Source Of Metabolic Energy Research Articles

Rapid colonization of a space‐returned Ryugu sample by terrestrial microorganisms

AbstractThe presence of microorganisms within meteorites has been used as evidence for extraterrestrial life, however, the potential for terrestrial contamination makes their interpretation highly controversial. Here, we report the discovery of rods and filaments of organic matter, which are interpreted as filamentous microorganisms, on a space‐returned sample from 162173 Ryugu recovered by the Hayabusa 2 mission. The observed carbonaceous filaments have sizes and morphologies consistent with microorganisms and are spatially associated with indigenous organic matter. The abundance of filaments changed with time and suggests the growth and decline of a prokaryote population with a generation time of 5.2 days. The population statistics indicate an extant microbial community originating through terrestrial contamination. The discovery emphasizes that terrestrial biota can rapidly colonize extraterrestrial specimens even given contamination control precautions. The colonization of a space‐returned sample emphasizes that extraterrestrial organic matter can provide a suitable source of metabolic energy for heterotrophic organisms on Earth and other planets.

Biodegradation potentials of soil-borne fungal cultures grown on haloxyfop R methyl ester herbicide medium

The heterotrophic and haloxyfop-R methyl ester utilizing fungal counts associated with two top soil samples was determined. Five (5) fungal isolates; Aspergillus niger, Candida sp., Trichoderma sp., Fusarium sp., and Alternaria sp. Were cultured from the soil samples using serial dilution as well as pour plate techniques. These isolates were sub-cultured and screened for their ability to use haloxyfop-R methyl ester as sole source of metabolic energy as well as using the turbidimeteric method. Two of the screened fungal isolates which exhibited maximal optical density (OD) difference values; A. niger and Fusarium sp. Were selected and utilized for the subsequent degradation/shake flask experiment. Growth profile parameters which included; pH, OD, dissolved CO2 and weighed dry fungal biomass were determined during the growth profiling test at a 96 hour interval for 16 days using appropriate methods and equipment. Mean soil pH values were 5.08 ± 0.02 and 4.62 ± 0.02 for samples A and B. The mean total heterotrophic fungal count was 8.7×10³ cfu/g ± 1.5 for A and 1.6 × 10⁴ cfu/g ±1.0 for B. The mean pH value observed for A. niger in the course of the growth profile test ranged from 6.0 ± 8.7 to 7.3 ± 8.0 and 7.3 ± 5.8. The mean OD values observed for A. niger and Fusarium sp. In the course of the shake flask experiment varied from 0.66 ± 7.1 to 1.96 ± 4.5 and 1.62 ± 5.4 to1.99 ± 3.6 respectively. With reference to the detection of mean dissolved CO2 values, utilized as an indirect indicator of herbicide mineralization, the axenic cultured A. niger was the most effective amongst the growth profile fungal cultures.

Circulating ketone bodies, genetic susceptibility, with left atrial structure, function and atrial fibrillation: A prospective study from the UK Biobank

BackgroundKetone bodies (KBs) are an important cardiac metabolic energy source. Metabolic remodeling has recently been found to play an important role in the pathological process of atrial fibrillation (AF). ObjectiveThe purpose of this study was to evaluate the associations of circulating KB levels with incident AF risk in the general population. MethodsWe studied 237,163 participants (mean age 56.5 ± 8.1 years; 55% women) from the UK Biobank who were free of AF at baseline and had data on circulating β-hydroxybutyrate (β-OHB), acetoacetate, and acetone. The associations of KB with new-onset AF were evaluated using Cox regression in the general population and across the 3 genetic risk groups: low, moderate, and high polygenic risk score of AF. ResultsDuring a median follow-up of 14.8 years, 16,638 participants (7.0%) developed AF. There was a U-shaped association of total KB and β-OHB with incident AF, with nadirs at 60.6 and 40.8 μmol/L, respectively (Pnonlinear < .05), whereas there was a positive association of acetoacetate and acetone with AF (Poverall < .001; Pnonlinear > .05). Consistently, there was a U-shaped association of total KB and β-OHB with left atrial (LA) volume parameters, including LA maximum volume, LA minimum volume, and their body surface area–indexed counterparts, and there was an inverted U-shaped association of total KB with LA ejection fraction (Pnonlinear < .05 for all). The association of KB with AF was stronger in individuals with low genetic risk (Pinteraction < .05), while the highest AF risk was in those with high genetic risk with high KB levels. Significant mediation effects of inflammatory markers on the associations between KB and AF were identified. ConclusionThere was a U-shaped association of circulating total KB and β-OHB with incident AF as well as a positive association of acetoacetate and acetone levels with AF risk in the general population.

