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Your search keyword '"Nakayasu, Ernesto S."' showing total 372 results
Start Over Author "Nakayasu, Ernesto S." Publication Type Academic Journals
372 results on '"Nakayasu, Ernesto S."'

2. Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis

Author

Sarkar, Soumyadeep, Deiter, Cailin, Kyle, Jennifer E., Guney, Michelle A., Sarbaugh, Dylan, Yin, Ruichuan, Li, Xiangtang, Cui, Yi, Ramos-Rodriguez, Mireia, Nicora, Carrie D., Syed, Farooq, Juan-Mateu, Jonas, Muralidharan, Charanya, Pasquali, Lorenzo, Evans-Molina, Carmella, Eizirik, Decio L., Webb-Robertson, Bobbie-Jo M., Burnum-Johnson, Kristin, Orr, Galya, Laskin, Julia, Metz, Thomas O., Mirmira, Raghavendra G., Sussel, Lori, Ansong, Charles, and Nakayasu, Ernesto S.

Published
2024
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3. EMC3 regulates trafficking and pulmonary toxicity of the [SFTPC.sup.I73T] mutation associated with interstitial lung disease

Author

Tang, Xiaofang, Wei, Wei, Sun, Yuqing, Weaver, Timothy E., Nakayasu, Ernesto S., Clair, Geremy, Snowball, John M., Na, Cheng-Lun, Apsley, Karen S., Martin, Emily P., Kotton, Darrell N., Alysandratos, Konstantinos-Dionysios, Huo, Jiuzhou, Molkentin, Jeffery D., Gower, William A., Lin, Xinhua, and Whitsett, Jeffrey A.

Subjects
Physiological aspects, Genetic aspects, Methods, Health aspects, Interstitial lung diseases -- Physiological aspects -- Genetic aspects, Mass spectrometry -- Methods, Endoplasmic reticulum -- Health aspects -- Physiological aspects, Lung diseases, Interstitial -- Physiological aspects -- Genetic aspects
Abstract

Introduction Pulmonary surfactant lipids and proteins, synthesized and secreted by alveolar type 2 epithelial (AT2) cells, are required for the adaptation to air breathing during evolution (1). The gene encoding [...], The most common mutation in surfactant protein C gene (SFTPC), [SFTPC.sup.I73T], causes interstitial lung disease with few therapeutic options. We previously demonstrated that EMC3, an important component of the multiprotein endoplasmic reticulum membrane complex (EMC), is required for surfactant homeostasis in alveolar type 2 epithelial (AT2) cells at birth. In the present study, we investigated the role of EMC3 in the control of [SFTPC.sup.I73T] metabolism and its associated alveolar dysfunction. Using a knock-in mouse model phenocopying the I73T mutation, we demonstrated that conditional deletion of Emc3 in AT2 cells rescued alveolar remodeling/simplification defects in neonatal and adult mice. Proteomic analysis revealed that Emc3 depletion reversed the disruption of vesicle trafficking pathways and rescued the mitochondrial dysfunction associated with I73T mutation. Affinity purification-mass spectrometry analysis identified potential EMC3 interacting proteins in lung AT2 cells, including valosin containing protein (VCP) and its interactors. Treatment of [Sftpc.sup.I73T] knock-in mice and [SFTPC.sup.I73T]-expressing iAT2 cells derived from [SFTPC.sup.I73T] patient-specific iPSCs with the VCP inhibitor CB5083 restored alveolar structure and [SFTPC.sup.I73T] trafficking, respectively. Taken together, the present work identifies the EMC complex and VCP in the metabolism of the disease-associated [SFTPC.sup.I73T] mutant, providing therapeutical targets for [SFTPC.sup.I73T]-associated interstitial lung disease.

Published
2024
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7. Inhibition of the eukaryotic initiation factor-2[alpha] kinase PERK decreases risk of autoimmune diabetes in mice

Author

Muralidharan, Charanya, Huang, Fei, Enriquez, Jacob R., Wang, Jiayi E., Nelson, Jennifer B., Nargis, Titli, May, Sarah C., Chakraborty, Advaita, Figatner, Kayla T., Navitskaya, Svetlana, Anderson, Cara M., Calvo, Veronica, Surguladze, David, Mulvihill, Mark J., Yi, Xiaoyan, Sarkar, Soumyadeep, Oakes, Scott A., Webb-Robertson, Bobbie-Jo M., Sims, Emily K., Staschke, Kirk A., Eizirik, Decio L., Nakayasu, Ernesto S., Stokes, Michael E., Tersey, Sarah A., and Mirmira, Raghavendra G.

