6,397 results on '"Kubo, A"'
Search Results
2. The Effects of Red Light on Neonicotinoid-Exposed Honey Bees
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Kubo, Kevin David Kazuyuki
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Ecology ,Entomology ,Biology ,honey bees ,mitochondria ,neonicotinoids ,red light - Abstract
Honey bees are important pollinators in ecosystems and for agriculture across the world. When they are exposed to neonicotinoid pesticides such as thiamethoxam (TMX), there are significant negative effects even at sublethal doses. Red light exposure may be able to reduce the harmful sublethal effects of pesticides in honey bees. By studying survival over time, phototactic behavior in acutely exposed bees, and using respirometry analysis to track mitochondrial function, this research tested the efficacy of different exposure times of 660 nm red light on bees exposed to varying amounts of the neonicotinoid pesticide thiamethoxam (TMX). Survival assays showed that at a low but field realistic dose of TMX, 5 min of 660 nm red light exposure once per day improved the survival rate of pesticide-exposed bees to the level of comparable bees not exposed to pesticide. Phototaxis assays indicated that at sufficiently high doses, a combination of acute pesticide exposure and 660 nm red light exacerbates the effects of TMX, increasing bee mortality and inducing more severe, deadly response to TMX. Mitochondrial respirometry revealed significant negative effects of the short dose of red light on the function of several functional mitochondrial complexes. These are the first results exploring the specific negative interactions neonicotinoids have on mitochondrial function. Thus, red light can rescue bees exposed to a low dose of TMX, but the combination of the two can also be harmful.
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- 2022
3. Mendelian Randomization on hs-CRP and eGFR
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Kiyonori Kuriki, Haruo Mikami, Chisato Shimanoe, Masahiro Nakatochi, Asahi Hishida, Hiroaki Ikezaki, Kenji Wakai, Yuichiro Nishida, Sadao Suzuki, Miki Watanabe, Sakurako Katsuura-Kamano, Masayuki Murata, Rie Ibusuki, Mineko Tsukamoto, Daisuke Matsui, Tanvir Chowdhury Turin, Hidemi Ito, Ryosuke Fujii, Takeshi Nishiyama, Takashi Tamura, Toshiro Takezaki, Keitaro Matsuo, Yukihide Momozawa, Yasuyuki Nakamura, Nagato Kuriyama, Yohko Nakamura, Yoko Kubo, Michiaki Kubo, Kokichi Arisawa, Kenji Takeuchi, and Takaaki Kondo
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Oncology ,medicine.medical_specialty ,genetic epidemiology ,Epidemiology ,Renal function ,030209 endocrinology & metabolism ,Single-nucleotide polymorphism ,Kidney ,Polymorphism, Single Nucleotide ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Mendelian randomization ,eGFR ,medicine ,Humans ,030212 general & internal medicine ,Mendelian randomization study ,Risk factor ,biology ,business.industry ,C-reactive protein ,General Medicine ,Mendelian Randomization Analysis ,medicine.disease ,hs-CRP ,C-Reactive Protein ,Genetic epidemiology ,inflammation ,biology.protein ,business ,Kidney disease ,Cohort study - Abstract
Background: Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches. Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively. Results: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval [CI], −0.019 to 0.020 and −0.003; 95% CI, −0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 0.005; 95% CI, −0.020 to 0.010 and −0.004; 95% CI, −0.020 to 0.012, respectively). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: −0.008; 95% CI, −0.058 to 0.042; IVAsian: 0.001; 95% CI, −0.036 to 0.036). Conclusion: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.
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- 2022
4. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
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Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holger, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Hung, Adriana M., Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, Heid, Iris M., Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, University of Helsinki, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, Research Programs Unit, Tampere University, Clinical Medicine, TAYS Heart Centre, Department of Clinical Chemistry, Department of Clinical Physiology and Nuclear Medicine, Internal Medicine, Pediatrics, Epidemiology, Radiology & Nuclear Medicine, Erasmus MC other, Home Office, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), UK DRI Ltd, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Winkler, Thomas W, Rasheed, Humaira, Teumer, Alexander, Gorski, Mathia, Rowan, Bryce X, Stanzick, Kira J, Thomas, Laurent F, Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y, Tayo, Bamidele, Thio, Chris H L, Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B, Horn, Katrin, Li, Man, Scholz, Marku, Cocca, Massimiliano, Wuttke, Matthia, van der Most, Peter J, Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abba, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P J, Zonderman, Alan B, Smith, Albert V, Oldehinkel, Albertine J, De Grandi, Alessandro, Rosenkranz, Alexander R, Franke, Andre, Teren, Andrej, Metspalu, Andre, Hicks, Andrew A, Morris, Andrew P, Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I, Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I, Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K, Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H, Ning, Boting, Penninx, Brenda W J H, Vanderwerff, Brett R, Psaty, Bruce M, Kammerer, Candace M, Langefeld, Carl D, Hayward, Caroline, Spracklen, Cassandra N, Robinson-Cohen, Cassianne, Hartman, Catharina A, Lindgren, Cecilia M, Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M, Schulz, Christina-Alexandra, Willer, Cristen J, Chasman, Daniel I, Gudbjartsson, Daniel F, Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J, Waterworth, Dawn M, Mascalzoni, Deborah, Mook-Kanamori, Dennis O, Reilly, Dermot F, Daw, E Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N, Delgado, Graciela E, Montgomery, Grant W, Snieder, Harold, Campbell, Harry, White, Harvey D, Gao, He, Stringham, Heather M, Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M, Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P, Wilson, James F, Halbritter, Jan, Felix, Janine F, Divers, Jasmin, Kooner, Jaspal S, Lee, Jeannette Jen-Mai, O'Connell, Jeffrey, Rotter, Jerome I, Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C, Whitfield, John B, Gaziano, John M, Marten, Jonathan, Coresh, Josef, Jonas, Jost B, Mychaleckyj, Josyf C, Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L, Endlich, Karlhan, Dittrich, Katalin, Ryan, Kathleen A, Rice, Kenneth M, Taylor, Kent D, Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lar, Wallentin, Lar, Yerges-Armstrong, Laura M, Raffield, Laura M, Phillips, Lawrence S, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Lange, Leslie A, Citterio, Lorena, Klaric, Lucija, Ikram, M Arfan, Ising, Marcu, Kleber, Marcus E, Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Marku, Perola, Marku, de Borst, Martin H, Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F, Biggs, Mary L, Wojczynski, Mary K, Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthia, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H, Stumvoll, Michael, Province, Michael A, Evans, Michele K, O'Donoghue, Michelle L, Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A, Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G, Tan, Nicholas Y Q, Palmer, Nicholette D, Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T, Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P, Sulem, Patrick, Magnusson, Patrik K E, Elliott, Paul, Ridker, Paul M, Hamet, Pavel, Svensson, Per O, Joshi, Peter K, Kovacs, Peter, Pramstaller, Peter P, Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z H, Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M, Carroll, Robert J, Gansevoort, Ron T, Loos, Ruth J F, Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A, Graham, Sarah E, Gordon, Scott D, Hwang, Shih-Jen, Kerr, Shona M, Vaccargiu, Simona, Patil, Snehal B, Hallan, Stein, Bakker, Stephan J L, Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S, Lehtimäki, Terho, Boutin, Thibaud S, Meitinger, Thoma, Wong, Tien-Yin, Bergler, Tobia, Rabelink, Ton J, Esko, Tõnu, Haller, Tooma, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmanta, Gudnason, Vilmundur, Jaddoe, Vincent W V, Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J, Stefansson, Kari, Böger, Carsten A, Hung, Adriana M, Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, Heid, Iris M, and Lee Kong Chian School of Medicine (LKCMedicine)
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Life Sciences & Biomedicine - Other Topics ,EXPRESSION ,Diabetic Nephropathies/genetics ,610 Medizin ,LOCI ,Medicine (miscellaneous) ,EFFICIENT ,Lifelines cohort study ,Kidney ,General Biochemistry, Genetics and Molecular Biology ,DISEASE ,QUALITY-CONTROL ,SDG 3 - Good Health and Well-being ,Diabetic Nephropathy ,Diabetes Mellitus ,Humans ,Medicine [Science] ,Diabetic Nephropathies ,GENOME-WIDE ASSOCIATION ,Biology ,DiscovEHR/MyCode study ,METAANALYSIS ,Glomerular Filtration Rate/genetics ,Medicinsk genetik ,ddc:610 ,Science & Technology ,genetic ,effects ,kidney ,diabetic ,JOINT ,Klinisk medicin ,Diabetes Mellitu ,3126 Surgery, anesthesiology, intensive care, radiology ,Multidisciplinary Sciences ,ENVIRONMENT INTERACTION ,Creatinine ,VA Million Veteran Program ,Science & Technology - Other Topics ,3111 Biomedicine ,Clinical Medicine ,SMOKING ,General Agricultural and Biological Sciences ,Life Sciences & Biomedicine ,Medical Genetics ,Human ,Genome-Wide Association Study ,Glomerular Filtration Rate - Abstract
Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM. Published version The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) supported the meta-analysis—Project-ID 387509280—SFB1350 (Subproject C6 to I.M.H.). A.M.H., B.R., and R.T. were supported by VACSR&D MVP grant CX001897. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by VACSR&D MVP grant CX001897 (A.M.H.). This publication does not represent the views of the Department of Veteran Affairs or the United States Government. We conducted this research using the UK Biobank resource under the application number 20272.
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- 2022
5. Microwear textures associated with experimental near-natural diets suggest that seeds and hard insect body parts cause high enamel surface complexity in small mammals
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Winkler, Daniela E, Clauss, Marcus, Kubo, Mugino O, Schulz-Kornas, Ellen, Kaiser, Thomas M, Tschudin, Anja, De Cuyper, Annelies, Kubo, Tai, Tütken, Thomas, and University of Zurich
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10253 Department of Small Animals ,Evolution ,F344/N ,DENTAL MICROWEAR ,mechanical properties ,microwear ,RATS ,hard-object feeding ,TEETH ,Behavior and Systematics ,550 Earth sciences ,THICKNESS ,RECONSTRUCTION ,Veterinary Sciences ,Ecology, Evolution, Behavior and Systematics ,OCCLUSAL TOOTH WEAR ,630 Agriculture ,Ecology ,MECHANICAL-PROPERTIES ,PRIMATES ,550 Geowissenschaften ,material ,properties ,ADAPTATIONS ,570 Life sciences ,biology ,dental wear ,MIOCENE - Abstract
In mammals, complex dental microwear textures (DMT) representing differently sized and shaped enamel lesions overlaying each other have traditionally been associated with the seeds and kernels in frugivorous diets, as well as with sclerotized insect cuticles. Recently, this notion has been challenged by field observations as well as in vitro experimental data. It remains unclear to what extent each food item contributes to the complexity level and is reflected by the surface texture of the respective tooth position along the molar tooth row. To clarify the potential of seeds and other abrasive dietary items to cause complex microwear textures, we conducted a controlled feeding experiment with rats. Six individual rats each received either a vegetable mix, a fruit mix, a seed mix, whole crickets, whole black soldier fly larvae, or whole day-old-chicks. These diets were subjected to material testing to obtain mechanical properties, such as Young’s modulus, yield strength, and food hardness (as indicated by texture profile analysis [TPA] tests). Seeds and crickets caused the highest surface complexity. The fruit mix, seed mix, and crickets caused the deepest wear features. Moreover, several diets resulted in an increasing wear gradient from the first to the second molar, suggesting that increasing bite force along the tooth row affects dental wear in rats on these diets. Mechanical properties of the diets showed different correlations with DMT obtained for the first and second molars. The first molar wear was mostly correlated with maximum TPA hardness, while the second molar wear was strongly correlated with maximum yield stress, mean TPA hardness, and maximum TPA hardness. This indicates a complex relationship between chewing mechanics, food mechanical properties, and observed DMT. Our results show that, in rats, seeds are the main cause of complex microwear textures but that hard insect body parts can also cause high complexity. However, the similarity in parameter values of surface textures resulting from seed and cricket consumption did not allow differentiation between these two diets in our experimental approach.
