Active Brownian Motion in Threshold Distribution of a Coulomb Blockade Model

Randomly-distributed offset charges affect the nonlinear current-voltage property via the fluctuation of the threshold voltage of Coulomb blockade arrays. We analytically derive the distribution of the threshold voltage for a model of one-dimensional locally-coupled Coulomb blockade arrays, and propose a general relationship between conductance and the distribution. In addition, we show the distribution for a long array is equivalent to the distribution of the number of upward steps for aligned objects of different height. The distribution satisfies a novel Fokker-Planck equation corresponding to active Brownian motion. The feature of the distribution is clarified by comparing it with the Wigner and Ornstein-Uhlenbeck processes. It is not restricted to the Coulomb blockade model, but instructive in statistical physics generally.Comment: 4pages, 3figure

Multi-locus sequence typing of Salmonella enterica subsp. enterica serovar Enteritidis strains in Japan between 1973 and 2004

Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) was responsible for a worldwide pandemic during the 1980s and 1990s; however, changes in the dominant lineage before and after this event remain unknown. This study determined S. Enteritidis lineages before and after this pandemic event in Japan using multilocus sequence typing (MLST). Thirty S. Enteritidis strains were collected in Japan between 1973 and 2004, consisting of 27 human strains from individual episodes, a bovine strain, a liquid egg strain and an eggshell strain. Strains showed nine phage types and 17 pulsed-field profiles with pulsed-field gel electrophoresis. All strains had homologous type 11 sequences without any nucleotide differences in seven housekeeping genes. These MLST results suggest that S. Enteritidis with the diversities revealed by phage typing and pulsed-field profiling has a highly clonal population. Although type 11 S. Enteritidis may exhibit both pleiotropic surface structure and pulsed-field type variation, it is likely to be a stable lineage derived from an ancestor before the 1980s and/or 1990s pandemic in Japan

GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region

The RET tyrosine kinase receptor and its ligand, glial cell line-derived neurotrophic factor (GDNF) are critical regulators of renal and neural development. It has been demonstrated that RET activates a variety of downstream signaling cascades, including the RAS/mitogen-activated protein kinase and phosphatidylinositol-3-kinase(PI3-K)/AKT pathways. However, nuclear targets specific to RET-triggered signaling still remain elusive. We have previously identified a novel zinc finger protein, GZF1, whose expression is induced during GDNF/RET signaling and may play a role in renal branching morphogenesis. Here, we report the DNA binding property of GZF1 and its potential target gene. Using the cyclic amplification and selection of targets technique, the consensus DNA sequence to which GZF1 binds was determined. This sequence was found in the 5′ regulatory region of the HOXA10 gene. Electrophoretic mobility shift assay revealed that GZF1 specifically binds to the determined consensus sequence and suppresses transcription of the luciferase gene from the HOXA10 gene regulatory element. These findings thus suggest that GZF1 may regulate the spatial and temporal expression of the HOXA10 gene which plays a role in morphogenesis

The Nature of Ultra-Luminous Compact X-Ray Sources in Nearby Spiral Galaxies

Studies were made of ASCA spectra of seven ultra-luminous compact X-ray sources (ULXs) in nearby spiral galaxies; M33 X-8 (Takano et al. 1994), M81 X-6 (Fabbiano 1988b; Kohmura et al. 1994; Uno 1997), IC 342 Source 1 (Okada et al. 1998), Dwingeloo 1 X-1 (Reynolds et al. 1997), NGC 1313 Source B (Fabbiano & Trinchieri 1987; Petre et al. 1994), and two sources in NGC 4565 (Mizuno et al. 1999). With the 0.5--10 keV luminosities in the range 10^{39-40} ergs/s, they are thought to represent a class of enigmatic X-ray sources often found in spiral galaxies. For some of them, the ASCA data are newly processed, or the published spectra are reanalyzed. For others, the published results are quoted. The ASCA spectra of all these seven sources have been described successfully with so called multi-color disk blackbody (MCD) emission arising from optically-thick standard accretion disks around black holes. Except the case of M33 X-8, the spectra do not exhibit hard tails. For the source luminosities not to exceed the Eddington limits, the black holes are inferred to have rather high masses, up to ~100 solar masses. However, the observed innermost disk temperatures of these objects, Tin = 1.1--1.8 keV, are too high to be compatible with the required high black-hole masses, as long as the standard accretion disks around Schwarzschild black holes are assumed. Similarly high disk temperatures are also observed from two Galactic transients with superluminal motions, GRO 1655-40 and GRS 1915+105. The issue of unusually high disk temperature may be explained by the black hole rotation, which makes the disk get closer to the black hole, and hence hotter.Comment: submitted to ApJ, December 199

Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin.

