Metabolic Rate Research Articles

Effect of hypoxia and acidification on metabolic rate of Ponto-Caspian gobies and their native competitors in the context of climate change

Effect of hypoxia and acidification on metabolic rate of Ponto-Caspian gobies and their native competitors in the context of climate change

Resting Metabolic Rate and Recovery From Sport-Related Concussion: A Critically Appraised Topic.

Critical appraisal of whole-body metabolism as a measure of concussion recovery is lacking in the available evidence. There has been extensive exploration of options for a gold standard assessment for concussion, including blood biomarkers, electroencephalogram, and neuroimaging, but none have yet to demonstrate good empirical evidence of efficacy. In patients with sport-related concussion (SRC), can resting metabolic rate (RMR), as measured through indirect calorimetry, be used as a physiologic assessment of recovery? Three studies demonstrated relevance to the clinical question. Of the selected studies, 2 studies were case-control, and 1 was a case series. All studies observed reduced total energy expenditure and increased energy balance when initially assessed between 24 and 72hours after injury. Evidence exists to suggest that RMR as measured with indirect calorimetry is a poor indicator of SRC recovery. All 3 articles found that RMR was not affected by SRC, even when compared with healthy controls. One article did observe a between sex difference in RMR, but a very small sample size was included in the case series. The findings of this critically appraised topic suggest a strength of recommendation of grade B, demonstrating that RMR is a poor indicator of recovery from SRC.

Barriers and enablers to measuring resting metabolic rate in the high-performance sporting system: A qualitative exploratory study

ABSTRACT Measurements of resting metabolic rate (RMR) may be undertaken for dietary planning purposes or to assess for low energy availability (LEA). This study investigated barriers and enablers to measuring RMR in real-world, high-performance sport environments. Twelve interviews were conducted with technicians (n = 6 dietitians, n = 6 physiologists) employed across six National Institute Networks, two National Sporting Organisations and one professional sporting code. RMR was predominantly measured to screen for LEA with measurements only occurring in a few instances for dietary planning purposes. Data was thematically analysed with six main themes identified. Barriers included lack of confidence in measuring RMR, burden of measurement on athlete and technician, confusion over measurement responsibility, and scepticism in RMR measurements as an indicator of LEA. Subthemes that contributed to scepticism included: the RMR thresholds used to indicate LEA, unanswered research questions, and measurement errors introduced by athlete presentation, testing equipment and/or environment. Enablers to use of RMR measurements included perceived value of RMR measurements as a ‘piece of the puzzle’ when assessing for LEA and its use as a longitudinal measure. Best practice guidelines for RMR measurements in athletic cohorts must consider these barriers and enablers as they highlight unique characteristics of athletes and their environment.

Role of neuropeptide Y in development of valproate-induced eating behaviour disorder

Background. Eating behaviour disorder (EBD) induced by valproic acid (VPA) is one of the components of the pathogenesis of a serious complication of therapy with VPA and its salts such as VPA-induced metabolic syndrome (MetS). About 20% of patients receiving VPA have weight gain, which is also a consequence of altered eating behaviour in such patients. Substances such as neuropeptide Y (NPY), leptin, orexin and ghrelin are involved in the regulation of eating behaviour. NPY has received special attention in recent years because it is one of the most potent brain orexigenic peptides and its expression level directly affects the quantity and quality of food intake. NPY overexpression is associated with EBD, food preferences, obesity, and MetS.Objective: to review preclinical and clinical studies of NPY role as a potential sensitive and specific serum biomarker of VPA-EBD, secondary weight gain and VPA-MetS development in children and adults with epilepsy.Material and methods. We analyzed Russian and foreign publications submitted to eLibrary, PubMed/MEDLINE, Scopus, and Google Scholar databases between 2014 and 2024. The full-text articles in Russian and English (original studies, systematic reviews, meta-analyses, Cochrane reviews, and clinical cases) were analyzed. After the selection procedure, 53 out of 1105 publications retrieved by query keywords were included in the analysis.Results. VPA-EDB refers to multifactorial diseases, requiring to take into account the additive contribution of external (food education, eating habits of the patient and family members) and internal (key hormones and neuropeptides regulating appetite and food preferences, the dose and duration of VPA intake, the metabolic rate of VPA) factors while assessing a risk of its development. NPY-associated VPA-EDB affects dietary preferences in favor of high-calorie food and beverages, increases the frequency of meals, the risks of insulin resistance, hyperglycemia as one of the major domains in MetS pathogenesis.Conclusion. VPA-EBD requires timely diagnosis, as it can cause VPA-MetS. NPY is an important biomarker of VPA-EBD, because recent studies have convincingly demonstrated that this neuropeptide is involved in the regulation of eating behavior in patients with epilepsy.

