bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of moderate hypoxia on circadian rhythm: implications in disease and treatment options (710.1)
Authors: Allwood Melissa , Foster Andrew , Huber Jason , Simpson Jeremy 
Published: June 2021

Impairments in O2 delivery are a common feature of many chronic diseases (e.g., COPD, diabetes, and anemia). It reduces quality of life and increases morbidity, mortality and hospitalizations in patients. Circadian rhythms in mammals, including humans, are essential to health whereas disruptions exacerbate disease pathogenesis. While severe hypoxia can abolish circadian rhythm, moderate hypoxia is more clinically relevant but its effects on circadian rhythm are unknown. Our objective was to investigate the effects of moderate hypoxia on circadian rhythm. Methods: Mice were implanted with telemetry devices to measure heart rate (HR) and body temperature (Tb). Baseline measurements were obtained and animals subjected to 24 hours of moderate hypoxia (O2 = 15%) followed by 24 hours of normoxic recovery. Results: Moderate hypoxia disrupted, but did not abolish, the circadian rhythm of HR and Tb. Amplitude of circadian rhythm for HR was altered during both sleep and active states whereas Tb amplitude was altered only during sleep. Importantly, these disruptions persisted following 24 hours of normoxic recovery. Conclusions: A single 24 hour exposure of moderate hypoxia is sufficient to alter HR and Tb circadian rhythm, which does not recover within 24 hours of reoxygenation. This suggests that moderate hypoxia may have a critical role in disease pathogenesis.Grant Funding Source: Supported by Canadian Institute of Health Research
Regulation of HIF‐alpha isoform expression and redox state by carotid body chemosensory reflex (710.5)
Authors: Kumar Ganesh , Peng Ying‐Jie , Yuan Guoxiang , Khan Shakil , Nanduri Jayasri , Semenza Gregg , Prabhakar Nanduri 
Published: June 2021

The carotid body (CB) chemosensory reflex regulates breathing and sympathetic activity during hypoxia. Here, we determined mechanisms underlying regulation of cardio‐vascular function by chemosensory reflex using a rat model of chronic intermittent hypoxia (CIH). Rats exposed to CIH exhibited hypertension and elevated sympathetic activity; these effects were associated with increased HIF‐1α, decreased HIF‐2α expression, and oxidative stress in brainstem regions that regulate sympathetic nervous system.Systemic, cellular and molecular effects of CIH in brainstem were abolished by selective ablation of the CB. CIH exposed adrenal medulla (AM), a major end organ of the sympathetic nervous system also exhibited imbalanced expressions of HIF‐α isoforms and oxidative stress. Selective ablation of CB or sympathetic innervation to the AM abolished these effects. Analysis of the mechanisms in the AM revealed that activation of mTOR pathway and Ca2+ activated calpain proteases by Ca2+ signaling coupled to muscarinic acetylcholine receptors (mAChR) contribute to increased HIF‐1α and decreased HIF‐2α expression, respectively. These observations demonstrate a novel reflex regulation of HIF‐α isoforms expression and redox state by the CB, which contributes to regulation of cardio‐vascular function during CIH (Supported by NIH‐HLBI PO1 NIH‐HL‐090554).Grant Funding Source: NIH‐HLBI‐P01HL‐090554
Time course of changes in glutamatergic transmission within NTS during CIH exposure and the role of ΔFosB (710.6)
Authors: Wu Qiong , Mifflin Steve 
Published: June 2021

