Article
Chemistry, Analytical
Francis Berthias, Hayden A. Thurman, Gayani Wijegunawardena, Haifan Wu, Alexandre A. Shvartsburg, Ole N. Jensen
Summary: Advances in proteomics have shown the ubiquity and biological importance of diverse proteoforms. The ability to separate and analyze intact isomeric proteoforms is crucial for understanding their functions. A novel technique using trapped IMS was demonstrated to achieve baseline resolution of isomeric proteoforms, opening new avenues in proteomics and epigenetics.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Philipp T. Kaulich, Liam Cassidy, Konrad Winkels, Andreas Tholey
Summary: In top-down proteomics, pre-fractionation is crucial for high confidence identification of proteoforms and increased proteome coverage. The use of field asymmetric ion mobility spectrometry (FAIMS) has shown to be beneficial, but only external compensation voltage (CV) stepping has been demonstrated. This study investigated the use of internal CV stepping for single-shot TD analysis and optimized MS parameters for different CVs. The optimized multi-CV method significantly increased the number of identified protein groups and proteoforms without increasing measurement time.
ANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jake A. Melby, Kyle A. Brown, Zachery R. Gregorich, David S. Roberts, Emily A. Chapman, Lauren E. Ehlers, Zhan Gao, Eli J. Larson, Yutong Jin, Justin R. Lopez, Jared Hartung, Yanlong Zhu, Sean J. McIlwain, Daojing Wang, Wei Guo, Gary M. Diffee, Ying Ge
Summary: Single-cell proteomics is a powerful method to study cellular heterogeneity and functional networks. However, it faces challenges in analyzing proteoforms from genetic mutations, alternative splicing, and post-translational modifications. In this study, a sensitive top-down proteomics method was developed to analyze proteoforms from single muscle fibers. The study identified heterogeneity in large proteoforms and a relationship between sarcomeric proteoforms and muscle fiber types.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Analytical
Yue Sun, Yu Liang, Chao Wang, Baofeng Zhao, Zhen Liang, Xiaodan Zhang, Yukui Zhang, Lihua Zhang
Summary: Comprehensive characterization of membrane proteins at the level of proteoforms in complex biological samples by top-down mass spectrometry (MS) is of vital importance in revealing their precise functions. However, severe peak broadening in the separation of hydrophobic membrane proteins, caused by resistance to mass transfer and strong adsorption on separation materials, leads to MS spectra overlap and signal suppression, which makes against the in-depth research on membrane proteoforms.
ANALYTICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Reynaldo Magalhaes Melo, Jaques Miranda Ferreira de Souza, Thomas Christopher Rhys Williams, Wagner Fontes, Marcelo Valle de Sousa, Carlos Andre Ornelas Ricart, Luis Henrique Ferreira do Vale
Summary: This study provides the first top-down proteome analysis of C. glutamicum, characterizing its proteoforms and post-translational modifications. The presence of various PTMs in proteoforms suggests their potential role in regulating biotechnologically relevant processes in this bacterium.
SCIENTIFIC REPORTS
(2023)
Article
Biochemical Research Methods
Zhe Zhang, Christian Hug, Yuanqi Tao, Francis Bitsch, Yang Yang
Summary: This study discusses complex truncation issues in protein therapeutics and introduces an online LC-MS workflow to successfully identify clipping locations, providing a valuable tool for resolving protein truncation problems.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Biochemical Research Methods
Qianyi Wang, Fei Fang, Qianjie Wang, Liangliang Sun
Summary: The characterization of histone proteoforms with various post-translational modifications is crucial for understanding their role in epigenetic control of gene expression. This study presents a novel approach combining capillary zone electrophoresis, ion mobility spectrometry, and mass spectrometry for online multi-dimensional separations of histone proteoforms. The results demonstrate that this technique can greatly improve the identification of histone proteoforms and provide a high sensitivity tool for their comprehensive characterization.
