Publications by authors named "Holloway G"

Background: The polyphenol oleuropein activates mitochondrial calcium import, which increases pyruvate dehydrogenase (PDH) activity. Preclinically, this increase in PDH activity following oleuropein supplementation resulted in improved mitochondrial bioenergetics and fatigue resistance.

Objectives: This study aimed to examine the effects of acute and chronic oleuropein supplementation on muscle energy metabolism, whole-body substrate metabolism, strength, and fatigue resistance in older males.

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The Na-K-ATPase is a critical regulator of ion homeostasis during contraction, buffering interstitial K accumulation, which is linked to muscle fatigue during intense exercise. Within this context, we adopted a recently reported methodology to examine exercise-induced alterations in maximal Na-K-ATPase activity. Eighteen trained healthy young males completed a repeated high-intensity cycling protocol consisting of three periods (EX1-EX3) of intermittent exercise.

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Background: Mitochondria represent key organelles influencing cellular homeostasis and have been implicated in the signalling events regulating protein synthesis.

Methods: We examined whether mitochondrial bioenergetics (oxidative phosphorylation and reactive oxygen species (HO) emission, ROS) measured in vitro in permeabilized muscle fibres represent regulatory factors for integrated daily muscle protein synthesis rates and skeletal muscle mass changes across the spectrum of physical activity, including free-living and bed-rest conditions: n = 19 healthy, young men (26 ± 4 years, 23.4 ± 3.

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Article Synopsis
  • * A study analyzed 4,685 sporadic FTD cases and found significant genetic variants at the MAPT and APOE loci that increase the risk for the disease, indicating potential genetic overlap with other neurodegenerative diseases.
  • * The genetic risk factors appear to vary by population, with MAPT and APOE associations predominantly found in Central/Nordic and Mediterranean Europeans, suggesting a need for further research into these population-specific features for better understanding of sporadic FTD.
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The prompt diagnosis of internal infections is an important, but surprisingly difficult, component of healthcare. Existing clinical and laboratory tests, such as complete blood counts, are low accuracy (~70%), time consuming (>90 min), and require expensive blood analyzers. More sensitive and specific tests, such as PCR or sequencing, require access to a sample of the infected tissue, genomic data for all potential pathogens and expensive equipment.

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While a definitive mechanism-of-action remains to be identified, recent findings indicate that ghrelin, particularly the unacylated form (UnAG), stimulates skeletal muscle fatty acid oxidation. The biological importance of UnAG-mediated increases in fat oxidation remains unclear, as UnAG peaks in the circulation before mealtimes, and decreases rapidly during the postprandial situation before increases in postabsorptive circulating lipids. Therefore, we aimed to determine if the UnAG-mediated stimulation of fat oxidation would persist long enough to affect the oxidation of meal-derived fatty acids, and if UnAG stimulated the translocation of fatty acid transporters to the sarcolemma as a mechanism-of-action.

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All examples of Anthrenus (Anthrenus) festivus were borrowed from the Natural History Museum, London for dissection to provide good images of external and internal features. Images of habitus, ventrites and antennae are presented along with aedeagus and sternite IX. The purpose of this was to provide clear information for future comparative taxonomic studies.

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During an examination of Spanish Anthrenus spp. held in Andreas Herrmann's private collection, four specimens of a new species were noted: Anthrenus (Anthrenus) semipallens. Images of habitus features, including antenna, are presented and compared with other Anthrenus species thought to occur in Spain.

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Obesity-related type II diabetes (diabesity) has increased global morbidity and mortality dramatically. Previously, the ancient drug salicylate demonstrated promise for the treatment of type II diabetes, but its clinical use was precluded due to high dose requirements. In this study, we present a nitroalkene derivative of salicylate, 5-(2-nitroethenyl)salicylic acid (SANA), a molecule with unprecedented beneficial effects in diet-induced obesity (DIO).

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Fuel interactions in contracting muscle represent a complex interplay between enzymes regulating carbohydrate and fatty acid catabolism, converging in the mitochondrial matrix. While increasing exercise intensity promotes carbohydrate use at the expense of fatty acid oxidation, the mechanisms underlying this effect remain poorly elucidated. As a potential explanation, we investigated whether exercise-induced reductions in intramuscular pH (acidosis) attenuate carnitine palmitoyltransferase-I (CPT-I)-supported bioenergetics, the rate-limiting step for fatty acid oxidation within mitochondria.

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Caloric restriction that promotes weight loss is an effective strategy for treating non-alcoholic fatty liver disease and improving insulin sensitivity in people with type 2 diabetes. Despite its effectiveness, in most individuals, weight loss is usually not maintained partly due to physiological adaptations that suppress energy expenditure, a process known as adaptive thermogenesis, the mechanistic underpinnings of which are unclear. Treatment of rodents fed a high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycaemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake.

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Skeletal muscle disuse reduces muscle protein synthesis rates and induces atrophy, events associated with decreased mitochondrial respiration and increased reactive oxygen species. Given that dietary nitrate can improve mitochondrial bioenergetics, we examined whether nitrate supplementation attenuates disuse-induced impairments in mitochondrial function and muscle protein synthesis rates. Female C57Bl/6N mice were subjected to single-limb casting (3 or 7 days) and consumed drinking water with or without 1 mM sodium nitrate.

