Cardiovascular responses to microinjection of L-glutamate into the NTS in AV3V-lesioned rats.

PubMed

Vieira, Alexandre Antonio; Colombari, Eduardo; De Luca, Laurival A; de Almeida Colombari, Débora Simões; Menani, José V

2004-10-29

The excitatory amino acid L-glutamate injected into the nucleus of the solitary tract (NTS) in unanesthetized rats similar to peripheral chemoreceptor activation increases mean arterial pressure (MAP) and reduces heart rate. In this study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the preoptic-periventricular tissue surrounding the anteroventral third ventricle (AV3V region) on the pressor and bradycardic responses induced by injections of L-glutamate into the NTS or peripheral chemoreceptor activation in unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the NTS were used. Differently from the pressor responses (28+/-3 mm Hg) produced by injections into the NTS of sham-lesioned rats, L-glutamate (5 nmol/100 nl) injected into the NTS reduced MAP (-26+/-8 mm Hg) or produced no effect (2+/-7 mm Hg) in acute and chronic AV3V-lesioned rats, respectively. The bradycardia to l-glutamate into the NTS and the cardiovascular responses to chemoreflex activation with intravenous potassium cyanide or to baroreflex activation with intravenous phenylephrine or sodium nitroprusside were not modified by AV3V lesions. The results show that the integrity of the AV3V region is essential for the pressor responses to L-glutamate into the NTS but not for the pressor responses to chemoreflex activation, suggesting dissociation between the central mechanisms involved in these responses.

NK1 receptor activation in rat rostral ventrolateral medulla selectively attenuates somato-sympathetic reflex while antagonism attenuates sympathetic chemoreflex.

PubMed

Makeham, John M; Goodchild, Ann K; Pilowsky, Paul M

2005-06-01

The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5-11) (DiMe-SP) or the highly selective NK1 agonist [Sar9, Met (O(2))11]SP into the RVLM resulted in an increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity. The effects of [Sar9, Met (O(2))11]SP were blocked by the selective nonpeptide NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation, while leaving the baroreflex and chemoreflex unaffected. This effect was again blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708 significantly attenuated the sympathoexcitatory response to hypoxia but had no effect on baseline respiratory function. Our findings suggest that substance P and the NK1 receptor play a significant role in the cardiorespiratory reflexes integrated within the RVLM.

Impaired central respiratory chemoreflex in an experimental genetic model of epilepsy

PubMed Central

Totola, Leonardo T.; Takakura, Ana C.; Oliveira, José Antonio C.

2016-01-01

Key points It is recognized that seizures commonly cause apnoea and oxygen desaturation, but there is still a lack in the literature about the respiratory impairments observed ictally and in the post‐ictal period.Respiratory disorders may involve changes in serotonergic transmission at the level of the retrotrapezoid nucleus (RTN).In this study, we evaluated breathing activity and the role of serotonergic transmission in the RTN with a rat model of tonic–clonic seizures, the Wistar audiogenic rat (WAR).We conclude that the respiratory impairment in the WAR could be correlated to an overall decrease in the number of neurons located in the respiratory column. Abstract Respiratory disorders may involve changes in serotonergic neurotransmission at the level of the chemosensitive neurons located in the retrotrapezoid nucleus (RTN). Here, we investigated the central respiratory chemoreflex and the role of serotonergic neurotransmission in the RTN with a rat model of tonic–clonic seizures, the Wistar audiogenic rat (WAR). We found that naive or kindled WARs have reduced resting ventilation and ventilatory response to hypercapnia (7% CO2). The number of chemically coded (Phox2b+/TH−) RTN neurons, as well as the serotonergic innervation to the RTN, was reduced in WARs. We detected that the ventilatory response to serotonin (1 mm, 50 nl) within the RTN region was significantly reduced in WARs. Our results uniquely demonstrated a respiratory impairment in a genetic model of tonic–clonic seizures, the WAR strain. More importantly, we demonstrated an overall decrease in the number of neurons located in the ventral respiratory column (VRC), as well as a reduction in serotonergic neurons in the midline medulla. This is an important step forward to demonstrate marked changes in neuronal activity and breathing impairment in the WAR strain, a genetic model of epilepsy. PMID:27633663

Neural Regulation of Cardiovascular Response to Exercise: Role of Central Command and Peripheral Afferents

PubMed Central

Nobrega, Antonio C. L.; O'Leary, Donal; Silva, Bruno Moreira; Piepoli, Massimo F.; Crisafulli, Antonio

2014-01-01

During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discussed. PMID:24818143

Cardiorespiratory interactions in neural circulatory control in humans.

PubMed

Shamsuzzaman, A S; Somers, V K

2001-06-01

The reflex mechanisms and interactions described in this overview provide some explanation for the range of neural circulatory responses evident during changes in breathing. The effects described represent the integrated responses to activation of several reflex mechanisms, including peripheral and central chemoreflexes, arterial baroreflexes, pulmonary stretch receptors, and ventricular mechanoreceptors. These interactions occur on a dynamic basis and the transfer characteristics of any single interaction are, in all likelihood, also highly dynamic. Nevertheless, it is only by attempting to understand individual reflexes and their modulating influences that a more thorough understanding of the responses to complex phenomena such as hyperventilation, apnea, and obstructive sleep apnea can be better understood.

Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia

PubMed Central

Hansen, Jim; Sander, Mikael

2003-01-01

Acute exposure to hypoxia causes chemoreflex activation of the sympathetic nervous system. During acclimatization to high altitude hypoxia, arterial oxygen content recovers, but it is unknown to what degree sympathetic activation is maintained or normalized during prolonged exposure to hypoxia. We therefore measured sympathetic nerve activity directly by peroneal microneurography in eight healthy volunteers (24 ± 2 years of age) after 4 weeks at an altitude of 5260 m (Chacaltaya, Bolivian Andes) and at sea level (Copenhagen). The subjects acclimatized well to altitude, but in every subject sympathetic nerve activity was highly elevated at altitude vs. sea level (48 ± 5 vs. 16 ± 3 bursts min−1, respectively, P < 0.05), coinciding with increased mean arterial blood pressure (87 ± 3 vs. 77 ± 2 mmHg, respectively, P < 0.05). To examine the underlying mechanisms, we administered oxygen (to eliminate chemoreflex activation) and saline (to reduce cardiopulmonary baroreflex deactivation). These interventions had minor effects on sympathetic activity (48 ± 5 vs. 38 ± 4 bursts min−1, control vs. oxygen + saline, respectively, P < 0.05). Moreover, sympathetic activity was still markedly elevated (37 ± 5 bursts min−1) when subjects were re-studied under normobaric, normoxic and hypervolaemic conditions 3 days after return to sea level. In conclusion, acclimatization to high altitude hypoxia is accompanied by a striking and long-lasting sympathetic overactivity. Surprisingly, chemoreflex activation by hypoxia and baroreflex deactivation by dehydration together could account for only a small part of this response, leaving the major underlying mechanisms unexplained. PMID:12563015

Evolution and physiology of neural oxygen sensing

PubMed Central

Costa, Kauê M.; Accorsi-Mendonça, Daniela; Moraes, Davi J. A.; Machado, Benedito H.

2014-01-01

Major evolutionary trends in animal physiology have been heavily influenced by atmospheric O2 levels. Amongst other important factors, the increase in atmospheric O2 which occurred in the Pre-Cambrian and the development of aerobic respiration beckoned the evolution of animal organ systems that were dedicated to the absorption and transportation of O2, e.g., the respiratory and cardiovascular systems of vertebrates. Global variations of O2 levels in post-Cambrian periods have also been correlated with evolutionary changes in animal physiology, especially cardiorespiratory function. Oxygen transportation systems are, in our view, ultimately controlled by the brain related mechanisms, which senses changes in O2 availability and regulates autonomic and respiratory responses that ensure the survival of the organism in the face of hypoxic challenges. In vertebrates, the major sensorial system for oxygen sensing and responding to hypoxia is the peripheral chemoreflex neuronal pathways, which includes the oxygen chemosensitive glomus cells and several brainstem regions involved in the autonomic regulation of the cardiovascular system and respiratory control. In this review we discuss the concept that regulating O2 homeostasis was one of the primordial roles of the nervous system. We also review the physiology of the peripheral chemoreflex, focusing on the integrative repercussions of chemoreflex activation and the evolutionary importance of this system, which is essential for the survival of complex organisms such as vertebrates. The contribution of hypoxia and peripheral chemoreflex for the development of diseases associated to the cardiovascular and respiratory systems is also discussed in an evolutionary context. PMID:25161625

RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 insensitive brown Norway rat

PubMed Central

Puissant, Madeleine M; Echert, Ashley E; Yang, Chun; Mouradian, Gary C; Novotny, Tyler; Liu, Pengyuan; Liang, Mingyu; Hodges, Matthew R

2015-01-01

Raphé-derived serotonin (5-HT) and thyrotropin-releasing hormone (TRH) play important roles in fundamental, homeostatic control systems such as breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5-HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphé gene expression and the consequent deficiencies in raphé-derived neuromodulators such as TRH. Medullary raphé transcriptome comparisons revealed lower expression of multiple 5-HT neuron-specific genes in BN compared to control Dahl salt-sensitive rats, predictive of reduced central nervous system monoamines by bioinformatics analyses and confirmed by high-performance liquid chromatography measurements. In particular, raphé Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analogue Taltirelin (TAL) stimulated breathing dose-dependently, with greater effects in BN versus control Sprague–Dawley rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control Sprague–Dawley rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex. PMID:25630262

Promising effects of xanthine oxidase inhibition by allopurinol on autonomic heart regulation estimated by heart rate variability (HRV) analysis in rats exposed to hypoxia and hyperoxia

PubMed Central

Ziółkowski, Wiesław; Badtke, Piotr; Zajączkowski, Miłosz A.; Flis, Damian J.; Figarski, Adam; Smolińska-Bylańska, Maria; Wierzba, Tomasz H.

2018-01-01

Background It has long been suggested that reactive oxygen species (ROS) play a role in oxygen sensing via peripheral chemoreceptors, which would imply their involvement in chemoreflex activation and autonomic regulation of heart rate. We hypothesize that antioxidant affect neurogenic cardiovascular regulation through activation of chemoreflex which results in increased control of sympathetic mechanism regulating heart rhythm. Activity of xanthine oxidase (XO), which is among the major endogenous sources of ROS in the rat has been shown to increase during hypoxia promote oxidative stress. However, the mechanism of how XO inhibition affects neurogenic regulation of heart rhythm is still unclear. Aim The study aimed to evaluate effects of allopurinol-driven inhibition of XO on autonomic heart regulation in rats exposed to hypoxia followed by hyperoxia, using heart rate variability (HRV) analysis. Material and methods 16 conscious male Wistar rats (350 g): control-untreated (N = 8) and pretreated with Allopurinol-XO inhibitor (5 mg/kg, followed by 50 mg/kg), administered intraperitoneally (N = 8), were exposed to controlled hypobaric hypoxia (1h) in order to activate chemoreflex. The treatment was followed by 1h hyperoxia (chemoreflex suppression). Time-series of 1024 RR-intervals were extracted from 4kHz ECG recording for heart rate variability (HRV) analysis in order to calculate the following time-domain parameters: mean RR interval (RRi), SDNN (standard deviation of all normal NN intervals), rMSSD (square root of the mean of the squares of differences between adjacent NN intervals), frequency-domain parameters (FFT method): TSP (total spectral power) as well as low and high frequency band powers (LF and HF). At the end of experiment we used rat plasma to evaluate enzymatic activity of XO and markers of oxidative stress: protein carbonyl group and 8-isoprostane concentrations. Enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measures in erythrocyte lysates. Results Allopurinol reduced oxidative stress which was the result of hypoxia/hyperoxia, as shown by decreased 8-isoprostane plasma concentration. XO inhibition did not markedly influence HRV parameters in standard normoxia. However, during hypoxia, as well as hyperoxia, allopurinol administration resulted in a significant increase of autonomic control upon the heart as shown by increased SDNN and TSP, with an increased vagal contribution (increased rMSSD and HF), whereas sympathovagal indexes (LF/HF, SDNN/rMSSD) remained unchanged. Conclusions Observed regulatory effects of XO inhibition did not confirm preliminary hypothesis which suggested that an antioxidant such as allopurinol might activate chemoreflex resulting in augmented sympathetic discharge to the heart. The HRV regulatory profile of XO inhibition observed during hypoxia as well as post-hypoxic hyperoxia corresponds to reported reduced risk of sudden cardiovascular events. Therefore our data provide a new argument for therapeutical use of allopurinol in hypoxic conditions. PMID:29432445

Promising effects of xanthine oxidase inhibition by allopurinol on autonomic heart regulation estimated by heart rate variability (HRV) analysis in rats exposed to hypoxia and hyperoxia.

PubMed

Zajączkowski, Stanisław; Ziółkowski, Wiesław; Badtke, Piotr; Zajączkowski, Miłosz A; Flis, Damian J; Figarski, Adam; Smolińska-Bylańska, Maria; Wierzba, Tomasz H

2018-01-01

It has long been suggested that reactive oxygen species (ROS) play a role in oxygen sensing via peripheral chemoreceptors, which would imply their involvement in chemoreflex activation and autonomic regulation of heart rate. We hypothesize that antioxidant affect neurogenic cardiovascular regulation through activation of chemoreflex which results in increased control of sympathetic mechanism regulating heart rhythm. Activity of xanthine oxidase (XO), which is among the major endogenous sources of ROS in the rat has been shown to increase during hypoxia promote oxidative stress. However, the mechanism of how XO inhibition affects neurogenic regulation of heart rhythm is still unclear. The study aimed to evaluate effects of allopurinol-driven inhibition of XO on autonomic heart regulation in rats exposed to hypoxia followed by hyperoxia, using heart rate variability (HRV) analysis. 16 conscious male Wistar rats (350 g): control-untreated (N = 8) and pretreated with Allopurinol-XO inhibitor (5 mg/kg, followed by 50 mg/kg), administered intraperitoneally (N = 8), were exposed to controlled hypobaric hypoxia (1h) in order to activate chemoreflex. The treatment was followed by 1h hyperoxia (chemoreflex suppression). Time-series of 1024 RR-intervals were extracted from 4kHz ECG recording for heart rate variability (HRV) analysis in order to calculate the following time-domain parameters: mean RR interval (RRi), SDNN (standard deviation of all normal NN intervals), rMSSD (square root of the mean of the squares of differences between adjacent NN intervals), frequency-domain parameters (FFT method): TSP (total spectral power) as well as low and high frequency band powers (LF and HF). At the end of experiment we used rat plasma to evaluate enzymatic activity of XO and markers of oxidative stress: protein carbonyl group and 8-isoprostane concentrations. Enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measures in erythrocyte lysates. Allopurinol reduced oxidative stress which was the result of hypoxia/hyperoxia, as shown by decreased 8-isoprostane plasma concentration. XO inhibition did not markedly influence HRV parameters in standard normoxia. However, during hypoxia, as well as hyperoxia, allopurinol administration resulted in a significant increase of autonomic control upon the heart as shown by increased SDNN and TSP, with an increased vagal contribution (increased rMSSD and HF), whereas sympathovagal indexes (LF/HF, SDNN/rMSSD) remained unchanged. Observed regulatory effects of XO inhibition did not confirm preliminary hypothesis which suggested that an antioxidant such as allopurinol might activate chemoreflex resulting in augmented sympathetic discharge to the heart. The HRV regulatory profile of XO inhibition observed during hypoxia as well as post-hypoxic hyperoxia corresponds to reported reduced risk of sudden cardiovascular events. Therefore our data provide a new argument for therapeutical use of allopurinol in hypoxic conditions.

Peripheral chemoreflex inhibition with low-dose dopamine: new insight into mechanisms of extreme apnea.

PubMed

Bain, Anthony R; Dujic, Zeljko; Hoiland, Ryan L; Barak, Otto F; Madden, Dennis; Drvis, Ivan; Stembridge, Mike; MacLeod, David B; MacLeod, Douglas M; Ainslie, Philip N

2015-11-01

The purpose of this study was to determine the impact of peripheral chemoreflex inhibition with low-dose dopamine on maximal apnea time, and the related hemodynamic and cerebrovascular responses in elite apnea divers. In a randomized order, participants performed a maximal apnea while receiving either intravenous 2 μg·kg(-1)·min(-1) dopamine or volume-matched saline (placebo). The chemoreflex and hemodynamic response to dopamine was also assessed during hypoxia [arterial O2 tension, (PaO2 ) ∼35 mmHg] and mild hypercapnia [arterial CO2 tension (PaCO2 ) ∼46 mmHg] that mimicked the latter parts of apnea. Outcome measures included apnea duration, arterial blood gases (radial), heart rate (HR, ECG), mean arterial pressure (MAP, intra-arterial), middle (MCAv) and posterior (PCAv) cerebral artery blood velocity (transcranial ultrasound), internal carotid (ICA) and vertebral (VA) artery blood flow (ultrasound), and the chemoreflex responses. Although dopamine depressed the ventilatory response by 27 ± 41% (vs. placebo; P = 0.01), the maximal apnea duration was increased by only 5 ± 8% (P = 0.02). The PaCO2 and PaO2 at apnea breakpoint were similar (P > 0.05). When compared with placebo, dopamine increased HR and decreased MAP during both apnea and chemoreflex test (P all <0.05). At rest, dopamine compared with placebo dilated the ICA (3.0 ± 4.1%, P = 0.05) and VA (6.6 ± 5.0%, P < 0.01). During apnea and chemoreflex test, conductance of the cerebral vessels (ICA, VA, MCAv, PCAv) was increased with dopamine; however, flow (ICA and VA) was similar. At least in elite apnea divers, the small increase in apnea time and similar PaO2 at breakpoint (∼31 mmHg) suggest the apnea breakpoint is more related to PaO2 , rather than peripheral chemoreflex drive to breathe. Copyright © 2015 the American Physiological Society.

The myths and physiology surrounding intrapartum decelerations: the critical role of the peripheral chemoreflex

PubMed Central

Lear, Christopher A.; Galinsky, Robert; Wassink, Guido; Yamaguchi, Kyohei; Davidson, Joanne O.; Westgate, Jenny A.; Bennet, Laura

2016-01-01

Abstract A distinctive pattern of recurrent rapid falls in fetal heart rate, called decelerations, are commonly associated with uterine contractions during labour. These brief decelerations are mediated by vagal activation. The reflex triggering this vagal response has been variably attributed to a mechanoreceptor response to fetal head compression, to baroreflex activation following increased blood pressure during umbilical cord compression, and/or a Bezold–Jarisch reflex response to reduced venous return from the placenta. Although these complex explanations are still widespread today, there is no consistent evidence that they are common during labour. Instead, the only mechanism that has been systematically investigated, proven to be reliably active during labour and, crucially, capable of producing rapid decelerations is the peripheral chemoreflex. The peripheral chemoreflex is triggered by transient periods of asphyxia that are a normal phenomenon associated with all uterine contractions. This should not cause concern as the healthy fetus has a remarkable ability to adapt to these repeated but short periods of asphyxia. This means that the healthy fetus is typically not at risk of hypotension and injury during uncomplicated labour even during repeated brief decelerations. The physiologically incorrect theories surrounding decelerations that ignore the natural occurrence of repeated asphyxia probably gained widespread support to help explain why many babies are born healthy despite repeated decelerations during labour. We propose that a unified and physiological understanding of intrapartum decelerations that accepts the true nature of labour is critical to improve interpretation of intrapartum fetal heart rate patterns. PMID:27328617

Hypothyroidism Attenuates SCH 23390-mediated Depression of Breathing and Decreases D1 Receptor Expression in Carotid Bodies, PVN and Striatum of Hamsters

PubMed Central

Schlenker, Evelyn H.; Schultz, Harold D.

