bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring Brown Adipose Tissue in Alaskan Sled Dogs: A Pilot Study
Authors: Kromrey Laura , Duffy Lawrence , Reynolds Arleigh , Dunlap Kriya 
Published: June 2021

Brown adipose tissue (BAT) has the unique function of burning energy to create heat through the process of non‐shivering thermogenesis. Activation of BAT in humans as a possible means of combating obesity is an active area of research, yet reliable methods for recognizing and monitoring BAT activation still need to be developed and validated. The purpose of this study was to assess the feasibility of thermal imaging for monitoring BAT activation in an in vivo animal model, specifically Alaskan sled dogs, which have been used extensively as models in cold‐weather metabolism and nutrition research. In this pilot study, BAT activation was monitored monthly over 4 months in a cohort of five sled dog puppies. Thermal images of the chest region and blood samples were collected before and after a cold exposure treatment. The thermal images were used to compare the temperature of the chest region pre‐ and post‐cold exposure, reasoning that a change in temperature would occur with BAT activation. Concentrations of two plasma biomarkers associated with non‐shivering thermogenesis, irisin and fibroblast growth factor 21 (FGF21), were measured in each blood sample. Although this pilot study did not have significant findings, it has produced a base of knowledge and methodology that is being used in current studies. Given the potential benefits of BAT activation for human health, the validation of thermal imaging as a non‐invasive monitoring technique and the use of an animal model could better inform the treatment of metabolic diseases.Support or Funding InformationFunding was provided by Nestlé Purina and the UAF BLaST Program. Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Numbers UL1GM118991, TL4GM118992, or RL5GM118990. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of K+ channels and NOS on human eccrine sweat gland function
Authors: Mack Gary W , Smith Ben , Rowland Ben 
Published: June 2021

The non‐selective NOS inhibitor L‐NAME has been shown to reduce cholinergic‐mediated sweating in humans. We tested the hypothesis that the effect of NOS inhibition on sweat gland out is mediated through the ability of NO to activate KCa1.1 channels. We generated stimulus response curves using: lactated‐Ringers, 50 mM TEA, 20 mM L‐NAME and a cocktail of 50 mM TEA plus 20 mM L‐NAME (n=10). Local sweat rate (SR) was measured by passing dry gas through a small sweat capsule mounted on the skin. The skin was stimulated at a constant current intensity of 2.5 mA for 30 s at frequencies of 0.2, 1, 2, 4, 6, 8, 12, 16, 32, and 64 Hz using two small stainless‐steel stimulating electrodes. We plotted the area under the SR‐time curve versus stimulus frequency. All data were expressed as the area under the local SR‐time curve (AUC) and normalize to the peak AUC response during Saline control trials (% AUC peak). During Ringers perfusion, peak local sweat output averaged 99.6 ± 5.7 AUC % peak which was significantly (p<0.0001) reduced by application of 50 mM TEA to 61.7 ± 22.7 AUC %peak. Addition of 20 mM L‐NAME to the 50 mM TEA solution produced an additional 20% reduction in peak SR to 42.5 ± 21.1 %AUC peak (p <0.05). These data support the hypothesis that sudomotor control of sweat gland activity is modulated by the presence of TEA sensitive K+ channels and the activity of an intrinsic NOS enzyme in the epithelial cells of the human sweat glands. Further, the ability of L‐NAME to produce an additional reduction in peak SR following 50 mM TEA indicates that the influence of NOS on local SR is not likely mediated via a modulation of TEA sensitive K+ channels.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Heat Acclimation Program for Firefighters Reduced Heat Stress and Improved Thermal Sensation and Thermal Comfort during Exercise Wearing a Firefighting Suit
Authors: Takeda Ryosuke , Imai Daiki , Kawai Eriko , Ota Akemi , Saho Kosuke , Morita Emiko , Suzuki Yuta , Yokoyama Hisayo , Takahashi Hideya , Hayashi Hideshi , Kimura Tasuku , Okazaki Kazunobu 
Published: June 2021

