Article
Clinical Neurology
Chun Chen, Emily Mossman, Philippa Malko, David McDonald, Alasdair P. Blain, Laura Bone, Daniel Erskine, Andrew Filby, Amy E. Vincent, Gavin Hudson, Amy K. Reeve
Summary: This study revealed the variability of OXPHOS deficiencies in astrocytes of Parkinson's disease patients, which may affect their ability to support neurons.
MOVEMENT DISORDERS
(2022)
Article
Multidisciplinary Sciences
Yannik Severin, Benjamin D. Hale, Julien Mena, David Goslings, Beat M. Frey, Berend Snijder
Summary: Phenotypic plasticity in the immune system is influenced by donor age, gender, and blood pressure, resulting in distinct polarization and activation-associated phenotypes across immune cell classes. The morphology of T cells is associated with their transcriptional state, with inflammation-associated polarized T cell morphology and age-associated loss of mitochondria observed. This study reveals that immune cell phenotypes reflect both molecular and personal health information, providing new perspectives for deep immune phenotyping in individuals' health and disease.
Article
Biology
Sierra M. Barone, Alberta G. A. Paul, Lyndsey M. Muehling, Joanne A. Lannigan, William W. Kwok, Ronald B. Turner, Judith A. Woodfolk, Jonathan M. Irish
Summary: T-REX is a machine learning workflow designed to identify changes in rare and common cells in human immune monitoring settings. It successfully identified hotspots of virus-specific T cells during rhinovirus and SARS-CoV-2 infections.
Article
Immunology
Cassandra E. Burnett, Trine Line Hauge Okholm, Iliana Tenvooren, Diana M. Marquez, Stanley Tamaki, Priscila Munoz Sandoval, Andrew Willmore, Carolyn M. Hendrickson, Kirsten N. Kangelaris, Charles R. Langelier, Matthew F. Krummel, Prescott G. Woodruff, Carolyn S. Calfee, David J. Erle, K. Mark Ansel, Matthew H. Spitzer
Summary: The immune cell composition and signaling profile of COVID-19 patients are associated with early discharge and recovery, including changes in myeloid and T cell frequencies, reduced immune cell signaling, and increased regulatory T cells.
Article
Cell Biology
Dorines Rosario, Gholamreza Bidkhori, Sunjae Lee, Janis Bedarf, Falk Hildebrand, Emmanuelle Le Chatelier, Mathias Uhlen, Stanislav Dusko Ehrlich, Gordon Proctor, Ullrich Wuellner, Adil Mardinoglu, Saeed Shoaie
Summary: Parkinson's disease (PD) is a common progressive neurological disorder that affects motor functions, with gastrointestinal (GI) dysfunction being an early nonmotor symptom. This study used metagenomics and serum metabolomics to investigate the gut microbiome of PD patients. The findings suggest that gut microbial composition and metabolism may play a role in PD pathophysiology.
Article
Immunology
Gabriela K. Fragiadakis, Zachary B. Bjornson-Hooper, Deepthi Madhireddy, Karen Sachs, Han Chen, David R. McIlwain, Matthew H. Spitzer, Sean C. Bendall, Garry P. Nolan
Summary: Evaluating the health and competence of the immune system is crucial for assessing vaccine responses, autoimmune conditions, cancer prognosis, and treatment. This study used mass cytometry to analyze blood samples from 86 individuals and provide reference ranges for cell-specific immune markers, highlighting differences across sex and age. The researchers identified modules of immune features that suggest an underlying structure to the immune system based on signaling pathway responses across different cell types. The study also found distinct immune responses in males and females, with increased MAPK signaling in inflammatory pathways in innate immune cells and greater overall coordination of immune cell responses in females.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Michael J. Geuenich, Jinyu Hou, Sunyun Lee, Shanza Ayub, Hartland W. Jackson, Kieran R. Campbell
Summary: Astir is a probabilistic model that assigns cells to cell types by integrating prior knowledge of marker proteins, enabling annotations at the million-cell scale with scalability and robustness.