ΔFosB is a transcription factor induced by chronic intermittent hypoxia (CIH), a model of the arterial hypoxemia seen in sleep apnea patients. We reported that 7 days of CIH increases the amplitude of mEPSCs recorded in 2nd order arterial chemoreceptor NTS neurons. We hypothesize that NTS injection of a dominant‐negative construct of ΔFosB (provided by Dr. E. Nestler) to block the function of ΔFosB will block the CIH increase in mEPSC. A brain slice preparation was used to record mEPSCs by whole cell patch clamp in a normoxia group and in rats exposed to CIH of differing durations. mEPSC amplitude in normoxia group and after 1, 3, 5, and 7 days CIH exposure averaged 12.3±0.8 pA (n=12), 19.6±1.3 pA (n=11), 17.5±1.6 pA (n=11), 16.7±1.2 pA (n=21), 18.2±0.8 pA (n=7), respectively (all p<.05 vs. normoxia). 1 day after a 7 day exposure, mEPSC amplitude remained increased (17.5±1.6 pA, n=4), after 3 day recovery mEPSC amplitude was similar to normoxia (12.9±1.0 pA, n=7). AAV‐GFP‐ΔJunD construct was microinjected into NTS to block the function of ΔFosB, then GFP labeled second order NTS neurons were recorded after 1 day and 7 days CIH exposure. ΔFosB inhibition decreased the amplitudes of mEPSCs to normoxia levels in both groups, 13.9±0.6 pA (n=10), 13.0±0.6 pA (n=19), respectively. CIH rapidly enhances the post‐synaptic response to glutamatergic synaptic transmission within the NTS and ΔFosB plays a role in mediating this enhancement.Grant Funding Source: HL088052
Long non‐coding RNA changed in expression in tumors growing on EP2 knockout mice (711.4)
Authors: Asting Annika , Iresjö Britt‐Marie , Nilsberth Camilla , Blomqvist Anders , Lundholm Kent 
Published: June 2021

Cyclooxygenase‐2 and prostaglandin E2 (PGE2) displayed increased expression in tumor tissue and promotes tumor progression. PGE2 exerts its action via four membrane receptors, EP1‐4, and patients with high EP2 receptor expression have worse prognosis. Accordingly, tumors growing on EP2 knockout mice display reduced tumor weight compared to wild type mice. Therefore, our aim was to evaluate the effect of EP2 on tumor growth by analyses of differences in RNA expression between tumors in EP2 knockout and wild type mice with gene expression arrays (Sureprint, Agilent). Results displayed that several long non‐coding RNA (lncRNA) had a more than 5‐fold decreased expression in tumor tissue at host EP2 knockout and more than 100 had a 2‐fold change. Many lncRNAs are not characterized and their function is unknown. However, lncRNAs are known to regulate transcription and expression of genes. Therefore, our observations on lncRNA expression may be involved in tumor growth regulation.Grant Funding Source: Supported by the Swedish Cancer Society (CAN 2010/255) and the Assar Gabrielsson foundation
Blood tissue expresses a molecular signature of endurance exercise training (711.9)
Authors: Silva Michelle , Dias Rodrigo , Bolani Wladimir , Alves Cleber , Junior Jose , Silva Jeferson , Oliveira Patricia , Oliveira Edilamar , Rocha Cristiane , Marsiglia Julia , Negrao Carlos , Krieger Eduardo , Krieger Jose , Pereira Alexandre 
Published: June 2021

Aim: The purpose of this study was to identify a PBMC gene expression signature in response to endurance training. We also aimed to identify transcripts associated with changes in peak oxygen uptake (VO2peak). Methods: Healthy untrained policemen recruits (n=13; 25 ± 3 yrs; BMI 27.0 ± 2.8 kg∙m‐2) were selected. VO2peak (cardiopulmonary exercise test) and total RNA were obtained before and after 18 weeks of running endurance training (3 times/wk; 60min), for whole‐genome expression analysis (GeneChip® Human Gene 1.0 ST). Results: Training induced changes (Δ) in VO2peak (0.27±0.28 l∙min‐1, P=0.09) and a differential regulation of 211 transcripts (P<0.05; fold change>1.3). Baseline expression levels of 98 transcripts were strongly correlated with absolute ΔVO2peak (r>0.75; P<0.01). Differentially regulated transcripts were mostly represented in immune response of heat shock proteins and cytokines (HSPA1A, IL‐1), cell cycle regulation of differentiation and post‐translational modification processes (Histone H1, PLK1, SUMO‐1) and growth factors (EGR1, GH) activation and signalling. Conclusions: We describe a transcriptional map regulated by endurance training, ocurring in easily accessed PBMCs. Future research will focus on establishing transcriptional markers of trainability.Grant Funding Source: Supported by FAPESP #2005/59740‐7; CNPq #482863/2011‐0
Endogenous opioids in the pre‐Bötzinger complex via action on mu opioid receptors are critical in maintaining normal breathing by preventing and/or depressing sighs (712.12)
Authors: Zhuang Jianguo , Zhang Zhenxiong , Zhang Cancan , Xu Fadi , Frazier Donald 
Published: June 2021