IntroductionFirefighters are exposed to an excessive heat stress and at the risk of heat‐related disorders and heat stroke during firefighting because they are wearing a firefighting suit with high insulation. Heat acclimation for firefighters would reduce the heat stress and the risk of heat‐related disorders during firefighting. Typical programs of heat acclimation require a few hours per day for 5 to 10 consecutive days and an artificial hot environment, those are unrealistic and impossible for them during their daily duty. In this study, we tested whether a heat acclimation program for firefighters performed in fire stations during daily duty with a simple exercise protocol wearing thermal insulation clothes would reduce heat stress and improve thermal sensation (TS) and thermal comfort (TC) during exercise wearing with a firefighting suit.MethodsTwenty male active firefighters (age; 20–50 years old) underwent a ~1‐month heat acclimation program (interval stair stepping exercise for 32 min, 4 sets of 5 min at high‐intensity – 3 min at low‐intensity, ~9 times/month) wearing a rain coat (9 subjects, RC group) or a firefighting suit (11 subjects, FS group) in addition to their regular training at their fire stations. Before and after intervention, they underwent a graded walking test (1.5, 3.0, 4.5, and 6.0 km/hour for 9 min each with 5% grade) wearing a firefighting suit in a climate chamber (25°C ambient temperature, 40% relative humidity). Heart rate (HR), esophageal (Tes) and mean skin temperatures (Tsk), skin blood flow (SkBF) and sweat rate (SR) at chest were continuously monitored and TS and TC were determined every minute. When Tes reached 38.5 °C, test was terminated before the end.ResultsAfter intervention, at rest, Tes and Tsk decreased and TS improved only in FS group, while TC improved in both groups (all, p < 0.05). In addition, Tes, Tsk, and also HR decreased and TS and TC improved during exercise in both groups (all, p < 0.05), though the reduction after intervention in these variables were prominent in FS group compared with RC group. SkBF and SR at chest in response to increased Tes were enhanced more in FS group than RC group.ConclusionsThe heat acclimation program performed in fire stations during daily duty in firefighters wearing thermal insulation clothes reduced heat stress with enhanced thermoregulatory responses and improve thermal sensation and comfort during exercise wearing a firefighting suit. Clothes that have higher thermal insulation (firefighting suit) would be more effective for the heat acclimation program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
N‐Acetyl cysteine improves dystrophic (mdx) mouse diaphragm muscle quality and strength
Authors: Burns David P , Drummond Sarah E , Bolger Dearbhla , Murphy Kevin H , Coiscaud Amélie P , Edge Deirdre , O'Halloran Ken D 
Published: June 2021

Respiratory muscle weakness occurs as a consequence of dystrophin deficiency in Duchenne muscular dystrophy (DMD), with implications for breathing and airway protective behaviours. The mdx mouse model of DMD shows evidence of impaired respiratory muscle performance with attendant inflammation and oxidative stress. N‐Acetyl cysteine (NAC) is a dietary antioxidant commonly used in the treatment of respiratory disease. We sought to examine the effects of NAC intervention on respiratory system performance in the mdx mouse.Young adult male wild‐type and mdx mice were studied; a subset of mdx received 1% NAC in the drinking water for 14 days. Ventilation was assessed in conscious mice using whole‐body plethysmography. Inspiratory pressure and respiratory muscle (diaphragm and external intercostal) EMG activity were assessed in anaesthetised mice during ventilatory and non‐ventilatory behaviours. Diaphragm ex vivo force‐generating capacity, muscle structure, cytokine concentrations, glutathione status and mRNA expression were determined. Data were statistically compared by unpaired Student's t test.Diaphragm function was severely impaired in mdx, evidenced by reductions in force‐generating capacity (40–160Hz range), total muscle shortening and maximal shortening velocity compared to wild‐type. Extensive diaphragm myofibre remodelling and damage was observed for mdx, characterised by increased muscle fibrosis, immune cell filtration, muscle fibre central nucleation and embryonic myosin expression. The pro‐inflammatory cytokines IL‐1β and IL‐6 were elevated in mdx diaphragm and plasma samples. mRNA studies indicate an increase in gene expression related to muscle atrophy, regeneration and inflammation in mdx diaphragm, and a reduction in anti‐oxidant related gene expression. NAC supplementation increased mdx diaphragm force (60–160Hz), maximal shortening and shortening velocity. Collagen deposition and the infiltration of putative inflammatory cells in mdx diaphragm was decreased following NAC. Mdx diaphragm and plasma IL‐1β and IL‐6 concentrations were decreased following NAC. Glutathione reductase and peroxidase activities were increased in mdx diaphragm; both were unaffected by NAC. mRNA expression of Nrf2 was increased in mdx diaphragm and increased further with NAC supplementation. No adverse effects of NAC intervention were observed on ventilation, inspiratory pressure and EMG, and growth measures.We reveal that NAC treatment improved mdx diaphragm force‐generating capacity by way of beneficial anti‐inflammatory and anti‐fibrotic effects. These data support the potential use of NAC as an adjunctive therapy in the dystrophinopathies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparing the Efficacy of Adeno‐associated Virus Serotype 9 (AAV9) Mediated Retrograde Transgene Delivery to Hypoglossal (XII) Motor Neurons (MNs) in Mouse Versus Rat Models
Authors: Doyle Brendan M , Jorgensen Marda , Falk Darin J , Mandel Ron J , Fuller David D 
Published: June 2021