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- 2022
6. Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation
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Saito, Akatsuki, Irie, Takashi, Suzuki, Rigel, Maemura, Tadashi, Nasser, Hesham, Uriu, Keiya, Kosugi, Yusuke, Shirakawa, Kotaro, Sadamasu, Kenji, Kimura, Izumi, Ito, Jumpei, Wu, Jiaqi, Iwatsuki-Horimoto, Kiyoko, Ito, Mutsumi, Yamayoshi, Seiya, Loeber, Samantha, Tsuda, Masumi, Wang, Lei, Ozono, Seiya, Butlertanaka, Erika P., Tanaka, Yuri L., Shimizu, Ryo, Shimizu, Kenta, Yoshimatsu, Kumiko, Kawabata, Ryoko, Sakaguchi, Takemasa, Tokunaga, Kenzo, Yoshida, Isao, Asakura, Hiroyuki, Nagashima, Mami, Kazuma, Yasuhiro, Nomura, Ryosuke, Horisawa, Yoshihito, Yoshimura, Kazuhisa, Takaori-Kondo, Akifumi, Imai, Masaki, Chiba, Mika, Furihata, Hirotake, Hasebe, Haruyo, Kitazato, Kazuko, Kubo, Haruko, Misawa, Naoko, Morizako, Nanami, Noda, Kohei, Oide, Akiko, Suganami, Mai, Takahashi, Miyoko, Tsushima, Kana, Yokoyama, Miyabishara, Yuan, Yue, Tanaka, Shinya, Nakagawa, So, Ikeda, Terumasa, Fukuhara, Takasuke, Kawaoka, Yoshihiro, and Sato, Kei
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Delta ,Male ,Lineage (genetic) ,Viral pathogenesis ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Biology ,medicine.disease_cause ,Antibodies, Viral ,Virus Replication ,Genome ,Giant Cells ,Membrane Fusion ,Virus ,Cricetinae ,medicine ,Animals ,Phylogeny ,Mutation ,Multidisciplinary ,Mesocricetus ,Virulence ,SARS-CoV-2 ,COVID-19 ,Phenotype ,Virology ,Antibodies, Neutralizing ,Amino Acid Substitution ,Spike Glycoprotein, Coronavirus - Abstract
During the current SARS-CoV-2 pandemic, a variety of mutations have accumulated in the viral genome, and currently, four variants of concern (VOCs) are considered potentially hazardous to human society1. The recently emerged B.1.617.2/Delta VOC is closely associated with the COVID-19 surge that occurred in India in the spring of 20212. However, its virological properties remain unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity., SARS-CoV-2デルタ株に特徴的なP681R変異は ウイルスの病原性を増大させる. 京都大学プレスリリース. 2021-11-26.
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- 2022
7. Pulmonary Aspergilloma and Allergic Bronchopulmonary Aspergillosis Following the 2018 Heavy Rain Event in Western Japan
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Masahiro Tabata, Katsuyuki Hotta, Nobuaki Miyahara, Toshio Kubo, Masaomi Yamane, Eiki Ichihara, Kammei Rai, Kiichiro Ninomiya, Yuka Kato, Katsuyuki Kiura, Takamasa Nakasuka, Eri Ando, Akihiko Taniguchi, Kadoaki Ohashi, and Yoshinobu Maeda
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Male ,medicine.medical_specialty ,Adolescent ,Rain ,Chest pain ,Aspergillus fumigatus ,Japan ,Internal medicine ,Internal Medicine ,medicine ,allergic bronchopulmonary aspergillosis ,Humans ,pulmonary aspergilloma ,Lung ,Asthma ,Voriconazole ,biology ,medicine.diagnostic_test ,business.industry ,Aspergillosis, Allergic Bronchopulmonary ,General Medicine ,biology.organism_classification ,medicine.disease ,respiratory tract diseases ,Bronchoalveolar lavage ,disaster ,Prednisolone ,Pulmonary Aspergillosis ,medicine.symptom ,Allergic bronchopulmonary aspergillosis ,business ,Aspergilloma ,medicine.drug - Abstract
A 16-year-old boy with asthma participated in recovery volunteer work following the 2018 heavy rains in Japan. One month later, he experienced chest pain and dyspnea. Chest computed tomography revealed a cavity with a fungal ball, and Aspergillus fumigatus was detected in his bronchoalveolar lavage fluid. He was treated with voriconazole, but new consolidations appeared rapidly. He also experienced allergic bronchopulmonary aspergillosis. After prednisolone prescription, the consolidations improved; however, his asthma worsened. He underwent partial lung resection to avoid allergens, and his symptoms improved. We must recognize cases of infection after a disaster, especially in patients with chronic respiratory diseases.
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- 2022
8. Identification of novel SSX1 fusions in synovial sarcoma
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Yasushi Yatabe, Koichi Ichimura, Natsuko Hama, Eijitsu Ryo, Taisuke Mori, Takashi Kubo, Kazuki Sudo, Motokiyo Komiyama, Akira Kawai, Yasuhito Arai, Yuko Matsushita, Tatsuhiro Shibata, Akihiko Yoshida, Hitoshi Ichikawa, and Kaishi Satomi
- Subjects
Sanger sequencing ,Pathology ,medicine.medical_specialty ,Oncogene Proteins, Fusion ,medicine.diagnostic_test ,medicine.drug_class ,Biology ,medicine.disease ,Monoclonal antibody ,Molecular biology ,Synovial sarcoma ,Pathology and Forensic Medicine ,Staining ,Repressor Proteins ,Fusion gene ,Sarcoma, Synovial ,symbols.namesake ,Proto-Oncogene Proteins ,medicine ,symbols ,Humans ,SMARCB1 ,Gene ,In Situ Hybridization, Fluorescence ,Fluorescence in situ hybridization - Abstract
Synovial sarcoma is characterized by variable epithelial differentiation and specific SS18-SSX gene fusions. The diagnosis is primarily based on phenotype, but fusion gene detection is increasingly being considered indispensable, with SS18 break-apart fluorescence in situ hybridization (FISH) being favored in many laboratories. However, SS18 FISH assay produces negative or atypical results in a minority of cases, leaving uncertainties in diagnosis and management. Here, we analyzed this challenging subset of SS18 FISH-negative/atypical synovial sarcoma using RNA sequencing and monoclonal antibodies that recognize SS18-SSX and the SSX C-terminus. Among 99 synovial sarcoma cases that were previously subjected to SS18 break-apart FISH, eight cases were reported as negative and three cases were indeterminate, owing to atypical signal patterns. Three of these 11 tumors (two monophasic and one biphasic) harbored novel EWSR1-SSX1 fusions, were negative for SS18-SSX staining, and were positive for SSX C-terminus staining. One monophasic tumor harbored a novel MN1-SSX1 fusion, and showed negative SS18-SSX expression and positive SSX C-terminus staining. Another monophasic tumor carried an SS18L1-SSX1 fusion, and was weakly positive for SS18-SSX, while SMARCB1 expression was reduced. The presence of these novel and/or rare fusions was confirmed using RT-PCR and Sanger sequencing. EWSR1-SSX1 was further validated by EWSR1 FISH assay. The remaining six tumors (five monophasic and one biphasic) showed strong SS18-SSX expression, and RNA sequencing successfully performed in three cases identified canonical SS18-SSX2 fusions. Based on a DNA methylation-based unsupervised clustering, the tumors with EWSR1-SSX1 and SS18L1-SSX1 clustered with synovial sarcoma, while the MN1-SSX1-positive tumor was not co-clustered despite classic histology and immunoprofile. In summary, we discovered novel and rare SSX1 fusions to non-SS18 genes in synovial sarcoma. The expanded genetic landscape carries significant diagnostic implications and advances our understanding of the oncogenic mechanism.
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- 2022
9. Preparation of Anti-Rabies Virus N Protein IgYs by DNA Immunization of Hens Using Different Types of Adjuvants
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Hajime Hatta, Mari Nishii, Satoshi Inoue, Nanase Kubo, and Akira Noguchi
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Dna immunization ,Rabies virus ,medicine ,Animal Science and Zoology ,Biology ,medicine.disease_cause ,Virology - Abstract
DNA immunization has been used to study vaccination methods and for production of specific antibodies. The present study aimed to apply DNA immunization to prepare specific IgYs, which react against rabies virus N protein (RV-N) and can be used to research and diagnose rabies virus. The DNA sequence of RV-N was ligated into a pcDNA 3.1 plasmid for constructing pcDNA-N. Eight hens were divided into four groups. Group 1 comprised the control group (non-immunized). In Groups 2, 3, and 4, hens were injected intramuscularly with pcDNA-N (400 µg/hen). Eight injections were administered every other week. From the 4th week, an adjuvant was injected in addition to pcDNA-N. Freund's complete adjuvant (FCA) and
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- 2022
10. Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro
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L.F.A. Diniz, B.K. Matsuba, P.S.S. Souza, B.R.P. Lopes, L.H. Kubo, J. Oliveira, K.A. Toledo, and Universidade Estadual Paulista (UNESP)
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QH301-705.5 ,vírus sincicial respiratório humano ,Science ,Respiratory Syncytial Virus Infections ,Biology ,Extracellular Traps ,Virus ,Microbiology ,neutrófilos ,Multiplicity of infection ,neutrophils ,medicine ,Cytotoxic T cell ,Humans ,Biology (General) ,Respiratory system ,Lung ,innate immunity ,Syncytium ,Innate immune system ,Botany ,Epithelial Cells ,NETs ,Neutrophil extracellular traps ,imunidade inata ,infecção viral ,medicine.anatomical_structure ,QL1-991 ,QK1-989 ,Child, Preschool ,Respiratory Syncytial Virus, Human ,viral infection ,General Agricultural and Biological Sciences ,human respiratory syncytial virus ,Zoology ,Respiratory tract - Abstract
The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5–16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV. Resumo O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,5–16 μg/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios semelhantes àqueles induzidos pelo vírus em células não tratadas, indicando danos citotóxicos e deletérios. Nossos resultados corroboram achados relatados anteriormente de que as NETs contribuem para a imunopatologia desenvolvida por pacientes infectados com hRSV.
- Published
- 2023
11. Stemness and immune evasion conferred by the TDO2‐AHR pathway are associated with liver metastasis of colon cancer
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Suyoun Chung, Hirokazu Taniguchi, Hiroaki Sakai, Takashi Kubo, Hitoshi Nakagama, Toshiaki Miyazaki, Kazunori Aoki, Yukihiro Mizoguchi, Daisuke Shiokawa, Yuuki Obata, Hitoshi Ichikawa, Hirokazu Ohata, Tomoyoshi Soga, and Koji Okamoto
- Subjects
cancer stem cells ,Cancer Research ,Colorectal cancer ,TDO2 ,Cancer Model ,Biology ,B7-H1 Antigen ,Dioxygenases ,Metastasis ,Mice ,chemistry.chemical_compound ,Cell, Molecular, and Stem Cell Biology ,Cancer stem cell ,Cell Line, Tumor ,Spheroids, Cellular ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Animals ,Humans ,Wnt Signaling Pathway ,aryl hydrocarbon receptor ,Liver Neoplasms ,Wnt signaling pathway ,Cancer ,Original Articles ,General Medicine ,medicine.disease ,kynurenine ,Up-Regulation ,Immunosurveillance ,liver metastasis ,Receptors, Aryl Hydrocarbon ,Oncology ,chemistry ,Colonic Neoplasms ,Neoplastic Stem Cells ,Cancer research ,Original Article ,Tumor Escape ,Neoplasm Transplantation ,Kynurenine - Abstract
The aryl hydrocarbon receptor (AHR) pathway modulates the immune system in response to kynurenine, an endogenous tryptophan metabolite. IDO1 and TDO2 catalyze kynurenine production, which promotes cancer progression by compromising host immunosurveillance. However, it is unclear whether the AHR activation regulates the malignant traits of cancer such as metastatic capability or cancer stemness. Here, we carried out systematic analyses of metabolites in patient‐derived colorectal cancer spheroids and identified high levels of kynurenine and TDO2 that were positively associated with liver metastasis. In a mouse colon cancer model, TDO2 expression substantially enhanced liver metastasis, induced AHR‐mediated PD‐L1 transactivation, and dampened immune responses; these changes were all abolished by PD‐L1 knockout. In patient‐derived cancer spheroids, TDO2 or AHR activity was required for not only the expression of PD‐L1, but also for cancer stem cell (CSC)‐related characteristics and Wnt signaling. TDO2 was coexpressed with both PD‐L1 and nuclear β‐catenin in colon xenograft tumors, and the coexpression of TDO2 and PD‐L1 was observed in clinical colon cancer specimens. Thus, our data indicate that the activation of the TDO2‐kynurenine‐AHR pathway facilitates liver metastasis of colon cancer via PD‐L1–mediated immune evasion and maintenance of stemness., We carried out systematic analyses of metabolites in patient‐derived colorectal cancer spheroids, and identified high levels of kynurenine and TDO2 that were positively associated with liver metastasis. Our data indicate that the activation of the TDO2‐kynurenine‐AHR pathway may lead to emergence of immune‐evasive cancer stem cells (CSCs) promoting liver metastasis.
