590 results on '"Yohei Watanabe"'
Search Results
102. Adaptively secure revocable hierarchical IBE from k-linear assumption
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Atsushi Takayasu, Yohei Watanabe, and Keita Emura
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Scheme (programming language) ,Theoretical computer science ,Delegation ,business.industry ,Applied Mathematics ,media_common.quotation_subject ,020206 networking & telecommunications ,Cryptography ,0102 computer and information sciences ,02 engineering and technology ,Extension (predicate logic) ,Encryption ,01 natural sciences ,Computer Science Applications ,Public-key cryptography ,010201 computation theory & mathematics ,Simple (abstract algebra) ,Pairing ,0202 electrical engineering, electronic engineering, information engineering ,business ,computer ,computer.programming_language ,Mathematics ,media_common - Abstract
Revocable identity-based encryption (RIBE) is an extension of IBE with an efficient key revocation mechanism. Revocable hierarchical IBE (RHIBE) is its further extension with key delegation functionality. Although there are various adaptively secure pairing-based RIBE schemes, all known hierarchical analogues only satisfy selective security. In addition, the currently known most efficient adaptively secure RIBE and selectively secure RHIBE schemes rely on non-standard assumptions, which are referred to as the augmented DDH assumption and q-type assumptions, respectively. In this paper, we propose a simple but effective design methodology for RHIBE schemes. We provide a generic design framework for RHIBE based on an HIBE scheme with a few properties. Fortunately, several state-of-the-art pairing-based HIBE schemes have the properties. In addition, our construction preserves the sizes of master public keys, ciphertexts, and decryption keys, as well as the complexity assumptions of the underlying HIBE scheme. Thus, we obtain the first RHIBE schemes with adaptive security under the standard k-linear assumption. We prove adaptive security by developing a new proof technique for RHIBE. Due to the compactness-preserving construction, the proposed R(H)IBE schemes have similar efficiencies to the most efficient existing schemes.
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- 2021
103. Efficient revocable identity-based encryption with short public parameters
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Yohei Watanabe, Jae Hong Seo, and Keita Emura
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Theoretical computer science ,General Computer Science ,Revocation ,business.industry ,Computer science ,Reliability (computer networking) ,Cryptography ,Context (language use) ,0102 computer and information sciences ,02 engineering and technology ,Encryption ,01 natural sciences ,Theoretical Computer Science ,010201 computation theory & mathematics ,0202 electrical engineering, electronic engineering, information engineering ,Key (cryptography) ,020201 artificial intelligence & image processing ,business - Abstract
Revocation functionality is vital to real-world cryptographic systems for managing their reliability. In the context of identity-based encryption (IBE), Boldyreva, Goyal, and Kumar (ACM CCS 2008) first showed an efficient revocation method for IBE, and such an IBE scheme with the scalable revocation method is called revocable IBE (RIBE). Seo and Emura (PKC 2013) introduced a new security notion, called decryption key exposure resistance (DKER), which is a desirable security notion for RIBE. However, all existing RIBE schemes that achieve adaptive security with DKER require long public parameters or composite-order bilinear groups. In this paper, we first show an RIBE scheme that (1) satisfies adaptive security; (2) achieves DKER; (3) realizes constant-size public parameters; and (4) is constructed over prime-order bilinear groups. Our core technique relies on Seo and Emura's one (PKC 2013), which transform the Waters IBE (EUROCRYPT 2005) to the corresponding RIBE scheme. Specifically, we construct an IBE scheme that satisfies constant-size public parameters over prime-order groups and some requirements for the Seo-Emura technique, and then transform the IBE scheme to an RIBE scheme. We also discuss how to extend the proposed RIBE scheme to a chosen-ciphertext secure one and server-aided one (ESORICS 2015).
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- 2021
104. Efficient Dynamic Searchable Encryption with Forward Privacy under the Decent Leakage
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Yohei Watanabe, Kazuma Ohara, Mitsugu Iwamoto, and Kazuo Ohta
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- 2022
105. Systemic inflammation score as a preoperative prognostic factor for patients with pT2-T4 resectable gastric cancer: a retrospective study
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Takuro Matsumoto, Shinji Ohki, Leo Yamada, Takeshi Tada, Hiroyuki Hanayama, Yohei Watanabe, Suguru Hayase, Hirokazu Okayama, Wataru Sakamoto, Tomoyuki Momma, Zenichiro Saze, and Koji Kono
- Abstract
BackgroundSystemic inflammation has been reported to be associated with cancer progression and metastasis. Systemic inflammation score (SIS), calculated from preoperative serum albumin level and lymphocyte-to-monocyte ratio, has been shown to be a novel prognostic factor for several types of tumors. This study aimed to evaluate the prognostic value of the SIS in patients with pT2-4 resectable gastric cancer (GC).MethodsTotal 97 patients with pT2-4 GC who underwent curative surgery between 2009 and 2015 in Fukushima Medical University Hospital were included. We performed univariate and multivariate analyses to evaluate the usefulness of preoperative SIS and other prognostic factors for relapse-free survival (RFS) and overall survival (OS).ResultsThe higher SIS score was associated with undifferentiated cancer and recurrence. Univariate analysis of RFS identified deeper tumor invasion and higher SIS were significant risk factors and multivariate analysis revealed that both of them were independent prognostic factors for RFS. As for OS, age, tumor invasion, SIS and LNR were significantly correlated with RFS. In multivariate analysis, tumor invasion, SIS and LNR were independent prognostic factors for OS.ConclusionsSIS was an independent prognostic factor for RFS and OS in pT2-4 resectable gastric cancer patients who underwent curative gastrectomy.
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- 2022
106. Visualization of probiotic-mediated Ca2+ signaling in intestinal epithelial cells in vivo
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Takahiro Adachi, Shigeru Kakuta, Yoshiko Aihara, Tomonori Kamiya, Yohei Watanabe, Naomi Osakabe, Naoki Hasato, Atsushi Miyawaki, Soichiro Yoshikawa, Takako Usami, Hajime Karasuyama, Hiromi Kimoto-Nira, Kazuhiro Hirayama, and Noriko Tsuji
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Lactococcus ,imaging ,Immune responses ,Ca2+ signaling ,gut ,intestine ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Probiotics, such as lactic acid bacteria (LAB) and Bacillus subtilis var. natto, have been shown to modulate immune responses. It is important to understand how probiotic bacteria impact intestinal epithelial cells (IECs), because IECs are the first line of defense at the mucosal surface barrier and their activities substantially affect the gut microenvironment and immunity. However, to date, their precise mechanism remains unknown due to a lack of analytical systems available for live animal models. Recently, we generated a conditional Ca2+ biosensor Yellow Cameleon (YC3.60) transgenic mouse line and established 5D (x, y, z, time, and Ca2+) intravital imaging systems of lymphoid tissues including those in Peyer’s patches and bone marrow. In the present study, we further advance our intravital imaging system for intestinal tracts to visualize IEC responses against orally administrated food compounds in real time. Using this system, heat-killed Bacillus subtilis natto, a probiotic TTCC012 strain, is shown to directly induce Ca2+ signaling in IECs in mice housed under specific pathogen-free conditions. In contrast, this activation is not observed in the Lactococcus lactis strain C60; however, when we generate germ-free YC3.60 mice and observe the LAB stimulation of IECs in the absence of gut microbiota, C60 is capable of inducing Ca2+ signaling. This is the first study to successfully visualize the direct effect of probiotics on IECs in live animals. These data strongly suggest that probiotic strains stimulate IECs under physiological conditions, and that their activity is affected by the microenvironment of the small intestine, such as commensal bacteria.
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- 2016
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107. Neoadjuvant Chemotherapy Induces IL34 Signaling and Promotes Chemoresistance via Tumor-Associated Macrophage Polarization in Esophageal Squamous Cell Carcinoma
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Takuro Matsumoto, Prajwal Neupane, Aung Kyi Thar Min, Motonobu Saito, Katsuharu Saito, Tomoyuki Momma, Zenichiro Saze, Shinji Ohki, Naoto Yamauchi, Suguru Hayase, Hiroshi Nakano, Hirokazu Okayama, Eisei Endo, Leo Yamada, Kosaku Mimura, Hiroyuki Hanayama, Yasuyuki Kanke, Yohei Watanabe, Hiromasa Ohira, Shotaro Nakajima, Koji Kono, Koji Kase, and Akinao Kaneta
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Male ,0301 basic medicine ,Cancer Research ,Esophageal Neoplasms ,medicine.medical_treatment ,Antigens, Differentiation, Myelomonocytic ,Receptors, Cell Surface ,Kaplan-Meier Estimate ,Tumor-associated macrophage ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Antigens, CD ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Tumor-Associated Macrophages ,Biopsy ,Tumor Microenvironment ,Humans ,Medicine ,neoplasms ,Molecular Biology ,Aged ,Cisplatin ,Tumor microenvironment ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,Interleukins ,Macrophage Activation ,Middle Aged ,Neoadjuvant Therapy ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,Drug Resistance, Neoplasm ,Cell culture ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Cancer research ,Female ,Fluorouracil ,business ,CD163 ,Signal Transduction ,medicine.drug - Abstract
The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (n = 33) or did not receive NAC (n = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163+ TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163+ TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC. Implications: The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.
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- 2021
108. Key bacterial taxa and metabolic pathways affecting gut short-chain fatty acid profiles in early life
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Taeko Hara, Satoshi Matsumoto, Kana Yahagi, Hiroshi Mori, Ken Kurokawa, Takahiro Matsuki, Hirokazu Tsuji, Hoshitaka Matsumoto, Yohei Watanabe, Naoki Tsukuda, and Koichi Higashi
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Butyrate ,Gut flora ,Microbiology ,digestive system ,Fucose ,Article ,Microbial ecology ,03 medical and health sciences ,chemistry.chemical_compound ,fluids and secretions ,Bacterial genetics ,Humans ,Formate ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Clostridiales ,biology ,Milk, Human ,030306 microbiology ,Short-chain fatty acid ,digestive, oral, and skin physiology ,Infant ,biology.organism_classification ,Fatty Acids, Volatile ,Gastrointestinal Microbiome ,Metabolic pathway ,chemistry ,Biochemistry ,Propionate ,Female ,Microbiome ,Metabolic Networks and Pathways - Abstract
Infant gut microbiota development affects the host physiology throughout life, and short-chain fatty acids (SCFAs) are promising key metabolites mediating microbiota-host relationships. Here, we investigated dense longitudinally collected faecal samples from 12 subjects during the first 2 years (n = 1048) to identify early life gut SCFA patterns and their relationships with the microbiota. Our results revealed three distinct phases of progression in the SCFA profiles: early phase characterised by low acetate and high succinate, middle-phase characterised by high lactate and formate and late-phase characterised by high propionate and butyrate. Assessment of the SCFA–microbiota relationships revealed that faecal butyrate is associated with increased Clostridiales and breastfeeding cessation, and that diverse and personalised assemblage of Clostridiales species possessing the acetyl-CoA pathway play major roles in gut butyrate production. We also found an association between gut formate and some infant-type bifidobacterial species, and that human milk oligosaccharides (HMO)-derived fucose is the substrate for formate production during breastfeeding. We identified genes upregulated in fucose and fucosylated HMO utilisation in infant-type bifidobacteria. Notably, bifidobacteria showed interspecific and intraspecific variation in the gene repertoires, and cross-feeding of fucose contributed to gut formate production. This study provides an insight into early life SCFA–microbiota relationships, which is an important step for developing strategies for modulating lifelong health.