Rapeseed Supports Hairy Vetch in Intercropping, Enhancing Root and Stem Morphology, Nitrogen Metabolism, Photosynthesis, and Forage Yield

The global shortage of high-quality forage has significantly constrained the development of animal husbandry. Leveraging the complementary effects of forage rapeseed and hairy vetch intercropping can enhance forage yield and quality; however, the underlying mechanisms of overyielding in forage rapeseed–hairy vetch intercropping systems remain unclear. Over two years of field experiments, three cropping systems—rapeseed sole cropping, hairy vetch sole cropping, and rapeseed–hairy vetch intercropping—were investigated to assess the effects of intercropping on root and stem morphology, canopy light distribution, leaf photosynthetic physiology, and nitrogen metabolism. Our results demonstrated that intercropping increased forage biomass and crude protein yield by 14.3–20.0% and 30.7–92.8%, respectively, compared to sole cropping. Intercropping significantly enhanced root biomass, increasing lateral root biomass by 81% compared to rapeseed sole cropping. It also improved stem anatomical traits, including the cortex area (58.8–80.7%), cortex thickness (25.1–38.3%), number of vascular bundles (18.0–37.3%), vascular bundle length (17.8–18.4%), vascular bundle perimeter (6.7–18.7%), vascular bundle area (34.6–63.9%), and stem breaking strength (25.7–76.6%). Additionally, intercropping optimized vertical canopy light interception, reduced the activity of antioxidant enzymes (CAT, POD, SOD) and reactive oxygen species (ROS) accumulation, and enhanced the activities of glutamine synthetase and nitrate reductase, stomatal traits, and photosynthetic rates in the leaves of both crops. Structural equation modeling revealed that, in the intercropping system, improved population lodging resistance directly promoted nitrogen metabolism and leaf photosynthetic rates, ultimately increasing population biomass. In summary, rapeseed–hairy vetch intercropping improved canopy light distribution, strengthened rapeseed stem anatomy and root penetration, and enhanced population lodging resistance, leaf photosynthetic physiology, and nitrogen metabolism, thereby boosting forage biomass and quality. The supportive role of rapeseed in the intercropping system elucidates the overyielding mechanisms of rapeseed–hairy vetch intercropping, offering a theoretical framework for optimizing forage production systems worldwide.

Bergmeyer Glucose Quantification for Microbiological Samples.

The glucose concentration is a key indicator of cellular metabolism and could indicate the total metabolism rate, an aberration in glucose metabolism, and, in some cases, how cells couple glucose metabolism to energetic metabolism. In addition, intracellular and extracellular glucose levels are indicative of the cellular metabolic status. Enzymatic techniques, such as Bergmeyer glucose quantification, are more accurate and sensitive than other techniques, such as dinitrosalicylic acid or fluorescence methods, which are usually utilized in microbiology. Although mainly used in the clinical area, Bergmeyer glucose quantification can also be applied to any cell but has not been reported in detail for bacteria, fungi, yeasts, or other microorganisms. Herein, we present a methodology to quantify glucose from bacteria and yeast samples using the enzymatic Bergmeyer glucose quantification method. The procedure involved the enzymes glucose oxidase, peroxidase, and o-dianisidine dihydrochloride incubated at 37 °C for 20 min, followed by the addition of sulfuric acid. The absorbance is then measured at 545 nm. It is important to highlight that although this technique presents difficulties in measuring high concentrations of glucose (above 60 g/L), it is possible to measure concentrations below 50 g/L using dilution factors. This enzymatic approach is valuable for research and analysis in microbiology and other scientific areas. The precision and sensitivity of the method make it helpful for detecting even low concentrations of glucose in microbiological samples.