The ultrastructure of peroxisomes in the kidney of the camel (Camelus dromedarius).

Dromedary camels can survive and reproduce in desert areas. The unique anatomical structure of the kidney enables the camel to prevent water loss. The present study aimed to investigate the ultrastructure of the peroxisomes in the normal kidney of the adult dromedary camel. Tissue samples were taken from the cortex and outer medulla of the kidney of eight camels. The samples were then processed for histological and ultrastructural investigations. The epithelial cells of the proximal tubules displayed peroxisomes with varying sizes and shapes. The peroxisomes were observed in either dispersed or clustered arrangement. Each peroxisome exhibited a homogenous matrix enveloped by a single membrane. Several peroxisomes exhibited one or more dark marginal plates that were always strongly associated with the smooth endoplasmic reticulum. The intensity of the peroxisomal matrix differed significantly, either within the same cell or across different cells. The intensity was light or dark, with a few peroxisomes presenting a similar intensity to that of the mitochondria. Some peroxisomes contained nucleoids within their matrix. The peroxisomes in the first and second sections of proximal convoluted tubules were scattered and primarily located in the region between the microvilli and the underlying mitochondria. The peroxisomes in the third region were abundant and frequently aggregated in clusters throughout the cytoplasm. In the fourth region, the number of peroxisomes was low. The proximal straight tubule had a limited quantity of peroxisomes. In conclusion, peroxisomes in the proximal tubule in kidney of normal dromedary camel were similar in shape and size to other mammals; however, heterogeneity exists as a result of differences in species-specific peroxisomal proteins. Peroxisomes are suggested to be a major source of metabolic energy and act as hydrogen peroxide (H2O2) scavengers, resulting in the release of water and oxygen.

Abstract We008: Hallmark Maturation of the Human Pluripotent Stem Cells-derived Cardiovascular Progenitors in Myocardial Infarcted Large Animal Model

For the goal of regenerative cardiology, cellular therapy may be used to restore injured heart muscle. The molecular mechanisms behind the engraftment and maturation of these transplanted cells, however, remain poorly understood. Thus, to obtain a comprehensive understanding of the complex transcriptional landscapes within their transplanted spatial context, we utilized spatial transcriptomics in this study. We have previously demonstrated the safety and effectiveness of transplanting our cardiovascular progenitors (CVPs) produced from laminin-221 into pig hearts that had suffered myocardial infarction (MI). Here, we undertake 10x spatial transcriptomics in chronic MI pig models at 1-, 4-, and 12 weeks post-transplantation to further our understanding of these cells in vivo. With confidence, we can distinguish between the transcripts from the pigs and the humans in the infarcted region. By using human-specific anti-Ku80 antibodies for immunohistochemical labeling of the pig tissue samples, this in silico prediction was verified. The CVPs' engraftment and longevity in the infracted region were shown by the long-term identification and staining of human cells at various time points. It is interesting to note that after 12 weeks, ribosomal and mitochondrial activity were higher than at 1 and 2 weeks. These results are consistent with the hallmarks of cardiac maturation, in which cells transit from immature fetal-like cells to mature cardiomyocytes (CMs) by switching their metabolic energy source from glucose to fatty acids. Also, by comparing the heart-specific genes, including MYH6 and MYH7, we were able to quantify the myosin isoform switches in the xenograft over time. Furthermore, to delineate the fate of the transplanted cells, we performed a ligand-receptor interaction analysis. Intriguing, we identified the midkine protein as a possible secreted human paracrine factor that enhances angiogenesis in the graft. In conclusion, we have shown the successful engraftment and maturation of human CVPs toward CMs using spatial transcriptomic technology. These data will be used to understand other aspects of regenerative cardiology such as the mechanism of VTs and in vivo cellular repair mechanisms. A shiny app atlas has been generated to share our transcriptomics data for all to explore gene expression of human transplanted cells in myocardial infarcted pig hearts.