Subjects
Diagnosis, Care and treatment, Health aspects, Stress (Physiology) -- Health aspects, Phosphotransferases -- Health aspects, Ligands (Biochemistry) -- Health aspects, Type 1 diabetes -- Diagnosis -- Care and treatment
Abstract

Introduction Type 1 diabetes (T1D) is a disorder of glucose homeostasis that results from the autoimmune destruction of insulin-producing islet [beta] cells. The importance of the immune system in initiating [...], Preventing the onset of autoimmune type 1 diabetes (T1D) is feasible through pharmacological interventions that target molecular stress-responsive mechanisms. Cellular stresses, such as nutrient deficiency, viral infection, or unfolded proteins, trigger the integrated stress response (ISR), which curtails protein synthesis by phosphorylating eukaryotic translation initiation factor-2[alpha] (eIF2[alpha]). In T1D, maladaptive unfolded protein response (UPR) in insulin-producing [beta] cells renders these cells susceptible to autoimmunity. We found that inhibition of the eIF2a kinase PKR-like ER kinase (PERK), a common component of the UPR and ISR, reversed the mRNA translation block in stressed human islets and delayed the onset of diabetes, reduced islet inflammation, and preserved [beta] cell mass in T1D-susceptible mice. Single-cell RNA-Seq of islets from PERK-inhibited mice showed reductions in the UPR and PERK signaling pathways and alterations in antigen-processing and presentation pathways in p cells. Spatial proteomics of islets from these mice showed an increase in the immune checkpoint protein programmed death-ligand 1 (PD-L1) in [beta] cells. Golgi membrane protein 1, whose levels increased following PERK inhibition in human islets and EndoC-[beta]H1 human [beta] cells, interacted with and stabilized PD-L1. Collectively, our studies show that PERK activity enhances [beta] cell immunogenicity and that inhibition of PERK may offer a strategy for preventing or delaying the development of T1D.

Published
2024
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8. Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP)

Author

Jain, Sanjay, Pei, Liming, Spraggins, Jeffrey M., Angelo, Michael, Carson, James P., Gehlenborg, Nils, Ginty, Fiona, Gonçalves, Joana P., Hagood, James S., Hickey, John W., Kelleher, Neil L., Laurent, Louise C., Lin, Shin, Lin, Yiing, Liu, Huiping, Naba, Alexandra, Nakayasu, Ernesto S., Qian, Wei-Jun, Radtke, Andrea, Robson, Paul, Stockwell, Brent R., Van de Plas, Raf, Vlachos, Ioannis S., Zhou, Mowei, Börner, Katy, and Snyder, Michael P.

Published
2023
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10. Elucidating regulatory processes of intense physical activity by multi-omics analysis

Author

Nakayasu, Ernesto S., Gritsenko, Marina A., Kim, Young-Mo, Kyle, Jennifer E., Stratton, Kelly G., Nicora, Carrie D., Munoz, Nathalie, Navarro, Kathleen M., Claborne, Daniel, Gao, Yuqian, Weitz, Karl K., Paurus, Vanessa L., Bloodsworth, Kent J., Allen, Kelsey A., Bramer, Lisa M., Montes, Fernando, Clark, Kathleen A., Tietje, Grant, Teeguarden, Justin, and Burnum-Johnson, Kristin E.

Published
2023
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13. Rapid remodeling of the soil lipidome in response to a drying-rewetting event

Author

Couvillion, Sneha P., Danczak, Robert E., Naylor, Dan, Smith, Montana L., Stratton, Kelly G., Paurus, Vanessa L., Bloodsworth, Kent J., Farris, Yuliya, Schmidt, Darren J., Richardson, Rachel E., Bramer, Lisa M., Fansler, Sarah J., Nakayasu, Ernesto S., McDermott, Jason E., Metz, Thomas O., Lipton, Mary S., Jansson, Janet K., and Hofmockel, Kirsten S.

Published
2023
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15. Author Correction: Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP)

Author

Jain, Sanjay, Pei, Liming, Spraggins, Jeffrey M., Angelo, Michael, Carson, James P., Gehlenborg, Nils, Ginty, Fiona, Gonçalves, Joana P., Hagood, James S., Hickey, John W., Kelleher, Neil L., Laurent, Louise C., Lin, Shin, Lin, Yiing, Liu, Huiping, Naba, Alexandra, Nakayasu, Ernesto S., Qian, Wei-Jun, Radtke, Andrea, Robson, Paul, Stockwell, Brent R., Van de Plas, Raf, Vlachos, Ioannis S., Zhou, Mowei, Börner, Katy, and Snyder, Michael P.

