bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effectiveness of Coenzyme Q1 and Q10 in Mitigating Myocardial Reperfusion/Ischemia (MI/R) Injury
Authors: Aahitey Myles , Sutton Jakob , Venditto Joseph , Kucharski Kevin , Robbie Jason , Kuo Daniel , Barsotti Robert , Young Lindon , Chen Qian 
Published: June 2021

Mitochondria may be a principle source of oxidative stress causing MI/R injury. Coenzyme Q10 (CoQ10) is essential for electron transport in normal mitochondria, has antioxidant properties but its bioavailability is likely reduced due to oxidative stress during MI/R. Coenzyme Q1 (CoQ1) is a derivative of CoQ10, but is a more potent antioxidant than CoQ10 due to a shorter isoprene chain. We hypothesize that CoQ1 will exhibit better cardioprotective effects during MI/R. CoQ1 (MW=250 g/mol; 20 μM, n=4) and CoQ10 (MW=863 g/mol; 20 μM, n=5) were given at reperfusion in isolated rat hearts subjected to I (30 min)/R (45 min). We found that MI/R hearts (n=7) and MI/R+DMSO hearts (n=4) (1% DMSO was used to solubilize CoQ1 and CoQ10) exhibited significantly compromised cardiac contractile/diastolic pressures and coronary flow during reperfusion compared to those of sham hearts (n=5). By contrast, the final left ventricular developed pressure was significantly improved by CoQ1 treatment (53.5±5.5 mmHg), but not CoQ10 treatment (38.4±8.6 mmHg), when compared to that in MI/R hearts (33.6±6.2 mmHg) and MI/R+DMSO hearts (36.4±9.7 mmHg) (p<0.05). Similarly, the final peak of the first derivative of left ventricular pressure was significantly higher in CoQ1 treatment (1180.2±103.0 mmHg/s), but not CoQ10 treatment (770.6±120.1 mmHg/s), when compared to that in MI/R hearts (700.6±134.7 mmHg/s) and MI/R+DMSO hearts (and 741.5±168.6 mmHg/s) (p<0.05). CoQ1 and CoQ10 treated hearts showed no improvement on diastolic pressure and coronary flow compared to the controls. Moreover, infarct size was reduced by CoQ1 treatment (25±3%) and CoQ10 treatment (29±4%) compared to that in untreated MI/R (44±6%) and MI/R+DMSO (32±4%). In summary, our preliminary results indicate that CoQ1 was more effective than CoQ10 in restoring post‐reperfused cardiac contractile function, but not infarct size during MI/R.Support or Funding InformationThis study was supported by Division of Research, the Center for Chronic Disorders of Aging, and Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.
Plant Alkaloid Desensitization of Fetal Muscle‐Type Nicotinic Acetylcholine Receptors
Authors: Green Benedict , Lee Stephen , Welch Kevin , Cook Daniel 
Published: June 2021

The exposure of a developing fetus to certain plant alkaloids has the potential to inhibit fetal movement which can then result in developmental defects. The putative mechanism of movement inhibition is the desensitization of fetal muscle‐type nicotinic acetylcholine receptors (nAChR) which is affected by agonist chemical structure. In this study, we tested the hypothesis that a 1,2‐dehydropiperidine alkaloid agonist is more effective at desensitizing nAChR than a saturated analogue. Agonists were evaluated in TE‐671 cells which express fetal muscle‐type nAChR, and SHSY‐5Y cells which express autonomic‐type nAChRs using a membrane potential sensing dye system. Anabaseine, a 1,2‐dehydropiperidine alkaloid, was more effective at desensitizing TE‐671 cells than anabasine which is fully saturated at the 1,2 position. The neurotransmitter acetylcholine which was included as a control was more effective than the pyridine alkaloid nicotine at desensitizing the agonist response in TE‐671 cells. Both nicotine and acetylcholine were equally effective at desensitizing the agonist response in SH‐SY5Y cells. These results suggest that anabaseine, a 1,2‐dehydropiperidine alkaloid agonist is more effective at desensitizing fetal muscle‐type nAChR than anabasine and has a greater potential to inhibit fetal movement.Support or Funding InformationThis research was supported by USDA/ARS.
Temperature‐Oxygen Interactions and the Evolution of Giant Antarctic Sea Spiders
Authors: Woods H. Arthur , Moran Amy L. , Tobalske Bret W , Lane Steven J , Shishido Caitlin L. 
Published: June 2021

