Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise.

In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue and reduces the risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance. We hypothesized that altered extracellular vesicle (EV) signalling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post-exertional malaise).

Dysregulation of extracellular vesicle protein cargo in female ME/CFS cases and sedentary controls in response to maximal exercise.

In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue, and reduces risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance. We hypothesized that altered extracellular vesicle (EV) signaling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post-exertional malaise).

Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown etiology or effective treatments. Post-exertional malaise (PEM) is a key symptom that distinguishes ME/CFS patients. Investigating changes in the urine metabolome between ME/CFS patients and healthy subjects following exertion may help us understand PEM.

Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome.

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.

In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disease with worldwide prevalence and limited therapies exclusively aimed at treating symptoms. To gain insights into the molecular disruptions in ME/CFS, we utilized an aptamer-based technology that quantified 4790 unique human proteins, allowing us to obtain the largest proteomics dataset yet available for this disease, detecting highly abundant proteins as well as rare proteins over a nine-log dynamic range. We report a pilot study of 20 ME/CFS patients and 20 controls, all females.

Letter to the Editor of .

A number in our recently published study in your Metabolites journal, Germain et al. (2020),entitled "Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism ofAcyl Lipids and Steroids" [1] has drawn a significant amount of attention on social media [..

Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids.

The latest worldwide prevalence rate projects that over 65 million patients suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an illness with known effects on the functioning of the immune and nervous systems. We performed an extensive metabolomics analysis on the plasma of 52 female subjects, equally sampled between controls and ME/CFS patients, which delivered data for about 1750 blood compounds spanning 20 super-pathways, subdivided into 113 sub-pathways. Statistical analysis combined with pathway enrichment analysis points to a few disrupted metabolic pathways containing many unexplored compounds.

Systematic sequencing of chloroplast transcript termini from Arabidopsis thaliana reveals >200 transcription initiation sites and the extensive imprints of RNA-binding proteins and secondary structures.

Chloroplast transcription requires numerous quality control steps to generate the complex but selective mixture of accumulating RNAs. To gain insight into how this RNA diversity is achieved and regulated, we systematically mapped transcript ends by developing a protocol called Terminome-seq. Using Arabidopsis thaliana as a model, we catalogued >215 primary 5' ends corresponding to transcription start sites (TSS), as well as 1628 processed 5' ends and 1299 3' ends.

Prospective Biomarkers from Plasma Metabolomics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Implicate Redox Imbalance in Disease Symptomatology.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease of enigmatic origin with no established cure. Its constellation of symptoms has silently ruined the lives of millions of people around the world. A plethora of hypotheses have been vainly investigated over the past few decades, so that the biological basis of this debilitating condition remains a mystery.

ORRM5, an RNA recognition motif-containing protein, has a unique effect on mitochondrial RNA editing.

Plants have an RNA editing mechanism that prevents deleterious organelle mutations from resulting in impaired proteins. A typical flowering plant modifies about 40 cytidines in chloroplast transcripts and many hundreds of cytidines in mitochondrial transcripts. The plant editosome, the molecular machinery responsible for this process, contains members of several protein families, including the organelle RNA recognition motif (ORRM)-containing family.

Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS. Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established. In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins.

Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome.

Background: Mitochondrial dysfunction has been hypothesized to occur in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a disease characterized by fatigue, cognitive difficulties, pain, malaise, and exercise intolerance. We investigated whether haplogroup, single nucleotide polymorphisms (SNPs), or heteroplasmy of mitochondrial DNA (mtDNA) were associated with health status and/or symptoms.

Methods: Illumina sequencing of PCR-amplified mtDNA was performed to analyze sequence and extent of heteroplasmy of mtDNAs of 193 cases and 196 age- and gender-matched controls from DNA samples collected by the Chronic Fatigue Initiative.

RNA Recognition Motif-Containing Protein ORRM4 Broadly Affects Mitochondrial RNA Editing and Impacts Plant Development and Flowering.

Plant RNA editosomes modify cytidines (C) to uridines (U) at specific sites in plastid and mitochondrial transcripts. Members of the RNA-editing factor interacting protein (RIP) family and Organelle RNA Recognition Motif-containing (ORRM) family are essential components of the Arabidopsis (Arabidopsis thaliana) editosome. ORRM2 and ORRM3 have been recently identified as minor mitochondrial editing factors whose silencing reduces editing efficiency at ∼6% of the mitochondrial C targets.

High-throughput quantification of chloroplast RNA editing extent using multiplex RT-PCR mass spectrometry.

RNA editing in plants, animals, and humans modifies genomically encoded cytidine or adenosine nucleotides to uridine or inosine, respectively, in mRNAs. We customized the MassARRAY System (Sequenom Inc., San Diego, CA, USA, www.

Usefulness of the Airtraq DL™ videolaryngoscope for placing a double-lumen tube.

Background: Endotracheal insertion of a double-lumen tube (DLT) may be difficult because of its size and shape. The Airtraq™ is a new videolaryngoscope that allows supraglottis exposure without needing to align the oro-pharyngo-laryngeal axis. A specific model (Airtraq DL™), with a large diameter, has been specifically designed to insert a DLT.