Published
2024
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16. Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections

Author

Bramer, Lisa M., Hontz, Robert D., Eisfeld, Amie J., Sims, Amy C., Kim, Young-Mo, Stratton, Kelly G., Nicora, Carrie D., Gritsenko, Marina A., Schepmoes, Athena A., Akasaka, Osamu, Koga, Michiko, Tsutsumi, Takeya, Nakamura, Morio, Nakachi, Ichiro, Baba, Rie, Tateno, Hiroki, Suzuki, Shoji, Nakajima, Hideaki, Kato, Hideaki, Ishida, Kazunari, Ishii, Makoto, Uwamino, Yoshifumi, Mitamura, Keiko, Paurus, Vanessa L., Nakayasu, Ernesto S., Attah, Isaac K., Letizia, Andrew G., Waters, Katrina M., Metz, Thomas O., Corson, Karen, Kawaoka, Yoshihiro, Gerbasi, Vincent R., Yotsuyanagi, Hiroshi, and Iwatsuki-Horimoto, Kiyoko

Published
2023
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19. Data from a multi-year targeted proteomics study of a longitudinal birth cohort of type 1 diabetes.

Author

Bramer, Lisa M., Nakayasu, Ernesto S., Flores, Javier E., Van Eyk, Jennifer E., MacCoss, Michael J., Parikh, Hemang M., Metz, Thomas O., and Webb-Robertson, Bobbie-Jo M.

Subjects
TYPE 1 diabetes, ANALYTICAL chemistry, QUALITY control, PROTEOMICS, MASS spectrometry, LIQUID chromatography-mass spectrometry
Abstract

The deployment of liquid chromatography-mass spectrometry-based plasma proteomics experiments in a large cohort is sparse, leading to a lack of data available for benchmarking, method development or validation. Comprised of 6,426 plasma analyses, The Environmental Determinants of Diabetes in the Young (TEDDY) proteomics validation study constitutes one of the largest targeted proteomics experiments in the literature to date. The proteomics data from this study were generated over the course of 2.5 years from over 900 study subjects, each providing up to 29 longitudinal samples. The data also includes 916 quality control samples. The targeted mass spectrometry assay was comprised of 694 peptides mapping to 167 proteins and the panel was measured in each subject and QC sample. The targeted proteomic dataset presented here can be used as a resource for new computational methods development, such as for batch correction, as well as for benchmarking and comparing the performance of different methods/tools. [ABSTRACT FROM AUTHOR]

Published
2025
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20. Protein carbamylation and proteomics: from artifacts to elucidation of biological functions.

Author

You, Youngki, Many, Gina, and Nakayasu, Ernesto S.

Subjects
POST-translational modification, BIOLOGICAL systems, ARCHAEOLOGY methodology, PROTEOMICS, RHEUMATOID arthritis
Abstract

Lysine carbamylation is a non-enzymatic protein post-translational modification (PTM) that plays important roles in regulating enzymatic activity and the pathogenesis of diseases such as atherosclerosis, rheumatoid arthritis, and uremia. The progress of understanding the roles of carbamylation in biological systems has been delayed due to lack of systematic assays to study its functions. To aggravate this scenario, carbamylation is a major artifact in proteomics analysis given that urea, which is used during sample preparation, induces carbamylation. In addition, anti-acetyllysine antibodies co-purify carbamylated and acetylated peptides. In a recent paper, we leveraged co-purification with anti-acetyllysine antibodies to develop a method for analyzing carbamylated proteomes. In this perspective article, we discuss how this method may be applied to characterize the physiological functions of carbamylation in humans and other biological models, as well as the utility of establishing novel disease biomarkers. [ABSTRACT FROM AUTHOR]

Published
2025
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25. Multicopy Single-Stranded DNA Directs Intestinal Colonization of Enteric Pathogens.

Author

Elfenbein, Johanna R, Knodler, Leigh A, Nakayasu, Ernesto S, Ansong, Charles, Brewer, Heather M, Bogomolnaya, Lydia, Adams, L Garry, McClelland, Michael, Adkins, Joshua N, and Andrews-Polymenis, Helene L

Subjects
Intestines, Animals, Mice, Escherichia coli, Salmonella typhimurium, DNA, Single-Stranded, Anaerobiosis, Developmental Biology, Genetics
Abstract

Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking its retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate, but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude that a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules.