Previous work by our group shows that AAV9 can robustly transduce XII MNs following direct intralingual injection and subsequent retrograde transport along the XII nerve. The current experiments compared the effectiveness of this approach in commonly studied strains of mouse and rat. In the adult C57BL/6 mouse, delivery of AAV9‐CBA‐GFP (1.20e10vg/μL, 8.33μL) via a unilateral or bilateral injection to the base of the tongue both produced a robust transgene expression in XII MNs as determined by immunohistochemistry (tissues harvested 6 weeks post‐injection). The extent of XII MN transduction was similar with uni‐ or bilateral tongue injection, presumably owing to the small volume of the mouse tongue. In contrast to the murine data, following intralingual delivery of AAV9‐CMV‐mCherry in adult Sprague‐Dawley (SD) rats (1.42e10vg/μL, 1.5 μL or 7.0μL), transgene expression in XII MNs was not detected using either fluorescence microscopy or antibodies against mCherry. Intralingual delivery was repeated in 3 separate cohorts (N=28 total) and MN transduction was never detected. We next tried a direct unilateral injection of AAV9‐mCherry into the main trunk of the XII nerve of adult SD rats (1.42e10vg/μL, 1.5μL). The nerve was injected in the neck, proximal to the point where it bifurcates into medial and lateral branches. At 6 wks post‐injection, we observed clear expression of mCherry in XII MNs detected using immunochemistry. Unexpectedly, MN transgene expression was seen in both XII motor nuclei, despite the unilateral nature of the AAV delivery. We are unaware of any neuroanatomical evidence to suggest that retrograde transport along a single XII nerve would result in bilateral targeting of XII motoneurons, and ongoing experiments are aimed at determining the mechanisms underlying this result. Collectively, these results indicate that retrograde transport of AAV9 following intramuscular delivery may show species variability. Problems with intralingual delivery in the rat were circumvented by direct delivery of AAV9 to the XII nerve.Support or Funding InformationFunding: 1R01HL139708‐01A1 (DDF)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Adenosine 2A Receptor Antagonism in Acute Cervical Contusion/Compression Injury Preserves Serotonin‐Dependent Phrenic Motor Plasticity
Authors: Seven Yasin B. , Allen Latoya L. , Tadjalli Arash , Zwick Amanda , El‐Chami Mohamad , Perim Raphael R. , Gonzalez‐Rothi Elisa J. , Mitchell Gordon S. 
Published: June 2021

Cervical spinal cord injury (cSCI) disrupts descending respiratory neural pathways, causing respiratory muscle paralysis and decreased breathing capacity. Immediately following acute trauma, a suite of pathogenic mechanisms contributes to secondary degeneration and respiratory failure including spinal ischemia, excitotoxicity and inflammation. These events are accompanied by increased extracellular adenosine that activates adenosine receptor signaling cascades. Adenosine 2A receptor (A2AR) antagonism is shown to preserve neurons in neurodegenerative diseases and ischemic injury, likely due to reduced excitotoxicity and inflammation. However, little is known concerning how A2AR activation immediately following cSCI impacts the respiratory control system and its neuromodulatory inputs. Thus, the fundamental hypothesis guiding this study is that A2ARs exert pathogenic effects on respiratory function and plasticity immediately following cSCI. Serotonergic plasticity plays a significant role in the respiratory control network. For example, the phrenic motor system exhibits phrenic long‐term facilitation (pLTF) following moderate acute intermittent hypoxia (AIH), a form of phrenic motor plasticity that requires raphe serotonergic neuron activation. Spinal trauma induces neurodegeneration in descending raphe serotonergic axons, undermining the capacity for pLTF following cSCI. Here, we tested the hypothesis that A2AR antagonism in acute cSCI preserves serotonin‐dependent, AIH‐induced pLTF in adult male Sprague‐Dawley rats with mid‐cervical spinal contusion with compression (cSCC). Addition of a brief compression with dwell time exacerbated the impact of C4/5 contusion as demonstrated by: 1) high death rates (~50% vs <10% without compression); 2) severe paralysis in all limbs for up to 5 days; 3) delays in regaining of the righting reflex; 4) ventilatory deficits when challenged with 7% CO2 + 10.5% O2; and 5) profound neurodegeneration extending rostrally to the brainstem. One week post‐cSCC, pLTF is abolished, consistent with degeneration in raphe serotonergic neurons. However, even a single administration of istradefylline 1‐hour post‐cSCC preserved and even augmented pLTF 1‐week post‐cSCC. Respiratory and locomotor functional studies are in progress. These exciting preliminary data suggest that plasticity outcomes are improved by A2AR antagonism in acute cSCC.Support or Funding InformationNIH OT2OD023854 (SPARC), HL69064, and K12 HD055929 (EGR), and the McKnight Brain Institute.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of TrkB Kinase Activity in Stabilization of Presynaptic Terminals Wanes in Old Age
Authors: Gransee Heather M. , Zhan Wen‐Zhi , Sieck Gary C. , Mantilla Carlos B. 
Published: June 2021