RNase J participates in a pentatricopeptide repeat protein-mediated 5' end maturation of chloroplast mRNAs.

Nucleus-encoded ribonucleases and RNA-binding proteins influence chloroplast gene expression through their roles in RNA maturation and stability. One mechanism for mRNA 5' end maturation posits that sequence-specific pentatricopeptide repeat (PPR) proteins define termini by blocking the 5'→3' exonucleolytic activity of ribonuclease J (RNase J). To test this hypothesis in vivo, virus-induced gene silencing was used to reduce the expression of three PPR proteins and RNase J, both individually and jointly, in Nicotiana benthamiana.

Quantitative trait locus mapping identifies REME2, a PPR-DYW protein required for editing of specific C targets in Arabidopsis mitochondria.

Targeted RNA editing by C-to-U alteration occurs at hundreds of sites in the mitochondrial transcriptome of flowering plants. By using natural variation and positional cloning on a population of Arabidopsis recombinant inbred lines between the ecotypes Col and Ler, we found that two of these occurrences involve the Arabidopsis PPR-DYW protein REME2 (Required for Efficiency of Mitochondrial Editing2). The analysis of a knockdown mutant along with silenced tissues confirms the specificity of REME2 for both sites located in mitochondrial ribosomal protein genes (rps3-1534 and rps4-175).

RNA processing and decay in plastids.

Plastids were derived through endosymbiosis from a cyanobacterial ancestor, whose uptake was followed by massive gene transfer to the nucleus, resulting in the compact size and modest coding capacity of the extant plastid genome. Plastid gene expression is essential for plant development, but depends on nucleus-encoded proteins recruited from cyanobacterial or host-cell origins. The plastid genome is heavily transcribed from numerous promoters, giving posttranscriptional events a critical role in determining the quantity and sizes of accumulating RNA species.

An RNA recognition motif-containing protein is required for plastid RNA editing in Arabidopsis and maize.

Plant RNA editing modifies cytidines (C) to uridines (U) at specific sites in the transcripts of both mitochondria and plastids. Specific targeting of particular Cs is achieved by pentatricopeptide proteins that recognize cis elements upstream of the C that is edited. Members of the RNA-editing factor interacting protein (RIP) family in Arabidopsis have recently been shown to be essential components of the plant editosome.

Ribonuclease II preserves chloroplast RNA homeostasis by increasing mRNA decay rates, and cooperates with polynucleotide phosphorylase in 3' end maturation.

Ribonuclease R (RNR1) and polynucleotide phosphorylase (cpPNPase) are the two known 3'→5' exoribonucleases in Arabidopsis chloroplasts, and are involved in several aspects of rRNA and mRNA metabolism. In this work, we show that mutants lacking both RNR1 and cpPNPase exhibit embryo lethality, akin to the non-viability of the analogous double mutant in Escherichia coli. We were successful, however, in combining an rnr1 null mutation with weak pnp mutant alleles, and show that the resulting chlorotic plants display a global reduction in RNA abundance.

Plastid non-coding RNAs: emerging candidates for gene regulation.

Recent advances in transcriptomics and bioinformatics, specifically strand-specific RNA sequencing, have allowed high-throughput, comprehensive detection of low-abundance transcripts typical of the non-coding RNAs studied in bacteria and eukaryotes. Before this, few plastid non-coding RNAs (pncRNAs) had been identified, and even fewer had been investigated for any functional role in gene regulation. Relaxed plastid transcription initiation and termination result in full transcription of both chloroplast DNA strands.

Mutational analysis of Arabidopsis chloroplast polynucleotide phosphorylase reveals roles for both RNase PH core domains in polyadenylation, RNA 3'-end maturation and intron degradation.

Polynucleotide phosphorylase (PNPase) catalyzes RNA polymerization and 3'→5' phosphorolysis in vitro, but its roles in plant organelles are poorly understood. Here, we have used in vivo and in vitro mutagenesis to study Arabidopsis chloroplast PNPase (cpPNPase). In mutants lacking cpPNPase activity, unusual RNA patterns were broadly observed, implicating cpPNPase in rRNA and mRNA 3'-end maturation, and RNA degradation.

Daily titration of neurally adjusted ventilatory assist using the diaphragm electrical activity.

Purpose: To determine the feasibility of daily titration of the neurally adjusted ventilatory assist (NAVA) level in relation to the maximal diaphragmatic electrical activity (EAdi(maxSBT)) measured during a spontaneous breathing trial (SBT) during pressure support ventilation (PSV).

Methods: The study included 15 consecutive patients in whom mechanical ventilation weaning was initiated with the NAVA mode. EAdi(maxSBT) was determined daily during an SBT using PSV with 7 cmH2O of inspiratory pressure and no positive end-expiratory pressure (PEEP).

Pneumocephalus following thoracic surgery: the implication of the epidural anesthesia is still exceptional.

Epidural analgesia is the gold standard for the management of pain after thoracopulmonary surgery. However, it is not without side-effects and complications. We report the case of a 52-year-old man who underwent left lower lobectomy for a carcinoid tumor.