bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lasting alterations to the exercise ventilatory response in adult survivors of prematurity
Authors: Welper Hannah M , Farrel Emily , Pegelow David , Jacobson Joseph , Baker Kim , Dagle John , Eldridge Marlowe , Bates Melissa 
Published: June 2021

IntroductionWe previously published that the ventilatory drive in adult survivors of prematurity is impaired in hypoxic conditions. Previously studies in adult survivors of prematurity demonstrate impairments in expiratory flow that limit ventilation during exercise. However, ventilatory drive during exercise has not been explored. Therefore, the purpose of this study was to evaluate the ventilatory drive during exercise, including exercise in hypoxia. We hypothesized that the ventilatory drive (VE/VCO2) to exercise would be limited in individuals born premature and not further impacted by hypoxia.MethodsPrematurely born adults (age 19–21) from the Newborn Lung Project cohort participated in two graded exercise tests breathing either 21% (normoxia) or 12% (hypoxia) oxygen. The term‐born control group was well‐matched in terms of sex, height, weight, baseline pulmonary function, and VO2max. We measured arterial blood gases, metabolism and ventilation at each workload to determine the ventilatory response to normoxic and hypoxic exercise.ResultsIn normoxic exercise, adults born prematurely have overall increased minute ventilation, compared to controls, explained by an increased frequency that compensated for their limited tidal volume. VE/VCO2 was also greater, suggesting reduced ventilatory efficiency. This is can be explained by the lower blood pH during exercise. In hypoxic exercise, the ventilatory drive in adults born prematurely is more similar to the control.ConclusionWe demonstrate the existence of a lifelong ventilation phenotype associated with prematurity that, contrary to our hypothesis, includes decreased ventilatory efficiency (increased VE/VCO2) and decreased blood pH. Prematurely‐born adults compensate for poor chemoreceptor function in hypoxic exercise via mechanisms currently being investigated by our group.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of blue light blocking glass on clock gene expression, melatonin secretion and sleep quality in humans
Authors: Sato Maki , Oishi Sayo , Kodama Chihiro , Inukai Yoko , Kamiya Mika , Nishimura Naoki , Kanikowska Dominika , Iwase Satoshi 
Published: June 2021

Light has a strong effect on the circadian rhythm. Blue light at night has a negative effect on melatonin secretion and sleep quality. Recently, a smart phone is popularly used in the whole day even including night, resulting in the increased rate of insomnia and difficulties of quality of sleep. In the present study, we investigated that the effect of blue light blocking glass on clock gene expression, melatonin secretion and sleep quality in humans. Seven men participated in this study for overnight from 18:00 h to 8:00 h of next day. Each subject underwent two conditions with and without wearing blue light blocking glass on a different day. Subjects sat in front of 5000 lux fluorescent and blue light lumps until sleep at 0:00 h in a climatic chamber set at 26°C and 50% relative humidity. Subjects were measured Electrocardiogram during the experiment and Electroencephalogram during the night. Saliva samples were collected at 20:00 h, 23:30 h, 6:00 h and 8:00 h. Total RNA was isolated from saliva sample and was measured the clock gene expressions of Clock, Bmal1, Per1 and Cry1 by real‐time PCR. Clock gene expression were not significantly different between the two groups. The melatonin concentrations were not significantly different between the two groups. Total percentage of slow‐wave sleep and the sleep latency to stage 3 were not significantly different with both conditions. Our results suggested that blue blocking glass have individual effects under strong light by 5000 lux.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 Effect of Mild Heat Stress on Event‐Related Potential in the Elderly
Authors: Ota Akemi , Takeda Ryosuke , Imai Daiki , Kawai Eriko , Saho Kosuke , Morita Emiko , Suzuki Yuta , Yokoyama Hisayo , Okazaki Kazunobu 
Published: June 2021