Brain derived neurotrophic factor (BDNF) acting through the high affinity tropomyosin‐related kinase receptor B (TrkB) plays an important role in synaptic plasticity and function at the neuromuscular junction (NMJ) as well as maintenance of neuromuscular transmission. Our previous studies showed that susceptibility to age‐related changes in diaphragm muscle (DIAm) NMJ morphology and denervation depends on trophic influences exerted by BDNF/TrkB signaling. Indeed, TrkB kinase activity is necessary to stabilize DIAm NMJ pre‐synaptic terminals in 18 month old mice (representing early old age; ~90% survival). However, by 24 months of age (~75% survival), BDNF/TrkB signaling has no effect on DIAm neuromuscular transmission, suggesting reduced TrkB kinase activity in the older age groups. We hypothesized that the NMJs that are resilient to old age do not depend on TrkB kinase activity for stabilization of pre‐synaptic terminals. Male and female 24 month old TrkBF616A mice were used to examine the structural properties of NMJs across various muscles with varying susceptibility to age‐related effects (DIAm, EDLm, and SOLm). Confocal microscopy was used to compare pre‐ and post‐synaptic morphology and denervation following a 7 day treatment with the phosphoprotein phosphatase‐1 derivative 1NMPP1, which inhibits TrkB kinase activity in TrkBF616A mice vs. vehicle treatment. Inhibition of TrkB kinase activity had no effect on pre‐synaptic or post‐synaptic terminal volume in DIAm, EDLm, and SOLm. Similarly, the overlap of pre‐ and post‐synaptic structures and the proportion of denervated NMJs did not change with 1NMPP1 treatment in all muscle types. The average percent of denervated NMJs was 8, 22, and 7% in DIAm, EDLm, and SOLm, respectively. Collectively these results suggest that the requirement of TrkB kinase activity for stabilization of NMJs in DIAm, EDLm and SOLm wanes in old age.Support or Funding InformationSupported by R01‐AG057052.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Distribution of Ipsilateral and Contralateral Glutamatergic Synaptic Inputs to Phrenic Motor Neurons
Authors: Rana Sabhya , Zhan Wen‐Zhi , Sieck Gary C. , Mantilla Carlos B. 
Published: June 2021

