bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rebuilding a heart: complete regeneration after myocardial infarction in the axolotl (1151.1)
Authors: Lauridsen Henrik , Pedersen Michael 
Published: June 2021

Intro: Cardiac failure resulting from myocardial infarction is a leading cause of death. This is the fatal result of the lack of regenerative capacity of the mammalian heart. Salamanders such as the axolotl possess unmatched regenerative capacity, mastering the ability to regenerate internal organs and whole limbs. To draw basic information about molecular and cellular mechanisms in cardiac repair, we have established and validated a myocardial infarction model in the axolotl.M&M: Myocardial infarction in the axolotl was induced by cryoinjury. Regeneration was described histologically at 4, 7, 14, 31, 40 and 94 days post infarction (dpi) and 4 days post sham (dps). Concurrently functional restoration of cardiac output was monitored using echocardiography and MRI. Protein profiles of myocardial tissue 4, 14 and 30 dpi and 4 dps were produced using LC‐MS/MS.Results & Discussion: The axolotl restores complete myocardial structure and functionality within 2‐3 months after a 25% myocardial infarction. Interestingly, the initial response to injury is fibrosis forming a scar as found in mammals. However, this response is replaced within a few weeks when cardiomyocytes are deposited in the fibrotic scaffold aiding a gradual recovery of cardiac output.This model can potentially improve our understanding of heart regeneration, and we seek to identify signaling events at the protein level using the proteomics data.
The effect of sitting and calf exercise on fluid accumulation below the knees (1156.13)
Authors: Singh Bhajan , Yadollahi Azadeh , Bradley T 
Published: June 2021

Background: Overnight rostral fluid shift from the legs to the neck correlates with the severity of obstructive sleep apnea (OSA) and time spent sitting. Sitting causes gravity‐dependent fluid accumulation in the legs that is counteracted by walking. However most office workers are required to sit for long periods and walking to preventing fluid accumulation in the legs is impractical. We hypothesized that sitting would cause fluid accumulation below the knees that could be attenuated by calf exercise while sitting.Methods: We measured fluid volume (FV) below both knees using bioelectrical impedance in 10 healthy subjects (8 men, age 50.8±6.2 yrs, BMI 23.7±2.4 kg/m2). Measurements were made in the supine, erect and seated postures and while sitting for 4 hours. Subjects were studied twice, a week apart, in a randomised double cross‐over design: control ‐ no calf exercise, intervention ‐ 15 calf muscle contractions against a pedal resistance (Step‐It) every 15 min. Paired t‐tests were used to analyze changes in FV and the effect of the intervention.Findings: Relative to the supine posture, FV below the knees increased in the erect (64.7±28.9 ml, p<0.0001) and seated postures (135.8.7±59.2 ml, p<0.0001) and after 4 hours of sitting (251.0±65.7 ml, p<0.0001). Modest exercise using the Step‐It device while sitting did not reduce fluid accumulation (control 115.2±47.0 ml, intervention 120.0±28.0 ml, p=0.72).Conclusions: Sitting for 4 hours results in substantial fluid accumulation in the legs of healthy subjects and this is not attenuated by modest intermittent calf exercise using a Step‐It device. This fluid could serve as a reservoir for redistribution to the neck and lungs during sleep, and contribute to OSA in predisposed individuals. A higher level of calf activity may be required to reduce fluid accumulation in the legs when sitting.
The importance of the thioredoxin system in muscle mitochondrial reactive oxygen species metabolism (1159.10)
Authors: Treberg Jason , Banh Sheena , Sotiri Emianka , Zacharias Pamela , Tamanna Nahid 
Published: June 2021