- Published
- 2021
12. Potential pathogenetic link between angiomyofibroblastoma and superficial myofibroblastoma in the female lower genital tract based on a novel MTG1-CYP2E1 fusion
- Author
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Kiyoshi Yoshino, Ryuji Iwamura, Aya Nawata, Eisuke Shiba, Chisachi Kubo, Ryosuke Tajiri, Masanori Hisaoka, and Hiroshi Harada
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Angiomyofibroblastoma ,Stromal cell ,Genital Neoplasms, Female ,Biology ,Angiofibroma ,GTP Phosphohydrolases ,Pathology and Forensic Medicine ,Neoplasms, Muscle Tissue ,Young Adult ,Biomarkers, Tumor ,medicine ,Humans ,Genetic Predisposition to Disease ,RNA-Seq ,Progenitor cell ,Reverse Transcriptase Polymerase Chain Reaction ,Mesenchymal stem cell ,Cytochrome P-450 CYP2E1 ,Middle Aged ,Immunohistochemistry ,Phenotype ,Fusion transcript ,Female ,Gene Fusion ,Angiomyxoma ,Myofibroblastoma - Abstract
Angiomyofibroblastoma and superficial myofibroblastoma are distinctive benign mesenchymal tumors occurring in the female lower genital tract. Despite their significant overlapping clinicopathologic features, including the presence of bland-looking spindle or oval cells with myofibroblastic or myoid differentiation, the tumors have been regarded as separate entities. Although subepithelial, hormone-sensitive mesenchymal cells of the female lower genital tract are considered as their potential common progenitor cells, their potential kinship or pathogenetic similarities remain elusive. Based on the identification of a novel RNA sequencing-based MTG1-CYP2E1 fusion transcript in an angiomyofibroblastoma index case, we investigated an additional ten samples of the tumor and its site-specific histological mimics, including eight superficial myofibroblastomas, four deep angiomyxomas, four cellular angiofibromas, three fibroepithelial stromal polyps, and eight non-site-specific mesenchymal tumors occurring in the female lower genital tract. Using reverse transcription-polymerase chain reaction, we showed that the MTG1-CYP2E1 fusion transcripts were consistently detectable in angiomyofibroblastomas (5/5, 100%) and often in superficial myofibroblastomas (3/5, 60%) but were not detected in the other examined site-specific or non-site-specific mesenchymal tumors. Our immunohistochemical experiments showed that CYP2E1, an isoenzyme belonging to the cytochrome P450 superfamily, exhibited increased positivity in tumors with MTG1-CYP2E1 than was observed in fusion-negative tumors (RR = 6.56, p = 0.001). The results of our study provide further evidence supporting the assertion that angiomyofibroblastoma and superficial myofibroblastoma represent phenotypic variants of site-specific mesenchymal tumors and share a common oncogenic mechanism.
- Published
- 2021
13. 'Shirayuri Nijo', a new two-rowed hulled barley cultivar for food with proanthocyanidin-free gene, moderate tolerance to pre-harvest sprouting and high-yield
- Author
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Naoyuki Kawada, Masaya Fujita, Koichi Hatta, Zenta Nishio, Hitoshi Matsunaka, Katashi Kubo, Tetsufumi Sakai, Mikiko Yanaka, Takuji Tonooka, Masato Taira, Tomohiko Sugita, Kazuhiro Nakamura, and Hitoshi Araki
- Subjects
Horticulture ,Proanthocyanidin ,Yield (wine) ,Pre-harvest sprouting ,General Medicine ,Cultivar ,Biology - Published
- 2021
14. A Synthetic Model for the Possible FeIV2(μ-O)2 Core of Methane Monooxygenase Intermediate Q Derived from a Structurally Characterized FeIIIFeIV(μ-O)2 Complex
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Yoshio Kobayashi, Hajime Katano, Sachiko Yanagisawa, Hiromi Nakayama, Fukue Kotegawa, Masahito Kodera, Minoru Kubo, Atsushi Kajiwara, Masafumi Harada, Arimasa Matsumoto, Yuri Aono, Chihiro Yamamoto, and Yuji Mikata
- Subjects
biology ,Extended X-ray absorption fine structure ,Methane monooxygenase ,Chemistry ,Electrochemistry ,Hydrogen atom abstraction ,Inorganic Chemistry ,Crystallography ,Reaction rate constant ,Tripodal ligand ,Mössbauer spectroscopy ,biology.protein ,Reactivity (chemistry) ,Physical and Theoretical Chemistry - Abstract
A bis(μ-oxo)diiron(IV,IV) complex as a model for intermediate Q in the methane monooxygenase reaction cycle has been prepared. The precursor complex with a [FeIIIFeIV(μ-O)2] core was fully characterized by X-ray crystallography and other spectroscopic analyses and was converted to the [FeIV2(μ-O)2] complex via electrochemical oxidation at 1000 mV (vs Ag/Ag+) in acetone at 193 K. The UV-vis spectral features, Mossbauer parameters (ΔEQ = 2.079 mm/s and δ = -0.027 mm/s), and EXAFS analysis (Fe-O/N = 1.73/1.96 A and Fe···Fe = 2.76 A) support the structure of the low-spin (S = 1, for each Fe) [FeIV2(μ-O)2] core. The rate constants of the hydrogen abstraction reaction from 9,10-dihydroanthracene at 243 K suggest the high reactivity of these synthetic bis(μ-oxo)diiron complexes supported by simple N4 tripodal ligand.
- Published
- 2021
15. Flowering and fruiting of the dioecious canopy tree Cercidiphyllum japonicum over an 8-year period in central Japan
- Author
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Hitoshi Sakio and Masako Kubo
- Subjects
Tree canopy ,Horticulture ,geography ,geography.geographical_feature_category ,biology ,Period (geology) ,Riparian forest ,Forestry ,Cercidiphyllum japonicum ,Life history ,biology.organism_classification - Abstract
To investigate the reproductive traits of the dioecious canopy tree Cercidiphyllum japonicum, we performed visual surveys from 2000 to 2007 to assess the flowering and fruiting of 59 individuals in...
- Published
- 2021
16. Long-term good outcome of the fibrocavitary form of pulmonary Mycobacterium avium complex disease with concomitant abatacept monotherapy in a patient with rheumatoid arthritis
- Author
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Yasuhiko Ito, Hirokazu Sugiyama, Satoru Ito, Akihito Kubo, Shiho Iwagaitsu, Takayuki Katsuno, Hiroshi Kinashi, Hironobu Nobata, Makoto Yamaguchi, Shogo Banno, and Etsuro Yamaguchi
- Subjects
Lung Diseases ,musculoskeletal diseases ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Gastroenterology ,Abatacept ,Arthritis, Rheumatoid ,Internal medicine ,Humans ,Medicine ,Mycobacterium avium-intracellulare Infection ,Chemotherapy ,biology ,business.industry ,Middle Aged ,Mycobacterium avium Complex ,biology.organism_classification ,medicine.disease ,Rheumatoid arthritis ,Concomitant ,Prednisolone ,Sputum ,Female ,Nontuberculous mycobacteria ,medicine.symptom ,business ,medicine.drug - Abstract
A 53-year-old woman diagnosed with rheumatoid arthritis (RA) demonstrated thick-walled large cavities with consolidation in the left upper lobe on chest computed tomography (CT). Mycobacterium avium was isolated from sputum cultures, and she was diagnosed as having the fibrocavitary (FC) form of pulmonary Mycobacterium avium complex (MAC) disease. Clarithromycin-containing, multidrug, anti-MAC chemotherapy was started immediately. After 7 months, the cavitary lesions improved, and sputum cultures showed negative conversion. Thereafter, abatacept monotherapy was started due to high RA disease activity. Clinical remission of RA has been sustained and cavitary lesions disappeared by concomitant abatacept and anti-MAC therapy for more than 5 years. Immediate initiation of anti-MAC therapy and prior confirmed efficacy are needed for the treatment of the FC form. Abatacept and anti-MAC therapy could be continued, leading to the withdrawal of prednisolone, along with careful observation by strict chest CT evaluation and repeated sputum cultures. Biologics are generally contraindicated for pulmonary MAC disease, particularly the FC form. When there is a pre-existing lung lesion apparently of FC type, abatacept cannot be started without prior anti-MAC chemotherapy. This case suggests that abatacept may be carefully used to avoid progressive joint destruction after FC lesions of pulmonary MAC disease are resolved.
- Published
- 2021
17. The role of IL-4 derived from follicular helper T (TFH) cells and type 2 helper T (TH2) cells
- Author
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Masato Kubo
- Subjects
T Follicular Helper Cells ,medicine.medical_treatment ,Immunology ,Germinal center ,General Medicine ,Biology ,Immunoglobulin E ,Th2 Cells ,medicine.anatomical_structure ,Cytokine ,Immune system ,Antigen ,medicine ,biology.protein ,Animals ,Humans ,Immunology and Allergy ,Interleukin-4 ,Enhancer ,Sensitization ,Interleukin 4 - Abstract
IL-4 is known to be the quintessential regulatory cytokine, playing a role in a vast number of immune and non-immune functions. This cytokine is commonly secreted by type 2 helper T (TH2) cells and follicular helper T (TFH) cells after antigenic sensitization. TH2 cells have been classically thought to be the major contributor to B-cell help as a source of IL-4 responsible for class-switch recombination to IgG1 in mice (IgG4 in humans) and to IgE in mice and humans. Recent in vivo observations have shown that IgE and IgG1 antibody responses are mainly controlled by IL-4-secreting TFH cells but not by classical TH2 cells. IL-4 is distinctively regulated in these two T-cell subsets by the GATA-3-mediated HS2 enhancer in TH2 cells and the Notch-mediated conserved non-coding sequence 2 (CNS-2) enhancer in TFH cells. Moreover, the IL-4 derived from TFH cells has an essential role in germinal center (GC) formation in the secondary lymphoid organs during humoral immune responses.
- Published
- 2021
18. Control of Fusarium and nematodes by entomopathogenic fungi for organic production of Zingiber officinale
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Surendra K. Dara, Shinichiro Sawa, Ni Putu Ratna Ayu Krishanti, Aya Yanagawa, Safendrri Komara Ragamustari, Akifumi Sugiyama, Masaru Kobayashi, Chihiro Furumizu, Minoru Kubo, and Emiria Chrysanti
- Subjects
Fusarium ,Cordyceps ,Horticulture ,biology ,Fusarium oxysporum ,Meloidogyne incognita ,Biological pest control ,Molecular Medicine ,Beauveria bassiana ,Zingiber officinale ,biology.organism_classification ,Terra incognita - Abstract
Ginger (genus Zingiber) is widely used as a spice and a medicinal herb worldwide and is the major ingredient of traditional local drinks such as jamu in Southeast Asia. Because ginger is frequently consumed, there is an increasing interest in organic ginger production without the use of synthetic agrochemicals. Recent studies have reported that certain kinds of entomopathogenic fungi (EPF) can establish endophytic- or mycorrhiza-like relationships with plants, thereby promoting plant growth and health, in addition to their typical role in crop protection as biological control agents. In this study, we explored the possibility of non-entomopathogenic effects of EPF Beauveria bassiana and Cordyceps fumosorosea on ginger plants (Zingiber officinale) via antagonism with Fusarium oxysporum or the parasitic nematode Meloidogyne incognita. The two EPF negatively affected the growth of F. oxysporum and survival of M. incognita in vitro. The application of EPF did not have any negative effect on the growth of ginger plants. Soil chemical properties were not different between the plots with or without EPF application, while the diversity of soil bacteria was observed to increase on application of EPF. At least C. fumosorosea appeared to persist in soil during the period of ginger cultivation. Thus, these EPF are potentially useful tools for producing chemical-free ginger.
- Published
- 2021
19. Population-level laterality in foraging finless porpoises
- Author
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Tsuyoshi Kuwahara, Hayao Kobayashi, Masao Amano, Yudai Kawano, and Taketo Kubo
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Population level ,Movement ,Science ,Foraging ,Population ,Zoology ,Porpoises ,Biology ,Functional Laterality ,Article ,Predation ,Feeding behavior ,Animals ,education ,education.field_of_study ,Multidisciplinary ,Behavior, Animal ,Brain ,Animal behaviour ,Dominance (ethology) ,Cerebral hemisphere ,Laterality ,Medicine - Abstract
aterality has been reported in many vertebrates, and asymmetrical cerebral hemisphere function has been hypothesized to cause a left-bias in social behavior and a right-bias in feeding behavior. In this paper, we provide the first report of behavioral laterality in free-ranging finless porpoises, which seems to support the aforementioned hypothesis. We observed the turning behavior of finless porpoises in Omura Bay, Japan, using land-based and unmanned aerial system observations. We found a strong tendency in finless porpoises to turn counterclockwise with their right side down when pursuing and catching fish at the surface of the water. Our results suggest that this population of finless porpoises shows consistent right-biased laterality. Right-biased laterality has been observed in various foraging cetaceans and is usually explained by the dominance of the right eye-left cerebral hemisphere in prey recognition; however, right-biased laterality in foraging cetaceans may have multiple causes., Scientific Reports, 11, art. no. 21164; 2021
- Published
- 2021
20. A cross-population atlas of genetic associations for 220 human phenotypes
- Author
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Yukinori Okada, Hiroki Yamaguchi, Kazuyoshi Ishigaki, Shigeo Murayama, Yosuke Tanigawa, Gen Tamiya, Masayuki Yamamoto, Yoichiro Kamatani, Akihide Masumoto, Manuel A. Rivas, Yusuke Nakamura, Issei Komuro, Akira Narita, Masahiro Kanai, Ken Yamaji, Shiro Minami, Yasuo Takahashi, Toshimasa Yamauchi, Takahiro Konuma, Mark J. Daly, Yoshinori Murakami, Chikashi Terao, Koichi Matsuda, Kazuhisa Takahashi, Michiaki Kubo, Masahiko Higashiyama, Kaoru Ito, Saori Sakaue, Akari Suzuki, Nobuaki Shinozaki, Takao Suzuki, Satoshi Asai, Ken Suzuki, Kazuhiko Yamamoto, Takashi Kadowaki, Yukihiro Koretsune, Wataru Obara, Kenichi Yamamoto, Seizo Koshiba, Juha Karjalainen, Kozo Yoshimori, FinnGen, Daisuke Obata, Masato Akiyama, Satoshi Nagayama, Mitja I. Kurki, and Aarno Palotie
- Subjects
education.field_of_study ,Evolutionary biology ,Pleiotropy ,Population ,Genetics ,Locus (genetics) ,Human leukocyte antigen ,Disease ,Biology ,education ,Biobank ,Subtyping ,Genetic association - Abstract
Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (ntotal = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.
