bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of environmental temperature and humidity on a model of exertional heat stroke in mice (1104.26)
Authors: King Michelle , Leon Lisa , Clanton Thomas 
Published: June 2021

Effects of environmental temperature and humidity on a model of exertional heat stroke in mice Michelle A. King1, Lisa R. Leon2, and Thomas L. Clanton1 1 Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida; 2U.S. Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, Massachusetts.The pathophysiology of exertional heat stroke (EHS) may differ from passive heat stroke, but limited models are available. We describe EHS in conscious C57Bl/6 mice, instrumented with telemeters and exposed to environmental temperatures (Tenv) from 37.5‐39.5C, and relative humidities (RH) from 30‐90%. Mice exercised on a forced running wheel using an incremental protocol until neurological symptoms (fainting) became limiting. All animals survived 4 d. No significant differences were seen between max core temperatures (Tmax=42.1‐42.5C) at differing Tenv, when RH=30‐50%. Paradoxically, at 90% RH, symptom‐limited Tmax averaged 41.50.1C (P<0.01). However, exercise time and peak running speed were highest at 90% RH (P<0.05). The minimum core temp reached during hypothermia was also significantly higher at 90% vs. 30% RH (P<0.025). Thermal loads were highest at Tenv=37.5C, irrespective of RH (P<0.01). However, the percent loss of body weight (3‐11.5%) was not different in any condition. The results demonstrate that similar forms of EHS can be observed in mice over a wide range of Tenv and RHs, resulting in symptoms, Tmax and other characteristics resembling human EHS. Author views not official US Army or DoD policy.Grant Funding Source: USARIEM, Natick MA
Computational modeling of the effects of temperature on chemosensitive locus coeruleus neurons from bullfrogs (1128.3)
Authors: Putnam Robert , Quintero Maria , Santin Joseph , Cordovez Juan , Hartzler Lynn 
Published: June 2021

Chemosensitive LC neurons from bullfrogs increase their firing rate and have altered action potential (AP) waveforms upon cooling from 20°C to 10°C (Santin et al., Amer. J. Physiol. Doi:10.1152/ajpregu.00348.2013). We developed a computational model to study this unusual neuronal response to cold temperature. Using MatLab, we have a 4 dimensional model based on a Hodgkin‐Huxley formulation that includes a voltage‐gated Na channel, a delayed‐rectifying K (Kdr) channel and a leak K channel. The model generates a firing rate of ~12 Hz and AP waveforms that are similar to those of bullfrog LC neurons at 20°C. For instance, values (neuron:model) for AP height (60 mV:51 mV), maximum rate of depolarization (36 mV/ms:40 mV/ms), maximum rate of repolarization (‐27 mV/ms:‐23 mV/ms), the AP width (2.1 ms:2.6 ms) and after hyperpolarization (AHP) (‐60 mV:‐66 mV) are similar comparing the model to the actual neuron. Colder temperature (10°C) decreases neuronal maximum rates of depolarization and repolarization, increases the AP width, and decreases the AHP. Changing, in a depolarizing direction, the voltage at which the time constant of inactivation for Kdr channels reaches a maximum and increasing the time constant for Na channel activation in the model results in similar changes in AP waveform parameters. However, the model changes result in decreased firing rate (~6 Hz) while temperature changes in neurons result in increased firing rate. This suggests that another channel is involved in the temperature effects on firing rate. In line with this, we found a hyperpolarization‐activated current (IH) in LC neurons that will be added in our model to determine if altering the parameters of the IH current contributes to cold temperature‐induced increased firing rate in bullfrog LC neurons. We ultimately plan to use both the model and electrophysiology studies to gain insights into the neuronal basis for chemosensitivity and cold temperature responses in chemosensitive LC neurons from bullfrog.Grant Funding Source: Supported by Admin. Dept. of Sci., Technol. & Innov. of Col (COLCIENCIAS) and NSF Grant IOS‐1257338.
Endocannabinoid effects on neuronal function in the NTS of hypertensive rats (1130.3)
Authors: Hopp Francis , Dean Caron , Seagard Jeanne 
Published: June 2021