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- 2021
109. Culm dynamics of dwarf bamboo (Sasa kurilensis Makino & Shibata) in relation to forest canopy conditions in beech forests
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Tomohiro Itabashi, Shinji Akada, Kiyoshi Ishida, Shirou Ishibashi, Misuzu Ohno, Kiyoshi Matsui, Yohei Watanabe, Tohru Nakashizuka, and Akifumi Makita
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- 2023
110. Lacking Interleukin-10 Regulates the Inflammasome-driven Alveolar Bone Loss
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Takashi Saito, Tomoko Kurita-Ochiai, Ryoki Kobayashi, Noriko M. Tsuji, Yohei Watanabe, Tetsuro Kono, Hiroyuki Okada, and Miyuki Toda
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Interleukin 10 ,Chemistry ,Cancer research ,medicine ,Inflammasome ,Dental alveolus ,medicine.drug - Published
- 2020
111. Stimulation of dysregulated IFN-β responses by aberrant SARS-CoV-2 small viral RNAs
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Yasuha Arai, Itaru Yamanaka, Toru Okamoto, Ayana Isobe, Naomi Nakai, Naoko Kamimura, Tatsuya Suzuki, Tomo Daidoji, Takao Ono, Takaaki Nakaya, Kazuhiko Matsumoto, Daisuke Okuzaki, and Yohei Watanabe
- Abstract
Patients with severe COVID-19 exhibit a cytokine storm characterized by greatly elevated levels of cytokines during worsening disease. Despite this, the interferon (IFN) response is delayed, contributing to disease progression. Here, we report that SARS-CoV-2 generates excessive amounts of small viral RNAs (svRNAs) encoding exact 5′ ends of positive-sense genes in human cells, whereas significantly fewer similar svRNAs are produced by endemic human coronaviruses (OC43 and 229E). SARS-CoV-2 5′ end svRNAs are RIG-I agonists associated with IFN-beta expression in later stages of infection. The first 60-nt ends bearing duplex structures and 5′-triphosphates are responsible for immune-stimulation. The 5′ end svRNAs were also produced during infection ex vivo and in vivo. The delta variant retains the robust 5′ end svRNA production of the parental strain, whereas omicron (BA.1 and BA.2) produces little of these erroneous svRNAs. We propose that RIG-I activation by accumulated 5′ end svRNAs overcomes the initial IFN antagonistic ability of viral proteins and contributes to drive late over-exuberant IFN production leading to the development of severe COVID-19 and suggest that evolutionary modification of SARS-CoV-2 5′ end svRNA production may correlate with the reduced disease severity likely seen with omicron (BA.1 and BA.2).
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- 2022
112. Stimulation of dysregulated IFN-β responses by aberrant SARS-CoV-2 small viral RNAs acting as RIG-I agonists
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Yohei Watanabe, Yasuha Arai, Itaru Yamanaka, Toru Okamoto, Ayana Isobe, Naomi Nakai, Naoko Kamimura, Tomo Daidoji, Takao Ono, Takaaki Nakaya, Kazuhiko Matsumoto, and Daisuke Okuzaki
- Abstract
Patients with severe COVID-19 exhibit a cytokine storm characterized by greatly elevated levels of cytokines during worsening disease1-4. Despite this, the interferon (IFN) response is delayed, contributing to disease progression5. Here, we report that SARS-CoV-2 generates excessive amounts of small viral RNAs (svRNAs) encoding exact 5′ ends of positive sense genes in human cells, whereas significantly fewer similar svRNAs are produced by endemic human coronaviruses (OC43 and 229E). SARS-CoV-2 5′ end svRNAs are potent RIG-I agonists associated with IFN-β expression in later stages of infection. The first 60-nt ends bearing duplex structures and 5′-triphosphates are responsible for immune-stimulation. The 5′ end svRNAs were also produced during infection in vivo. The delta variant retains the robust 5’ end svRNA production of the parental strain, whereas omicron no longer produces these erroneous svRNAs. We propose that RIG-I activation by accumulated 5′ end svRNAs overcomes the initial IFN antagonistic ability of viral proteins and drives late over-exuberant IFN production leading to the development of severe COVID-19 and suggest that evolutionary modification of SARS-CoV-2 5’ end svRNA production may correlate with the reduced disease severity likely seen with omicron.
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- 2022
113. Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses.
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Yasuha Arai, Norihito Kawashita, Tomo Daidoji, Madiha S Ibrahim, Emad M El-Gendy, Tatsuya Takagi, Kazuo Takahashi, Yasuo Suzuki, Kazuyoshi Ikuta, Takaaki Nakaya, Tatsuo Shioda, and Yohei Watanabe
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
A major determinant in the change of the avian influenza virus host range to humans is the E627K substitution in the PB2 polymerase protein. However, the polymerase activity of avian influenza viruses with a single PB2-E627K mutation is still lower than that of seasonal human influenza viruses, implying that avian viruses require polymerase mutations in addition to PB2-627K for human adaptation. Here, we used a database search of H5N1 clade 2.2.1 virus sequences with the PB2-627K mutation to identify other polymerase adaptation mutations that have been selected in infected patients. Several of the mutations identified acted cooperatively with PB2-627K to increase viral growth in human airway epithelial cells and mouse lungs. These mutations were in multiple domains of the polymerase complex other than the PB2-627 domain, highlighting a complicated avian-to-human adaptation pathway of avian influenza viruses. Thus, H5N1 viruses could rapidly acquire multiple polymerase mutations that function cooperatively with PB2-627K in infected patients for optimal human adaptation.
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- 2016
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114. Disturbance in the Mucosa-Associated Commensal Bacteria Is Associated with the Exacerbation of Chronic Colitis by Repeated Psychological Stress; Is That the New Target of Probiotics?
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Sohei Arase, Yohei Watanabe, Hiromi Setoyama, Noriko Nagaoka, Mitsuhisa Kawai, and Satoshi Matsumoto
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Medicine ,Science - Abstract
Psychological stress can exacerbate inflammatory bowel disease. However, the mechanisms underlying how psychological stress affects gut inflammation remain unclear. Here, we focused on the relationship between changes in the microbial community of mucosa-associated commensal bacteria (MACB) and mucosal immune responses induced by chronic psychological stress in a murine model of ulcerative colitis. Furthermore, we examined the effect of probiotic treatment on exacerbated colitis and MACB composition changes induced by chronic psychological stress. Repeated water avoidance stress (rWAS) in B6-Tcra-/- mice severely exacerbated colitis, which was evaluated by both colorectal tissue weight and histological score of colitis. rWAS treatment increased mRNA expression of UCN2 and IFN-γ in large intestinal lamina propria mononuclear cells (LI-LPMC). Interestingly, exacerbated colitis was associated with changes in the microbial community of MACB, specifically loss of bacterial species diversity and an increase in the component ratio of Clostridium, revealed by 16S rRNA gene amplicon analysis. Finally, the oral administration of a probiotic Lactobacillus strain was protective against the exacerbation of colitis and was associated with a change in the bacterial community of MACB in rWAS-exposed Tcra-/- mice. Taken together, these results suggested that loss of species diversity in MACB might play a key role in exacerbated colitis induced by chronic psychological stress. In addition, probiotic treatment may be used as a tool to preserve the diversity of bacterial species in MACB and alleviate gut inflammation induced by psychological stress.
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- 2016
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115. Microbiota of the Small Intestine Is Selectively Engulfed by Phagocytes of the Lamina Propria and Peyer's Patches.
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Masatoshi Morikawa, Satoshi Tsujibe, Junko Kiyoshima-Shibata, Yohei Watanabe, Noriko Kato-Nagaoka, Kan Shida, and Satoshi Matsumoto
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Medicine ,Science - Abstract
Phagocytes such as dendritic cells and macrophages, which are distributed in the small intestinal mucosa, play a crucial role in maintaining mucosal homeostasis by sampling the luminal gut microbiota. However, there is limited information regarding microbial uptake in a steady state. We investigated the composition of murine gut microbiota that is engulfed by phagocytes of specific subsets in the small intestinal lamina propria (SILP) and Peyer's patches (PP). Analysis of bacterial 16S rRNA gene amplicon sequences revealed that: 1) all the phagocyte subsets in the SILP primarily engulfed Lactobacillus (the most abundant microbe in the small intestine), whereas CD11bhi and CD11bhiCD11chi cell subsets in PP mostly engulfed segmented filamentous bacteria (indigenous bacteria in rodents that are reported to adhere to intestinal epithelial cells); and 2) among the Lactobacillus species engulfed by the SILP cell subsets, L. murinus was engulfed more frequently than L. taiwanensis, although both these Lactobacillus species were abundant in the small intestine under physiological conditions. These results suggest that small intestinal microbiota is selectively engulfed by phagocytes that localize in the adjacent intestinal mucosa in a steady state. These observations may provide insight into the crucial role of phagocytes in immune surveillance of the small intestinal mucosa.
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- 2016
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116. Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease.
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Yohei Watanabe, Sohei Arase, Noriko Nagaoka, Mitsuhisa Kawai, and Satoshi Matsumoto
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Medicine ,Science - Abstract
The effect of psychological stress on the gastrointestinal microbiota is widely recognized. Chronic psychological stress may be associated with increased disease activity in inflammatory bowel disease, but the relationships among psychological stress, the gastrointestinal microbiota, and the severity of colitis is not yet fully understood. Here, we examined the impact of 12-week repeated water-avoidance stress on the microbiota of two inbred strains of T cell receptor alpha chain gene knockout mouse (background, BALB/c and C57BL/6) by means of next-generation sequencing of bacterial 16S rRNA genes. In both mouse strains, knockout of the T cell receptor alpha chain gene caused a loss of gastrointestinal microbial diversity and stability. Chronic exposure to repeated water-avoidance stress markedly altered the composition of the colonic microbiota of C57BL/6 mice, but not of BALB/c mice. In C57BL/6 mice, the relative abundance of genus Clostridium, some members of which produce the toxin phospholipase C, was increased, which was weakly positively associated with colitis severity, suggesting that expansion of specific populations of indigenous pathogens may be involved in the exacerbation of colitis. However, we also found that colitis was not exacerbated in mice with a relatively diverse microbiota even if their colonic microbiota contained an expanded phospholipase C-producing Clostridium population. Exposure to chronic stress also altered the concentration of free immunoglobulin A in colonic contents, which may be related to both the loss of bacterial diversity in the colonic microbiota and the severity of the colitis exacerbation. Together, these results suggest that long-term exposure to psychological stress induces dysbiosis in the immunodeficient mouse in a strain-specific manner and also that alteration of microbial diversity, which may be related to an altered pattern of immunoglobulin secretion in the gastrointestinal tract, might play a crucial role in the development of chronic stress-induced colitis.