For more than a hundred years, scientists have known that many marine invertebrate taxa grow to unusually large size in polar waters. This biogeographic pattern has become known as polar gigantism, and it occurs in taxa as diverse as glass sponges, ctenophores, foraminiferans, polychaete annelids, isopod crustaceans, copepods, amphipod crustaceans, and pycnogonids. Despite being common, polar gigantism remains a physiological and evolutionary mystery; how and why do polar taxa grow to such large sizes? Using Antarctic sea spiders (pycnogonids), we tested one of the leading physiological hypotheses about polar gigantism—the oxygen hypothesis, proposed by Chapelle and Peck, which states that polar giants are permitted in very cold water by high levels of oxygen supply coupled to low metabolic demand for that oxygen. We measured whole‐body metabolic rates spanning three orders of magnitude in body size. Metabolic rate scaled to body mass with an exponent of 0.9, indicating that giant sea spiders do not require unusually low metabolic rates. Using oxygen electrodes and dye‐tracer experiments, we examined the details of oxygen transport across the cuticle and of oxygen levels and transport in the hemocoel. Oxygen is taken up across the cuticle (there is no distinct respiratory organ), and the cuticle is a much greater barrier to oxygen movement than is the mix of fluids and tissues inside the legs and trunk. Oxygen levels in the hemocoel were high everywhere in the body, but were consistently highest in distal parts of the legs and lowest in the trunk. In addition, larger sea spiders had lower central levels of oxygen. Our dye tracer experiments suggested that contractions of the heart and muscles in the legs drive relatively rapid blood circulation, especially between the trunk and proximal parts of the legs. This indicates that sea spiders use their proximal leg segments as respiratory surfaces. Building on these physiological details, we constructed a mathematical model of oxygen transport and consumption, which we applied to the range of body sizes we studied in Antarctica. The model accurately predicted measured levels of oxygen in the blood. We then used the model along with realistic Q10s for key oxygen processes to simulate how polar sea spiders would perform in warmer water. These simulations strongly suggest that gigantic forms would not obtain oxygen rapidly enough in warm water to support their higher metabolic rates. Thus, together our empirical and theoretical studies support the oxygen hypothesis: it appears that the giant forms found in the Ross Sea can balance their oxygen budgets only because supply is so high and demand is so low.Support or Funding InformationNational Science Foundation grant 1341476
Heart Rate Regulation in the Killer Whale
Authors: Bickett Natalie , Tift Michael , St. Leger Judy , Ponganis Paul 
Published: June 2021

Heart rate responses and gas exchange ultimately underlie the diving capacity/foraging ecology of cetaceans, and may well contribute to the morbidity/mortality of whales stranded after exposure to naval sonar. In order to examine cardiac responses in mid‐sized whales, and eventually measure cetacean heart rates in the wild, we applied a digital electrocardiogram (ECG) recorder with a suction cup attachment technique to a 3868 kg killer whale, Orcinus orca. Heart rate during 10‐min spontaneous, voluntary rest periods ( both apneic and eupneic heart rate) ranged from 21 to 82 beats min−1 between eupnea and apnea, was variable during apnea, and averaged 50 ± 3 SD beats min−1, 1.6 × the resting heart rate predicted by Stahl's allometric equation. During trained, stationary submersions of two to three‐min duration, and during one‐min duration, leisurely underwater swims at 0.5 Hz fluke stroke rate, heart rate was 34 ± 5 SD, and 59 ± 4 SD, respectively. Large oscillations in heart rate with rapid return to baseline occasionally occurred under all conditions. The “resting” heart rate of this killer whale was appropriate for its body mass, but probably elevated due to study conditions (non‐fasting). Sub‐surface swimming elicited an increase in heart rate, and voluntary, trained submersions resulted in a dive response with a variable bradycardia. This approach shows promise to further investigate heart regulation in mid‐sized cetaceans and eventually record heart rates of free‐diving whales.Support or Funding InformationONR Award No N000141410404
An Optogenetic Test for the Functional Specificity of Bulbospinal Sympathoexcitatory Neurons
Authors: Pracejus Natasha H , Farmer David GS , McAllen Robin M 
Published: June 2021