Efficacy and Safety of Exogenous Ketones in People with Mild Neurocognitive Disorder and Alzheimer's Disease: A Systematic Literature Review.

Mild neurocognitive disorder (NCD), formally known as mild cognitive impairment, is usually the clinical stage preceding the development of Alzheimer's disease (AD), the most prevalent major NCD, and other causes of dementia. Glucose is a major source of energy for human brain metabolism and the uptake of glucose is reduced in patients with mild NCD, AD, and other NCDs. Unlike glucose, the uptake of ketones remains normal in people with mild NCD and AD, suggesting that the use of ketone bodies may compensate for glucose energy deficiency in patients with mild NCD and AD. The aim of this systematic review was to summarize the efficacy and safety of exogenic ketones, including medium chain triglycerides (MCTs), on cognitive function in patients with mild NCD and AD. The Embase, MEDLINE, MEDLINE In-Process, PubMed Ahead-of-Print, Cochrane Central Register of Controlled Trials, Europe PMC databases were searched from inception to April 2022. Studies reporting cognitive function efficacy and safety outcomes from randomized controlled trials of exogenic ketones in patients with mild NCD and AD were included. Data were extracted by 1 reviewer and checked by a second reviewer. Risk of bias was assessed using the Cochrane risk of bias tool, version 2. This review identified 13 individual trials investigating the efficacy and safety of MCT or coconut oil for patients with mild NCD or with AD. Because of the heterogeneity of the studies, a narrative synthesis was used. Overall, improvements associated with exogenic ketones were observed in multiple aspects of cognitive abilities, although the large heterogeneity between the included studies makes it difficult to draw firm conclusions from the current literature. Although some studies investigated the impact of the apolipoprotein E ε4 allele status on treatment efficacy, the current data are insufficient to conclude whether such an effect is present. PROSPERO registration No. CRD42022336664.

Phosphorus: Chronicles of the epistemology of a vital element.

It was in the philosopher's stone quest that the alchemist Hennig Brand isolated chemiluminescent white phosphorus (P), Greek for "light bearer", from urine in 1669. By 1771 phosphorus was isolated from bone, and in 1777 it was identified by Antoine Lavoisier as a highly reactive element that exists predominantly in nature as ionic phosphate (PO43-) and in solution as phosphoric acid (H3PO4). Early 20th century studies revealed phosphorylated biomolecules as essential components of replicative nuclear material (RNA, DNA), a metabolic source of energy (ATP), and structural components of cellular membrane (phospholipid bilayer). Life on earth began as organophosphates of a self-replicating RNA that evolved into DNA and acquired a membrane to form the original eukaryotes, which eventually joined to form multicellular organisms of the deep sea. Tissue mineralization during transition from the ocean to land generated the endoskeleton, the largest phosphorus stores of evolving vertebrates. Subsequent studies of phosphate homeostasis elucidated its complex regulatory system based on the interaction of the kidney, small intestine, bone, and parathyroid glands, orchestrated by hormones (PTH, calcitriol, FGF23, Klotho), and carried out by phosphate-specific transporters (SLC34 and SLC20 families) all to ensure adequate phosphate for survival and health. Paradoxically, kidney replacement therapy in the 1970s, by prolonging the lives of millions of individuals with kidney failure, revealed the hazards of phosphorus excess. "Phosphorus the light bearer" has become in the eyes of many nephrologists "Phosphorus the cardiovascular toxin".

Metabolic alterations and cellular responses to β-Hydroxybutyrate treatment in breast cancer cells

BackgroundThe ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells in vitro.MethodsUsing two cancer and one non-cancer breast cell line, we evaluate the effect of β-hydroxybutyrate (βHb) treatment on cell growth, survival, proliferation, colony formation, and migration. We also assess the effect of KB on metabolic profile of the cells. Using RNAseq analysis, we elucidate the effect of βHb on the gene expression profile.ResultsSignificant effects were observed following treatment by βHb which include effects on viability, proliferation, and colony formation of MCF7 cells, and different effects on colony formation of MDA-MB-231 cells, with no such effects on non-cancer HB2 cells. We found no changes in glucose intake or lactate output following βHb treatment as measured by LC-MS, but an increase in reactive oxygen species (ROS) level was detected. RNAseq analysis demonstrated significant changes in genes involved in lipid metabolism, cancer, and oxidative phosphorylation.ConclusionsBased on our results, we conclude that differential response of cancer cell lines to βHb treatment, as alternative energy source or signal to alter lipid metabolism and oncogenicity, supports the need for a personalized approach to breast cancer patient treatment.

