Article
Food Science & Technology
Carmen Haro, Maria H. Guzman-Lopez, Miriam Marin-Sanz, Susana Sanchez-Leon, Luis Vaquero, Jorge Pastor, Isabel Comino, Carolina Sousa, Santiago Vivas, Blanca B. Landa, Francisco Barro
Summary: This study characterized the immunogenic epitopes of tritordeum bread and found that it has fewer peptides related to gluten proteins compared to gluten-free bread. Healthy individuals rated tritordeum bread higher and short-term consumption did not have significant effects on gut microbiota diversity or composition.
Review
Food Science & Technology
Kalekristos Yohannes Woldemariam, Juanli Yuan, Zhen Wan, Qinglin Yu, Yating Cao, Huijia Mao, Yingli Liu, Jing Wang, Hongyan Li, Baoguo Sun
Summary: Wheat mainly consists of gluten with 30% gliadin and 50% glutenin, which are associated with celiac disease. The challenge lies in discovering new gluten-based peptides with high affinity toward T-cells. The highly immunogenic 33-mer gliadin peptide is considered the main cause, so consistent data on different gluten peptides and their immunogenicity is urgently needed.
FOOD REVIEWS INTERNATIONAL
(2022)
Article
Food Science & Technology
Mitchell G. Nye-Wood, Keren Byrne, Sally Stockwell, Angela Juhasz, Utpal Bose, Michelle L. Colgrave
Summary: Gluten content labels are important for those on a gluten-free diet, but regulations vary between jurisdictions, especially for fermented food like beer. ELISA testing for gluten has limitations when it comes to testing fermented or hydrolysed food. Mass spectrometry can directly identify gluten peptides and reveal false negatives from ELISA testing. This study found that some beers claiming to be gluten-free and with low gluten content as measured by ELISA actually contained gluten protein fragments with immunogenic epitopes, and some had higher levels than regular beers. The study discusses the limitations of ELISA testing for beer gluten content and the suitability of current regulations.
Article
Biochemistry & Molecular Biology
Maria Georgina Herrera, Maria Julia Amundarain, Franscesco Nicoletti, Marcus Drechsler, Marcelo Costabel, Pier Luigi Gentili, Veronica Isabel Dodero
Summary: This study reports the formation of thin-plate superstructures by a 33-mer amino acid fragment and provides insights into the early stages of structure formation and the conformational changes of Tyr residues through fluorescence decay measurements and molecular dynamics simulations.
Article
Chemistry, Applied
Robert M. Hnasko, Eric S. Jackson, Alice Lin, Ronald P. Haff, Jeffery A. McGarvey
Summary: A new lateral flow immunoassay (LFIA) method for sensitive gluten detection in complex food substrates was developed using novel gliadin monoclonal antibodies (MAbs) and a visual gold reporter. The study also introduced a novel plug-and-play test strip platform with integrated test components for single-use format.
Article
Plant Sciences
Jan G. Schaart, Elma M. J. Salentijn, Svetlana V. Goryunova, Charity Chidzanga, Danny G. Esselink, Nick Gosman, Alison R. Bentley, Luud J. W. J. Gilissen, Marinus J. M. Smulders
Summary: The study reveals that the genetic diversity of alpha-gliadins in A. tauschii is wider compared to bread wheat, with some A. tauschii accessions containing the CD-triggering 33-mer peptide, while most accessions do not have this epitope, presenting a potential opportunity to breed wheat varieties with fewer or no coeliac disease epitopes through synthetic hexaploid wheats.
