Article
Chemistry, Analytical
Madisson Chabas, Olivier Pible, Jean Armengaud, Beatrice Alpha-Bazin
Summary: To accurately and rapidly identify microorganisms from complex microbiota for clinical diagnostic purposes, an innovative label-free multiplexing method for the identification of microorganisms using tandem mass spectrometry is proposed in this paper. The method involves offline reversed-phase fractionation of individual peptidomes and achieves multiplexing by mixing fractions of staged hydrophobicity. This approach enables the identification of up to 21 microorganisms in a single 60-minute run without the use of labeling reagents, providing new perspectives for high-throughput proteotyping of bacteria in large culturomics projects.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Yuming Jiang, Alexandre Hutton, Caleb W. Cranney, Jesse G. Meyer
Summary: This article introduces an improved direct infusion and ion mobility method for proteome analysis, and proposes a label-free quantification method DISPA-LFQ, which can rapidly identify and quantify proteins in complex mixtures. This technology has important applications in drug screening, biomarker discovery, and clinical analysis.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Ximena Sanchez-Avila, Thy Truong, Xiaofeng Xie, Kei G. I. Webber, S. Madisyn Johnston, Hsien-Jung L. Lin, Nathaniel B. B. Axtell, Veronica Puig-Sanvicens, Ryan T. T. Kelly
Summary: Single-cell proteomics provides unique information that is not obtainable through bulk-scale protein measurements or single-cell profiling of other omics. However, the high cost and technical expertise required for existing commercial platforms hinder the accessibility of SCP to many laboratories. In this study, the HP D100 Single Cell Dispenser was evaluated and proved to be a low-cost and accurate tool for label-free SCP, enabling rapid and easy-to-use workflow with no reduction in proteome coverage.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Biochemical Research Methods
Daniel G. Delafield, Hannah N. Miles, William A. Ricke, Lingjun Li
Summary: The ubiquity of mass spectrometry-based bottom-up proteomic analyses highlights the importance of validating methodologies for increased efficiency, coverage, and profiling depth. This study demonstrates the potential of porous graphitic carbon chromatography (PGC) as a means to enhance proteomic coverage without altering sample preparation, instrument configuration, or acquisition methods.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Medicine, Research & Experimental
Qingbo Shu, Shan Liu, Tonino Alonzi, Sylvia M. LaCourse, Dhiraj Kumar Singh, Duran Bao, Dalton Wamalwa, Li Jiang, Christopher J. Lyon, Grace John-Stewart, Deepak Kaushal, Delia Goletti, Tony Hu
Summary: Using mass spectrometry (MS) to read immunoassays for biomarker-derived peptides can improve sensitivity and specificity, allowing for better identification of tuberculosis cases and differentiation between disease and asymptomatic infection. This approach shows strong potential for infectious disease diagnosis and monitoring changes in Mycobacterium tuberculosis burden for more effective disease control.
Article
Biochemistry & Molecular Biology
Kazuto Yamashita, Shunsuke Watanabe, Kengo Ishiki, Masahiro Miura, Yasuhiro Irino, Toshiko Kubo, Jun Matsui, Kei Hagino, Shigeki Iwanaga, Tomokazu Yoshida
Summary: The study developed plasma A beta 40 and A beta 42 immunoassays with high sensitivity and reproducibility, showing potential to accurately detect amyloid positivity in the brain. The new method provides clinicians and patients with a way to continuously monitor disease progression.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Mengji Zhang, Lin Huang, Jing Yang, Wei Xu, Haiyang Su, Jing Cao, Qian Wang, Jun Pu, Kun Qian
Summary: This study introduces a deep stabilizer for ultra-fast, label-free MS detection in serum metabolic diagnosis of coronary heart disease (CHD). By utilizing nanoparticle-assisted laser desorption/ionization-MS, direct metabolic analysis of trace unprocessed serum can be achieved in seconds, leading to advanced accuracy in CHD diagnosis. The development of this stabilized platform advances the design of metabolic analysis tools for disease detection in clinics.