Adipocytes and metabolism: Contributions to multiple myeloma

Obesity contributes to many cancers, including breast cancer and multiple myeloma, two cancers that often colonize the bone marrow (BM). Obesity often causes metabolic disease, but at the cellular level, there is uncertainty regarding how these shifts affect cellular phenotypes. Evidence is building that different types of fuel affect tumor cell metabolism, mitochondrial function, and signaling pathways differently, but tumor cells are also flexible and adapt to less-than ideal metabolic conditions, suggesting that single-pronged attacks on tumor metabolism may not be efficacious enough to be effective clinically. In this review, we describe the newest research at the pre-clinical level on how tumor metabolic pathways and energy sources affect cancer cells, with a special focus on multiple myeloma (MM). We also describe the known forward-feedback loops between bone marrow adipocytes (BMAds) and local tumor cells that support tumor growth. We describe how metabolic targets and transcription factors related to fatty acid (FA) oxidation, FA biosynthesis, glycolysis, oxidative phosphorylation (OXPHOS), and other pathways hold great promise as new vulnerabilities in myeloma cells. Specifically, we describe the importance of the acetyl-CoA synthetase (ACSS) and the acyl-CoA synthetase long chain (ACSL) families, which are both involved in FA metabolism. We also describe new data on the importance of lactate metabolism and lactate transporters in supporting the growth of tumor cells in a hypoxic BM microenvironment. We highlight new data showing the dependency of myeloma cells on the mitochondrial pyruvate carrier (MPC), which transports pyruvate to the mitochondria to fuel the tricarboxylic acid (TCA) cycle and electron transport chain (ETC), boosting OXPHOS. Inhibiting the MPC affects myeloma cell mitochondrial metabolism and growth, and synergizes with proteosome inhibitors in killing myeloma cells. We also describe how metabolic signaling pathways intersect established survival and proliferation pathways; for example, the fatty acid binding proteins (FABPs) affect MYC signaling and support growth, survival, and metabolism of myeloma cells. Our goal is to review the current the field so that novel, metabolic-focused therapeutic interventions and treatments can be imagined, developed and tested to decrease the burden of MM and related cancers.

Neuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion.

Glucose homeostasis is mainly under the control of the pancreatic islet hormones insulin and glucagon, which, respectively, stimulate glucose uptake and utilization by liver, fat, and muscle and glucose production by the liver. The balance between the secretions of these hormones is under the control of blood glucose concentrations. Indeed, pancreatic islet β-cells and α-cells can sense variations in glycemia and respond by an appropriate secretory response. However, the secretory activity of these cells is also under multiple additional metabolic, hormonal, and neuronal signals that combine to ensure the perfect control of glycemia over a lifetime. The central nervous system (CNS), which has an almost absolute requirement for glucose as a source of metabolic energy and thus a vital interest in ensuring that glycemic levels never fall below ∼5 mM, is equipped with populations of neurons responsive to changes in glucose concentrations. These neurons control pancreatic islet cell secretion activity in multiple ways: through both branches of the autonomic nervous system, through the hypothalamic-pituitary-adrenal axis, and by secreting vasopressin (AVP) in the blood at the level of the posterior pituitary. Here, we present the autonomic innervation of the pancreatic islets; the mechanisms of neuron activation by a rise or a fall in glucose concentration; how current viral tracing, chemogenetic, and optogenetic techniques allow integration of specific glucose sensing neurons in defined neuronal circuits that control endocrine pancreas function; and, finally, how genetic screens in mice can untangle the diversity of the hypothalamic mechanisms controlling the response to hypoglycemia.

Neural circuits of long-term thermoregulatory adaptations to cold temperatures and metabolic demands.

