肉食性カラヌス目カイアシ類の摂餌様式の多様性と分子進化

内容の要約広島大学(Hiroshima University)博士(学術)Doctor of Philosophydoctora

Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

ACE発現ヒトiPS細胞を用いたSARS-CoV-2感染の個人差再現と原因究明. 京都大学プレスリリース. 2021-04-19.Stem cells show gender differences in COVID-19 risk. 京都大学プレスリリース. 2021-04-19.Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. As induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in SARS-CoV-2 infection in vitro. We found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected w SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, and production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ embryonic stem (ES) cells from eight individuals. Male iPS/ES cells were more capable of producing the virus compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro but also are a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences

Photoinduced hydrogen release from hydrogen boride sheets

Hydrogen boride nanosheets (HB sheets) are facilely synthesized via ion-exchange treatment on magnesium diboride (MgB2) in an acetonitrile solution. Optical absorption and fluorescence spectra of HB sheets indicate that their bandgap energy is 2.8 eV. According to first-principles calculations, optical absorption seen at 2.8 eV is assigned to the electron transition between the sigma-bonding states of B and H orbitals. In addition, density functional theory (DFT) calculations suggest the other allowed transition from the s-bonding state of B and H orbitals to the antibonding state with the gap of 3.8 eV. Significant gaseous H-2 release is found to occur only under photoirradiation, which causes the electron transition from the s-bonding state to the antibonding state even under mild ambient conditions. The amount of H-2 released from the irradiated HB sheets is estimated to be 8 wt%, indicating that the sheets have a high H-2-storage capacity compared with previously reported metal H-2-storage materials

精神科における多職種チームに関する評価尺度の開発と妥当性の検討

Currently, no evaluative scale exists to assess the quality of interprofessional teamwork in mental health settings across the globe. As a result, little is known about the detailed process of team development within this setting. The purpose of this study is to develop and validate a global interprofessional scale that assesses teamwork in mental health settings using an international comparative study based in Japan and the United States. This report provides a description of this study and reports progress made to date. Specifically, it outlines work on literature reviews to identify evaluative teamwork tools as well as identify relevant teamwork models and theories. It also outlines plans for empirical work that will be undertaken in both Japan and the United States.首都大学東京学位論文乙第146号 副論

An Up-to-Date Anti-Cancer Treatment Strategy Focusing on HIF-1α Suppression: Its Application for Refractory Ovarian Cancer

Hypoxia inducible factor-1α (HIF-1α) predominantly determines the transcriptional activity of HIF-1, which induces the certain genetic expressions to participate in the proliferation and progression of the tumor. It is supposed that HIF-1α is also an extremely important factor in cancer treatment. Based on the results of our recent analyses using ovarian tumors, which indicated the close association of HIF-1α expression with the acquisition of malignancy and the characterization of histology, we further investigated the possibility of a new strategy of cancer therapy that targeted HIF-1α inhibition in the ovarian carcinoma. The cell line HUOCA-II, which originates from the refractory ovarian clear cell adenocarcinoma, was treated with rapamycin. The inhibitory effect of HIF-1α was analyzed by immunohistochemistry and western blotting. It was demonstrated that inhibition of HIF-1α and vascular endothelial growth factor (VEGF) expressions would lead to the down-regulation of tumor cell proliferation. Interestingly, there was little or no change in GLUT-1 expression by rapamycin administration. Thus, the inhibition of GLUT-1 may also be a key for the new strategy of cancer therapy as well as HIF-1α and VEGF

Alterations in Mucin Expression in Ovarian Mucinous Tumors: Immunohistochemical Analysis of MUC2, MUC5AC, MUC6, and CD10 Expression

