Biallelic PTPMT1 variants disrupt cardiolipin metabolism and lead to a neurodevelopmental syndrome.

Primary mitochondrial diseases (PMDs) are among the most common inherited neurological disorders. They are caused by pathogenic variants in mitochondrial or nuclear DNA that disrupt mitochondrial structure and/or function, leading to impaired oxidative phosphorylation (OXPHOS). One emerging subcategory of PMDs involves defective phospholipid (PL) metabolism.

Transforming research systems for meaningful engagement: a reflexive thematic analysis of spinal cord injury researchers' barriers and facilitators to using the integrated knowledge translation guiding principles.

Purpose: To develop an in-depth understanding of spinal cord injury (SCI) researchers' barriers and facilitators to deciding to use 1) a partnered approach to research and, 2) systematically developed principles for guiding Integrated Knowledge Translation (IKT) in spinal cord injury research (IKT Guiding Principles).

Methods: Qualitative interview study with North American SCI researchers who were interested in using a partnered research approach. The research was conducted using an IKT approach, and interview data were analyzed using reflexive thematic analysis.

Assessing Susceptibility to Carbon Dioxide Gas in Three Rat Strains Using the Loss of Righting Reflex.

Overdose of carbon dioxide gas (CO₂) is a common euthanasia method for rodents; however, CO₂ exposure activates nociceptors in rats at concentrations equal to or greater than 37% and is reported to be painful in humans at concentrations equal to or greater than 32.5%. Exposure of rats to CO₂ could cause pain before loss of consciousness.

Mitochondrial aminoacyl-tRNA synthetases trigger unique compensatory mechanisms in neurons.

Mitochondrial aminoacyl-tRNA synthetase (mt-ARS) mutations cause severe, progressive, and often lethal diseases with highly heterogeneous and tissue-specific clinical manifestations. This study investigates the molecular mechanisms triggered by three different mt-ARS defects caused by biallelic mutations in AARS2, EARS2, and RARS2, using an in vitro model of human neuronal cells. We report distinct molecular mechanisms of mitochondrial dysfunction among the mt-ARS defects studied.

Use of Loss of Righting Reflex to Assess Susceptibility to Carbon Dioxide Gas in Three Mouse Strains.

Exposure to CO₂ gas is a common rodent euthanasia method. CO₂ activates nociceptors in rats and is painful to humans at concentrations equal to or greater than 32.5% The concentration of CO₂ at which rodents become unconsciousness is inadequately defined.

Plasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions.

Objectives: Plasmapheresis (PLEX) and intravenous immunoglobulin (IVIg) are commonly used to treat autoimmune neuromuscular disorders, including myasthenia gravis, acute inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and other autoimmune neurological disorders. The side effect profiles of these therapies vary, and concern has been raised regarding the safety of PLEX in the elderly population. In this study, we have examined the pattern of PLEX and IVIg use for autoimmune neurological disorders at a single facility and in a national database, focusing on the complications in elderly patients.

Supporting meaningful research partnerships: an interview study applying behavior change theory to develop relevant recommendations for researchers.

Research partnerships, while promising for ensuring translation of relevant and useable findings, are challenging and need support. This study aimed to apply behavior change theory to understand and support researchers' adoption of a research partnership approach and the Integrated Knowledge Translation (IKT) Guiding Principles for conducting and disseminating spinal cord injury (SCI) research in partnership. Using an IKT approach, SCI researchers across Canada and the USA completed a survey (n = 22) and were interviewed (n = 13) to discuss barriers and facilitators to deciding to partner and follow the IKT Guiding Principles.

Quality of reporting of prospective in vivo and ex vivo studies published in the Journal of Veterinary Emergency and Critical Care over a 10-year period (2009-2019).

Objective: To evaluate the reporting of key items associated with risk of bias and weak study design over a 10-year period.

Design: Literature survey.

Setting: Not applicable.

TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease.

Mutations in the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA biology. The TEFM gene encodes the mitochondrial transcription elongation factor responsible for enhancing the processivity of mitochondrial RNA polymerase, POLRMT.

