Journal Articles

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    Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise
    (MDPI (Basel, Switzerland), 2025-09-03) Sharma S; Hodges LD; Peppercorn K; Davis J; Edgar CD; Rodger EJ; Chatterjee A; Tate WP; Oltra E
    Post-exertional malaise (PEM) is a defining symptom of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), yet its molecular underpinnings remain elusive. This study investigated the temporal–longitudinal DNA methylation changes associated with PEM using a structured two-day maximum repeated effort cardiopulmonary exercise testing (CPET) protocol involving pre- and two post-exercise blood samplings from five ME/CFS patients. Cardiopulmonary measurements revealed complex heterogeneous profiles among the patients compared to typical healthy controls, and VO2 peak indicated all patients had poor normative fitness. The switch to anaerobic metabolism occurred at a lower workload in some patients on Day Two of the test. Reduced Representation Bisulphite Sequencing followed by analysis with Differential Methylation Analysis Package-version 2 (DMAP2) identified differentially methylated fragments (DMFs) present in the DNA genomes of all five ME/CFS patients through the exercise test compared with ‘before exercise’. With further filtering for >10% methylation differences, there were early DMFs (0–24 h after first exercise test) and late DMFs between (24–48 h after the second exercise test), as well as DMFs that changed gradually (between 0 and 48 h). Of these, 98% were ME/CFS-specific, compared with the two healthy controls accompanying the longitudinal study. Principal component analysis illustrated the three distinct clusters at the 0 h, 24 h, and 48 h timepoints, but with heterogeneity among the patients within the clusters, highlighting dynamic methylation responses to exertion in individual patients. There were 24 ME/CFS-specific DMFs at gene promoter fragments that revealed distinct patterns of temporal methylation across the timepoints. Functional enrichment of ME-specific DMFs revealed pathways involved in endothelial function, morphogenesis, inflammation, and immune regulation. These findings uncovered temporally dynamic epigenetic changes in stress/immune functions in ME/CFS during PEM and suggest molecular signatures with potential for diagnosis and of mechanistic significance.
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    Genetic Rescue and the Plight of Ponui Hybrids
    (Frontiers Media S.A., 2021-01-15) Undin M; Lockhart PJ; Hills SFK; Castro I; Vernesi C
    Long-term sustainable and resilient populations is a key goal of conservation. How to best achieve this is controversial. There are, for instance, polarized views concerning the fitness and conservation value of hybrid populations founded through multi-origin translocations. A classic example concerns Apteryx (kiwi) in New Zealand. The A. mantelli of Ponui Island constitute a hybrid population where the birds are highly successful in their island habitat. A key dilemma for managers is understanding the reason for this success. Are the hybrid birds of Ponui Island of “no future conservation value” as recently asserted, or do they represent an outstanding example of genetic rescue and an important resource for future translocations? There has been a paradigm shift in scientific thinking concerning hybrids, but the ecological significance of admixed genomes remains difficult to assess. This limits what we can currently predict in conservation science. New understanding from genome science challenges the sufficiency of population genetic models to inform decision making and suggests instead that the contrasting outcomes of hybridization, “outbreeding depression” and “heterosis,” require understanding additional factors that modulate gene and protein expression and how these factors are influenced by the environment. We discuss these findings and the investigations that might help us to better understand the birds of Ponui, inform conservation management of kiwi and provide insight relevant for the future survival of Apteryx.