In clathrin-mediated endocytosis (CME), specificity and selectivity for cargoes are thought to be tightly regulated by cargo-specific adaptors for distinct cellular functions. Here, we show that the actin-binding protein girdin is a regulator of cargo-selective CME. Girdin interacts with dynamin 2, a GTPase that excises endocytic vesicles from the plasma membrane, and functions as its GTPase-activating protein. Interestingly, girdin depletion leads to the defect in clathrin-coated pit formation in the center of cells. Also, we find that girdin differentially interacts with some cargoes, which competitively prevents girdin from interacting with dynamin 2 and confers the cargo selectivity for CME. Therefore, girdin regulates transferrin and E-cadherin endocytosis in the center of cells and their subsequent polarized intracellular localization, but has no effect on integrin and epidermal growth factor receptor endocytosis that occurs at the cell periphery. Our results reveal that girdin regulates selective CME via a mechanism involving dynamin 2, but not by operating as a cargo-specific adaptor

Regulation of Transgene Expression in Tumor Cells by Exploiting Endogenous Intracellular Signals

Recently, we have proposed a novel strategy for a cell-specific gene therapy system based on responses to intracellular signals. In this system, an intracellular signal that is specifically and abnormally activated in the diseased cells is used for the activation of transgene expression. In this study, we used protein kinase C (PKC)α as a trigger to activate transgene expression. We prepared a PKCα-responsive polymer conjugate [PPC(S)] and a negative control conjugate [PPC(A)], in which the phosphorylation site serine (Ser) was replaced with alanine (Ala). The phosphorylation for polymer/DNA complexes was determined with a radiolabel assay using [γ-32P]ATP. PPC(S)/DNA complexes were phosphorylated by the addition of PKCα, but no phosphorylation of the PPC(A)/DNA complex was observed. Moreover, after microinjection of polymer/GFP-encoding DNA complexes into HepG2 cells at cation/anion (C/A) ratios of 0.5 to 2.0, significant expression of GFP was observed in all cases using PPC(S)/DNA complexes, but no GFP expression was observed in the negative control PPC(A)/DNA complex-microinjected cells at C/A ratios of 1.0 and 2.0. On the other hand, GFP expression from PPC(S)/DNA complexes was completely suppressed in cells pretreated with PKCα inhibitor (Ro31-7549). These results suggest that our gene regulation system can be used for tumor cell-specific expression of a transgene in response to PKCα activity

大学ダンス授業における鏡の利用が動作習得に関する自己評価に及ぼす影響

本研究は、ダンス授業における鏡の利用の有無が動作習得に及ぼす影響について、エアロビクスダンス実施後の自己評価から比較・検討した。対象は、東京都内私立大学に所属する一般教養体育のダンス授業の受講者18名とし、ビデオで自身の動きを見る前「自身の動きの感覚」の自己評価と、ビデオで自身の動きを見た後「先生との比較」の自己評価および「ダンスの授業では鏡を利用した方が良いと思うか」についてのアンケート調査を行った。調査の結果、「自身の動きの感覚」についての自己評価においては、鏡の有無によっての自己評価に有意な差は認められなかったが、「先生との比較」についての自己評価において、鏡ありの自己評価が有意に高い結果を示した。これらのことから、動きやすさや振りの真似のしやすさ、さらに鏡利用の有無についてのメリット・デメリットをふまえても、ダンス授業において鏡を利用することは、ダンスの動作習得に有効である可能性が示唆された

A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2

The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2–3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARS-CoV-2 and may be useful for development of antiviral therapies

Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities

We developed a simple algorithm, i-Score (inhibitory-Score), to predict active siRNAs by applying a linear regression model to 2431 siRNAs. Our algorithm is exclusively comprised of nucleotide (nt) preferences at each position, and no other parameters are taken into account. Using a validation dataset comprised of 419 siRNAs, we found that the prediction accuracy of i-Score is as good as those of s-Biopredsi, ThermoComposition21 and DSIR, which employ a neural network model or more parameters in a linear regression model. Reynolds and Katoh also predict active siRNAs efficiently, but the numbers of siRNAs predicted to be active are less than one-eighth of that of i-Score. We additionally found that exclusion of thermostable siRNAs, whose whole stacking energy (ΔG) is less than −34.6 kcal/mol, improves the prediction accuracy in i-Score, s-Biopredsi, ThermoComposition21 and DSIR. We also developed a universal target vector, pSELL, with which we can assay an siRNA activity of any sequence in either the sense or antisense direction. We assayed 86 siRNAs in HEK293 cells using pSELL, and validated applicability of i-Score and the whole ΔG value in designing siRNAs