The PBC is pivotal in generating augmented breathings (sighs), but local endogenous neurotransmitters responsible for control of sigh are not fully understood. Owing to the abundant presence of MORs in the PBC and centrally inhibitory effect of opioids on VT, we hypothesized that endogenous PBC opioids, via action on local MORs, would play an important role in maintaining normal respiration by preventing and/or depressing sighs. In anesthetized and spontaneously breathing rats, we recorded the cardiorespiratory activities before and after microinjection of naloxone methiodide, a MOR antagonist (10 mM, ~15 nl), into the PBC (PBCNLX). PBCNLX triggered sighs or if present, enhanced the frequency of sighs (from 0.7 ± 0.3 to 13.6 ± 1.6 sighs/10 min, P < 0.001). We further defined the effect of intravenous (5 μg/kg) and intracisternal injection of fentanyl (1 μg/kg), a MOR agonist, on the PBCNLX‐induced sighs. The sighs were abolished by intravenous injection of fentanyl and largely suppressed by intracisternal injection. In conclusion, endogenous PBC opioids via action on MORs are essential in maintaining normal respiration by preventing and/or suppressing sighs, consistent with centrally inhibitory effect of exogenous MOR agent on sighs.Grant Funding Source: Supported by HL 107462 and ALA Grant RG‐191095‐N
Comparison of the neurochemical response to atropine dialysis in pontine and medullary nuclei in goats (712.9)
Authors: Langer Thomas , Bonis Josh , Neumueller Suzanne , Olesiak Samantha , Miller Justin , Muere Clarissa , Pan Lawrence , Hodges Matthew , Forster Hubert 
Published: June 2021

To gain insight into neuromodulatory role of cholinergic signaling in different brainstem regions, we dialyzed atropine (50mM), a non‐specific muscarinic receptor blocker, into the brainstems of chronically cannulated goats. Atropine dialysis into the pontine Kölliker‐Fuse nucleus (KFN) at night decreased breathing (J. Appl. Physiol. 109: 159‐170, 2010). Atropine dialysis into the medullary pre‐Bötzinger complex (preBötC) increased breathing both at night and during the day (J. Appl. Physiol 114: 694‐704, 2013) with increases observed in substance P and glycine in the effluent mock cerebral spinal fluid (mCSF). Herein we report levels of neurochemicals in effluent mCSF during 50mM atropine dialysis into the KFN and lateral and medial parabrachial nuclei. There were no pontine site‐related differences in levels of tested neurochemicals; thus the data were pooled. In all pontine cannulated goats, during the day and at night, atropine dialysis increased substance P to the same level as atropine dialysis into the medulla (preBötC). In contrast, atropine dialysis into the pontine nuclei did not change levels of glutamine, glycine, or GABA in the effluent mCSF. These findings suggest that the site specific differences in the respiratory response to atropine dialysis are not due to alterations in substance P levels.Grant Funding Source: Supported by NIH HL007852, NIH HL25739, NIH HL112996, and the Department of Veteran Affairs
Systemic inflammation impairs phrenic long‐term facilitation following moderate, but not severe acute intermittent hypoxia (713.3)
Authors: Agosto Ibis , Nichols Nicole , Mitchell Gordon 
Published: June 2021