Chronic high fat diet-induced cerebrovascular remodeling impairs recovery of blood flow after cerebral ischemia in mice.

Obesity and associated metabolic disturbances worsen brain ischemia outcome. High fat diet (HFD)-fed mice are obese and have cerebrovascular remodeling and worsened brain ischemia outcome. We determined whether HFD-induced cerebrovascular remodeling impaired reperfusion to the ischemic penumbra. Six-week-old C57BL/6J or matrix metalloprotease-9 knockout (MMP-9-/-) mice were on HFD or regular diet (RD) for 12 to 14 months before a 60-min left middle cerebral arterial occlusion (MCAO). Photoacoustic microscopy was performed at left cerebral frontal cortex. HFD increased cerebrovascular density and tortuosity in C57BL/6J mice but not in MMP-9-/- mice. Blood flow to the ischemic penumbra slowly recovered but did not reach the baseline 2 h after MCAO in RD-fed mice. Oxygen extraction fraction was increased to maintain cerebral metabolic rate of oxygen (CMRO2) throughout brain ischemia and reperfusion period. This blood flow recovery was worsened in HFD-fed mice, leading to decreased CMRO2. MMP-9-/- attenuated these HFD effects. HFD increased MMP-9 activity and interleukin 1β. Pyrrolidine dithiocarbamate, an anti-inflammatory agent, abolished the HFD effects. Interleukin 1β increased MMP-9 activity. In summary, HFD induces cerebrovascular remodeling, leading to worsened recovery of blood supply to the ischemic penumbra to contribute to poor outcome after brain ischemia. Neuroinflammation may activate MMP-9 in HFD-fed mice.

Metabolic Performance of Mealworms and Black Soldier Fly Larvae Reared on Food and Agricultural Waste and By-Products.

Mealworms and black soldier fly (BSF) larvae are two of the most reared insects at an industrial scale. Both may feed on by-products from agricultural and food industries. Feed efficiency is one of the most important aspects of such processes and varies between species and feed substrates and depends on the metabolic performance of the larvae. Compared to each other, both species may hold advantageous capabilities affecting their feed efficiency, likely depending on the feed substrate. We reared mealworms and BSF larvae on a diverse selection of by-products from agricultural and food industries, quantified major metabolic rates across their life spans, and compared their performances. The type of feed substrates had stronger effects on the growth of mealworms than on black soldier fly larvae. Generally, BSF larvae were advantageous in terms of the highest maximal specific growth rate (0.50-0.77 day-1) and feed assimilation rate (0.81-1.16 day-1) and shortest development period (23-25 days) but disadvantageous in terms of metabolic maintenance cost (0.07-0.21 day-1). In mealworms, the maximal specific growth rates were 0.02-0.11 day-1, the highest feed assimilation rates were 0.16-0.37 day-1, and the development period was at least 65-93 days, while maintenance was only 0.02-0.05 day-1. In contrast to the BSF larvae, the specific maintenance rate was weight dependent in the mealworms and lowest in the largest individuals. The combined outcome of these metabolic rates resulted in an average carbon net growth efficiency, NGE*avg of 0.16-0.40 in mealworms and 0.33-0.56 in BSF larvae across their life span. It thus seems that BSF larvae are more versatile and somewhat more efficient at converting diverse feed substrates into growth than mealworms. Differences in NGE*avg affected the substrate conversion efficiencies (i.e., the ratio of the weight gain of the larvae to the reduced weight of feed substrates) and may thus impact the overall outcome of insect farming.

Predaceous and Phytophagous Pentatomidae Insects Exhibit Contrasting Susceptibilities to Imidacloprid.