Mitochondria are widely recognized as a potential source of reactive oxygen species (ROS); however, mitochondria also possess a strong capacity for ROS consumption that is often underappreciated. In skeletal muscle the glutathione and thioredoxin based peroxidase systems are likely the major H2O2 consumption pathways. Here we demonstrate the thioredoxin‐based pathway is the major H2O2 consumer in isolated rat skeletal muscle mitochondria. Unlike 1‐chloro‐2,4‐dinitrobenzene, the thioredoxin reductase inhibitor auranofin does not elevate ROS production in disrupted membranes that are devoid of the capacity to consume H2O2. Inhibition of thioredoxin reductase with auranofin leads to a marked increase in apparent ROS production but no change in mitochondrial bioenergetic characteristics (oxygen consumption, membrane potential, %NAD(P)H). Moreover, auranofin also inhibits the capacity for H2O2 consumption by isolated mitochondria and does not appear to act through the inhibition of the glutathione reduction system. We conclude that the apparent increase is H2O2 release by treatment with auranofin is due to impaired matrix level thioredoxin‐dependent H2O2 consumption and not reflective of an activation of ROS production.Grant Funding Source: Supported by Canada Research Chairs (CRC), CFI, Manitoba Research and Innovation Fund and NSERC
The enzyme nagarse modifies parameters associated with function of mechanically‐liberated mitochondria (1159.7)
Authors: Kras Katon , Willis Wayne , Barker Natalie , Czyzyk Traci , Katsanos Christos 
Published: June 2021

Nagarse (N) is traditionally used to isolate mitochondria (mito) from skeletal muscle (SM). We investigated the effects of N on functional parameters of mechanically liberated mito. Mito from mouse (n = 7) gastrocnemius muscle (119‐175 mg tissue) was isolated using a glass on glass homogenizer followed by differential centrifugation. The 800g supernatant from the first centrifugation, containing mito, was divided into two equal volumes. One was exposed to N and the other was not. In each volume, mito were isolated by standard differential centrifugation. State 3 max ADP‐stimulated O2 consumption rates (Jo) were measured using polarography with malate + pyruvate + glutamate. N increased state 3 Jo, 16.1 ± 1.1 vs. 11.9 ± 1.4 nmol O2 / ml mito suspension / min; P < 0.004, while it decreased protein concentration in the final mito suspension (typically used to adjust final Jo values), 1.9 ± 0.1 vs. 2.5 ± 0.1 mg / ml; P < 0.004. Citrate synthase activity in the final mito suspension, indicative of the available mito, was not different in the preparation treated with N vs. that not treated with N (0.067 ± 0.01 vs. 0.065 ± 0.01μmol / min; P = 0.8). These findings suggest that N treatment: 1) hydrolyzes non‐mito contaminating proteins in the final mito pellet, and 2) induces apparent qualitative changes in mito function. Therefore, calculated functional parameters of mito treated with N are not directly comparable to mito not treated with N.Grant Funding Source: Supported by NIH/NIDDK RO1 DK094062
Leukemia inhibitory factor stimulates muscle glucose uptake by a PI3‐kinase dependent pathway that is maintained in white muscle in obesity (1162.4)
Authors: Brandt Nina , O'Neill Hayley , Kleinert Maximilian , Schjerling Peter , Steinberg Gregory , Richter Erik , Jorgensen Sebastian 
Published: June 2021

OBJECTIVE: To investigates the metabolic effects of leukemia inhibitory factor (LIF) in mouse skeletal muscle.METHODS: Effects of LIF on muscle glucose transport, palmitate oxidation and cellular signaling were investigated in soleus and extensor digitorum longus (EDL) muscles from chow and highfat diet fed wildtype (WT) mice or chow fed muscle‐specific AMPKα2 kinase‐dead (KD) and suppressors of cytokine signaling (SOCS) 3 muscle‐specific knockout mice.RESULTS: LIF increased muscle glucose transport in a dose‐ and time‐dependent manner. LIF increased Akt Ser473‐P, whereas AMPK Thr172‐P was unaffected. Incubation of muscles from KD or WT mice with Wortmannin, LY294002 and Parthenolide demonstrated that PI3‐kinase, but not AMPK, was essential for LIF‐stimulated glucose transport. Incubation with Rapamycin and AZD8055 demonstrated that mammalian target of rapamycin complex (mTORC)2 and not mTORC1 is necessary for LIF‐stimulated glucose transport. LIF‐stimulated glucose transport was maintained in EDL muscle from obese insulin resistant mice. Lack of SOCS3 did not affect LIF‐stimulated glucose uptake.CONCLUSIONS: LIF acutely increases muscle glucose transport by a mechanism involving the PI3‐kinase/mTORC2/Akt pathway which is maintained in EDL muscle from obese insulin resistant mice.
ATP release induced by electrical stimuli increase ROS production and RyR glutathionylation via P2Y1‐PKC‐NOX2 in skeletal muscle fibers (1164.5)
Authors: Díaz Alexis , Campos Cristian , Jaimovich Enrique , Espinosa Alejandra 
Published: June 2021