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While impairments in peripheral tissue insulin signalling have a well-characterized role in the development of insulin resistance and type 2 diabetes (T2D), the specific mechanisms that contribute to these impairments remain debatable. Nonetheless, a prominent hypothesis implicates the presence of a high-lipid environment, resulting in both reactive lipid accumulation and increased mitochondrial reactive oxygen species (ROS) production in the induction of peripheral tissue insulin resistance. While the etiology of insulin resistance in a high lipid environment is rapid and well documented, physical inactivity promotes insulin resistance in the absence of redox stress/lipid-mediated mechanisms, suggesting alternative mechanisms-of-action.

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Previous research supports that low-load resistance exercise with blood flow restriction (LL-BFR) acutely increases physiological responses and muscle mass accrual compared with low-load resistance exercise (LL-RE) alone. However, most studies have work-matched LL-BFR and LL-RE. Completing sets to similar perceived efforts, thereby allowing for a variable amount of work, may provide a more ecologically valid approach to compare LL-BFR and LL-RE.

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Unlabelled: Impaired heart function can develop in individuals with diabetes in the absence of coronary artery disease or hypertension, suggesting mechanisms beyond hypertension/increased afterload contribute to diabetic cardiomyopathy. Identifying therapeutic approaches that improve glycemia and prevent cardiovascular disease are clearly required for clinical management of diabetes-related comorbidities. Since intestinal bacteria are important for metabolism of nitrate, we examined whether dietary nitrate and fecal microbial transplantation (FMT) from nitrate-fed mice could prevent high-fat diet (HFD)-induced cardiac abnormalities.

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Independent supplementation with nitrate (NIT) and resveratrol (RSV) enriches various aspects of mitochondrial biology in key metabolic tissues. Although RSV is known to activate Sirt1 and initiate mitochondrial biogenesis, the metabolic benefits elicited by dietary nitrate appear to be dependent on 5'-adenosine monophosphate-activated protein kinase (AMPK)-mediated signaling events, a process also linked to the activation of Sirt1. Although the benefits of individual supplementation with these compounds have been characterized, it is unknown if co-supplementation may produce superior metabolic adaptations.

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Within brown adipose tissue (BAT), the brain isoform of creatine kinase (CKB) has been proposed to regulate the regeneration of ADP and phosphocreatine in a futile creatine cycle (FCC) that stimulates energy expenditure. However, the presence of FCC, and the specific creatine kinase isoforms regulating this theoretical model within white adipose tissue (WAT), remains to be fully elucidated. In the present study, creatine did not stimulate respiration in cultured adipocytes, isolated mitochondria or mouse permeabilized WAT.

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Rapid oscillations in cytosolic calcium (Ca) coordinate muscle contraction, relaxation, and physical movement. Intriguingly, dietary nitrate decreases ATP cost of contraction, increases force production, and increases cytosolic Ca, which would seemingly necessitate a greater demand for sarcoplasmic reticulum Ca ATPase (SERCA) to sequester Ca within the sarcoplasmic reticulum (SR) during relaxation. As SERCA is highly regulated, we aimed to determine the effect of 7-day nitrate supplementation (1 mM via drinking water) on SERCA enzymatic properties and the functional interaction between SERCA and mitochondrial oxidative phosphorylation.

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Intestinal homeostasis is highly dependent on optimal epithelial barrier function and permeability. Intestinal epithelial cells (IEC) regulate these properties acting as cellular gatekeepers by selectively absorbing nutrients and controlling the passage of luminal bacteria. These functions are energy demanding processes that are presumably met through mitochondrial-based processes.

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Dietary nitrate supplementation, and the subsequent serial reduction to nitric oxide, has been shown to improve glucose homeostasis in several pre-clinical models of obesity and insulin resistance. While the mechanisms remain poorly defined, the beneficial effects of nitrate appear to be partially dependent on AMPK-mediated signaling events, a central regulator of metabolism and mitochondrial bioenergetics. Since AMPK can activate SIRT1, we aimed to determine if nitrate supplementation (4 mM sodium nitrate via drinking water) improved skeletal muscle mitochondrial bioenergetics and acetylation status in mice fed a high-fat diet (HFD: 60% fat).

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Increased digitisation of day-to-day activities was occurring prior to the COVID-19 pandemic. The pandemic only accelerated the virtual shift, making web accessibility an urgent issue, especially for marginalised populations. Despite decades of work to develop, refine, and implement web accessibility standards, people with cognitive disabilities regularly experience many barriers to web accessibility.

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We aimed to determine the combined effects of overexpressing plasma membrane fatty acid binding protein (FABPpm) and fatty acid translocase (CD36) on skeletal muscle fatty acid transport to establish if these transport proteins function collaboratively. Electrotransfection with either FABPpm or CD36 increased their protein content at the plasma membrane (+75% and +64%), increased fatty acid transport rates by +24% for FABPpm and +62% for CD36, resulting in a calculated transport efficiency of ∼0.019 and ∼0.

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