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- 2016
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117. Transient Creatine Kinase Elevation Followed by Hypocomplementemia in a Case of Rotavirus Myositis
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Yuka Rokugo, Satoru Kumaki, Ryoichi Onuma, Rie Noguchi, Saeko Suzuki, Natsuko Kusaka, Yohei Watanabe, and Setsuko Kitaoka
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Pediatrics ,RJ1-570 - Abstract
We report an infant case of rotavirus myositis, a rare complication of rotavirus infection. Complement levels of the patient were normal when serum creatine kinase (CK) level was at its peak and then decreased when the CK level became normalized. In a previous case report of rotavirus myositis, transient decrease of serum albumin, immunoglobulin, and complement levels was reported. The authors speculated that intravascular complement activation was caused by rotavirus and resulted in the pathogenesis of myositis, although complement levels at onset were not measured by the authors. In this report, however, we demonstrate that the complement activation of our patient is a result of, rather than the cause of, skeletal muscle damage.
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- 2016
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118. A case of rheumatoid arthritis with multiple lung rheumatoid nodules successfully treated with tofacitinib
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Yohko Murakawa, Mayuko Moriyama, Takashi Yanagawa, Makoto Nagasaki, Manabu Honda, Yohei Watanabe, Hiroyuki Kakimaru, and Masahiro Kondo
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Lung Diseases ,medicine.medical_specialty ,Rheumatoid nodule ,Gastroenterology ,Etanercept ,Arthritis, Rheumatoid ,Piperidines ,Refractory ,Internal medicine ,Biopsy ,medicine ,Humans ,Protein Kinase Inhibitors ,Aged ,Tofacitinib ,Lung ,medicine.diagnostic_test ,business.industry ,Abatacept ,respiratory system ,medicine.disease ,respiratory tract diseases ,Pyrimidines ,Treatment Outcome ,medicine.anatomical_structure ,Rheumatoid arthritis ,Female ,Tumor Necrosis Factor Inhibitors ,medicine.symptom ,Rheumatoid Nodule ,Tomography, X-Ray Computed ,business ,medicine.drug - Abstract
Sporadic cases of rheumatoid nodules (RNs) in the lung during treatment with tumour necrosis factor (TNF) inhibitors have been reported, but no treatment has been established. Here, we report a case of symptomatic lung RNs refractory to abatacept (ABT) and intravenous cyclophosphamide (IVCY) that improved with tofacitinib (TOF) treatment. A 75-year-old Japanese woman with a 10-year history of rheumatoid arthritis (RA) presented with a cough and haemoptysis during treatment with etanercept (ETN). Radiographic examinations revealed multiple nodules that were diagnosed as lung RNs via biopsy. The ETN was discontinued and ABT followed by IVCY was introduced; however, neither was sufficiently effective against the lung RNs. Thereafter, TOF was started and the lung RNs improved rapidly. The precise mechanisms that induce RNs during treatment with TNF inhibitors are unknown. Cytokines (IL-23 and IL-6) are suspected to be involved. TOF may be a reasonable strategy for treating symptomatic lung RNs.
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- 2020
119. Distinct decrease in peripheral lymphocytes in EBER-positive cases of MTX-LPD
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Mayuko Moriyama, Tomoko Sugiura, Keiichi Onoda, Manabu Honda, Hiroyuki Kakimaru, Yohko Murakawa, Masahiro Kondo, and Yohei Watanabe
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Male ,musculoskeletal diseases ,Lymphocyte ,EBER Positive ,Arthritis, Rheumatoid ,Japan ,Rheumatology ,Recurrence ,immune system diseases ,hemic and lymphatic diseases ,Outcome Assessment, Health Care ,medicine ,Humans ,heterocyclic compounds ,Lymphocyte Count ,Lymphocytes ,skin and connective tissue diseases ,Aged ,business.industry ,Lymphoproliferative Disorders ,Peripheral ,Methotrexate ,medicine.anatomical_structure ,Withholding Treatment ,Immunology ,Female ,business ,Immunosuppressive Agents - Abstract
To determine the clinical characteristics of methotrexate-associated lymphoproliferative disorder (MTX-LPD).In this study, 12 RA patients who developed MTX-LPD were assessed. The peripheral blood lymphocyte (PBL) count at the onset of MTX-LPD was compared to that 6 months before the onset, in Epstein-Barr virus-encoded RNA (EBER)-positive and -negative subgroups. We examined the change in the PBL count after MTX withdrawal. In patients with relapsed LPD, changes in the PBL count before relapse were also examined.Regression of LPD after MTX withdrawal was noted in eight patients. In these patients, the PBL count was decreased at the onset of MTX-LPD compared to 6 months before the onset; the decrease was significantly more prominent in EBER-positive patients. In cases of spontaneous regression of LPD, the PBL count recovered quickly after MTX withdrawal. Four of eight patients showed a recurrence of LPD after they improved following MTX withdrawal. These patients also exhibited a decreased PBL count at recurrence compared to 6 months before recurrence.A decrease in the PBL count might be involved in the pathogenesis of MTX-LPD, especially in EBER-positive cases and in patients with LPD relapse after MTX withdrawal following initial improvement.
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- 2020
120. Ionic strength-sensitive and pH-insensitive interactions between C-reactive protein (CRP) and an anti-CRP antibody
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Yuka Oka, Shota Ushiba, Naruto Miyakawa, Madoka Nishio, Takao Ono, Yasushi Kanai, Yohei Watanabe, Shinsuke Tani, Masahiko Kimura, and Kazuhiko Matsumoto
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General Medicine - Abstract
C-reactive protein (CRP) is an important biomarker of infection and inflammation, as CRP is one of the most prominent acute-phase proteins. CRP is usually detected using anti-CRP antibodies (Abs), where the intermolecular interactions between CRP and the anti-CRP Ab are largely affected by the pH and ionic strength of environmental solutions. Therefore, it is important to understand the environmental effects of CRP-anti-CRP Ab interactions when designing highly sensitive biosensors. Here, we investigated the efficiency of fluorescently labeled CRP-anti-CRP monoclonal antibody (mAb) interactions at different pHs and ionic strengths. Our results indicate that the affinity was insensitive to pH changes in the range of 5.9 to 8.1, while it was significantly sensitive to ionic strength changes. The binding affinity decreased by 55% at an ionic strength of 1.6 mM, when compared to that under a physiological condition (~150 mM). Based on the isoelectric focusing results, both the labeled CRP and anti-CRP mAb were negatively charged in the studied pH range, which rendered the system insensitive to pH changes, but sensitive to ionic strength changes. The decreased ionic strength led to a significant enhancement of the repulsive force between CRP and the anti-CRP mAb. Although the versality of the findings is not fully studied yet, the results provide insights into designing highly sensitive CRP sensors, especially field-effect transistor-based sensors.
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- 2021
121. Functional benefits of the double flap technique after proximal gastrectomy for gastric cancer
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Tomoyuki Momma, Hiroyuki Hanayama, Koji Kono, Yohei Watanabe, Suguru Hayase, Koji Kase, Naoto Yamauchi, Akinao Kaneta, Zenichiro Saze, and Hiroshi Nakano
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Gastrointestinal ,medicine.medical_specialty ,Proximal gastrectomy ,RD1-811 ,Surgical Flaps ,Postoperative Complications ,Gastrectomy ,Stomach Neoplasms ,Gastric Stump ,medicine ,Performed Procedure ,Humans ,Reflux esophagitis ,Laparoscopy ,Retrospective Studies ,Nutrition ,medicine.diagnostic_test ,business.industry ,Research ,Stomach ,Cancer ,General Medicine ,Consecutive case series ,Body Weight Maintenance ,medicine.disease ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,business - Abstract
Background Proximal gastrectomy is a widely performed procedure that has become more common with an increasing number of proximal gastric cancer cases. Several types of reconstructive procedures after proximal gastrectomy have been developed, and it remains controversial which procedure is the most advantageous with regard to the preservation of postoperative gastric stump function and nutritional status. In the present study, we retrospectively analyzed reconstructive procedures in a consecutive case series for proximal gastrectomy, primarily focusing on postoperative body weight maintenance, nutritional status, and gastric remnant functional preservation. Methods We enrolled 69 patients who had undergone proximal gastrectomy for gastric cancer in our institute between 2005 and 2020. Short-term complications, preservation of gastric remnant functions, nutritional status, and post-operative weight changes were compared. Results After proximal gastrectomy, the numbers of patients who underwent direct esophago-gastrostomy, jejunal interposition, double tract reconstruction, and the double flap technique were 9, 10, 14, and 36, respectively. The patients in whom the double flap technique was performed suffered no reflux esophagitis after surgery. Prevalence of gastric residual at 12 months after surgery was lowest in the double flap technique group. Moreover, the double flap technique group had a better tendency regarding post-operative changes of serum albumin ratios. Furthermore, the post-operative body weight change ratio of the double flap technique group was smallest among all groups and was significantly better than that of the double tract group. Conclusions The double flap technique after proximal gastrectomy was considered the most effective technique for reconstruction which leads to better bodyweight maintenance, and results in less reflux esophagitis.
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- 2021
122. Xylan utilisation promotes adaptation of Bifidobacterium pseudocatenulatum to the human gastrointestinal tract
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Takahiro Matsuki, Takashi Kurakawa, Taeko Hara, Yuki Saito, Kaoru Moriyama-Ohara, Yoshimi Aiyama-Suzuki, Yohei Watanabe, Satoshi Matsumoto, Naoki Tsukuda, and Kana Tanigawa-Yahagi
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chemistry.chemical_classification ,Bifidobacterium pseudocatenulatum ,Human gastrointestinal tract ,General Medicine ,Biology ,Polysaccharide ,biology.organism_classification ,Microbiology ,medicine.anatomical_structure ,chemistry ,Gene cluster ,medicine ,Bacteroides ,Gene ,Dietary Carbohydrates ,Bacteria - Abstract
Dietary carbohydrates impact the composition of the human gut microbiota. However, the relationship between carbohydrate availability for individual bacteria and their growth in the intestinal environment remains unclear. Here, we show that the availability of long-chain xylans (LCX), one of the most abundant dietary fibres in the human diet, promotes the growth of Bifidobacterium pseudocatenulatum in the adult human gut. Genomic and phenotypic analyses revealed that the availability of LCX-derived oligosaccharides is a fundamental feature of B. pseudocatenulatum, and that some but not all strains possessing the endo-1,4-β-xylanase (BpXyn10A) gene grow on LCX by cleaving the xylose backbone. The BpXyn10A gene, likely acquired by horizontal transfer, was incorporated into the gene cluster for LCX-derived oligosaccharide utilisation. Co-culturing with xylanolytic Bacteroides spp. demonstrated that LCX-utilising strains are more competitive than LCX non-utilising strains even when LCX-derived oligosaccharides were supplied. In LCX-rich dietary interventions in adult humans, levels of endogenous B. pseudocatenulatum increased only when BpXyn10A was detected, indicating that LCX availability is a fitness determinant in the human gut. Our findings highlight the enhanced intestinal adaptability of bifidobacteria via polysaccharide utilisation, and provide a cornerstone for systematic manipulation of the intestinal microbiota through dietary intervention using key enzymes that degrade polysaccharide as biomarkers.