2011-01-01

Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)–induced hypothyroidism in hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for three months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390, a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O2 in N2), hypoxic (10% O2 in N2) and hypercapnic (5% CO2 in O2) air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH 23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH 23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH. PMID:21669406

The ins and outs of breath holding: simple demonstrations of complex respiratory physiology.

PubMed

Skow, Rachel J; Day, Trevor A; Fuller, Jonathan E; Bruce, Christina D; Steinback, Craig D

2015-09-01

The physiology of breath holding is complex, and voluntary breath-hold duration is affected by many factors, including practice, psychology, respiratory chemoreflexes, and lung stretch. In this activity, we outline a number of simple laboratory activities or classroom demonstrations that illustrate the complexity of the integrative physiology behind breath-hold duration. These activities require minimal equipment and are easily adapted to small-group demonstrations or a larger-group inquiry format where students can design a protocol and collect and analyze data from their classmates. Specifically, breath-hold duration is measured during a number of maneuvers, including after end expiration, end inspiration, voluntary prior hyperventilation, and inspired hyperoxia. Further activities illustrate the potential contribution of chemoreflexes through rebreathing and repeated rebreathing after a maximum breath hold. The outcome measures resulting from each intervention are easily visualized and plotted and can comprise a comprehensive data set to illustrate and discuss complex and integrated cardiorespiratory physiology. Copyright © 2015 The American Physiological Society.

Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

PubMed

Donnelly, William T; Bartlett, Donald; Leiter, J C

2016-07-01

What is the central question of this study? Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who died of SIDS. Therefore, we tested the hypothesis that serotonin in the nucleus of the solitary tract (NTS) would shorten reflex apnoea. What is the main finding and its importance? Serotonin microinjected into the NTS shortened the apnoea and respiratory inhibition associated with the laryngeal chemoreflex. Moreover, this effect was achieved through a 5-HT3 receptor. This is a new insight that is likely to be relevant to the pathogenesis of SIDS. The laryngeal chemoreflex (LCR), an airway-protective reflex that causes apnoea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome. Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of sudden infant death syndrome, and 5-HT seems to be important in terminating apnoeas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anaesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C fibre afferents of the superior laryngeal nerve, and serotonergic shortening of the LCR may be mediated presynaptically by enhanced activation of inhibitory interneurons within the NTS. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Acrolein Causes TRPA1-Mediated Sensory Irritation and Indirect Potentiation of TRPV1-Mediated Pulmonary Chemoreflex Response

EPA Science Inventory

We previously demonstrated that acute exposure to acrolein causes immediate sensory irritation, with rapid decrease in heart rate (HR) and increase in inspiratory time (Ti), and potentiation of pulmonary chemoreflex response 24hrs later; of these effects only the latter is mediat...

The Ins and Outs of Breath Holding: Simple Demonstrations of Complex Respiratory Physiology

ERIC Educational Resources Information Center

Skow, Rachel J.; Day, Trevor A.; Fuller, Jonathan E.; Bruce, Christina D.; Steinback, Craig D.

2015-01-01

The physiology of breath holding is complex, and voluntary breath-hold duration is affected by many factors, including practice, psychology, respiratory chemoreflexes, and lung stretch. In this activity, we outline a number of simple laboratory activities or classroom demonstrations that illustrate the complexity of the integrative physiology…

Exercise training effects on hypoxic and hypercapnic ventilatory responses in mice selected for increased voluntary wheel running.

PubMed

Kelly, Scott A; Rezende, Enrico L; Chappell, Mark A; Gomes, Fernando R; Kolb, Erik M; Malisch, Jessica L; Rhodes, Justin S; Mitchell, Gordon S; Garland, Theodore

2014-02-01

What is the central question of this study? We used experimental evolution to determine how selective breeding for high voluntary wheel running and exercise training (7-11 weeks) affect ventilatory chemoreflexes of laboratory mice at rest. What is the main finding and its importance? Selective breeding, although significantly affecting some traits, did not systematically alter ventilation across gas concentrations. As with most human studies, our findings support the idea that endurance training attenuates resting ventilation. However, little evidence was found for a correlation between ventilatory chemoreflexes and the amount of individual voluntary wheel running. We conclude that exercise 'training' alters respiratory behaviours, but these changes may not be necessary to achieve high levels of wheel running. Ventilatory control is affected by genetics, the environment and gene-environment and gene-gene interactions. Here, we used an experimental evolution approach to test whether 37 generations of selective breeding for high voluntary wheel running (genetic effects) and/or long-term (7-11 weeks) wheel access (training effects) alter acute respiratory behaviour of mice resting in normoxic, hypoxic and hypercapnic conditions. As the four replicate high-runner (HR) lines run much more than the four non-selected control (C) lines, we also examined whether the amount of exercise among individual mice was a quantitative predictor of ventilatory chemoreflexes at rest. Selective breeding and/or wheel access significantly affected several traits. In normoxia, HR mice tended to have lower mass-adjusted rates of oxygen consumption and carbon dioxide production. Chronic wheel access increased oxygen consumption and carbon dioxide production in both HR and C mice during hypercapnia. Breathing frequency and minute ventilation were significantly reduced by chronic wheel access in both HR and C mice during hypoxia. Selection history, while significantly affecting some traits, did not systematically alter ventilation across all gas concentrations. As with most human studies, our findings support the idea that endurance training (access to wheel running) attenuates resting ventilation. However, little evidence was found for a correlation at the level of the individual variation between ventilatory chemoreflexes and performance (amount of individual voluntary wheel running). We tentatively conclude that exercise 'training' alters respiratory behaviours, but these changes may not be necessary to achieve high levels of wheel running.

Potentiation of pulmonary reflex response to capsaicin 24h following whole-body acrolein exposure is mediated by TRPV1.

PubMed

Hazari, Mehdi S; Rowan, William H; Winsett, Darrell W; Ledbetter, Allen D; Haykal-Coates, Najwa; Watkinson, William P; Costa, Daniel L

2008-02-01

Pulmonary C-fibers are stimulated by irritant air pollutants producing apnea, bronchospasm, and decrease in HR. Chemoreflex responses resulting from C-fiber activation are sometimes mediated by TRPV1 and release of substance P. While acrolein has been shown to stimulate C-fibers, the persistence of acrolein effects and the role of C-fibers in these responses are unknown. These experiments were designed to determine the effects of whole-body acrolein exposure and pulmonary chemoreflex response post-acrolein. Rats were exposed to either air or 3 ppm acrolein for 3 h while ventilatory function and HR were measured; 1-day later response to capsaicin challenge was measured in anesthetized rats. Rats experienced apnea and decrease in HR upon exposure to acrolein, which was not affected by either TRPV1 antagonist or NK(1)R antagonist pretreatment. Twenty-four hours later, capsaicin caused apnea and bronchoconstriction in control rats, which was potentiated in rats exposed to acrolein. Pretreatment with TRPV1 antagonist or NK(1)R antagonist prevented potentiation of apneic response and bronchoconstriction 24h post-exposure. These data suggest that although potentiation of pulmonary chemoreflex response 24h post-acrolein is mediated by TRPV1 and release of substance P, cardiopulmonary inhibition during whole-body acrolein exposure is mediated through other mechanisms.

Phrenic motor outputs in response to bronchopulmonary C‐fibre activation following chronic cervical spinal cord injury

PubMed Central

2016-01-01

Key points Activation of bronchopulmonary C‐fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity.Following chronic cervical spinal cord injury, bronchopulmonary C‐fibre activation‐induced inhibition of phrenic activity was exaggerated.Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C‐fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord‐injured animals.These data suggest that activation of bronchopulmonary C‐fibres may retard phrenic output recovery following cervical spinal cord injury.The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity. Abstract Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin‐induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8–9 weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra‐jugular capsaicin (1.5 μg kg−1) injection was performed to activate the bronchopulmonary C‐fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin‐induced prolongation of expiratory duration was significantly attenuated in C2Hx animals. However, ipsilateral phrenic activity was robustly reduced after capsaicin treatment compared to uninjured animals. Single phrenic fibre recording experiments demonstrated that C2Hx animals had a higher proportion of late‐inspiratory phrenic motoneurons that were relatively sensitive to capsaicin treatment compared to early‐inspiratory phrenic motoneurons. Moreover, late‐inspiratory phrenic motoneurons in C2Hx animals had a weaker discharge frequency and slower recovery time than uninjured animals. These results suggest bilateral phrenic nerves differentially respond to bronchopulmonary C‐fibre activation following unilateral cervical hemisection, and the severe inhibition of phrenic bursting is due to a shift in the discharge pattern of phrenic motoneurons. PMID:27106483

POTENTIATION OF PULMONARY REFLEX RESPONSE TO CAPSAICIN 24 HOURS FOLLOWING WHOLE-BODY ACROLEIN EXPOSURE IS MEDIATED BY TRPV1

EPA Science Inventory

Pulmonary C-fibers are stimulated by irritant air pollutants producing apnea, bronchospasm, and decrease in HR. C-fiber chemoreflex activation is mediated by TRPV1 and release of substance P. While acrolein has been shown to stimulate C-fibers, the persistence of acrolein effect...

An adenosine A(2A) antagonist injected in the NTS reverses thermal prolongation of the LCR in decerebrate piglets.

PubMed

Xia, Luxi; Bartlett, Donald; Leiter, J C

2008-12-31

Hyperthermia prolongs the laryngeal chemoreflex (LCR). Under normothermic conditions, adenosine antagonists shorten and adenosine A(2A) (Ad-A(2A)) agonists prolong the LCR. Therefore, we tested the hypothesis that SCH-58261, an Ad-A(2A) receptor antagonist, would prevent thermal prolongation of the LCR when injected unilaterally within the nucleus of the solitary tract (NTS). We studied decerebrate piglets aged 4-13 days. We elicited the LCR by injecting 0.1ml of water into the larynx and recorded integrated phrenic nerve activity. The laryngeal chemoreflex was prolonged when the body temperature of each piglet was raised approximately 2.5 degrees C, and SCH-58261 reversed the thermal prolongation of the LCR when injected into the NTS (n=13), but not when injected in the nucleus ambiguus (n=9). Injections of vehicle alone into the NTS did not alter the thermal prolongation of the LCR (n=9). We conclude that activation of adenosine receptors, perhaps located on GABAergic neurons in the NTS, contributes to thermal prolongation of the LCR.

Guinea Pig as a Model to Study the Carotid Body Mediated Chronic Intermittent Hypoxia Effects.

PubMed

Docio, Inmaculada; Olea, Elena; Prieto-LLoret, Jesus; Gallego-Martin, Teresa; Obeso, Ana; Gomez-Niño, Angela; Rocher, Asuncion

2018-01-01

Clinical and experimental evidence indicates a positive correlation between chronic intermittent hypoxia (CIH), increased carotid body (CB) chemosensitivity, enhanced sympatho-respiratory coupling and arterial hypertension and cardiovascular disease. Several groups have reported that both the afferent and efferent arms of the CB chemo-reflex are enhanced in CIH animal models through the oscillatory CB activation by recurrent hypoxia/reoxygenation episodes. Accordingly, CB ablation or denervation results in the reduction of these effects. To date, no studies have determined the effects of CIH treatment in chemo-reflex sensitization in guinea pig, a rodent with a hypofunctional CB and lacking ventilatory responses to hypoxia. We hypothesized that the lack of CB hypoxia response in guinea pig would suppress chemo-reflex sensitization and thereby would attenuate or eliminate respiratory, sympathetic and cardiovascular effects of CIH treatment. The main purpose of this study was to assess if guinea pig CB undergoes overactivation by CIH and to correlate CIH effects on CB chemoreceptors with cardiovascular and respiratory responses to hypoxia. We measured CB secretory activity, ventilatory parameters, systemic arterial pressure and sympathetic activity, basal and in response to acute hypoxia in two groups of animals: control and 30 days CIH exposed male guinea pigs. Our results indicated that CIH guinea pig CB lacks activity elicited by acute hypoxia measured as catecholamine (CA) secretory response or intracellular calcium transients. Plethysmography data showed that only severe hypoxia (7% O 2 ) and hypercapnia (5% CO 2 ) induced a significant increased ventilatory response in CIH animals, together with higher oxygen consumption. Therefore, CIH exposure blunted hyperventilation to hypoxia and hypercapnia normalized to oxygen consumption. Increase in plasma CA and superior cervical ganglion CA content was found, implying a CIH induced sympathetic hyperactivity. CIH promoted cardiovascular adjustments by increasing heart rate and mean arterial blood pressure without cardiac ventricle hypertrophy. In conclusion, CIH does not sensitize CB chemoreceptor response to hypoxia but promotes cardiovascular adjustments probably not mediated by the CB. Guinea pigs could represent an interesting model to elucidate the mechanisms that underlie the long-term effects of CIH exposure to provide evidence for the role of the CB mediating pathological effects in sleep apnea diseases.

The pattern of breathing following a 10-breath voluntary hyperventilation during hyperoxic rebreathing.

PubMed

Chatha, D; Duffin, J

1997-06-01

The pattern of breathing following a 10-breath voluntary hyperventilation period during hyperoxic rebreathing was compared to that without hyperventilation in 6 subjects (3 male and 3 female). The aim was to measure the posthyperventilation short-term potentiation of ventilation without changes in respiratory chemoreflex drives induced by the voluntary hyperventilation. Hyperoxia was used to reduce the peripheral chemoreflex drive, and rebreathing to prevent the decrease in arterial carbon dioxide tension normally produced by hyperventilation. There were significant differences between the male and female responses. However, in all subjects, ventilation and heart rate were increased during hyperventilation but end-tidal partial pressures of carbon dioxide and oxygen were unchanged. Following hyperventilation, ventilation immediately returned to the values observed when hyperventilation was omitted. Hyperventilation did not induce a short-term potentiation of ventilation under these conditions; changes in chemoreflex stimuli brought about by cardiovascular changes induced by hyperventilation may play a role in the short-term potentiation observed under other circumstances.

[Individual-typological evaluation of cardiorespiratory responses to hypoxia and hypercapnia in young healthy men].

PubMed

Divert, V E; Krivoshchekov, S G; Vodyanitsky, S N

2015-01-01

The aim of the study was the approaches development to a substantiation of recommendations on the persons selection for different types of physical exercise on the basis of individual chemoreflex reactivity of cardiorespiratory system. That's for the ventilatory and cardial responses in tests with increasing inhalation hypoxia and hypercapnia on the group of young healthy man was performed. It was shown that hypoxia induce predominantly cardial response, but hypercapnia--ventilatory response. On that predominantly chemoreflex reactions (respiration system to hypercarbia and cardiac--to hypoxaemia) four types of in parts were defined: small reactions in both parts (type 1), small reaction of cardiac system and strong of respiratory system (type 2), strong for heart response and small for respiration (type 3), and strong for both parts (type 4). Statistical analysis has shown that each type of reactions is specific to certain kind of sports training: 1 type for swimmers, 2 and 3 types for skiers, 4 type for boxers, weight lifters and wrestlers. For skiers group the inverse regression dependence between the growth of heart reactivity to hypoxaemia and depression of the pulmonary ventilation reactivity to hypercarbia is revealed at joint rising of the oxygen consumption per unit body weight. High quality skiers are distinguished by relative balance of chemoreflex responses of respiration and heart. It was found that physically untrained persons have pronounced individual variability of cardiorespiratory system chemoreflex reactions, what can be used for personal recommendations for choosing the kind of sports to employment.

Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation

PubMed Central

Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Hodges, Matthew R.

2013-01-01

A current and major unanswered question is why the highly sensitive central CO2/H+ chemoreceptors do not prevent hypoventilation-induced hypercapnia following carotid body denervation (CBD). Because perturbations involving the carotid bodies affect central neuromodulator and/or neurotransmitter levels within the respiratory network, we tested the hypothesis that after CBD there is an increase in inhibitory and/or a decrease in excitatory neurochemicals within the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic use were implanted bilaterally in the VMC within or near the pre-Bötzinger Complex (preBötC) through which mock cerebrospinal fluid (mCSF) was dialyzed. Effluent mCSF was collected and analyzed for neurochemical content. The goats hypoventilated (peak +22.3 ± 3.4 mmHg PaCO2) and exhibited a reduced CO2 chemoreflex (nadir, 34.8 ± 7.4% of control ΔV̇E/ΔPaCO2) after CBD with significant but limited recovery over 30 days post-CBD. After CBD, GABA and glycine were above pre-CBD levels (266 ± 29% and 189 ± 25% of pre-CBD; P < 0.05), and glutamine and dopamine were significantly below pre-CBD levels (P < 0.05). Serotonin, substance P, and epinephrine were variable but not significantly (P > 0.05) different from control after CBD. Analyses of brainstem tissues collected 30 days after CBD exhibited 1) a midline raphe-specific reduction (P < 0.05) in the percentage of tryptophan hydroxylase–expressing neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five medullary respiratory nuclei. We conclude that after CBD, an increase in inhibitory neurotransmitters and a decrease in excitatory neuromodulation within the VMC/preBötC likely contribute to the hypoventilation and attenuated ventilatory CO2 chemoreflex. PMID:23869058

Adenosine A2a receptors and O2 sensing in development

PubMed Central

2011-01-01

Reduced mitochondrial oxidative phosphorylation, via activation of adenylate kinase and the resulting exponential rise in the cellular AMP/ATP ratio, appears to be a critical factor underlying O2 sensing in many chemoreceptive tissues in mammals. The elevated AMP/ATP ratio, in turn, activates key enzymes that are involved in physiologic adjustments that tend to balance ATP supply and demand. An example is the conversion of AMP to adenosine via 5′-nucleotidase and the resulting activation of adenosine A2A receptors, which are involved in acute oxygen sensing by both carotid bodies and the brain. In fetal sheep, A2A receptors associated with carotid bodies trigger hypoxic cardiovascular chemoreflexes, while central A2A receptors mediate hypoxic inhibition of breathing and rapid eye movements. A2A receptors are also involved in hypoxic regulation of fetal endocrine systems, metabolism, and vascular tone. In developing lambs, A2A receptors play virtually no role in O2 sensing by the carotid bodies, but brain A2A receptors remain critically involved in the roll-off ventilatory response to hypoxia. In adult mammals, A2A receptors have been implicated in O2 sensing by carotid glomus cells, while central A2A receptors likely blunt hypoxic hyperventilation. In conclusion, A2A receptors are crucially involved in the transduction mechanisms of O2 sensing in fetal carotid bodies and brains. Postnatally, central A2A receptors remain key mediators of hypoxic respiratory depression, but they are less critical for O2 sensing in carotid chemoreceptors, particularly in developing lambs. PMID:21677265

α1- and α2-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats.