During exercise, skeletal muscle produces ROS via NOX2 while inducing some adaptations associated with contractile activity; the signals involved in this mechanism are debated.ATP is released from skeletal muscle during electrical stimulation and can signal autocrinely through purinergic receptors, we hypothesized that it may influence ROS production. The aim of this work was to measure ROS production induced by electrical stimulation and extracellular ATP. Electrical stimulation triggered a ROS transient increase in muscle fibers. The ROS production was mimicked by extracellular ATP and was prevented by CBX and suramin, antagonists of pannexin channel and purinergic receptors respectively. MRS2365, a P2Y1 receptor agonist induced a large signal while UTPyS (P2Y2 agonist) elicited a much smaller signal that was mimicked using ATP plus MRS2179, an antagonist of P2Y1. Inhibitors suggest that ROS production induced by ES or extracellular ATP was mediated by NOX2 via PKC. Extracellular ATP induced glutathionylation of RyR via NOX2. Electrical stimulation increase ROS production via P2Y1‐NOX2 and this effect appears to be involved in the regulation of RyR oxidation and thus in the regulation of calcium signaling in skeletal muscle fibers.Grant Funding Source: ACT 1111, Fondecyt 11090301
Effect of sub‐occipital release and systemic acetylsalicylic acid administration on pain perception and autonomic reflex responses to pain (1170.9)
Authors: Metzler‐Wilson Kristen , Schaub Andrew , Vrable Abby , Krause B. , Wilson Thad 
Published: June 2021

To determine the autonomic effects of sub‐occipital release (SOR) during experimentally induced pain, 16 healthy subjects (8 women, 8 men) experienced ischemic (forearm post‐exercise muscle ischemia; PEMI) and cold (hand cold pressor test; CPT) pain. Heart rate (HR; ECG) and mean arterial blood pressure (MAP; photoplethysmography) were measured. SOR or a sham control (modified yaw; 30 cycles/min) was performed in the final min of experimental pain. PEMI caused increases in MAP of 23±2 and 20±2 mmHg, but no differences were observed with the addition of either SOR or yaw. PEMI modestly elevated HR during ischemia, followed by a significant reduction with SOR (‐3±2 bpm) and yaw (‐4±2 bpm) from baseline, but no differences were observed between treatment and sham. CPT increased MAP (11±1 and 9±2 mmHg) and HR (10±2 and 8±3 bpm) prior to SOR and yaw. Neither treatment nor sham blunted MAP increases (SOR = 25±2, yaw = 22±2 mmHg) to CPT, but both decreased HR (SOR = 3±2, yaw = 2±2 bpm) from baseline. To further probe potential mechanisms, systemic acetylsalicylic acid (ASA; 967 mg) was given 60 min prior to testing to reduce prostaglandin (PG) synthesis. ASA blunted pain perception but did not alter cardiovascular changes to PEMI and did not interact with SOR or yaw. These data indicate that that both SOR and sham may be affecting the parasympathetic nervous system via a non‐PG mechanism.Grant Funding Source: Supported by a grant from the American Osteopathic Association
H2O2 decreases ASIC1 plasma membrane localization in rat pulmonary arterial smooth muscle cells (1175.3)
Authors: Plomaritas Danielle , Herbert Lindsay , Resta Thomas , Walker Benjimen , Jernigan Nikki 
Published: June 2021