BackgroundThe cognitive function is generally decreased with healthy aging. The cognitive processing evaluated by electroencephalogram event‐related potentials (ERPs) has been reported to be decreased with heat stress in young individuals, while remained unclear in the elderly. Therefore we tested the hypothesis that the cognitive processing would be decreased in the elderly compared with the youth during mild hyperthermia.MethodsFive elderly and 11 young healthy men underwent auditory oddball paradigms under two thermal conditions; Normothermia (NT) and mild hyperthermia (HT; esophageal temperature, +1°C) with lower legs immersion of 42°C and with water perfusion suits of 45°C. The reaction time by pushing a button and the latency and amplitude of P300 component to the auditory oddball paradigms were measured.ResultsThe reaction time was decreased during HT compared to NT (P < 0.05). In contrast, the latency of the P300 component did not change with heat stress in both age groups. The amplitude of P300 component decreased in the elderly group while increased in the young group with heat stress (age x thermal condition, P < 0.05), and the amplitude during HT was lower in the elderly than the young group (P < 0.05).ConclusionsMild heat stress reduced the cognitive processing evaluated by ERPs in the elderly while not in the young subjects.Support or Funding InformationThis study was supported in part by a Grant‐in‐Aid for Scientific Research (17K01656), from Japan Society for the Promotion of Science for Akemi OtaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Caffeine Prevents Prostaglandin E1‐induced Disturbances in Respiratory Neural Control: Therapeutic Implications for Infants Treated for Congenital Heart Disease
Authors: Mitchell Lisa , Mayer Catherine , Raffay Thomas , DiFiore Juliann , MacFarlane Peter 
Published: June 2021

Prostaglandin E1 (PGE1) is frequently infused in human neonates with congenital heart disease to maintain ductus arteriosus patency; however this can cause central apnea which may necessitate endotracheal intubation. Caffeine is commonly used in the neonatal intensive care unit as a treatment for apnea of prematurity, and is believed to exert its effects primarily through adenosine receptor antagonism. In a prior study in preterm infants, a higher incidence of intermittent hypoxia events (a surrogate measure of apnea) correlated with an augmented ventilatory response to acute hypoxia (HVR). In the present study we sought to elucidate whether PGE1 enhances the HVR in 10‐day old rats and whether this effect would be prevented via pre‐treatment with caffeine. Rat pups received intraperitoneal injections of PGE1 (1μg/kg) and two hours later the HVR (10% O2, 5 min) was assessed using whole‐body plethysmography. PGE1 increased the HVR relative to saline (control) animals. Pre‐treatment with caffeine (5mg/kg) 1 hour prior to PGE1 injection prevented the increased HVR, as did pre‐treatment with MSX‐3 (100 mg/kg; a selective adenosine 2A antagonist). We propose that PGE1 exerts adenosine‐mediated effects on brainstem mechanisms of respiratory control, which may lead to destabilization of breathing in human infants being treated for congenital heart disease. Caffeine could be a convenient treatment to prevent respiratory instability in infants receiving PGE1 infusions.Support or Funding InformationDepartment of Pediatrics FRAP awardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inspiratory pressure‐generating capacity is preserved during ventilatory and non‐ventilatory behaviours despite profound diaphragm muscle weakness in young adult dystrophic (mdx) mice
Authors: Burns David P , Murphy Kevin H , Lucking Eric F , O'Halloran Ken D 
Published: June 2021