PubMed

Oliveira, Luiz M; Moreira, Thiago S; Kuo, Fu-Shan; Mulkey, Daniel K; Takakura, Ana C

2016-09-01

Norepinephrine (NE) is a potent modulator of breathing that can increase/decrease respiratory activity by α1-/α2-adrenergic receptor (AR) activation, respectively. The retrotrapezoid nucleus (RTN) is known to contribute to central chemoreception, inspiration, and active expiration. Here we investigate the sources of catecholaminergic inputs to the RTN and identify respiratory effects produced by activation of ARs in this region. By injecting the retrograde tracer Fluoro-Gold into the RTN, we identified back-labeled catecholaminergic neurons in the A7 region. In urethane-anesthetized, vagotomized, and artificially ventilated male Wistar rats unilateral injection of NE or moxonidine (α2-AR agonist) blunted diaphragm muscle activity (DiaEMG) frequency and amplitude, without changing abdominal muscle activity. Those inhibitory effects were reduced by preapplication of yohimbine (α2-AR antagonist) into the RTN. Conversely, unilateral RTN injection of phenylephrine (α1-AR agonist) increased DiaEMG amplitude and frequency and facilitated active expiration. This response was blocked by prior RTN injection of prazosin (α1-AR antagonist). Interestingly, RTN injection of propranolol (β-AR antagonist) had no effect on respiratory inhibition elicited by applications of NE into the RTN; however, the combined blockade of α2- and β-ARs (coapplication of propranolol and yohimbine) revealed an α1-AR-dependent excitatory response to NE that resulted in increase in DiaEMG frequency and facilitation of active expiration. However, blockade of α1-, α2-, or β-ARs in the RTN had minimal effect on baseline respiratory activity, on central or peripheral chemoreflexes. These results suggest that NE signaling can modulate RTN chemoreceptor function; however, endogenous NE signaling does not contribute to baseline breathing or the ventilatory response to central or peripheral chemoreceptor activity in urethane-anesthetized rats. Copyright © 2016 the American Physiological Society.

Cardiorespiratory interactions to external stimuli.

PubMed

Bernardi, L; Porta, C; Spicuzza, L; Sleight, P

2005-09-01

Respiration is a powerful modulator of heart rate variability, and of baro- or chemo-reflex sensitivity. This occurs via a mechanical effect of breathing that synchronizes all cardiovascular variables at the respiratory rhythm, particularly when this occurs at a particular slow rate coincident with the Mayer waves in arterial pressure (approximately 6 cycles/min). Recitation of the rosary prayer (or of most mantras), induces a marked enhancement of these slow rhythms, whereas random verbalization or random breathing does not. This phenomenon in turn increases baroreflex sensitivity and reduces chemoreflex sensitivity, leading to increases in parasympathetic and reductions in sympathetic activity. The opposite can be seen during either verbalization or mental stress tests. Qualitatively similar effects can be obtained even by passive listening to more or less rhythmic auditory stimuli, such as music, and the speed of the rhythm (rather than the style) appears to be one of the main determinants of the cardiovascular and respiratory responses. These findings have clinical relevance. Appropriate modulation of breathing, can improve/restore autonomic control of cardiovascular and respiratory systems in relevant diseases such as hypertension and heart failure, and might therefore help improving exercise tolerance, quality of life, and ultimately, survival.

Development of an anaesthetized-rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram.

PubMed

Miyamoto, Tadayoshi; Manabe, Kou; Ueda, Shinya; Nakahara, Hidehiro

2018-05-01

What is the central question of this study? The lack of useful small-animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise-induced ventilatory abnormalities in various disease states. What is the main finding and its importance? We developed an anaesthetized-rat model for studying exercise hyperpnoea, using a respiratory equilibrium diagram for quantitative characterization of the respiratory chemoreflex feedback system. This experimental model will provide an opportunity to clarify the major determinant mechanisms of exercise hyperpnoea, and will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. Exercise-induced ventilatory abnormalities in various disease states seem to arise from pathological changes of respiratory regulation. Although experimental studies in small animals are essential to investigate the pathophysiological basis of various disease models, the lack of an integrated framework for quantitatively characterizing respiratory regulation during exercise prevents us from resolving these problems. The purpose of this study was to develop an anaesthetized-rat model for studying exercise hyperpnoea for quantitative characterization of the respiratory chemoreflex feedback system. In 24 anaesthetized rats, we induced muscle contraction by stimulating bilateral distal sciatic nerves at low and high voltage to mimic exercise. We recorded breath-by-breath respiratory gas analysis data and cardiorespiratory responses while running two protocols to characterize the controller and plant of the respiratory chemoreflex. The controller was characterized by determining the linear relationship between end-tidal CO 2 pressure (P ETC O2) and minute ventilation (V̇E), and the plant by the hyperbolic relationship between V̇E and P ETC O2. During exercise, the controller curve shifted upward without change in controller gain, accompanying increased oxygen uptake. The hyperbolic plant curve shifted rightward and downward depending on exercise intensity as predicted by increased metabolism. Exercise intensity-dependent changes in operating points (V̇E and P ETC O2) were estimated by integrating the controller and plant curves in a respiratory equilibrium diagram. In conclusion, we developed an anaesthetized-rat model for studying exercise hyperpnoea, using systems analysis for quantitative characterization of the respiratory system. This novel experimental model will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. © 2018 Morinomiya University of Medical Sciences. Experimental Physiology © 2018 The Physiological Society.

Central mechanisms for exercise training-induced reduction in sympatho-excitation in chronic heart failure.

PubMed

Haack, Karla K V; Zucker, Irving H

2015-03-01

The control of sympathetic outflow in the chronic heart failure (CHF) state is markedly abnormal. Patients with heart failure present with increased plasma norepinephrine and increased sympathetic nerve activity. The mechanism for this sympatho-excitation is multiple and varied. Both depression in negative feedback sensory control mechanisms and augmentation of excitatory reflexes contribute to this sympatho-excitation. These include the arterial baroreflex, cardiac reflexes, arterial chemoreflexes and cardiac sympathetic afferent reflexes. In addition, abnormalities in central signaling in autonomic pathways have been implicated in the sympatho-excitatory process in CHF. These mechanisms include increases in central Angiotensin II and the Type 1 receptor, increased in reactive oxygen stress, upregulation in glutamate signaling and NR1 (N-methyl-D-aspartate subtype 1) receptors and others. Exercise training in the CHF state has been shown to reduce sympathetic outflow and result in increased survival and reduced cardiac events. Exercise training has been shown to reduce central Angiotensin II signaling including the Type 1 receptor and reduce oxidative stress by lowering the expression of many of the subunits of NADPH oxidase. In addition, there are profound effects on the central generation of nitric oxide and nitric oxide synthase in sympatho-regulatory areas of the brain. Recent studies have pointed to the balance between Angiotensin Converting Enzyme (ACE) and ACE2, translating into Angiotensin II and Angiotensin 1-7 as important regulators of sympathetic outflow. These enzymes appear to be normalized following exercise training in CHF. Understanding the precise molecular mechanisms by which exercise training is sympatho-inhibitory will uncover new targets for therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Alternative approaches to treatment of Central Sleep Apnea.

PubMed

Thomas, Robert Joseph

2014-03-01

Divergent approaches to treatment of hypocapnic central sleep apnea syndromes reflect the difficulties in taming a hyperactive respiratory chemoreflex. As both sleep fragmentation and a narrow CO 2 reserve or increased loop gain drive the disease, sedatives (to induce longer periods of stable non-rapid eye movement (NREM) sleep and reduce the destabilizing effects of arousals in NREM sleep) and CO 2 -based stabilization approaches are logical. Adaptive ventilation reduces mean hyperventilation yet can induce ventilator-patient dyssynchrony, while enhanced expiratory rebreathing space (EERS, dead space during positive pressure therapy) and CO 2 manipulation directly stabilize respiratory control by moving CO 2 above the apnea threshold. Carbonic anhydrase inhibition can provide further adjunctive benefits. Provent and Winx may be less likely to trigger central apneas or periodic breathing in those with a narrow CO 2 reserve. An oral appliance can meaningfully reduce positive pressure requirements and thus enable treatment of complex apnea. Novel pharmacological approaches may target mediators of carotid body glomus cell excitation, such as the balance between gas neurotransmitters. In complex apnea patients, single mode therapy is not always successful, and multi-modality therapy might need to be considered. Phenotyping of sleep apnea beyond conventional scoring approaches is the key to optimal management.

Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anesthetized neonatal rats

PubMed Central

Donnelly, William T.; Bartlett, Donald; Leiter, J.C.

2017-01-01

The laryngeal chemoreflex (LCR), an airway protective reflex that causes apnea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome (SIDS). Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of SIDS, and 5-HT seems to be important in terminating apneas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT 1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C-fiber afferents of the superior laryngeal nerve, and serotonergic shortening of the LCR may be mediated presynaptically by enhanced activation of inhibitory interneurons within the NTS that terminate during the LCR. PMID:27121960

[The prediction of atrial fibrillation recurrence after electrical cardioversion with the chemoreflex sensitivity].

PubMed

Budeus, M; Hennersdorf, M; Perings, C; Strauer, B E

2004-04-01

Patients with paroxysmal atrial fibrillation have a lower chemoreflex sensitivity (CHRS) which is characterized as an autonomic dysfunction. Because of this observation we examined the theory of an autonomic dysfunction as the reason for the reccurrence of atrial fibrilation after electrical cardioversion. We measured the CHRS among 43 patients 24 h after successful electrical cardioversion and the patients were controlled for at least 6 months. During the six months of follow-up a recurrence was observed in 18 patients with a mean of 8.3 days. There was no difference in organic heart disease or in the use of drugs. Left atrial diameter was not significantly larger in patients with a recurrence. Patients with a recurrence have a significantly lower CHRS than patients with sinus rhythm (2.41 +/- 1.82 vs 5.62 +/- 3.02 ms/mmHg, p < 0.04). The diagnostic value of a CHRS below 3.0 ms/mmHg achieved a specificity of 68%, a sensitivity of 67%, a positive and negative predictive value of 60% and 74%. An analysis of CHRS seems to be an appropriate method to predict a recurrence of atrial fibrillation. The predictive power of the method has to be examined by prospective investigations of a larger patient population and a longer follow-up. Patients with paroxysmal atrial fibrillation have a lower chemoreflex sensitivity (CHRS) which is characterized as an autonomic dysfunction. Because of this observation we examined the theory of an autonomic dysfunction as the reason for the recurrence of atrial fibrillation after electrical cardioversion.

Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation

PubMed Central

Rivera, Eileen; Clarke, Debbie A.; Baugham, Ila L.; Ocon, Anthony J.; Taneja, Indu; Terilli, Courtney; Medow, Marvin S.

2011-01-01

Increasing arterial blood pressure (AP) decreases ventilation, whereas decreasing AP increases ventilation in experimental animals. To determine whether a “ventilatory baroreflex” exists in humans, we studied 12 healthy subjects aged 18–26 yr. Subjects underwent baroreflex unloading and reloading using intravenous bolus sodium nitroprusside (SNP) followed by phenylephrine (“Oxford maneuver”) during the following “gas conditions:” room air, hypoxia (10% oxygen)-eucapnia, and 30% oxygen-hypercapnia to 55–60 Torr. Mean AP (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), expiratory minute ventilation (VE), respiratory rate (RR), and tidal volume were measured. After achieving a stable baseline for gas conditions, we performed the Oxford maneuver. VE increased from 8.8 ± 1.3 l/min in room air to 14.6 ± 0.8 l/min during hypoxia and to 20.1 ± 2.4 l/min during hypercapnia, primarily by increasing tidal volume. VE doubled during SNP. CO increased from 4.9 ± .3 l/min in room air to 6.1 ± .6 l/min during hypoxia and 6.4 ± .4 l/min during hypercapnia with decreased TPR. HR increased for hypoxia and hypercapnia. Sigmoidal ventilatory baroreflex curves of VE versus MAP were prepared for each subject and each gas condition. Averaged curves for a given gas condition were obtained by averaging fits over all subjects. There were no significant differences in the average fitted slopes for different gas conditions, although the operating point varied with gas conditions. We conclude that rapid baroreflex unloading during the Oxford maneuver is a potent ventilatory stimulus in healthy volunteers. Tidal volume is primarily increased. Ventilatory baroreflex sensitivity is unaffected by chemoreflex activation, although the operating point is shifted with hypoxia and hypercapnia. PMID:21317304

Exercise training attenuates chemoreflex-mediated reductions of renal blood flow in heart failure

PubMed Central

Pügge, Carolin; Mediratta, Jai; Schiller, Alicia M.; Del Rio, Rodrigo; Zucker, Irving H.; Schultz, Harold D.

2015-01-01

In chronic heart failure (CHF), carotid body chemoreceptor (CBC) activity is increased and contributes to increased tonic and hypoxia-evoked elevation in renal sympathetic nerve activity (RSNA). Elevated RSNA and reduced renal perfusion may contribute to development of the cardio-renal syndrome in CHF. Exercise training (EXT) has been shown to abrogate CBC-mediated increases in RSNA in experimental heart failure; however, the effect of EXT on CBC control of renal blood flow (RBF) is undetermined. We hypothesized that CBCs contribute to tonic reductions in RBF in CHF, that stimulation of the CBC with hypoxia would result in exaggerated reductions in RBF, and that these responses would be attenuated with EXT. RBF was measured in CHF-sedentary (SED), CHF-EXT, CHF-carotid body denervation (CBD), and CHF-renal denervation (RDNX) groups. We measured RBF at rest and in response to hypoxia (FiO2 10%). All animals exhibited similar reductions in ejection fraction and fractional shortening as well as increases in ventricular systolic and diastolic volumes. Resting RBF was lower in CHF-SED (29 ± 2 ml/min) than in CHF-EXT animals (46 ± 2 ml/min, P < 0.05) or in CHF-CBD animals (42 ± 6 ml/min, P < 0.05). In CHF-SED, RBF decreased during hypoxia, and this was prevented in CHF-EXT animals. Both CBD and RDNX abolished the RBF response to hypoxia in CHF. Mean arterial pressure increased in response to hypoxia in CHF-SED, but was prevented by EXT, CBD, and RDNX. EXT is effective in attenuating chemoreflex-mediated tonic and hypoxia-evoked reductions in RBF in CHF. PMID:26001414

Exercise training attenuates chemoreflex-mediated reductions of renal blood flow in heart failure.

PubMed

Marcus, Noah J; Pügge, Carolin; Mediratta, Jai; Schiller, Alicia M; Del Rio, Rodrigo; Zucker, Irving H; Schultz, Harold D

2015-07-15

In chronic heart failure (CHF), carotid body chemoreceptor (CBC) activity is increased and contributes to increased tonic and hypoxia-evoked elevation in renal sympathetic nerve activity (RSNA). Elevated RSNA and reduced renal perfusion may contribute to development of the cardio-renal syndrome in CHF. Exercise training (EXT) has been shown to abrogate CBC-mediated increases in RSNA in experimental heart failure; however, the effect of EXT on CBC control of renal blood flow (RBF) is undetermined. We hypothesized that CBCs contribute to tonic reductions in RBF in CHF, that stimulation of the CBC with hypoxia would result in exaggerated reductions in RBF, and that these responses would be attenuated with EXT. RBF was measured in CHF-sedentary (SED), CHF-EXT, CHF-carotid body denervation (CBD), and CHF-renal denervation (RDNX) groups. We measured RBF at rest and in response to hypoxia (FiO2 10%). All animals exhibited similar reductions in ejection fraction and fractional shortening as well as increases in ventricular systolic and diastolic volumes. Resting RBF was lower in CHF-SED (29 ± 2 ml/min) than in CHF-EXT animals (46 ± 2 ml/min, P < 0.05) or in CHF-CBD animals (42 ± 6 ml/min, P < 0.05). In CHF-SED, RBF decreased during hypoxia, and this was prevented in CHF-EXT animals. Both CBD and RDNX abolished the RBF response to hypoxia in CHF. Mean arterial pressure increased in response to hypoxia in CHF-SED, but was prevented by EXT, CBD, and RDNX. EXT is effective in attenuating chemoreflex-mediated tonic and hypoxia-evoked reductions in RBF in CHF. Copyright © 2015 the American Physiological Society.

Alternative approaches to treatment of Central Sleep Apnea

PubMed Central

2013-01-01

Synopsis Divergent approaches to treatment of hypocapnic central sleep apnea syndromes reflect the difficulties in taming a hyperactive respiratory chemoreflex. As both sleep fragmentation and a narrow CO2 reserve or increased loop gain drive the disease, sedatives (to induce longer periods of stable non-rapid eye movement (NREM) sleep and reduce the destabilizing effects of arousals in NREM sleep) and CO2-based stabilization approaches are logical. Adaptive ventilation reduces mean hyperventilation yet can induce ventilator-patient dyssynchrony, while enhanced expiratory rebreathing space (EERS, dead space during positive pressure therapy) and CO2 manipulation directly stabilize respiratory control by moving CO2 above the apnea threshold. Carbonic anhydrase inhibition can provide further adjunctive benefits. Provent and Winx may be less likely to trigger central apneas or periodic breathing in those with a narrow CO2 reserve. An oral appliance can meaningfully reduce positive pressure requirements and thus enable treatment of complex apnea. Novel pharmacological approaches may target mediators of carotid body glomus cell excitation, such as the balance between gas neurotransmitters. In complex apnea patients, single mode therapy is not always successful, and multi-modality therapy might need to be considered. Phenotyping of sleep apnea beyond conventional scoring approaches is the key to optimal management. PMID:24772053

Sensing hypoxia: physiology, genetics and epigenetics

PubMed Central

Prabhakar, Nanduri R

2013-01-01

The carotid body is a sensory organ for detecting arterial blood O2 levels and reflexly mediates systemic cardiac, vascular and respiratory responses to hypoxia. This article presents a brief review of the roles of gaseous messengers in the sensory transduction at the carotid body, genetic and epigenetic influences on hypoxic sensing and the role of the carotid body chemoreflex in cardiorespiratory diseases. Type I (also called glomus) cells, the site of O2 sensing in the carotid body, express haem oxygenase-2 and cystathionine-γ-lyase, the enzymes which catalyse the generation of CO and H2S, respectively. Physiological studies have shown that CO is an inhibitory gas messenger, which contributes to the low sensory activity during normoxia, whereas H2S is excitatory and mediates sensory stimulation by hypoxia. Hypoxia-evoked H2S generation in the carotid body requires the interaction of cystathionine-γ-lyase with haem oxygenase-2, which generates CO. Hypoxia-inducible factors 1 and 2 constitute important components of the genetic make-up in the carotid body, which influence hypoxic sensing by regulating the intracellular redox state via transcriptional regulation of pro- and antioxidant enzymes. Recent studies suggest that developmental programming of the carotid body response to hypoxia involves epigenetic changes, e.g. DNA methylation of genes encoding redox-regulating enzymes. Emerging evidence implicates heightened carotid body chemoreflex in the progression of autonomic morbidities associated with cardiorespiratory diseases, such as sleep-disordered breathing with apnoea, congestive heart failure and essential hypertension. PMID:23459758

Changes in glutamate receptor subunits within the medulla in goats after section of the carotid sinus nerves

PubMed Central

Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Bukowy, John D.; Daghistany, Asem O.; Hodges, Matthew R.