Sensory enhancement of warm-up amplifies subsequent grip strength and cycling performance.

Purpose: In sport and exercise, warm-ups induce various physiological changes that facilitate subsequent performance. We have shown that delivering patterned stimulation to cutaneous afferents during sprint cycling mitigates fatigue-related decrements in performance, and that repeated sensory stimulation amplifies spinal reflex excitability. Therefore, the purpose of this study was to assess whether sensory enhancement of warm-up would affect subsequent high-intensity arm cycling performance.

Randomization, blinding, data handling and sample size estimation in papers published in Veterinary Anaesthesia and Analgesia in 2009 and 2019.

Objective: To evaluate reporting of items indicative of bias and weak study design.

Study Design: Literature survey.

Population: Papers published in Veterinary Anaesthesia and Analgesia.

Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperone .

Recessive mutations in , an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. To further unravel these pathomechanisms, we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways, suggesting a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergetics, ER-Golgi function, and amyloid-beta processing. Further functional investigations in fibroblasts of patients with mutations detected cellular accumulation of lipids and an increased sensitivity to cholesterol stress, which led to activation of the unfolded protein response (UPR), alterations of the ER-Golgi machinery, and a defect of amyloid precursor protein.

Sustained low-dose ergot alkaloids minimally affect post-thaw sperm characteristics in mature and yearling Angus bulls.

Our objectives were to determine if feeding mature and yearling Angus bulls ergot alkaloids (from Claviceps purpurea) within the Canadian permissible limit (∼3 mg/kg) affect post-thaw sperm quality. In Experiment 1, mature Angus bulls were group-fed ergot alkaloids (∼1 and ∼2 mg/kg of daily dry matter intake, DMI; n = 8 and n = 6 bulls, respectively) for 61 d; semen was collected and cryopreserved bi-weekly, from 12 wk pre-exposure to 10 wk post-exposure. In Experiment 2, yearling Angus bulls (12-13 mo) were individually fed placebo or ergot alkaloids (3.

Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease.

TARS2 encodes human mitochondrial threonyl tRNA-synthetase that is responsible for generating mitochondrial Thr-tRNAThr and clearing mischarged Ser-tRNAThr during mitochondrial translation. Pathogenic variants in TARS2 have hitherto been reported in a pair of siblings and an unrelated patient with an early onset mitochondrial encephalomyopathy and a combined respiratory chain enzyme deficiency in muscle. We here report five additional unrelated patients with TARS2-related mitochondrial diseases, expanding the clinical phenotype to also include epilepsy, dystonia, hyperhidrosis and severe hearing impairment.

The impact and effectiveness of the general public wearing masks to reduce the spread of pandemics in the UK: a multidisciplinary comparison of single-use masks versus reusable face masks.

During the coronavirus (COVID-19) pandemic, the UK government mandated the use of face masks in various public settings and recommended the use of reusable masks to combat shortages of medically graded single-use masks in healthcare. To assist decision-making on the choice of masks for future pandemics, where shortages may not be a contributing factor, the University College London (UCL) Plastic Waste Innovation Hub has carried out a multidisciplinary comparison between single-use and reusable masks based on their anatomy, standalone effectiveness, behavioural considerations, environmental impact and costs. Although current single-use masks have a higher standalone effectiveness against bacteria and viruses, studies show that reusable masks have adequate performance in slowing infection rates of respiratory viruses.

Compression socks enhance sensory feedback to improve standing balance reactions and reflex control of walking.

Background: Compression garments are generally used for their potential benefits in exercise performance and post-exercise recovery. Previous studies show that compression sleeves worn at the elbow change neuromuscular control and improve performance during reaching movement. Cutaneous stimulation of the foot skin produces location-specific reflexes in the lower limb that guide foot placement during locomotion.

Feeding yearling Angus bulls low-level ergot daily for 9 weeks decreased serum prolactin concentrations and had subtle effects on sperm end points.