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- 2021
123. 'Nano Adhesion Technology' and 'Coating Reinforcement Technology' Solve 'Trouble...' in the World
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Yohei Watanabe
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Materials science ,Coating ,Mechanical Engineering ,Nano ,Media Technology ,engineering ,General Materials Science ,General Chemistry ,Adhesion ,Composite material ,engineering.material ,Reinforcement - Published
- 2021
124. [A Case of Laparoscopic Surgery for Preoperatively Diagnosed Gastric Metastasis of Lung Cancer]
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Shotaro, Mochizuki, Leo, Yamada, Koji, Kase, Misato, Ito, Hiroshi, Nakano, Naoto, Yamauchi, Takuro, Matsumoto, Akinao, Kaneta, Yasuyuki, Kanke, Takahiro, Nakajima, Hiroyuki, Hanayama, Yohei, Watanabe, Hisashi, Onozawa, Suguru, Hayase, Hirokazu, Okayama, Shotaro, Fujita, Wataru, Sakamoto, Motonobu, Saito, Tomoyuki, Momma, Zenichiro, Saze, Kousaku, Mimura, Shinji, Ohki, and Koji, Kono
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Male ,Lung Neoplasms ,Gastrectomy ,Stomach Neoplasms ,Positron Emission Tomography Computed Tomography ,Humans ,Laparoscopy ,Aged - Abstract
The patient was a 66-year-old male who had undergone an operation for lung cancer and solitary brain metastases. Follow- up PET-CT after 1 year detected FDG accumulation in the stomach. We performed esophagogastroscopy and found an approximately 20 mm-sized Type 2 tumor on the greater curvature of the upper stomach. A pathological diagnosis of lung adenocarcinoma metastasis in the stomach was made. Laparoscopic surgery was performed on the metastatic lesion to prevent bleeding and perforation, and resection was achieved with minimal invasion. The current development of chemotherapy, including immunotherapy, has contributed to the improved prognosis of cancer patients, including those with lung metastasis in the stomach. Considering these backgrounds, preventive surgical resection under laparoscopy may be an effective approach for improving prognosis and preventing acute life-threatening adverse events. We report this case along with a literature review.
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- 2021
125. Characterization of H5N1 Influenza Virus Variants with Hemagglutinin Mutations Isolated from Patients
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Yohei Watanabe, Yasuha Arai, Tomo Daidoji, Norihito Kawashita, Madiha S. Ibrahim, Emad El-Din M. El-Gendy, Hiroaki Hiramatsu, Ritsuko Kubota-Koketsu, Tatsuya Takagi, Takeomi Murata, Kazuo Takahashi, Yoshinobu Okuno, Takaaki Nakaya, Yasuo Suzuki, and Kazuyoshi Ikuta
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Microbiology ,QR1-502 - Abstract
ABSTRACT A change in viral hemagglutinin (HA) receptor binding specificity from α2,3- to α2,6-linked sialic acid is necessary for highly pathogenic avian influenza (AI) virus subtype H5N1 to become pandemic. However, details of the human-adaptive change in the H5N1 virus remain unknown. Our database search of H5N1 clade 2.2.1 viruses circulating in Egypt identified multiple HA mutations that had been selected in infected patients. Using reverse genetics, we found that increases in both human receptor specificity and the HA pH threshold for membrane fusion were necessary to facilitate replication of the virus variants in human airway epithelia. Furthermore, variants with enhanced replication in human cells had decreased HA stability, apparently to compensate for the changes in viral receptor specificity and membrane fusion activity. Our findings showed that H5N1 viruses could rapidly adapt to growth in the human airway microenvironment by altering their HA properties in infected patients and provided new insights into the human-adaptive mechanisms of AI viruses. IMPORTANCE Circulation between bird and human hosts may allow H5N1 viruses to acquire amino acid changes that increase fitness for human infections. However, human-adaptive changes in H5N1 viruses have not been adequately investigated. In this study, we found that multiple HA mutations were actually selected in H5N1-infected patients and that H5N1 variants with some of these HA mutations had increased human-type receptor specificity and increased HA membrane fusion activity, both of which are advantageous for viral replication in human airway epithelia. Furthermore, HA mutants selected during viral replication in patients were likely to have less HA stability, apparently as a compensatory mechanism. These results begin to clarify the picture of the H5N1 human-adaptive mechanism.
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- 2015
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126. Double Flap Technique is an Effective Reconstruction Procedure After Proximal Gastrectomy for Gastric Cancer
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Hiroyuki Hanayama, Tomoyuki Momma, Akinao Kaneta, Naoto Yamauchi, Zenichiro Saze, Koji Kono, Hiroshi Nakano, Suguru Hayase, Koji Kase, and Yohei Watanabe
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medicine.medical_specialty ,Text mining ,Proximal gastrectomy ,business.industry ,Medicine ,Cancer ,business ,medicine.disease ,Reconstruction procedure ,Surgery - Abstract
Background In accordance with an increase of proximal gastric cancer, proximal gastrectomy came to be widely performed. Several types of reconstructive procedures after proximal gastrectomy have been developed and it is still controversial which procedure has the advantages in preservation of postoperative gastric stump function and nutritional status after proximal gastrectomy. In this study, we retrospectively analyzed reconstructive procedures in our consecutive case series for proximal gastrectomy, with particular focus on postoperative body weight maintenance, nutritional status, and gastric remnant functional preservation. Methods We enrolled 69 patients who received proximal gastrectomy for gastric cancer in our institute from 2005 to 2020. Short-term complications, preservation of gastric remnant functions, nutritional status, and post-operative weight changes were compared. Results After proximal gastrectomy, the numbers of cases receiving Direct Esophago-Gastrostomy, Jejunal Interposition, Double Tract Reconstruction, and Double Flap Technique were 9, 10, 14, and 36, respectively. Double Flap Technique cases suffered no reflux esophagitis after surgery. Prevalence of gastric residual at 12-month after surgery of Double Flap Technique was the lowest. Double Flap Technique group has better tendency in post-operative changes of serum albumin ratios. Furthermore, post-operative body weight changes ratio of Double Flap Technique was the smallest and significantly better than Double Tract at all the time points. Conclusions Double Flap Technique after proximal gastrectomy was considered as the most effective reconstruction which can maintain body weight, cause less reflux esophagitis and gastric residual.
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- 2021
127. Double mutations in the H9N2 avian influenza virus PB2 gene act cooperatively to increase viral host adaptation and replication for human infections
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Kazuhiko Matsumoto, Yasuha Arai, Tomo Daidoji, Norihito Kawashita, Takao Ono, Yohei Watanabe, Takaaki Nakaya, Emad Mohamed Elgendy, Ayana Isobe, Tatsuya Takagi, and Madiha S. Ibrahim
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0301 basic medicine ,Models, Molecular ,Genes, Viral ,Genotype ,viruses ,030106 microbiology ,Virulence ,Biology ,medicine.disease_cause ,Host Adaptation ,Virus Replication ,Viral Zoonoses ,Virus ,Poultry ,Cell Line ,Birds ,03 medical and health sciences ,Mice ,Viral Proteins ,Orthomyxoviridae Infections ,Virology ,Influenza, Human ,medicine ,Influenza A Virus, H9N2 Subtype ,Animals ,Humans ,Gene ,Phylogeny ,Mutation ,Mice, Inbred BALB C ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,RNA-Dependent RNA Polymerase ,Influenza A virus subtype H5N1 ,030104 developmental biology ,HEK293 Cells ,Influenza in Birds ,Host adaptation ,Human Virus ,Reassortant Viruses - Abstract
Avian H9N2 influenza viruses in East Asia are genetically diversified and multiple genotypes (A-W) have been established in poultry. Genotype S strains are currently the most prevalent strains, have caused many human infections and pose a public health threat. In this study, human adaptation mutations in the PB2 polymerase in genotype S strains were identified by database screening. Several PB2 double mutations were identified that acted cooperatively to produce higher genotype S virus polymerase activity and replication in human cells than in avian cells and to increase viral growth and virulence in mice. These mutations were chronologically and phylogenetically clustered in a new group within genotype S viruses. Most of the relevant human virus isolates carry the PB2-A588V mutation together with another PB2 mutation (i.e. K526R, E627V or E627K), indicating a host adaptation advantage for these double mutations. The prevalence of PB2 double mutations in human H9N2 virus isolates has also been found in genetically related human H7N9 and H10N8 viruses. These results suggested that PB2 double mutations in viruses in the field acted cooperatively to increase human adaptation of the currently prevalent H9N2 genotype S strains. This may have contributed to the recent surge of H9N2 infections and may be applicable to the human adaptation of several other avian influenza viruses. Our study provides a better understanding of the human adaptation pathways of genetically related H9N2, H7N9 and H10N8 viruses in nature.
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- 2021
128. Clinical Impact of Upper Extremity Deep Vein Thrombosis in the Retrosternal Reconstruction After Esophagectomy
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Leo Yamada, Hiroya Suzuki, Tomoyuki Momma, Misato Ito, Zenichiro Saze, Eisei Endo, Koji Kono, Yasuyuki Kanke, Yohei Watanabe, Hiroshi Nakano, Akinao Kaneta, Takuro Matsumoto, Motonobu Saito, Suguru Hayase, Hirokazu Okayama, Hisashi Onozawa, Wataru Sakamoto, Shinji Ohki, Naoto Yamauchi, Hiroyuki Hanayama, Shotaro Mochizuki, Shotaro Fujita, and Koji Kase
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medicine.medical_specialty ,business.industry ,Esophagectomy ,medicine.medical_treatment ,Medicine ,Upper Extremity Deep Vein Thrombosis ,business ,Surgery - Abstract
Background Upper extremity deep vein thrombosis (UEDVT) is relatively rare but cannot be negligible because it can cause fatal complications. Although it is reported that the occurrence rate of UEDVT has increased due to central venous catheter (CVC), cancer, and surgical invasion, there are still limited information for esophagectomy. The aim of this study was to evaluate the clinical factors, including CVC placement and thromboprophylaxis approach, as well as retrosternal space’s width as a predictive factor for UEDVT in patients receiving esophagectomy. Methods This study included 66 patients who underwent esophagectomy with retrosternal reconstruction using a gastric tube. All patients routinely underwent contrast-enhanced computed tomography (CT) on the 4th postoperative day. Low-molecular-weight-heparin (LMWH) was routinely administered by the 2nd postoperative day. To evaluate retrosternal space’s width, (a) The distance from sternum to brachiocephalic artery and (b) the distance from sternum to vertebra were measured by preoperative CT, and the ratio of (a) to (b) was defined as the width of retrosternal space. Results Among all patients, 11(16.7%) suffered from UEDVT, and none was preoperatively received CVC placement, while 7 were inserted in non-UEDVT cases. Retrosternal space’s width in patients with UEDVT was significantly smaller than that in patients without UEDVT (0.17 vs. 0.26; P < 0.0001). A cutoff value of the width was 0.21, which has high sensitivity (87%) and specificity (82%) for UEDVT prediction, respectively. Conclusion The existence of CVC may not affect the development of UEDVT, but preoperative evaluation of retrosternal ratio may predict the occurrence of UEDVT.