Article
Chemistry, Analytical
Goksu Ozcelikay, Ahmet Cetinkaya, Esen Bellur Atici, Sibel A. Ozkan
Summary: In this study, an electroanalytical quantification method for sugammadex was developed using molecular imprinting via the electropolymerization technique. The EP-MIP(SUG)/SPAuE sensor exhibited high sensitivity and specificity/selectivity, as demonstrated by its ability to detect sugammadex in biological fluids and differentiate it from similar molecules. The EP-MIP(SUG)/SPAuE sensor showed good analytical performance and validation parameters according to ICH guidelines, making it a promising tool for quantitative analysis of sugammadex in various samples.
ANALYTICAL METHODS
(2023)
Article
Chemistry, Multidisciplinary
Xin Wen, Yangyang Wang, Jianjun Ding, Xiaojing Dong, Yiqiang Sun, Bo Xu
Summary: Building heterogeneous structures improves electron transport, creates synergistic effects, and overcomes limitations of single component. A label-free electrochemical immunological sensor was created using ZIF-67 to fabricate nanosheets with dual-heterogeneous structure (Co9S8/Co3C@C). Sensitivity detection of diethylstilbestrol (DES) in environmental samples (groundwater and lake water) was achieved. The sensor exhibits acceptable detection ability, wide linear response range (0.000384-6 ng mL(-1)), and low detection limit (3.24 fg mL(-1)) due to excellent conductivity of the nanosheets. The stability, selectivity, and sensitivity of the electrochemical immunosensor are satisfactory. It is an effective, practical, and quantitative detection technique.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Analytical
Frederic Dewez, Edwin De Pauw, Ron M. A. Heeren, Benjamin Balluff
Summary: The multilabel approach in quantitative mass spectrometry imaging provides more accurate quantitation compared to a single-label approach, particularly when the target compound is unevenly distributed at a wide concentration range in the tissue.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Kei G. I. Webber, Thy Truong, S. Madisyn Johnston, Sebastian E. Zapata, Yiran Liang, Jacob M. Davis, Alexander D. Buttars, Fletcher B. Smith, Hailey E. Jones, Arianna C. Mahoney, Richard H. Carson, Andikan J. Nwosu, Jacob L. Heninger, Andrey V. Liyu, Gregory P. Nordin, Ying Zhu, Ryan T. Kelly
Summary: Single-cell proteomics has the potential to advance biomedical research and personalized medicine. A two-column liquid chromatography system is developed to improve the throughput and efficiency of label-free single-cell proteomics.
ANALYTICAL CHEMISTRY
(2022)
Article
Oncology
Georgia Arentz, Parul Mittal, Manuela Klingler-Hoffmann, Mark R. Condina, Carmela Ricciardelli, Noor A. Lokman, Gurjeet Kaur, Martin K. Oehler, Peter Hoffmann
Summary: Eighty percent of ovarian cancer patients respond to chemotherapy initially, but most experience relapse and die from acquired chemoresistance. In addition, 20% of patients are intrinsically resistant. A study found that the protein markers gelsolin (GSN), calmodulin (CALM1), and thioredoxin (TXN) were elevated in chemotherapy-responsive ovarian cancer tissues compared to non-responsive ones. The differential expression of these markers was confirmed in carboplatin-resistant cells, suggesting their potential as biomarkers for predicting chemotherapy response and understanding resistance mechanisms.
Article
Chemistry, Analytical
Li Luo, Jiewei Yang, Zhi Li, Hua Xu, Lei Guo, Lili Wang, Yuxia Wang, Longlong Luo, Jing Wang, Pingping Zhang, Ruifu Yang, Weijun Kang, Jianwei Xie
Summary: A novel label-free immunosensor method was developed in this study for differentiation and quantification of ricin and abrin, showing rapid and accurate measurement in various complex matrices. The results demonstrate the potential practical application value of this method.
