Neuroprotective effects of carnitinoid compounds in rodent cellular and in vivo models of mitochondrial complex I dysfunction

Rotenone-mediated mitochondrial complex I inhibition was used to model Parkinson’s disease-like syndrome in Lewis rats. Tyrosine hydroxylase immunolabeling demonstrated a decrease in the number of dopaminergic neurons as well as aberrant morphology in surviving neurons. Administration of carnitinoid compounds (synthetic lipoylcarnitine or butyrylcarnitine compounds) reduced dopaminergic neuronal cell loss with characteristic morphology observed in surviving neurons. In a rat primordial hippocampal cell line (H19-7/IGF-IR), rotenone treatment resulted in increased ROS and reduced cellular ATP, while co-treatment with lipoylcarnitine maintained ROS and ATP at control levels. These results illustrate the therapeutic potential of small-molecule carnitinoids in treating neurodegenerative diseases associated with mitochondrial dysfunction.https://mesford.ca/journals/cab/articles-on-biotechnology/neuroprotective-effects-of-carnitinoid-compounds-in-rodent-cellular-and-in-vivo-models-of-mitochondrial-complex-i-dysfunction/Published versio

A Survey into Piano Teachers’ Perceptions of Music Memorization in One-to-one Piano Lessons: A Preliminary Study

Despite more than a century of research on music memorization and practicing strategies, there is a lack of comprehensive evidence on how instrumental music teachers teach memorization to children and adolescents in one-to-one lessons. The present qualitative study investigated the diversity of ways in which music memorization is taught in one-to-one piano lessons. Piano teachers (N = 37) completed an online survey collecting qualitative responses regarding music memorization. Participants were asked to give a brief description of music memorization, how they memorize as performers and how they teach music memorization to their students, amongst other questions. Results indicate that music memorization is perceived by most teachers as a skill that develops through practice rather than a natural talent. Reported strategies for teaching memorization fell into four categories: aural, visual, kinesthetic, and analytical, which align with previous theoretical conceptualizations of musical memorization. Recurring mentions of muscle memory practice and music theory knowledge suggest that kinesthetic and analytical methods are qualitatively dominant in the way teachers 1) define music memorization, 2) memorize as performers, and 3) teach music memorization. This suggests that aural and visual memorization methods might be less explored by piano teachers of children and adolescents and future research could be conducted in this area

Co-operatives, credit unions and principles: a post 2008 critique

This thesis examines the adherence of credit unions to their co-operative principles. Noting the financial crisis of 2008 and the calls for change to a more ethical, transparent and fairer financial industry co-operatives appear to be a plausible way forward. The analysis of the corporate governance of co-operatives indicates that they are founded on co-operative principles, the cornerstone being the active participation by its members. The study of the previous literature demonstrates instances where co-operatives did not adhere to their principles as well as instances where members were not very active. Credit unions in Cyprus were selected as the specific co-operative industry and geographic location for the collection of data; one of the reasons being that in March 2013, six months prior to the first collection of data, Cyprus suffered a second financial crisis, giving the opportunity to investigate these two issues in a time of scrutiny and pressure. Structured interviews with thirty credit union employees, documents (statistics) from the ex-supervisory body and three focus groups with thirty members (in total) were carried out. The findings show that credit unions do not seem to adhere to their principles and members do not seem to be actively involved with their credit unions. As the warning bells for their long-term survival may have already sounded, credit unions must encourage their members to get involved, rebuild their trust amongst them, among membership and the society in general, provide co-operative-related training and restrict the involvement of the political parties. Finally, ways must be found so that credit unions remain closely involved with the societies they serve. To this extent, Service-Dominant Logic is proposed as a possible way in assisting credit unions to re-focus on their membership

Bite Force and EMG Studies on the Jaw-Closing Muscles

The jaw-closing muscles perform movements of the mandible, provide force for a variety of natural functions, and are subject to disorders often manifested as jaw muscle pain. Bite force measurement and surface electromyography have been used in the present investigation to assess jaw-closing muscle activity and strength in young healthy adult subjects and in older edentulous patients

Klotho pathways, myelination disorders, neurodegenerative diseases, and epigenetic drugs

In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.https://www.liebertpub.com/doi/10.1089/biores.2020.0004Published versio

Carnitinoid lipoic acid derivatives protect photoreceptors after experimental retinal detachment