Our objective was to determine whether feeding yearling bulls with the higher recommended Canadian limit of ergot alkaloids (∼3 mg/kg dry matter intake, DMI) would affect sperm characteristics and plasma prolactin concentrations. Aberdeen Angus bulls (12-13 mo old, n = 7/group) allocated by blocking for sperm concentration and body weight, were fed placebo or ergot alkaloids in gelatin capsules (60 μg/kg body weight daily, 3.4 mg/kg of DMI) for 9 wk.

Experimentally based structural model of Yih1 provides insight into its function in controlling the key translational regulator Gcn2.

Yeast impact homolog 1 (Yih1), or IMPACT in mammals, is part of a conserved regulatory module controlling the activity of General Control Nonderepressible 2 (Gcn2), a protein kinase that regulates protein synthesis. Yih1/IMPACT is implicated not only in many essential cellular processes, such as neuronal development, immune system regulation and the cell cycle, but also in cancer. Gcn2 must bind to Gcn1 in order to impair the initiation of protein translation.

RNA exosome mutations in pontocerebellar hypoplasia alter ribosome biogenesis and p53 levels.

The RNA exosome is a ubiquitously expressed complex of nine core proteins (EXOSC1-9) and associated nucleases responsible for RNA processing and degradation. Mutations in , , , and the exosome cofactor cause pontocerebellar hypoplasia and motor neuronopathy. We investigated the consequences of exosome mutations on RNA metabolism and cellular survival in zebrafish and human cell models.

Confirmation of TACO1 as a Leigh Syndrome Disease Gene in Two Additional Families.

Background: In 2009, we identified TACO1 as a novel mitochondrial disease gene in a single family, however no second family has been described to confirm the role of TACO1 in mitochondrial disease.

Objective: In this report, we describe two independent consanguineous families carrying pathogenic variants in TACO1, confirming the phenotype.

Methods: Detailed clinical investigations and whole exome sequencing with haplotype analysis have been performed in several members of the two reported families.

Identification of Cellular Pathogenicity Markers for SIL1 Mutations Linked to Marinesco-Sjögren Syndrome.

Recessive mutations in the gene cause Marinesco-Sjögren syndrome (MSS), a rare neuropediatric disorder. MSS-patients typically present with congenital cataracts, intellectual disability, cerebellar ataxia and progressive vacuolar myopathy. However, atypical clinical presentations associated with mutations have been described over the last years; compound heterozygosity of SIL1 missense mutations even resulted in a phenotype not fulfilling the clinical diagnostic criteria of MSS.

The short-term effects of recorded ocean sound with and without alpha frequency binaural beats on tinnitus perception.

Background: The dichotic presentation of two auditory stimuli with a small frequency difference in each ear produces the perception of a third, fused auditory image called a binaural beat. Neural activity has been found to synchronize with these perceived beats. It is for this reason that binaural beats are often used in an attempt to induce certain psychological states that are associated with particular cortical rhythms.

Nucleoside supplementation modulates mitochondrial DNA copy number in the dguok -/- zebrafish.

Deoxyguanosine kinase (dGK) is an essential rate-limiting component of the mitochondrial purine nucleotide salvage pathway, encoded by the nuclear gene encoding deoxyguanosine kinase (DGUOK). Mutations in DGUOK lead to mitochondrial DNA (mtDNA) depletion typically in the liver and brain, causing a hepatocerebral phenotype. Previous work has shown that in cultured DGUOK patient cells it is possible to rescue mtDNA depletion by increasing substrate amounts for dGK.

Lipidomic profiling of extracellular vesicles derived from prostate and prostate cancer cell lines.

Background: Extracellular vesicles (EVs) are produced and secreted from most cells of the body and can be recovered in biological fluids. Although there has been extensive characterisation of the protein and nucleic acid component of EVs, their lipidome has received little attention and may represent a unique and untapped source of biomarkers for prostate cancer diagnosis and prognosis.

Methods: EVs were isolated from non-tumourigenic (RWPE1), tumourigenic (NB26) and metastatic (PC-3) prostate cell lines.