Review
Biochemical Research Methods
Vilmos Kertesz, John F. Cahill
Summary: Mass spectrometry has become the primary tool for routine quantitative analysis of biomolecules, and is increasingly used to reveal the spatial distribution of proteins, metabolites, and pharmaceuticals in tissue. However, most spatially resolved MS measurements are qualitative due to potential biases. As demand for quantitative MS imaging and profiling data increases in pharmacological and clinical fields, various technologies now exist to provide different levels of spatial and quantitative information.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Matthew P. Confer, Brooke M. Holcombe, Abigail G. Foes, John M. Holmquist, Savannah C. Walker, Sanghamitra Deb, Ayanjeet Ghosh
Summary: The study demonstrates the heterogeneities of Aβ plaques in terms of secondary structure and phospholipid content in AD brains using infrared spectroscopic imaging. Discrete frequency infrared imaging (DFIR) is shown to be effective in characterizing amyloid deposits and identifying non-plaque β-sheet aggregates throughout brain tissues. The presence of phospholipid-rich β-sheet deposits outside of plaques suggests potential clinical significance and offers insights for future therapeutic strategies.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Review
Pediatrics
Daniel O'Reilly, Claire A. Murphy, Richard Drew, Afif El-Khuffash, Patricia B. Maguire, Fionnuala Ni Ainle, Naomi Mc Callion
Summary: This article discusses the role of platelets in childhood sepsis, focusing on their function in the immune system and interactions with other immune cells. It also analyzes the physiological differences between adult and pediatric platelets, as well as the potential impact of platelet transfusions on infant immune responses.
PEDIATRIC RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Shane P. Comer, Ana Le Chevillier, Paulina B. Szklanna, Sarah Kelliher, Khalid Saeed, Steven Cullen, Osasere Edebiri, Tiina O'Neill, Niamh Stephens, Luisa Weiss, Claire A. Murphy, Saraswathi Rajakumar, Alexandra Tierney, Conor Hughes, Aine Lennon, Niamh Moran, Patricia B. Maguire, Fionnuala Ni ainle, Barry Kevane
Summary: This study reports platelet hypergranularity in a VITT patient, which may be associated with thrombotic risk in VITT. Further research is needed to determine the optimal approach for monitoring recovery from VITT, but our findings can help inform therapeutic decisions regarding anticoagulation treatment in this novel pathology.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Frederikus A. Klok, Gregory Piazza, Andrew S. P. Sharp, Fionnuala Ni Ainle, Michael R. Jaff, Nikhil Chauhan, Binal Patel, Stefano Barco, Samuel Z. Goldhaber, Nils Kucher, Irene M. Lang, Irene Schmidtmann, Keith M. Sterling, Dorothea Becker, Nadine Martin, Kenneth Rosenfield, Stavros V. Konstantinides
Summary: This study aims to evaluate the clinical benefits of catheter-directed treatment and determine the first-line treatment for pulmonary embolism patients.
AMERICAN HEART JOURNAL
(2022)
Article
Cell Biology
Simona Catozzi, Camille Ternet, Alize Gourrege, Kieran Wynne, Giorgio Oliviero, Christina Kiel
Summary: This study reconstructed the downstream effector network of Ras, consisting of 2290 proteins connected by 19,080 binary protein-protein interactions. The study identified a high level of crosstalk among different effector classes and revealed novel functions of specific effector pathways through functional enrichment analysis.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Immunology
Subash Raj Susai, David Mongan, Colm Healy, Mary Cannon, Gerard Cagney, Kieran Wynne, Jonah F. Byrne, Connie Markulev, Miriam R. Schafer, Maximus Berger, Nilufar Mossaheb, Monika Schlogelhofer, Stefan Smesny, Ian B. Hickie, Gregor E. Berger, Eric Y. H. Chen, Lieuwe de Haan, Dorien H. Nieman, Merete Nordentoft, Anita Riecher-Rossler, Swapna Verma, Rebekah Street, Andrew Thompson, Alison Ruth Yung, Barnaby Nelson, Patrick D. McGorry, Melanie Focking, G. Paul Amminger, David Cotter
Summary: This study examined the predictive ability of biological and clinical variables on functional outcomes in individuals at clinical high-risk for psychosis. The results showed that plasma proteomics, erythrocyte fatty acids, and cytokine data had poor predictive power for functional outcomes in CHR participants. However, complement protein levels were significantly associated with clinical outcomes, suggesting a role for the complement system in functional impairments and positive symptom severity in CHR patients.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Oncology