- Published
- 2021
21. Loop-mediated isothermal amplification (LAMP) and machine learning application for early pregnancy detection using bovine vaginal mucosal membrane
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Ahmed Z. Balboula, Hisato Kobayashi, Hiroki Kunii, Yu Hamaguchi, Masashi Takahashi, Hanako Bai, Tomoaki Kubo, Manabu Kawahara, Natsuki Asaoka, Hidehiko Ogawa, and Tomoya Shimasaki
- Subjects
medicine.medical_treatment ,Biophysics ,Loop-mediated isothermal amplification ,Gene Expression ,Early pregnancy factor ,Machine learning ,computer.software_genre ,Biochemistry ,Sensitivity and Specificity ,Pregnancy ,medicine ,False positive paradox ,Early pregnancy detection ,Cutoff ,Animals ,Molecular Biology ,Ubiquitins ,Vaginal mucosa ,Adaptor Proteins, Signal Transducing ,Estrous cycle ,Mucous Membrane ,amplification(LAMP) ,biology ,business.industry ,Artificial insemination ,Cow ,Membrane Proteins ,RNA-Binding Proteins ,Reproducibility of Results ,Cell Biology ,medicine.disease ,Molecular Diagnostic Techniques ,CA-125 Antigen ,Vagina ,biology.protein ,Cytokines ,Cattle ,Female ,Artificial intelligence ,Ultrasonography ,business ,computer ,Nucleic Acid Amplification Techniques ,Biomarkers ,Loop-mediated isothermal - Abstract
An early and accurate pregnancy diagnosis method is required to improve the reproductive performance of cows. Here we developed an easy pregnancy detection method using vaginal mucosal membrane (VMM) with application of Reverse Transcription-Loop-mediated Isothermal Amplification (RT-LAMP) and machine learning. Cows underwent artificial insemination (AI) on day 0, followed by VMMcollection on day 17-18, and pregnancy diagnosis by ultrasonography on day 30. By RNA sequencing of VMM samples, three candidate genes for pregnancy markers (ISG15 and IFIT1: up-regulated, MUC16: down-regulated) were selected. Using these genes, we performed RT-LAMP and calculated the rise-up time (RUT), the first-time absorbance exceeded 0.05 in the reaction. We next determined the cutoff value and calculated accuracy, sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) for each marker evaluation. The IFIT1 scored the best performance at 92.5% sensitivity, but specificity was 77.5%, suggesting that it is difficult to eliminate false positives. We then developed a machine learning model trained with RUT of each marker combination to predict pregnancy. The model created with the RUT of IFIT1 and MUC16 combination showed high specificity (86.7%) and sensitivity (93.3%), which were higher compared to IFIT1 alone. In conclusion, using VMM with RT-LAMP and machine learning algorithm can be used for early pregnancy detection before the return of first estrus. (c) 2021 Published by Elsevier Inc.
- Published
- 2021
22. Insulin-Like Growth Factor 2 and Incidence of Liver Cancer in a Nested Case–Control Study
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Yingsong Lin, Toshiyuki Kubo, Kenji Wakai, Noriyuki Akutsu, Masanori Nojima, Youichi Kurozawa, Ryogo Himori, Yasushi Adachi, Akiko Tamakoshi, and Mitsuru Mori
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Carcinogenesis ,Epidemiology ,medicine.disease_cause ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Prospective Studies ,Insulin-Like Growth Factor I ,Aged ,biology ,business.industry ,Incidence ,Incidence (epidemiology) ,Liver Neoplasms ,Middle Aged ,medicine.disease ,Cancer incidence ,Case-Control Studies ,Insulin-like growth factor 2 ,Nested case-control study ,biology.protein ,Biomarker (medicine) ,Female ,Liver cancer ,business ,Cohort study - Abstract
Background: Insulin-like growth factor (IGF)2 is a potent mitogen. To elucidate the relationship between IGF2 and risk of tumorigenesis, we analyzed associations between serum levels of IGF2 and incidence of liver cancer in a prospective case–control study nested in the Japan Collaborative Cohort study. Methods: A baseline survey was conducted from 1988 using blood samples from 39,242 subjects. Those who had been diagnosed with liver cancer by 1997 were regarded as cases. For each case, we randomly selected two or three controls matched for sex, age, and residential area. Conditional logistic regression was used to estimate ORs for cancer incidence associated with IGF2. Results: This analysis included 86 cases and 294 controls. Low IGF2 was associated with risk of future liver cancer (Ptrend Conclusions: Our findings suggest that low serum IGF2 level, especially below 460 ng/mL, is related to future risk of liver cancer. Impact: Our findings highlight this important biomarker for further analysis in large prospective cohorts and pooled investigation with other cohorts.
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- 2021
23. Tumor-infiltrating CD8+ T cells recognize a heterogeneously expressed functional neoantigen in clear cell renal cell carcinoma
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Masahiro Matsuki, Aiko Murai, Serina Tokita, Tomohide Tsukahara, Munehide Nakatsugawa, Yoshihiko Hirohashi, Takayuki Kanaseki, Toshihiko Torigoe, Sachiyo Nishida, Naoya Masumori, Terufumi Kubo, Toshiaki Tanaka, Hiroshi Kitamura, Shinichi Hashimoto, and Kenji Murata
- Subjects
Cancer Research ,Tumor-infiltrating lymphocytes ,medicine.medical_treatment ,Immunology ,Clone (cell biology) ,chemical and pharmacologic phenomena ,Immunotherapy ,Biology ,Gene mutation ,medicine.disease ,Neoantigen Peptide ,Clear cell renal cell carcinoma ,Oncology ,Cancer immunotherapy ,Cancer research ,medicine ,Immunology and Allergy ,Clear cell - Abstract
Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy to block programmed death-1 and cytotoxic T-lymphocyte antigen 4, but the response rate for ICIs is still low and tumor cell heterogeneity is considered to be responsible for resistance to immunotherapy. Tumor-infiltrating lymphocytes (TILs) have an essential role in the anti-tumor effect of cancer immunotherapy; however, the specificity of TILs in renal cell carcinoma (RCC) is elusive. In this study, we analyzed a 58-year-old case with clear cell RCC (ccRCC) with the tumor showing macroscopic and microscopic heterogeneity. The tumor was composed of low-grade and high-grade ccRCC. A tumor cell line (1226 RCC cells) and TILs were isolated from the high-grade ccRCC lesion, and a TIL clone recognized a novel neoantigen peptide (YVVPGSPCL) encoded by a missense mutation of the tensin 1 (TNS1) gene in a human leukocyte antigen-C*03:03-restricted fashion. The TNS1 gene mutation was not detected in the low-grade ccRCC lesion and the TIL clone did not recognized low-grade ccRCC cells. The missense mutation of TNS1 encoding the S1309Y mutation was found to be related to cell migration by gene over-expression. These findings suggest that macroscopically and microscopically heterogenous tumors might show heterogenous gene mutations and reactivity to TILs.
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- 2021
24. Preoperative C-reactive protein to albumin ratio predicts anastomotic leakage after esophagectomy for thoracic esophageal cancer: a single-center retrospective cohort study
- Author
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Atsushi Sugimoto, Naoshi Kubo, Mami Yoshii, Yuichiro Miki, Takahiro Toyokawa, Masaichi Ohira, Kazuya Muguruma, Tatsuro Tamura, Katsunobu Sakurai, Shigeru Lee, Hiroaki Tanaka, and Masakazu Yashiro
- Subjects
medicine.medical_specialty ,Esophageal Neoplasms ,RD1-811 ,medicine.medical_treatment ,Esophageal cancer ,Anastomotic Leak ,Single Center ,Gastroenterology ,Albumins ,Internal medicine ,medicine ,Humans ,Anastomotic leakage ,Retrospective Studies ,Univariate analysis ,biology ,Receiver operating characteristic ,business.industry ,Research ,C-reactive protein ,Retrospective cohort study ,General Medicine ,Prognosis ,medicine.disease ,Surgery ,Esophagectomy ,C-Reactive Protein ,biology.protein ,Esophageal Squamous Cell Carcinoma ,C-reactive protein-to-albumin ratio ,business ,Body mass index - Abstract
Background Postoperative anastomotic leakage (AL) is associated with not only prolonged hospital stay and increased medical costs, but also poor prognosis in esophageal cancer. Several studies have addressed the utility of various inflammation-based and/or nutritional markers as predictors for postoperative complications. However, none have been documented as specific predictors for AL in esophageal cancer. We aimed to identify predictors of AL after esophagectomy for thoracic esophageal cancer, focusing on preoperative inflammation-based and/or nutritional markers. Methods We retrospectively analyzed 295 patients who underwent radical esophagectomy for thoracic esophageal squamous cell carcinoma between June 2007 and July 2020. As inflammation-based and/or nutritional markers, Onodera prognostic nutritional index, C-reactive protein (CRP)-to-albumin ratio (CAR) and modified Glasgow prognostic score were investigated. Optimal cut-off values of inflammation-based and/or nutritional markers for AL were determined by receiver operating characteristic curves. Predictors for AL were analyzed by logistic regression modeling. Results AL was observed in 34 patients (11.5%). In univariate analyses, preoperative body mass index (≥ 22.1 kg/m2), serum albumin level (≤ 3.8 g/dL), serum CRP level (≥ 0.06 mg/dL), CAR (≥ 0.0139), operation time (> 565 min) and blood loss (≥ 480 mL) were identified as predictors of AL. Multivariate analyses revealed higher preoperative CAR (≥ 0.0139) as an independent predictor of AL (p = 0.048, odds ratio = 3.02, 95% confidence interval 1.01–9.06). Conclusion Preoperative CAR may provide a useful predictor of AL after esophagectomy for thoracic esophageal squamous cell carcinoma.