2014-01-01

The mechanisms which contribute to the time-dependent recovery of resting ventilation and the ventilatory CO2 chemoreflex after carotid body denervation (CBD) are poorly understood. Herein we tested the hypothesis that there are time-dependent changes in the expression of specific AMPA, NMDA, and/or neurokinin-1 (NK1R) receptors within respiratory-related brain stem nuclei acutely or chronically after CBD in adult goats. Brain stem tissues were collected acutely (5 days) or chronically (30 days) after sham or bilateral CBD, immunostained with antibodies targeting AMPA (GluA1 or GluA2), NMDA (GluN1), or NK-1 receptors, and optical density (OD) compared. Physiological measurement confirmed categorization of each group and showed ventilatory effects consistent with bilateral CBD (Miller et al. J Appl Physiol 115: 1088–1098, 2013). Acutely after CBD, GluA1 OD was unchanged or slightly increased, but GluA2 and GluN1 OD were reduced 15–30% within the nucleus tractus solitarius (NTS) and in other medullary respiratory nuclei. Chronically after CBD, GluA1 was reduced (P < 0.05) within the caudal NTS and in other nuclei, but there was significant recovery of GluA2 and GluN1 OD. NK1 OD was not significantly different from control after CBD. We conclude that the initial decrease in GluA2 and GluN1 after CBD likely contributes to hypoventilation and the reduced CO2 chemoreflex. The partial recovery of ventilation and the CO2 chemoreflex after CBD parallel a time-dependent return of these receptors to near control levels but likely depend upon additional initiating and maintenance factors for neuroplasticity. PMID:24790015

Comparison of the metabolic and ventilatory response to hypoxia and H2S in unsedated mice and rats.

PubMed

Haouzi, Philippe; Bell, Harold J; Notet, Veronique; Bihain, Bernard

2009-07-31

Hypoxia alters the control of breathing and metabolism by increasing ventilation through the arterial chemoreflex, an effect which, in small-sized animals, is offset by a centrally mediated reduction in metabolism and respiration. We tested the hypothesis that hydrogen sulfide (H(2)S) is involved in transducing these effects in mammals. The rationale for this hypothesis is twofold. Firstly, inhalation of a 20-80 ppm H(2)S reduces metabolism in small mammals and this effect is analogous to that of hypoxia. Secondly, endogenous H(2)S appears to mediate some of the cardio-vascular effects of hypoxia in non-mammalian species. We, therefore, compared the ventilatory and metabolic effects of exposure to 60 ppm H(2)S and to 10% O(2) in small and large rodents (20g mice and 700g rats) wherein the metabolic response to hypoxia has been shown to differ according to body mass. H(2)S and hypoxia produced profound depression in metabolic rate in the mice, but not in the large rats. The depression was much faster with H(2)S than with hypoxia. The relative hyperventilation produced by hypoxia in the mice was replaced by a depression with H(2)S, which paralleled the drop in metabolic rate. In the larger rats, ventilation was stimulated in hypoxia, with no change in metabolism, while H(2)S affected neither breathing nor metabolism. When mice were simultaneously exposed to H(2)S and hypoxia, the stimulatory effects of hypoxia on breathing were abolished, and a much larger respiratory and metabolic depression was observed than with H(2)S alone. H(2)S had, therefore, no stimulatory effect on the arterial chemoreflex. The ventilatory depression during hypoxia and H(2)S in small mammals appears to be dependent upon the ability to decrease metabolism.

The role of excitatory amino acids and substance P in the mediation of the cough reflex within the nucleus tractus solitarii of the rabbit.

PubMed

Mutolo, Donatella; Bongianni, Fulvia; Fontana, Giovanni A; Pantaleo, Tito

2007-09-28

We hypothesized that cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit is primarily mediated by glutamatergic neurotransmission at the level of the caudal portions of the medial subnucleus of the nucleus tractus solitarii (NTS) and the lateral commissural NTS where cough-related afferents terminate, and that this reflex is potentiated by local release of substance P. To test our hypothesis, we performed bilateral microinjections (30-50 nl) of ionotropic glutamate receptor antagonists or substance P into these locations in pentobarbitone anaesthetized, spontaneously breathing rabbits. Blockade of NMDA and non-NMDA receptors by 50mM kynurenic acid abolished the cough reflex without affecting the Breuer-Hering inflation reflex or the pulmonary chemoreflex. Blockade of non-NMDA receptors using 10mM CNQX or 5mM NBQX caused identical effects. Blockade of NMDA receptors by 10mM D-AP5 strongly reduced, but did not abolish cough responses. Microinjections of 1mM substance P increased peak and rate of rise of abdominal muscle activity as well as cough number. These results are the first to provide evidence that ionotropic glutamate receptors, especially non-NMDA receptors, located within specific regions of NTS are primarily involved in the mediation of cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit. Present findings on substance P cough-enhancing effects extend previous observations and are relevant to the tachykinin-mediated central sensitization of the cough reflex. They also may provide hints for further studies on centrally acting antitussive drugs.

Pathogenesis of Central and Complex Sleep Apnoea

PubMed Central

Orr, Jeremy E.; Malhotra, Atul; Sands, Scott A.

2016-01-01

Central sleep apnoea (CSA)—the temporary absence or diminution of ventilator effort during sleep—is seen in a variety of forms including periodic breathing in infancy and healthy adults at altitude and Cheyne-Stokes respiration in heart failure. In most circumstances, the cyclic absence of effort is paradoxically a consequence of hypersensitive ventilatory chemoreflex responses to oppose changes in airflow, i.e. elevated loop gain, leading to overshoot/undershoot ventilatory oscillations. Considerable evidence illustrates overlap between CSA and obstructive sleep apnoea (OSA), including elevated loop gain in patients with OSA and the presence of pharyngeal narrowing during central apnoeas. Indeed, treatment of OSA, whether via CPAP, tracheostomy, or oral appliances, can reveal CSA, an occurrence referred to as complex sleep apnoea. Factors influencing loop gain include increased chemosensitivity (increased controller gain), reduced damping of blood gas levels (increased plant gain) and increased lung to chemoreceptor circulatory delay. Sleep-wake transitions and pharyngeal dilator muscle responses effectively raise the controller gain and therefore also contribute to total loop gain and overall instability. In some circumstances, for example apnoea of infancy and central congenital hypoventilation syndrome, central apnoeas are the consequence of ventilatory depression and defective ventilatory responses, i.e. low loop gain. The efficacy of available treatments for CSA can be explained in terms of their effects on loop gain, e.g. CPAP improves lung volume (plant gain), stimulants reduce the alveolar-inspired PCO2 difference, supplemental oxygen lowers chemosensitivity. Understanding the magnitude of loop gain and the mechanisms contributing to instability may facilitate personalised interventions for CSA. PMID:27797160

Pathogenesis of central and complex sleep apnoea.

PubMed

Orr, Jeremy E; Malhotra, Atul; Sands, Scott A

2017-01-01

Central sleep apnoea (CSA) - the temporary absence or diminution of ventilatory effort during sleep - is seen in a variety of forms including periodic breathing in infancy and healthy adults at altitude and Cheyne-Stokes respiration in heart failure. In most circumstances, the cyclic absence of effort is paradoxically a consequence of hypersensitive ventilatory chemoreflex responses to oppose changes in airflow, that is elevated loop gain, leading to overshoot/undershoot ventilatory oscillations. Considerable evidence illustrates overlap between CSA and obstructive sleep apnoea (OSA), including elevated loop gain in patients with OSA and the presence of pharyngeal narrowing during central apnoeas. Indeed, treatment of OSA, whether via continuous positive airway pressure (CPAP), tracheostomy or oral appliances, can reveal CSA, an occurrence referred to as complex sleep apnoea. Factors influencing loop gain include increased chemosensitivity (increased controller gain), reduced damping of blood gas levels (increased plant gain) and increased lung to chemoreceptor circulatory delay. Sleep-wake transitions and pharyngeal dilator muscle responses effectively raise the controller gain and therefore also contribute to total loop gain and overall instability. In some circumstances, for example apnoea of infancy and central congenital hypoventilation syndrome, central apnoeas are the consequence of ventilatory depression and defective ventilatory responses, that is low loop gain. The efficacy of available treatments for CSA can be explained in terms of their effects on loop gain, for example CPAP improves lung volume (plant gain), stimulants reduce the alveolar-inspired PCO 2 difference and supplemental oxygen lowers chemosensitivity. Understanding the magnitude of loop gain and the mechanisms contributing to instability may facilitate personalized interventions for CSA. © 2016 Asian Pacific Society of Respirology.

Effect of treatment with nasal continuous positive airway pressure on ventilatory response to hypoxia and hypercapnia in patients with sleep apnea syndrome.

PubMed

Spicuzza, Lucia; Bernardi, Luciano; Balsamo, Rossella; Ciancio, Nicola; Polosa, Riccardo; Di Maria, Giuseppe

2006-09-01

The increase in peripheral chemoreflex sensitivity in patients with obstructive sleep apnea (OSA) is associated with activation of autonomic nervous system and hemodynamic responses. Nasal CPAP (nCPAP) is an effective treatment for OSA, but little is known on its effect on chemoreflex sensitivity. To assess the effect of nCPAP treatment or placebo (sham nCPAP) on ventilatory control in patients with OSA. Sleep laboratory of Azienda Ospedaliera Garibaldi. Twenty-five patients with moderate-to-severe OSA. Patients were randomly assigned to either therapeutic nCPAP (use of optimal pressure, n = 15) or sham nCPAP (suboptimal pressure of 1 to 2 cm H2O, n = 10) in a double-blind fashion and treated for 1 month. A rebreathing test to assess ventilatory response to normocapnic hypoxia and normoxic hypercapnia was performed at basal condition and after 1 month of treatment. The use of therapeutic nCPAP or sham nCPAP did not affect daytime percentage of arterial oxygen saturation (SaO2%) or end-tidal P(CO2). The normocapnic hypoxic ventilatory response was reduced after 1 month of treatment with nCPAP (the slope was 1.08 +/- 0.02 L/min/SaO2% at basal condition and 0.53 +/- 0.07 L/min/SaO2% after 1 month of treatment, p = 0.008) [mean +/- SD], but not in patients treated with sham nCPAP (slope, 0.83 +/- 0.09 L/min/SaO2% and 0.85 +/- 0.19 L/min/SaO2% at basal condition and after 1 month, respectively). The normoxic hypercapnic ventilatory response remained unchanged after 1 month in both groups. No changes in ventilatory response to either hypoxia or hypercapnia were observed after a single night of nCPAP treatment. The ventilatory response to hypoxia is reduced during regular treatment, but not after short-term treatment, with nCPAP. Readjusted peripheral oxygen chemosensitivity during nCPAP treatment may be a side effect of both reduced sympathetic activity and increased baroreflex activity, or a possible continuous positive airway pressure-related mechanism leading to a reduced activation of autonomic nervous system per se.

Hypoxia Silences Retrotrapezoid Nucleus Respiratory Chemoreceptors via Alkalosis

PubMed Central

Basting, Tyler M.; Burke, Peter G.R.; Kanbar, Roy; Viar, Kenneth E.; Stornetta, Daniel S.; Stornetta, Ruth L.

2015-01-01

In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (ΔfR) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔVT) followed the same trend. The effect of hypoxia on ΔfR was not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). ΔfR was highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN. PMID:25589748

Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis.

PubMed

Basting, Tyler M; Burke, Peter G R; Kanbar, Roy; Viar, Kenneth E; Stornetta, Daniel S; Stornetta, Ruth L; Guyenet, Patrice G

2015-01-14

In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (Δf(R)) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔV(T)) followed the same trend. The effect of hypoxia on Δf(R) was not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). Δf(R) was highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN. Copyright © 2015 the authors 0270-6474/15/350527-17$15.00/0.

Interactions between CO2 chemoreflexes and arterial baroreflexes

NASA Technical Reports Server (NTRS)

Henry, R. A.; Lu, I. L.; Beightol, L. A.; Eckberg, D. L.

1998-01-01

We studied interactions between CO2 chemoreflexes and arterial baroreflexes in 10 supine healthy young men and women. We measured vagal carotid baroreceptor-cardiac reflexes and steady-state fast Fourier transform R-R interval and photoplethysmographic arterial pressure power spectra at three arterial pressure levels (nitroprusside, saline, and phenylephrine infusions) and three end-tidal CO2 levels (3, 4, and 5%, fixed-frequency, large-tidal-volume breathing, CO2 plus O2). Our study supports three principal conclusions. First, although low levels of CO2 chemoreceptor stimulation reduce R-R intervals and R-R interval variability, statistical modeling suggests that this effect is indirect rather than direct and is mediated by reductions of arterial pressure. Second, reductions of R-R intervals during hypocapnia reflect simple shifting of vagally mediated carotid baroreflex responses on the R-R interval axis rather than changes of baroreflex gain, range, or operational point. Third, the influence of CO2 chemoreceptor stimulation on arterial pressure (and, derivatively, on R-R intervals and R-R interval variability) depends critically on baseline arterial pressure levels: chemoreceptor effects are smaller when pressure is low and larger when arterial pressure is high.

The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

PubMed Central

Diogo, Lucilia N.; Monteiro, Emília C.

2014-01-01

Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CPAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT. PMID:25295010

Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats.

PubMed

Souza, George M P R; Kanbar, Roy; Stornetta, Daniel S; Abbott, Stephen B G; Stornetta, Ruth L; Guyenet, Patrice G

2018-04-18

The retrotrapezoid nucleus (RTN) is one of several CNS nuclei that contribute, in various capacities (e.g. CO 2 detection, neuronal modulation) to the central respiratory chemoreflex (CRC). Here we test how important the RTN is to PCO 2 homeostasis and breathing during sleep or wake. RTN Nmb positive neurons were killed with targeted microinjections of substance-P-saporin conjugate in adult rats. Under normoxia, rats with large RTN lesions (92 ± 4 % cell loss) had normal blood pressure (BP) and arterial pH but were hypoxic (-8 mmHg PaO 2 ) and hypercapnic (+10 mmHg PaCO 2 ). In resting conditions, minute-volume (V E ) was normal but breathing frequency (f R ) was elevated and tidal volume (V T ) reduced. Resting O 2 consumption and CO 2 production were normal. The hypercapnic ventilatory reflex in 65% FiO 2 had an inverse exponential relationship with the number of surviving RTN neurons and was decreased by up to 92%. The hypoxic ventilatory reflex (HVR; FiO 2 21-10%) persisted after RTN lesions, hypoxia-induced sighing was normal and hypoxia-induced hypotension reduced. In rats with RTN lesions, breathing was lowest during slow-wave sleep (SWS), especially under hyperoxia, but apneas and sleep-disordered breathing were not observed. In conclusion, near complete RTN destruction in rats virtually eliminates the CRC but HVR persists and sighing and the state-dependence of breathing are unchanged. Under normoxia, RTN lesions cause no change in V E but alveolar ventilation is reduced by at least 21%, probably because of increased physiological dead volume. RTN lesions do not cause sleep apnea during SWS, even under hyperoxia. Background: the retrotrapezoid nucleus (RTN) drives breathing proportionally to brain PCO 2 but its role during various states of vigilance needed clarification. New result: Under normoxia, RTN lesions increase the arterial PCO 2 set-point, lower the PO 2 set-point and reduce alveolar ventilation relative to CO 2 production. Tidal volume is reduced and breathing frequency increased to a comparable degree during wake, slow-wave sleep and REM sleep. RTN lesions do not produce apneas or disordered breathing during sleep. New result: RTN lesions in rats virtually eliminate the central respiratory chemoreflex (CRC) while preserving the cardiorespiratory responses to hypoxia; the relationship between CRC and number of surviving RTN Nmb neurons is an inverse exponential. the CRC does not function without the RTN. In the quasi-complete absence of the RTN and CRC, alveolar ventilation is reduced despite an increased drive to breathe from the carotid bodies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Daily and seasonal rhythms in the respiratory sensitivity of red-eared sliders (Trachemys scripta elegans).

PubMed

Reyes, Catalina; Milsom, William K

2009-10-01

The purpose of the present study was to determine whether the daily and seasonal changes in ventilation and breathing pattern previously documented in red-eared sliders resulted solely from daily and seasonal oscillations in metabolism or also from changes in chemoreflex sensitivity. Turtles were exposed to natural environmental conditions over a one year period. In each season, oxygen consumption, ventilation and breathing pattern were measured continuously for 24 h while turtles were breathing air and for 24 h while they were breathing a hypoxic-hypercapnic gas mixture (H-H). We found that oxygen consumption was reduced equally during the day and night under H-H in all seasons except spring. Ventilation was stimulated by H-H but the magnitude of the response was always less at night. On average, it was also less in the winter and greater in the reproductive season. The data indicate that the day-night differences in ventilation and breathing pattern seen previously resulted from daily changes in chemoreflex sensitivity whereas the seasonal changes were strictly due to changes in metabolism. Regardless of mechanism, the changes resulted in longer apneas at night and in the winter at any given level of total ventilation, facilitating longer submergence at times of the day and year when turtles are most vulnerable.

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex

PubMed Central

Corcoran, Andrea E.; Brust, Rachael D.; Chang, YoonJeung; Nattie, Eugene E.

2017-01-01

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1, referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO2. Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 (Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO2. Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. PMID:28073937

Breath-to-breath hypercapnic response in neonatal rats: temperature dependency of the chemoreflexes and potential implications for breathing stability.

