Contaminating transfection complexes can masquerade as small extracellular vesicles and impair their delivery of RNA.

One of the functions of small extracellular vesicles (sEVs) which has received the most attention is their capacity to deliver RNA into the cytoplasm of target cells. These studies have often been performed by transfecting RNAs into sEV-producing cells, to later purify and study sEV delivery of RNA. Transfection complexes and other delivery vehicles accumulate in late endosomes where sEV are formed and over 50% of transfection complexes or delivery vehicles administered to cells are released again to the extracellular space by exocytosis.

Guillain-Barré syndrome in an era of global infections and 21st century vaccination.

Purpose Of Review: Guillain-Barre syndrome is sometimes a severe and disabling postinfectious neuromuscular paralysis that is causally associated with a number of well defined infections, and occasionally with immunization. The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) pandemic and the worldwide immunization programme provoked fears of an epidemic of coronavirus disease 2019 (COVID-19) related disease. As we emerge from the pandemic this review summarises some of the huge volume of publications about Guillain-Barre syndrome (GBS), COVID-19 and immunisation against it.

Daratumumab-bortezomib-dexamethasone use in relapsed POEMS syndrome.

POEMS syndrome is a rareparaneoplastic disorder driven by an underlying low level plasma cell dyscrasiaand associated with elevated serum vascular endothelial growth factor (VEGF). Dueto its rarity, there are no internationally agreed standards of care, with verylimited data to guide management in the relapse setting. Agents used in myelomaare rational choices and have been employed.

Combinatorial treatment with exercise and AICAR potentiates the rescue of myotonic dystrophy type 1 mouse muscles in a sex-specific manner.

Targeting AMP-activated protein kinase (AMPK) is emerging as a promising strategy for treating myotonic dystrophy type 1 (DM1), the most prevalent form of adult-onset muscular dystrophy. We previously demonstrated that 5-aminomidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and exercise, two potent AMPK activators, improve disease features in DM1 mouse skeletal muscles. Here, we employed a combinatorial approach with these AMPK activators and examined their joint impact on disease severity in male and female DM1 mice.

Sex-dependent role of Pannexin 1 in regulating skeletal muscle and satellite cell function.

The development and regeneration of skeletal muscle are mediated by satellite cells (SCs), which ensure the efficient formation of myofibers while repopulating the niche that allows muscle repair following injuries. Pannexin 1 (Panx1) channels are expressed in SCs and their levels increase during differentiation in vitro, as well as during skeletal muscle development and regeneration in vivo. Panx1 has recently been shown to regulate muscle regeneration by promoting bleb-based myoblast migration and fusion.

Evidence-based medical treatment of POEMS syndrome.

POEMS syndrome is a rare multisystem paraneoplastic disorder due to an underlying low-level plasma cell dyscrasia. Due to its rarity, there are limited data to guide treatment and there are no consensus guidelines. Therapy choices are dictated by patient characteristics, disease factors and local funding arrangements.

Nutritional Regulation of Muscle Stem Cells in Exercise and Disease: The Role of Protein and Amino Acid Dietary Supplementation.

Human skeletal muscle is a remarkedly plastic tissue that has a high capacity to adapt in response to various stimuli. These adaptations are due in part to the function of muscle-resident stem/progenitor cells. Skeletal muscle regeneration and adaptation is facilitated by the activation and expansion of muscle stem cells (MuSCs).

The CARM1 transcriptome and arginine methylproteome mediate skeletal muscle integrative biology.

Objective: Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins to regulate critical processes in health and disease. A mechanistic understanding of the role(s) of CARM1 in skeletal muscle biology is only gradually emerging. The purpose of this study was to elucidate the function of CARM1 in regulating the maintenance and plasticity of skeletal muscle.

Pharmacological and exercise-induced activation of AMPK as emerging therapies for myotonic dystrophy type 1 patients.

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder with variable clinical features. Currently, there is no cure or effective treatment for DM1. The disease is caused by an expansion of CUG repeats in the 3' UTR of DMPK mRNAs.

Episodic Ataxia Type 1: Natural History and Effect on Quality of Life.

Episodic ataxia type 1 (EA1) is a rare autosomal potassium channelopathy, due to mutations in KCNA1. Patients have childhood onset of intermittent attacks of ataxia, dizziness or imbalance. In order to quantify the natural history of EA1, its effect on quality of life and in preparation for future clinical trials, we set up an international multi-centre study of EA1.