Article
Immunology
Nolan Ung, Cameron Goldbeck, Cassandra Man, Julianne Hoeflich, Ren Sun, Arianna Barbetta, Naim Matasci, Jonathan Katz, Jerry S. H. Lee, Shefali Chopra, Shahab Asgharzadeh, Mika Warren, Linda Sher, Rohit Kohli, Omid Akbari, Yuri Genyk, Juliet Emamaullee
Summary: This study developed an Imaging Mass Cytometry (IMC) panel and a single cell segmentation analysis pipeline to analyze the immune histology of chronic rejection (CR) in clinical tissue samples from liver transplant recipients. The results showed increased and spatially related immune subpopulations in CR, including cytotoxic T-cells and macrophages, which were not observed in non-rejected livers. Statistical modeling using single cell data demonstrated high consistency. The study highlights the potential of IMC in investigating the alloimmune microenvironment and identifying biomarkers and therapeutic targets in solid organ transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Qing Zhang, Wenlong Zhang, Tingsheng Lin, Wenfeng Lu, Xin He, Yuanzhen Ding, Wei Chen, Wenli Diao, Meng Ding, Pingping Shen, Hongqian Guo
Summary: This study analyzed the immune profiles of urothelial carcinoma tissue samples and identified multiple T-cell and tumor-associated macrophage phenotypes. The findings revealed exhausted T-cell states in the tumor tissue and suggested that targeting CD38 may be more suitable for immunotherapy in urothelial carcinoma compared to PD1/PDL1.
Article
Immunology
Anto Sam Crosslee Louis Sam Titus, Ying Tan, Phuongthy Tran, Julius Lindblom, Maryann Ivbievbiokun, Yitian Xu, Junjun Zheng, Ioannis Parodis, Qi Cai, Anthony Chang, Shu-Hsia Chen, Minghui Zhao, Chandra Mohan
Summary: Using imaging mass cytometry (IMC), this study examines the spatial expression profiles of 50 proteins in proliferative lupus nephritis (LN) and control kidneys. The results show immune infiltration dominated by specific immune cells in LN glomeruli and similar changes in tubulointerstitial regions. Macrophages are the primary antigen presenting cells and are found in the cellular crescents. The study also reveals signs of epithelial to mesenchymal plasticity in tubular and parietal epithelial cells. IMC is a powerful tool for investigating the spatial architecture of LN at the protein level.
CLINICAL IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Matthew R. Alexander, Bethany L. Dale, Charles D. Smart, Fernando Elijovich, Cara E. Wogsland, Sierra M. Lima, Jonathan M. Irish, Meena S. Madhur
Summary: Evidence from nonhuman animal models suggests that immune cells play a crucial role in hypertension, but their changes in human hypertension are unclear. Using mass cytometry, this study reveals reduced levels of CCR10+ regulatory T cells (Tregs) and PD-1+CD57-CD8+ memory T cells, indicating potential decreases in anti-inflammatory and hypofunctional T-cell populations in human hypertension.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Immunology
Yufeng Liu, Jialiang Zhou, Baozhu Chen, Xiao Liu, Yao Cai, Wei Liu, Hu Hao, Sitao Li
Summary: Mass cytometry time-of-flight technology was used to identify specific immune cell populations in the blood and intestinal mucosa tissue of patients with necrotizing enterocolitis, providing insights into the dysregulated immune response and cell localization in this disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Ben Mulhearn, Lysette Marshall, Megan Sutcliffe, Susan K. Hannes, Chamith Fonseka, Tracy Hussell, Soumya Raychaudhuri, Anne Barton, Sebastien Viatte
Summary: By using deep immunophenotyping techniques, this study captures the previously reported imbalance between different subsets of CD4(+) T cells in rheumatoid arthritis (RA). In contrast to conventional analysis techniques, an unbiased approach with automated clustering algorithms was able to identify non-canonical imbalances in RA blood.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Banglun Pan, Zengbin Wang, Rui Chen, Xiaoxia Zhang, Jiacheng Qiu, Xiaoxuan Wu, Yuxin Yao, Yue Luo, Xiaoqian Wang, Nanhong Tang
Summary: In this study, we analyzed the changes in intrahepatic leukocytes in mouse liver diseases and hepatocellular carcinoma (HCC) patients using mass cytometry, flow cytometry, and immunofluorescence. Our findings revealed the functional differences in intrahepatic leukocytes caused by different liver disease factors and highlighted the unique changes in HBV-related HCC. This study is of great importance for discovering new HCC targeted immunotherapy strategies.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Ines Felix, Heli Jokela, Joonas Karhula, Noora Kotaja, Eriika Savontaus, Marko Salmi, Pia Rantakari
Summary: This study reveals the diversity and developmental origin of resident adipose tissue macrophages through comprehensive single-cell mass cytometry analysis, as well as the functional differences in their in vitro and in vivo activities. A high-fat diet induces changes in the quantity and functionality of macrophages, which can be reversed by dietary intervention.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Ashwin Sachdeva, Claire A. Hart, Christopher D. Carey, Amy E. Vincent, Laura C. Greaves, Rakesh Heer, Pedro Oliveira, Michael D. Brown, Noel W. Clarke, Doug M. Turnbull
Summary: Advances in multiplex immunofluorescence and digital image analysis have allowed simultaneous assessment of protein defects in electron transport chain components. We developed an automated high-throughput mIF workflow for quantitative single-cell level assessment of formalin fixed paraffin embedded tissue. Using this method, we identified alterations in mitochondrial oxidative phosphorylation protein in prostate samples and observed differences in OXPHOS protein abundance.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Ashwin Sachdeva, Claire A. Hart, Kyungmin Kim, Thomas Tawadros, Pedro Oliveira, Jonathan Shanks, Mick Brown, Noel Clarke
Summary: This study investigated the influence of EphA2 signaling in prostate cancer (PCa) progression and long-term survival. The results showed that non-canonical EphA2 signaling, mediated by pEphA2(S897), plays a key role in transendothelial migration of PCa to bone marrow endothelium. High expression of EphA2 or pEphA2(S897) in a PTENlow background is associated with poor overall survival.