PubMed

Cummings, Kevin J; Frappell, Peter B

2009-07-01

The breathing of newborns is destabilized by warm temperatures. We hypothesized that in unanesthetized, intact newborn rats, body temperature (T(B)) influences the peripheral chemoreflex response (PCR response) to hypercapnia. To test this, we delivered square-wave challenges of 8% CO(2) in air to postnatal day 4-5 (P4-P5) rats held at a T(B) of 30 degrees C (Cold group, n = 11), 33 degrees C (Cool group, n = 10), and 35 degrees C thermoneutral zone group [thermoneutral zone (TNZ) group, n = 11], while measuring ventilation (Ve) directly with a pneumotach and mask. Cool animals were challenged with 8% CO(2) balanced in either air or hyperoxia (n = 10) to identify the PCR response. Breath-to-breath analysis was performed on 30 room air breaths and every breath of the 1-min CO(2) challenge. As expected, warmer T(B) was associated with an unstable breathing pattern in room air: TNZ animals had a coefficient of variation in Ve (Ve CV%) that was double that of animals held at cooler T(B) (P < 0.001). Hyperoxia markedly suppressed the hypercapnic ventilatory response over the first 10 breaths (or approximately 4 s), suggesting that this domain is dominated by the PCR response. The PCR response (P = 0.03) and total response (P = 0.04) were significantly greater in TNZ animals compared with hypothermic animals. The total response had a significant, negative relationship with Vco(2) (R(2) = 0.53; P < 0.001). Breathing stability was positively related to the total response (R(2) = 0.36; P < 0.001) and to a lesser extent, the PCR response (R(2) = 0.19; P = 0.01) and was negatively related to Vco(2) (R(2) = 0.34; P < 0.001). ANCOVA confirmed a significant effect of T(B) alone on breathing stability (P < 0.01), with no independent effects of Vco(2) (P = 0.41), the PCR response (P = 0.82), or the total Ve response (P = 0.08). Our data suggest that in early postnatal life, the chemoreflex responses to CO(2) are highly influenced by T(B), and while related to breathing stability, are not predictors of stability after accounting for the independent effect of T(B).

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

PubMed

Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

2016-05-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. Copyright © 2016 the American Physiological Society.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats

PubMed Central

Kaplan, Kara; Echert, Ashley E.; Massat, Ben; Puissant, Madeleine M.; Palygin, Oleg; Geurts, Aron M.

2016-01-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DATph2−/−) rats. DATph2−/− rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DATph2−/− rats. Body temperature was also maintained in adult DATph2−/− rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DATph2−/− rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID:26869713

Control of the exercise hyperpnoea in humans: a modeling perspective.

PubMed

Ward, S A

2000-09-01

Models of the exercise hyperpnoea have classically incorporated elements of proportional feedback (carotid and medullary chemosensory) and feedforward (central and/or peripheral neurogenic) control. However, the precise details of the control process remain unresolved, reflecting in part both technical and interpretational limitations inherent in isolating putative control mechanisms in the intact human, and also the challenges to linear control theory presented by multiple-input integration, especially with regard to the ventilatory and gas-exchange complexities encountered at work rates which engender a metabolic acidosis. While some combination of neurogenic, chemoreflex and circulatory-coupled processes are likely to contribute to the control, the system appears to evidence considerable redundancy. This, coupled with the lack of appreciable error signals in the mean levels of arterial blood gas tensions and pH over a wide range of work rates, has motivated the formulation of innovative control models that reflect not only spatial interactions but also temporal interactions (i.e. memory). The challenge is to discriminate between robust competing control models that: (a) integrate such processes within plausible physiological equivalents; and (b) account for both the dynamic and steady-state system response over a range of exercise intensities. Such models are not yet available.

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex.

PubMed

Hennessy, Morgan L; Corcoran, Andrea E; Brust, Rachael D; Chang, YoonJeung; Nattie, Eugene E; Dymecki, Susan M

2017-02-15

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 ( Tac1 ) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1 , referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine -N- oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO 2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO 2 Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 ( Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO 2 Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. Copyright © 2017 the authors 0270-6474/17/371807-13$15.00/0.

Sleep-induced periodic breathing and apnea: a theoretical study.

PubMed

Khoo, M C; Gottschalk, A; Pack, A I

1991-05-01

To elucidate the mechanisms that lead to sleep-disordered breathing, we have developed a mathematical model that allows for dynamic interactions among the chemical control of respiration, changes in sleep-waking state, and changes in upper airway patency. The increase in steady-state arterial PCO2 accompanying sleep is shown to be inversely related to the ventilatory response to CO2. Chemical control of respiration becomes less stable during the light stage of sleep, despite a reduction in chemoresponsiveness, due to a concomitant increase in "plant gain" (i.e., responsiveness of blood gases to ventilatory changes). The withdrawal of the "wakefulness drive" during sleep onset represents a strong perturbation to respiratory control: higher magnitudes and rates of withdrawal of this drive favor instability. These results may account for the higher incidence of periodic breathing observed during light sleep and sleep onset. Periodic ventilation can also result from repetitive alternations between sleep onset and arousal. The potential for instability is further compounded if the possibility of upper airway occlusion is also included. In systems with high controller gains, instability is mediated primarily through chemoreflex overcompensation. However, in systems with depressed chemoresponsiveness, rapid sleep onset and large blood gas fluctuations trigger repetitive episodes of arousal and hyperpnea alternating with apneas that may or may not be obstructive. Between these extremes, more complex patterns can arise from the interaction between chemoreflex-mediated oscillations of shorter-cycle-duration (approximately 36 s) and longer-wavelength (approximately 60-80 s) state-driven oscillations.

Obstructive Sleep Apnoea/Hypopnoea Syndrome and Hypertension

PubMed Central

Al-Abri, Mohammed A; Al-Hashmi, Khamis M

2008-01-01

The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a common disorder, affecting around 2–4% of the middle-aged population. There is a strong association between OSAHS and hypertension, based on animal, large epidemiological and interventional studies. The epidemiological studies have shown a dose-response relationship between apnoea/hypopnoea index (AHI) and the risk of developing hypertension. Different mechanisms may have a role in the process of elevated blood pressure in OSAHS. Sympathetic activity is increased in OSAHS patients during sleep and wakefulness. This increase in sympathetic activity is probably due to activation of baroreflexes and chemoreflexes by frequent arousals and hypoxaemia a result of apnoea or hypopnoea events. Continuous positive airway pressure (CPAP) has been shown to reduce sympathetic stimulation and blood pressure in OSAHS patients. Altered endothelial function may also have a role in the pathogenesis of hypertension in OSAHS subjects. Reduction of nitric oxide (NO) production and increase in the formation of free radicals may be responsible for the impairment of the vasodilatation of micro-vasculature in these subjects as a result of hypoxaemia. It has been shown that effective CPAP therapy has a reversible effect on endothelial dysfunction. PMID:21748071

Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia

PubMed Central

King, T. Luise; Ruyle, Brian C.; Kline, David D.; Heesch, Cheryl M.

2015-01-01

Brainstem catecholamine neurons modulate sensory information and participate in control of cardiorespiratory function. These neurons have multiple projections, including to the paraventricular nucleus (PVN), which contributes to cardiorespiratory and neuroendocrine responses to hypoxia. We have shown that PVN-projecting catecholaminergic neurons are activated by hypoxia, but the function of these neurons is not known. To test the hypothesis that PVN-projecting catecholamine neurons participate in responses to respiratory challenges, we injected IgG saporin (control; n = 6) or anti-dopamine β-hydroxylase saporin (DSAP; n = 6) into the PVN to retrogradely lesion catecholamine neurons projecting to the PVN. After 2 wk, respiratory measurements (plethysmography) were made in awake rats during normoxia, increasing intensities of hypoxia (12, 10, and 8% O2) and hypercapnia (5% CO2-95% O2). DSAP decreased the number of tyrosine hydroxylase-immunoreactive terminals in PVN and cells counted in ventrolateral medulla (VLM; −37%) and nucleus tractus solitarii (nTS; −36%). DSAP produced a small but significant decrease in respiratory rate at baseline (during normoxia) and at all intensities of hypoxia. Tidal volume and minute ventilation (VE) index also were impaired at higher hypoxic intensities (10-8% O2; e.g., VE at 8% O2: IgG = 181 ± 22, DSAP = 91 ± 4 arbitrary units). Depressed ventilation in DSAP rats was associated with significantly lower arterial O2 saturation at all hypoxic intensities. PVN DSAP also reduced ventilatory responses to 5% CO2 (VE: IgG = 176 ± 21 and DSAP = 84 ± 5 arbitrary units). Data indicate that catecholamine neurons projecting to the PVN are important for peripheral and central chemoreflex respiratory responses and for maintenance of arterial oxygen levels during hypoxic stimuli. PMID:26157062

Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males.

PubMed

Deacon, Naomi L; McEvoy, R Doug; Stadler, Daniel L; Catcheside, Peter G

2017-09-01

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO 2 levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO 2 and 3.0 ± 0.2% O 2 ) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO 2 , O 2 saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea. NEW & NOTEWORTHY Both arousal state and concomitant CO 2 levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity. Copyright © 2017 the American Physiological Society.

Characterisation of putative oxygen chemoreceptors in bowfin (Amia calva).

PubMed

Porteus, Cosima S; Wright, Patricia A; Milsom, William K

2014-04-15

Serotonin containing neuroepithelial cells (NECs) are putative oxygen sensing cells found in different locations within the gills of fish. In this study we wished to determine the effect of sustained internal (blood) hypoxaemia versus external (aquatic) hypoxia on the size and density of NECs in the first gill arch of bowfin (Amia calva), a facultative air breather. We identified five different populations of serotonergic NECs in this species (Types I-V) based on location, presence of synaptic vesicles (SV) that stain for the antibody SV2, innervation and labelling with the neural crest marker HNK-1. Cell Types I-III were innervated, and these cells, which participate in central O2 chemoreflexes, were studied further. Although there was no change in the density of any cell type in bowfin after exposure to sustained hypoxia (6.0 kPa for 7 days) without access to air, all three of these cell types increased in size. In contrast, only Type II and III cells increased in size in bowfin exposed to sustained hypoxia with access to air. These data support the suggestion that NECs are putative oxygen-sensing cells, that they occur in several locations, and that Type I cells monitor only hypoxaemia, whereas both other cell types monitor hypoxia and hypoxaemia.

High fat diet blunts the effects of leptin on ventilation and on carotid body activity.

PubMed

Ribeiro, Maria J; Sacramento, Joana F; Gallego-Martin, Teresa; Olea, Elena; Melo, Bernardete F; Guarino, Maria P; Yubero, Sara; Obeso, Ana; Conde, Silvia V

2017-12-22

Leptin plays a role in the control of breathing, acting mainly on central nervous system; however, leptin receptors have been recently shown to be expressed in the carotid body (CB), and this finding suggests a physiological role for leptin in the regulation of CB function. Leptin increases minute ventilation in both basal and hypoxic conditions in rats. It increases the frequency of carotid sinus nerve discharge in basal conditions, as well as the release of adenosine from the CB. However, in a metabolic syndrome animal model, the effects of leptin in ventilatory control, carotid sinus nerve activity and adenosine release by the CB are blunted. Although leptin may be involved in triggering CB overactivation in initial stages of obesity and dysmetabolism, resistance to leptin signalling and blunting of responses develops in metabolic syndrome animal models. Leptin plays a role in the control of breathing, acting mainly on central nervous system structures. Leptin receptors are expressed in the carotid body (CB) and this finding has been associated with a putative physiological role of leptin in the regulation of CB function. Since, the CBs are implicated in energy metabolism, here we tested the effects of different concentrations of leptin administration on ventilatory parameters and on carotid sinus nerve (CSN) activity in control and high-fat (HF) diet fed rats, in order to clarify the role of leptin in ventilation control in metabolic disease states. We also investigated the expression of leptin receptors and the neurotransmitters involved in leptin signalling in the CBs. We found that in non-disease conditions, leptin increases minute ventilation in both basal and hypoxic conditions. However, in the HF model, the effect of leptin in ventilatory control is blunted. We also observed that HF rats display an increased frequency of CSN discharge in basal conditions that is not altered by leptin, in contrast to what is observed in control animals. Leptin did not modify intracellular Ca 2+ in CB chemoreceptor cells, but it produced an increase in the release of adenosine from the whole CB. We conclude that CBs represent an important target for leptin signalling, not only to coordinate peripheral ventilatory chemoreflexive drive, but probably also to modulate metabolic variables. We also concluded that leptin signalling is mediated by adenosine release and that HF diets blunt leptin responses in the CB, compromising ventilatory adaptation. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Homeostasis of exercise hyperpnea and optimal sensorimotor integration: the internal model paradigm.

PubMed

Poon, Chi-Sang; Tin, Chung; Yu, Yunguo

2007-10-15

Homeostasis is a basic tenet of biomedicine and an open problem for many physiological control systems. Among them, none has been more extensively studied and intensely debated than the dilemma of exercise hyperpnea - a paradoxical homeostatic increase of respiratory ventilation that is geared to metabolic demands instead of the normal chemoreflex mechanism. Classical control theory has led to a plethora of "feedback/feedforward control" or "set point" hypotheses for homeostatic regulation, yet so far none of them has proved satisfactory in explaining exercise hyperpnea and its interactions with other respiratory inputs. Instead, the available evidence points to a far more sophisticated respiratory controller capable of integrating multiple afferent and efferent signals in adapting the ventilatory pattern toward optimality relative to conflicting homeostatic, energetic and other objectives. This optimality principle parsimoniously mimics exercise hyperpnea, chemoreflex and a host of characteristic respiratory responses to abnormal gas exchange or mechanical loading/unloading in health and in cardiopulmonary diseases - all without resorting to a feedforward "exercise stimulus". Rather, an emergent controller signal encoding the projected metabolic level is predicted by the principle as an exercise-induced 'mental percept' or 'internal model', presumably engendered by associative learning (operant conditioning or classical conditioning) which achieves optimality through continuous identification of, and adaptation to, the causal relationship between respiratory motor output and resultant chemical-mechanical afferent feedbacks. This internal model self-tuning adaptive control paradigm opens a new challenge and exciting opportunity for experimental and theoretical elucidations of the mechanisms of respiratory control - and of homeostatic regulation and sensorimotor integration in general.

Baroreflex activation therapy lowers arterial pressure without apparent stimulation of the carotid bodies.

PubMed

Alnima, Teba; Goedhart, Emilie J B M; Seelen, Randy; van der Grinten, Chris P M; de Leeuw, Peter W; Kroon, Abraham A

2015-06-01

Carotid baroreflex activation therapy produces a sustained fall in blood pressure in patients with resistant hypertension. Because the activation electrodes are implanted at the level of the carotid sinus, it is conceivable that the nearby located carotid body chemoreceptors are stimulated as well. Physiological stimulation of the carotid chemoreceptors not only stimulates respiration but also increases sympathetic activity, which may counteract the effects of baroreflex activation. The aim of this exploratory study is to investigate whether there is concomitant carotid chemoreflex activation during baroreflex activation therapy. Fifteen participants with the Rheos system were included in this single-center study. At arrival at the clinic, the device was switched off for 2 hours while patients were at rest. Subsequently, the device was switched on at 6 electric settings of high and low frequencies and amplitudes. Respiration and blood pressure measurements were performed during all device activation settings. Multilevel statistical models were adjusted for age, sex, body mass index, antihypertensive therapeutic index, sleep apnea, coronary artery disease, systolic blood pressure, and heart rate. There was no change in end-tidal carbon dioxide, partial pressure of carbon dioxide, breath duration, and breathing frequency during any of the electric settings with the device. Nevertheless, mean arterial pressure showed a highly significant decrease during electric activation (P<0.001). Carotid baroreflex activation therapy using the Rheos system did not stimulate respiration at several electric device activation energies, which suggests that there is no appreciable coactivation of carotid body chemoreceptors during device therapy. © 2015 American Heart Association, Inc.

Chemosensitive Phox2b-expressing neurons are crucial for hypercapnic ventilatory response in the nucleus tractus solitarius.

PubMed

Fu, Congrui; Xue, Jinyu; Wang, Ri; Chen, Jinting; Ma, Lan; Liu, Yixian; Wang, Xuejiao; Guo, Fang; Zhang, Yi; Zhang, Xiangjian; Wang, Sheng

2017-07-15

Central hypercapnic hypoventilation is highly prevalent in children suffering from congenital central hypoventilation syndrome (CCHS). Mutations of the gene for paired-like homeobox 2b (Phox2b) are aetiologically associated with CCHS and Phox2b is present in central components of respiratory chemoreflex, such as the nucleus tractus solitarius (NTS). Injection of the neurotoxin substance P-saporin into NTS destroys Phox2b-expressing neurons. Impaired hypercapnic ventilatory response caused by this neurotoxin is attributable to a loss of CO 2 -sensitive Phox2b-expressing NTS neurons. A subgroup of Phox2b-expressing neurons exhibits intrinsic chemosensitivity. A background K + channel-like current is partially responsible for such chemosensitivity in Phox2b-expressing neurons. The present study helps us better understand the mechanism of respiratory deficits in CCHS and potentially locates a brainstem site for development of precise clinical intervention. The nucleus tractus solitarius (NTS) neurons have been considered to function as central respiratory chemoreceptors. However, the common molecular marker defined for these neurons remains unknown. The present study investigated whether paired-like homeobox 2b (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR) and whether these neurons exhibit intrinsic chemosensitivity. HCVR was assessed using whole body plethysmography and neuronal chemosensitivity was examined by patch clamp recordings in brainstem slices or dissociated neurons from Phox2b-EGFP transgenic mice. Injection of the neurotoxin substance P-saporin (SSP-SAP) into NTS destroyed Phox2b-expressing neurons. Minute ventilation and tidal volume were both reduced by 13% during exposure to 8% CO 2 in inspired air when ∼13% of the Phox2b-expressing neurons were eliminated. However, a loss of ∼18% of these neurons was associated with considerable decreases in minute ventilation by ≥18% and in tidal volume by≥22% when challenged by ≥4% CO 2 . In both cases, breathing frequency was unaffected. Most CO 2 -activated neurons were immunoreactive to Phox2b. In brainstem slices, ∼43% of Phox2b-expressing neurons from Phox2b-EGFP mice displayed a sustained or transient increase in firing rate during physiological acidification (pH 7.0 or 8% CO 2 ). Such a response was also present in dissociated neurons in favour of an intrinsic property. In voltage clamp recordings, a background K + channel-like current was found in a subgroup of Phox2b-expressing neurons. Thus, the respiratory deficits caused by injection of SSP-SAP into the NTS are attributable to proportional lesions of CO 2 /H + -sensitive Phox2b-expressing neurons. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia.

PubMed

Prabhakar, Nanduri R; Peng, Ying-Jie; Yuan, Guoxiang; Nanduri, Jayasri

2018-05-01

Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H 2 S production in the CB. Blockade of H 2 S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H 2 S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H 2 S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H 2 S. Inhibiting H 2 S synthesis prevented IH-evoked sympathetic activation and hypertension.

Determinants of ventilation and pulmonary artery pressure during early acclimatization to hypoxia in humans

PubMed Central

Fatemian, Marzieh; Herigstad, Mari; Croft, Quentin P. P.; Formenti, Federico; Cardenas, Rosa; Wheeler, Carly; Smith, Thomas G.; Friedmannova, Maria; Dorrington, Keith L.