Article
Chemistry, Analytical
Kevin Jeanne Dit Fouque, Samuel A. Miller, Khoa Pham, Natarajan Bhanu, Yarixa L. Cintron-Diaz, Dennys Leyva, Desmond Kaplan, Valery G. Voinov, Mark E. Ridgeway, Melvin A. Park, Benjamin A. Garcia, Francisco Fernandez-Lima
Summary: This study demonstrates a novel analytical method for characterizing intact histone H4 proteoforms in HeLa cells and identifies multiple types and positions of modifications. The method enables fast data acquisition and high resolution, showing great potential for global proteoform analysis.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alessandra Olianas, Giulia Guadalupi, Tiziana Cabras, Cristina Contini, Simone Serrao, Federica Iavarone, Massimo Castagnola, Irene Messana, Simona Onali, Luchino Chessa, Giacomo Diaz, Barbara Manconi
Summary: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are autoimmune liver diseases with chronic inflammation and fibrosis. Saliva has potential as a diagnostic tool. Proteomics is emerging as a field for personalized medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Arianna Luise, Elena De Cecco, Erika Ponzini, Martina Sollazzo, PierLuigi Mauri, Frank Sobott, Giuseppe Legname, Rita Grandori, Carlo Santambrogio
Summary: Post-translational modifications can lead to diverse functional roles for a single protein, with oxidation being a common modification. Analyzing the interaction of proteins with dopamine and characterizing the proteoforms generated by dopamine-induced oxidation through top-down fragmentation can provide insights into the structural changes and relative abundance of different protein states.
Article
Biochemical Research Methods
Philipp T. Kaulich, Liam Cassidy, Andreas Tholey
Summary: Efficient proteoform separation is crucial for top-down (TD) proteomics. A two-dimensional low pH/low pH reversed-phase liquid chromatography separation scheme was developed. The optimized separation scheme led to the identification of more than 4900 proteoforms from 1250 protein groups in Caco-2 cells. The low/low pH separation strategy resulted in a higher number of proteoform identifications below 20 kDa compared to the previously published high pH/low pH strategy.
Article
Chemistry, Analytical
Holden T. Rogers, David S. Roberts, Eli J. Larson, Jake A. Melby, Kalina J. Rossler, Austin V. Carr, Kyle A. Brown, Ying Ge
Summary: We have developed a rapid and robust top-down proteomics method to extract and comprehensively characterize endogenous PLN from cardiac tissue, enabling a better understanding of its role in cardiac contractility.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Daoyang Chen, Zhichang Yang, Xiaojing Shen, Liangliang Sun
Summary: Top-down proteomics (TDP) is an ideal approach for deciphering the histone code and requires new analytical tools with high-capacity separation and highly sensitive detection of proteoforms. In this study, capillary zone electrophoresis (CZE) -MS/MS was used to identify a large number of histone proteoforms with higher sensitivity compared to traditional methods.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Stephanie Biedka, Brigitte F. Schmidt, Nolan M. Frey, Sarah M. Boothman, Jonathan S. Minden, Amber Lucas
Summary: This study presents a new protein sample preparation method, ProMTag, which enables whole proteome capture, cleanup, and release of intact proteins, as well as generation of peptides for downstream analysis. The ProMTag workflow yields high percentages for both intact proteins and proteome digests, making it a versatile and high-quality approach for proteome sample preparation.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemical Research Methods
Katrina Carbonara, Matthew P. Padula, Jens R. Coorssen
Summary: Integrative top-down proteomics aims to comprehensively analyze the breadth and depth of proteomes. This study disproves long-held beliefs about protein losses during front-end proteome resolution and confirms that standard facedown rehydration method has minimal impact on overall proteome resolution. This research demonstrates the importance of quantitative front-end 2DE/LC/MS/MS in analyzing proteomes by resolving their constituent proteoforms.