Acid sensing ion channel 1 (ASIC1) mediates enhanced store operated calcium entry (SOCE) in pulmonary arterial smooth muscle cells (PASMC) and contributes to the development of chronic hypoxia (CH)‐induced pulmonary hypertension. ASIC1 is a redox sensitive ion channel, such that reducing agents increase and oxidizing agents decrease channel activity. Recent studies from our laboratory have shown that 1) hydrogen peroxide (H2O2) inhibits ASIC1‐dependent SOCE in PASMC and 2) pulmonary arterial H2O2 levels are decreased following CH which may contribute to the enhanced SOCE. Considering that H2O2 has additionally been shown to decrease ASIC1 cell surface expression in neurons, we hypothesized that H2O2 inhibits plasma membrane localization of ASIC1 in PASMC. Using a cell surface biotinylation assay, we found a 2.9 ± 0.1 fold increase in plasma membrane ASIC1 expression in PASMC from CH animals compared to control (two‐tailed P value=0.0002). In PASMC from control rats pretreatment with PEG‐catalase (250 U/ml; 1 hr at 37°C) increased and H2O2 (25 µM; 1 hr at 37°C) decreased ASIC1 surface expression compared to vehicle treated PASMC (one way ANOVA P value<0.001). We conclude that ASIC1 plasma membrane localization is inhibited by H2O2 in PASMC and this represents one potential mechanism by which the loss of H2O2 following CH enhances ASIC1‐dependent Ca2+ influx in PASMC.Grant Funding Source: Supported by T32‐HL07736; R01‐HL111084; K01 HL092598
Excessively increased pulmonary artery systolic pressure during exercise in adults with a history of extreme premature birth is unresponsive to sildenafil (1175.8)
Authors: Mangum Tyler , Duke Joseph , Elliott Jonathan , Goodman Randall , Gladstone Igor , Lovering Andrew 
Published: June 2021

Extreme preterm birth results in abnormal alveologenesis and pulmonary vasculogenesis. Abnormal pulmonary vasculature may be unable to accommodate increased cardiac output during exercise, thereby resulting in an abnormally increased pulmonary artery systolic pressure (PASP) and exercise‐induced pulmonary hemorrhage (EIPH) in adult with a history of extreme preterm birth (PRE). We hypothesized that 1) PRE would have increased PASP during exercise thereby causing EIPH and 2) oral sildenafil would reduce PASP thereby preventing EIPH. PRE (n = 2) performed exercise at 80% of max power output to exhaustion on a cycle ergometer 60 mins after 100 mg sildenafil (p.o.) and, on a separate day, without sildenafil. Age and sex matched full term controls (CON; n = 2) exercised at the same workload and for the same time as PRE. PASP was measured via ultrasonography at rest and within the last minute of exercise. Induced sputum samples were collected post‐exercise and analyzed for cellular constituents. PASP was not different at rest between groups. During exercise, PASP was greater in PRE (54 Torr) vs CONT (48 Torr) without drug, and was unchanged in PRE (59 Torr) but decreased in CONT (41 Torr), with sildenafil. There was no evidence of EIPH in either group. These data suggest that excessive PASP during exercise in PRE may be the result of abnormal pulmonary vascular architecture, which cannot be ameliorated by oral sildenafil.Grant Funding Source: Supported by AHA Scientist Development Grant and OHSU Early Clinical Investigator Grant
Elevation of glucose to levels associated with type I diabetes impairs bone cell mechanosignaling (1180.10)
Authors: Maung Stephanie , Wang Xiaonan , Basta‐Pljakic Jelena , Schaffler Mitchell , Spray David , Suadicani Sylvia , Thi Mia 
Published: June 2021