2015-01-01

Key points Lung ventilation and pulmonary artery pressure rise progressively in response to 8 h of hypoxia, changes described as ‘acclimatization to hypoxia’. Acclimatization responses differ markedly between humans for unknown reasons.We explored whether the magnitudes of the ventilatory and vascular responses were related, and whether the degree of acclimatization could be predicted by acute measurements of ventilatory and vascular sensitivities.In 80 healthy human volunteers measurements of acclimatization were made before, during, and after a sustained exposure to 8 h of isocapnic hypoxia.No correlation was found between measures of ventilatory and pulmonary vascular acclimatization.The ventilatory chemoreflex sensitivities to acute hypoxia and hypercapnia all increased in proportion to their pre‐acclimatization values following 8 h of hypoxia. The peripheral (rapid) chemoreflex sensitivity to CO2, measured before sustained hypoxia against a background of hyperoxia, was a modest predictor of ventilatory acclimatization to hypoxia. This finding has relevance to predicting human acclimatization to the hypoxia of altitude. Abstract Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxia were related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8‐h isocapnic exposure to hypoxia (end‐tidal P O2=55 Torr) in a purpose‐built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (GpO2) and hyperoxic hypercapnia, the latter divided into peripheral (G pC O2) and central (G cC O2) components. Substantial acclimatization was observed in both ventilation and PASP, the latter being 40% greater in women than men. No correlation was found between the magnitudes of pulmonary ventilatory and pulmonary vascular responses. For GpO2, G pC O2 and G cC O2, but not the sensitivity of PASP to acute hypoxia, the magnitude of the increase during acclimatization was proportional to the pre‐acclimatization value. Additionally, the change in GpO2 during acclimatization to hypoxia correlated well with most other measures of ventilatory acclimatization. Of the initial measurements prior to sustained hypoxia, only G pC O2 predicted the subsequent rise in ventilation and change in GpO2 during acclimatization. We conclude that the magnitudes of the ventilatory and pulmonary vascular responses to sustained hypoxia are predominantly determined by different factors and that the initial G pC O2 is a modest predictor of ventilatory acclimatization. PMID:25907672

Nonuniformity in the von Bezold-Jarisch reflex.

PubMed

Salo, Lauren M; Woods, Robyn L; Anderson, Colin R; McAllen, Robin M

2007-08-01

The von Bezold-Jarisch reflex (BJR) is a vagally mediated chemoreflex from the heart and lungs, causing hypopnea, bradycardia, and inhibition of sympathetic vasomotor tone. However, cardiac sympathetic nerve activity (CSNA) has not been systematically compared with vasomotor activity during the BJR. In 11 urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats, we measured CSNA simultaneously with lumbar sympathetic activity (LSNA) while the BJR was evoked by right atrial bolus injections of phenylbiguanide (0.5, 1.0, 1.5, and 2 microg). Nerve and heartbeat responses were analyzed by calculating normalized cumulative sums. LSNA and heartbeats were always reduced by the BJR. An excitatory "rebound" component often followed the inhibition of LSNA but never outweighed it. For CSNA, however, excitation usually (in 7 of 11 rats) outweighed any initial inhibition, such that the net response to phenylbiguanide was excitatory. The differences in net response between LSNA, CSNA, and heartbeats were all significant (P < 0.01). A second experimental series on seven rats showed that methyl atropine (1 mg/kg iv) abolished the bradycardia of the BJR, whereas subsequent bilateral vagotomy substantially reduced LSNA and CSNA responses, both excitatory and inhibitory. These findings show that, during the BJR, 1) CSNA is often excited, 2) there may be coactivation of sympathetic and parasympathetic drives to the heart, 3) divergent responses may be evoked simultaneously in cardiac vagal, cardiac sympathetic, and vasomotor nervous pathways, and 4) those divergent responses are mediated primarily by the vagi.

Influence of ventilation and hypocapnia on sympathetic nerve responses to hypoxia in normal humans.

PubMed

Somers, V K; Mark, A L; Zavala, D C; Abboud, F M

1989-11-01

The sympathetic response to hypoxia depends on the interaction between chemoreceptor stimulation (CRS) and the associated hyperventilation. We studied this interaction by measuring sympathetic nerve activity (SNA) to muscle in 13 normal subjects, while breathing room air, 14% O2, 10% O2, and 10% O2 with added CO2 to maintain isocapnia. Minute ventilation (VE) and blood pressure (BP) increased significantly more during isocapnic hypoxia (IHO) than hypocapnic hypoxia (HHO). In contrast, SNA increased more during HHO [40 +/- 10% (SE)] than during IHO (25 +/- 19%, P less than 0.05). To determine the reason for the lesser increase in SNA with IHO, 11 subjects underwent voluntary apnea during HHO and IHO. Apnea potentiated the SNA responses to IHO more than to HHO. SNA responses to IHO were 17 +/- 7% during breathing and 173 +/- 47% during apnea whereas SNA responses to HHO were 35 +/- 8% during breathing and 126 +/- 28% during apnea. During ventilation, the sympathoexcitation of IHO (compared with HHO) is suppressed, possibly for two reasons: 1) because of the inhibitory influence of activation of pulmonary afferents as a result of a greater increase in VE, and 2) because of the inhibitory influence of baroreceptor activation due to a greater rise in BP. Thus in humans, the ventilatory response to chemoreceptor stimulation predominates and restrains the sympathetic response. The SNA response to chemoreceptor stimulation represents the net effect of the excitatory influence of the chemoreflex and the inhibitory influence of pulmonary afferents and baroreceptor afferents.

Role of Autonomic Reflex Arcs in Cardiovascular Responses to Air Pollution Exposure

PubMed Central

Hazari, Mehdi S.; Farraj, Aimen K.

2016-01-01

The body responds to environmental stressors by triggering autonomic reflexes in the pulmonary receptors, baroreceptors, and chemoreceptors to maintain homeostasis. Numerous studies have shown that exposure to various gases and airborne particles can alter the functional outcome of these reflexes, particularly with respect to the cardiovascular system. Modulation of autonomic neural input to the heart and vasculature following direct activation of sensory nerves in the respiratory system, elicitation of oxidative stress and inflammation, or through other mechanisms is one of the primary ways that exposure to air pollution affects normal cardiovascular function. Any homeostatic process that utilizes the autonomic nervous system to regulate organ function might be affected. Thus, air pollution and other inhaled environmental irritants have the potential to alter both local airway function and baro-and chemoreflex responses, which modulate autonomic control of blood pressure and detect concentrations of key gases in the body. While each of these reflex pathways causes distinct responses, the systems are heavily integrated and communicate through overlapping regions of the brainstem to cause global effects. This short review summarizes the function of major pulmonary sensory receptors, baroreceptors, and carotid body chemoreceptors and discusses the impacts of air pollution exposure on these systems. PMID:25123706

Postural Change Alters Autonomic Responses to Breath-Holding

PubMed Central

Taneja, Indu; Medow, Marvin S.; Clarke, Debbie; Ocon, Anthony; Stewart, Julian M.

2011-01-01

We used breath-holding during inspiration as a model to study the effect of pulmonary stretch on sympathetic nerve activity. Twelve healthy subjects (7 females, 5 males; 19–27 yrs) were tested while they performed an inspiratory breath-hold, both supine and during a 60° head-up tilt (HUT 60). Heart rate (HR), mean arterial blood pressure (MAP), respiration, muscle sympathetic nerve activity (MSNA), oxygen saturation (SaO2) and end tidal carbon dioxide (ETCO2) were recorded. Cardiac output (CO) and total peripheral resistance (TPR) were calculated. While breath-holding, ETCO2 increased significantly from 41±2 to 60±2 Torr during supine (p<0.05) and 38±2 Torr to 58±2 during HUT60 (p<0.05); SaO2 decreased from 98±1.5% to 95±1.4% supine, and from 97±1.5% to 94±1.7% during HUT60 (p=NS). MSNA showed three distinctive phases - a quiescent phase due to pulmonary stretch associated with decreased MAP, HR, CO and TPR; a second phase of baroreflex-mediated elevated MSNA which was associated with recovery of MAP and HR only during HUT60; CO and peripheral resistance returned to baseline while supine and HUT60; a third phase of further increased MSNA activity related to hypercapnia and associated with increased TPR. Breath-holding results in initial reductions of MSNA, MAP and HR by the pulmonary stretch reflex followed by increased sympathetic activity related to the arterial baroreflex and chemoreflex. PMID:20012144

AV3V lesions reduce the pressor response to L-glutamate into the RVLM.

PubMed

Vieira, Alexandre Antonio; Colombari, Eduardo; De Luca, Laurival A; Colombari, Débora Simões de Almeida; Menani, José V

2006-05-01

Neurons from the rostral ventrolateral medulla (RVLM) directly activate sympathetic pre-ganglionic neurons in the spinal cord. Hypertensive responses and sympathetic activation produced by different stimuli are strongly affected by lesions of the preoptic periventricular tissue surrounding the anteroventral third ventricle (AV3V region). Therefore, in the present study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the AV3V region on the pressor responses produced by injections of the excitatory amino acid L-glutamate into the RVLM of unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the RVLM were used. The pressor responses produced by injections of L-glutamate (1, 5 and 10 nmol/100 nl) into the RVLM were reduced 1 day (9 +/- 4, 39 +/- 6 and 37 +/- 4 mm Hg, respectively) and 15 days after AV3V lesions (13 +/- 6, 39 +/- 4 and 43 +/- 4 mm Hg, respectively, vs. sham lesions: 29 +/- 3, 50 +/- 2 and 58 +/- 3 mm Hg, respectively). Injections of L-glutamate into the RVLM in sham or AV3V-lesioned rats produced no significant change in the heart rate (HR). Baroreflex bradycardia and tachycardia produced by iv phenylephrine or sodium nitroprusside, respectively, and the pressor and bradycardic responses to chemoreflex activation with iv potassium cyanide were not modified by AV3V lesions. The results suggest that signals from the AV3V region are important for sympathetic activation induced by L-glutamate into the RVLM.

Tetrodotoxin as a Tool to Elucidate Sensory Transduction Mechanisms: The Case for the Arterial Chemoreceptors of the Carotid Body

PubMed Central

Rocher, Asuncion; Caceres, Ana Isabel; Obeso, Ana; Gonzalez, Constancio

2011-01-01

Carotid bodies (CBs) are secondary sensory receptors in which the sensing elements, chemoreceptor cells, are activated by decreases in arterial PO2 (hypoxic hypoxia). Upon activation, chemoreceptor cells (also known as Type I and glomus cells) increase their rate of release of neurotransmitters that drive the sensory activity in the carotid sinus nerve (CSN) which ends in the brain stem where reflex responses are coordinated. When challenged with hypoxic hypoxia, the physiopathologically most relevant stimulus to the CBs, they are activated and initiate ventilatory and cardiocirculatory reflexes. Reflex increase in minute volume ventilation promotes CO2 removal from alveoli and a decrease in alveolar PCO2 ensues. Reduced alveolar PCO2 makes possible alveolar and arterial PO2 to increase minimizing the intensity of hypoxia. The ventilatory effect, in conjunction the cardiocirculatory components of the CB chemoreflex, tend to maintain an adequate supply of oxygen to the tissues. The CB has been the focus of attention since the discovery of its nature as a sensory organ by de Castro (1928) and the discovery of its function as the origin of ventilatory reflexes by Heymans group (1930). A great deal of effort has been focused on the study of the mechanisms involved in O2 detection. This review is devoted to this topic, mechanisms of oxygen sensing. Starting from a summary of the main theories evolving through the years, we will emphasize the nature and significance of the findings obtained with veratridine and tetrodotoxin (TTX) in the genesis of current models of O2-sensing. PMID:22363245

Sustained sympathetic activity in altitude acclimatizing lowlanders and high-altitude natives.

PubMed

Lundby, C; Calbet, J; van Hall, G; Saltin, B; Sander, M

2018-03-01

Combined results from different independent studies suggest that acclimatization to high altitude induces a slowly developing sympathetic activation, even at levels of hypoxia that cause no acute chemoreflex-mediated sympathoexcitation. We here provide direct neurophysiological evidence for this phenomenon. In eight Danish lowlanders, we quantified mean arterial blood pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA), twice at sea level (normoxia and with acute hypoxic exposure to 12.6% O 2 ) and twice at high altitude (after 10 and 50 days of exposure to 4100 m). Measurements were also obtained in eight Bolivian highlanders on one occasion at high altitude. Acute hypoxic exposure caused no increase in MSNA (15 ± 2 vs 16 ± 2 bursts per min, respectively, and also MAP and HR remained stable). In contrast, from sea level to 10 and 50 days in high-altitude increases were observed in MAP: 72 ± 2 vs 78 ± 2 and 75 ± 2 mm Hg; HR: 54 ± 3 vs 67 ± 3 and 65 ± 3 beats per min; MSNA: 15 ± 2 vs 42 ± 5 and 42 ± 5 bursts per min, all P < .05. Bolivian subjects had high levels of MSNA: 34 ± 4 bursts per min. The simultaneous increase in MAP, HR, and MSNA suggests high altitude-induced sympathetic activity, which is sustained in well-acclimatized lowlanders. The high MSNA levels in the Bolivian highlanders suggest lifelong sympathetic activation at high altitude. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Polycythemia and high levels of erythropoietin in blood and brain blunt the hypercapnic ventilatory response in adult mice.

PubMed

Menuet, Clément; Khemiri, Hanan; de la Poëze d'Harambure, Théodora; Gestreau, Christian

2016-05-15

Changes in arterial Po2, Pco2, and pH are the strongest stimuli sensed by peripheral and central chemoreceptors to adjust ventilation to the metabolic demand. Erythropoietin (Epo), the main regulator of red blood cell production, increases the hypoxic ventilatory response, an effect attributed to the presence of Epo receptors in both carotid bodies and key brainstem structures involved in integration of peripheral inputs and control of breathing. However, it is not known whether Epo also has an effect on the hypercapnic chemoreflex. In a first attempt to answer this question, we tested the hypothesis that Epo alters the ventilatory response to increased CO2 levels. Basal ventilation and hypercapnic ventilatory response (HCVR) were recorded from control mice and from two transgenic mouse lines constitutively expressing high levels of human Epo in brain only (Tg21) or in brain and plasma (Tg6), the latter leading to polycythemia. To tease apart the potential effects of polycythemia and levels of plasma Epo in the HCVR, control animals were injected with an Epo analog (Aranesp), and Tg6 mice were treated with the hemolytic agent phenylhydrazine after splenectomy. Ventilatory parameters measured by plethysmography in conscious mice were consistent with data from electrophysiological recordings in anesthetized animals and revealed a blunted HCVR in Tg6 mice. Polycythemia alone and increased levels of plasma Epo blunt the HCVR. In addition, Tg21 mice with an augmented level of cerebral Epo also had a decreased HCVR. We discuss the potential implications of these findings in several physiopathological conditions. Copyright © 2016 the American Physiological Society.

Sympathetic activation in exercise is not dependent on muscle acidosis. Direct evidence from studies in metabolic myopathies

NASA Technical Reports Server (NTRS)

Vissing, J.; Vissing, S. F.; MacLean, D. A.; Saltin, B.; Quistorff, B.; Haller, R. G.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

Muscle acidosis has been implicated as a major determinant of reflex sympathetic activation during exercise. To test this hypothesis we studied sympathetic exercise responses in metabolic myopathies in which muscle acidosis is impaired or augmented during exercise. As an index of reflex sympathetic activation to muscle, microneurographic measurements of muscle sympathetic nerve activity (MSNA) were obtained from the peroneal nerve. MSNA was measured during static handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in patients in whom exercise-induced muscle acidosis is absent (seven myophosphorylase deficient patients; MD [McArdle's disease], and one patient with muscle phosphofructokinase deficiency [PFKD]), augmented (one patient with mitochondrial myopathy [MM]), or normal (five healthy controls). Muscle pH was monitored by 31P-magnetic resonance spectroscopy during handgrip exercise in the five control subjects, four MD patients, and the MM and PFKD patients. With handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute [bpm] and total activity [%]) was not impaired in patients with MD (17+/-2 bpm, 124+/-42%) or PFKD (65 bpm, 307%), and was not enhanced in the MM patient (24 bpm, 131%) compared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia studied in one McArdle patient, caused sustained elevation of MSNA above basal suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an enhanced drop in muscle pH of 0.51 U in the MM patient compared with the decrease in controls of 0.13+/-0.02 U. In contrast, muscle pH increased with exercise in MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with glycogenolytic, glycolytic, and oxidative phosphorylation defects show normal muscle sympathetic nerve responses to static exercise. These findings indicate that muscle acidosis is not a prerequisite for sympathetic activation in exercise.

Sex differences in sleep disordered breathing in adults.

PubMed

Lozo, Tijana; Komnenov, Dragana; Badr, M Safwan; Mateika, Jason H

2017-11-01

The prevalence of sleep disordered breathing is greater in men compared to women. This disparity could be due to sex differences in the diagnosis and presentation of sleep apnea, and the pathophysiological mechanisms that instigate this disorder. Women tend to report more non-typical symptoms of sleep apnea compared to men, and the presentation of apneic events are more prevalent in rapid compared to non-rapid eye movement sleep. In addition, there is evidence of sex differences in upper airway structure and mechanics and in neural mechanisms that impact on the control of breathing. The purpose of this review is to summarize the literature that addresses sex differences in sleep-disordered breathing, and to discuss the influence that upper airway mechanics, chemoreflex properties, and sex hormones have in modulating breathing during sleep in men and women. Published by Elsevier B.V.

Some aspects of clinical relevance in the maturation of respiratory control in infants.

PubMed

Thach, Bradley T

2008-06-01

Two reflex mechanisms important for survival are discussed. Brain stem and cardiovascular mechanisms that are responsible for recovery from severe hypoxia (autoresuscitation) are important for survival in acutely hypoxic infants and adults. Failure of this mechanism may be important in sudden infant death syndrome (SIDS), because brain stem-mediated hypoxic gasping is essential for successful autoresuscitation and because SIDS infants appear to attempt to autoresuscitate just before death. A major function of another mechanism is to protect the airway from fluid aspiration. The various components of the laryngeal chemoreflex (LCR) change during maturation. The LCR is an important cause of prolonged apneic spells in infants. Consequently, it also may have a role in causing SIDS. Maturational changes and/or inadequacy of this reflex may be responsible for pulmonary aspiration and infectious pneumonia in both children and adults.

Alteration of carotid body chemoreflexes after neonatal intermittent hypoxia and caffeine treatment in rat pups.

PubMed

Julien, Cécile A; Joseph, Vincent; Bairam, Aida

2011-08-15

In human neonates, caffeine therapy for apnoea of prematurity, especially when associated with hypoxemia, is maintained for several weeks after birth. In the present study, we used newborn rats and whole-body plethysmography to test whether chronic exposure to neonatal caffeine treatment (NCT), alone or combined with neonatal intermittent hypoxia (n-IH) alters: (1) baseline ventilation and response to hypoxia (12% O(2), 20 min); and (2) response to acute i.p. injection of caffeine citrate (20 mg/kg) or domperidone, a peripheral dopamine D2 receptor antagonist (1 mg/kg). Four groups of rats were studied as follows: raised under normal conditions with daily gavage with water (NWT) or NCT, or exposed to n-IH (n-IH+NWT and n-IH+NCT) from postnatal days 3 to 12. In n-IH+NCT rats, baseline ventilation was higher than in the other groups. Caffeine or domperidone enhanced baseline ventilation only in NWT and n-IH+NWT rats, but neither caffeine nor domperidone affected the hypoxic ventilatory response in these groups. In n-IH+NWT rats, the response during the early phase of hypoxia (<10 min) was higher than in other groups. During the late response phase to hypoxia (20 min), ventilation was lower in n-IH+NWT and n-IH+NCT rats compared to NWT or NCT, and were not affected by caffeine or domperidone injection. NCT or caffeine injection decreased baseline apnoea frequency in all groups. These data suggest that chronic exposure to NCT alters both carotid body dopaminergic and adenosinergic systems and central regulation of breathing under baseline conditions and in response to hypoxia. Copyright © 2011 Elsevier B.V. All rights reserved.