Systemic inflammation impairs phrenic long‐term facilitation following moderate, but not severe acute intermittent hypoxia Ibis M. Agosto, Nicole L. Nichols and Gordon S. Mitchell Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706 Phrenic long‐term facilitation (pLTF) is a form of respiratory motor plasticity elicited by acute intermittent hypoxia (AIH). When elicited by moderate AIH (mAIH, 35‐45mmHg), pLTF is serotonin‐dependent; in contrast, pLTF is adenosine‐dependent (serotonin‐independent) when the same AIH protocol is used, but with more severe hypoxic episodes (sAIH, 25‐30mmHg). Systemic inflammation induced by lipopolysaccharide (LPS) blocks mAIH induced, serotonin‐dependent pLTF (Huxtable et al. 2013). Here, we tested the hypothesis that sAIH induced pLTF is inflammation resistant, since sAIH elicits pLTF through a distinct adenosine‐dependent mechanism. mAIH and sAIH induced pLTF were assessed in anesthetized Sprague Dawley rats 24 hrs post‐LPS (100ug/kg, i.p.) or saline injections. Whereas mAIH induced pLTF was reduced by LPS (LPS: 25±3%, n=5; control: 54±2%, n=5; p0.05). Thus, systemic inflammation undermines serotonin‐, but not adenosine‐dependent pLTF. Our results give insight concerning the functional significance of multiple cellular mechanisms that give rise to respiratory motor plasticity. Specifically, inflammation resistance of adenosine‐dependent pLTF may provide a “back up” as animals regulate breathing in conditions where normal regulatory mechanism have been lost.[Supported by: NIH HL111598, and Francis Families Foundation (NLN)]Grant Funding Source: Supported by: NIH HL111598, and Francis Families Foundation (NLN)
Repetitive acute intermittent hypoxia differentially affects CD11b+ cell phenotypes after C2 spinal hemisection (713.6)
Authors: Small Alissa , Nikodemova Maria , Dougherty Brendan , Mitchell Gordon , Watters Jyoti 
Published: June 2021

Inflammation is a hallmark of spinal cord injury (SCI), mediated in part by CD11b+ resident microglia (MG) and infiltrating macrophages (MP). Although neuroinflammation is well‐characterized at the lesion site, little is known about MG/MP activities above or below the injury. Repetitive acute intermittent hypoxia (rAIH) elicits somatic motor plasticity following chronic spinal injury, and this plasticity is undermined by neuroinflammation. Since recent microarray data suggest that rAIH (4 weeks) suppresses spinal inflammation, we tested the hypothesis that rAIH shifts the MG/MP phenotype following C2 spinal hemisection (C2HS), decreasing inflammatory (M1) and increasing reparative/trophic (M2) activities. We further posited that these effects would differ above vs. below the injury site. mRNAs for molecular markers of M1 and M2 phenotype were assessed (qRT‐PCR) on immunomagnetically isolated MG/MP from sham‐ and C2HS‐operated rats exposed to normoxia or rAIH (10 episodes per day, 3 x per week, 4 wks) beginning 3 days post‐surgery. In normoxia, whereas M1 genes were unaffected by C2HS above the injury site (brainstem), M2 genes were increased. In contrast, below the injury (C4‐C6), M2 genes were unaffected, and there was little indication of increased M1 expression. Treatment with rAIH decreased both M1 and M2 gene expression in brainstem MG/MP, but increased M2 and decreased M1 gene expression below the injury, suggesting a switch to a supportive phenotype below the injury. Thus, rAIH elicits differential effects on MG/MP activities above and below the injury, and its beneficial effects on spinal plasticity and functional recovery following SCI may involve alterations in CD11b+ cell phenotypes.Grant Funding Source: Supported by NIH R01 HL111598, The Craig H. Neilsen Foundation, and Wisconsin Hilldale Fellowship
Dopamine receptor blockade improves pulmonary gas exchange during exercise in healthy humans (717.1)
Authors: Tedjasaputra Vince , Bryan Tracey , Moore Linn , van Diepen Sean , Bouwsema Melissa , Petersen Stewart , Welsh Robert , Stickland Michael 
Published: June 2021