Published
2015

27. A deep learning‐guided automated workflow in LipidOz for detailed characterization of fungal fatty acid unsaturation by ozonolysis.

Author

Ross, Dylan H., Bredeweg, Erin L., Eder, Josie G., Orton, Daniel J., Burnet, Meagan C., Kyle, Jennifer E., Nakayasu, Ernesto S., and Zheng, Xueyun

Subjects
FATTY acid desaturase, DOUBLE bonds, LIPID metabolism, SACCHAROMYCES cerevisiae, MASS spectrometry
Abstract

Understanding fungal lipid biology and metabolism is critical for antifungal target discovery as lipids play central roles in cellular processes. Nuances in lipid structural differences can significantly impact their functions, making it necessary to characterize lipids in detail to understand their roles in these complex systems. In particular, lipid double bond (DB) locations are an important component of lipid structure that can only be determined using a few specialized analytical techniques. Ozone‐induced dissociation mass spectrometry (OzID‐MS) is one such technique that uses ozone to break lipid DBs, producing pairs of characteristic fragments that allow the determination of DB positions. In this work, we apply OzID‐MS and LipidOz software to analyze the complex lipids of Saccharomyces cerevisiae yeast strains transformed with different fatty acid desaturases from Histoplasma capsulatum to determine the specific unsaturated lipids produced. The automated data analysis in LipidOz made the determination of DB positions from this large dataset more practical, but manual verification for all targets was still time‐consuming. The DL model reduces manual involvement in data analysis, but since it was trained using mammalian lipid extracts, the prediction accuracy on yeast‐derived data was reduced. We addressed both shortcomings by retraining the DL model to act as a pre‐filter to prioritize targets for automated analysis, providing confident manually verified results but requiring less computational time and manual effort. Our workflow resulted in the determination of detailed DB positions and enzymatic specificity. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Comprehensive characterization of extracellular vesicles produced by environmental (Neff) and clinical (T4) strains of Acanthamoeba castellanii.

Author

Gonçalves Medeiros, Elisa, Ramos Valente, Michele, Honorato, Leandro, da Silva Ferreira, Marina, Ruiz Mendoza, Susana, de Souza Gonçalves, Diego, Martins Alcântara, Lucas, Xavier Gomes, Kamilla, Ribeiro Pinto, Marcia, Nakayasu, Ernesto S., Clair, Geremy, Munhoz da Rocha, Isadora Filipaki, Dos Reis, Flavia C. G., Rodrigues, Marcio L., Alves, Lysangela R., Nimrichter, Leonardo, Casadevall, Arturo, and Jefferson Guimarães, Allan

Published
2024
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32. Quality Control Analysis in Real-time (QC-ART): A Tool for Real-time Quality Control Assessment of Mass Spectrometry-based Proteomics Data

Author

Stanfill, Bryan A., Nakayasu, Ernesto S., Bramer, Lisa M., Thompson, Allison M., Ansong, Charles K., Clauss, Therese R., Gritsenko, Marina A., Monroe, Matthew E., Moore, Ronald J., Orton, Daniel J., Piehowski, Paul D., Schepmoes, Athena A., Smith, Richard D., Webb-Robertson, Bobbie-Jo M., and Metz, Thomas O.

Published
2018
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33. The impact of proinflammatory cytokines on the β-cell regulatory landscape provides insights into the genetics of type 1 diabetes

Author

Ramos-Rodríguez, Mireia, Raurell-Vila, Helena, Colli, Maikel L., Alvelos, Maria Inês, Subirana-Granés, Marc, Juan-Mateu, Jonàs, Norris, Richard, Turatsinze, Jean-Valery, Nakayasu, Ernesto S., Webb-Robertson, Bobbie-Jo M., Inshaw, Jamie R. J., Marchetti, Piero, Piemonti, Lorenzo, Esteller, Manel, Todd, John A., Metz, Thomas O., Eizirik, Décio L., and Pasquali, Lorenzo

Published
2019
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35. Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides

Author

Cruz, Carlos E, Fogaça, Andréa C, Nakayasu, Ernesto S, Angeli, Cláudia B, Belmonte, Rodrigo, Almeida, Igor C, Miranda, Antônio, Miranda, Maria, Tanaka, Aparecida S, Braz, Glória R, Craik, Charles S, Schneider, Eric, Caffrey, Conor R, and Daffre, Sirlei

