bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute alcohol intoxication antagonizes contraction‐induced mTOR signaling in skeletal muscle (702.1)
Authors: Steiner Jennifer , Navaratnarajah Maithili , Lang Charles 
Published: June 2021

Acute alcohol (ethanol; EtOH) intoxication impairs basal protein synthesis and mTOR signaling in skeletal muscle but whether EtOH also blunts contraction‐induced anabolic signaling is unknown. Fasted male mice were injected IP with 3g/kg EtOH or saline (Con), after which they were anesthetized and the right hindlimb was electrically stimulated (10 sets of 6 contractions) via the sciatic nerve. The gastrocnemius (GAS) was collected 30 min, 4 h or 12 h after stimulation. In vivo protein synthesis (PS) determined by the flooding dose technique was decreased 17% at 30min and increased 14% at 4 h in Con mice but was unchanged in EtOH‐treated mice. EtOH blunted the stimulation‐induced increase in phosphorylation of S6K1 T389 (45‐57%), S6K1 T421/S424 (15‐52%), rpS6 S240/244 (37‐72%) and 4E‐BP1 (37‐56%) at 30min, 4 h and 12 h, and eIF4B S422 at 30min. Akt S473 was unchanged by alcohol and/or stimulation as were S6K1 downstream signaling factors eEF2 T56 and PDCD4 S67. Injection of Torin2 in separate mice suggested that stimulation‐induced increases were mTOR‐mediated. Therefore, acute alcohol intoxication (i.e. binge drinking) attenuated the stimulation‐induced increase in protein synthesis and related mTOR signaling and this anabolic resistance may contribute to chronic alcohol induced muscle wasting and myopathy.Grant Funding Source: R37 AA011290
Effects of Pueraria lobata/Rehmannia glutinosa combination with exercise on metabolic changes in ovariectomized rats (702.6)
Authors: Oh Sang A , Kim Haein , Lim Yeni , OK Hyang Mok , Do Gyeong‐Min , Kwon Oran 
Published: June 2021

There is a fair amount of evidence showing that increased risks of obesity and insulin resistance are associated with postmenopausal state, but can be modulated by diet and exercise. In this study, we evaluated the effects of Pueraria lobata/Rehmannia glutinosa combination (PR), exercise, or both on metabolic changes in ovariectomized (OVX) Sprague Dawley rats for 8 weeks: Sham control, OVX control, OVX+PR (200 and 400 mg/kg bw), OVX+EX, OVX+EX+PR (200 and 400 mg/kg bw) (n=10/group). PR was fed by gavage and incremental treadmill exercise was used. Oral glucose tolerance test was measured at week 4 and week 8. After 8 weeks, fasting plasma levels of glucose, insulin, C‐peptide, total cholesterol, free fatty acids, leptin, and adiponectin were measured. mRNA expressions (Glut 4 and FOXO) and western blotting (p‐IRS and p‐AKT) were also studied in the muscle. Together, the results suggest the additive effects of PR supplementation and exercise in the management of postmenopausal metabolic changes.Grant Funding Source: This research was supported by MOTIE/KIAT (N0000697) and MEST/BK 21 PLUS (22A20130012143).
The influence of two different menstrual cycle phases on the relationship between DNA oxidation and hydration status following exercise (705.5)
Authors: Yasuda Nobuo 
Published: June 2021