Annalisa Contursi, Rosa Fullone, Paulina Szklanna-Koszalinska, Simone Marcone, Paola Lanuti, Francesco Taus, Alessandra Meneguzzi, Giulia Turri, Melania Dovizio, Annalisa Bruno, Corrado Pedrazzani, Stefania Tacconelli, Marco Marchisio, Patrizia Ballerini, Pietro Minuz, Patricia Maguire, Paola Patrignani
Summary: This study aimed to investigate the release of EVs from activated platelets in CRC patients and healthy controls and their effect on gene expression and lipid mediator synthesis. The protein content of thrombin-stimulated mEVs was found to be modulated in CRC and could potentially serve as a noninvasive tool to discriminate patients from healthy subjects. Furthermore, the interaction between platelet mEVs and cancer cells may provide valuable prognostic information and aid in the development of targeted anticancer strategies.
Article
Multidisciplinary Sciences
Thomas Sevrin, Lisa Strasser, Camille Ternet, Philipp Junk, Miriam Caffarini, Stella Prins, Cian D'Arcy, Simona Catozzi, Giorgio Oliviero, Kieran Wynne, Christina Kiel, Philip J. Luthert
Summary: Cellular utilization of available energy drives various forms of cellular work and is a major biological constraint. This study presents a whole-cell energy framework that integrates proteomic analysis and an energetics-based gene ontology. The framework separates analysis of metabolic supply, high-energy phosphate generation, and cellular work demand. Using mouse embryonic fibroblast cell lines with different phenotypes, the study observes shifts in energy-requiring processes and creates a predictive whole-cell energy budget.
Article
Biotechnology & Applied Microbiology
Cian D'Arcy, Olivia Bass, Philipp Junk, Thomas Sevrin, Giorgio Oliviero, Kieran Wynne, Melinda Halasz, Christina Kiel
Summary: Melanin, a pigment that absorbs light and free radicals, is produced by melanocyte cells in various organs. Mutations in genes involved in melanin synthesis are associated with pigmentation diseases. In our study, we reconstructed gene-disease/phenotype associations and protein-protein interaction networks related to pigmentation. We also analyzed protein expression in melanoma cell lines. This work provides a comprehensive network representation of pigmentation and melanin biosynthesis pathways, facilitating hypothesis testing and new drug target identification.
BIOENGINEERING-BASEL
(2023)
Article
Respiratory System
Anne Trappe, Navya Lakkappa, Suzanne Carter, Eugene Dillon, Kieran Wynne, Edward Mckone, Paul Mcnally, Judith A. Coppinger
Summary: In this study, extracellular vesicles (EVs) were isolated from the blood of cystic fibrosis (CF) patients using size exclusion chromatography (SEC) and compared to ultracentrifugation (UC). The results showed a significant difference in the number of EVs obtained from the serum of children and adults with CF. Furthermore, significant protein expression changes were observed in CF patient serum EVs, with potential implications for CF disease progression and treatment response.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Multidisciplinary Sciences
Jane Howard, John Browne, Stephanie Bollard, Susan Peters, Ciara Sweeney, Kieran Wynne, Shirley Potter, Amanda McCann, Pamela Kelly
Summary: This study investigates whether miRNAs associated with FMA tumors are secreted in extracellular vesicles (EVs) and can be used as a cancer biomarker in feline plasma. The study finds that miR-20a and miR-15b are significantly increased in tumor tissue but decreased in FMA EVs compared to healthy feline EVs. These miRNAs and their protein targets are detectable markers in plasma EVs, which may contribute to future non-invasive diagnostic tests for FMA. Further investigation of the clinical relevance of miR-20a and miR-15b is warranted.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Luis F. Iglesias-Martinez, Nora Rauch, Kieran Wynne, Brendan McCann, Walter Kolch, Jens Rauch
Summary: RAF kinases are important in cancer, particularly the BRAFV600E mutants. Although potent kinase inhibitors exist, their effects vary in different cancer types and can even induce paradoxical RAF kinase activation. Enhanced dimerization between RAF1 and BRAF contributes to both paradoxical activation and drug resistance. Mapping the interactomes of RAF1 monomers, RAF1-BRAF, and RAF1-BRAFV600E dimers, we identified and quantified over 1,000 proteins. Additionally, we analyzed the effects of vemurafenib and sorafenib, two clinically used RAF inhibitors, and found overlapping core interactomes with distinct condition-specific differences. Understanding these dynamic interactome changes may provide insights into RAF signaling and resistance mechanisms.