The aim of this study was to evaluate the immunohistochemical expression of MUC2, MUC5AC, MUC6, and CD10 in ovarian mucinous adenoma (MA), mucinous borderline tumor (MB), and mucinous adenocarcinoma (MC), and to analyze the relationship between prognosis and these expressions. The expression of MUC2, MUC5AC, MUC6, and CD10 was evaluated by immunohistochemical analysis in 29 cases of MA, 29 cases of MB, and 26 cases of MC and scored based on the percentage of positive cells. Moreover, the ovarian mucinous tumors were classified into 4 phenotypes based on the staining patterns: intestinal, gastrointestinal, gastric, and unclassified patterns. The gastrointestinal pattern and the expression of MUC2 and CD10 increased from MA to MC. Conversely, the gastric pattern and MUC5AC expression decreased from MA to MC. Low MUC2 expression in MC was correlated with a better long-term survival rate. MUC2 expression in MC may be a useful predictor of the clinical outcome. The expression patterns of MUC2, MUC5AC, MUC6, and CD10 indicated that intestinal metaplasia may arise from the gastric-like epithelium in MA and that a close association exists between carcinogenesis and intestinal metaplasia in major ovarian mucinous tumors

Chemogenetic attenuation of cortical seizures in nonhuman primates

「てんかん」の発生を時間的・空間的にピンポイントで抑える画期的な治療法を開発 --世界で初めてサルでの有効性を実証、臨床応用に向け大きく前進--. 京都大学プレスリリース. 2023-03-01.Epilepsy is a disorder in which abnormal neuronal hyperexcitation causes several types of seizures. Because pharmacological and surgical treatments occasionally interfere with normal brain function, a more focused and on-demand approach is desirable. Here we examined the efficacy of a chemogenetic tool—designer receptors exclusively activated by designer drugs (DREADDs)—for treating focal seizure in a nonhuman primate model. Acute infusion of the GABAA receptor antagonist bicuculline into the forelimb region of unilateral primary motor cortex caused paroxysmal discharges with twitching and stiffening of the contralateral arm, followed by recurrent cortical discharges with hemi- and whole-body clonic seizures in two male macaque monkeys. Expression of an inhibitory DREADD (hM4Di) throughout the seizure focus, and subsequent on-demand administration of a DREADD-selective agonist, rapidly suppressed the wide-spread seizures. These results demonstrate the efficacy of DREADDs for attenuating cortical seizure in a nonhuman primate model

A POS-based preordering approach for English-to-Arabic statistical machine translation

In this work, we present a POS-based preordering approach that tackles both long- and short-distance reordering phenomena. Syntactic unlexicalized reordering rules are automatically extracted from a parallel corpus using only word alignment and a source-side language tagging. The reordering rules are used in a deterministic manner; this prevents the decoding speed from being bottlenecked in the reordering procedure. A new approach for both rule filtering and rule application is used to ensure a fast and efficient reordering. The tests performed on the IWSLT2016 English-to-Arabic evaluation benchmark show a noticeable increase in the overall Blue Score for our system over the baseline PSMT system

Ribosomal RNAs are tolerant toward genetic insertions: evolutionary origin of the expansion segments

Ribosomal RNAs (rRNAs), assisted by ribosomal proteins, form the basic structure of the ribosome, and play critical roles in protein synthesis. Compared to prokaryotic ribosomes, eukaryotic ribosomes contain elongated rRNAs with several expansion segments and larger numbers of ribosomal proteins. To investigate architectural evolution and functional capability of rRNAs, we employed a Tn5 transposon system to develop a systematic genetic insertion of an RNA segment 31 nt in length into Escherichia coli rRNAs. From the plasmid library harboring a single rRNA operon containing random insertions, we isolated surviving clones bearing rRNAs with functional insertions that enabled rescue of the E. coli strain (Δ7rrn) in which all chromosomal rRNA operons were depleted. We identified 51 sites with functional insertions, 16 sites in 16S rRNA and 35 sites in 23S rRNA, revealing the architecture of E. coli rRNAs to be substantially flexible. Most of the insertion sites show clear tendency to coincide with the regions of the expansion segments found in eukaryotic rRNAs, implying that eukaryotic rRNAs evolved from prokaryotic rRNAs suffering genetic insertions and selections