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- 2021
129. Session details: Session 2
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Yohei Watanabe
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Multimedia ,Session (computer science) ,Psychology ,computer.software_genre ,computer - Published
- 2021
130. 'Genetic tuning' of avian influenza virus host adaptation from birds to humans
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Yohei Watanabe and Yasuha Arai
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Microbiology (medical) ,Avian influenza virus ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Public Health, Environmental and Occupational Health ,Infectious and parasitic diseases ,RC109-216 ,Biology ,medicine.disease_cause ,Virology ,Deep sequencing ,Influenza A virus subtype H5N1 ,Virus ,Article ,Infectious Diseases ,Pandemic ,medicine ,Host adaptation ,Public aspects of medicine ,RA1-1270 ,Adaptation ,Biotechnology - Abstract
Avian influenza viruses can adapt to infect humans by accumulating mutations or reassortments, potentially leading to a pandemic. However, the adaptation dynamics of zoonotic avian influenza viruses in their transition from animal hosts to human hosts remains largely unknown. In a recent PNAS report, Liu et al. have presented deep sequencing data showing host adaptation by “genetic tuning” of a zoonotic H7N9 avian influenza virus to cross the species barrier to infect humans. This provides the first in-depth data on avian influenza virus adaptation at the bird-human interface. As a one-health approach, the deep sequencing approach as implemented by Liu et al. is applicable to the study of emerging zoonotic viruses and provides valuable data on “genetic tuning” in virus-host adaptation. This experimental design should be useful for studying other zoonotic viruses, including SARS-CoV-2 and the novel swine influenza virus, and helpful for mitigating future pandemic public health risks.
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- 2021
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131. Stromal expression of cancer-associated fibroblast-related molecules, versican and lumican, is strongly associated with worse relapse-free and overall survival times in patients with esophageal squamous cell carcinoma
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Shotaro Nakajima, Katsuharu Saito, Leo Yamada, Takuro Matsumoto, Hiroshi Nakano, Shoki Yamada, Zenichiro Saze, Hiroyuki Hanayama, Hirokazu Okayama, Kosaku Mimura, Koji Kase, Yasuyuki Kanke, Yohei Watanabe, Yuko Hashimoto, Shinji Oki, Tomoyuki Momma, Koji Kono, Motonobu Saito, Suguru Hayase, Naoto Yamauchi, and Eisei Endo
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0301 basic medicine ,squamous cell carcinoma ,Cancer Research ,Stromal cell ,Lumican ,Periostin ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Survival analysis ,versican ,esophagus ,periostin ,Tumor microenvironment ,biology ,business.industry ,Cancer ,lumican ,Articles ,medicine.disease ,digestive system diseases ,carbohydrates (lipids) ,030104 developmental biology ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Versican ,business ,cancer-associated fibroblasts - Abstract
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment play an essential role in the tumor progression of esophageal squamous cell carcinoma (ESCC). The present study aimed to investigate the expression of CAF-related molecules, versican, periostin and lumican, in cancer stroma, to provide prognostic stratification for patients with ESCC after surgery. A total of 106 patients with ESCC who underwent curative esophagectomy without preoperative chemotherapy or radiotherapy were enrolled. The expression of CAF-related stromal proteins, including versican, periostin and lumican, was examined using immunohistochemistry, and the prognostic value was assessed by Kaplan-Meier survival analysis, and univariate and multivariate Cox regression models. The expression of versican, periostin and lumican was found specifically in the stromal component of ESCC. Kaplan-Meier analysis demonstrated that, compared with a low expression level, a high expression level of versican, periostin or lumican in the cancer stroma was significantly associated with worse relapse-free survival (RFS) and overall survival times in patients with ESCC. The prognostic values of stromal versican and lumican remained significant in a stratified analysis of stage I patients. Moreover, univariate and multivariate analysis revealed that high stromal versican or lumican expression was an independent prognostic factor for RFS in the patients. The present study demonstrated that CAF-related molecules, including versican, periostin and lumican, were expressed in the stroma of ESCC, and that stromal expression of versican and lumican in particular may have clinical utility as a prognostic biomarker for poor RFS in postoperative patients with ESCC.
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- 2021
132. Multi-Party Computation for Modular Exponentiation Based on Replicated Secret Sharing
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Kazuo Ohta, Yohei Watanabe, Kazuma Ohara, and Mitsugu Iwamoto
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Modular exponentiation ,replicated secret sharing ,Theoretical computer science ,Computer science ,Applied Mathematics ,Computation ,Signal Processing ,modular exponentiation ,Electrical and Electronic Engineering ,multi-party computation ,Computer Graphics and Computer-Aided Design ,Secret sharing - Abstract
In recent years, multi-party computation (MPC) frameworks based on replicated secret sharing schemes (RSSS) have attracted the attention as a method to achieve high efficiency among known MPCs. However, the RSSS-based MPCs are still inefficient for several heavy computations like algebraic operations, as they require a large amount and number of communication proportional to the number of multiplications in the operations (which is not the case with other secret sharing-based MPCs). In this paper, we propose RSSS-based three-party computation protocols for modular exponentiation, which is one of the most popular algebraic operations, on the case where the base is public and the exponent is private. Our proposed schemes are simple and efficient in both of the asymptotic and practical sense. On the asymptotic efficiency, the proposed schemes require O(n)-bit communication and O(1) rounds,where n is the secret-value size, in the best setting, whereas the previous scheme requires O(n^2)-bit communication and O(n) rounds. On the practical efficiency, we show the performance of our protocol by experiments on the scenario for distributed signatures, which is useful for secure key management on the distributed environment (e.g., distributed ledgers). As one of the cases, our implementation performs a modular exponentiation on a 3,072-bit discrete-log group and 256-bit exponent with roughly 300ms, which is an acceptable parameter for 128-bit security, even in the WAN setting.
- Published
- 2019
133. Key-updatable public-key encryption with keyword search (Or: How to realize PEKS with efficient key updates for IoT environments)
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Hiroaki Anada, Akira Kanaoka, Yohei Watanabe, and Natsume Matsuzaki
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Computer Networks and Communications ,Computer science ,Raspberry Pi ,0211 other engineering and technologies ,02 engineering and technology ,Encryption ,Computer security ,computer.software_genre ,Public-key cryptography ,Server ,Public-key encryption with keyword search ,Safety, Risk, Reliability and Quality ,Cloud server ,021110 strategic, defence & security studies ,SIMPLE (military communications protocol) ,business.industry ,Keyword search ,IoT environments ,Key updates ,Searchable encryption ,Internet of Things ,business ,Mobile device ,computer ,Software ,Information Systems - Abstract
Security and privacy are the key issues for the Internet of Things (IoT) systems. Especially, secure search is an important functionality for cooperation among users' devices and non-trusted servers. Public-key encryption with keyword search (PEKS) enables us to search encrypted data and is expected to be used between a cloud server and users' mobile devices or IoT devices. However, those mobile devices might be lost or stolen. For IoT devices, it might be difficult to store keys in a tamper-proof manner due to prohibitive costs. In this paper, we deal with such a key-exposure problem on PEKS and introduce the concept of PEKS with key-updating functionality, which we call key-updatable PEKS (KU-PEKS). Specifically, we propose two models of KU-PEKS: the key-evolution model and the key-insulation model. In the key-evolution model, a pair of public and secret keys can be updated if needed (e.g., the secret key is exposed). In the key-insulation model, the public key remains fixed while the secret key can be updated if needed. The former model makes a construction simple and more efficient than the latter. On the other hand, the latter model is preferable for practical use since a user never updates their public key. We show constructions in each model in a black-box manner. We also give implementation results on Raspberry Pi 3, which can be regarded as a reasonable platform of IoT devices.
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- 2019
134. Electrical Biosensing at Physiological Ionic Strength Using Graphene Field-Effect Transistor in Femtoliter Microdroplet
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Kazuhiko Matsumoto, Takao Ono, Yasushi Kanai, Yasuo Suzuki, Koichi Inoue, Yohei Watanabe, Toshio Kawahara, and Shin-ichi Nakakita
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Electron mobility ,Materials science ,Transistors, Electronic ,Microfluidics ,Bioengineering ,Nanotechnology ,Biosensing Techniques ,02 engineering and technology ,Helicobacter Infections ,law.invention ,symbols.namesake ,law ,Lab-On-A-Chip Devices ,Humans ,General Materials Science ,Debye length ,Debye ,Helicobacter pylori ,Graphene ,Mechanical Engineering ,Osmolar Concentration ,Femtoliter ,Equipment Design ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Urease ,Canavalia ,Ionic strength ,symbols ,Graphite ,0210 nano-technology ,Biosensor - Abstract
Graphene has strong potential for electrical biosensing owing to its two-dimensional nature and high carrier mobility which transduce the direct contact of a detection target with a graphene channel to a large conductivity change in a graphene field-effect transistor (G-FET). However, the measurable range from the graphene surface is highly restricted by Debye screening, whose characteristic length is less than 1 nm at physiological ionic strength. Here, we demonstrated electrical biosensing utilizing the enzymatic products of the target. We achieved quantitative measurements of a target based on the site-binding model and real-time measurement of the enzyme kinetics in femtoliter microdroplets. The combination of a G-FET and microfluidics, named a "lab-on-a-graphene-FET", detected the enzyme urease with high sensitivity in the zeptomole range in 100 mM sodium phosphate buffer. Also, the lab-on-a-graphene-FET detected the gastric cancer pathogen Helicobacter pylori captured at a distance greater than the Debye screening length from the G-FET.
- Published
- 2019
135. Identity-based encryption with hierarchical key-insulation in the standard model
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Yohei Watanabe and Junji Shikata
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Scheme (programming language) ,Theoretical computer science ,Identity-based hierarchical key-insulated encryption ,business.industry ,Applied Mathematics ,Asymmetric pairing ,020206 networking & telecommunications ,Cryptography ,0102 computer and information sciences ,02 engineering and technology ,Encryption ,01 natural sciences ,Identity (music) ,Computer Science Applications ,Random oracle ,010201 computation theory & mathematics ,Hierarchical identity-based encryption ,0202 electrical engineering, electronic engineering, information engineering ,Key-insulated encryption ,business ,computer ,Mathematics ,Standard model (cryptography) ,computer.programming_language - Abstract
A key exposure problem is unavoidable since it seems human error can never be eliminated completely, and key-insulated encryption is one of the cryptographic solutions to the problem. At Asiacrypt’05, Hanaoka et al. introduced hierarchical key-insulation functionality, which is attractive functionality that enhances key exposure resistance, and proposed an identity-based hierarchical key-insulated encryption (hierarchical IKE) scheme in the random oracle model. In this paper, we first propose the hierarchical IKE scheme in the standard model (i.e., without random oracles). Our hierarchical IKE scheme is secure under the symmetric external Diffie–Hellman ( $$\mathsf{SXDH}$$ ) assumption, which is a static assumption. Particularly, in the non-hierarchical case, our construction is the first IKE scheme that achieves constant-size parameters including public parameters, secret keys, and ciphertexts. Furthermore, we also propose the first public-key-based key-insulated encryption (PK-KIE) in the hierarchical setting by using our technique.