The mammalian brain controls heat generation and heat loss mechanisms that regulate body temperature and energy metabolism. Thermoeffectors include brown adipose tissue, cutaneous blood flow and skeletal muscle, and metabolic energy sources include white adipose tissue. Neural and metabolic pathways modulating the activity and functional plasticity of these mechanisms contributenot only to the optimization of function during acute challenges, such as ambient temperature changes, infection and stress, but also to longitudinal adaptations to environmental and internal changes. Exposure of humans to repeated and seasonal cold ambient conditions leads to adaptations in thermoeffectors such as habituation of cutaneous vasoconstriction and shivering. In animals that undergo hibernation and torpor, neurally regulated metabolic and thermoregulatory adaptations enable survival during periods of significant reduction in metabolic rate. In addition, changes in diet can activate accessory neural pathways that alter thermoeffector activity. This knowledge may be harnessed for therapeutic purposes, including treatments for obesity and improved means of therapeutic hypothermia.

Energy yields for acetylenotrophy on Enceladus and Titan

Saturn's moons Titan and Enceladus appear to satisfy three key criteria for life: presence of liquid water, nutrient availability, and metabolic energy sources. Consequently, these ocean worlds are the focus of astrobiology research investigations that aim to assess the potential for life beyond Earth. One plausible source of metabolic energy on these moons is acetylene (C2H2), a simple organic compound that is the second most abundant photochemical product in Titan's atmosphere and has been identified as a likely constituent of Enceladus' ocean. Acetylenotrophy, or the microbial fermentation of acetylene, is utilized by microbes on Earth in a number of environments. Here, we have calculated the energy yield of acetylenotrophy to be 69–78 kJ/mol C within the oceans of Titan and Enceladus, greater than the widely considered, hydrogenotrophic methanogenesis, at 25–65 kJ/mol C. Therefore, we propose acetylenotrophy as a potential metabolism on these moons that should be considered in future astrobiology studies on worlds with abundant acetylene.

The therapeutic potential of ketones in cardiometabolic disease: impact on heart and skeletal muscle.

β-Hydroxybutyrate (βOHB) is the major ketone in the body, and it is recognized as a metabolic energy source and an important signaling molecule. While ketone oxidation is essential in the brain during prolonged fasting/starvation, other organs such as skeletal muscle and the heart also use ketones as metabolic substrates. Additionally, βOHB-mediated molecular signaling events occur in heart and skeletal muscle cells, and via metabolism and/or signaling, ketones may contribute to optimal skeletal muscle health and cardiac function. Of importance, when the use of ketones for ATP production and/or as signaling molecules becomes disturbed in the presence of underlying obesity, type 2 diabetes, and/or cardiovascular diseases, these changes may contribute to cardiometabolic disease. As a result of these disturbances in cardiometabolic disease, multiple approaches have been used to elevate circulating ketones with the goal of optimizing either ketone metabolism or ketone-mediated signaling. These approaches have produced significant improvements in heart and skeletal muscle during cardiometabolic disease with a wide range of benefits that include improved metabolism, weight loss, better glycemic control, improved cardiac and vascular function, as well as reduced inflammation and oxidative stress. Herein, we present the evidence that indicates that ketone therapy could be used as an approach to help treat cardiometabolic diseases by targeting cardiac and skeletal muscles.

РЫЖИК ПОСЕВНОЙ В РАЦИОНЕ ДОЙНЫХ КОРОВ

Milk cows need high metabolic energy sources that are often to be found among plant crops with high fat content. This study featured Camelina sativa, an oilseed crop, as an energy supplement in the diet of lactating cows: 5 % thermally-treated C.sativa seeds were introduced into the grain feed mix. The experiment lasted 35 days and increased the total polyunsaturated fatty acids in milk fat by 1.1 % while the fat content in the milk increased by 0.35 %. The average daily milk yield increased by 3.7 %.