Previously, we showed that endocannabinoid activation of cannabinoid 1 receptors (CB1Rs) in the nucleus tractus solitarius (NTS) activates barosensitive neurons and prolongs baroreflex inhibition of renal sympathetic nerve activity in normotensive Sprague Dawley (SD) rats, but reflex responses were attenuated in spontaneously hypertensive rats (SHR). This study examined the effect of CB1Rs on NTS barosensitive neurons in SHRs to determine if the lack of reflex responses is associated with diminished effects on neuronal firing. NTS neuronal activity was recorded in the working heart brainstem preparation in SHR or SD rats, with increases in perfusion pressure used to identify barosensitive firing. To examine the effects of CB1Rs on neuronal discharge, picoejections of the CB1R agonist anandamide (AEA), antagonist SR141716, or blocker of AEA catabolism, AM404, were made through a multibarrel pipette array which contained the carbon fiber recording electrode. AEA acting at CB1Rs increased barosensitive neuronal firing in SD versus SHR rats. In addition, discharge of respiratory I neurons, identified by correlation to phrenic nerve discharge, was found to respond more to CB1R activation in SD rats versus SHRs. The data indicate that neuronal function of CB1Rs in the NTS is blunted in SHRs.Grant Funding Source: Suppoted by VA Merit Review I01 BX000481 (JLS), NSF Award IOS 0751613 (CD)
Role of histamine in the sensory motor integration of gill lateral cell cilia in the bivalve mollusc, Crassostrea virginica (1131.1)
Authors: Akande Patrick , Duncan Jened , Catapane Edward , Carroll Margaret 
Published: June 2021

Lateral gill cells of Crassostrea virginica are innervated by serotonin and dopamine nerves from their ganglia. Most bivalves have lateral cell cilia that respond to serotonin and dopamine. The motor aspects have been well studied, but not the sensory side. There is limited information about sensory inputs. We found C. virginica can sense and adjust gill cilia beating to the presence of food and a variety of chemical cues including histamine (HIS). HIS does not alter beating when applied to gill, but when applied to mantle rim decreases beating. Detaching the mantle rim or transecting the branchial nerve prevents this. We hypothesize HIS is a sensory neurotransmitter in mantle rim involved in sensory‐motor integration of gill lateral cilia. We studied actions of HIS and 3 different classes of HIS receptor antagonists. Cilia beating was measured by stroboscopic microscopy. Adding HIS (10‐6 ‐ 10‐3 M) to mantle rim decreased cilia beating. H1 antagonist diphenhydramine and H2 antagonist famotidine blocked HIS over the range of 10‐3 ‐ 10‐9. Conessine a H3 antagonist did not block HIS. The study further demonstrates a sensory‐motor integration of beating of lateral cilia involving the sensory mantle rim and visceral ganglia and suggests HIS is a sensory neurotransmitter in mantle receptor cells that synapses with afferents going to the VG where signals are integrated resulting in a motor response to the gill lateral cells.Grant Funding Source: NIH‐2R25GM06003, NSF‐0622197, NYSED‐ 0516041071
miRNA expression profile in non‐human primate in response to Yersinia pestis infection (1138.3)
Authors: Dimitrov George , Moyler Candace , Gautam Aarti , Kumar Raina , Hammamieh Rasha , Jett Marti 
Published: June 2021

miRNA expression profile in non‐human primate in response to Yersinia pestis infection George Dimitrov, Candace Moyler, Aarti Gautam, Raina Kumar, Rasha Hammamieh and Marti Jett Integrative Systems Biology Program, US Army Center for Environmental Health Research 568 Doughten Drive, Fort Detrick, MD 21702‐5010 MicroRNAs (miRNAs) are small non‐coding RNA molecules, 20‐30 nucleotides in size, that suppress gene expression at both transcriptional and post‐transcriptional levels. Recent studies indicate that miRNAs play significant roles in pathogen‐host interactions. Yersinia pestis is a gram‐negative obligate pathogen and the causative agent of plague, which throughout history has had a devastating effect on human population. We carried out miRNA profiling studies in tissues and blood samples collected from African green monkeys (Cercopithecus aethiops) exposed to aerosolized Y. pestis CO92. These studies enabled us to examine and identify the tissue‐specific differences in small RNA expression profiles during pathogen‐host interactions, and to detect their regulation patterns during the progression of disease. For this study, we used a small RNA Illumina deep sequencing method. Total yields of clean sequencing reads ranging from 17009208 to 11126920 were obtained after removing adaptor contamination and quality filtering. The size distribution of small RNAs (miRNA) ranged from 20 to 24 nt, which accounted for 38 percent of the total reads. The miRNA precursor and mature miRNA expression profiles were created. These will allow us to study the expression profile for tissue‐specific miRNA across different time points.Grant Funding Source: TMTI0029_09_WR_T from the Department of Defense
Prenatal hypoxia modifies cardiac performance in adult bobwhite quail, assessed by pressure‐volume loop analysis (1150.10)
Authors: Flores‐Santin Josele , Burggren Warren 
Published: June 2021