It has been shown that patients with insulin dependent diabetes mellitus (IDDM; Type 1 diabetes) manifest a range of bone problems, including increased risk for bone fractures and defective bone healing. However, the underlying mechanisms are still not well understood. Given that the maintenance of skeletal integrity in response to daily physical activity relies homeostasis between bone forming cells, osteoblasts, and the primary load sensing cells, osteocytes, we hypothesized that bone loss in Type 1 diabetes is primarily triggered by exposure to high glucose levels which in turn compromises ability of bone cells to perceive and respond to mechanical loading as a result of altered expression of mechanosignaling mediators: specific purinergic receptor (P2Rs) and pannexin 1 (Panx1) channels. Our in situ (Akita, Type 1 diabetic and age‐matched wild type mouse model) morphometric analysis and in vitro (MLO‐Y4 osteocytes and MOB‐C osteoblasts) findings indicate that exposure to elevated glucose (10 days in α‐MEM containing 450 mg/dL (25 mM) glucose) alters P2R (specifically P2Y2R, P2Y4R and P2X7R) and Panx1 expression in both osteoblastic and osteocytic cells and blunts proper Ca2+ signaling in response to oscillatory fluid shear stress mechanical loading. Our findings indicate that Type 1 diabetes impairs the proper response of bone cells to mechanical loads, which is required to maintain bone health.Grant Funding Source: Supported by DK091466; DK081435; AR057139
Epithelial cell modeling: standards‐based simulation experiments (1180.4)
Authors: Nickerson David , Hamilton Kirk , Beard Daniel , Hunter Peter 
Published: June 2021

We have developed a simulation tool, get‐simulator, for performing simulation experiments with user‐defined epithelial cell models. Users are able to define their epithelial cell model de novo or through the assembly of pre‐existing modules. Existing cell models may also be re‐used in new simulation experiments. Cell models are encoded in the CellML format (http://cellml.org) and the SED‐ML format (http://sed‐ml.org) descriptions of the simulation experiments. SED‐ML allows a given collection of models to be instantiated into one or more specific computational tasks to be executed in order to generate unambiguously defined outputs. In addition to the models and simulation experiment descriptions themselves, get‐simulator makes use of relevant annotations of these source data to enable the automatic generation of executable code for each of the required computational tasks. Following the execution of these tasks, the user is presented with the resulting outputs defined in the SED‐ML document. get‐simulator and example models are available from https://bitbucket.org/get under a free and open‐source license.Grant Funding Source: Supported by the Virtual Physiological Rat Project, NIH grant [P50‐GM094503].
The consumption of beef vs. soy lunch meals on food cravings and cortico‐limbic brain regions controlling food motivation/reward in healthy adults (120.5)
Authors: Ortinau Laura , Lasley Tyler , Douglas Steve , Shafer Rebecca , Leidy Heather 
Published: June 2021

Objective: To determine whether protein source, specifically comparing beef vs. soy‐rich foods, alters food cravings and neural responses controlling food motivation and reward in healthy adults. Methods: Using a randomized, crossover design, 23 healthy adults (age 23 ± 1 y; BMI: 23.4 ± 0.6 kg/m2) consumed, on separate days, 400 kcal beef vs. soy‐based lunch meals that were 1) matched for macronutrient and fiber content or 2) matched for serving size (which allowed macronutrient and fiber content to vary). Pre and post‐lunch food craving questionnaires and food cue‐stimulated functional MRI (fMRI) brain scans were completed. Results: When comparing macronutrient and fiber‐matched meals, the consumption of beef tended to reduce post‐lunch cravings for sweet foods vs. soy (P=0.09) and tended to reduce hippocampal brain activation vs. soy (P=0.08). When comparing serving size‐matched meals, the consumption of beef tended to reduce post‐lunch cravings for sweet foods vs. soy (P=0.08) and reduced anterior cingulate and insular brain activation vs. soy (both, P<0.05). Conclusions: Taken together, these data suggest that protein source significantly alters the signals that control food cravings and reward with the consumption of beef‐rich foods leading to greater reductions in sweet cravings and cortico‐limbic activation in regions controlling food motivation/reward compared to soy‐rich foods.Grant Funding Source: Supported by The Beef Checkoff
Effect of dietary resistant starch on the inhibition of preneoplasia in azoxymethane‐induced A/J mouse model (123.5)
Authors: Birt Diane , Nelson Bridget , Cray Nicole , Ai Yongfeng , Jane Jay‐Lin 
Published: June 2021