Imidacloprid, a widely used neonicotinoid insecticide, targets insect pests but also affects natural enemies. However, the effects of neonicotinoid insecticides on closely related insects remain unclear. We evaluated the harmful effects of imidacloprid on the phytophagous Halyomorpha halys and predaceous Arma chinensis. Bioassays revealed that imidacloprid was more toxic to H. halys than to A. chinensis and more harmful to the males than to the females of the two insects. A. chinensis adults recovered from imidacloprid-induced knockdown, as evidenced by restored respiratory rates, metabolic rates, and locomotion. Surviving A. chinensis showed reduced fecundity, suggesting a trade-off between detoxification and reproduction. Bioinformatics analysis of nicotinic acetylcholine receptors (nAChRs) and molecular docking simulations indicated a lower diversity of the nAChR gene family in A. chinensis than in H. halys, with weaker binding to imidacloprid, consistent with the relatively low toxicity of the insecticide in this species. This might account for the susceptibility differences to imidacloprid between the species. These findings underscore the efficacy of imidacloprid against H. halys and provide insights into the toxicities of neonicotinoids to target and non-target insects.

Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to the benzimidazole (BZ) drug class is nearly ubiquitous in many species and is associated with mutations in beta-tubulin genes. However, mutations in beta-tubulin alone do not fully explain all BZ resistance. We performed a genome-wide association study using a genetically diverse panel of Caenorhabditis elegans strains to identify loci that contribute to resistance to the BZ drug thiabendazole (TBZ). We identified a quantitative trait locus (QTL) on chromosome V independent of all beta-tubulin genes and overlapping with two promising candidate genes, the cytochrome P450 gene cyp-35D1 and the nuclear hormone receptor nhr-176. Both genes were previously demonstrated to play a role in TBZ metabolism. NHR-176 binds TBZ and induces the expression of CYP-35D1, which metabolizes TBZ. We generated single gene deletions of cyp-35D1 and nhr-176 and found that both genes play a role in TBZ response. A predicted high-impact lysine-to-glutamate substitution at position 267 (K267E) in CYP-35D1 was identified in a sensitive strain, and reciprocal allele replacement strains in different genetic backgrounds were used to show that the lysine allele conferred increased TBZ resistance. Using competitive fitness assays, we found that neither allele was deleterious, but the lysine allele was selected in the presence of TBZ. Additionally, we found that the lysine allele significantly increased the rate of TBZ metabolism compared to the glutamate allele. Moreover, yeast expression assays showed that the lysine version of CYP-35D1 had twice the enzymatic activity of the glutamate allele. To connect our results to parasitic nematodes, we analyzed four Haemonchus contortus cytochrome P450 orthologs but did not find variation at the 267 position in fenbendazole-resistant populations. Overall, we confirmed that variation in this cytochrome P450 gene is the first locus independent of beta-tubulin to play a role in BZ resistance.

Ultrastructural Study and Immunohistochemical Characteristics of Mesencephalic Tegmentum in Juvenile Chum Salmon (Oncorhynchus keta) Brain After Acute Traumatic Injury.

