Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease with no known cause or mechanism. There is an increasing appreciation for the role of immune and metabolic dysfunction in the disease. ME/CFS has historically presented in outbreaks, often has a flu-like onset, and results in inflammatory symptoms. Patients suffer from severe fatigue and postexertional malaise. There is little known about the metabolism of specific immune cells in patients with ME/CFS. To investigate immune metabolism in ME/CFS, we isolated CD4⁺ and CD8⁺ T cells from 53 patients with ME/CFS and 45 healthy controls. We analyzed glycolysis and mitochondrial respiration in resting and activated T cells, along with markers related to cellular metabolism and plasma cytokines. We found that ME/CFS CD8⁺ T cells had reduced mitochondrial membrane potential compared with those from healthy controls. Both CD4⁺ and CD8⁺ T cells from patients with ME/CFS had reduced glycolysis at rest, whereas CD8⁺ T cells also had reduced glycolysis following activation. Patients with ME/CFS had significant correlations between measures of T cell metabolism and plasma cytokine abundance that differed from correlations seen in healthy control subjects. Our data indicate that patients have impaired T cell metabolism consistent with ongoing immune alterations in ME/CFS that may illuminate the mechanism behind this disease.

Post-exertional malaise (PEM) is a hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We monitored the evolution of 1157 plasma metabolites in 60 ME/CFS (45 female, 15 male) and 45 matched healthy control participants (30 female, 15 male) before and after 2 maximal cardiopulmonary exercise test (CPET) challenges separated by 24 hours, with the intent of provoking PEM in patients. Four time points allowed exploration of the metabolic response to maximal energy-producing capacity and the recovery pattern of participants with ME/CFS compared with the healthy control group. Baseline comparison identified several significantly different metabolites, along with an enriched percentage of yet-to-be identified compounds. Additionally, temporal measures demonstrated an increased metabolic disparity between cohorts, including unknown metabolites. The effects of exertion in the ME/CFS cohort predominantly highlighted lipid-related as well as energy-related pathways and chemical structure clusters, which were disparately affected by the first and second exercise sessions. The 24-hour recovery period was distinct in the ME/CFS cohort, with over a quarter of the identified pathways statistically different from the controls. The pathways that are uniquely different 24 hours after an exercise challenge provide clues to metabolic disruptions that lead to PEM. Numerous altered pathways were observed to depend on glutamate metabolism, a crucial component of the homeostasis of many organs in the body, including the brain.

Over the last dozen years, increasingly powerful DNA sequencing methods have allowed characterization of the microbes residing on and in humans in much greater detail than ever possible before. Abnormalities present in the gut microbiome--those microbial communities residing in our intestines--have now been observed in a number of diseases. One such illness is Myalgic Encephalomyelitis (ME), also known as Chronic Fatigue Syndrome (CFS). CFS was a name coined by the US Centers for Disease Control (CDC) in 1988, and reviled by patients for the resultant trivializing of this serious illness. Recently, the US National Academy of Medicine (NAM) recommended a new name: Systemic Exertion Intolerance Disease, though this name is not yet widely used. In ME, as in other diseases, the diversity of the bacterial species in the gut microbiome is lower than in healthy individuals. Furthermore, the abundances of different bacterial residents of the gut, which influence health both favourably and negatively, differ between ME patients and healthy controls. Bacteria translocate into the blood in greater amount in ME, leading to inflammation. Dysbiosis in the gut likely contributes to symptoms in this life-limiting disease.

OZ1, an RNA editing factor that controls the editing of 14 cytidine targets in Arabidopsis chloroplasts, contains two RanBP2-type zinc finger (Znf) domains. The RanBP2 Znf is a C4-type member of the broader zinc finger family with unique functions and an unusually diverse distribution in plants. The domain can mediate interactions with proteins or RNA and appears in protein types such as proteases, RNA editing factors, and chromatin modifiers; however, few characterized Arabidopsis proteins containing RanBP2 Znfs have been studied specifically with the domain in mind. In humans, RanBP2 Znf-containing proteins are involved in RNA splicing, transport, or transcription initiation. We present a phylogenetic overview of Arabidopsis RanBP2 Znf proteins and the functional niches that these proteins occupy in plants. OZ1 and its four-member family represent a branch of this family with major impact on the RNA biology of chloroplasts and mitochondria in Arabidopsis. We discuss what is known about other plant proteins carrying the RanBP2 Znf domain and point out how phylogenetic information can provide clues to functions of uncharacterized Znf proteins.

Previous studies of in situ bioremediation of uranium-contaminated groundwater with acetate injections have focused on the role of Geobacter species in U(VI) reduction because of a lack of other abundant known U(VI)-reducing microorganisms. Monitoring the levels of methyl CoM reductase subunit A ( mcrA ) transcripts during an acetate-injection field experiment demonstrated that acetoclastic methanogens from the genus Methanosarcina were enriched after 40 days of acetate amendment. The increased abundance of Methanosarcina corresponded with an accumulation of methane in the groundwater. An enrichment culture dominated by a Methanosarcina species with the same Methanosarcina mcrA sequence that predominated in the field experiment could effectively convert acetate to methane. In order to determine whether Methanosarcina species could be participating in U(VI) reduction in the subsurface, cell suspensions of M. barkeri were incubated in the presence of U(VI) with acetate provided as the electron donor. U(VI) was reduced by metabolically active M. barkeri cells, however, no U(VI) reduction was observed in inactive controls. These results demonstrate that Methanosarcina species could play an important role in the long-term bioremediation of uranium-contaminated aquifers after depletion of Fe(III) oxides limits the growth of Geobacter species. The results also suggest that Methanosarcina have the potential to influence uranium geochemistry in a diversity of anaerobic sedimentary environments.