Variable Salinity and Hydrogen Production in Europa's Ocean

AbstractEuropa's long‐term habitability depends on thermodynamics—modulated by tidal evolution—and geochemical pathways that define chemical and energy inventories for use by putative biology. Hydrogen produced from the reaction of water and rock during serpentinization is one potential source of metabolic energy. Here, we demonstrate how thermally modulated volumetric changes to Europa's ice shell, ocean, and fluid‐accessible rocky mantle influence oceanic salinity and serpentinization rates in Europa's interior. During periods of steady cooling, hydrogen flux into the ocean remains relatively constant because of the continuous propagation of thermal cracking into the rocky mantle regardless of ocean composition. However, during periods of fluctuating heat production driven by changes in orbital eccentricity, modulation of the ice shell volume, and consequently the salinity and water activity of the ocean, alters the serpentinization rate. In parallel, the extent of fracturing within the seafloor varies, changing the volume of reactable rock available. Our results show that the stability of serpentinization reactions on Europa over time highly depends on the thermal‐orbital evolution and oceanic salt content. The variability in the hydrogen production rate is significant across potential orbital histories, varying by up to 15 orders of magnitude for the lowest salinity and most kosmotropic ocean conditions, such as dilute MgSO4 compositions. We also show that this variability decreases with increasing ocean salinity and more chaotropic compositions, such as a concentrated NaCl ocean. These results suggest new ways that ocean composition and water activity are essential to stable habitable conditions in ocean worlds.

Microbial Production of Biopolymer Polyhydroxybutyrate (PHB): Current Challenges and its Application

Plastics are suitable for many industrial applications as they are inexpensive, sturdy, resistant to deterioration and highly versatile. Asadvantageous as plastics made from petroleum are, it remains the most major topic of concern among environmentalists and the scientists. Polyhydroxyalkanoates are biodegradable polyesters produced by a wide range of microbes as a source of energy for metabolism, carbon, and oxidoreduction; since they exhibit some properties, which are remarkably similar to those of polyolefins derived from fossil fuels. he literature review conducted over the past decade reveals that polyhydroxybutyrate (PHB) has the potential physical qualities for food packaging material, single-use plastic goods and medicinal sectors. Polyhydroxybutyrate (PHB) is a bacterial biopolymer that has begun to replace petrochemical plastics due to the present trend towards the efficient utilisation of relatively cheaper substrates for its production. This review discusses explicitly the developments in the analysis of microbial biopolymer PHB and additionally provides an outline of current industrial applications, Production, Extraction methods, genes involved, microbes that are capable of producing PHB, challenges faced during production and degradation of PHB.

Therapeutic potential of dietary phytochemicals from Drynaria quercifolia to modulate gut microbiome: an in silico approach

Drynaria quercifolia is one of the pioneer medicinal plants which exert many beneficial effects on humans. Fatty acids are hydrophobic ligands that act as membrane substrates, metabolic signalling molecules, and metabolic energy sources. It could enhance the mucus production in the intestine which maintain mucosal homeostasis. The inflammatory responses were also regulated by 5-HT receptors. Serotonin 2 A receptors are G-protein coupled receptors targeted by various types of ligands viz. antidepressants, antipsychotics and anti-migraine drugs. The interaction of mucin protein and fatty acid could increase the antimicrobial activity and anti-inflammatory activity of gut microbiome. In this study, dietary phytochemicals were extracted from D. quercifolia and characterized using GC-MS analysis. The result shows presence of 38 various compounds viz. decanoic acid, indole, and dodecanoic acid and etc., Among the all, dodecanoic acid showed good drug likeness and pharmaceutical properties. Target proteins viz. 3IFB (Intestinal fatty acid binding protein) and 7WC4 (5-hydroxytryptamine receptor 2 A) were docked with dodecanoic acid using Auto dock software. The fatty acids produced in the gut could interact with 3IFB and 7WC4 proteins to maintain intestinal integrity and improved gut-brain function respectively. Dodecanoic acid exhibits the highest binding energy with mutated 3IFB (-6.01) than native whereas 7WC4 native protein showed (-7.3 kal/mol) the highest affinity than mutated protein. Structural changes were predicted by using SOPMA and ProSA. Evaluation results indicate that 3IFB was having more stability, good quality, and enhanced affinity than 7WC4. Further, MD simulations were done for 3IFB to check the stability of protein-ligand complex using WebGro platform. The model was investigated by root mean square deviation and fluctuations. Therefore, dodecanoic acids have been considered as a potential agonists and offer opportunities for developing innovative medications for gastrointestinal diseases. Communicated by Ramaswamy H. Sarma

Abstract P1130: Enhanced Electrophysiological Maturation Of Human Pluripotent Stem Cell Derived Cardiomyocytes By An Optimal Combination Of Metabolic Modulators