Sympathetic preganglionic neurons are functionally specialised, each belonging to one of a limited number of functional classes (e.g. muscle vasoconstrictor, cutaneous vasoconstrictor, sudomotor). How far this functional specificity applies to the premotor neurons that drive them is uncertain. We devised an optogenetic test for the existence of premotor neurons that are collateralised to drive more than one functional class of sympathetic neuron.Bulbospinal neurons were transduced by a retrogradely transported viral vector (canine adenovirus) encoding Cre recombinase (CAV‐CMV‐Cre; provided by Eric Kremer, Montpellier). This was injected around sympathetic preganglionic neurons at the T12‐L1 spinal levels. At the same time, a Cre‐activated adeno‐associated virus (AAV) encoding Channelrhodopsin‐2 (ChR2) and the fluorescent label mCherry (AAV1.EF1.dflox.hChR2(H134R)‐mCherry.WPRE.hGH; provided by Deisseroth, Stanford via UPenn) was injected into the left RVLM. Only neurons transduced by both viral vectors should then express the ChR2 and mCherry. Spinal injections were made at T12‐L1 because they were considered unlikely to overlap with the preganglionic supply to the heart. The bulbospinal presynaptic terminals infected with CAV‐Cre were thus presumably on preganglionic neurons that supplied end organs such as hindlimb muscle, but not the heart.Terminal functional experiments under urethane anaesthesia were performed 2–8 weeks after the viral injections. Activity was simultaneously recorded from the left cardiac and lumbar sympathetic nerves, whilst pulses of blue laser light (473 nm, 10–12 mW, 20 ms) were flashed onto the left RVLM through a 100 μm diameter fibre‐optic probe.In about one‐third of experiments, we were able to show functional activation of sympathetic nerves that was time‐locked to the flashed laser light. In all successful experiments, we found cardiac sympathetic activation as well as lumbar sympathetic activation (peak response latencies 135–150 ms and 215–230 ms, respectively). Subsequent fluorescence microscopy on brainstem sections confirmed the presence of small numbers of mCherry expressing bulbospinal neurons in those rats.This study demonstrates that at least some bulbospinal neurons send excitatory synaptic inputs to preganglionic neurons of more than one functional type. It also demonstrates the feasibility of using anatomically‐based optogenetic transduction as a test for functional collateralisation in central pathways.Support or Funding InformationAustralian Research Council DP13014661
Long‐term Leucine and BCAA Inclusion in a 30% Protein and Energy Restricted Diet Increases mTORC1 Signaling in Skeletal Muscle of Neonatal Pigs
Authors: Manjarin Rodrigo , Columbus Daniel A , Solis Jessica , Suryawan Agus , Hernández‐García Adriana D , Nguyen Hanh V , Fiorotto Marta L , Davis Teresa 
Published: June 2021

Suboptimal nutrient intake during the shift from parenteral to oral feeding represents a limiting factor for growth of low‐birth weight infants. Leucine has been shown to have anabolic properties in skeletal muscle and can promote lean gain when supplemented to neonatal pigs fed a milk replacement formula. The objective of this study was to test if enteral leucine supplementation alone, or in combination with isoleucine and valine, can increase muscle protein synthesis in neonate pigs who consume 30% less crude protein (CP) and metabolizable energy than their requirements, and whether this effect is mediated through changes in muscle protein synthesis and degradation pathways, and amino acid (AA) transporter expression. Piglets (4‐d‐old) were fed by gastric tube 1 of 4 diets providing (kg BW/d) 15 g CP and 215 kcal (CON), 10.5 g CP and 156 kcal (R), 10.5 g CP + 1.19 g leucine and 156 kcal (RL), or 10.5 g CP + 1.67 g branched‐chain amino acids and 156 kcal (RBCAA) at 4‐h intervals for 9 d (n = 24). Body weights (BW) were recorded on d 0, 3, 6, and 9. On d 9, plasma AA and insulin concentrations and muscle protein synthesis rate, abundance of Na+‐coupled neutral AA transporter (SNAT2) and L‐type AA transporter (LAT1), and phosphorylation and/or abundance of insulin receptor substrate 1 (IRS‐1, Ser1101), protein kinase B (PKB), S6 kinase (S6K1), 4E‐binding protein (4EBP1), eukaryotic initiation factor 4 complex (eIF4E·eIF4G), forkhead box O (FOXO1, Ser256), atrophy F‐Box/Atrogin‐1 and muscle RING‐finger protein (MuRF1) were determined post‐feeding. Plasma leucine levels were greater in RL and RBCAA compared to CON (P ≤ 0.01). BW gain and muscle protein synthesis rate, phosphorylation of S6K1 and 4EBP1, and formation of eIF4E·eIF4G were lower in R, RL, and RBCAA than CON (P < 0.01). RBCAA and RL upregulated (P ≤ 0.01) S6K1 and 4EBP1 phosphorylation and eIF4E·eIF4G formation compared to R. Phosphorylation of FOXO1 was lower in R compared to CON (P ≤ 0.05). There were no differences in phosphorylation and/or abundance of IRS‐1, PKB, SNAT2, LAT1, atrogin‐1 and MURF1 among diets. In conclusion, when protein and energy intakes are restricted, leucine or BCAA supplementation for 9 d increases the activation of the mammalian target of rapamycin pathway, but does not enhance skeletal muscle protein synthesis or promote body weight gain in neonatal pigs. Furthermore, protein degradation signaling, AA transporter abundance, and insulin signaling are unaffected by leucine or BCAA supplementation of a protein and energy restricted diet suggesting that when both dietary protein and/or energy supplies are deficient, the anabolic effect of leucine or BCAA supplementation on muscle protein accretion is limited.Support or Funding InformationNIH AR444474, NIH HD072891, NIH AR46308, USDA NIFA 2013‐67015‐20438, and USDA/ARS 6250‐51000‐055
White Blood Cell Counts during Lower Body Negative Pressure vs. Blood Loss in Humans
Authors: van Helmond Noud , Johnson Blair D , Curry Timothy B , Cap Andrew P , Convertino Victor A , Joyner Michael J 
Published: June 2021