Excitatory descending glutamatergic (Glu) synaptic input to phrenic motor neurons (PhMNs) emanates from the ventrolateral medulla and is responsible for inspiratory drive and a range of higher force behaviors. Disruption of this excitatory input following unilateral C2 hemisection (C2SH) results in cessation of inspiratory‐related diaphragm muscle (DIAm) activity ipsilateral to injury, but DIAm activity during higher force behaviors persists, reflecting the contribution of spared contralateral inputs. In a model of PhMN (DIAm motor unit) recruitment, we proposed that smaller PhMNs innervating more fatigue resistant DIAm motor units are recruited to accomplish ventilatory behaviors, whereas larger PhMNs innervating more fatigable motor units are recruited to accomplish more forceful expulsive and straining behaviors. We hypothesized that differences in the distribution of ipsilateral and contralateral Glu synaptic inputs to PhMNs contribute to the effects of C2SH on the range of motor behaviors accomplished by the DIAm. Accordingly, we hypothesized that C2SH primarily disrupts ipsilateral Glu synaptic inputs to smaller PhMNs, whereas Glu synaptic inputs to larger PhMNs are minimally impacted after C2SH. To address this hypothesis, we examined changes in Glu presynaptic input onto retrogradely labeled PhMNs using immunohistochemistry for VGLUT1 and VGLUT2. We found that following C2SH (by 7 days), there was a ~45% reduction in ipsilateral Glu synaptic input to PhMNs compared to a ~20% reduction contralaterally. In addition, ipsilateral to C2SH, Glu synaptic input to smaller PhMNs was reduced to a greater extent compared to that to larger PhMNs (55 vs. 35% reduction, respectively). Contralateral to C2SH, inputs to PhMNs were similarly reduced independent of motor neuron size. These results are consistent with more uniformly distributed contralateral inputs to all PhMNs and predominant input to smaller PhMNs ipsilaterally. These results also indicate that the source of Glu synaptic input to PhMNs varies depending on motor neuron size and likely reflects different motor control, including possibly distinct central pattern generator and premotor circuits.Support or Funding InformationGrant Support: NIH Grant R01 HL96750 and Mayo Clinic Graduate School of Biomedical SciencesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Extracellular Vesicle Sphingolipids from Stored Platelets Mediate Transfusion Related Acute Lung Injury
Authors: McVey Mark John , Maishan Mazharul , Spring Chris , Semple John W , Kuebler Wolfgang M 
Published: June 2021

BACKGROUNDTransfusion‐related acute lung injury (TRALI) leads to chest infiltrates and hypoxia after 0.02–1% of transfusions with an associated mortality up to 15%. Sphingolipid ceramide weakens endothelial barriers while sphingosine‐1‐phosphate (S1P) is barrier protective. Aged stored platelets elicit TRALI by acid sphingomyelinase (ASM) dependent ceramide formation, which causes lung injury (in vivo) and impairs pulmonary endothelial cell (EC) barrier integrity (in vitro). Concomitantly, aged platelets form extracellular vesicles (EVs) which can shuttle hydrophobic lipids such as sphingolipids to target cells. Combining these concepts, we hypothesized that 5‐day but not 1‐day stored platelets generate EVs which mediate TRALI in a sphingolipid‐dependent manner.METHODSEVs from male C57BL/6 wild type (WT) or Smpd1−/− (ASM knockout) platelets stored for 1‐ or 5‐days duration were isolated by differential centrifugation and filtration prior to enumeration (flow cytometry) and sphingolipid analysis (mass spectroscopy). For TRALI induction, BALB/c male mice were primed with 2 mg/kg intraperitoneal lipopolysaccharide (LPS) two hours prior to intravenous infusion of 10 ml/kg EVs (≈ 5×106) or saline (sham) and were assessed (6 hours later) by measuring lung tissue wet‐to‐dry (W/D) weight ratios, bronchoalveolar lavage fluid protein (BAL‐p) and lung tissue myeloperoxidase activity (MPO). Transendothelial electrical resistance (TEER) was measured in cultured human microvascular pulmonary ECs treated with PBS (sham) or 5×105 EVs (from 1‐ vs 5‐day stored platelets) for 4 hours.RESULTSCompared with 1‐day EVs, 5‐day EVs were more numerous, ceramide enriched and S1P depleted. 5‐day EVs from ASM KO platelets were less numerous than 5‐day WT EVs, but had similar sphingolipid profiles. LPS primed mice receiving 5‐day EVs had increased W/D (p < 0.05), MPO and BAL‐p (p<0.05) relative to mice receiving LPS priming in addition to saline (sham), 1‐day EVs or ASM KO 5‐day EVs. 5‐day EVs but not 1‐day EVs led to reductions in TEER (< 2 hours) in vitro in keeping with EC loss of barrier integrity which persisted for > 4 hours. 5‐day EVs could be made to resemble 1‐day EVs (no injury) with addition of exogenous S1P at levels equivalent to those found in 1‐day EVs.CONCLUSIONSCeramide formation in aged platelets contributes to EV formation and impairs human EC barrier integrity resulting in TRALI. Removal or modification of aged EVs from stored platelets may prove a therapeutic option to reduce the risk of aged cellular blood products from causing TRALI.Support or Funding InformationThis work was jointly funded by Canadian Blood Services and the Canadian Institute of Health Research (CIHR). MJM is supported by a CIHR Vanier ScholarshipThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.