Abstract

Abstract Background Hemoglobin is a rich source of biologically active peptides, some of which are potent antimicrobials (hemocidins). A few hemocidins have been purified from the midgut contents of ticks. Nonetheless, how antimicrobials are generated in the tick midgut and their role in immunity is still poorly understood. Here we report, for the first time, the contribution of two midgut proteinases to the generation of hemocidins. Results An aspartic proteinase, designated BmAP, was isolated from the midgut of Rhipicephalus (Boophilus) microplus using three chromatographic steps. Reverse transcription-quantitative polymerase chain reaction revealed that BmAP is restricted to the midgut. The other enzyme is a previously characterized midgut cathepsin L-like cysteine proteinase designated BmCL1. Substrate specificities of native BmAP and recombinant BmCL1 were mapped using a synthetic combinatorial peptide library and bovine hemoglobin. BmCL1 preferred substrates containing non-polar residues at P2 subsite and polar residues at P1, whereas BmAP hydrolysed substrates containing non-polar amino acids at P1 and P1'. Conclusions BmAP and BmCL1 generate hemocidins from hemoglobin alpha and beta chains in vitro. We postulate that hemocidins may be important for the control of tick pathogens and midgut flora.

Published
2010

38. An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells

Author

Colli, Maikel L., Ramos-Rodríguez, Mireia, Nakayasu, Ernesto S., Alvelos, Maria I., Lopes, Miguel, Hill, Jessica L. E., Turatsinze, Jean-Valery, Coomans de Brachène, Alexandra, Russell, Mark A., Raurell-Vila, Helena, Castela, Angela, Juan-Mateu, Jonàs, Webb-Robertson, Bobbie-Jo M., Krogvold, Lars, Dahl-Jorgensen, Knut, Marselli, Lorella, Marchetti, Piero, Richardson, Sarah J., Morgan, Noel G., Metz, Thomas O., Pasquali, Lorenzo, and Eizirik, Décio L.

Published
2020
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39. PTPN2 Regulates Metabolic Flux to Affect β-Cell Susceptibility to Inflammatory Stress.

Author

Kim, Yong Kyung, Kim, Youngjung Rachel, Wells, Kristen L., Sarbaugh, Dylan, Guney, Michelle, Tsai, Chia-Feng, Zee, Tiffany, Karsenty, Gerard, Nakayasu, Ernesto S., and Sussel, Lori

Subjects
PROTEIN-tyrosine phosphatase, TYPE 1 diabetes, PHOSPHOPROTEIN phosphatases, GENOME-wide association studies, PROTEOMICS, MITOCHONDRIAL pathology, HYPERGLYCEMIA
Abstract

Protein tyrosine phosphatase N2 (PTPN2) is a type 1 diabetes (T1D) candidate gene identified from human genome-wide association studies. PTPN2 is highly expressed in human and murine islets and becomes elevated upon inflammation and models of T1D, suggesting that PTPN2 may be important for β-cell survival in the context of T1D. To test whether PTPN2 contributed to β-cell dysfunction in an inflammatory environment, we generated a β-cell–specific deletion of Ptpn2 in mice (PTPN2-β knockout [βKO]). Whereas unstressed animals exhibited normal metabolic profiles, low- and high-dose streptozotocin-treated PTPN2-βKO mice displayed hyperglycemia and accelerated death, respectively. Furthermore, cytokine-treated Ptpn2 -KO islets resulted in impaired glucose-stimulated insulin secretion, mitochondrial defects, and reduced glucose-induced metabolic flux, suggesting β-cells lacking Ptpn2 are more susceptible to inflammatory stress associated with T1D due to maladaptive metabolic fitness. Consistent with the phenotype, proteomic analysis identified an important metabolic enzyme, ATP-citrate lyase, as a novel PTPN2 substrate. Article Highlights: Although the type 1 diabetes (T1D) susceptibility factor protein tyrosine phosphatase N2 (PTPN2) has been shown to function in β-cells in vitro, an unbiased assessment of its in vivo function in the context of T1D was lacking. β-Cells deleted for Ptpn2 have reduced mitochondrial function with age and are more susceptible to inflammatory stress associated with T1D due to maladaptive metabolic fitness. Consistent with the phenotype, the metabolic enzyme ATP-citrate lyase was identified as a novel PTPN2 substrate. In the absence of PTPN2, β-cells are not able to metabolically compensate for an inflammatory environment. [ABSTRACT FROM AUTHOR]

Published
2024
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