Hypovolemia‐induced sympathoexcitation might initiate an immune response through an increase in circulating epinephrine and splenic demargination. We tested the hypothesis that lower body negative pressure (LBNP) and blood loss (BL) result in comparable increases in white blood cell counts (WBCs). We determined WBCs and epinephrine levels in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5‐minute stages at 0, ‐15, ‐30, and ‐45 mmHg of suction. BL included 5 minutes at baseline and following three stages of 333 mL of blood removal (up to 1000 mL total). Blood draws were performed at baseline and after the last stage of each protocol. LBNP to −45mmHg was a greater central hypovolemic stimulus vs. BL, therefore WBCs and epinephrine concentrations were plotted against central venous pressure (CVP) to obtain stimulus‐response relationships using the linear regression line slopes for both protocols. Paired tests were used to determine if the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes fell on similar trajectories for total WBC (LBNP 183±46 vs. BL 155±109 mcL−1 *mmHg−1, p=0.15), neutrophils (LBNP 110±29 vs. BL 96±72 mcL−1 *mmHg−1, p=0.15) and lymphocytes (LBNP 65±21 vs. BL 59±38 mcL−1 *mmHg−1, p=0.90). Mean regression line slopes for epinephrine were similar as well (LBNP 15±5 vs. BL 16±4 pg *mL−1 *mmHg−1, p=0.84). Our results indicate that LBNP models the stimulus‐response relationship between CVP and WBCs observed during BL. Central hypovolemia, induced by LBNP or BL, elicits a relative leukocytosis with a predominantly neutrophil‐based response.Support or Funding InformationUS Army MRMC Combat Casualty Care Research Program Grant # W81XWH‐11‐1‐0823
Hemodynamic responses to simulated hemorrhage: Role for the carotid bodies
Authors: Holbein Walter W , Johnson Blair D , Convertino Victor A , Curry Timothy B , Joyner Michael J 
Published: June 2021