Article
Cell Biology
Saborni Chakraborty, Joseph C. Gonzalez, Benjamin L. Sievers, Vamsee Mallajosyula, Srijoni Chakraborty, Megha Dubey, Usama Ashraf, Bowie Yik-Ling Cheng, Nimish Kathale, Kim Quyen Thi Tran, Courtney Scallan, Aanika Sinnott, Arianna Cassidy, Steven T. Chen, Terri Gelbart, Fei Gao, Yarden Golan, Xuhuai Ji, Seunghee Kim-Schulze, Mary Prahl, Stephanie L. Gaw, Sacha Gnjatic, Thomas U. Marron, Miriam Merad, Prabhu S. Arunachalam, Scott D. Boyd, Mark M. Davis, Marisa Holubar, Chaitan Khosla, Holden T. Maecker, Yvonne Maldonado, Elizabeth D. Mellins, Kari C. Nadeau, Bali Pulendran, Upinder Singh, Aruna Subramanian, Paul J. Utz, Robert Sherwood, Sheng Zhang, Prasanna Jagannathan, Gene S. Tan, Taia T. Wang
Summary: A damaging inflammatory response in severe COVID-19 is associated with early non-neutralizing, afucosylated IgG antibodies specific to SARS-CoV-2. Human IgG-Fc-gamma receptor interactions regulate inflammation in the lung, and antibodies elicited by mRNA SARS-CoV-2 vaccines have reduced inflammatory potential.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Brad A. Palanski, Nielson Weng, Lichao Zhang, Andrew J. Hilmer, Lalla A. Fall, Kavya Swaminathan, Bana Jabri, Carolina Sousa, Nielsen Q. Fernandez-Becker, Chaitan Khosla, Joshua E. Elias
Summary: In this study, a new technique was used to discover various dietary peptides in urine. These peptides play important roles in celiac disease-related T cell and innate immune responses, and have qualitative and quantitative differences in patients with celiac disease compared to healthy individuals. These findings are significant for understanding gluten immunogenicity, improving celiac disease management, and characterizing the dietary and urinary peptidomes.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Joseph A. Murray, Jack A. Syage, Tsung-Teh Wu, Matthew A. Dickason, Ana G. Ramos, Carol Van Dyke, Irina Horwath, Philip T. Lavin, Markku Maki, Isabel Hujoel, Konstantinos A. Papadakis, Adam C. Bledsoe, Chaitan Khosla, Jennifer A. Sealey-Voyksner
Article
Biochemistry & Molecular Biology
Sasilada Sirirungruang, Omer Ad, Thomas M. Privalsky, Swetha Ramesh, Joel L. Sax, Hongjun Done, Edward E. K. Baidoo, Bashar Amer, Chaitan Khosla, Michelle C. Y. Chang
Summary: A method to selectively incorporate fluorine into complex structures has been developed, which allows for the production of regioselectively fluorinated full-length polyketides. This approach combines the attributes of synthetic and natural molecules, offering potential for the identification and development of bioactive fluorinated small molecules.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Siavash Mashayekh, Lee M. Stunkard, Maryline Kienle, Irimpan I. Mathews, Chaitan Khosla
Summary: Two classes of promising inhibitors that noncompetitively inhibit UCK2 activity have been identified through structure-based drug prototyping. These inhibitors have the potential to dial the fractional inhibition of pyrimidine salvage and achieve the desired antiviral effect with minimal host toxicity by reducing the kcat of human UCK2 without altering its KM.
Article
Biology
Zicheng Hu, Kattria van der Ploeg, Saborni Chakraborty, Prabhu S. Arunachalam, Diego A. M. Mori, Karen B. Jacobson, Hector Bonilla, Julie Parsonnet, Jason R. Andrews, Marisa Holubar, Aruna Subramanian, Chaitan Khosla, Yvonne Maldonado, Haley Hedlin, Lauren de la Parte, Kathleen Press, Maureen Ty, Gene S. Tan, Catherine Blish, Saki Takahashi, Isabel Rodriguez-Barraquer, Bryan Greenhouse, Atul J. Butte, Upinder Singh, Bali Pulendran, Taia T. Wang, Prasanna Jagannathan, Miles P. Davenport
Summary: Using host proteomics and transcriptomics, the trajectory of immune response in COVID-19 patients was characterized. Early immune markers were found to be associated with disease progression, control of viral shedding, and SARS-CoV-2-specific T cell and antibody responses. Machine-learning models accurately predicted patient outcomes.
Article
Biochemistry & Molecular Biology
Jake Hsu, Nina Fatuzzo, Nielson Weng, Wojciech Michno, Wentao Dong, Maryline Kienle, Yuqin Dai, Anca Pasca, Monther Abu-Remaileh, Natalie Rasgon, Benedetta Bigio, Carla Nasca, Chaitan Khosla
Summary: In eukaryotes, carnitine plays a crucial role in shuttling fatty acids and acetyl groups across mitochondrial membranes for energy production and cellular processes. However, the mechanism by which exogenous LAC affects cellular metabolism is not well understood.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Immunology
Katharine S. Walter, Eugene Kim, Renu Verma, Jonathan Altamirano, Sean Leary, Yuan J. Carrington, Prasanna Jagannathan, Upinder Singh, Marisa Holubar, Aruna Subramanian, Chaitan Khosla, Yvonne Maldonado, Jason R. Andrews
Summary: This study found that there is limited genetic diversity among SARS-CoV-2 samples from the same household, while individuals infected with the same viral strain from different households have lower genetic similarity. Shared within-host variations in a household are significantly associated with household membership. However, current sequencing and bioinformatic workflows may not consistently detect low-frequency within-host variants.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Katarina M. Guzman, Dillon P. Cogan, Krystal L. Brodsky, Alexander M. Soohoo, Xiuyuan Li, Natalia Sevillano, Irimpan I. Mathews, Khanh P. Nguyen, Charles S. Craik, Chaitan Khosla
Summary: This study discovered and characterized two F(ab) antibodies (AC2 and BB1) that potently inhibit the catalytic activity of the ketosynthase-acyltransferase (KS-AT) core of Module 2 in the synthesis of 6-deoxyerythronolide B synthase (DEBS). The antibodies were found to modulate ACP-mediated reactions catalyzed by Module 2 through different mechanisms. Another F(ab) antibody, AA5, was identified to bind to the KS-AT fragment of DEBS Module 2 without altering any parameter, similar to a previously characterized antibody, 1B2, which primarily recognizes the N-terminal helical docking domain of DEBS Module 3. Crystal structures of AA5 and 1B2 bound to the KS-AT fragment of Module 2 were solved, revealing distinct recognition features of the two antibodies. These findings provide valuable tools and insights for understanding the structure-function relationships of DEBS Module 2, one of the most well-studied modules of an assembly line polyketide synthase (PKS).