The ultrastructural organization of the nuclei of the tegmental region in juvenile chum salmon (Oncorhynchus keta) was examined using transmission electron microscopy (TEM). The dorsal tegmental nuclei (DTN), the nucleus of fasciculus longitudinalis medialis (NFLM), and the nucleus of the oculomotor nerve (NIII) were studied. The ultrastructural examination provided detailed ultrastructural characteristics of neurons forming the tegmental nuclei and showed neuro-glial relationships in them. Neurons of three size types with a high metabolic rate, characterized by the presence of numerous mitochondria, polyribosomes, Golgi apparatus, and cytoplasmic inclusions (vacuoles, lipid droplets, and dense bodies), were distinguished. It was found that large interneurons of the NFLM formed contacts with protoplasmic astrocytes. Excitatory synaptic structures were identified in the tegmentum and their detailed characteristic are provided for the first time. Microglia-like cells were found in the NIII. The ultrastructural characteristics of neurogenic zones of the tegmentum of juvenile chum salmon were also determined for the first time. In the neurogenic zones of the tegmentum, adult-type neural stem progenitor cells (aNSPCs) corresponding to cells of types III and IVa Danio rerio. In the neurogenic zones of the tegmentum, neuroepithelial-like cells (NECs) corresponding to cells previously described from the zebrafish cerebellum were found and characterized. In the tegmentum of juvenile chum salmon, patterns of paracrine neurosecretion were observed and their ultrastructural characteristics were recorded. Patterns of apoptosis in large neurons of the tegmentum were examined by TEM. Using immunohistochemical (IHC) labeling of the brain lipid-binding protein (BLBP) and aromatase B (AroB), patterns of their expression in the tegmentum of intact animals and in the post-traumatic period after acute injury to the medulla oblongata were characterized. The response to brainstem injury in chum salmon was found to activate multiple signaling pathways, which significantly increases the BLBP and AroB expression in various regions of the tegmentum and valvula cerebelli. However, post-traumatic patterns of BLBP and AroB localizations are not the same. In addition to a general increase in BLBP expression in the tegmental parenchyma, BLBP overexpression was observed in the rostro-lateral tegmental neurogenic zone (RLTNZ), while AroB expression in the RLTNZ was completely absent. Another difference was the peripheral overexpression of AroB and the formation of dense reactive clusters in the ventro-medial zone of the tegmentum. Thus, in the post-traumatic period, various pathways were activated whose components were putative candidates for inducers of the "astrocyte-like" response in the juvenile chum salmon brain that are similar to those present in the mammalian brain. In this case, BLBP acted as a factor enhancing the differentiation of both radial glia and neurons. Estradiol from AroB+ astrocytes exerted paracrine neuroprotective effects through the potential inhibition of inflammatory processes. These results indicate a new role for neuronal aromatization as a mechanism preventing the development of neuroinflammation. Moreover, our findings support the hypothesis that BLBP is a factor enhancing neuronal and glial differentiation in the post-traumatic period in the chum salmon brain.

Effects of Short-Term Low Energy Availability on Metabolism and Performance-Related Parameters in Physically Active Adults.

Low energy availability (LEA) can cause impaired reproductive function, bone health issues, and suppressed immune function, and may result in decreased performance and overall health status. The purpose of this study was to investigate adaptions of body composition, blood status, resting metabolic rate, and endurance performance to gain more comprehensive insights into the symptoms of LEA and the adaptive effects in the athlete population (active women (n = 11) and men (n = 11)). Three treatments were defined as 45 (EA45, control), 30 (EA30), and 10 (EA10) kcal/kg FFM/day and randomly assigned. Pre- and post-intervention measurements were performed through blood sampling, bioelectrical impedance analysis, resting metabolic rate measurement, the oral glucose tolerance test (OGTT), and the incremental endurance test to exhaustion. There was a significant reduction in body weight and fat mass in EA10 compared to EA45 (p ≤ 0.05). Blood serum levels were altered in triglyceride, uric acid, and creatinine concentrations in EA10 compared to EA45 (p ≤ 0.05). Furthermore, blood glucose was still accumulated after 120 min during OGTT in EA10 compared to EA45 (p ≤ 0.05). The respiratory exchange ratio was reduced during submaximal stages of the incremental treadmill test to exhaustion without influencing performance output after treatment EA10 (p ≤ 0.05). However, the resting metabolic rate did not change (p > 0.05). In conclusion, this short-term study indicates that energy restriction can lead to several metabolic-related adaptations, which suggests that the availability and regulation of glucose and fats are significantly influenced after only five days of LEA in physically active women and men. Future research should focus on longer exposures of LEA and sex-specific comparisons (including the menstrual cycle) on LEA symptoms.

Common Variants in PLXNA4 and Correlation to Neuroimaging Phenotypes in Healthy, Mild Cognitive Impairment, and Alzheimer's Disease Cohorts.