Prenatal hypoxia modifies cardiac performance in adult bobwhite quail, assessed by pressure‐volume loop analysis Josele Flores‐Santin1 joselefloressantin@my.unt.edu, Warren Burggren1 Burggren@unt.edu1University of North Texas, Biology department, 1155 Union circle, Denton Texas U.S.The consequences of early embryonic stressors and how they affect subsequent adult life reflects the concept of “fetal programming”. This programming potentially produces functional anomalies in major organs including the lungs, the kidneys and the heart, based on studies of a limited number of “traditional” animal models for fetal programming. The aim of this project is to use a non‐traditional model ‐ the rapidly maturing bobwhite quail ‐ to study the effects of embryonic stressors as they manifest themselves in adults, with an emphasis on the working heart. The fast development along with the small size of quail makes them a potentially important alternative animal model to study cardiovascular physiology and the changes that prenatal stressors produce on it. In this study we submitted quail eggs to hypoxia (15%). This treatment accelerated hatching by one day (26±0.11) in comparison to controls (27.6±.12). The treatment also induced a lower hatching mass (6.9±1.0) than controls (5.9±0.1). Pressure‐volume loop SVL catheter technology was used to evaluate cardiovascular performance in adult birds (controls and following embryonic hypoxia). Hypoxic birds presented a phenotype resembling mammalian left ventricular hypertrophy, with a decreased cardiac output (38660±817), ejection fraction (38.8±0.4) and stroke work (11750±376). We conclude that bobwhite quail are a viable alternative model to study cardiovascular fetal programming.Grant Funding Source: Supported by NSF & CoMeCyT/CONACYT
Extracellular matrix‐mediated endothelial differentiation of human induced pluripotent stem cells (1152.4)
Authors: Hou Luqia , Huang Ngan 
Published: June 2021

Over 8 million Americans are suffering from Peripheral Arterial Disease (PAD), which is due to atherosclerotic occlusion of the peripheral arteries of the limbs. Recent studies suggest that human induced pluripotent stem cell (iPSC)‐derived endothelial cells (iPSC‐ECs) can serve as a promising source for treatment of PAD. However, the low differentiation efficiency of iPSC‐ECs is a major limitation to their clinical use. The purpose of this study was to investigate the role of extracellular matrix (ECM) and cell‐ECM interactions in endothelial differentiation of iPSCs utilizing high throughput ECM microarray technique. We developed a high‐throughput ECM microarray that contains circular printed areas of ECMs on glass slides using a robotic DNA microarrayer. Multi‐component mixtures of purified ECMs components (gelatin, fibronectin, laminin, heparin sulfate proteoglycans, collagen IV, and matrigel) were deposited onto glass slides at fixed distances. A total of 280 spotted matrix features were fabricated with multi‐component mixtures of the ECM components. After dissociating and culturing iPSCs onto ECM microarrays, differentiation was induced by adding VEGF (50ng/ml) for 5 days. EC differentiation was confirmed with CD31 staining, whose expression was scored semi‐quantitatively and averaged among the six replicates on the slide. A greater abundance of CD31 with higher score was observed in ECM features composed of gelatin + laminin + fibronectin tri‐component mixtures comparing to other conditions. Gene expressions of various integrin subunits were compared between iPSCs and iPSC‐ECs to elucidate the role of cell‐ECM interactions. The expression of integrins α1 through α6 and β1 through β4 were elevated in iPSC‐ECs comparing to iPSCs. On the other hand, β5 shows a significant decrease in iPSC‐ECs. In total, this data suggested that ECM differentially promote iPSC differentiation into EC, possibly through binding to various types of integrins.Grant Funding Source: NIH, NSF, Stanford CVI
Short‐term naproxcinod treatment ameliorates functional muscle ischemia in dystrophin‐deficient mdx mice (1156.1)
Authors: Li Liang , Miglietta Daniela , Thomas Gail 
Published: June 2021