Impaired pulmonary gas exchange during heavy exercise, manifested as an increase in the alveolar‐arterial oxygen difference (A‐aDO2), may be due to anatomical intrapulmonary (IP) shunt recruitment. Dopamine (DA) has been shown to recruit IP shunts at rest and circulating DA increases with exercise, and thus may contribute to the increased A‐aDO2 during exercise. We hypothesized that gas exchange impairment during exercise will decrease with DA receptor blockade. Ten healthy males (Age: 25±6 yrs, VO2max: 56.3±6.6 ml∙kg‐1∙min‐1) performed two incremental staged cycling exercise sessions after ingestion of either placebo (P) or DA blockade (B) (Metoclopramide 20mg). Arterial blood gas sampling and cardiorespiratory data were obtained at rest and during 4 exercise intensities (30%, 50%, 75% and 90% of previously determined VO2max). At 90% VO2max, DA blockade decreased A‐aDO2 (P: 19.3±8.5 torr, B: 14.8±6.8 torr, p=0.038 and increased arterial O2 saturation (P: 95.4±1.0%, B: 96.2±0.9%, p=0.004). Blood gases were similar between the two groups at rest, 30%, 50% and 75% of VO2max. Compared to placebo, DA blockade did not change O2 consumption, CO2 production, or respiratory exchange ratio at any intensity. Administration of a DA receptor blockade decreased A‐aDO2 during near‐maximal exercise, suggesting that endogenous DA affects affects pulmonary gas exchange during exercise.Grant Funding Source: Supported by The National Sciences and Engineering Research Council of Canada
Hypothalamic control of pulmonary renal reflex (718.3)
Authors: Choudhary Rishabh , Gulati Kavita , Ravi Krishnan 
Published: June 2021

Pulmonary lymphatic obstruction (PLO) is associated with a reflex increase in urine flow. The central integration of this reflex termed PRR is not known. Thus the aim of the present study is to observe the role of paraventricular nucleus (PVN) on PRR.Experiments were performed on anesthetized, artificially ventilated adult New Zealand white rabbits. After routine cannulations, an isolated venous pouch was created in the right external jugular vein in the neck region. A cannula was positioned in this pouch and the other end of it was connected to a saline reservoir. To cause PLO, the reservoir was raised to a height of 30 cm. The urinary bladder was cannulated for collecting urine. Each rabbit was hydrated by giving saline infusion (rate ‐ 12 ml/10 min). The rabbit was then fixed to a stereotaxic apparatus. A dorsal incision was made and activity from right renal sympathetic nerve (RSN) was recorded. Electrodes were placed on either PVN. Urine was collected every 10 min during the initial control period, during PLO and after releasing PLO each for a period of 20 min. The study was repeated after electrolytic lesion of PVN bilaterally. The significant increases in urine flow and RSN activity observed before lesion were abolished after the lesion.It is concluded that along with an increase in urine flow, there is an increase in RSN activity also during PLO and PVN functions as an integrating centre in PRR.Grant Funding Source: Supported by: CSIR,UGC India
Teaching healthy eating and cooking helps Polynesian and Pacific Islander participants make nutritious food choices (721.26)
Authors: Vogelsang David , Clayton Craig , Frampton S , Ray Gaye , Brown Laura , Lassetter Jane , Wisco Jonathan 
Published: June 2021

According to the Centers for Disease Control (CDC) and Prevention (2013), more than one‐third of U.S. adults (35.7%) are obese, and since 1980, obesity among adolescents has risen from 5% to 18%. To prevent obesity the National Heart, Lung and Blood Institute suggests healthy eating. Cooking Anatomy Academy (CAA) teaches anatomy, physiology, and nutrition, and promotes healthy eating and cooking among parents and students in the Polynesian and Pacific Islander communities. CAA is composed of seven, one hour cooking lessons offered as an afterschool program at Mana Academy Charter School (West Valley, UT). The CAA curriculum incorporates nutrition guidelines on MyPlate.gov, and focuses on moderation, variety, and raw/unrefined foods. We studied the impact of CAA using a qualitative analysis of journal entries responding to questions about how participants' experiences in CAA have influenced how they prepare meals at home, and feedback received during the lessons. Preliminary data shows that CAA is helping participants make healthy food choices. Several parents have indicated that their kids are asking to eat healthier foods at home because of the foods they ate in class.Grant Funding Source: Mentoring Research Grant, College of Life Sciences, Brigham Young University
The low‐level laser and natural latex protein applied on the sciatic nerve crushed: morphometric and scanning electron microscopy study (726.11)
Authors: Dias Fernando , Issa Joao Paulo , Coutinho‐Netto Joaquim , Fazan Valeria , Iyomasa Mamie , Watanabe Ii‐sei 
Published: June 2021