A comprehensive genome-wide association study (GWAS) has validated the identification of the Plexin-A 4 (PLXNA4) gene as a novel susceptibility factor for Alzheimer's disease (AD). Nonetheless, the precise role of PLXNA4 gene polymorphisms in the pathophysiology of AD remains to be established. Consequently, this study is aimed at exploring the relationship between PLXNA4 gene polymorphisms and neuroimaging phenotypes intimately linked to AD. This study encompassed 812 subjects with PLXNA4 genotype data, procured from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Employing a tagging strategy, we identified five common variant sites within the PLXNA4 gene and assessed their associations with glucose metabolism, atrophy in AD-related brain regions (including the medial temporal lobe, hippocampus, and parahippocampal gyrus), and intracerebral Aβ deposition. We conducted a comprehensive analysis using a multiple linear regression model, with neuroimaging phenotypes as the dependent variable and PLXNA4 gene polymorphisms as the independent variable while incorporating APOE e4 carrier status, education level, age, and gender as covariates. The subjects were stratified into three groups based on their disease status: the Alzheimer's disease (AD) group, the mild cognitive impairment (MCI) group, and the cognitively normal healthy control (CN) group. Within each group, we examined the associations between PLXNA4 gene polymorphisms and various neuroimaging phenotypes. Our study identified significant associations between the rs156676-A and rs78036292-G alleles and the baseline volumes of the anterior cingulate and middle temporal gyrus, respectively, across the entire population. After 1year of follow-up, a significant correlation was observed between the rs6467431-G allele and accelerated volumetric atrophy of the parahippocampal gyrus in the overall population. Additionally, at the 2-year follow-up, significant correlations were observed between three PLXNA4 loci (rs1863015, rs6467431, rs67468325) and volumetric atrophy in the anterior cingulate, middle temporal gyrus, and hippocampus across the entire population. Specifically, the rs1863015-G allele notably accelerated atrophy of the left middle temporal gyrus and bilateral hippocampus, whereas the A alleles of rs6467431 and rs67468325 markedly accelerated atrophy specifically in the bilateral hippocampus. Subgroup analysis further validated these findings. Additionally, in the baseline CN group, the rs78036292 allele showed a significant correlation with intracerebral Aβ deposition, while in the 2-year follow-up CN group, rs67468325 was significantly associated with alterations in glucose metabolism rates in the right cingulate gyrus. Our findings indicate that PLXNA4 genotypes may modulate the development of AD through their regulation of intracerebral Aβ deposition. Additionally, PLXNA4 genotypes are strongly associated with AD-related brain atrophy and glucose metabolism, suggesting that they may alter susceptibility to AD by modulating neurodegenerative biomarkers.

Seed pretreatment with cloquintocet-mexyl protects wheat seedlings from fomesafen injury by promoting photosynthesis and decreasing oxidative stress.

Fomesafen is a selective herbicide widely used to control post-emergent broad-leaf weeds in soybean and peanut fields. Because of its persistent nature in soil, it can suppress subsequent crops, including wheat. There is limited information focusing on methods of protecting wheat from fomesafen injury by soil residue. Bioassay results showed slight variations in tolerance to fomesafen among 31 wheat cultivars. Soil-applied biochar (200 g m-2) could alleviate fomesafen injury at 2 mg L-1, and partially alleviate fomesafen injury at 4 mg L-1. Seed soaking in safeners cloquintocet-mexyl and mefenpyr-diethyl was more effective in protecting seedlings from fomesafen injury at 4 mg L-1 compared with 1,8-naphthalic anhydride, fenclorim or dichlormid. Indoor tests suggested that the combined application of biochar and cloquintocet-mexyl or mefenpyr-diethyl had a synergistic alleviating effect on wheat injury caused by fomesafen, which was further confirmed in a field trial. Wheat seeds treated with cloquintocet-mexyl increased expression of the fomesafen target protoporphyrinogen IX oxidase and light-harvesting chlorophyll a/b binding protein, leading to an increase in chlorophyll content and a decrease in oxidative stress of wheat exposed to fomesafen. Cloquintocet-mexyl treatment had no influence on the expression of P450 genes, toxic transport genes, most glutathione S-transferase (GST) genes, the enzyme activity of P450 or GSTs, and the metabolism rate of fomesafen. These results suggested that cloquintocet-mexyl acted by increasing photosynthesis and decreasing oxidative stress to alleviate injury to wheat exposed to fomesafen stress, showing no influence on fomesafen metabolism in wheat. This study provided valuable information for fomesafen injury management in wheat. © 2025 Society of Chemical Industry.

Cerebral Metabolic Rate of Oxygen and Accelerometry-Based Fatigability in Community-Dwelling Older Adults.