Review
Cell Biology
Sophie Hamstra, Kennedy C. Whitley, Ryan W. Baranowski, Nigel Kurgan, Jessica L. Braun, Holt N. Messner, Val A. Fajardo
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2020)
Article
Environmental Sciences
Brandon J. McKinlay, Alexandros Theocharidis, Tony Adebero, Nigel Kurgan, Val A. Fajardo, Brian D. Roy, Andrea R. Josse, Heather M. Logan-Sprenger, Bareket Falk, Panagiota Klentrou
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2020)
Article
Anthropology
Abrisham Beigpoor, Brandon J. McKinlay, Nigel Kurgan, Michael J. Plyley, Deborah O'Leary, Bareket Falk, Panagiota Klentrou
Summary: The study compared salivary and plasma concentrations of inflammatory cytokines in adolescent swimmers. The results showed discrepancies in cytokine levels and responses to exercise, indicating that salivary cytokine levels are not an accurate representation of blood cytokine levels and should not be used as a surrogate measure in pediatric studies.
ANNALS OF HUMAN BIOLOGY
(2021)
Article
Nutrition & Dietetics
Efthymios Papadopoulos, Jenna Gillen, Daniel Moore, Darren Au, Nigel Kurgan, Panagiota Klentrou, Antonio Finelli, Shabbir M. H. Alibhai, Daniel Santa Mina
Summary: This study found that high-intensity interval training and resistance training can improve muscle strength in men with prostate cancer on active surveillance. Resistance training may also increase serum IGFBP-3 levels. Strategies to recruit such patients are crucial before conducting a phase II trial.
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM
(2021)
Article
Nutrition & Dietetics
Lauren E. Skelly, Erin N. Barbour-Tuck, Nigel Kurgan, Melissa Calleja, Panagiota Klentrou, Bareket Falk, Andrea R. Josse
Summary: Increased dairy product consumption as part of a lifestyle modification intervention did not affect cardiometabolic disease risk factors in adolescent females with overweight/obesity. Changes in adiposity were significantly correlated with changes in some cardiometabolic variables in this population.
FRONTIERS IN NUTRITION
(2021)
Article
Pediatrics
Panagiota Klentrou, Katherine McKee, Brandon J. McKinlay, Nigel Kurgan, Brian D. Roy, Bareket Falk
Summary: The study showed that short-term high-impact intense training had no direct catabolic impact on bone metabolism, with Greek yogurt providing no additional benefit beyond that of an isocaloric carbohydrate control pudding.
Article
Biochemistry & Molecular Biology
Hang-Soo Park, Rishi Man Chugh, Melissa R. Pergande, Esra Cetin, Hiba Siblini, Sahar Esfandyari, Stephanie M. Cologna, Ayman Al-Hendy
Summary: The study identified a subset of proteins in the hBM-MSC secretome that effectively inhibit androgen synthesis genes, offering a novel therapeutic approach for treating PCOS by regulating androgen production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Brandon J. McKinlay, Phillip J. Wallace, Shai Olansky, Stacey Woods, Nigel Kurgan, Brian D. Roy, Andrea R. Josse, Bareket Falk, Panagiota Klentrou
Summary: This study aimed to examine the effects of increased dairy protein consumption on performance and recovery indices in adolescent female soccer players during an intensified training camp. The results showed that the consumption of Greek yogurt did not offer any additional recovery benefits in terms of performance measures and the attenuation of exercise-induced muscle damage. However, regular consumption of Greek yogurt may assist with the acute anti-inflammatory response during periods of intensified training in adolescent athletes.
JOURNAL OF THE INTERNATIONAL SOCIETY OF SPORTS NUTRITION
(2022)
Article
Physiology
Nigel Kurgan, Hashim Islam, Jennifer B. L. Matusiak, Bradley J. Baranowski, Joshua Stoikos, Val A. Fajardo, Rebecca E. K. MacPherson, Brendon J. Gurd, Panagiota Klentrou
Summary: A study found that subcutaneous adipose tissue in young men with obesity showed a decrease in sclerostin content and an increase in beta-catenin content after sprint interval training. Additionally, there were reductions in serum inflammatory factors and an increase in VO2peak.