This study evaluated the effects of low‐level laser (LLL 15J/cm2, 780nm) and F1 protein (natural latex ‐ 0,1%) on the sciatic nerve crushed (15 kgf, axonotmesis). We used 72 rats (♂, 200‐250g) divided into 6 groups (n = 12): GC ‐ control; EG ‐ exposed nerve; IG ‐ injured nerve; LG ‐ LLL; PG ‐ F1; LPG ‐ LLL and F1. After 4 or 8 weeks, the animals were euthanized, the sciatic nerve was processed for morphometric (nerve fibers minimum diameter, myelin thickness and G‐ratio) and scanning electron microscope (SEM) analyzes.The morphometric data after 4 weeks showed improvements with the applied treatments, PG showed better results. After 8 weeks it was observed greater homogeneity among the groups. The G‐ratio showed no tendency to change (4 or 8 weeks), the values were closer after 8 weeks.The SEM data showed normal features in CG and EG, the IG (4 weeks) revealed a huge loss of nerve fibers and endoneurial collagen synthesis, the LG and PG (4 weeks) showed small clusters of nerve fibers. PG and LPG (8 weeks) revealed larger and more juxtaposed fibers in comparison to the injured groups discussed at 4 weeks.The treatment with the F1 and LLL suggest an improvement in the recovery of crushed peripheral nerve (4 and 8 weeks). After 8 weeks, the treated groups were more similar to each other, revealing the time‐dependency. The groups that received F1 associated or not to LLL showed the better results.Grant Funding Source: FAPESP 2010/12018‐3
Effect of dietary supplementation of pomegranate fruit grown in Oman on the memory, anxiety and learning skills in a transgenic mice model of Alzheimer's disease (728.10)
Authors: Subash Selvaraju , Essa Musthafa , Al‐Buraiki Zayana , Al‐Asmi Abdullah , Al‐Adawi Samir , Vaishnav Ragini , Lakhtatika Ritu , Al‐Senawi Hamad , Awlad‐Thani Kathiya , Al‐Jabri Ahood , Samuoi Maha 
Published: June 2021

Several reports have suggested neurotoxic effects of Aβ and role of oxidative stress in AD. Oman grown fruit; Pomegranates contain very high levels of antioxidants and several medicinal properties. We studied the effect of dietary supplementation of pomegranate on the memory, anxiety and learning skills in double Swedish APP mutation (APPsw/Tg2576) AD mouse model. Animals were divided into 3 groups; group 1 was wild type non‐transgenic; group 2 and 3‐ transgenic mice. Group 1and 2 fed with normal diet and group 3 were fed custom‐mix diets (pellets) containing 4% pomegranate. At age of 4‐5 months and 14‐15 months the behaviors of the animals were analyzed for memory, learning and anxiety. APPsw/Tg2576 at the age of 4‐5 months and 14‐15 months that were fed control diet without pomegranates showed memory deficit, anxiety‐related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination compared to the wild type mice on the same diet. Diets rich in 4% pomegranate fed tg mice showed a significant improvement above behavior abnormalities compared to AD tg mice on normal diet. Our results suggest that dietary supplementation of pomegranate grown in Oman may have the beneficial effect in reducing the risk, delaying the onset or slowing the progression of Alzheimer's disease. Further studies needed to validate and determine the mechanism of action of Omani pomegranates against AD. Financial support came from The Research Council, Oman (RC/AGR/FOOD/11/01).Grant Funding Source: Supported by The Research Council, Oman (RC/AGR/FOOD/11/01).