Impaired nitric oxide (NO) signaling in the dystrophin‐deficient muscles of patients with Duchenne muscular dystrophy (DMD) and the mdx mouse model of DMD renders the diseased muscles susceptible to functional ischemia, which enhances both fatigue and exercise‐induced muscle injury. We therefore asked if short‐term treatment with naproxcinod, a NO‐donating naproxen, would prevent functional muscle ischemia and restore normal blood flow regulation in the exercising muscles of mdx mice. Norepinephrine (NE) evoked similar decreases in femoral vascular conductance (FVC) in resting and contracting hindlimbs of vehicle‐treated mdx mice, indicating functional muscle ischemia (ΔFVC contraction/rest: 0.93 ± 0.16, n=5). Naproxcinod (40 mg/kg, po) modestly reduced muscle ischemia when given as a single dose and markedly ameliorated it when treatment was extended to 1 wk (ΔFVC contraction/rest: 0.67 ± 0.18 and 0.39 ± 0.08, respectively; n=9 each), while treatment with equimolar naproxen was without effect (n=5). Daily treatment with a lower dose of naproxcinod (20 mg/kg) was equally effective in preventing functional ischemia in mdx and nNOS null mice (ΔFVC contraction/rest: 0.39 ± 0.05, n=10 and 0.31 ± 0.02, n=4, respectively). These findings suggest that naproxcinod’s ability to donate NO rather than inhibit cyclooxygenase is the main mechanism by which the drug improves muscle blood flow regulation in mdx mice.Grant Funding Source: Supported by DoD, W81XWH‐12‐1‐0256
Antioxidant activity of currently available resuscitation fluids in vitro (1157.5)
Authors: Barr Johnny , Jacobson David , Grubbs Dana , Dubick Michael 
Published: June 2021

Addition of antioxidants to resuscitation from hemorrhage reportedly improves outcomes in experimental animals. The present study investigated whether currently available resuscitation fluids have intrinsic antioxidant activity. Direct antioxidant activity of normal saline, hypertonic saline alone or with Dextran, Ringer’s solution alone or with lactate, pyruvate, or β‐hydroxybutyrate, Hextend, Voluven, plasma, 5% albumin and Hyvisc drag‐reducing compounds were investigated in duplicate in systems to either inhibit xanthine oxidase (XO) or superoxide dismutase (SOD) generated oxidant production or measure antioxidant status. N‐acetylcysteine (NAC) was included as a positive control. In the XO system, Hextend showed minor antioxidant activity, whereas Hyvisc preparations, plasma and Ringer’s showed antioxidant activity similar to NAC. All fluids tested inhibited superoxide production in the SOD system about 10% compared to over 30% by NAC. There did not appear to be any significant difference between colloids and crystalloids or compounds such as pyruvate or albumin at the concentrations selected. Taken together these data suggest that currently available resuscitation fluids have minor, if any, intrinsic antioxidant activity. Reported antioxidant properties of these compounds in vivo, most likely reflects indirect activity through their interactions with biological systems.Grant Funding Source: US Army Medical Research Materiel Command
Regulation of the browning of human white adipose: evidence for sympathetic control and sexual dimorphic responses to sprint interval training (1160.4)
Authors: Scalzo Rebecca , Peltonen Garrett , Giordano Gregory , Binns Scott , Klochak Anna , Paris Hunter , Schweder Melani , Szallar Steve , Wood Lacey , Larson Dennis , Luckasen Gary , Hickey Matthew , Bell Christopher 
Published: June 2021

The conversion of white to thermogenic beige adipose tissue has been proposed as an obesity treatment. 3 regulators of this conversion have emerged but information regarding their control is limited. We present 2 studies examining control of these regulators. Study 1: In 10 men, plasma irisin and fibroblast growth factor 21 (FGF21) concentrations were determined prior‐to/during sympathetic activation via hypoxic gas breathing (FIO2=0.11). The measurements were performed twice: with and without sympathetic inhibition (clonidine). FGF21 was unaffected by basal sympathetic inhibition (338±113 vs. 295±80 pg/mL; P=0.43; mean±SE), but was increased during sympathetic activation (368±135); clonidine abrogated this response (269±93; P=0.035). Irisin was unaffected by sympathetic inhibition and/or hypoxia (P>0.21). Study 2: Plasma irisin and FGF21 concentrations, and skeletal muscle protein content of fibronectin type III domain containing 5 (FNDC5) was determined in 19 adults pre/post 3 weeks of sprint interval training (SIT). SIT decreased FGF21 (338±78 vs. 251±36; P=0.046) but did not affect FNDC5 (P=0.79). Irisin was decreased in males (127±18 vs. 90±23 ng/mL; P=0.045) and increased in females (139±14 vs. 170±18). These data suggest a regulatory role of acute sympathetic activation pertaining to the browning of white adipose; further, there appears to be a sexual dimorphic response of irisin to SIT.Grant Funding Source: Supported by DARPA: N66001‐10‐c‐2134
Differential response of microRNA to contraction in aged and obese mice (1168.4)
Authors: Rice Nicholas , Haran Prashanth , Fielding Roger , Rivas Donato 
Published: June 2021