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- 2021
25. Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
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Bhagwat Prasad, Ahmed El-Boraie, Rachel F. Tyndale, Kenneth E. Thummel, Caryn Lerman, Katrina G. Claw, Julie-Anne Tanner, Koya Fukunaga, Taisei Mushiroda, Michiaki Kubo, Neal L. Benowitz, Andy Z. X. Zhu, and Erin G. Schuetz
- Subjects
Metabolite ,Cardiorespiratory Medicine and Haematology ,Cardiovascular ,Oral and gastrointestinal ,Nicotine ,Cytochrome P-450 CYP2A6 ,chemistry.chemical_compound ,Gene Frequency ,Missing heritability problem ,2.1 Biological and endogenous factors ,General Pharmacology, Toxicology and Pharmaceutics ,Aetiology ,CYP2A6 ,General Clinical Medicine ,Genetics ,Clinical Trials as Topic ,General Neuroscience ,General Medicine ,Single Nucleotide ,Articles ,Treatment Outcome ,Public aspects of medicine ,RA1-1270 ,medicine.drug ,Genotype ,In silico ,Oncology and Carcinogenesis ,RM1-950 ,Biology ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Article ,In vivo ,Clinical Research ,Tobacco ,medicine ,Humans ,Polymorphism ,Other Medical and Health Sciences ,Tobacco Smoke and Health ,Prevention ,Research ,Human Genome ,Heritability ,Minor allele frequency ,Good Health and Well Being ,chemistry ,Smoking Cessation ,Therapeutics. Pharmacology ,Digestive Diseases - Abstract
CYP2A6 activity, phenotyped by the nicotine metabolite ratio (NMR), is a predictor of several smoking behaviors, including cessation and smoking‐related disease risk. The heritability of the NMR is 60–80%, yet weighted genetic risk scores (wGRSs) based on common variants explain only 30–35%. Rare variants (minor allele frequency
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- 2021
26. GRIK2 is a target for bladder cancer stem-like cell-targeting immunotherapy
- Author
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Aiko Murai, Tomohide Tsukahara, Yoshihiko Hirohashi, Takayuki Kanaseki, Takashige Abe, Terufumi Kubo, Shinichi Hashimoto, Kanta Hori, Haruka Miyata, Junko Yanagawa, Serina Tokita, Shuhei Yamada, Nobuo Shinohara, and Toshihiko Torigoe
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Cancer Research ,Bladder cancer ,medicine.medical_treatment ,Immunology ,Clone (cell biology) ,Human leukocyte antigen ,Immunotherapy ,Biology ,medicine.disease ,CTL ,Oncology ,Antigen ,Cancer stem cell ,Cancer research ,medicine ,Immunology and Allergy ,Cytotoxic T cell - Abstract
Recent studies have revealed that treatment-resistant cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be targeted by cytotoxic T lymphocytes (CTLs). CTLs recognize antigenic peptides derived from tumor-associated antigens; thus, the identification of tumor-associated antigens expressed by CSCs/CICs is essential. Human leucocyte antigen (HLA) ligandome analysis using mass spectrometry enables the analysis of naturally expressed antigenic peptides; however, HLA ligandome analysis requires a large number of cells and is challenging for CSCs/CICs. In this study, we established a novel bladder CSC/CIC model from a bladder cancer cell line (UM-UC-3 cells) using an ALDEFLUOR assay. CSCs/CICs were isolated as aldehyde dehydrogenase (ALDH)-high cells and several ALDHhigh clone cells were established. ALDHhigh clone cells were enriched with CSCs/CICs by sphere formation and tumorigenicity in immunodeficient mice. HLA ligandome analysis and cap analysis of gene expression using ALDHhigh clone cells revealed a distinctive antigenic peptide repertoire in bladder CSCs/CICs, and we found that a glutamate receptor, ionotropic, kainite 2 (GRIK2)-derived antigenic peptide (LMYDAVHVV) was specifically expressed by CSCs/CICs. A GRIK2 peptide-specific CTL clone recognized GRIK2-overexpressing UM-UC-3 cells and ALDHhigh clone cells, indicating that GRIK2 peptide can be a novel target for bladder CSC/CIC-targeting immunotherapy.
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- 2021
27. Vonoprazan-Associated Gastric Mucosal Redness in Non-Helicobacter pylori-Infected and Helicobacter pylori-Eradicated Stomach
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Masayuki Higashino, Ryosuke Watanabe, Mototsugu Kato, Kimitoshi Kubo, Noriko Kimura, and Momoko Tsuda
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Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,biology ,Esophagogastroduodenoscopy ,business.industry ,Vonoprazan ,Stomach ,Gastroenterology ,Helicobacter pylori ,biology.organism_classification ,Curvatures of the stomach ,medicine.anatomical_structure ,medicine ,Gastric mucosa ,business ,Pathological ,Parietal cell - Abstract
Vonoprazan-associated gastric mucosal redness is rare, and its endoscopic and pathological features remain poorly described. We report 4 cases of vonoprazan-associated gastric mucosal redness, that is, 2 cases each in non-Helicobacter pylori-infected and -eradicated stomach. In all cases, esophagogastroduodenoscopy demonstrated spotty and linear redness newly appearing in the greater curvature of the gastric body after initiation of vonoprazan but disappearing after its discontinuation. A tissue biopsy taken from the gastric mucosa with redness revealed various pathological findings and included inflammatory cell infiltration, parietal cell protrusions, oxyntic gland dilatations, congestion, focal hemorrhage with congestion beneath the basement membrane, and vacuolar degeneration of parietal cells. To our knowledge, this is the second report describing the endoscopic and pathological features of vonoprazan-associated gastric mucosal redness.
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- 2021
28. Wild-Type Transthyretin Amyloidosis in Female Patients ― Consideration of Sex Differences ―
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Toru Kubo, Kenta Sugiura, Motoko Ueda, Takayoshi Hirota, Naohito Yamasaki, Kazuya Miyagawa, Tomoyuki Hamada, Yuri Ochi, Hiroaki Kitaoka, Yuichi Baba, and Tatsuya Noguchi
- Subjects
medicine.medical_specialty ,Myocardial Disease ,medicine.drug_class ,Cardiac amyloidosis ,Internal medicine ,Sex differences ,Biopsy ,medicine ,Natriuretic peptide ,Ejection fraction ,biology ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Original article ,General Medicine ,Stroke volume ,medicine.disease ,Wild-type transthyretin amyloidosis ,Transthyretin ,Female patient ,Heart failure ,biology.protein ,Cardiology ,business - Abstract
Background: With recent advances in non-invasive diagnostic tools, some studies indicate that wild-type transthyretin amyloidosis (ATTRwt) may be more common in females than previously reported. However, the clinical characteristics of female ATTRwt patients have not been determined. Methods and Results: Of the 78 consecutive patients with ATTRwt in our cohort, 14 (17.9 %) were female. Compared with male patients, female ATTRwt patients had smaller left ventricular (LV) wall thicknesses (ventricular septum thickness 12.9 vs. 14.2 mm [P=0.081]; posterior wall thickness 12.7 vs. 13.6 mm [P=0.035]) and a higher LV ejection fraction (EF; mean [±SD] 58.4±8.9% vs. 48.9±11.8%; P=0.006). However, the severity of heart failure (HF), as assessed by HF stage, New York Heart Association functional class and B-type natriuretic peptide concentrations, did not differ between female and male patients. Moreover, LV mass index and relative wall thickness were increased and the stroke volume index was reduced in both female and male patients. In organ biopsies, female patients had a higher sensitivity to transthyretin deposition from abdominal fat than male patients (positive abdominal fat biopsy 80.0 % vs. 26.5%; P=0.016). Conclusions: This study suggests that a relatively large proportion of elderly females have ATTRwt. Female ATTRwt patients had HF symptoms even at the stage of mild LV hypertrophy and preserved EF. Abdominal fat biopsy may be useful to diagnose ATTRwt, especially in female patients with HF.
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- 2021
29. Contribution of monocarboxylate transporter 12 to blood supply of creatine on the sinusoidal membrane of the hepatocytes
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Masanori Tachikawa, Ryuta Jomura, Ken Ichi Hosoya, Shin Ichi Akanuma, Yoshiyuki Kubo, and Yu Tanno
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Male ,Monocarboxylic Acid Transporters ,0301 basic medicine ,Physiology ,Xenopus ,Creatine ,Phosphocreatine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,Physiology (medical) ,Animals ,Rats, Wistar ,Monocarboxylate transporter ,Gene knockdown ,Hepatology ,biology ,Chemistry ,Gastroenterology ,Transporter ,Capillaries ,Rats ,Cell biology ,030104 developmental biology ,Hepatocytes ,biology.protein ,Female ,Rabbits ,Efflux ,030217 neurology & neurosurgery ,Intracellular - Abstract
Creatine (Cr)/phosphocreatine has the ability to buffer the high-energy phosphate, thereby contributing to intracellular energy homeostasis. As Cr biosynthetic enzyme deficiency is reported to increase susceptibility to colitis under conditions of inflammatory stress, Cr is critical for maintaining intestinal homeostasis under inflammatory stress. Cr is mainly produced in the hepatocytes and then distributed to other organs of the body by the circulatory system. Since monocarboxylate transporter 9 (MCT9) and monocarboxylate transporter 12 (MCT12) have been reported to accept Cr as a substrate, these transporters are proposed as candidates for Cr efflux transporter in the liver. The aim of this study was to elucidate the transport mechanism on Cr supply from the hepatocytes. Immunohistochemical staining of the rat liver sections revealed that both MCT9 and MCT12 were localized on the sinusoidal membrane of the hepatocytes. In the transport studies using Xenopus laevis oocyte expression system, [14C]Cr efflux from MCT9- or MCT12-expressing oocytes was significantly greater than that from water-injected oocytes. [14C]Cr efflux from primary cultured hepatocytes was significantly decreased following MCT12 mRNA knockdown, whereas this efflux was not decreased after mRNA knockdown of MCT9. Based on the extent of MCT12 protein downregulation and Cr efflux after knockdown of MCT12 in primary cultured rat hepatocytes, the contribution ratio of MCT12 in Cr efflux was calculated as 76.4%. Our study suggests that MCT12 substantially contributes to the efflux of Cr at the sinusoidal membrane of the hepatocytes.NEW & NOTEWORTHY Our study is the first to identify the role of monocarboxylate transporter 12 (MCT12) as a transporter of creatine (Cr) in the liver. MCT12 was found to significantly contribute to the efflux of Cr on the sinusoidal membrane of the hepatocytes. Since hepatocytes are known to be involved in creatine biosynthesis, the present findings can be beneficial for the regulation of Cr biosynthesis and supply.
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- 2021
30. Genetic epidemiological analysis of hypouricaemia from 4993 Japanese on non-functional variants of URAT1/SLC22A12 gene
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Satoko Iwasawa, Keiichi Ito, Yu Toyoda, Seiko Shimizu, Toshihiko Imakiire, Yoko Kubo, Yuka Aoki, Akiyoshi Nakayama, Yusuke Kawamura, Hirotaka Matsuo, Masashi Tsunoda, Kimiyoshi Ichida, Hiroo Kumagai, Tappei Takada, Makoto Kawaguchi, Rieko Okada, Nariyoshi Shinomiya, Hiroshi Nakashima, and Kenji Takeuchi
- Subjects
Male ,medicine.medical_specialty ,Renal Tubular Transport, Inborn Errors ,Genotype ,Organic Cation Transport Proteins ,Population ,Organic Anion Transporters ,Gastroenterology ,chemistry.chemical_compound ,Japan ,Rheumatology ,Internal medicine ,Epidemiology ,medicine ,Humans ,Pharmacology (medical) ,Hypouricemia ,education ,Genotyping ,education.field_of_study ,biology ,business.industry ,Genetic Variation ,medicine.disease ,chemistry ,Genetic epidemiology ,Cohort ,biology.protein ,Uric acid ,Female ,Urinary Calculi ,SLC22A12 ,business - Abstract
Objectives Up to 0.3% of Japanese have hypouricaemia. Most cases appear to result from a hereditary disease, renal hypouricaemia (RHUC), which causes exercise-induced acute kidney injury and urolithiasis. However, to what extent RHUC accounts for hypouricaemia is not known. We therefore investigated its frequency and evaluated its risks by genotyping a general Japanese population. Methods A cohort of 4993 Japanese was examined by genotyping the non-functional variants R90H (rs121907896) and W258X (rs121907892) of URAT1/SLC22A12, the two most common causative variants of RHUC in Japanese. Results Participants’ fractional excretion of uric acid and risk allele frequencies markedly increased at lower serum uric acid (SUA) levels. Ten participants (0.200%) had an SUA level ≤2.0 mg/dl and nine had R90H or W258X and were likely to have RHUC. Logistic regression analysis revealed these URAT1 variants to be significantly and independently associated with the risk of hypouricaemia and mild hypouricaemia (SUA ≤3.0 mg/dl) as well as sex, age and BMI, but these URAT1 variants were the only risks in the hypouricaemia population (SUA ≤2.0 mg/dl). W258X was only a risk in males with SUA ≤3.0 mg/dl. Conclusion Our study accurately reveals the prevalence of RHUC and provides genetic evidence for its definition (SUA ≤2.0 mg/dl). We also show that individuals with SUA ≤3.0 mg/dl, especially males, are prone to RHUC. Our findings will help to promote a better epidemiological understanding of RHUC as well as more accurate diagnosis, especially in males with mild hypouricaemia.