PHYSIOLOGICAL REPORTS
(2022)
Article
Physiology
Emily N. Copeland, Colton J. F. Watson, Kennedy C. Whitley, Bradley J. Baranowski, Nigel Kurgan, Adam J. MacNeil, Rebecca E. K. MacPherson, Val A. Fajardo, David J. Allison
Summary: This study found that muscle diseases such as muscular dystrophy can negatively influence kynurenine metabolism, which is associated with anxiety-like behavior. Regular exercise can improve kynurenine metabolism and contribute to mental resilience.
EXPERIMENTAL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Indira Singaram, Ashutosh Sharma, Shashank Pant, Muyun Lihan, Mi-Jeong Park, Melissa Pergande, Pawanthi Buwaneka, Yusi Hu, Nadim Mahmud, You-Me Kim, Stephanie Cologna, Vladimir Gevorgyan, Irum Khan, Emad Tajkhorshid, Wonhwa Cho
Summary: Membrane lipids control the cellular activity of kinases containing the SH2 domain. In this study, new nonlipidic small molecule inhibitors of the lipid-SH2 domain interaction were developed to block the cellular activity of their host proteins. The research shows that targeting lipid-protein interaction is a powerful approach to developing new small molecule drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Wenping Li, Melissa R. R. Pergande, Christopher A. A. Crutchfield, Brian C. C. Searle, Peter S. S. Backlund, Jaqueline A. A. Picache, Kathryn Burkert, Nicole M. M. Yanjanin-Farhat, Paul S. S. Blank, Cynthia L. L. Toth, Christopher A. A. Wassif, Forbes D. D. Porter, Stephanie M. M. Cologna
Summary: Niemann-Pick, type C1 (NPC1) is a fatal, neurodegenerative disease characterized by endo/lysosomal accumulation of unesterified cholesterol and sphingolipids. In this study, CSF samples from NPC1 individuals and controls were used to identify protein biomarkers. Pro-neuropeptide Y (NPY) was found to be significantly increased in NPC1 individuals, but levels were comparable to controls in individuals treated with miglustat. NPY could be a potential therapeutic target for NPC1 due to its roles in attenuating neuroinflammation and reducing excitotoxicity.
Correction
Environmental Sciences
Brandon J. McKinlay, Alexandros Theocharidis, Tony Adebero, Nigel Kurgan, Val A. Fajardo, Brian D. Roy, Andrea R. Josse, Heather M. Logan-Sprenger, Bareket Falk, Panagiota Klentrou
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Oncology
Amrita Salvi, Laura R. Hardy, Kimberly N. Heath, Samantha Watry, Melissa R. Pergande, Stephanie M. Cologna, Joanna E. Burdette
Summary: High grade serous ovarian cancer (HGSC) originates from the fallopian tube epithelium and ovarian surface epithelium. PAX8 is a biomarker for HGSC and its loss leads to tumor cell death, reduced cell migration and invasion, as well as decreased deposition of extracellular matrix components. The study identifies losartan and captropril as potential inhibitors of PAX8 for HGSC treatment.
Article
Endocrinology & Metabolism
Anne Guzman, Nigel Kurgan, Sara C. Moniz, Seth F. McCarthy, Craig Sale, Heather Logan-Sprenger, Kirsty J. Elliott-Sale, Tom J. Hazell, Panagiota Klentrou
Summary: This study examined potential fluctuations in bone metabolic markers across the menstrual cycle, finding no effect of menstrual cycle phase on resting bone marker concentrations or on the bone metabolic marker response to intense exercise.
CALCIFIED TISSUE INTERNATIONAL
(2022)