Diaphragm dysfunction is recognized in the mdx mouse model of muscular dystrophy, however there is a paucity of information concerning the neural control of dystrophic respiratory muscles. In young adult (8 weeks of age) male wild‐type and mdx mice, we assessed ventilatory capacity, neural activation of the diaphragm and external intercostal (EIC) muscles and inspiratory pressure‐generating capacity during ventilatory and non‐ventilatory behaviours. We hypothesized that respiratory muscle weakness is associated with impaired peak inspiratory pressure‐generating capacity in mdx mice.Ventilatory responsiveness to hypercapnic hypoxia was determined in conscious mice by whole‐body plethysmography. Diaphragm isometric and isotonic contractile properties were determined ex vivo. In anaesthetized mice, thoracic oesophageal pressure, and diaphragm and EIC electromyogram (EMG) activities were recorded during baseline conditions and sustained tracheal occlusion for 30–40s.Despite substantial diaphragm weakness, mdx mice retain the capacity to enhance ventilation during hypercapnic hypoxia. Peak volume‐ and flow‐related measures were also maintained in anaesthetized, vagotomized mdx mice. Peak inspiratory pressure was remarkably well preserved during chemoactivated breathing, augmented breaths, and maximal sustained efforts during airway obstruction in mdx mice. Diaphragm and EIC EMG activities were lower during airway obstruction in mdx compared with wild‐type mice.We conclude that ventilatory capacity is preserved in young mdx mice. Despite profound respiratory muscle weakness and lower diaphragm and EIC EMG activities during high demand in mdx mice, peak inspiratory pressure is preserved, owing to sufficient compensatory recruitment of accessory muscles beyond the primary muscles of inspiration. We suggest that a loss of compensation during progressive disease, combined with diaphragm dysfunction, underpins the development of respiratory system morbidity in dystrophic diseases.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protrusion Strength Training of the Tongue in Adult Humans
Authors: Davenport Paul Wesley , Berry Richard B , Vann William J , Kizza Rosie , Purdy Susan , Ryals Scott 
Published: June 2021

Upper airway patency is regulated by the integrated function multiple muscle system. Of particular importance is the position, strength and tone of the tongue. Tongue protrusion moves the tongue anterior in the mouth and expands the pharyngeal passage. Reduced tongue protrusion strength and tone may affect swallow and breathing. We hypothesized that the tongue can be strengthened to increase protrusion force. A placebo controlled study was performed in adult volunteers. A unique spring‐loaded device was constructed to provide protrusion strength training. The pre‐treatment maximum tongue protrusion force (MTPF) was measured and subjects randomly assigned to placebo or trained groups. The subjects were provided the device with low spring constant (placebo) or high spring constant (trained). The subjects performed a once‐daily tongue protrusion exercise by placing the device in their mouth, holding the device in place with their teeth, pushing the tongue onto a spring‐loaded piston and forcing the piston 0.5–1.0 cm into the device cylinder. The subjects performed 25–35 protrusion efforts per training session, 1 training session per day, 5 days per week for 8 weeks. Post‐treatment MTPF was recorded at the completion of the 8‐week exercise protocol. The trained group exercised with the device set to 70–80% MTPF. The placebo device was approximately 15% MTPF. The MTPF significantly increased in both the placebo and trained groups. The MTPF was significantly greater (38%) for the trained group compared to the placebo group (17%). The results of this study demonstrated that tongue protrusion strength can be increased by protrusion specific exercises using a spring‐loaded device. The placebo group had a significant training effect suggesting low intensity tongue protrusion exercise will increase MTPF.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Pharmacological Approach to Treat Acute Lung Injury
Authors: Qu Xinyan , Hitchinson Ben , Banerjee Avik , Zhao Shuangping , Zhang Chongxu , Gaponenko Vadim , Komarova Yulia 
Published: June 2021