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- 2021
31. Author Correction: Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs
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Masako Ochiai, Kenji Matsumoto, Shigeki Sekine, Teruhiko Yoshida, Hirokazu Taniguchi, Takashi Kubo, Atsushi Ochiai, Hitoshi Ichikawa, Toshio Imai, Hiromi Sakamoto, and Mie Naruse
- Subjects
Multidisciplinary ,Science ,Organoid ,Cancer research ,Medicine ,Biology ,Gene ,Co culturing - Published
- 2021
32. Benchmark of 16S rRNA gene amplicon sequencing using Japanese gut microbiome data from the V1–V2 and V3–V4 primer sets
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Shoichiro Kameoka, Ryuichi Kubo, Nicolas Jung, Satoshi Watanabe, Aya K. Takeda, Shota Nakamura, Yuki Midorikawa, Yu Sawai, Natsuko O. Shinozaki, and Daisuke Motooka
- Subjects
QH426-470 ,DNA sequencing ,law.invention ,03 medical and health sciences ,Japan ,law ,RNA, Ribosomal, 16S ,Genetics ,Humans ,16S rRNA ,Polymerase chain reaction ,030304 developmental biology ,Bifidobacterium ,0303 health sciences ,biology ,030306 microbiology ,Research ,Microbiota ,Verrucomicrobia ,High-Throughput Nucleotide Sequencing ,Genes, rRNA ,Akkermansia ,biology.organism_classification ,16S ribosomal RNA ,Gastrointestinal Microbiome ,Benchmarking ,Next-generation sequencing ,DNA microarray ,Primer (molecular biology) ,TP248.13-248.65 ,Biotechnology - Abstract
Background 16S rRNA gene amplicon sequencing (16S analysis) is widely used to analyze microbiota with next-generation sequencing technologies. Here, we compared fecal 16S analysis data from 192 Japanese volunteers using the modified V1–V2 (V12) and the standard V3–V4 primer (V34) sets to optimize the gut microbiota analysis protocol. Results QIIME1 and QIIME2 analysis revealed a higher number of unclassified representative sequences in the V34 data than in the V12 data. The comparison of bacterial composition demonstrated that at the phylum level, Actinobacteria and Verrucomicrobia were detected at higher levels with V34 than with V12. Among these phyla, we observed higher relative compositions of Bifidobacterium and Akkermansia with V34. To estimate the actual abundance, we performed quantitative real-time polymerase chain reaction (qPCR) assays for Akkermansia and Bifidobacterium. We found that the abundance of Akkermansia as detected by qPCR was close to that in V12 data, but was markedly lower than that in V34 data. The abundance of Bifidobacterium detected by qPCR was higher than that in V12 and V34 data. Conclusions These results indicate that the bacterial composition derived from the V34 region might differ from the actual abundance for specific gut bacteria. We conclude that the use of the modified V12 primer set is more desirable in the 16S analysis of the Japanese gut microbiota.
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- 2021
33. Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis
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Seiya Imoto, Atsushi Niida, Michiaki Kubo, Yuichi Shiraishi, Yukihide Momozawa, Ryunosuke Saiki, Yasuhito Nannya, Takayuki Morisaki, Tetsuichi Yoshizato, Chikashi Terao, Seishi Ogawa, Shuichi Matsuda, Hideki Makishima, Yoichiro Kamatani, Yutaka Kuroda, Yotaro Ochi, Yoshinori Murakami, Masahiro Nakagawa, Koichi Matsuda, Kenichi Chiba, Hiroko Tanaka, and Satoru Miyano
- Subjects
clone (Java method) ,Genetics ,Somatic cell ,Clonal hematopoiesis ,food and beverages ,Cancer ,General Medicine ,Disease ,Biology ,medicine.disease ,Phenotype ,General Biochemistry, Genetics and Molecular Biology ,medicine ,Indel ,Gene - Abstract
Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11,234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH. Analysis of single-nucleotide variants and copy number alterations gives a more complete picture of clonal hematopoiesis and its impact on hematological malignancy and cardiovascular disease.
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- 2021
34. High membrane expression of CMTM6 in hepatocellular carcinoma is associated with tumor recurrence
- Author
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Takamichi Igarashi, Tetsunari Oyama, Kouki Hoshino, Gantumur Dolgormaa, Yuki Shimoda, Kenichiro Araki, Norifumi Harimoto, Norihiro Ishii, Norio Kubo, Kei Hagiwara, Hiroshi Saeki, Takahiro Yamanaka, Mariko Tsukagoshi, Takehiko Yokobori, Ryo Muranushi, Akira Watanabe, Batbayar Chingunjav, Ken Shirabe, and Rie Sano
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Carcinoma, Hepatocellular ,recurrence ,CD8-Positive T-Lymphocytes ,Biology ,cytotoxic T lymphocytes ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Humans ,Cytotoxic T cell ,Proliferation Marker ,Aged ,Cell Proliferation ,Aged, 80 and over ,MARVEL Domain-Containing Proteins ,Cell Membrane ,Liver Neoplasms ,Epidemiology and Prevention ,biomarkers ,Original Articles ,hepatocellular carcinoma ,General Medicine ,Middle Aged ,medicine.disease ,digestive system diseases ,Transmembrane protein ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,CTL ,030104 developmental biology ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,immunohistochemistry ,Cancer research ,Immunohistochemistry ,Female ,Original Article ,Neoplasm Recurrence, Local ,Myelin Proteins ,T-Lymphocytes, Cytotoxic - Abstract
CKLF‐like MARVEL transmembrane domain–containing protein 6 (CMTM6) maintains membrane PD‐L1 expression by controlling its endosomal recycling. However, in patients with hepatocellular carcinoma (HCC), the correlation among CMTM6, B7 family ligands, and CD8‐positive cytotoxic T lymphocytes (CTLs), and the molecular function of CMTM6 in HCC have not been established. We performed immunohistochemistry to evaluate the relationships among CMTM6 expression, clinicopathological factors, B7 family ligands expression, and CTL infiltration in HCC samples. Moreover, we established CMTM6‐knockout human HCC cell lines to evaluate the function of human CMTM6 in immune regulation and tumor viability. CMTM6 expression was positively associated with membrane B7 family ligands expression and CTL infiltration in HCC samples. High CMTM6 expression in HCC tissues was associated with the expression of the proliferation marker Ki‐67 and shorter recurrence‐free survival. In vitro analysis showed the downregulation of membrane B7 family ligands and proliferation potency in the CMTM6‐knockout human HCC cell line. High membrane CMTM6 expression was associated with tumor recurrence and proliferation via the regulation of membranous B7 family ligands expression. Thus, CMTM6 might be a biomarker to predict the risk of HCC recurrence and a therapeutic target to suppress tumor growth and increase CTL activity., CMTM6 expression was positively associated with B7 family ligand expression and cytotoxic T lymphocyte (CTL) infiltration in hepatocellular carcinoma (HCC) samples. The CMTM6‐knockout human HCC cell line showed the downregulation of membrane B7 family ligands expression and proliferation potency. High membrane CMTM6 expression was associated with tumor recurrence and proliferation via the regulation of membranous B7 family expression.
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- 2021
35. Rab3a, a small GTP-binding protein, is required for the stabilization of the murine leukaemia virus Gag protein
- Author
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Hideki Hayashi, Mai Izumida, Katsura Kakoki, Yoshinao Kubo, and Toshifumi Matsuyama
- Subjects
viruses ,Cell ,Rab3a ,Gene Products, gag ,Biology ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Retrovirus ,GTP-Binding Proteins ,Lysosome ,Murine leukaemia virus ,gag protein ,CD63 ,medicine ,Gene silencing ,Animals ,Humans ,030304 developmental biology ,Infectivity ,0303 health sciences ,fungi ,Cell Membrane ,Virion ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,Group-specific antigen ,biology.organism_classification ,Cell biology ,Leukemia Virus, Murine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Research Paper - Abstract
We recently identified a CD63-interacting protein to understand the role of CD63 in virion production of the human immunodeficiency virus type 1, and we have found that Rab3a forms a complex with CD63. In this study, we analysed the effect of Rab3a on virion production of the murine leukaemia virus (MLV), which is another member of the retrovirus family. We found that Rab3a silencing induced lysosomal degradation of the MLV Gag protein, and recovery of the Rab3a expression restored the level of the Gag protein through a complex formation of MLV Gag and Rab3a, indicating that Rab3a is required for MLV Gag protein expression. In contrast, CD63 silencing decreased the infectivity of released virions but had no effect on virion production, indicating that CD63 facilitates the infectivity of released MLV particles. Although Rab3a induced CD63 degradation in uninfected cells, the complex of MLV Gag and Rab3a suppressed the Rab3a-mediated CD63 degradation in MLV-infected cells. Finally, we found that the MLV Gag protein interacts with Rab3a to stabilize its own protein and CD63 that facilitates the infectivity of released MLV particles. Considering the involvement of Rab3a in lysosome trafficking to the plasma membrane, it may also induce cell surface transport of the MLV Gag protein., Small GTPases, 13(1), pp.162-182; 2022
- Published
- 2021
36. Proton Pump Inhibitor-Associated Large Hyperplastic Polyp in Non-Helicobacter pylori-Infected Stomach
- Author
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Momoko Tsuda, Kimitoshi Kubo, Mototsugu Kato, Noriko Kimura, Takeshi Mizushima, Soichiro Matsuda, and Norishige Maiya
- Subjects
medicine.medical_specialty ,biology ,business.industry ,medicine.drug_class ,Stomach ,Gastroenterology ,Proton-pump inhibitor ,Endoscopic mucosal resection ,Pedunculated polyp ,Helicobacter pylori ,biology.organism_classification ,Curvatures of the stomach ,Lesion ,medicine.anatomical_structure ,Hyperplastic Polyp ,Internal medicine ,medicine ,medicine.symptom ,business - Abstract
A proton pump inhibitor (PPI)-associated hyperplastic polyp (HP) in the non-Helicobacter pylori-infected stomach is rare, and its endoscopic features remain poorly described. A 42-year-old man with tarry stool was referred to our hospital for examination and treatment. He had taken PPI for 14 years and was confirmed to be H. pylori-negative. Transnasal endoscopy revealed bleeding from a 20-mm, reddish pedunculated polyp with a nodular surface, located in the greater curvature of the upper gastric body. Endoscopic mucosal resection was performed, and the lesion was diagnosed as an HP. To our knowledge, this report represents a valuable addition to the HP literature describing a rare case of PPI-associated large HP in the non-H. pylori-infected stomach.
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- 2021
37. Genetic diversity among Japanese local populations of an edible and medicinal coastal plant Glehnia littoralis F. Schmidt ex Miq
- Author
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Yasuhiro Tamura, Takanori Ohsako, and Nakao Kubo
- Subjects
0106 biological sciences ,0301 basic medicine ,Panmixia ,Genetic diversity ,Outcrossing ,Plant Science ,Biology ,01 natural sciences ,Analysis of molecular variance ,03 medical and health sciences ,Fixation (population genetics) ,030104 developmental biology ,Genetic drift ,Evolutionary biology ,Genetic variation ,Genetics ,Inbreeding depression ,Agronomy and Crop Science ,Ecology, Evolution, Behavior and Systematics ,010606 plant biology & botany - Abstract
To assess the current genetic status of a useful coastal plant Glehnia littoralis F. Schmidt ex Miq. in Japan, the genetic diversity within and among natural populations was investigated. A total of 601 individuals from 32 local populations were genotyped using inter-primer binding site (iPBS) markers. In addition, most likelihood inference of the outcrossing rate was determined based on genotyping of maternal families from two populations using newly developed microsatellite markers. A total of 34 polymorphic bands were detected with seven iPBS primers. All populations showed genetic variation, with Shannon’s I ranging from 0.577 to 0.107. Analysis of molecular variance (AMOVA), neighbor-joining analysis, and Bayesian cluster analysis revealed that the populations were differentiated into a group on the Sea of Japan coast and another on the Pacific Ocean coast. Furthermore, populations in geographic proximity were genetically more similar to each other. These results suggested that long-distance gene flow among local populations is limited. Nonetheless, a high within-population component of genetic diversity after AMOVA (77.4%) and high population’s Q values (an average of 0.781) indicated that the level of genetic differentiation among populations is moderate. Outcrossing rate estimates based on eight microsatellite loci were 0.88 to 0.80 for two different populations, showing the mostly panmictic nature of the species. Substantial level of genetic variation within and among populations implicates that genetic improvement on desirable traits is possible via artificial selection. On the other hand, the present study showed that maintenance of population size is critical to avoid fitness decline in natural populations via inbreeding depression and fixation of deleterious alleles by genetic drift.
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- 2021
38. Nuclear and mitochondrial DNA polymorphisms suggest introgression contributed to garden beet (Beta vulgaris L.) domestication
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Kazuyoshi Kitazaki, Kosuke Satoh, Tomohiko Kubo, Ryo Hayakawa, Yosuke Kuroda, Jun Kashikura, Yohei Kanomata, and Hiroaki Matsuhira
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0106 biological sciences ,0301 basic medicine ,Mitochondrial DNA ,Introgression ,Plant Science ,Biology ,Population structure ,01 natural sciences ,Domestication ,03 medical and health sciences ,Botany ,Garden beet ,Genetics ,Ecology, Evolution, Behavior and Systematics ,Genetic diversity ,fungi ,technology, industry, and agriculture ,food and beverages ,Plant physiology ,030104 developmental biology ,Minisatellite ,Genetic marker ,Gene pool ,Mitoype ,Agronomy and Crop Science ,geographic locations ,010606 plant biology & botany - Abstract
Garden beet is the ancestor of fodder beets and sugar beets, but the origin of garden beet’s genetic potential to evolve novel beet types is debatable. In this study, we analyzed nuclear and mitochondrial DNAs in 47 garden beet accessions using DNA markers. Multiple analytical methods revealed a unified population structure with subpopulations evi- dent in the European and Caucasian accessions. We diagnosed mitochondrial genome types (mitotypes) based on mitochondrial minisatellite loci in 541 plants from the 47 accessions, revealing a major mitotype and 11 minor mitotypes in garden beets from Europe and the Caucasus region that were also present in endemic leaf beets and wild beets. Our data indicate that European and Caucasian garden beets include genetically differentiated subpopulations. Provided that the occurrence of minor mitotypes is a vestige from crosses with leaf beets and wild beets, the notion that introgression contributed to increasing the genet ic diversity in the garden beet gene pool is substantiated at the molecular level.