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- 2019
136. Combination of oligo-fractionated irradiation with nivolumab can induce immune modulation and replacement of T cell clones in patients with gastric cancer (phase I/II clinical study)
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Koji Kono, Kousaku Mimura, Takashi Ogata, Yuya Yoshimoto, Daisaku Yoshida, Shotaro Nakajima, Hisashi Sato, Nozomu Machida, Takanobu Yamada, Yohei Watanabe, Tomoaki Tamaki, Hirohito Fujikawa, Yasuhiro Inokuchi, Suguru Hayase, Hiroyuki Hanayama, Zenichiro Saze, Hiroyuki Katoh, Takashi Oshima, Yoshiyuki Suzuki, and Alessandra Nardin
- Subjects
Cancer Research ,Oncology - Abstract
4027 Background: Although basic, translational and clinical research suggest a possibility of synergistic effect of radiation-induced immunogenic cell death with immune checkpoint inhibitors, the effectiveness of the combination therapy is not fully established. Therefore, we conducted a single-arm, phase 1/2 trial (ClinicalTrials.gov, NCT03453164) in gastric cancer (GC) patients treated with a combination of nivolumab and oligo-fractionated irradiation (22.5 Gy/5 fractions/5 days). Methods: Eligible patients (n = 40) had un-resectable advanced or recurrent GC which progressed after primary and secondary chemotherapy with more than one lesion assessable in diagnostic imaging (one lesion must be ≥2cm). PBMCs from enrolled patients underwent high-dimensional flow cytometry-based, multiplexed MHC multimer analysis using a total of 46 tumor-associated antigens (TAA) and 10 virus epitopes and next-generation sequencing-based repertoire analysis of TCR β-chain. Results: The disease control rate (DCR) for the non-irradiated target as abscopal effect as the primary endpoint was 22.5%, and the DCR for the irradiated lesion was 40.0%. The median survival time was 230 days (157-330 days, 95%CI) and probability of 1-year survival rate was 28.6%. Although most TAA-specific T cells could be tracked longitudinally pre- and post-treatment, some several novel TAA-specific CD8 T cells were detected de novo after irradiation, indicating that potential irradiation-driven antigen spreading. Moreover, irradiation was associated with phenotypical changes of TAA-specific CD8 T cells towards higher expressions of KLRG1, HLA-DR, TIGIT and CD160 and lower expression of CD27 and CD127. Furthermore, the T cell clonality evaluated by the inverted Pielou’s evenness indicated that longer survival patients had more diverse TCR beta repertoire during treatment in comparison to shorter survivors. Also, we confirmed several new sequence-reads after radiation and nivolumab treatment in the top 30 most frequent clonotypes. Conclusions: Taken together, our results suggest that irradiation may induce, through immunogenic cell death, an immune-modulating effect with potential antigen spreading and a more diverse TCR repertoire, ultimately resulting in better survival during combination therapy of radiation with nivolumab. Clinical trial information: NCT03453164.
- Published
- 2022
137. Improvement of Intestinal Immune Cell Function by Lactic Acid Bacteria for Dairy Products
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Tomonori Kamiya, Yohei Watanabe, Seiya Makino, Hiroshi Kano, and Noriko M Tsuji
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Lactic acid bacteria ,Peyer’s patches ,Dendritic cells ,T helper cells ,Lactobacillus bulgaricus ,Streptococcus thermophilus ,Interferon γ ,Interleukin 17 ,Mucosal immunity ,Probiotics ,Biology (General) ,QH301-705.5 - Abstract
Lactic acid bacteria (LAB) form a major component of gut microbiota and are often used as probiotics for fermented foods, such as yoghurt. In this study, we aimed to evaluate immunomodulatory activity of LAB, especially that of Lactobacillus bulgaricus ME-552 (ME552) and Streptococcus thermophilus ME-553 (ME553). In vivo/in vitro assay was performed in order to investigate their effects on T cell function. After oral administration of ME553 to C57BL/6 mice, the amount of both interferon γ (IFN-γ) and interleukin 17 (IL-17) produced by cluster of differentiation (CD) 4+ T cells from Peyer’s patches (PPs) were significantly enhanced. On the other hand, ME552 only up-regulated the production of IL-17 from PP cells. The extent of induction for IFN-γ production differed between ME552 and ME553. These results suggest that LAB modulate T cell effector functions and mucosal immunity.
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- 2016
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138. [A Case of Pelvic Liposarcoma Resected by Hybrid Approach]
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Shotaro, Fujita, Tomoyuki, Momma, Hiroshi, Nakano, Naoto, Yamauchi, Leo, Yamada, Takuro, Matsumoto, Yasuyuki, Kanke, Hiroyuki, Hanayama, Yohei, Watanabe, Hisashi, Onozawa, Hirokazu, Okayama, Wataru, Sakamoto, Motonobu, Saito, Zenichiro, Saze, and Koji, Kono
- Subjects
Rectum ,Humans ,Laparoscopy ,Liposarcoma ,Neoplasm Recurrence, Local ,Pelvis - Abstract
Surgical resection is the most effective treatment for liposarcoma, a retroperitoneal malignant soft tissue tumor, and a reliable negative margin is required because of the high risk of local recurrence. We reported a case of pelvic liposarcoma that could be resected by laparoscopic and transsacral hybrid approach. A 60's-man had a mixed liposarcoma occupying the right rear of the pelvis in the rectum. The operation was preceded by a laparoscopic operation, and the right internal iliac artery and vein and the superior rectal artery were dissected. The tumor was separated along the right pelvic wall. The oral rectum was transected and the colon was elevated by the extraperitoneal route. After conversion to the Jackknife position, the anterior sacrum was exfoliated with the right transsacral approach, the coccyx was resected, and the rectal anus, tumor, and surrounding fatty tissue were removed as an en bloc fasion. Histopathological examination showed mixed type of liposarcoma and negative margin of the stump. The patient is alive without recurrence 8 months after the surgery.
- Published
- 2021
139. Anonymous Broadcast Authentication for Securely Remote-Controlling IoT Devices
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Yohei Watanabe, Junji Shikata, and Naoto Yanai
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Cryptographic primitive ,Syntax (programming languages) ,Computer science ,business.industry ,Broadcast authentication ,Wireless ,business ,Internet of Things ,Computer network - Abstract
In this paper, we present a basic system for controlling IoT devices in remote environments with the following requirements: (1) in a situation where an operation center broadcasts information to IoT devices, e.g., wireless environment, only the designated devices can identify operations sent from the center; (2) the devices can detect manipulation of the broadcast information and hence prevents maliciously generated operations from being executed. We formalize a model of the basic system and its essential requirements and propose anonymous broadcast authentication (ABA) as its core cryptographic primitive. We formally define the syntax and security notions for ABA and show provably-secure ABA constructions.
- Published
- 2021
140. New Revocable IBE in Prime-Order Groups: Adaptively Secure, Decryption Key Exposure Resistant, and with Short Public Parameters.
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Yohei Watanabe 0001, Keita Emura, and Jae Hong Seo
- Published
- 2016
141. Circulating tumor cells after neoadjuvant chemotherapy are related with recurrence in esophageal squamous cell carcinoma
- Author
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Hiroyuki Hanayama, Eisei Endo, Suguru Hayase, Shotaro Fujita, Hirokazu Okayama, Koji Kono, Shinji Ohki, Daisuke Ujiie, Yasuyuki Kanke, Yohei Watanabe, Zenichirou Saze, and Takuro Matsumoto
- Subjects
Oncology ,medicine.medical_specialty ,Esophageal Neoplasms ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Surgical oncology ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Epithelial–mesenchymal transition ,Liquid biopsy ,Chemotherapy ,business.industry ,Gastroenterology ,Cancer ,medicine.disease ,Neoplastic Cells, Circulating ,Neoadjuvant Therapy ,Regimen ,030220 oncology & carcinogenesis ,Cancer cell ,030211 gastroenterology & hepatology ,Esophageal Squamous Cell Carcinoma ,business - Abstract
Circulating tumor cells (CTCs) are known to be a systemic process of malignant progression of cancer cells and there is a possibility that analysis for CTCs as a liquid biopsy become predictive or prognostic tools for cancer patients. In the present study with the novel CTCs detection system (Celsee system®), we performed quantitative and qualitative analysis of CTCs in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemotherapy (NAC) with 5FU + CDDP regimen. CTCs are defined as having both DAPI positive and CD45 negative. Vimentin-positive CTCs were defined as mesenchymal-type CTCs (M-CTCs), while epithelial-type CTCs (E-CTCs) were only positive for pan-cytokeratin. At the baseline, there are detectable amounts of CTCs in all patients (n = 30) at all stages, and there were no significant differences of total CTCs, E-CTCs, or M-CTCs numbers between stages. Of importance, among total CTCs, M-CTCs are more dominant than E-CTCs in number. Also, there was no significant change of detectable amounts and phenotype of CTCs before and after NAC (n = 24). Of note, early recurrent group indicated that there was an elevated total CTCs number before NAC and an increased M-CTCs after NAC in comparison to those in non-recurrent group. Quantitative and qualitative analysis of CTCs may provide useful complementary predictive and prognostic information in ESCC.
- Published
- 2020
142. Multiple Transporters and Glycoside Hydrolases Are Involved in Arabinoxylan-Derived Oligosaccharide Utilization in Bifidobacterium pseudocatenulatum
- Author
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Taeko Hara, Kaoru Moriyama-Ohara, Takahiro Matsuki, Yohei Watanabe, Satoshi Matsumoto, Yuki Saito, Hirokazu Tsuji, Akira Shigehisa, and Naoki Tsukuda
- Subjects
Arabinose ,Bifidobacterium longum ,Glycoside Hydrolases ,medicine.medical_treatment ,Bifidobacterium pseudocatenulatum ,Oligosaccharides ,Genetics and Molecular Biology ,bifidobacteria ,ATP-binding cassette transporter ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,Arabinoxylan ,medicine ,glycoside hydrolase ,Glycoside hydrolase ,GH43 ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Ecology ,biology ,030306 microbiology ,Prebiotic ,Oligosaccharide ,dietary fiber ,biology.organism_classification ,arabinoxylan ,ABC transporters ,chemistry ,Biochemistry ,Xylans ,Carrier Proteins ,Food Science ,Biotechnology - Abstract
Bifidobacteria commonly reside in the human intestine and possess abundant genes involved in carbohydrate utilization. Arabinoxylan hydrolysates (AXH) are hydrolyzed products of arabinoxylan, one of the most abundant dietary fibers, and they include xylooligosaccharides and those decorated with arabinofuranosyl residues. The molecular mechanism by which B. pseudocatenulatum, a common bifidobacterial species found in adult feces, utilizes structurally and compositionally variable AXH has yet to be extensively investigated. In this study, we identified three gene clusters (encoding five GH43 enzymes and three solute-binding proteins of ABC transporters) that were upregulated in B. pseudocatenulatum YIT 4072T during AXH utilization. By investigating their substrate specificities, we revealed how these proteins are involved in the uptake and degradation of AXH. These molecular insights may provide a better understanding of how resident bifidobacteria colonize the colon., Arabinoxylan hydrolysates (AXH) are the hydrolyzed products of the major components of the dietary fiber arabinoxylan. AXH include diverse oligosaccharides varying in xylose polymerization and side residue modifications with arabinose at the O-2 and/or O-3 position of the xylose unit. Previous studies have reported that AXH exhibit prebiotic properties on gut bifidobacteria; moreover, several adult-associated bifidobacterial species (e.g., Bifidobacterium adolescentis and Bifidobacterium longum subsp. longum) are known to utilize AXH. In this study, we tried to elucidate the molecular mechanisms of AXH utilization by Bifidobacterium pseudocatenulatum, which is a common bifidobacterial species found in adult feces. We performed transcriptomic analysis of B. pseudocatenulatum YIT 4072T, which identified three upregulated gene clusters during AXH utilization. The gene clusters encoded three sets of ATP-binding cassette (ABC) transporters and five enzymes belonging to glycoside hydrolase family 43 (GH43). By characterizing the recombinant proteins, we found that three solute-binding proteins of ABC transporters showed either broad or narrow specificity, two arabinofuranosidases hydrolyzed either single- or double-decorated arabinoxylooligosaccharides, and three xylosidases exhibited functionally identical activity. These data collectively suggest that the transporters and glycoside hydrolases, encoded in the three gene clusters, work together to utilize AXH of different sizes and with different side residue modifications. Thus, our study sheds light on the overall picture of how these proteins collaborate for the utilization of AXH in B. pseudocatenulatum and may explain the predominance of this symbiont species in the adult human gut. IMPORTANCE Bifidobacteria commonly reside in the human intestine and possess abundant genes involved in carbohydrate utilization. Arabinoxylan hydrolysates (AXH) are hydrolyzed products of arabinoxylan, one of the most abundant dietary fibers, and they include xylooligosaccharides and those decorated with arabinofuranosyl residues. The molecular mechanism by which B. pseudocatenulatum, a common bifidobacterial species found in adult feces, utilizes structurally and compositionally variable AXH has yet to be extensively investigated. In this study, we identified three gene clusters (encoding five GH43 enzymes and three solute-binding proteins of ABC transporters) that were upregulated in B. pseudocatenulatum YIT 4072T during AXH utilization. By investigating their substrate specificities, we revealed how these proteins are involved in the uptake and degradation of AXH. These molecular insights may provide a better understanding of how resident bifidobacteria colonize the colon.