BackgroundLower body negative pressure (LBNP) increases carotid body chemosensitivity. Whether the increase in chemosensitivity is functionally significant in the hemodynamic response to LBNP was previously unknown. We tested the hypothesis that desensitization of the carotid body chemoreceptors would improve the hemodynamic response to LBNP.MethodsTen healthy, non‐obese male subjects (35 ± 3 years, BMI: 25 ± 1 kg/m2) completed 2 study visits (Saline, Dopamine), separated by a minimum of 4 weeks. Intravenous dopamine was infused at an individualized dose (1–2 mg/kg/min) shown to maximally blunt the hypoxic ventilatory response (a measure of carotid body chemosensitivity). Arterial blood pressure (brachial catheter) and heart rate (ECG) were continuously recorded. On each study day subjects underwent step‐wise exposures of LBNP (−15, −30, and −45 mmHg) to simulate hemorrhage. Cumulative stress index (CSI) was calculated by summating the product of negative pressure (mmHg) by the time (min) during each LBNP level (−15, −30, and −45 mmHg).ResultsDopamine tended to reduce CSI (Saline: 503 ± 52; Dopamine: 408 ± 45 mmHg*min; p=0.07). Changes in heart rate from baseline during graded LBNP were not statistically distinguishable between Saline and Dopamine conditions (−15 mmHg: +4 ± 1 vs +3 ± 2 BPM, p=0.99; −30 mmHg: +12 ± 1 vs +12 ± 3 BPM, p=0.99; −45 mmHg: HR +21 ± 2 vs +19 ± 5 BPM, p=0.99). Similarly, change in systolic blood pressure from baseline during graded LBNP was not different between Saline and Dopamine conditions (−15 mmHg: +1 ± 1 vs −1 ± 2 mmHg p=0.99; −30 mmHg: −7 ± 3 vs −6 ± 4 mmHg, p=0.99; −45 mmHg: −12 ± 4 vs −22 ± 6 mmHg, p=0.19). However, change in diastolic blood pressure from baseline during graded LBNP was higher at −45 mmHg between Saline and Dopamine conditions (−15 mmHg: +2 ± 1 vs −0 ± 1 mmHg p=0.47; −30 mmHg: −1 ± 2 vs −2 ± 2 mmHg p=0.26; −45 mmHg: −2 ± 2 vs −12 ±3 mmHg, p=0.0004).ConclusionsDesensitization of the carotid body chemoreceptors reduced diastolic blood pressure responses to LBNP at −45 mmHg only, with minimal effect at lower levels. These data suggest chemoreflex activity during LBNP may be functionally significant in the blood pressure responses only during higher levels of simulated hemorrhage.Support or Funding InformationFunding: W81XWH‐13‐2‐0038 (DOD)
Reduced Short‐chain Fatty Acid Producing Microbiota are Linked to Increased Energy Intake and Susceptibility to High Fat Diet Induced Hepatic Steatosis in Low Aerobic Capacity Rats
Authors: Panasevich Matthew R , Morris E M , Chintapalli S V , Wankhade U , Shankar K , Britton S L , Koch L G , Thyfault J P , Rector R S 
Published: June 2021

Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all‐cause mortality. We have previously shown that low aerobically fit, low capacity running (LCR) rats fed an acute high fat diet (HFD; 45% kcal from fat) for 3 days displayed a greater positive energy balance due to a greater increase in energy intake and reduced energy expenditure, which likely played a role in their susceptibility for hepatic steatosis compared with high aerobically fit, high capacity running (HCR) rats. Here, we tested the hypothesis that poor physiological outcomes in LCR rats following acute HFD feeding are associated with alterations in cecal microbiota. Through amplification of the V4 region of bacterial 16S rDNA, we found that at the phylum level, the LCR rats had a reduced relative abundance of cecal Proteobacteria (P<0.05) and increased Cyanobacteria (P<0.05) compared with HCR rats. Interestingly within Proteobacteria, Desulfovibrionaceae, and unassigned genera within Desulfovibrionaceae, were increased (P<0.05) in HCR compared with LCR rats, suggesting increased sulfur reduction from endogenous substrates (i.e. mucins and proteins). Conversely, the Proteobacteria family Alcaligenaceae was increased (P<0.05) in LCR compared with HCR rats, which may be related to susceptibility to NAFLD in the LCR rats. While acute HFD feeding reduced the overall relative abundance of Firmicutes in both strains, short‐chain fatty acid (SCFA)‐producing Phascolarctobacterium and Butyricimonas were reduced (P<0.05) only in the LCR rats. In addition, SCFA‐producing Ruminococcae (r=−0.75) and Ruminococcus (r=−0.73, P<0.01) were negatively correlated with energy intake only in the LCR rats. Overall, these data suggest that the susceptibility to acute HFD‐induced increases in energy intake and hepatic steatosis in low aerobically fit animals is associated with changes in the cecal microbiome, particularly suppression of SCFA‐producing bacteria.Support or Funding InformationAHA 14POST20110034 (EMM), NIH R01DK088940 (JPT), P40OD021331 and R01DK099034 (LGK and SLB), USDA‐CRIS 6206‐51000‐007‐00D‐05 (KS), VA‐CDA2 IK2BX001299 (RSR).