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- 2021
39. Primary Pancreatic Mantle Cell Lymphoma Diagnosed via Endoscopic Ultrasound-Guided Fine-Needle Aspiration
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Kazuyoshi Ohkawa, Yutaro Abe, Kenji Ikezawa, Tasuku Nakabori, Chiaki Kubo, Kazuma Daiku, Shingo Maeda, Ryoji Takada, Takuo Yamai, Kaori Ishida, Nobuyasu Fukutake, Yugo Kai, Hiroyuki Uehara, and Hiroaki Masaie
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Immunoglobulin gene ,CD20 ,Endoscopic ultrasound ,medicine.medical_specialty ,Chemotherapy ,biology ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Single Case ,Gastroenterology ,RC799-869 ,Diseases of the digestive system. Gastroenterology ,Primary pancreatic lymphoma ,medicine.disease ,Pancreatic tumor ,Cyclin D1 ,Fine-needle aspiration ,Endoscopic ultrasound-guided fine-needle aspiration ,biology.protein ,medicine ,Mantle cell lymphoma ,Radiology ,business - Abstract
Primary pancreatic lymphomas (PPLs) are rare, and the histological classification of these tumors is difficult. To accurately diagnose and determine the appropriate treatment for PPLs, sufficient sample amounts are necessary. Here, we report a 73-year-old man with a primary pancreatic mantle cell lymphoma. Histological samples were obtained via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The tumor cells predominantly composed of atypical small to medium round cells, with diffuse immunoreactivity of CD20 and cyclin D1. In addition, immunoglobulin gene H chain rearrangement was detected. The patient underwent chemotherapy, resulting in complete remission. Eight years after the initiation of chemotherapy, the patient was still alive. EUS-FNA could be a useful and safe diagnostic modality for PPLs by providing enough samples for testing.
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- 2021
40. A case of dramatic reduction in cancer-associated thrombus following initiation of pembrolizumab in patient with a poor performance status and PD-L1+ lung adenocarcinoma harboring CCDC6–RET fusion gene and NF1/TP53 mutations
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Toshio Kubo, Shingo Matsumoto, Hiromi Watanabe, Koichi Goto, Kadoaki Ohashi, Katsuyuki Kiura, Takamasa Nakasuka, Katsuyuki Hotta, and Yoshinobu Maeda
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,endocrine system diseases ,medicine.medical_treatment ,Pembrolizumab ,Fusion gene ,03 medical and health sciences ,0302 clinical medicine ,PD-L1 ,medicine ,neoplasms ,CCDC6/RET Fusion Gene ,biology ,business.industry ,Standard treatment ,Cancer ,Immunotherapy ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Adenocarcinoma ,business - Abstract
Objectives Pembrolizumab is a standard treatment for non-small cell lung cancer (NSCLC) with high-PD-L1 expression; however, its effect is dismal in patients with poor physical condition. Additionally, the effect of immunotherapy is generally limited in NSCLC harboring driver mutations such asEGFR, ALK, or RET gene aberrations. Results We report the beneficial effect of pembrolizumab in a patient with poor performance status and PD-L1+ lung adenocarcinoma with theCCDC6–RET fusion gene and co-occurring NF1/TP53 mutations, complicated by multiple cancer-associated thrombi and respiratory failure. Conclusions Further studies are warranted to establish the role of co-occurring NF1/TP53 mutations as a positive predictive biomarker for pembrolizumab in NSCLC harboring RET fusion genes.
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- 2021
41. Neoantigens elicit T cell responses in breast cancer
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Jae-Hyun Park, Sachiko Yoshimura, Mai Yamada, Masafumi Nakamura, Masayo Umebayashi, Poh Yin Yew, Takafumi Morisaki, Makoto Kubo, Yoshinao Oda, Takashi Morisaki, Yusuke Nakamura, Kazuma Kiyotani, and Masaya Kai
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Adult ,T cell ,Science ,Immunology ,Breast Neoplasms ,Human leukocyte antigen ,Biology ,Article ,Immune system ,Breast cancer ,Lymphocytes, Tumor-Infiltrating ,Antigen ,Antigens, Neoplasm ,Exome Sequencing ,medicine ,Cytotoxic T cell ,Humans ,Cancer ,Aged ,Immunity, Cellular ,Multidisciplinary ,integumentary system ,ELISPOT ,Dendritic Cells ,Middle Aged ,medicine.disease ,Computational biology and bioinformatics ,medicine.anatomical_structure ,Oncology ,Cancer research ,Medicine ,Female ,Ex vivo ,T-Lymphocytes, Cytotoxic - Abstract
Neoantigens are tumor-specific antigens that arise from non-synonymous mutations in tumor cells. However, their effect on the immune responses in tumor microenvironment are still unclear in breast cancer.We performed whole exome and RNA sequencing of 31 fresh breast cancer tissues and neoantigen prediction on the non-synonymous single nucleotide variants (nsSNVs) among exonic mutations. Neoantigen profiles were determined by predictive HLA binding affinity (IC50ex vivo. These results suggest that neoantigen analysis may show utility in developing strategies to elicit T cell responses.
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- 2021
42. 3-Hydroxykynurenine Regulates Lipopolysaccharide-Stimulated IL-6 Production and Protects against Endotoxic Shock in Mice
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Kuniaki Saito, Kentaro Nakamoto, Yasuko Yamamoto, Masato Hoshi, Chieko Tashita, Hisako Kubo, Hiroyuki Tezuka, and Tatsuya Ando
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Lipopolysaccharides ,Male ,Lipopolysaccharide ,Immunology ,3-Hydroxykynurenine ,Activating Transcription Factor 4 ,Pharmacology ,Sepsis ,Mice ,chemistry.chemical_compound ,Kynurenine 3-Monooxygenase ,medicine ,Adjuvant therapy ,Animals ,Humans ,Immunology and Allergy ,Interleukin 6 ,Kynurenine ,Mice, Knockout ,Sulfonamides ,biology ,Interleukin-6 ,business.industry ,Macrophages ,ATF4 ,General Medicine ,medicine.disease ,Shock, Septic ,Disease Models, Animal ,Thiazoles ,Liver ,chemistry ,biology.protein ,business ,Signal Transduction - Abstract
Despite advances in our understanding of endotoxic shock, novel therapeutic interventions that can reduce the burden of sepsis remain elusive. Current treatment options are limited, and it is only through refinements in the ways that we deliver supportive care that mortality has fallen over the years. In this study, the role of kynurenine 3-monooxygenase (KMO) in immune regulation was examined in LPS-induced endotoxemia using KMO−/− and KMO+/+ mice treated with the KMO inhibitor Ro61-8048. We showed that LPS-induced or cecal ligation and puncture–induced mortality and hepatic IL-6 production increased in the absence of KMO, possibly involving increased activating transcription factor 4 (ATF4) signaling in hepatic macrophages. Moreover, treatment of septic mice with 3-hydroxykynurenine reduced mortality rates and inflammatory responses regardless of the presence or absence of KMO. According to our results, the administration of 3-hydroxykynurenine as part of the treatment approach for sepsis or as an adjuvant therapy might reduce the overproduction of IL-6, which is responsible for severe endotoxemia, and ultimately improve the survival rates of patients with sepsis.
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- 2021
43. Influenza virus infection expands the breadth of antibody responses through IL-4 signalling in B cells
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Taiki Yajima, Masato Kubo, Osamu Ohara, Yoichiro Iwakura, Akihiko Yoshimura, Hideki Hasegawa, Yu Adachi, Keisuke Tonouchi, Yasuyo Harada, Senka Deno, Kosuke Miyauchi, Yoshimasa Takahashi, Hidehiro Fukuyama, Katsuyuki Yugi, and Shin-ichiro Fujii
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0301 basic medicine ,T Follicular Helper Cells ,Science ,Hemagglutinins, Viral ,General Physics and Astronomy ,Hemagglutinin (influenza) ,Antibodies, Viral ,Article ,Antibodies ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,Virus ,Influenza A Virus, H2N2 Subtype ,Epitopes ,Mice ,03 medical and health sciences ,Influenza A Virus, H1N1 Subtype ,0302 clinical medicine ,Immune system ,Orthomyxoviridae Infections ,Immunity ,Animals ,Mice, Knockout ,B cells ,B-Lymphocytes ,Multidisciplinary ,biology ,Interleukins ,Influenza A Virus, H3N2 Subtype ,Vaccination ,Germinal center ,virus diseases ,General Chemistry ,Virology ,Mice, Inbred C57BL ,030104 developmental biology ,Viral replication ,Influenza Vaccines ,Immunoglobulin G ,biology.protein ,Female ,Interleukin-4 ,Antibody ,Influenza virus ,Broadly Neutralizing Antibodies ,Signal Transduction ,030215 immunology - Abstract
Influenza viruses are a major public health problem. Vaccines are the best available countermeasure to induce effective immunity against infection with seasonal influenza viruses; however, the breadth of antibody responses in infection versus vaccination is quite different. Here, we show that nasal infection controls two sequential processes to induce neutralizing IgG antibodies recognizing the hemagglutinin (HA) of heterotypic strains. The first is viral replication in the lung, which facilitates exposure of shared epitopes that are otherwise hidden from the immune system. The second process is the germinal center (GC) response, in particular, IL-4 derived from follicular helper T cells has an essential role in the expansion of rare GC-B cells recognizing the shared epitopes. Therefore, the combination of exposure of the shared epitopes and efficient proliferation of GC-B cells is critical for generating broadly-protective antibodies. These observations provide insight into mechanisms promoting broad protection from virus infection., The reasons why influenza infection promotes a broader antibody response compared with vaccines are not fully understood. Here the authors show that unmasking of haemagglutinin epitopes and IL-4 signals in the germinal centre contribute to broader antibody responses after infection.
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- 2021
44. Secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs: A case report
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Hiroyuki Yanai, Daisuke Ennishi, Toshio Kubo, Tadashi Yoshino, Akira Hirasawa, Kohei Taniguchi, and Tatsuya Kaji
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Pathology ,medicine.medical_specialty ,SUBCUTANEOUS MASS ,Histology ,integumentary system ,biology ,business.industry ,Skin tumor ,Dermatology ,Pathology and Forensic Medicine ,Fusion gene ,SWEAT ,Secretory Carcinoma ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Mammaglobin ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,medicine ,ETV6-NTRK3 gene fusion ,business ,Lymph node - Abstract
Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31-year-old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next-generation sequencing-based multiplex gene assay performed on the metastatic tissue revealed an ETV6-NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs.