Article
Biology
Camille Ternet, Philipp Junk, Thomas Sevrin, Simona Catozzi, Erik Wa, Johan Heldin, Giorgio Oliviero, Kieran Wynne, Christina Kiel
Summary: Ras is a key switch controlling cell behavior and interacts with effectors in a exclusive manner. The molecular details of these complexes and their alteration in specific contexts are not understood. Environmental contexts have a larger impact on interaction rewiring than genetic contexts. This study provides insights into tissue-specific signaling mechanisms and may explain the tissue-specificity of KRAS oncogenic mutants.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemical Research Methods
Viola Previtali, Samuel H. Myers, Laura Poppi, Kieran Wynne, Irene Casamassima, Stefania Girotto, Giuseppina Di Stefano, Fulvia Farabegoli, Marinella Roberti, Giorgio Oliviero, Andrea Cavalli
Summary: BRCA2 and RAD51 are two proteins involved in homologous recombination and DNA double strand break repair. The study used a mass spectrometry proteomic approach to obtain a proteomic fingerprint after cellular treatment with the myr-BRC4 peptide, and identified three downregulated proteins (FANCI, FANCD2, and RPA3). The downregulation of these proteins could be used as an indicator for monitoring HR impairment.
JOURNAL OF PROTEOMICS
(2023)
Article
Oncology
Aoife Nolan, Cinzia Raso, Walter Kolch, Alex von Kriegsheim, Kieran Wynne, David Matallanas
Summary: RAS proteins play a crucial role in cell signalling, regulating cell functions such as proliferation, differentiation, and death. Mutations in genes of this family, particularly KRAS, are common and were believed to constitutively activate KRAS. However, recent findings show that some mutants can switch between active and inactive states. This, along with the development of covalent KRASG12C inhibitors, has led to the emergence of KRAS inhibitors in clinical use. Despite this, resistance to targeted therapies remains a challenge, and effective treatments for other KRAS mutants are lacking. To overcome these hurdles and accelerate RAS targeting therapies, a comprehensive understanding of the molecular mechanisms underlying KRAS signalling networks and the differences in downstream signalling of KRAS mutants is needed. This study employed affinity purification mass-spectrometry proteomics to analyze the interactome of KRAS wild-type and three KRAS mutants. Through bioinformatic analysis and experimental validation, the researchers mapped the signalling network mediated by different KRAS proteins. The study also revealed novel crosstalk between KRAS and effector pathways, including AKT and JAK-STAT signalling modules.
Article
Biochemistry & Molecular Biology
Zhi Liu, Aleksandar Krstic, Ashish Neve, Cristina Casalou, Nora Rauch, Kieran Wynne, Hilary Cassidy, Amanda McCann, Emma Kavanagh, Brendan McCann, Alfonso Blanco, Jens Rauch, Walter Kolch
Summary: KSR1 plays a critical role in mutant BRAF transformation, and its loss results in impaired cell proliferation and migration, cell cycle abnormalities, cellular senescence, and apoptosis. The study reveals that KSR1 directs ERK to phosphorylate substrates essential for cell survival, and its loss activates p38 MAPK pathway leading to cell cycle aberrations and senescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