Colorectal cancer (CRC) occurrence is believed to be affected by diet and lifestyle factors. Resistant starch, a type of dietary fiber, is resistant to normal digestion in the small intestine and is instead available for fermentation in the larger intestine by gut microbes. Four starches, varying in digestibility resistance, were used: normal control cornstarch (CS), native high amylose cornstarch (HA7), high amylose complexed with octenyl succinic anhydride (OS‐HA7), and high amylose complexed with stearic acid (SA‐HA7). Preneoplastic lesions were induced in male A/J mice with azoxymethane (AOM), a known colon carcinogen, and saline was used as a control. Treatment groups of mice were fed one of the experimental diets for 10 weeks. Colons were collected and analyzed for common preneoplastic lesions aberrant crypt foci (ACF) and mucin‐depleted foci (MDF). It was hypothesized that the SA‐HA7 diet would provide the greatest inhibition of preneoplasia as it contained the greatest resistant starch content, allowing for greater fermentation and greater production of SCFA. Body weights were recorded weekly. The saline and AOM treated, OS‐HA7 fed mice were not significantly different in body weights at any week. The OS‐HA7‐AOM group, however, was significantly different from all other groups at weeks 7, 12, and 17. The mice fed the SA‐HA7 diet actually had the greatest number of ACF compared to the other diet groups. The HA7 diet had the lowest number of ACF but was not significantly different from the SA‐HA7 diet (p=0.09). No MDF were observed in any of the diet groups. The results from this study suggest that the SA‐HA7 diet may enhance preneoplasia rather than inhibit it if ACF are reliable biomarkers for CRC. Long term studies are needed to determine the impact of resistant starch on CRC.Grant Funding Source: supported by USDA‐AFRI
Improvement of learning and memory by sprouted garlic extract through antioxidant activity in mouse model (124.8)
Authors: Zakharova Alexandra , Seo Ji Yeon , Kim Seong Soon , Kang Hye Ryung , Kim Bo Ram , Woo Ji Eun , Kim Mi Hye , Han Mi Kyung , Kim Jong‐Sang 
Published: June 2021

Garlic is known for its biological function including anticancer, antioxidant, anti‐inflammation and anti‐bacterial activities. This study was conducted to examine comparatively neuroprotective and memory improving effects of sprouted garlic extract and garlic extract. Garlic was sprouted for 1, 2, 3, 4, 5, 6 days and extracted with 100% ethanol. The antioxidant activity of sprouted garlic extract was assessed by various in vitro assays. The effect of sprouted garlic extract on intracellular ROS levels and cell viability were measured in murine hippocampal HT22 cells. Sprouted garlic extracts showed cytoprotective effect, and reduced intracellular ROS levels in the cells insulted with glutamate. Based on these results, we were interested in examining if sprouted garlic extract prevents the scopolamine‐induced memory impairment in mice, using Y‐maze, Morris water maze and passive avoidance tests. The current study demonstrated that sprouting of garlic enhanced the antioxidant activity depending on the period, with the highest activity at 5 days of sprouting. Additionally, our data indicated that sprouted garlic treatment was effective in improving the memory and cognition deficits triggered by scopolamine treatment. Henceforth, further mechanism study of sprouted garlic extracts would be needed.Grant Funding Source: Supported by NRF‐2010‐0027204 and 2011‐0009782 and IPET (High Value‐added Food TechnologyDevelopment Program, 2012, 112066‐3), S. Korea