, respectively. This result may support the view that Population III very massive stars are responsible for the origin of intermediate mass black holes which were recently reported to be discovered.Comment: 49 pages, 49 figure files, accepted to ApJ (2006, 645, 2

Silencing of p53 and CDKN1A establishes sustainable immortalized megakaryocyte progenitor cells from human iPSCs

iPS細胞を用いた人工血小板の作製の効率化に成功 血小板のテイラーメイド医療に向けた一歩. 京都大学プレスリリース. 2021-12-03.Platelet transfusions are critical for severe thrombocytopenia but depend on blood donors. The shortage of donors and the potential of universal HLA-null platelet products have stimulated research on the ex vivo differentiation of human pluripotent stem cells (hPSCs) to platelets. We recently established expandable immortalized megakaryocyte cell lines (imMKCLs) from hPSCs by transducing MYC, BMI1, and BCL-XL (MBX). imMKCLs can act as cryopreservable master cells to supply platelet concentrates. However, the proliferation rates of the imMKCLs vary with the starting hPSC clone. In this study, we reveal from the gene expression profiles of several MKCL clones that the proliferation arrest is correlated with the expression levels of specific cyclin-dependent kinase inhibitors. Silencing CDKN1A and p53 with the overexpression of MBX was effective at stably inducing imMKCLs that generate functional platelets irrespective of the hPSC clone. Collectively, this improvement in generating imMKCLs should contribute to platelet industrialization and platelet biology

一般大学生の心電図所見 : ホルター心電計を中心として

学会報告要

Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling

In the absence of Tara, Trio binds to E-cadherin and increases activation of the E-cadherin transcriptional repressor Tbx3

Role of the RNA-Binding Protein Nrd1 in Stress Granule Formation and Its Implication in the Stress Response in Fission Yeast

We have previously identified the RNA recognition motif (RRM)-type RNA-binding protein Nrd1 as an important regulator of the posttranscriptional expression of myosin in fission yeast. Pmk1 MAPK-dependent phosphorylation negatively regulates the RNA-binding activity of Nrd1. Here, we report the role of Nrd1 in stress-induced RNA granules. Nrd1 can localize to poly(A)-binding protein (Pabp)-positive RNA granules in response to various stress stimuli, including heat shock, arsenite treatment, and oxidative stress. Interestingly, compared with the unphosphorylatable Nrd1, Nrd1DD (phosphorylation-mimic version of Nrd1) translocates more quickly from the cytoplasm to the stress granules in response to various stimuli; this suggests that the phosphorylation of Nrd1 by MAPK enhances its localization to stress-induced cytoplasmic granules. Nrd1 binds to Cpc2 (fission yeast RACK) in a phosphorylation-dependent manner and deletion of Cpc2 affects the formation of Nrd1-positive granules upon arsenite treatment. Moreover, the depletion of Nrd1 leads to a delay in Pabp-positive RNA granule formation, and overexpression of Nrd1 results in an increased size and number of Pabp-positive granules. Interestingly, Nrd1 deletion induced resistance to sustained stresses and enhanced sensitivity to transient stresses. In conclusion, our results indicate that Nrd1 plays a role in stress-induced granule formation, which affects stress resistance in fission yeast

Prognostic Value of Podoplanin Expression in Oral Squamous Cell Carcinoma―A Regression Model Auxiliary to UICC Classification

Podoplanin, a type I transmembrane glycoprotein with an effect of platelet aggregation, has been reported to be one of the possible prognostic factors of oral squamous cell carcinoma (OSCC). However, the biological significance of podoplanin is largely unclear. The aim of this study was to develop a practical model for the prediction of prognosis using the grade of podoplanin expression, and also to evaluate the biological function of podoplanin. Eighty-two specimens of patients with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed. These 82 cases were composed of 66 well-differentiated, 10 moderately differentiated and 6 poorly differentiated OSCC. Podoplanin was successfully immunostained in 78 specimens, and was detected in most cases, but the frequency of positive cells varied. The prognosis of patients with more than 50 % podoplanin-positive tumor cells was significantly poorer than that of the other patients. Multivariate hazards regression analysis suggested that a linear combination of covariates, OSCC patients with more or less than 50 % podoplanin expression, age of more or less than 70 years old, mode of invasion and T3, T4 or T2 versus T1 of the UICC T-stage classification was the most effective model for evaluating the prognosis of OSCC patients. Additionally, podoplanin expression had a significant relationship to UICC clinical stage and the expression of Ki-67. An effective regression model using podoplanin expression was developed for evaluating the prognosis of OSCC and the biological significance of podoplanin was suggested to be associated with the growth and/or progression of OSCC