Human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) have emerged as ideal cell source for heart regeneration. Transplantation of hPSC-CMs to the damaged heart restores contractile function via electromechanical coupling between host and graft CMs. However, a few hurdles still remain in safety for clinical application, especially a transient period of ventricular arrhythmias after transplantation into large animals. Automaticity of graft cells, related to the electrical immaturity of hPSC-CMs, most likely triggers arrhythmic events. Here, we hypothesized that modulating metabolism toward an adult-like state would control ion channel gene expression and enhance electrophysiological maturation of hPSC-CMs in vitro. We systematically optimized combination of major metabolic components, including metabolic hormones, energy source and energy sensing, to achieve ion channel gene expression and electrophysiological phenotypes that more closely resemble adult cardiomyocytes. hPSC-CMs treated with optimized media displayed slower beat rates, longer field potentials, faster conduction velocities, and improved Ca 2+ kinetics. Moreover, optimized media increased mitochondrial content, respiratory capacity and fatty acid utilization for larger energy production, induced cell cycle exit, improved global transcriptome and sarcomere structure, and increased cell size. Subsequently, the matured cells were transplanted to mouse hearts, showing the engraftment comparable to immature hPSC-CMs. These results indicate that metabolic reprogramming can enhance many elements of maturation, including electrophysiology, myofibril organization, cell cycle, and capacity for oxidative phosphorylation.

Role of glucose in daily torpor of Djungarian hamsters (Phodopus sungorus): challenge of continuous in vivo blood glucose measurements.

Djungarian hamsters use daily torpor to save energy during winter. This metabolic downstate is part of their acclimatization strategy in response to short photoperiod and expressed spontaneously without energy challenges. During acute energy shortage, torpor incidence, depth, and duration can be modulated. Torpor induction might rely on glucose availability as acute metabolic energy source. To investigate this, the present study provides the first continuous in vivo blood glucose measurements of spontaneous daily torpor in short photoperiod-acclimated and fasting-induced torpor in long photoperiod-acclimated Djungarian hamsters. Glucose levels were almost identical in both photoperiods and showed a decrease during resting phase. Further decreases appeared during spontaneous daily torpor entrance, parallel with metabolic rate but before body temperature, while respiratory exchange rates were rising. During arousal, blood glucose tended to increase, and pretorpor values were reached at torpor termination. Although food-restricted hamsters underwent a considerable energetic challenge, blood glucose levels remained stable during the resting phase regardless of torpor expression. The activity phase preceding a torpor bout did not reveal changes in blood glucose that might be used as torpor predictor. Djungarian hamsters show a robust, circadian rhythm in blood glucose irrespective of season and maintain appropriate levels throughout complex acclimation processes including metabolic downstates. Although these measurements could not reveal blood glucose as proximate torpor induction factor, they provide new information about glucose availability during torpor. Technical innovations like in vivo microdialysis and in vitro transcriptome or proteome analyses may help to uncover the connection between torpor expression and glucose metabolism.

Upper limit efficiency estimates for electromicrobial production of drop-in jet fuels

Microbes which participate in extracellular electron uptake (EEU) or H2 oxidation have the ability to manufacture organic compounds using electricity as the primary source of metabolic energy. So-called electromicrobial production could be valuable to efficiently synthesize drop-in jet fuels using renewable energy. Here, we calculate the upper limit electrical-to-fuel conversion efficiency for a model jet fuel blend containing 85% straight-chain alkanes and 15% terpenoids. When using the Calvin cycle for carbon-fixation, the energy conversion efficiency is 37.8-4.3+1.8% when using EEU for electron delivery and 40.1-4.6+0.7% when using H2 oxidation. The production efficiency can be raised to 44.2-3.7+0.5% when using the Formolase formate-assimilation pathway, and to 49.2-2.1+0.3% with the Wood-Ljungdahl pathway. This efficiency can be further raised by swapping the well-known Aldehyde Deformolating Oxygenase (ADO) termination pathway with the recently discovered Fatty Acid Photodecarboxylase (FAP) pathway. If these systems were supplied with electricity from a maximally-efficient silicon solar photovoltaic, even the least efficient pathway exceeds the maximum solar-to-fuel efficiency of all known forms of photosynthesis.