Sex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups

PubMed Central

Baldy, Cécile; Chamberland, Simon

2017-01-01

Abstract The presence of liquid near the larynx of immature mammals triggers prolonged apneas with significant O2 desaturations and bradycardias. When excessive, this reflex (the laryngeal chemoreflex; LCR) can be fatal. Our understanding of the origins of abnormal LCR are limited; however, perinatal stress and male sex are risk factors for cardio-respiratory failure in infants. Because exposure to stress during early life has deleterious and sex-specific consequences on brain development it is plausible that respiratory reflexes are vulnerable to neuroendocrine dysfunction. To address this issue, we tested the hypothesis that neonatal maternal separation (NMS) is sufficient to exacerbate LCR-induced cardio-respiratory inhibition in anesthetized rat pups. Stressed pups were separated from their mother 3 h/d from postnatal days 3 to 12. At P14–P15, pups were instrumented to monitor breathing, O2 saturation (Spo2), and heart rate. The LCR was activated by water injections near the larynx (10 µl). LCR-induced apneas were longer in stressed pups than controls; O2 desaturations and bradycardias were more profound, especially in males. NMS increased the frequency and amplitude of spontaneous EPSCs (sEPSCs) in the dorsal motor nucleus of the vagus (DMNV) of males but not females. The positive relationship between corticosterone and testosterone observed in stressed pups (males only) suggests that disruption of neuroendocrine function by stress is key to sex-based differences in abnormal LCR. Because testosterone application onto medullary slices augments EPSC amplitude only in males, we propose that testosterone-mediated enhancement of synaptic connectivity within the DMNV contributes to the male bias in cardio-respiratory inhibition following LCR activation in stressed pups. PMID:29308430

Developmental programming of O2 sensing by neonatal intermittent hypoxia via epigenetic mechanisms

PubMed Central

Nanduri, Jayasri; Prabhakar, Nanduri R.

2014-01-01

Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in infants born preterm. Carotid body chemo-reflex and catecholamine secretion from adrenal medullary chromaffin cells (AMC) are important for maintenance of cardio-respiratory homeostasis during hypoxia. This article highlights studies on the effects of IH on O2 sensing by the carotid body and AMC in neonatal rodents. Neonatal IH augments hypoxia-evoked carotid body sensory excitation and catecholamine secretion from AMC which are mediated by reactive oxygen species (ROS)-dependent recruitment of endothelin-1 and Ca2+ signaling, respectively. The effects of neonatal IH persist into adulthood. Evidence is emerging that neonatal IH initiates epigenetic mechanisms involving DNA hypermethylation contributing to long-lasting increase in ROS levels. Since adult human subjects born preterm exhibit higher incidence of sleep-disordered breathing and hypertension, DNA hypomethylating agents might offer a novel therapeutic intervention to decrease long-term cardio-respiratory morbidity caused by neonatal IH. PMID:22846496

Purines and Carotid Body: New Roles in Pathological Conditions

PubMed Central

Conde, Silvia V.; Monteiro, Emilia C.; Sacramento, Joana F.

2017-01-01

It is known that adenosine and adenosine-5′-triphosphate (ATP) are excitatory mediators involved in carotid body (CB) hypoxic signaling. The CBs are peripheral chemoreceptors classically defined by O2, CO2, and pH sensors. When hypoxia activates the CB, it induces the release of neurotransmitters from chemoreceptor cells leading to an increase in the action potentials frequency at the carotid sinus nerve (CSN). This increase in the firing frequency of the CSN is integrated in the brainstem to induce cardiorespiratory compensatory responses. In the last decade several pathologies, as, hypertension, diabetes, obstructive sleep apnea and heart failure have been associated with CB overactivation. In the first section of the present manuscript we review in a concise manner fundamental aspects of purine metabolism. The second section is devoted to the role of purines on the hypoxic response of the CB, providing the state-of-the art for the presence of adenosine and ATP receptors in the CB; for the role of purines at presynaptic level in CB chemoreceptor cells, as well as, its metabolism and regulation; at postsynaptic level in the CSN activity; and on the ventilatory responses to hypoxia. Recently, we have showed that adenosine is involved in CB hypersensitization during chronic intermittent hypoxia (CIH), which mimics obstructive sleep apnea, since caffeine, a non-selective adenosine receptor antagonist that inhibits A2A and A2B adenosine receptors, decreased CSN chemosensory activity in animals subjected to CIH. Apart from this involvement of adenosine in CB sensitization in sleep apnea, it was recently found that P2X3 ATP receptor in the CB contributes to increased chemoreflex hypersensitivity and hypertension in spontaneously hypertension rats. Therefore the last section of this manuscript is devoted to review the recent findings on the role of purines in CB-mediated pathologies as hypertension, diabetes and sleep apnea emphasizing the potential clinical importance of modulating purines levels and action to treat pathologies associated with CB dysfunction. PMID:29311923

Reciprocal modulation of O2 and CO2 cardiorespiratory chemoreflexes in the tambaqui.

PubMed

Reid, Stephen G; Perry, Steve F; Gilmour, Kathleen M; Milsom, William K; Rantin, F Tadeu

2005-04-15

This study examined the effect of acute hypoxic and hypercapnic cardiorespiratory stimuli, superimposed on existing cardiorespiratory disturbances in tambaqui. In their natural habitat, these fish often encounter periods of hypoxic hypercapnia that can be acutely exacerbated by water turnover. Tambaqui were exposed to periods of normoxia, hypoxia, hyperoxia and hypercapnia during which, externally oriented O2 and CO2 chemoreceptors were further stimulated, by administration into the inspired water of sodium cyanide and CO2-equilibrated water, respectively. Hyperoxic water increased the sensitivity of the NaCN-evoked increase in breathing frequency (f(R)) and decrease in heart rate. Hypoxia and hypercapnia attenuated the increase in f(R) but, aside from blood pressure, did not influence the magnitude of NaCN-evoked cardiovascular changes. Water PO2 influenced the magnitude of the CO2-evoked cardiorespiratory changes and the sensitivity of CO2-evoked changes in heart rate and blood flow. The results indicate that existing respiratory disturbances modulate cardiorespiratory responses to further respiratory challenges reflecting both changes in chemosensitivity and the capacity for further change.

Influence of prior hyperventilation duration on respiratory chemosensitivity and cerebrovascular reactivity during modified hyperoxic rebreathing.

PubMed

Boulet, Lindsey M; Tymko, Michael M; Jamieson, Alenna N; Ainslie, Philip N; Skow, Rachel J; Day, Trevor A

2016-07-01

What is the central question of this study? We characterized and compared the cardiorespiratory and cerebrovascular responses to the 'Duffin' modified hyperoxic CO2 rebreathing test by randomly altering the prior hyperventilation duration. What is the main finding and its importance? Our main finding was that prior hyperventilation duration (1, 3 or 5 min) had no effect on cardiorespiratory and cerebrovascular responses to the hyperoxic rebreathing test, within individuals. These findings suggest that the standard 5 min prior hyperventilation duration used to clear body CO2 stores is unnecessary and can reasonably be shortened to 1 min, reducing protocol times and improving participant comfort. The 'Duffin' modified hyperoxic rebreathing test allows investigators to characterize and quantify the ventilatory and cerebrovascular responses to CO2 across a large physiological range, allowing quantification of basal ventilation and the ventilatory recruitment threshold (VRT). Although the standard protocol includes 5 min of prior hyperventilation to clear body CO2 stores, there is no experimental evidence that a full 5 min is required. We hypothesized that there would be no within-individual differences in the cardiorespiratory or cerebrovascular responses to rebreathing with shortened hyperventilation duration prior to hyperoxic rebreathing. Using a rebreathing apparatus, transcranial Doppler ultrasound and beat-to-beat blood pressure monitoring, we tested 19 participants in the supine position using three randomly assigned hyperoxic rebreathing tests with 1, 3 or 5 min of prior hyperventilation. We measured VRT (in Torr CO2 ), time to VRT (in seconds), central respiratory chemoreflex (breathing frequency, tidal volume and minute ventilation), cerebrovascular (middle and posterior cerebral artery velocity) and cardiovascular (heart rate and mean arterial pressure) responses to CO2 during hyperoxic rebreathing. Using linear regression and repeated-measures ANOVAs, we found no differences in any of the cardiorespiratory or cerebrovascular response magnitudes between trials (P > 0.05). The only difference observed was in the time to VRT (in seconds), whereby 1 min prior hyperventilation duration was shorter (135.4 ± 19.7 s) than with 3 or 5 min prior hyperventilation (176.3 ± 15.1 and 187.2 ± 11.6 s, respectively; P < 0.001). Our findings indicate that 5 min of prior hyperventilation is unnecessary during modified rebreathing when using it to quantify respiratory or cerebrovascular responses and can be reasonably shortened to 1 min, reducing protocol times and improving participant comfort. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Post-exercise heart rate recovery in healthy, obeses, and COPD subjects: relationships with blood lactic acid and PaO2 levels.

PubMed

Ba, Abdoulaye; Delliaux, Stephane; Bregeon, Fabienne; Levy, Samuel; Jammes, Yves

2009-01-01

Because blood acidosis and arterial oxygenation (PaO(2)) play key roles in the chemoreflex control of cardiac activity, we hypothesized that heart rate (HR) decay rate after maximal exercise may be linked to post-exercise increase in blood lactate (LA) level and/or the resting PaO(2). Twenty healthy subjects and thirty five patients at risks of cardiovascular diseases (20 obeses; 15 patients with chronic obstructive pulmonary disease, COPD) performed a maximal cycling exercise. During the recovery period, HR was continuously measured for consecutive 10-s epochs allowing to compute linear or second order polynomial equations and to calculate every minute HR variations compared to peak HR value (DeltaHR). PaO(2) was measured at rest and post-exercise maximal LA level was determined. A second order polynomial equation (y = a(2) x (2) + b(2) x + c) best fitted the post-exercise HR decay rate. The a(2) and b(2) coefficients and DeltaHR did not depend on age, sex, and body mass index. Despite a large scattering of HR decay rate, even present in healthy subjects, a(2) and DeltaHR were significantly lower in obeses and COPDs. In the whole population, both a(2) coefficient and DeltaHR were negatively correlated with maximal post-exercise LA level. DeltaHR was lowered in hypoxemic patients. Thus, the slowest post-exercise HR decay rate was measured in subjects having the highest peak LA increase or hypoxemia. Thus, even in healthy subjects, the post-exercise HR decay rate is lowered in individuals having an accentuated exercise-induced LA increase and/or hypoxemia. The mechanisms of delayed post-exercise HR recovery are only suspected because significant correlations cannot assess cause-to-effect relationships.

The physiological effects of slow breathing in the healthy human

PubMed Central

Russo, Marc A.; Santarelli, Danielle M.; O’Rourke, Dean

2017-01-01

Slow breathing practices have been adopted in the modern world across the globe due to their claimed health benefits. This has piqued the interest of researchers and clinicians who have initiated investigations into the physiological (and psychological) effects of slow breathing techniques and attempted to uncover the underlying mechanisms. The aim of this article is to provide a comprehensive overview of normal respiratory physiology and the documented physiological effects of slow breathing techniques according to research in healthy humans. The review focuses on the physiological implications to the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems, with particular focus on diaphragm activity, ventilation efficiency, haemodynamics, heart rate variability, cardiorespiratory coupling, respiratory sinus arrhythmia and sympathovagal balance. The review ends with a brief discussion of the potential clinical implications of slow breathing techniques. This is a topic that warrants further research, understanding and discussion. Key points Slow breathing practices have gained popularity in the western world due to their claimed health benefits, yet remain relatively untouched by the medical community. Investigations into the physiological effects of slow breathing have uncovered significant effects on the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems. Key findings include effects on respiratory muscle activity, ventilation efficiency, chemoreflex and baroreflex sensitivity, heart rate variability, blood flow dynamics, respiratory sinus arrhythmia, cardiorespiratory coupling, and sympathovagal balance. There appears to be potential for use of controlled slow breathing techniques as a means of optimising physiological parameters that appear to be associated with health and longevity, and that may extend to disease states; however, there is a dire need for further research into the area. Educational aims To provide a comprehensive overview of normal human respiratory physiology and the documented effects of slow breathing in healthy humans. To review and discuss the evidence and hypotheses regarding the mechanisms underlying slow breathing physiological effects in humans. To provide a definition of slow breathing and what may constitute “autonomically optimised respiration”. To open discussion on the potential clinical implications of slow breathing techniques and the need for further research. PMID:29209423

Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans

PubMed Central

Niewinski, Piotr; Tubek, Stanislaw; Banasiak, Waldemar; Paton, Julian F R; Ponikowski, Piotr

2014-01-01

Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function. PMID:24396060

Systemic Administration of the Potential Countermeasure Huperzine Reversibly Inhibits Central and Peripheral Acetylcholinesterase Activity Without Adverse Cognitive-Behavioral Effects

DTIC Science & Technology

2010-01-01

reversibly inhibits 5a. CONTRACT NUMBER central and peripheral acetylcholinesterase activity without adverse cognitive–behavioral effects 5b. GRANT...huperzine reversibly inhibits central and peripheral acetylcholinesterase activity without adverse cognitive–behavioral effects Todd M. Myers a,⁎, Wei Sun b...HUP to enter the brain is also evidenced by studies that use well-documented centrally active anticholinergics to induce cognitive impairments that are

Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors

PubMed Central

Wang, Lei; de Kloet, Annette D.; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A.; Pioquinto, David J.; Ludin, Jacob A.; Oh, S. Paul; Katovich, Michael J.; Frazier, Charles J.; Raizada, Mohan K.; Krause, Eric G.

2016-01-01

Over-activation of brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme (ACE2) inhibits RAS activity by converting angiotensin II, the effector peptide of RAS, to angiotensin-(1-7), which activates Mas receptors (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ~62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the BLA. PMID:26767952

Minocycline encapsulated chitosan nanoparticles for central antinociceptive activity.

PubMed

Nagpal, Kalpana; Singh, S K; Mishra, D N

2015-01-01

The purpose of the study is to explore the central anti-nociceptive activity of brain targeted nanoparticles (NP) of minocycline hydrochloride (MH). The NP were formulated using the modified ionotropic gelation method (MHNP) and were coated with Tween 80 (T80) to target them to brain (cMHNP). The formulated nanoparticles have already been characterized for particle size, zeta potential, drug entrapment efficiency and in vitro drug release. The nanoparticles were then evaluated for pharmacodynamic activity using thermal methods. The pure drug and the formulation, MHNP were not able to show a statistically significant central analgesic activity. cMHNP on the other hand evidenced a significant central analgesic activity. Animal models evidenced that brain targeted nanoparticles may be utilized for effective delivery of central anti-nociceptive effect of MH. Further clinical studies are required to explore the activity for mankind. Copyright © 2014 Elsevier B.V. All rights reserved.

Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

PubMed Central

Pavlov, Valentin A.; Ochani, Mahendar; Gallowitsch-Puerta, Margot; Ochani, Kanta; Huston, Jared M.; Czura, Christopher J.; Al-Abed, Yousef; Tracey, Kevin J.

2006-01-01

TNF has a critical mediator role in inflammation and is an important therapeutic target. We recently discovered that TNF production is regulated by neural signals through the vagus nerve. Activation of this “cholinergic antiinflammatory pathway” inhibits the production of TNF and other cytokines and protects animals from the inflammatory damage caused by endotoxemia and severe sepsis. Here, we describe a role for central muscarinic acetylcholine receptors in the activation of the cholinergic antiinflammatory pathway. Central muscarinic cholinergic activation by muscarine, the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF levels significantly during endotoxemia. Centrally administered methoctramine stimulated vagus-nerve activity measured by changes in instantaneous heart-rate variability. Blockade of peripheral muscarinic receptors did not abolish antiinflammatory signaling through the vagus nerve, indicating that peripheral muscarinic receptors on immune cells are not required for the cytokine-regulating activities of the cholinergic antiinflammatory pathway. The role of central muscarinic receptors in activating the cholinergic antiinflammatory pathway is of interest for the use of centrally acting muscarinic cholinergic enhancers as antiinflammatory agents. PMID:16549778

TRPV1 channels in the nucleus of the solitary tract mediate thermal prolongation of the LCR in decerebrate piglets

PubMed Central

Xia, Luxi; Bartlett, Donald; Leiter, J.C.

2011-01-01

Elevating body temperature or just the temperature of the dorsal medulla by approximately 2 °C prolongs the laryngeal chemoreflex (LCR) in decerebrate neonatal piglets. We tested the hypothesis that transient receptor potential vanilloid 1 (TRPV1) receptors in the nucleus of the solitary tract (NTS) mediate thermal prolongation of the LCR. We studied the effect of a selective TRPV1 receptor antagonist on thermal prolongation of the LCR, and we tested the effect of a TRPV1 agonist on the duration of the LCR under normothermic conditions. We studied 37 decerebrate neonatal piglets between the ages of post-natal days 4 and 7. The TRPV1 receptor antagonist, 5−iodoresiniferatoxin (65 microM/L in 100 nL), blocked thermal prolongation of the LCR when injected bilaterally into the region of the NTS. The TRPV1 agonist, resiniferatoxin (0.65-1.0 mM/L in 100 nL), prolonged the LCR after bilateral injection into the NTS even when the body temperature of each piglet was normal. The effect of the TRPV1 agonists could be blocked by treatment with the GABAA receptor antagonist, bicuculline, whether given intravenously (0.3 mg/kg) or focally injected bilaterally into the NTS (10 mM in 100nL). We conclude that TRPV1 receptors in the NTS mediate thermal prolongation of the LCR. PMID:21276877

Reflex cardioventilatory responses to hypoxia in the flathead gray mullet (Mugil cephalus) and their behavioral modulation by perceived threat of predation and water turbidity.

PubMed

Shingles, A; McKenzie, D J; Claireaux, G; Domenici, P

2005-01-01

In hypoxia, gray mullet surface to ventilate well-oxygenated water in contact with air, an adaptive response known as aquatic surface respiration (ASR). Reflex control of ASR and its behavioral modulation by perceived threat of aerial predation and turbid water were studied on mullet in a partly sheltered aquarium with free surface access. Injections of sodium cyanide (NaCN) into either the bloodstream (internal) or ventilatory water stream (external) revealed that ASR, hypoxic bradycardia, and branchial hyperventilation were stimulated by chemoreceptors sensitive to both systemic and water O2 levels. Sight of a model avian predator elicited bradycardia and hypoventilation, a fear response that inhibited reflex hyperventilation following external NaCN. The time lag to initiation of ASR following NaCN increased, but response intensity (number of events, time at the surface) was unchanged. Mullet, however, modified their behavior to surface under shelter or near the aquarium edges. Turbid water abolished the fear response and effects of the predator on gill ventilation and timing of ASR following external NaCN, presumably because of reduced visibility. However, in turbidity, mullet consistently performed ASR under shelter or near the aquarium edges. These adaptive modulations of ASR behavior would allow mullet to retain advantages of the chemoreflex when threatened by avian predators or when unable to perceive potential threats in turbidity.