Alterations in energy metabolism may drive fatigue in older age, but prior research primarily focused on skeletal muscle energetics without assessing other systems, and utilized self-reported measures of fatigue. We tested the association between energy metabolism in the brain and an objective measure of fatigability in the Study of Muscle, Mobility and Aging (N=119, age 76.8±4.0 years, 59.7% women). Total brain cerebral metabolic rate of oxygen (CMRO 2 ) was measured using arterial spin labeling and T 2 -relaxation under spin tagging MRI protocols. Accelerometry-based fatigability status during a fast-paced 400m walk was determined using the Pittsburgh Fatigability Index (PPFI, higher=worse). Confounders included skeletal muscle energetics, measured in vivo using spectroscopy and ex vivo using respirometry, cardiorespiratory fitness (VO 2 peak), weight, medication count, and multimorbidity. Multivariable logistic regression models were used to estimate the association (odds ratio (OR)) of CMRO 2 with PPFI>0 compared to the referent group PPFI=0. Models were first adjusted for age and sex, and further adjusted for confounders. In this sample, 41.2% had PPFI>0 (median 3.3% [0.4-8.0%]). CMRO 2 was positively associated with PPFI>0 (age and sex adjusted OR=1.61, 95% CI: 1.06, 2.45, p=0.03); adjustment for confounders attenuated the association. The positive association of brain energetics and fatigability warrants further study in older adults.

Circular mRNA Vaccine against SARS-COV-2 Variants Enabled by Degradable Lipid Nanoparticles.

The emergence of mRNA vaccines offers great promise and a potent platform in combating various diseases, notably COVID-19. Nevertheless, challenges such as inherent instability and potential side effects of current delivery systems underscore the critical need for the advancement of stable, safe, and efficacious mRNA vaccines. In this study, a robust mRNA vaccine (cmRNA-1130) eliciting potent immune activation has been developed from a biodegradable lipid with eight ester bonds in the branched tail (AX4) and synthetic circular mRNA (cmRNA) encoding the trimeric Delta receptor binding domain of the SARS-CoV-2 spike protein. Notably, the cmRNA-1130 vaccine exhibits outstanding stability, remaining effective after six months of storage at 4 °C and multiple freeze-thaw cycles. In comparison with the commercial MC3 lipid, the nanoparticles formed from the degradable AX4 lipid revealed a much faster metabolic rate from the liver and spleen, affording negligible impairment to the hepatorenal function. Following intramuscular administration, cmRNA-1130 generates robust and sustained neutralizing antibodies and induces the activation of Delta RBD-specific CD4+ and CD8+ T effector memory cells (TEM) and Th1-biased T cells in mice. Featured with potent immune activation, high stability, and decent safety, vaccines formed from cmRNA and AX4 hold a huge clinical potential for the prophylaxis and treatment of different diseases.

Locally Adapted Coral Species Withstand a 2-Week Hypoxic Event

One approach to improve long-term coral restoration success utilizes naturally stress-tolerant corals from the wild. While the focus has primarily been on thermal stress, low oxygen is a growing threat to coral reefs and restoration efforts should also consider hypoxia tolerance. Here we determine if Siderastrea siderea and Agaricia tenuifolia populations from a reef with a historical record of low oxygen exhibit evidence of local adaptation to hypoxic events, compared to populations from a reference reef. We employed a laboratory-based reciprocal transplant experiment mimicking a severe 14-night hypoxic event and monitored bleaching responses, photo-physiology, metabolic rates, and survival of all four populations during, and for two weeks following the event. In both species, we found the populations from the hypoxic reef either fully persisted or recovered within 3 days of the event. In contrast, the conspecific naïve populations from the well-oxygenated reference reef experienced bleaching and death. This showcases the vulnerability of naïve corals exposed to low oxygen but also suggests that corals from the hypoxic reef locally adapted to survive severe episodic hypoxia. Other reefs with past episodic low oxygen may also be home to corals with adaptation signatures to hypoxia and may be useful for restoration efforts.