The purpose of this study was to determine the relationship between urinary 8‐hydroxy‐2’‐deoxyguanosine (8‐OHdG) and urine specific gravity (USG) following two hours of cycling exercise over the follicular and luteal phases. Twelve recreationally active eumenorrheic women served as the subjects [age: 20.9±0.3 year; height: 160.1±5.6 cm; body weight: 54.7±5.8 kg; body mass index: 21.3±1.8 kg/m2; body fat: 21.9±3.1 %; peak oxygen uptake (VO2peak): 44.4±5.0 ml/kg/min (mean±SD)]. Before and after 2 hours of cycling exercise performed at 60%VO2peak, 8‐OHdG and USG were determined with high performance liquid chromatography and a handheld refractometer, respectively. All subjects performed the same exercise protocol during the follicular (F: 5~8 days after the onset of the menses) and luteal (L: 22~25 days after the onset of the menses) phase. In order to delay fatigue and prevent hypoglycemia and dehydration, carbohydrate‐electrolyte solution were consumed every twenty minutes (2 ml/kg body mass) during each exercise protocol. No menstrual cycle differences were observed in the relationship between urinary 8‐OHdG and USG following exercise, assessed with an ANCOVA. The findings of the present study indicate that the follicular and luteal phases appear to be similar in terms of the relationship between oxidative DNA damage and hydration status following exercise.Grant Funding Source: Supported partly by funds from the Grant‐in‐Aid for Scientific Research (C) in Japan (No.23500867)
Cardiothoracic impedance does not reflect beat‐to‐beat changes in cardiac stroke volume during mild lower body negative pressure (707.1)
Authors: Holme Nathalie , Elstad Maja , Rein Erling , Walløe Lars 
Published: June 2021

Background: Variability in cardiac stroke volume (SVV) has been proposed as a clinical tool to assess the magnitude of acute hemorrhage. We investigated how three non‐invasive methods represent the beat‐to‐beat changes of cardiac stroke volume (SV).Methods: Ten healthy subjects underwent mild simulated hemorrhage through lower body negative pressure (LBNP) at ‐30 mmHg after a five minutes resting period at baseline. SV beat‐to‐beat was estimated simultaneously by three non‐invasive methods: Ultrasound Doppler (SV_usd), finger arterial blood pressure curve (SV_bpc) and cardiothoracic impedance (SV_imp). SVV was calculated at respiratory frequency between 0.15 and 0.40 Hz from spectral analysis. The median and 95% confidence intervals (CI) were calculated by Hodges‐Lehman’s estimates from epochs of 120 seconds at baseline and at ‐30 mmHg of LBNP. Statistical differences were calculated by Wilcoxon matched‐pairs signed rank test.Results: SVV_usd and SVV_bpc decreased at ‐30 mmHg LBNP to 32% (18%, 47%) and 32% (21%, 43%) of baseline variability. In contrast, SVV_imp was unchanged at ‐30 mmHg (88% (42%, 182%), p=0.82) relative to baseline.Conclusion: Cardiac stroke volume estimated by Ultrasound Doppler and finger arterial blood pressure curve reflect the same variations beat‐to‐beat during simulated hemorrhage. Cardiothoracic impedance does not reflect beat‐to‐beat changes in SV.Grant Funding Source: The Research Council of Norway
Intermittent hypoxia conditioning restricts iNOS and eNOS expression in rat myocardium: a mechanism for protection from ischemia and reperfusion injury (710.4)
Authors: Manukhina Eugenia , Goryacheva Anna , Belkina Ludmila , Terekhina Olga , Mallet Robert , Downey H 
Published: June 2021

Recently we demonstrated that intermittent, normobaric hypoxia conditioning (IHC) prevented injuries of myocardium and coronary blood vessels induced by myocardial ischemia and reperfusion (IR). This cardio‐ and vasoprotection of was associated with alleviation of nitric oxide overproduction. The aim of this study was to identify specific NO synthase(s) responsible for the IR‐induced NO overproduction and to determine the effect of IHC on these NO synthases. IHC of rats was performed in a normobaric chamber (5‐8 cycles/d for 20 d, FIO2 9.5 ‐ 10% for 5 ‐ 10 min/cycle, with intervening 4‐min normoxia). IR was produced by ligation of the left anterior descending coronary artery for 30 min followed by 60‐min reperfusion. The protein nitration marker, nitrotyrosine (3‐NT) and neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) nitric oxide synthases were measured by immunoblot. IR induced appreciable 3‐NT accumulation in the left ventriclular free wall, increasing the 3‐NT content by 42% (p<0.01), but not in septum. In IHC rats, 3‐NT after IR was similar to that of control rats without IR. IHC decreased iNOS by 71% (p<0.05) and eNOS by 41% (p<0.05) in the left ventricular myocardium; the myocardial content of nNOS remained unchanged. Therefore, IHC prevents IR‐induced NO overproduction in myocardium by restricting myocardial expression of iNOS and eNOS.Grant Funding Source: Supported by the Russian Foundation for Basic Research grant 10‐04‐00980
Chronic intermittent hypoxia alters blood pressure and mesenteric small resistance arterial responsiveness in mice (710.9)
Authors: Wang Youhua , Chen Ling , Zhang Jin 
Published: June 2021