Severe Muscle Deconditioning Triggers Early Extracellular Matrix Remodeling and Resident Stem Cell Differentiation into Adipocytes in Healthy Men.

Besides the loss of muscle mass and strength, increased intermuscular adipose tissue (IMAT) is now a well-recognized consequence of muscle deconditioning as experienced in prolonged microgravity. IMAT content may alter the muscle stem cell microenvironment. We hypothesized that extracellular matrix structure alterations and microenvironment remodeling induced by fast and severe muscle disuse could modulate fibro-adipogenic progenitor fate and behavior.

Curing SMA: Are we there yet?

Loss or deletion of survival motor neuron 1 gene (SMN1) is causative for a severe and devastating neuromuscular disease, Spinal Muscular Atrophy (SMA). SMN1 produces SMN, a ubiquitously expressed protein, that is essential for the development and survival of motor neurons. Major advances and developments in SMA therapeutics are shifting the natural history of the disease.

Combinatorial therapies for rescuing myotonic dystrophy type 1 skeletal muscle defects.

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder for which there is no cure. In recent years, progress has been made in defining disease mechanisms and in developing novel therapies, especially for skeletal muscle defects. Here, we highlight the potential of activating AMP-activated protein kinase (AMPK) with different approaches in combinatorial therapies.

MicroRNAs in oligodendrocyte development and remyelination.

Oligodendrocytes are the glial cells responsible for the formation of myelin around axons of the central nervous system (CNS). Myelin is an insulating layer that allows electrical impulses to transmit quickly and efficiently along neurons. If myelin is damaged, as in chronic demyelinating disorders such as multiple sclerosis (MS), these impulses slow down.

Central and peripheral delivered AAV9-SMN are both efficient but target different pathomechanisms in a mouse model of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the SMN1 gene and low SMN protein levels. Although lower motor neurons are a primary target, there is evidence that peripheral organ defects contribute to SMA. Current SMA gene therapy and clinical trials use a single intravenous bolus of the blood-brain-barrier penetrant scAAV9-cba-SMN by either systemic or central nervous system (CNS) delivery, resulting in impressive amelioration of the clinical phenotype but not a complete cure.

Survival motor neuron protein deficiency alters microglia reactivity.

Survival motor neuron (SMN) protein deficiency results in loss of alpha motor neurons and subsequent muscle atrophy in patients with spinal muscular atrophy (SMA). Reactive microglia have been reported in SMA mice and depleting microglia rescues the number of proprioceptive synapses, suggesting a role in SMA pathology. Here, we explore the contribution of lymphocytes on microglia reactivity in SMA mice and investigate how SMN deficiency alters the reactive profile of human induced pluripotent stem cell (iPSC)-derived microglia.

Differences in nerve excitability properties across upper limb sensory and motor axons.

Objective: The excitability of motor and sensory axons of the main upper limb nerves were compared to characterise the differences between nerves and provide a guide for future studies in human diseases with median neuropathy at the wrist.

Methods: Axonal excitability studies were undertaken on median and ulnar motor (APB and ADM) and sensory axons (D2 and D5) and the superficial radial axons (D1) using a threshold tracking technique.

Results: Compared to the median, ulnar motor axons had reduced early depolarising threshold electrotonus (TEd40(10-20 ms) p = 0.

Enhanced Expression of TRAP1 Protects Mitochondrial Function in Motor Neurons under Conditions of Oxidative Stress.

TNF-receptor associated protein (TRAP1) is a cytoprotective mitochondrial-specific member of the Hsp90 heat shock protein family of protein chaperones that has been shown to antagonise mitochondrial apoptosis and oxidative stress, regulate the mitochondrial permeability transition pore and control protein folding in mitochondria. Here we show that overexpression of TRAP1 protects motor neurons from mitochondrial dysfunction and death induced by exposure to oxidative stress conditions modelling amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease in which motor neurons degenerate, leading to muscle weakness and atrophy and death, typically within 3 years of diagnosis.

Laryngospasm in amyotrophic lateral sclerosis.

Introduction: Laryngospasm is an involuntary, sustained closure of sphincter musculature that leads to an unpleasant subjective experience of dyspnea and choking. It is an underreported symptom in amyotrophic lateral sclerosis (ALS). In this study we aimed to better characterize the prevalence and clinical characteristics of laryngospasm in ALS patients.