BRITISH JOURNAL OF CANCER
(2022)
Article
Hematology
Benjamin J. Stewart, Martin Fergie, Matthew D. Young, Claire Jones, Ashwin Sachdeva, Alex Blain, Chris M. Bacon, Vikki Rand, John R. Ferdinand, Kylie R. James, Krishnaa T. Mahbubani, Liz Hook, Nicolaas Jonas, Nicholas Coleman, Kourosh Saeb-Parsy, Matthew Collin, Menna R. Clatworthy, Sam Behjati, Christopher D. Carey
Summary: Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate and malignant Hodgkin Reed-Sternberg cells create an immunosuppressive microenvironment. Mononuclear phagocytes (MNPs) in the vicinity of HRSCs express similar regulatory mechanisms and are associated with inferior patient outcomes. MNPs in cHL comprise multiple subsets of monocytes, macrophages, and dendritic cells, and express immunoregulatory checkpoints at the same level as macrophages.
Review
Urology & Nephrology
Oscar R. Brouwer, Maarten Albersen, Arie Parnham, Chris Protzel, Curtis A. Pettaway, Benjamin Ayres, Tiago Antunes-Lopes, Lenka Barreto, Riccardo Campi, Juanita Crook, Sergio Fernandez-Pello, Isabella Greco, Michiel S. van der Heijden, Peter A. S. Johnstone, Mithun Kailavasan, Kenneth Manzie, Jack David Marcus, Andrea Necchi, Pedro Oliveira, John Osborne, Lance C. Pagliaro, Herney A. Garcia-Perdomo, R. Bryan Rumble, Ashwin Sachdeva, Vasileios I. Sakalis, Lukasz Zapala, Diego F. Sanchez Martinez, Philippe E. Spiess, Scott T. Tagawa
Summary: Penile cancer is a rare disease with a significant impact on quality of life. This collaborative guideline aims to provide worldwide physician and patient guidance for managing penile cancer, offering updated information on diagnosis and treatment. The incidence of penile cancer is increasing globally, and human papillomavirus (HPV) is the main risk factor.
Article
Multidisciplinary Sciences
Charley Xia, Sarah J. Pickett, David C. M. Liewald, Alexander Weiss, Gavin Hudson, W. David Hill
Summary: Neuroticism is a heritable trait influenced by mitochondrial DNA, and associations between mitochondrial haplogroups and genetic variation have been found. The study reveals the links between neuroticism and various facets, as well as the relationships between mitochondrial genetic variation and overall health.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Laura A. Smith, Chun Chen, Nichola Z. Lax, Robert W. Taylor, Daniel Erskine, Robert McFarland
Summary: Refractory epilepsy is the main neurological manifestation of Alpers' syndrome caused by mitochondrial DNA (mtDNA) polymerase gamma gene (POLG) variants. Astrocytic pathology with decreased mitochondrial oxidative phosphorylation (OXPHOS) proteins and altered expression of key astrocytic proteins is found in the primary visual cortex of Alpers' syndrome patients, suggesting their involvement in disease pathogenesis.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yuko Takeda, Louise Hyslop, Meenakshi Choudhary, Fiona Robertson, Angela Pyle, Ian Wilson, Mauro Santibanez-Koref, Douglass Turnbull, Mary Herbert, Gavin Hudson
Summary: Mitochondrial replacement technology (MRT) aims to reduce the risk of disease in children born to women with pathogenic mitochondrial DNA (mtDNA) variants. Haplogroup matching between egg donors and women undergoing MRT has been proposed, but this study finds that it would limit the availability of donors and does not necessarily reduce mtDNA sequence divergence between donor/recipient pairs.