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- 2021
45. Relationship of hemoglobin level and plasma coproporphyrin‐I concentrations as an endogenous probe for phenotyping OATP1B
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Masahiro Nakatochi, Michiaki Kubo, Keiko Ohno, Teruhide Koyama, Ayako Oda, Chisato Yoshijima, Ritei Uehara, Yukihide Momozawa, Yosuke Suzuki, and Yuri Sasamoto
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Adult ,Male ,Coproporphyrins ,medicine.medical_specialty ,Population ,Endogeny ,RM1-950 ,Heme ,Polymorphism, Single Nucleotide ,Article ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,Hemoglobins ,Basal (phylogenetics) ,Polymorphism (computer science) ,Internal medicine ,medicine ,Humans ,Precision Medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Allele ,education ,Alleles ,Aged ,education.field_of_study ,biology ,Liver-Specific Organic Anion Transporter 1 ,Chemistry ,Research ,General Neuroscience ,Articles ,General Medicine ,Middle Aged ,Organic anion-transporting polypeptide ,Endocrinology ,biology.protein ,Biomarker (medicine) ,Female ,Therapeutics. Pharmacology ,Hemoglobin ,Public aspects of medicine ,RA1-1270 ,Biomarkers ,Genome-Wide Association Study - Abstract
Plasma coproporphyrin‐I (CP‐I) concentration is used as a sensitive and selective endogenous probe for phenotyping organic anion transporting polypeptides 1B (OATP1B) activity in many studies. CP‐I is produced in the process of heme synthesis, but the relationship between plasma CP‐I concentrations and heme synthesis activity is unknown. In this study, we evaluated the relationship between plasma CP‐I concentration and hemoglobin level as a biomarker of heme synthesis activity. The data of 391 subjects selected from the Japanese general population were analyzed. One hundred twenty‐six participants had OATP1B1*15 allele, 11 of whom were homozygous (OATP1B1*15/*15). Multiple regression analysis identified hemoglobin level as an independent variable associated with plasma CP‐I concentration (p
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- 2021
46. Tenosynovial and Cardiac Transthyretin Amyloidosis in Japanese Patients Undergoing Carpal Tunnel Release
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Hiroaki Kitaoka, Yuri Ochi, Yuichi Baba, Masahiko Ikeuchi, Tatsuya Noguchi, Toru Kubo, Takayoshi Hirota, Hiroki Kozuki, Kenta Sugiura, Hiroaki Ueba, Naohito Yamasaki, Junko Nakashima, Kazuya Miyagawa, Noriko Wada, and Ichiro Murakami
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medicine.medical_specialty ,Myocardial Disease ,biology ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Original article ,Carpal tunnel surgery ,General Medicine ,Cardiac amyloidosis ,medicine.disease ,Scintigraphy ,Transthyretin ,Concomitant ,Biopsy ,biology.protein ,medicine ,Radiology ,business ,Progressive disease - Abstract
Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is a life-threatening progressive disease. Recent studies have shown that the detection of transthyretin (TTR) amyloid in tenosynovial tissue may play an important role in the diagnosis of cardiac amyloidosis. The aim of this study was to determine the prevalence of TTR amyloid deposits in surgical tissue of patients undergoing carpal tunnel surgery and to clarify the clinical significance of concomitant cardiac examination with 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy in those patients with TTR deposition. Methods and Results: We evaluated 79 consecutive patients undergoing carpal tunnel release surgery and biopsy of tenosynovial tissue. The mean (±SD) age of the patients at surgery was 71.6±12.5 years (range 30-95 years); 32 patients (41%) were male. TTR amyloid deposition in tenosynovial tissue was observed in 27 patients (34%). Sixteen of those 27 patients underwent 99 mTc-PYP scintigraphy. Of those 16 patients, 3 (19%) had Grade 2 uptake on 99 mTc-PYP scintigraphy. None of the 3 patients with a diagnosis of ATTRwt-CA had apparent cardiac symptoms and left ventricular wall thickness >13 mm. Conclusions: Concomitant cardiac examination with 99 mTc-PYP scintigraphy in patients who had TTR amyloid deposition in tenosynovial tissue resulted in the identification of 19% of patients with a diagnosis of ATTRwt-CA. This diagnostic approach seems to be useful for the early diagnosis of the disease.
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- 2021
47. Neuregulin-1-β1 and γ-secretase play a critical role in sphere-formation and cell survival of urothelial carcinoma cancer stem-like cells
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Terufumi Kubo, Toshiaki Tanaka, Ryuta Inoue, Masahiro Matsuki, Hiroshi Kitamura, Shinichi Hashimoto, Sachiyo Nishida, Kenji Murata, Takayuki Kanaseki, Yoshihiko Hirohashi, Toshihiko Torigoe, Aiko Murai, Tomohide Tsukahara, and Naoya Masumori
- Subjects
0301 basic medicine ,Urologic Neoplasms ,Cell Survival ,Neuregulin-1 ,Population ,Biophysics ,Apoptosis ,medicine.disease_cause ,Biochemistry ,Receptor tyrosine kinase ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,ErbB ,Epidermal growth factor ,Cell Line, Tumor ,Spheroids, Cellular ,Presenilin-2 ,mental disorders ,Presenilin-1 ,medicine ,Humans ,Neuregulin 1 ,Receptor ,education ,Molecular Biology ,education.field_of_study ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Chemistry ,Cell Biology ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,biology.protein ,Cancer research ,RNA Interference ,Amyloid Precursor Protein Secretases ,Urothelium ,Carcinogenesis - Abstract
Previously, we investigated gene expression in a high aldehyde dehydrogenase 1 expression (ALDH1high) population of urothelial carcinoma (UC) cells as UC cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) and found that NRG1 expression was upregulated in ALDH1high cells. NRG1 is a trophic factor that contains an epidermal growth factor (EGF)-like domain that signals by stimulating ERBB receptor tyrosine kinases and the cytoplasmic domain. NRG1 has been determined to be involved in frequent gene fusions with other partners in several malignancies and has a role in carcinogenesis through the NRG1 EGF-like domain and its cognitive receptor ERBBs. We thus aimed to elucidate the function of NRG1 in UC CSCs/CICs in this study. Both NRG1α and NRG1-β1 were preferentially expressed in ALDH1high cells compared with ALDH1low cells; however, siRNA experiments revealed that NRG1-β1 but not NRG1-α has a role in sphere formation. The EGF-like domain of NRG1 had a role in sphere formation of UC cells to some extent but was not essential. The intracellular domain of NRG1 did not have a role in sphere-formation. Inhibition of γ-secretase suppressed sphere formation. These findings indicate that cleavage of NRG1-β1 by γ-secretase plays an important role in UC CSC/CIC proliferation; however, the downstream targets of NRG1-β1 remain elusive.
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- 2021
48. A case of bullous pemphigoid after a long‐term administration of anti‐PD‐1 antibodies in a patient with non‐small‐cell lung cancer
- Author
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Norito Ishii, Hiroshi Koga, Toshio Kubo, Osamu Yamasaki, Emi Yokoyama, and Shin Morizane
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medicine.medical_specialty ,biology ,business.industry ,Anti pd 1 ,Dermatology ,RC581-607 ,medicine.disease ,Gastroenterology ,Internal medicine ,RL1-803 ,medicine ,biology.protein ,Immunology and Allergy ,Bullous pemphigoid ,Non small cell ,Antibody ,Immunologic diseases. Allergy ,business ,Lung cancer - Abstract
We described a case of BP that developed 2.5 years after the administration of nivolumab for metastatic non‐small cell lung cancer. Our report highlights the fact that dermatologists should be aware of anti PD‐1‐related BP, which can appear very late during treatment.
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- 2021
49. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
- Author
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Mlcochova, Petra, Kemp, Steven A., Dhar, Mahesh Shanker, Papa, Guido, Meng, Bo, Ferreira, Isabella A. T. M., Datir, Rawlings, Collier, Dami A., Albecka, Anna, Singh, Sujeet, Pandey, Rajesh, Brown, Jonathan, Zhou, Jie, Goonawardane, Niluka, Mishra, Swapnil, Whittaker, Charles, Mellan, Thomas, Marwal, Robin, Datta, Meena, Sengupta, Shantanu, Ponnusamy, Kalaiarasan, Radhakrishnan, Venkatraman Srinivasan, Abdullahi, Adam, Charles, Oscar, Chattopadhyay, Partha, Devi, Priti, Caputo, Daniela, Peacock, Tom, Wattal, Chand, Goel, Neeraj, Satwik, Ambrish, Vaishya, Raju, Agarwal, Meenakshi, Chauhan, Himanshu, Dikid, Tanzin, Gogia, Hema, Lall, Hemlata, Verma, Kaptan, Singh, Manoj K., Soni, Namita, Meena, Namonarayan, Madan, Preeti, Singh, Priyanka, Sharma, Ramesh, Sharma, Rajeev, Kabra, Sandhya, Kumar, Sattender, Kumari, Swati, Sharma, Uma, Chaudhary, Urmila, Sivasubbu, Sridhar, Scaria, Vinod, Oberoi, J. K., Raveendran, Reena, Datta, S., Das, Saumitra, Maitra, Arindam, Chinnaswamy, Sreedhar, Biswas, Nidhan Kumar, Parida, Ajay, Raghav, Sunil K., Prasad, Punit, Sarin, Apurva, Mayor, Satyajit, Ramakrishnan, Uma, Palakodeti, Dasaradhi, Seshasayee, Aswin Sai Narain, Thangaraj, K., Bashyam, Murali Dharan, Dalal, Ashwin, Bhat, Manoj, Shouche, Yogesh, Pillai, Ajay, Abraham, Priya, Potdar, Varsha Atul, Cherian, Sarah S., Desai, Anita Sudhir, Pattabiraman, Chitra, Manjunatha, M. V., Mani, Reeta S., Udupi, Gautam Arunachal, Nandicoori, Vinay, Tallapaka, Karthik Bharadwaj, Sowpati, Divya Tej, Kawabata, Ryoko, Morizako, Nanami, Sadamasu, Kenji, Asakura, Hiroyuki, Nagashima, Mami, Yoshimura, Kazuhisa, Ito, Jumpei, Kimura, Izumi, Uriu, Keiya, Kosugi, Yusuke, Suganami, Mai, Oide, Akiko, Yokoyama, Miyabishara, Chiba, Mika, Saito, Akatsuki, Butlertanaka, Erika P., Tanaka, Yuri L., Ikeda, Terumasa, Motozono, Chihiro, Nasser, Hesham, Shimizu, Ryo, Yuan, Yue, Kitazato, Kazuko, Hasebe, Haruyo, Nakagawa, So, Wu, Jiaqi, Takahashi, Miyoko, Fukuhara, Takasuke, Shimizu, Kenta, Tsushima, Kana, Kubo, Haruko, Shirakawa, Kotaro, Kazuma, Yasuhiro, Nomura, Ryosuke, Horisawa, Yoshihito, Takaori-Kondo, Akifumi, Tokunaga, Kenzo, Ozono, Seiya, Baker, Stephen, Dougan, Gordon, Hess, Christoph, Kingston, Nathalie, Lehner, Paul J., Lyons, Paul A., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Maxwell, Patrick, Shaw, Ashley, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O'Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Graf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O'Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Bergamaschi, Laura, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Krishna, Ben, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Potts, Martin, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, De Bie, Eckart M. D. D., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Allison, John, Butcher, Helen, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Graves, Barbara, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Le Gresley, Emma, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Scholtes, Ingrid, Hein, Sabine, King, Rebecca, Mavousian, Antranik, Lee, Joo Hyeon, Bassi, Jessica, Silacci-Fegni, Chiara, Saliba, Christian, Pinto, Dora, Irie, Takashi, Yoshida, Isao, Hamilton, William L., Sato, Kei, Bhatt, Samir, Flaxman, Seth, James, Leo C., Corti, Davide, Piccoli, Luca, Barclay, Wendy S., Rakshit, Partha, Agrawal, Anurag, Gupta, Ravindra K., (INSACOG), Indian SARS-CoV-2 Genomics Consortium, Consortium, Genotype to Phenotype Japan (G2P-Japan), Collaboration, CITIID-NIHR BioResource COVID-19, Gupta, Ravindra K [0000-0001-9751-1808], Apollo - University of Cambridge Repository, and Gupta, Ravindra K. [0000-0001-9751-1808]
- Subjects
Male ,COVID-19 Vaccines ,medicine.drug_class ,Health Personnel ,India ,Monoclonal antibody ,Virus Replication ,Antibodies ,Cell Line ,Cell Fusion ,Immune system ,13/100 ,medicine ,Humans ,Neutralizing antibody ,Antibodies, Neutralizing ,Female ,Kinetics ,SARS-CoV-2 ,Spike Glycoprotein, Coronavirus ,Vaccination ,Immune Evasion ,Neutralizing ,631/326/596/4130 ,Syncytium ,Multidisciplinary ,Cell fusion ,biology ,article ,Vaccine efficacy ,631/250/254 ,Virology ,Spike Glycoprotein ,Coronavirus ,13/31 ,biology.protein ,Antibody ,Infection - Abstract
The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era., A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.
- Published
- 2022
50. Capsanthin Production in Escherichia coli by Overexpression of Capsanthin/Capsorubin Synthase from Capsicum annuum
- Author
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Yasuo Mitani, Yuko Otani, Kohji Ohdan, Katsuro Yaoi, Norihiko Misawa, Akiko Kubo, Yoshinobu Terada, Miho Takemura, Maiko Furubayashi, and Takashi Maoka
- Subjects
chemistry.chemical_classification ,ATP synthase ,biology ,Chemistry ,fungi ,food and beverages ,General Chemistry ,medicine.disease_cause ,Lycopene ,Capsicum annuum ,chemistry.chemical_compound ,Enzyme ,Biochemistry ,Pepper ,medicine ,biology.protein ,General Agricultural and Biological Sciences ,Gene ,Carotenoid ,Escherichia coli - Abstract
Capsanthin, a characteristic red carotenoid found in the fruits of red pepper (Capsicum annuum), is widely consumed as a food and a functional coloring additive. An enzyme catalyzing capsanthin synthesis was identified as capsanthin/capsorubin synthase (CCS) in the 1990s, but no microbial production of capsanthin has been reported. We report here the first successful attempt to biosynthesize capsanthin in Escherichia coli by carotenoid-pathway engineering. Our initial attempt to coexpress eight enzyme genes required for capsanthin biosynthesis did not detect the desired product. The dual activity of CCS as a lycopene β-cyclase as well as a capsanthin/capsorubin synthase likely complicated the task. We demonstrated that a particularly high expression level of the CCS gene and the minimization of byproducts by regulating the seven upstream carotenogenic genes were crucial for capsanthin formation in E. coli. Our results provide a platform for further study of CCS activity and capsanthin production in microorganisms.
- Published
- 2021
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