Blood pressure (BP) is elevated in rats and mice exposed to chronic intermittent hypoxia (CIH). It is unclear if altered vascular function, such as myogenic reactivity (MR), contributes to BP elevation in CIH. We aimed to characterize the vascular alterations in small resistance arteries from CIH‐exposed mice. C57BL/6J mice were exposed to either CIH (1 min alterations of 5% and 21% O2) or normoxia (sham control, constant 21% O2), 8 hrs/day for 5 weeks. Compared to sham controls, CIH‐exposed mice had significantly higher BP, measured by radio telemetry. Mesenteric small resistance arteries were isolated and pressurized for diameter and wall thickness measurement. Myogenic constriction in response to intraluminal pressure increase (i.e., MR) was significantly attenuated, especially at pressures 蠅 70 mm Hg. At 70 mm Hg, vasodilations to acetylcholine and sodium nitroprusside, but not to external Ca2+ removal, were significantly impaired in CIH, whereas vasoconstrictions to phenylephrine (PE), endothelin‐1, U46619, and high [K+]o were similar between sham and CIH arteries. When intraluminal pressure was increased to 110 mm Hg, however, PE‐induced vasoconstriction was significantly reduced, and nitric oxide‐dependent vasodilation was further attenuated in CIH arteries. Arterial remodeling was not obvious since wall thickness, wall to lumen ratio, and passive diameters in Ca2+‐free solution were similar between two groups. Thus, CIH 1) elevates BP; 2) reduces MR; 3) reduces arterial responsiveness to vasodilators, and, at higher intraluminal pressure, to vasoconstrictors; 4) has no effect on arterial remodeling in mouse mesenteric small resistance arteries. It is likely that the altered arterial responsiveness is involved in the regulation of BP in CIH.Grant Funding Source: NIH/NHLBI R01 HL107654
Regulation of inflammatory gene expression by diabetes induced long noncoding RNA in macrophages (711.1)
Authors: Reddy Marpadga , Chen Zhuo , Park Jung‐Tak , Wang Mei , Lanting Linda , Zhang Qian , Wu Xiewie , Putta Sumanth , Natarajan Rama 
Published: June 2021

Long noncoding RNAs (lncRNAs) regulate gene expression in diverse patho‐physiological conditions, but their role in diabetes complications is not clear. We hypothesized that diabetes induced lncRNAs could mediate macrophage dysfunction implicated in vascular complications. We profiled gene expression in bone marrow derived macrophages (BMM) from type 2 diabetic db/db and control db/+ mice, after differentiation with GMCSF or MCSF. RT‐QPCR showed dysregulated polarization of BMM from db/db mice. RNA‐Seq revealed differential expression of 2000 transcripts including lncRNAs in BMM from db/db mice relative to db/+ mice. Differentially expressed genes were enriched in networks relevant to fibrosis, adhesion and inflammation, suggesting altered regulation of macrophage function. We validated the increased expression of a lncRNA E330013P06 (E33) in BMM and peritoneal macrophages from db/db and diet induced type 2 diabetic mice as well as macrophages treated with high glucose and palmitic acid. Furthermore, overexpression and siRNA mediated gene silencing demonstrated that E33 can increase inflammatory genes and foam cell formation in macrophages, establishing a novel role for a diabetes induced lncRNA in key macrophage functions involved in diabetic complications. Our findings suggest that understanding of lncRNA dependent mechanisms in macrophages could lead to novel therapeutic interventions.Grant Funding Source: NIH‐NIDDK
Protease‐activated receptor‐2 regulates BK channel activity in rat vagal bronchopulmonary sensory neurons (712.4)
Authors: Moss Charles , Gabriel Sabry , Gu Qihai 
Published: June 2021