Purpose: Retinal detachment (RD) is a vision threatening disease that is characterized by the separation of photoreceptors (PR) from the underlying retinal pigment epithelium(RPE). Since photoreceptors have high demand in energy and metabolism, nutrient deprivation after RD can lead to a compromised function of mitochondria and the generation of reactive oxygen species (ROS) in the photoreceptor layer. However, natural antioxidants have concerns of reduced efficacy due to their limited and transient accumulation following oral intake. Thus, we wanted to investigate the effects of mitoprotectant and antioxidant lipoic acid derivatives in experimental RD. Methods: Retinal detachment in mice was induced by subretinal administration of hyalauronic acid 1%. The novel synthetic lipoylcarnitine derivative, lipoyl-L-carnitine methylester iodide (PMX-500FI) was administered intraperitoneally at 40 mg/kg daily. Cyclodextrin was injected as vehicle control. Animals were euthanized at day 1, 3 and 7post RD induction. The effects on PR was examined via TUNEL staining and outer nuclear layer (ONL) thickness evaluation. Inflammatory reaction was evaluated via CD11b staining. Results: PMX-500FI administration led to a significant reduction of TUNEL positive cells in the photo receptor layer compared to vehicle group (p = 0.009) at 24 hours after RD (Fig. 1). Furthermore, a suppression of infiltrating macrophages in the subretinal space 3 days after RD was noted (p = 0.048) (Fig. 2). Administration of PMX-500FI resulted in a substantial preservation of ONL thickness after 7 days of treatment (p = 0.002). Conclusions: These results suggest that bioavailable lipoic acid derivative, PMX-500FI,results in protection of photoreceptors after RD and suggest that lipoic acid derivatives may serve as neuroprotectants.https://iovs.arvojournals.org/article.aspx?articleid=276924

Pathogenic mitochondrial dysfunction and metabolic abnormalities

Herein we trace links between biochemical pathways, pathogenesis, and metabolic diseases to set the stage for new therapeutic advances. Cellular and acellular microorganisms including bacteria and viruses are primary pathogenic drivers that cause disease. Missing from this statement are subcellular compartments, importantly mitochondria, which can be pathogenic by themselves, also serving as key metabolic disease intermediaries. The breakdown of food molecules provides chemical energy to power cellular processes, with mitochondria as powerhouses and ATP as the principal energy carrying molecule. Most animal cell ATP is produced by mitochondrial synthase; its central role in metabolism has been known for >80 years. Metabolic disorders involving many organ systems are prevalent in all age groups. Progressive pathogenic mitochondrial dysfunction is a hallmark of genetic mitochondrial diseases, the most common phenotypic expression of inherited metabolic disorders. Confluent genetic, metabolic, and mitochondrial axes surface in diabetes, heart failure, neurodegenerative disease, and even in the ongoing coronavirus pandemic.https://doi.org/10.1016/j.bcp.2021.11480

Chronic exposure to short chain fatty acids modulates transport and metabolism of microbiome-derived phenolics in human intestinal cells

Dietary fibre-derived short chain fatty acids (SCFA) and phenolics produced by the gut microbiome have multiple effects on health. We have tested the hypothesis that long term exposure to physiological concentrations of SCFA can affect the transport and metabolism of (poly)phenols by the intestinal epithelium using the Caco-2 cell model. Metabolites and conjugates of hesperetin (HT) and ferulic acid (FA), gut-derived from dietary hesperidin and chlorogenic acid respectively, were quantified by LC–MS with authentic standards following transport across differentiated cell monolayers. Changes in metabolite levels were correlated with effects on mRNA and protein expression of key enzymes and transporters. Propionate and butyrate increased both FA transport and rate of appearance of FA-glucuronide apically and basolaterally, linked to an induction of MCT1. Propionate was the only SCFA that augmented the rate of formation of basolateral FA-sulfate conjugates, possibly via basolateral transporter upregulation. In addition, propionate enhanced the formation of HT-glucuronide conjugates and increased HT-sulfate efflux towards the basolateral compartment. Acetate treatment amplified transepithelial transport of FA in the apical to basolateral direction, associated with lower levels of MCT1 protein expression. Metabolism and transport of both HT and FA were curtailed by the organic acid lactate owing to a reduction of UGT1A1 protein levels. Our data indicate a direct interaction between microbiota-derived metabolites of (poly)phenols and SCFA through modulation of transporters and conjugating enzymes, and increase our understanding of how dietary fibre, via the microbiome, may affect and enhance uptake of bioactive molecules

Participant and musical diversity in music psychology research

Research on music psychology has increased exponentially over the past half century, providing insights on a wide range of topics underpinning the perception, cognition, and production of music. This wealth of research means we are now in a place to develop broad, testable theories on the psychology of music, with the potential to impact our wider understanding of human biology, culture, and communication. However, the development of widely applicable and inclusive theories of human responses to music requires these theories to be informed by data that is representative of the global human population and its diverse range of music-making practices. The goal of the present paper is to survey the current state of the field of music psychology in terms of the participant samples and musical samples used. We reviewed and coded relevant details from all articles published in Music Perception, Musicae Scientiae, and Psychology of Music between 2010 to 2022. We found that music psychologists show a substantial tendency to collect data from young adults and university students in Western countries in response to Western music, replicating trends seen across psychology research as a whole. Even data collected in non-Western countries tends to come from a similar demographic to studies of Western participants (e.g., university students, young adults). Some positive trends toward increasing participant diversity have been evidenced over the past decade, although there is still much work to be done, and certain subtopics in the field appear to be more prone to these sampling biases than others. Recommendations for future diversification of research in our field are made, with the aim of increasing our confidence in music psychological theories and their relevance to humans and music in the broadest sense