Resistance to anabolic stimuli in skeletal muscle occurs within both aging and obese populations. However, the mechanisms responsible for this ‘anabolic resistance’ are unknown. MicroRNA (miRNA), small (20‐24 nucleotides) post‐transcriptional regulators, have recently been shown to play a role in the response of skeletal muscle to anabolic stimulation. We aimed to compare the response of miRNA to an acute bout of contraction via sciatic nerve electrical stimulation (ES) in skeletal muscle within three groups of C57BL/6 mice aged, 24 wks and fed a control (CON, 10% fat/kcal) or high‐fat (FAT, 60% fat/kcal) diet or aged 124 wks (OLD, 10% fat/kcal). The expressions of miRNA that are known (miR‐378, miR‐27a) and putative (miR‐126, miR‐324) regulators of skeletal muscle development were measured by qPCR at baseline (BL) and after ES. Obesity increased the BL expression of miR‐27a and miR‐324, while miR‐27a and mir‐378 expression was increased with age, compared to CON. After contraction, miR‐126 and miR‐378 were decreased in CON, while miR‐27a and miR‐324 were decreased in FAT. However, the only contraction‐induced change in OLD was a decrease of miR‐378 expression back to control levels. These results illustrate the differential responses of miRNA in skeletal muscle as a result of ES within these distinct groups.Grant Funding Source: USDA and NIH/NIA
Dual actions of octopamine on heart rate of Crassostrea virginica (1169.1)
Authors: Jean Louis Addy , Carroll Margaret , Catapane Edward 
Published: June 2021

Octopamine (OA) is well studied in arthropods. OA’s presence and functions have rarely been reported in bivalves. Previously we found OA present in ganglia and tissues of the oyster Crassostrea virginica. OA was cardio‐acceleratory when applied in situ to animals but cardio‐inhibitory when applied to isolated hearts. We hypothesize the divergent results of OA on heart rate is due to separate actions of OA on visceral ganglia (VG) compared to isolated hearts. We applied OA to VG of animal preparations, with and without transecting the cardiac nerve. We also tested OA on isolated hearts and ventricular muscle strips. We found average basal heart rate of animal preparations was 15 beats/min. Superfusing OA (10‐6 ‐ 10‐3 M) onto animal or VG preparations caused dose‐dependent increases of up to 70%. Applying OA to isolated hearts or heart strips decreased rates to 0. The OA antagonist metoclopramide produced a dose‐dependent blockage of OA actions on animals and heart strips. In animals transecting the cardiac nerve prevented the cardio‐acceleratory effects of OA. The study shows OA affects heart rate in 2 fashions depending on site of application, inhibitory when applied to isolated heart or acceleratory when applied to the animals or VG. At the VG, OA may be stimulating cardio‐acceleratory neurons innervating the heart.Grant Funding Source: Nih‐2R25GM06003, NYSE 0516041171, NSF‐0622197
Renal cell transplantation reverses PKD progression (1180.22)
Authors: Kelly Katherine , Dominguez Jesus 
Published: June 2021

Polycystic kidney disease (PKD, including ADPKD1, ADPKD2, ARPKD) are diseases with overlapping phenotypes and are not curable. They can progress to ESRD, and then the only hope to get off of dialysis is kidney transplantation. We have introduced intravenous renal cell transplantation (IRCT) in rats as an alternative to kidney transplantation, and tested the hypothesis that IRCT with Serum Amyloid A protein (SAA) expressing normal adult renal cells improves structure and function in PKD by coordinating the re‐orientation of adjacent host PKD cells. We tested this idea in the PCK rat, an orthologus model of ARPKD. We included six rat groups starting with surgery at 6 weeks of age and IRCT at 6, 8, and 10 weeks of age, termination was at 26 weeks of age: SA, were sham operated and given SAA negative cells, n=7. SB, were sham operated and given SAA positive cells, n=7. IA, had unilateral renal ischemia for 50 min and given SAA negative cells, n=8. IB, had unilateral renal ischemia for 50 min and given SAA positive cells, n=8. CS, were sham operated PCK rats that did not receive cells, n = 5. CI, were PCK rats subjected to unilateral renal ischemia and did not receive cells. We followed renal function and structure with Dynamic Contrast Enhanced CT (DCE‐CT). Donor cells were found on the cyst walls and damaged tubules. The donor cells were identified 16 weeks post‐transplant by PCR of the SRY (male gene in female kidneys), transferred SAA gene, as well as FISH of the Y chromosome, and by renal genotype revealing mutated (endogenous) and wild type (donor) ARPKD genes. The SAA positive “B” cells drastically improved function and structure and diminished the number of cysts. Transplanted “A” cells also had a positive effect but were less effective than “B” cells. IRCT is an effective means to retard cyst development and progression (all “B” groups significantly different than corresponding “A” groups, p <0.05) in the PCK and has a great potential for PKD therapy.Grant Funding Source: NIH, DoD, VA