Activation of protease‐activated receptor‐2 (PAR2) by endogenous or exogenous agonists contributes to airway inflammation and airway hyperresponsiveness, the hallmark features of allergic asthma; and a neurogenic mechanism involving PAR2 activation‐induced hypersensitivity of bronchopulmonary sensory nerves has been indicated. Large‐conductance Ca2+‐activated potassium (BK) channels are known to play an important role in shaping the neuronal excitability. The aim of this study was to investigate the role of BK channels in contributing to the PAR2‐induced neuronal hyperexcitability. Our immunohistochemical and RT‐PCR experiments demonstrated the expression of BK channels in rat bronchopulmonary sensory neurons. In whole‐cell perforated patch‐clamp recordings, BK currents were isolated from total K+ currents with an application of selective BK channel blocker paxilline. Our results showed that pretreatment with PAR2‐activating peptide (100 µM, 2 min) significantly reduced the BK current density in these sensory neurons. Our data suggest that the depression of BK channel activity and subsequent elevation of neuronal excitability of bronchopulmonary afferents may contribute to the pro‐inflammatory effects of PAR2 activation in the lungs and airways.Grant Funding Source: Supported by funds from MEDCEN and MUSM
Differential contributions of M2 and M3 muscarinic receptors to breathing and neurokinin and amino acid concentration in the ventral respiratory column (712.8)
Authors: Muere Clarissa , Neumueller Suzanne , Olesiak Samantha , Miller Justin , Langer Thomas , Hodges Matthew , Pan Lawrence , Forster Hubert 
Published: June 2021

Previously, it has been shown that dialysis of the non‐selective muscarinic receptor (mAChR) antagonist, Atropine (ATR, 50 mM), in vivo into the ventral respiratory column (VRC) of goats elicits an increase in breathing frequency associated with increases in substance P (SP), glycine, and GABA (Muere et al., J Appl Physiol, 114: 694‐704, 2013). To determine the specific mAChR subtype(s) mediating these effects, the specific M2 mAChR antagonist, Methoctramine (ME, 50 μM), and the specific M3 mAChR antagonist, 4‐DAMP (5 mM), were individually dialyzed into various sites in the VRC of adult goats chronically implanted with microtubules. Breathing was continuously measured and the effluent dialysate collected for quantification of neurochemical content. Preliminary results show that dialysis of ME tended to increase breathing frequency (n=4). ME tended to decrease levels of the amino acids glutamine, glycine, and GABA, while having no effect on SP concentration. Dialysis of 4‐DAMP had no effect on breathing frequency (n=2) and had variable effects on amino acid concentration. However, 4‐DAMP increased SP concentration to levels comparable with dialysis of ATR at a lower dose of 5 mM. These data suggest that the effect of ATR on breathing and neurochemical content is not due to a predominant effect on a specific mAChR subtype. Rather, a combination of mAChR subtypes differentially regulates multiple neuromodulators that affect respiration.Grant Funding Source: Supported by NHLBI Grants HL‐25739 & HL‐007852 & Department of Veterans Affairs
Enhanced phrenic long‐term facilitation in rats with motor neuron death from intrapleural CTB‐saporin injections (713.1)
Authors: Nichols Nicole , Mitchell Gordon 
Published: June 2021

Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to progressive motor neuron degeneration and death by ventilatory failure. In a model of ALS (SOD1G93A), pLTF following acute intermittent hypoxia is enhanced at disease end‐stage by unknown mechanisms (Nichols et al., ibid, 2010). Intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB‐SAP) selectively kills respiratory motor neurons and mimics motor neuron death observed in ALS rats (Nichols et al., ibid, 2013). This CTB‐SAP model allows us to study the impact of respiratory motor neuron death on breathing without many complications attendant to ALS. Here, we tested the hypothesis that phrenic motor neuron death is sufficient to enhance pLTF. pLTF was assessed in anesthetized, paralyzed and ventilated Sprague Dawley rats 7 and 28 days following bilateral intrapleural injections of: 1) CTB‐SAP (25μg), or 2) un‐conjugated CTB and SAP (control). CTB‐SAP enhanced pLTF at 7 (CTB‐SAP: 145±22%, n=10 vs. Control: 54±5%; n=15; p<0.05), but not 28 days post‐injection (CTB‐SAP: 61±14%, n=11 vs. Control: 37±9; n=5; p>0.05). Thus, pLTF at 7 (not 28) days post‐CTB‐SAP more closely resembles pLTF in end‐stage ALS rats, suggesting that processes unique to the period of active motor neuron death enhance pLTF. This project increases our understanding of respiratory plasticity and its implications for breathing in motor neuron disease.[Supported by NIH HL080209, HL69024 and the Francis Families Foundation]Grant Funding Source: Supported by NIH HL080209, HL69024 and the Francis Families Foundation
Inactivity‐induced phrenic motor facilitation does not require new protein synthesis (713.8)
Authors: Baertsch Nathan , Strey Kristi , Baker‐Herman Tracy 
Published: June 2021

Reduced respiratory neural activity elicits a TNFα‐ and atypical PKC‐dependent form of spinal plasticity in phrenic motor output termed inactivity‐induced phrenic motor facilitation (iPMF), a long‐lasting increase in phrenic nerve burst amplitude apparent once respiratory neural activity is restored. Many forms of neuroplasticity require protein synthesis for long‐term expression, including the most widely studied form of spinal respiratory plasticity, phrenic long‐term facilitation (pLTF; Baker‐Herman and Mitchell, 2002) elicited following acute intermittent hypoxia. We hypothesized that iPMF would also require de novo protein synthesis. Briefly, Sprague Dawley rats were urethane anesthetized, vagotomized, paralyzed, and prepared for electrophysiological recording. Rats received intrathecal injection (C4) of vehicle (aCSF; n=5) or the protein synthesis inhibitor emetine (n=6; 1ug/kg; Baker‐Herman and Mitchell, 2002) ~15 min prior to a prolonged (30min) period of neural apnea. As expected, in aCSF treated rats, phrenic nerve amplitude was significantly increased compared to baseline 5 min following reversal of neural apnea (53±11, %baseline) and was maintained for >60 min (54±16, %baseline), indicating long‐lasting iPMF. Contrary to our hypothesis, rats receiving emetine also expressed long‐lasting iPMF such that phrenic nerve burst amplitude was significantly increased from baseline at both 5 (41±8, %baseline) and 60 min (42±12,%baseline) following neural apnea (p<0.05). Importantly, phrenic nerve burst amplitude in rats receiving intrathecal emetine was not significantly different from rats receiving aCSF at any time point following neural apnea (p>0.05). Together, these data suggest that iPMF is a form of long‐lasting plasticity that does not require new protein synthesis.Grant Funding Source: Supported by NIH HL105511
NF‐kappaB activation in the fetal lung promotes macrophage maturation (715.3)
Authors: Stouch Ashley , Zaynagetdinov Rinat , Barham Whitney , Stinnett Amanda , Yull Fiona , Hoffman Hal , Blackwell Timothy , Prince Lawrence 
Published: June 2021