Acute Respiratory Distress Syndrome (ARDS) is a lung disease characterized by acute respiratory failure, morbidity, and mortality. There are no effective therapies for ARDS, and standard care remains largely supportive. Here, we offer a novel pharmacological approach to treat ARDS by inhibiting microtubule accessory factor end binding protein 3 (EB3), which contribute to vascular leakage by amplifying pathological calcium signaling in endothelial cells. We employed structure‐activity‐relationship studies by nuclear magnetic resonance to design an allosteric inhibitor of EB3 that has optimal physicochemical and biochemical properties and is suitable for future clinical applications. Using standard methods for backbone rigidification and non‐proteinogenic amino acids, we have designed and tested sixty‐one drug‐like compounds, twenty‐six of which demonstrate remarkable similarity in binding the C‐terminus of EB3. Further screens using a cell‐based system identified four compounds with cell‐penetrating properties. These compounds are potent in inhibiting agonist‐evoked calcium release from endoplasmic reticulum stores and mitigating the effect of pro‐inflammatory mediators on the endothelial barrier. Based on in vitro stability in human blood plasma, we selected one lead and two backup compounds for further in vivo pre‐clinical studies. All three compounds inhibit endothelial capillary leakage in mice challenged with IV administration of PAR‐1 agonist peptide. Our studies establish a workflow for rational drug design to allosterically modulate EB3 function. Novel drug‐like compounds are stable and efficacious in treating lung endothelial microvascular hyperpermeability and may provide an important future clinical use in treating pulmonary edema associated with ARDS.Support or Funding InformationThis project has been funded in whole with Federal funds from the National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN268201700007C to YAK.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fos‐CreER Based Genetic Mapping of Forebrain Regions Activated by Acupuncture
Authors: Guo Zhi‐Ling , Lin Xiaoxiao , Samaniego Tracy , Isreb Alexander , Cao Stacey , Malik Shaista , Xu Xiangmin 
Published: June 2021

Acupuncture is an important practice used in traditional Chinese medicine (TCM), and it generates therapeutic effects through the insertion of thin needles through the skin at specific acupoint(s) in the body to stimulate sensory nerves. Many of the acupoints have multiple therapeutic indications. Using rodent models, we have found that manual acupuncture (MA) at the Neiguan (P6) acupoint overlying median nerve inhibits excitatory cardiovascular reflex responses through its influence on specific regions involving in the regulation of autonomic nervous system in the brain stem. However, in TCM, it is also the acupoint for treating nausea and headaches. It is largely unknown whether MA at this acupoint activates neurons in the brain regions beyond the brain stem. To further understand neural mechanisms underlying acupuncture effects, in this study, we map P6 specific neural activation by MA in the forebrain using a Fos‐CreER based mouse genetic strategy. Identification of c‐Fos expression is achieved using the Fos‐CreER mice crossed with the Cre reporter Ai9 mice to express the tdTomato fluorescent protein. This genetic method allows for enhanced sensitivity and efficiency compared to conventional immunohistochemical staining. Specifically, at 30 min following 4‐OHT (a metabolite of tamoxifen; i.p., 1 mg/per mouse) administration, MA or sham‐MA at P6 were conducted under anesthesia with ketamine: xylazine (75:10 μg/g, i.m.). MA was performed by gentle manual rotation of the acupuncture needle at a frequency of □2 Hz for 3 min every 10 min during a 30 min period. Identical procedures without the rotation of the needle at P6 were carried out in the mice treated with sham‐MA. With tissue collection after ten days, we observed that MA at P6 markedly increases c‐Fos/tdTomato+ neuronal labels in a number of the forebrain regions, compared to the sham‐MA group (n=5 in each group). These regions include accumbens nucleus, caudate putamen, bed nucleus of the stria terminalis, amygdaloid nucleus, ventral posterior division of the thalamic nucleus, paraventricular hypothalamic nucleus, arcuate hypothalamic nucleus, primary and secondary sensory cortex, ectorhinal cortex, dorsolateral entorhinal cortex, and claustrum. These data indicate that MA at P6 activates neurons in relatively broad brain networks beyond the brain stem, suggesting that acupuncture at this acupoint has the potential to influence physiological functions, associated with autonomic and non‐autonomic nervous systems through its effects on multiple brain regions.Support or Funding InformationNIH NCCIH AT009347 and NIH MH113026This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
V3 neurons regulate sensory transmission as well as locomotion
Authors: Lin Shihao , Lucas‐Osma Ana M , Li Yaqing , Hari Krishnapriya , Fouad Karim , Fenrich Keith K , Bennett David James 
Published: June 2021