- Published
- 2020
143. CELF family RNA-binding protein UNC-75 regulates two sets of mutually exclusive exons of the unc-32 gene in neuron-specific manners in Caenorhabditis elegans.
- Author
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Hidehito Kuroyanagi, Yohei Watanabe, and Masatoshi Hagiwara
- Subjects
Genetics ,QH426-470 - Abstract
An enormous number of alternative pre-mRNA splicing patterns in multicellular organisms are coordinately defined by a limited number of regulatory proteins and cis elements. Mutually exclusive alternative splicing should be strictly regulated and is a challenging model for elucidating regulation mechanisms. Here we provide models of the regulation of two sets of mutually exclusive exons, 4a-4c and 7a-7b, of the Caenorhabditis elegans uncoordinated (unc)-32 gene, encoding the a subunit of V0 complex of vacuolar-type H(+)-ATPases. We visualize selection patterns of exon 4 and exon 7 in vivo by utilizing a trio and a pair of symmetric fluorescence splicing reporter minigenes, respectively, to demonstrate that they are regulated in tissue-specific manners. Genetic analyses reveal that RBFOX family RNA-binding proteins ASD-1 and FOX-1 and a UGCAUG stretch in intron 7b are involved in the neuron-specific selection of exon 7a. Through further forward genetic screening, we identify UNC-75, a neuron-specific CELF family RNA-binding protein of unknown function, as an essential regulator for the exon 7a selection. Electrophoretic mobility shift assays specify a short fragment in intron 7a as the recognition site for UNC-75 and demonstrate that UNC-75 specifically binds via its three RNA recognition motifs to the element including a UUGUUGUGUUGU stretch. The UUGUUGUGUUGU stretch in the reporter minigenes is actually required for the selection of exon 7a in the nervous system. We compare the amounts of partially spliced RNAs in the wild-type and unc-75 mutant backgrounds and raise a model for the mutually exclusive selection of unc-32 exon 7 by the RBFOX family and UNC-75. The neuron-specific selection of unc-32 exon 4b is also regulated by UNC-75 and the unc-75 mutation suppresses the Unc phenotype of the exon-4b-specific allele of unc-32 mutants. Taken together, UNC-75 is the neuron-specific splicing factor and regulates both sets of the mutually exclusive exons of the unc-32 gene.
- Published
- 2013
- Full Text
- View/download PDF
144. PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range
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Yasuha Arai, Kazuhiko Matsumoto, Yohei Watanabe, Takao Ono, Madiha S. Ibrahim, Tatsuya Takagi, Takaaki Nakaya, Emad Mohamed Elgendy, Norihito Kawashita, and Tomo Daidoji
- Subjects
Models, Molecular ,viruses ,Immunology ,Viral Nonstructural Proteins ,medicine.disease_cause ,Virus Replication ,Microbiology ,Virus ,Host Specificity ,influenza virus ,Cell Line ,Evolution, Molecular ,Mice ,Orthomyxoviridae Infections ,Virology ,evolution ,medicine ,Animals ,Humans ,Clade ,Polymerase ,Phylogeny ,Mutation ,biology ,Influenza A Virus, H5N1 Subtype ,virus diseases ,H5N1 ,host adaptation ,RNA-Dependent RNA Polymerase ,Adaptation, Physiological ,Influenza A virus subtype H5N1 ,Viral replication ,Insect Science ,Viral evolution ,biology.protein ,Pathogenesis and Immunity ,Egypt ,Host adaptation ,Chickens - Abstract
Clade 2.2.1 avian influenza viruses (H5N1) are unique to Egypt and have caused the highest number of human H5N1 influenza cases worldwide, presenting a serious global public health threat. These viruses may have the greatest evolutionary potential for adaptation from avian hosts to human hosts. Using a comprehensive phylogenetic approach, we identified several novel clade 2.2.1 virus polymerase mutations that increased viral replication in vitro in human cells and in vivo in mice. These mutations were in the polymerase PA subunit and acted cooperatively with the E627K mutation in the PB2 polymerase subunit to provide higher replication in contemporary clade 2.2.1.2 viruses than in ancestral clade 2.2.1 viruses. These data indicated that ongoing clade 2.2.1 dissemination in the field has driven PA mutations to modify viral replication to enable host range expansion, with a higher public health risk for humans., Adaptive mutations and/or reassortments in avian influenza virus polymerase subunits PA, PB1, and PB2 are one of the major factors enabling the virus to overcome the species barrier to infect humans. The majority of human adaptation polymerase mutations have been identified in PB2; fewer adaptation mutations have been characterized in PA and PB1. Clade 2.2.1 avian influenza viruses (H5N1) are unique to Egypt and generally carry the human adaptation PB2-E627K substitution during their dissemination in nature. In this study, we identified other human adaptation polymerase mutations by analyzing phylogeny-associated PA mutations that H5N1 clade 2.2.1 viruses have accumulated during their evolution in the field. This analysis identified several PA mutations that produced increased replication by contemporary clade 2.2.1.2 viruses in vitro in human cells and in vivo in mice compared to ancestral clade 2.2.1 viruses. The PA mutations acted cooperatively to increase viral polymerase activity and replication in both avian and human cells, with the effect being more prominent in human cells at 33°C than at 37°C. These results indicated that PA mutations have a role in establishing contemporary clade 2.2.1.2 virus infections in poultry and in adaptation to infect mammals. Our study provided data on the mechanism for PA mutations to accumulate during avian influenza virus evolution and extend the viral host range. IMPORTANCE Clade 2.2.1 avian influenza viruses (H5N1) are unique to Egypt and have caused the highest number of human H5N1 influenza cases worldwide, presenting a serious global public health threat. These viruses may have the greatest evolutionary potential for adaptation from avian hosts to human hosts. Using a comprehensive phylogenetic approach, we identified several novel clade 2.2.1 virus polymerase mutations that increased viral replication in vitro in human cells and in vivo in mice. These mutations were in the polymerase PA subunit and acted cooperatively with the E627K mutation in the PB2 polymerase subunit to provide higher replication in contemporary clade 2.2.1.2 viruses than in ancestral clade 2.2.1 viruses. These data indicated that ongoing clade 2.2.1 dissemination in the field has driven PA mutations to modify viral replication to enable host range expansion, with a higher public health risk for humans.
- Published
- 2020
145. H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity
- Author
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Yohei Watanabe, Kazuhiko Matsumoto, Madiha S. Ibrahim, Takao Ono, Yasuha Arai, Nongluk Sriwilaijaroen, Yasuo Suzuki, Takaaki Nakaya, Emad Mohamed Elgendy, and Tomo Daidoji
- Subjects
Gene Expression Regulation, Viral ,Glycosylation ,Genotype ,viruses ,Immunology ,Virulence ,Hemagglutinin (influenza) ,host range ,Neuraminidase ,Hemagglutinin Glycoproteins, Influenza Virus ,medicine.disease_cause ,Virus Replication ,Microbiology ,Virus ,H9N2 influenza virus ,Host Specificity ,Mice ,Structure-Activity Relationship ,Orthomyxoviridae Infections ,Viral entry ,Virology ,medicine ,Influenza A Virus, H9N2 Subtype ,Animals ,Humans ,hemagglutinin ,Amino Acid Sequence ,Phylogeny ,Sequence Deletion ,biology ,functional balance ,neuraminidase stalk ,Virus Internalization ,Influenza A virus subtype H5N1 ,infection ,Virus-Cell Interactions ,Hemagglutinins ,Phenotype ,Stalk ,Viral replication ,Insect Science ,Influenza in Birds ,Host-Pathogen Interactions ,biology.protein ,Receptors, Virus ,Chickens - Abstract
H9N2 avian influenza (AI) virus, one of the most prevalent AI viruses, has caused repeated poultry and human infections, posing a huge public health risk. The H9N2 virus has diversified into multiple lineages, with the G1 lineage being the most prevalent worldwide. In this study, we isolated G1 variants carrying an 8-amino-acid deletion in their NA stalk, which is, to our knowledge, the longest deletion found in H9N2 viruses in the field. The NA stalk length was found to modulate G1 virus entry into host cells, with the effects being species specific and dependent on the corresponding HA binding affinity. Our results suggest that, in nature, H9N2 G1 viruses balance their HA and NA functions by the NA stalk length, leading to the possible association of host range and virulence in poultry and mammals during the evolution of G1 lineage viruses., Some avian influenza (AI) viruses have a deletion of up to 20 to 30 amino acids in their neuraminidase (NA) stalk. This has been associated with changes in virus replication and host range. Currently prevalent H9N2 AI viruses have only a 2- or 3-amino-acid deletion, and such deletions were detected in G1 and Y280 lineage viruses, respectively. The effect of an NA deletion on the H9N2 phenotype has not been fully elucidated. In this study, we isolated G1 mutants that carried an 8-amino-acid deletion in their NA stalk. To systematically analyze the effect of NA stalk length and concomitant (de)glycosylation on G1 replication and host range, we generated G1 viruses that had various NA stalk lengths and that were either glycosylated or not glycosylated. The stalk length was correlated with NA sialidase activity, using low-molecular-weight substrates, and with virus elution efficacy from erythrocytes. G1 virus replication in avian cells and eggs was positively correlated with the NA stalk length but was negatively correlated in human cells and mice. NA stalk length modulated G1 virus entry into host cells, with shorter stalks enabling more efficient G1 entry into human cells. However, with a hemagglutinin (HA) with a higher α2,6-linked sialylglycan affinity, the effect of NA stalk length on G1 virus infection was reversed, with shorter NA stalks reducing virus entry into human cells. These results indicate that a balance between HA binding affinity and NA sialidase activity, modulated by NA stalk length, is required for optimal G1 virus entry into human airway cells. IMPORTANCE H9N2 avian influenza (AI) virus, one of the most prevalent AI viruses, has caused repeated poultry and human infections, posing a huge public health risk. The H9N2 virus has diversified into multiple lineages, with the G1 lineage being the most prevalent worldwide. In this study, we isolated G1 variants carrying an 8-amino-acid deletion in their NA stalk, which is, to our knowledge, the longest deletion found in H9N2 viruses in the field. The NA stalk length was found to modulate G1 virus entry into host cells, with the effects being species specific and dependent on the corresponding HA binding affinity. Our results suggest that, in nature, H9N2 G1 viruses balance their HA and NA functions by the NA stalk length, leading to the possible association of host range and virulence in poultry and mammals during the evolution of G1 lineage viruses.