In preterm infants, exposure to inflammation increases the risk of chronic, developmental lung disease bronchopulmonary dysplasia. While macrophages are the key cells that initiate lung inflammation, little is known about lung macrophage phenotype and maturation. We hypothesized that fetal lung macrophages mature into distinct subpopulations during mouse development, and that activation could influence macrophage maturation. Expression of the fetal macrophage markers CD68, CD86, CD206, Ym1, fibrinogen‐like protein 2 (FGL2), and indolamine‐2, 3‐dioxygenase (Ido1) was developmentally regulated. Flow cytometry analysis measured a narrow spectrum of CD11b expression in fetal lung macrophages, with separation into CD11bloF4/80hi and CD11bhiF4/80lo subpopulations in newborn and adult lung. Similar to adult alveolar macrophages, fetal lung macrophages responded to the TLR4 agonist LPS and the alternative activation cytokines IL‐4 and IL‐13. Using a macrophage‐specific constitutively active IKKβeta transgenic model (IKFM), we demonstrated that macrophage activation increased proinflammatory gene expression and reduced the response of fetal lung macrophages to IL‐4 and IL‐13. Fetal IKFM lungs contained increased percentages of more mature, CD11bloF4/80hi cells that also expressed higher levels of the alternative activation markers CD204 and CD206. The maturational programming of fetal lung macrophages into mature alveolar macrophages therefore did not follow traditional proinflammatory and alternative activation paradigms.Grant Funding Source: Supported by National Institutes of Health Grants HL097195, HL086324, HL116358, HL069765
Apical volume expansion results in an immediate ENaC activation but in delayed onset of water resorption (718.1)
Authors: Wittekindt Oliver , Schmidt Hanna , Michel Christiane , Neubauer Daniel , Frick Manfred , Mizaikoff Boris , Dietl Paul 
Published: June 2021

Apical volume expansion results in an activation of the epithelial sodium channel ENaC. Its activation is proposed to facilitate water resorption and thus to counteract increases of apical surface liquid (ASL) volume e.g. in lung edema. In this study we investigated the adaptation of epithelial water resorption to apical volume expansion (AVE) in NCI‐H441 epithelia. Cells were cultivated at air‐liquid interface. AVE was introduced by adding isotonic NaCl solution onto the apical surface. Water resorption was measured by the recently established deuterium oxide dilution method (Neubauer et al. 2013, Anal Chem). ENaC channel activation was quantified in Ussing chamber experiments as amiloride sensitive short circuit currents. As expected, ENaC activity increases to its maximum within 15 min after AVE. Water resorption does not follow ENaC activation but starts 4 to 6 h after AVE. When ASL volume is reduced to 3.7 ±0.2 μl / 0.33 cm^2 water resorption stops and ENaC activity is reduced to basal levels. Our data demonstrate that AVE results in a rapid ENaC upregulation but ENaC activation is not the only trigger of onset of water resorption. However, off set of water resorption is associated with ENaC down regulation.Supported by BIU D.5007Grant Funding Source: Supported by BIU.5007
The ubiquitylated protein profile of rat cortical neurons is altered in a primary culture model of stroke (728.12)
Authors: Chua Michael Dominic , Pasqualotto Bryce , Rintoul Gordon , Guttman Julian 
Published: June 2021

Ischemic stroke is initiated by the lack of oxygen and glucose that are normally involved in maintaining the ion gradients at the presynaptic terminals. Overstimulation of postsynaptic glutamate receptors induces a massive influx of calcium, mitochondrial depolarization, and accumulation of reactive oxygen species causing neuronal death. To begin to understand the cellular effects on neurons following a stroke, we hypothesized that protein ubiquitylation would be altered due to its crucial role in cell signalling and protein labeling for subsequent degradation. To test this hypothesis, we analyzed immunoblots of glutamate‐treated primary rat cortical neuron cultures. We found that several low‐molecular weight proteins in the glutamate‐treated neuron lysates showed increased ubiquitylation levels as compared to untreated neuron lysates. The altered ubiquitylation profile of only a subset of proteins suggests that select small proteins are tightly regulated during stroke. Through this study, we have identified proteins specifically targeted during stroke. Their identification opens the door to targets for therapeutic intervention to rescue neurons following ischemic brain injury.Grant Funding Source: This study was funded through Departmental Funds