It has been shown that the V3 spinal interneurons contribute to locomotion. Here we examined the role of V3 interneurons on sensory transmission. Using confocal microscopy, we found that V3 interneurons receive monosynaptic contacts from sensory afferents and also project monosynaptically back to sensory afferents. Furthermore, intracellular recording of afferents revealed that optogenetic activation of V3 neurons monosynaptically produce a primary afferent depolarization (PAD), with a large NMDA component as well as a classic GABA component. This PAD excites afferents, produces spiking, and in turn drives motoneurons. Furthermore, following V3 neuron activation, subsequent direct activation of sensory afferents caused much attenuated reflexes, likely because the reflex and PAD pathways employ shared V3 neurons. These results suggest that V3 neurons provide an anticipatory activation of afferents (afferent copy). This prepares the spinal cord for actual sensory input and attenuates unwanted sensory evoked motor output during voluntary movements like walking.Support or Funding InformationCanadian Institutes of Health Research; National Institutes of HealthThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neurotransmitter Receptor Antagonism Inhibits the Sea Urchin Righting Response
Authors: Shelley Chris , Dyar Andrew , Schieber Marquis 
Published: June 2021

The deuterostome superphylum comprises the chordates, which includes all vertebrates, echinoderms (including sea urchins and sea stars), and hemichordates (acorn worms). Despite the close phylogenetic relationship between invertebrate echinoderms and vertebrates, the understanding of echinoderm neurobiology lags far behind that of many other invertebrate species. To investigate molecular components of echinoderm behavior, we used the righting response, in which an inverted sea urchin will use its tube feet and spines to right itself, as a behavioral assay. Using purple sea urchins (Strongylocentrotus purpuratus) we demonstrate that immersion in drug solution is a simple and effective drug administration route. Using the drug immersion procedure, we show that the sea urchin righting response is inhibited in a dose‐dependent manner by the nicotinic acetylcholine receptor antagonist hexamethonium and also affected by the GABAA receptor antagonist bicuculline. In addition, decreasing the concentration of extracellular Ca2+ also inhibited the righting response. These data start to elucidate the receptor systems involved the control of sea urchin motor activity.Support or Funding InformationFunding was provided by the University of the South Conduff Fund and the University of the South Kresge Fund.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Enhancement of apneic reflex induced by sumatriptan: Role of bronchopulmonary C‐fibers in rats
Authors: Chan Nai‐Ju , Chen Yueh‐Yin , Lin You Shuei , Hsu Chun‐Chun 
Published: June 2021

Sumatriptan (Imigran®), an agonist of 5‐hydroxytryptophan (5HT)1B and 5HT1D receptors, is widely and effectively used to alleviate migraine headaches. Two of the most frequent side effects reported by patients are somatic hyperalgesia and chest discomfort. The chest syndromes are represented by chest tightness and dyspnea. Bronchopulmonary sensory C‐fibers innervate all levels of respiratory tract. Stimulation of the sensory fibers elicit airway reflexes including bronchoconstriction, shortness of breath, and dyspnea. This study was carried out to determine the effect of intravenous infusion of sumatriptan on sensitivity of ventilatory reflexes and bronchopulmonary sensory C‐fibers. In anesthetized, spontaneously breathing Brown‐Norway rats, the apneic response to right‐atrial injection of capsaicin was markedly enhanced 3 min after termination of sumatriptan infusion, which returned toward baseline within 80 min. In contrast, infusion of vehicle of sumatriptan failed to cause the enhancing effect. In our electrophysiological study, sumatriptan infusion did not influence the baseline activity of bronchopulmonary sensory C‐fibers in open‐chest, and artificially ventilated rats. However, these C‐fiber responses to right atrial injection of capsaicin were markedly potentiated 3 min after termination of sumatriptan infusion. The results suggest that sumatriptan enhances the excitability of bronchopulmonary sensory C‐fibers, which may, in turn, contribute to airway hypersensitivity.Support or Funding InformationSupported in part by grants TMU105‐AE1‐B17, MOST‐107‐2320‐B‐038‐041 and MOST‐107‐2320‐B‐038‐049‐MY3This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.