Development of the Approaches Using Otolith Carbon and Oxygen Isotopes to Reconstruct Metabolic Histories and Experienced Temperatures of Juvenile Chum Salmon

To better understand the intrinsic and extrinsic factors that contribute to the high mortality of juvenile chum salmon Oncorhynchus keta during primary ocean migration, this study developed approaches using otolith carbon and oxygen isotopes to reconstruct their metabolic histories and experienced temperatures. Given that carbon in the otolith aragonite calcium carbonate is composed of metabolically derived carbon released from food respiration and dissolved inorganic carbon (DIC) in ambient water, and that the carbon in fish blood physiologically regulate blood pH to an optimum state, the relative contribution of metabolically derived carbon in otoliths can therefore reflect fish metabolic rates, relating to their physiological conditions. Since the metabolism-derived carbon is isotopically distinct from DIC (> 15‰ lower than DIC; Solomon et al. 2006), otolith carbon isotopes (δ13Cotolith) theoretically vary with fish metabolic activities and have been shown to be a useful metabolic indicator (Chung et al. 2019; Martino et al. 2020). Oxygen isotopes in otoliths (δ18Ootolith) are believed to be precipitated in or near isotopic equilibrium, and the precipitation process is primarily influenced by temperature (Morrissett et al. 2023). The species-specific fractionation of δ18Ootolith with temperatures has also been determined in chum salmon (Gou et al. 2022), thus δ18Ootolith is available to reliably reconstruct the experienced temperatures of juvenile chum salmon during primary migration.

Glutamine metabolism is systemically different between primary and induced pluripotent stem cell-derived brain microvascular endothelial cells.

Human primary (hpBMEC) and induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial-like cells (hiBMEC) are interchangeably used in blood-brain barrier models to study neurological diseases and drug delivery. Both hpBMEC and hiBMEC use glutamine as a source of carbon and nitrogen to produce metabolites and build proteins essential to cell function and communication. We used metabolomic, transcriptomic, and computational methods to examine how hpBMEC and hiBMEC metabolize glutamine, which may impact their utility in modeling the blood-brain barrier. We found that glutamine metabolism was systemically different between the two cell types. hpBMEC had a higher metabolic rate and produced more glutamate and GABA, while hiBMEC rerouted glutamine to produce more glutathione, fatty acids, and asparagine. Higher glutathione production in hiBMEC correlated with higher oxidative stress compared to hpBMEC. α-ketoglutarate (α-KG) supplementation increased glutamate secretion from hiBMEC to match that of hpBMEC; however, α-KG also decreased hiBMEC glycolytic rate. These fundamental metabolic differences between BMEC types may impact in vitro blood-brain barrier model function, particularly communication between BMEC and surrounding cells, and emphasize the importance of evaluating the metabolic impacts of iPSC-derived cells in disease models.

Season and Flow Drive Productivity of a Regulated River

Flow regimes of river ecosystems worldwide have undergone substantial changes because of water resource development, altering the way in which organic matter is generated and cycled throughout entire river catchments. Flow–ecology studies have focused on structural variables measured at small spatial scales. This creates a challenging mismatch when applying adaptive flow management for ecosystem functioning at a catchment or regional scale. Here, we sought to inform flow management by evaluating the drivers of ecosystem metabolism in a regulated river and assessing our ability to predict metabolism at unmonitored locations. We estimated rates of ecosystem metabolism from high-frequency monitoring of dissolved oxygen concentration at eight sites on the Lachlan River of Australia’s Murray–Darling Basin. We then applied a spatio-temporal stream network model to predict metabolism at unmonitored locations using only remotely sensed and gauging station predictor variables. Gross primary productivity (GPP) was higher at sites with lower mean annual discharge, and strong seasonal patterns in rates of productivity tended to be disrupted by rising flows. Similarly, ecosystem respiration (ER) was higher at sites with lower mean annual discharge and lower annual flow variation, but increased slightly in response to higher daily flows. Predictions at validation sites were generally accurate, albeit with substantial site-to-site variation. Our results suggest that flow changes may have altered metabolic rates from conditions prior to water abstraction and dam construction. These findings will assist in managing flows for ecosystem function outcomes and support extrapolation from monitored sites to the broad scales required for evaluating catchment-scale outcomes of river management.