Article
Immunology
Joseph E. Levitt, Haley Hedlin, Sophie Duong, Di Lu, Justin Lee, Bryan Bunning, Nadia Elkarra, Benjamin A. Pinsky, Eileen Heffernan, Eric Springman, Richard B. Moss, Hector F. Bonilla, Julie Parsonnet, Roham T. Zamanian, Jamison J. Langguth, Jenna Bollyky, Chaitan Khosla, Mark R. Nicolls, Manisha Desai, Angela J. Rogers
Summary: The study aimed to evaluate the effectiveness of Acebilustat in treating outpatients with COVID-19, and the results showed that the medication did not shorten symptom duration.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Chemistry, Multidisciplinary
Elise Loppinet, Harrison A. Besser, Christina E. E. Lee, Wei Zhang, Bianxiao Cui, Chaitan Khosla
Summary: Protein dysregulation is a common cause of various diseases. Targeted protein degradation is a promising therapeutic approach for proteins without easily druggable pockets or catalytic sites. This study presents the synthesis and validation of heterobifunctional molecules that bind to a target protein via a small molecule ligand and deliver it to the lysosome using a short gluten peptide. The results demonstrate the effective endocytosis and degradation of representative secreted, cell surface, and transmembrane proteins. Optimizing these prototype molecules could lead to pharmacologically relevant LYTAC agents.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Pharmacology & Pharmacy
Harrison A. Besser, Chaitan Khosla
Summary: This review summarizes the pathogenesis of celiac disease, focusing on the interactions between three molecular families and the potential for pharmacological targeting.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shreya Kishore, Chaitan Khosla
Summary: By mining genomic data from the NCBI database, this study presents an updated catalogue of 8799 non-redundant assembly line polyketide synthase clusters across 4083 species, showing a threefold increase in the past 4 years. Furthermore, 95% of the clusters are 'orphan clusters' with no known chemical or biological characterization. These findings suggest that the diversity of assembly line PKSs remains largely unexplored and highlight the potential of genomics-driven approaches for natural product discovery.
Article
Biochemistry & Molecular Biology
Elise Loppinet, Harrison A. Besser, Agnele Sylvia Sewa, Fu-Chen Yang, Bana Jabri, Chaitan Khosla
Summary: Celiac disease is caused by gluten-derived antigens triggering inflammation through presenting to CD4+ T cells. In this study, we propose a mechanism for the deamidation and concentration of gluten peptides in the lysosomes of antigen-presenting cells, which explains the high concentration of gluten peptides required for an inflammatory response in CeD patients. We found that a ternary complex formed between a gluten peptide, transglutaminase-2 (TG2), and a2-macroglobulin, which was endocytosed by LRP-1. The covalent TG2-peptide adduct underwent endolysosomal decoupling, resulting in the expected deamidated epitope. Our findings suggest a pathogenic role for dendritic cells and/or macrophages in CeD and implicate TG2 in the lysosomal clearance of unwanted proteins.
CELL CHEMICAL BIOLOGY
(2023)
Article
Medicine, Research & Experimental
William R. Goodyer, Benjamin M. Beyersdorf, Lauren Duan, Nynke S. van den Berg, Sruthi Mantri, Francisco X. Galdos, Nazan Puluca, Jan W. Buikema, Soah Lee, Darren Salmi, Elise R. Robinson, Stephan Rogalla, Dillon P. Cogan, Chaitan Khosla, Eben L. Rosenthal, Sean M. Wu
Summary: Researchers have successfully developed targeted antibody-dye conjugates for visualizing the cardiac conduction system (CCS) in mice with high sensitivity, specificity, and resolution. They also created a fully human monoclonal antibody fragment that specifically targets the CCS and demonstrated its potential in modulating CCS biology. Furthermore, they identified a suite of additional cell surface markers for molecularly targeting different subcomponents of the CCS.
JOURNAL OF CLINICAL INVESTIGATION
(2022)