- Published
- 2020
146. [A Case of Rectovaginal Fistula after Rectal Cancer Surgery Cured with Estriol Vaginal Tablet and Vaginal Lavage]
- Author
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Shotaro, Fujita, Tomoyuki, Momma, Eisei, Endo, Koji, Kase, Daisuke, Ujiie, Hiroyuki, Hanayama, Yohei, Watanabe, Hirokazu, Okayama, Wataru, Sakamoto, Hisahito, Endo, Motonobu, Saito, Zenichiro, Saze, Shinji, Ohki, and Koji, Kono
- Subjects
Estriol ,Rectal Neoplasms ,Rectovaginal Fistula ,Vaginal Creams, Foams, and Jellies ,Humans ,Vaginal Douching ,Female ,Neoplasm Recurrence, Local ,Digestive System Surgical Procedures ,Aged - Abstract
Although rectovaginal fistula is a rare complication of rectal cancer surgery, it is usually difficult to cure with conservative treatment, and patients generally need surgical intervention. A woman in her 70s underwent laparoscopic low anterior resection with right lateral lymph node dissection for rectal cancer. On postoperative day(POD)6, she had an anastomotic leakage and received conservative treatment. On POD 9, she underwent emergent laparotomy for urinary peritonitis as well as ileostomy and ureteral stenting. On POD 21, the rectovaginal fistula was confirmed with lower gastrointestinal tract fluoroscopic examination. The patient received conservative therapy for the rectovaginal fistula with estriol vaginal tablets and vaginal lavage for 2 weeks. Subsequently, the fistula was completely cured. After continuation of the estriol vaginal tablets for 4 weeks, the rectovaginal fistula has not recurred at the most recent follow-up.
- Published
- 2020
147. Immune suppression caused by PD-L2 expression on tumor cells in gastric cancer
- Author
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Katsuharu Saito, Yuko Nakayama, Yoshiyuki Suzuki, Shinji Ohki, Hiroyuki Hanayama, Motonobu Saito, Yohei Watanabe, Ley-Fang Kua, Aung Kyi Thar Min, Kosaku Mimura, Hirokazu Okayama, Daisuke Ichikawa, Zenichiro Saze, Wei Peng Yong, Koji Kono, and Tomoyuki Momma
- Subjects
Cancer Research ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Clone (cell biology) ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Stomach Neoplasms ,Cell Line, Tumor ,Medicine ,Cytotoxic T cell ,Humans ,Cytotoxicity ,Immunosuppression Therapy ,business.industry ,Gastroenterology ,General Medicine ,Immunotherapy ,Programmed Cell Death 1 Ligand 2 Protein ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,CTL ,Oncology ,Cell culture ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents ,T-Lymphocytes, Cytotoxic - Abstract
Gastric cancer (GC) patients with PD-L1-negative tumor occasionally have a favorable response to anti-PD-1 mAb. The aim of the present study was to investigate the regulatory mechanism and immunosuppressive role of PD-L2 in GC. We used immunohistochemistry to evaluate the expression of PD-L2 in primary tumors from 194 patients with GC. The mechanism of PD-L2 expression was assessed in TCGA stomach adenocarcinoma tissue dataset and in vitro assay using GC cell lines. The immunosuppressive role of PD-L2 was evaluated by cytotoxicity of CTL clone against PD-L2 expressing GC cells. PD-L2 was expressed on tumor cells (TCs) of 28.4% patients and PD-L2 expression on TCs was significantly associated with tumor progression. TCGA dataset revealed that IFN-γ and, to a lesser extent, IL-4 signature significantly correlated with PD-L2 expression. In vitro assay showed that IFN-γ and, also to a lesser extent, IL-4 can upregulate PD-L2 expression on GC cells. Anti-PD-L2 mAb significantly enhanced the cytotoxicity of CTL clone against GC cell lines expressing PD-L2. PD-L2 is expressed on GC cells and PD-1/PD-L2 interaction are functionally involved in anti-tumor CTL activities. PD-L2 expression should be considered when determining the optimal immunotherapy for GC.
- Published
- 2020
148. Infection of Human Tracheal Epithelial Cells by H5 Avian Influenza Virus Is Regulated by the Acid Stability of Hemagglutinin and the pH of Target Cell Endosomes
- Author
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Ryohei Hirose, Takaaki Nakaya, Yohei Watanabe, Junichi Kajikawa, Tomo Daidoji, and Yasuha Arai
- Subjects
0301 basic medicine ,Endosome ,animal diseases ,030106 microbiology ,Cell ,lcsh:QR1-502 ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Endosomes ,avian influenza virus ,Biology ,medicine.disease_cause ,lcsh:Microbiology ,Article ,Microbiology ,03 medical and health sciences ,Virology ,medicine ,Humans ,hemagglutinin ,Tropism ,Cell Line, Transformed ,Influenza A Virus, H5N1 Subtype ,Lipid bilayer fusion ,virus diseases ,Epithelial Cells ,tracheal epithelial cells ,Hydrogen-Ion Concentration ,respiratory system ,Influenza A virus subtype H5N1 ,Trachea ,Viral Tropism ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,endosomal pH ,Tissue tropism ,biology.protein ,Receptors, Virus ,Acids ,Respiratory tract - Abstract
Despite the possible relationships between tracheal infection and concomitant infection of the terminal part of the lower respiratory tract (bronchioles/alveoli), the behavior of avian influenza viruses (AIVs), such as H5N1, in the conducting airways is unclear. To examine the tropism of AIVs for cells lining the conducting airways of humans, we established human tracheal epithelial cell clones (HTEpC-Ts) and examined their susceptibility to infection by AIVs. The HTEpC-Ts showed differing susceptibility to H5N1 and non-zoonotic AIVs. Viral receptors expressed by HTEpC-Ts bound all viruses, however, the endosomal pH was associated with the overall susceptibility to infection by AIVs. Moreover, H5N1 hemagglutinin broadened viral tropism to include HTEpC-Ts, because it had a higher pH threshold for viral&ndash, cell membrane fusion. Thus, H5N1 viruses infect human tracheal epithelial cells as a result of their higher pH threshold for membrane fusion which may be one mechanism underlying H5N1 pathogenesis in human airway epithelia. Efficient replication of H5N1 in the conducting airways of humans may facilitate infection of the lower respiratory tract.
- Published
- 2020
- Full Text
- View/download PDF
149. Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice.
- Author
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Kunihiko Moriya, Makiko Suzuki, Yohei Watanabe, Takeshi Takahashi, Yoko Aoki, Toru Uchiyama, Satoru Kumaki, Yoji Sasahara, Masayoshi Minegishi, Shigeo Kure, Shigeru Tsuchiya, Kazuo Sugamura, and Naoto Ishii
- Subjects
Medicine ,Science - Abstract
Mixed-lineage-leukemia (MLL) fusion oncogenes are intimately involved in acute leukemia and secondary therapy-related acute leukemia. To understand MLL-rearranged leukemia, several murine models for this disease have been established. However, the mouse leukemia derived from mouse hematopoietic stem cells (HSCs) may not be fully comparable with human leukemia. Here we developed a humanized mouse model for human leukemia by transplanting human cord blood-derived HSCs transduced with an MLL-AF10 oncogene into a supra-immunodeficient mouse strain, NOD/Shi-scid, IL-2Rγ(-/-) (NOG) mice. Injection of the MLL-AF10-transduced HSCs into the liver of NOG mice enhanced multilineage hematopoiesis, but did not induce leukemia. Because active mutations in ras genes are often found in MLL-related leukemia, we next transduced the gene for a constitutively active form of K-ras along with the MLL-AF10 oncogene. Eight weeks after transplantation, all the recipient mice had developed acute monoblastic leukemia (the M5 phenotype in French-American-British classification). We thus successfully established a human MLL-rearranged leukemia that was derived in vivo from human HSCs. In addition, since the enforced expression of the mutant K-ras alone was insufficient to induce leukemia, the present model may also be a useful experimental platform for the multi-step leukemogenesis model of human leukemia.
- Published
- 2012
- Full Text
- View/download PDF
150. Muscle-specific splicing factors ASD-2 and SUP-12 cooperatively switch alternative pre-mRNA processing patterns of the ADF/cofilin gene in Caenorhabditis elegans.
- Author
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Genta Ohno, Kanako Ono, Marina Togo, Yohei Watanabe, Shoichiro Ono, Masatoshi Hagiwara, and Hidehito Kuroyanagi
- Subjects
Genetics ,QH426-470 - Abstract
Pre-mRNAs are often processed in complex patterns in tissue-specific manners to produce a variety of protein isoforms from single genes. However, mechanisms orchestrating the processing of the entire transcript are not well understood. Muscle-specific alternative pre-mRNA processing of the unc-60 gene in Caenorhabditis elegans, encoding two tissue-specific isoforms of ADF/cofilin with distinct biochemical properties in regulating actin organization, provides an excellent in vivo model of complex and tissue-specific pre-mRNA processing; it consists of a single first exon and two separate series of downstream exons. Here we visualize the complex muscle-specific processing pattern of the unc-60 pre-mRNA with asymmetric fluorescence reporter minigenes. By disrupting juxtaposed CUAAC repeats and UGUGUG stretch in intron 1A, we demonstrate that these elements are required for retaining intron 1A, as well as for switching the processing patterns of the entire pre-mRNA from non-muscle-type to muscle-type. Mutations in genes encoding muscle-specific RNA-binding proteins ASD-2 and SUP-12 turned the colour of the unc-60 reporter worms. ASD-2 and SUP-12 proteins specifically and cooperatively bind to CUAAC repeats and UGUGUG stretch in intron 1A, respectively, to form a ternary complex in vitro. Immunohistochemical staining and RT-PCR analyses demonstrate that ASD-2 and SUP-12 are also required for switching the processing patterns of the endogenous unc-60 pre-mRNA from UNC-60A to UNC-60B in muscles. Furthermore, systematic analyses of partially spliced RNAs reveal the actual orders of intron removal for distinct mRNA isoforms. Taken together, our results demonstrate that muscle-specific splicing factors ASD-2 and SUP-12 cooperatively promote muscle-specific processing of the unc-60 gene, and provide insight into the mechanisms of complex pre-mRNA processing; combinatorial regulation of a single splice site by two tissue-specific splicing regulators determines the binary fate of the entire transcript.
- Published
- 2012
- Full Text
- View/download PDF
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