Article
Genetics & Heredity
Sarah J. J. Pickett, Gavin Hudson, Laura C. C. Greaves
Summary: Single large-scale mitochondrial DNA deletions result in a range of diseases with varying levels of severity and tissue expression. Examining single-cell deletion levels through multi-modal cellular readouts allows for better understanding of hematopoietic cell fate and disease manifestation.
Article
Neurosciences
Chun Chen, David McDonald, Alasdair Blain, Emily Mossman, Kiera Atkin, Michael F. F. Marusich, Roderick Capaldi, Laura Bone, Anna Smith, Andrew Filby, Daniel Erskine, Oliver Russell, Gavin Hudson, Amy E. E. Vincent, Amy K. K. Reeve
Summary: Using imaging mass cytometry, researchers found a generalized reduction in mitochondrial quality control proteins in dopaminergic neurons from Parkinson's patients. There were also significant differences in protein-protein abundance relationships between PD and disease control tissue. Additionally, abnormal increases in mitochondrial and pathology-related proteins were observed in Parkinson's neurons, suggesting a disturbance in mitochondrial quality control regulation.
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Valeria Di Leo, Conor Lawless, Marie-Pier Roussel, Tiago B. Gomes, Grainne S. Gorman, Oliver M. Russell, Helen A. L. Tuppen, Elise Duchesne, Amy E. Vincent
Summary: This study found that 12-week resistance exercise training can partially rescue mitochondrial dysfunction in DM1 patients. Most patients showed a significant increase in mitochondrial mass, and all patients had a significant increase in protein levels of respiratory chain complexes. Improvements in mitochondrial mass were correlated with strength evaluation.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Article
Oncology
Gerhardt Attard, Laura Murphy, Noel W. Clarke, Ashwin Sachdeva, Craig Jones, Alex Hoyle, William Cross, Robert J. Jones, Christopher C. Parker, Silke Gillessen, Adrian Cook, Chris Brawley, Clare Gilson, Hannah Rush, Hoda Abdel-Aty, Claire L. Amos, Claire Murphy, Simon Chowdhury, Zafar Malik, J. Martin Russell, Nazia Parkar, Cheryl Pugh, Carlos Diaz-Montana, Carmel Pezaro, Warren Grant, Helen Saxby, Ian Pedley, Joe M. O'Sullivan, Alison Birtle, Joanna Gale, Narayanan Srihari, Carys Thomas, Jacob Tanguay, John Wagstaff, Prantik Das, Emma Gray, Mymoona Alzouebi, Omi Parikh, Angus Robinson, Amir H. Montazeri, James Wylie, Anjali Zarkar, Richard Cathomas, Michael D. Brown, Yatin Jain, David P. Dearnaley, Malcolm D. Mason, Duncan Gilbert, Ruth E. Langley, Robin Millman, David Matheson, Matthew R. Sydes, Louise C. Brown, Mahesh K. B. Parmar, Nicholas D. James
Summary: This study analyzed two open-label, randomized, controlled phase 3 trials and evaluated the long-term outcomes and survival benefits of combining abiraterone and enzalutamide with androgen deprivation therapy in metastatic prostate cancer patients. The results showed that the combination of abiraterone and enzalutamide did not improve survival compared to androgen deprivation therapy alone, but the addition of abiraterone to androgen deprivation therapy had clinically significant improvements in survival.
Review
Surgery
Adewale Adisa
Summary: This study aims to prioritize feasible interventions to reduce the environmental impact of operating theatres. Through a four-phase Delphi consensus methodology, the results suggest that actionable interventions applicable to both high- and low-middle-income countries can be taken to achieve environmentally sustainable operating environments.
BRITISH JOURNAL OF SURGERY
(2023)
Review
Biochemistry & Molecular Biology
Valeria Di Leo, Tiago M. Bernardino Gomes, Amy E. Vincent
Summary: Mitochondrial dysfunction in skeletal muscle fibres is common in both healthy aging and neuromuscular diseases, and understanding the impact and adaptation of muscle fibres to this dysfunction is crucial for disease mechanisms and therapeutic interventions. This review provides an overview of current knowledge on interactions between mitochondrial dysfunction and skeletal muscle biology, covering topics such as metabolic remodeling, mitochondrial morphology, mitochondrial turnover, cellular processes, and muscle cell structure and function. The understanding of these interactions is at different stages, with some extensively researched and understood, while others are still in the early stages. The goal of this review is to discuss what is known, highlight what remains unknown, and provide insights into future research directions in this field.
BIOCHEMICAL JOURNAL
(2023)