Network analysis of inter-organizational relationships and policy use among active living organizations in Alberta, Canada.

PubMed

Loitz, Christina C; Stearns, Jodie A; Fraser, Shawn N; Storey, Kate; Spence, John C

2017-08-09

Coordinated partnerships and collaborations can optimize the efficiency and effectiveness of service and program delivery in organizational networks. However, the extent to which organizations are working together to promote physical activity, and use physical activity policies in Canada, is unknown. This project sought to provide a snapshot of the funding, coordination and partnership relationships among provincial active living organizations (ALOs) in Alberta, Canada. Additionally, the awareness, and use of the provincial policy and national strategy by the organizations was examined. Provincial ALOs (N = 27) answered questions regarding their funding, coordination and partnership connections with other ALOs in the network. Social network analysis was employed to examine network structure and position of each ALO. Discriminant function analysis determined the extent to which degree centrality was associated with the use of the Active Alberta (AA) policy and Active Canada 20/20 (AC 20/20) strategy. The funding network had a low density level (density = .20) and was centralized around Alberta Tourism Parks and Recreation (ATPR; degree centralization = 48.77%, betweenness centralization = 32.43%). The coordination network had a moderate density level (density = .31), and was low-to-moderately centralized around a few organizations (degree centralization = 45.37%, betweenness centrality = 19.92%). The partnership network had a low density level (density = .15), and was moderate-to-highly centralized around ATPR. Most organizations were aware of AA (89%) and AC 20/20 (78%), however more were using AA (67%) compared to AC 20/20 (33%). Central ALOs in the funding network were more likely to use AA and AC 20/20. Central ALOs in the coordination network were more likely to use AC 20/20, but not AA. Increasing formal and informal relationships between organizations and integrating disconnected or peripheral organizations could increase the capacity of the network to promote active living across Alberta. Uptake of the AA policy within the network is high and appears to be facilitated by the most central ALO. Promoting policy use through a central organization appeared to be an effective strategy for disseminating the province-level physical activity policy and could be considered as a policy-uptake strategy by other regions.

Tremor amplitude and tremor frequency variability in Parkinson's disease is dependent on activity and synchronisation of central oscillators in basal ganglia.

PubMed

Bartolić, Andrej; Pirtosek, Zvezdan; Rozman, Janez; Ribaric, Samo

2010-02-01

Rest tremor is one of the four main clinical features of Parkinson's disease (PD), besides rigidity, bradykinesia and postural instability. While rigidity, bradykinesia and postural instability can be explained with changes in neurotransmitter concentrations and neuronal activity in basal ganglia, the pathogenesis of parkinsonian tremor is not fully understood. According to the leading hypothesis tremor is generated by neurons or groups of neurons in the basal ganglia which act as central oscillators and generate repetitive impulses to the muscles of the body parts involved. The exact morphological substrate for central oscillators and the mechanisms leading to their activation are still an object of debate. Peripheral neural structures exert modulatory influence on tremor amplitude, but not on tremor frequency. We hypothesise that rest tremor in PD is the result of two mechanisms: increased activity and increased synchronisation of central oscillators. We tested our hypothesis by demonstrating that the reduction in rest tremor amplitude is accompanied by increased variability of tremor frequency. The reduction of tremor amplitude is attributed to decreased activity and poor synchronisation of central oscillators in basal ganglia; the increased variability of tremor frequency is attributed to poor synchronisation of the central oscillators. In addition, we demonstrated that the recurrence of clinically visible rest tremor is accompanied by a reduction in tremor frequency variability. This reduction is attributed to increased synchronisation of central oscillators in basal ganglia. We argue that both mechanisms, increased activity of central oscillators and increased synchronisation of central oscillators, are equally important and we predict that tremor becomes clinically evident only when both mechanisms are active at the same time. In circumstances when one of the mechanisms is suppressed tremor amplitude becomes markedly reduced. On the one hand, if the number of active central oscillators is very low, the muscle-stimulating impulses are too weak to cause clinically evident tremor. On the other hand, if central oscillator synchronisation is poor, the impulses originating from different central oscillators are not in phase and thus cancel out, again leading to reduced stimulation of muscles and reduced tremor amplitude. Our hypothesis is supported by our measurements on patients with PD and by experimental data cited in the literature. The proposed two mechanisms could have clinical implications. New medical treatments, which would specifically target only one of the proposed mechanisms (oscillator activity or synchronisation), could be effective in reducing tremor amplitude and thus supplement established antiparkinsonian treatments.

The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

PubMed

Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

2014-06-01

To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process. © 2013 Japanese Society of Neuropathology.

Neurotoxicity and other pharmacological activities of the snake venom phospholipase A2 OS2: The N-terminal region is more important than enzymatic activity

PubMed Central

Rouault, Morgane; Rash, Lachlan D.; Escoubas, Pierre; Boilard, Eric; Bollinger, James; Lomonte, Bruno; Maurin, Thomas; Guillaume, Carole; Canaan, Stéphane; Deregnaucourt, Christiane; Schrével, Joseph; Doglio, Alain; Gutiérrez, José María; Lazdunski, Michel; Gelb, Michael H.; Lambeau, Gérard

2009-01-01

Several snake venom secreted phospholipases A2 (sPLA2s) including OS2 exert a variety of pharmacological effects ranging from central neurotoxicity to anti-HIV activity by mechanisms that are not yet fully understood. To conclusively address the role of enzymatic activity and map the key structural elements of OS2 responsible for its pharmacological properties, we have prepared single point OS2 mutants at the catalytic site and large chimeras between OS2 and OS1, an homologous but non toxic sPLA2. Most importantly, we found that the enzymatic activity of the active site mutant H48Q is 500-fold lower than that of the wild-type protein, while central neurotoxicity is only 16-fold lower, providing convincing evidence that catalytic activity is at most a minor factor that determines central neurotoxicity. The chimera approach has identified the N-terminal region (residues 1–22) of OS2, but not the central one (residues 58–89), as crucial for both enzymatic activity and pharmacological effects. The C-terminal region of OS2 (residues 102–119) was found to be critical for enzymatic activity, but not for central neurotoxicity and anti-HIV activity, allowing us to further dissociate enzymatic activity and pharmacological effects. Finally, direct binding studies with the C-terminal chimera which poorly binds to phospholipids while it is still neurotoxic, led to the identification of a subset of brain N-type receptors which may be directly involved in central neurotoxicity. PMID:16669624

Local conduction during acute myocardial infarction in rats: Interplay between central sympathetic activation and endothelin.

PubMed

Kolettis, Theofilos M; Kontonika, Marianthi; La Rocca, Vassilios; Vlahos, Antonios P; Baltogiannis, Giannis G; Kyriakides, Zenon S

2017-04-01

We investigated the effects of autonomic dysfunction and endothelin on local conduction and arrhythmogenesis during myocardial infarction. We recorded ventricular tachyarrhythmias, monophasic action potentials, and activation sequences in wild-type and ET B -deficient rats displaying high endothelin levels. Central sympathetic inputs were examined after clonidine administration. Clonidine mitigated early and delayed arrhythmogenesis in ET B -deficient and wild-type rats, respectively. The right ventricular activation delay increased in clonidine-treated ET B -deficient rats and slightly decreased in wild-type rats. The left ventricular voltage rise decreased in all groups, whereas the activation delay increased mainly in clonidine-treated ET B -deficient rats. Central sympathetic activation and endothelin modulate ischemia-induced arrhythmogenesis. Ischemia alters excitability, whereas endothelin impairs local conduction, an action partly counterbalanced by central sympathetic activity.

[Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice].

PubMed

Zhang, Li-quan; Xu, Jia-ni; Wang, Zhen-zhen; Zeng, Li-jun; Ye, Yi-lu; Zhang, Wei-ping; Wei, Er-qing; Zhang, Qi

2014-05-01

To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice. GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum. Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (Ps<0.05). However, minocycline significantly reduced the central distance and central time and increased the periphery time (Ps<0.05). Neurons were damaged in hippocampus, cortex and striatum after GCI, which manifested by decreased neurons and the most serious damage in hippocampal CA1 region. Minocycline significantly improved the neuron appearance and increased the neuron number in hippocampus and striatum (P<0.001 or P<0.05). Locomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.

Central carbon metabolism in marine bacteria examined with a simplified assay for dehydrogenases.

PubMed

Wen, Weiwei; Wang, Shizhen; Zhou, Xiaofen; Fang, Baishan

2013-06-01

A simplified assay platform was developed to measure the activities of the key oxidoreductases in central carbon metabolism of various marine bacteria. Based on microplate assay, the platform was low-cost and simplified by unifying the reaction conditions of enzymes including temperature, buffers, and ionic strength. The central carbon metabolism of 16 marine bacteria, involving Pseudomonas, Exiguobacterium, Marinobacter, Citreicella, and Novosphingobium were studied. Six key oxidoreductases of central carbon metabolism, glucose-6-phosphate dehydrogenase, pyruvate dehydrogenase, 2-ketoglutarate dehydrogenase, malate dehydrogenase, malic enzyme, and isocitrate dehydrogenase were investigated by testing their activities in the pathway. High activity of malate dehydrogenase was found in Citreicella marina, and the specific activity achieved 22 U/mg in cell crude extract. The results also suggested that there was a considerable variability on key enzymes' activities of central carbon metabolism in some strains which have close evolutionary relationship while they adapted to the requirements of the niche they (try to) occupy.

Corticosterone level and central dopaminergic activity involved in agile and exploratory behaviours in formosan wood mice (Apodemus semotus).

PubMed

Shieh, Kun-Ruey; Yang, Shu-Chuan

2018-03-27

The native Formosan wood mouse (Apodemus semotus) is the dominant rodent in Taiwan. In their natural environment, Formosan wood mice exhibit high locomotor activity, including searching and exploratory behaviours, which is observed similarly in the laboratory environment. How the behavioural responses of Formosan wood mice exhibit in elevated plus maze and marble burying tests remains unclear. How corticosterone levels and central dopaminergic activities are related to the behaviours in these tests is also unclear. This study compared the behaviours of Formosan wood mice with that of C57BL/6J mice using the elevated plus maze and marble burying tests, and measured the corticosterone levels and central dopaminergic activities. Formosan wood mice showed greater locomotor and exploratory activity than the C57BL/6J mice. Similarly, the marble burying and rearing numbers were higher for Formosan wood mice. High locomotor and exploratory behaviours were strongly correlated with corticosterone levels after acute mild restraint stress in Formosan wood mice. The anxiolytic, diazepam, reduced the high exploratory activity, corticosterone levels and central dopaminergic activities. The high locomotor and exploratory behaviours of Formosan wood mice are related to the corticosterone levels and central dopaminergic activities. These data may explain Formosan wood mice dominance in the intermediate altitude of Taiwan.

NCEP Operational HWRF Forecasting System

Science.gov Websites

2010 Basin: North Atlantic Eastern North Pacific Central North Pacific Western North Pacific North ALBERTO01L North Atlantic: (1) active ALBERTO01L Eastern North Pacific: (0) active Central North Pacific: (0 ) active Western North Pacific: (0) active North Indian Ocean: (0) active Southern Hemisphere: (0) active Â

Active tectonics and strain partitioning along dextral fault system in Central Iran: Analysis of geomorphological observations and geophysical data in the Kashan region

NASA Astrophysics Data System (ADS)

Jamali, Farshad; Hessami, Khaled; Ghorashi, Manoochehr

2011-03-01

This paper uses high-resolution images and field investigations, in conjunction with seismic reflection data, to constrain active structural deformation in the Kashan region of Central Iran. Offset stream beds and Qanats indicate right-lateral strike slip motion at a rate of about 2 mm/yr along the NW-SE trending Qom-Zefreh fault zone which has long been recognized as one of the major faults in Central Iran. However, the pattern of drainage systems across the active growing folds including deep incision of stream beds and deflected streams indicate uplift at depth on thrust faults dipping SW beneath the anticlines. Therefore, our studies in the Kashan region indicate that deformation occurs within Central Iran which is often considered to behave as a non-deforming block within the Arabia-Eurasia collision zone. The fact that the active Qom-Zefreh strike-slip fault runs parallel to the active folds, which overlie blind thrust faults, suggests that oblique motion of Arabia with respect to Eurasia is partitioned in this part of Central Iran.

TRPV1 channels in the nucleus of the solitary tract mediate thermal prolongation of the LCR in decerebrate piglets.

PubMed

Xia, Luxi; Bartlett, Donald; Leiter, J C

2011-04-30

Elevating body temperature or just the temperature of the dorsal medulla by approximately 2°C prolongs the laryngeal chemoreflex (LCR) in decerebrate neonatal piglets. We tested the hypothesis that transient receptor potential vanilloid 1 (TRPV1) receptors in the nucleus of the solitary tract (NTS) mediate thermal prolongation of the LCR. We studied the effect of a selective TRPV1 receptor antagonist on thermal prolongation of the LCR, and we tested the effect of a TRPV1 agonist on the duration of the LCR under normothermic conditions. We studied 37 decerebrate neonatal piglets between the ages of post-natal days 4 and 7. The TRPV1 receptor antagonist, 5'-iodoresiniferatoxin (65μM/L in 100nL), blocked thermal prolongation of the LCR when injected bilaterally into the region of the NTS. The TRPV1 agonist, resiniferatoxin (0.65-1.0mM/L in 100nL), prolonged the LCR after bilateral injection into the NTS even when the body temperature of each piglet was normal. The effect of the TRPV1 agonists could be blocked by treatment with the GABA(A) receptor antagonist, bicuculline, whether given intravenously (0.3mg/kg) or focally injected bilaterally into the NTS (10mM in 100nL). We conclude that TRPV1 receptors in the NTS mediate thermal prolongation of the LCR. Copyright © 2011 Elsevier B.V. All rights reserved.

Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha.

PubMed

Fernández, Ricardo; González, Sergio; Rey, Sergio; Cortés, Paula P; Maisey, Kevin R; Reyes, Edison-Pablo; Larraín, Carolina; Zapata, Patricio

2008-07-01

In the absence of information on functional manifestations of carotid body (CB) inflammation, we studied an experimental model in which lipopolysaccharide (LPS) administration to pentobarbitone-anaesthetized cats was performed by topical application upon the CB surface or by intravenous infusion (endotoxaemia). The latter caused: (i) disorganization of CB glomoids, increased connective tissue, and rapid recruitment of polymorphonuclear cells into the vascular bed and parenchyma within 4 h; (ii) increased respiratory frequency and diminished ventilatory chemoreflex responses to brief hypoxia (breathing 100% N(2) for 10 s) and diminished ventilatory chemosensory drive (assessed by 100% O(2) tests) during normoxia and hypoxia; (iii) tachycardia, increased haematocrit and systemic hypotension in response to LPS i.v.; and (iv) increased basal frequency of carotid chemosensory discharges during normoxia, but no change in maximal chemoreceptor responses to brief hypoxic exposures. Lipopolysaccharide-induced tachypnoea was prevented by prior bilateral carotid neurotomy. Apoptosis was not observed in CBs from cats subjected to endotoxaemia. Searching for pro-inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha) was localized by immunohistochemistry in glomus and endothelial cells; reverse transcriptase-polymerase chain reaction revealed that the CB expresses the mRNAs for both type-1 (TNF-R1) and type-2 TNF-alpha receptors (TNF-R2); Western blot confirmed a band of the size expected for TNF-R1; and histochemistry showed the presence of TNF-R1 in glomus cells and of TNF-R2 in endothelial cells. Experiments in vitro showed that the frequency of carotid nerve discharges recorded from CBs perfused and superfused under normoxic conditions was not significantly modified by TNF-alpha, but that the enhanced frequency of chemosensory discharges recorded along responses to hypoxic stimulation was transiently diminished in a dose-dependent manner by TNF-alpha injections. The results suggest that the CB may operate as a sensor for immune signals, that the CB exhibits histological features of acute inflammation induced by LPS, that TNF-alpha may participate in LPS-induced changes in chemosensory activity and that some pathophysiological reactions to high levels of LPS in the bloodstream may originate from changes in CB function.

From the Cover: Prenatal Nicotinic Exposure Attenuates Respiratory Chemoreflexes Associated With Downregulation of Tyrosine Hydroxylase and Neurokinin 1 Receptor in Rat Pup Carotid Body.

PubMed

Zhao, Lei; Zhuang, Jianguo; Gao, Xiuping; Ye, Chunyan; Lee, Lu-Yuan; Xu, Fadi

2016-09-01

Maternal cigarette smoke is the major risk of sudden infant death syndrome (SIDS). A depressed ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) is thought to be responsible for the pathogenesis of SIDS and the carotid body is critically involved in these responses. We have recently reported that prenatal nicotinic exposure (PNE) over the full gestation induces depressed HVR in rat pups. Here, we asked whether PNE (1) depressed not only HVR but also HCVR that were dependent on the carotid body, (2) affected some important receptors and neurochemicals expressed in the carotid body, such as tyrosine hydroxylase (TH), neurokinin-1 receptor (NK1R), and α7 nicotinic acetylcholine receptor (α7nAChR), and (3) blunted the ventilatory responses to activation of these receptors. To this end, HVR and HCVR in Ctrl and PNE pups were measured with plethysmography before and after carotid body ablation (Series I), mRNA expression and/or immunoreactivity (IR) of TH, NK1R, and α7nAChR in the carotid body were examined by RT-PCR and immunohistochemistry (Series II), and the ventilatory responses were tested before and after intracarotid injection of substance P (NK1R agonist) and AR-R17779 (α7nAChR agonist) (Series III). Our results showed that PNE (1) significantly depressed both HVR and HCVR and these depressions were abolished by carotid body ablation, (2) reduced the relative population of glomus cells, mRNA NK1R, and α7nAChR and IR of NK1R and TH in the carotid body, and (3) decreased ventilatory responses to intracarotid injection of substance P or AR-R17779. These results suggest that PNE acting via the carotid body could strikingly blunt HVR and HCVR, likely through downregulating TH and NK1R. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effect of sodium intake on sympathetic and hemodynamic response to thermal receptor stimulation.

PubMed

DiBona, Gerald F; Jones, Susan Y

2003-02-01

Low dietary sodium intake increases central nervous system angiotensin activity, which increases basal renal sympathetic nerve activity and shifts its arterial baroreflex control to a higher level of arterial pressure. This results in a higher level of renal sympathetic nerve activity for a given level of arterial pressure during low dietary sodium intake than during either normal or high dietary sodium intake, in which there is less central angiotensin activity. Peripheral thermal receptor stimulation overrides arterial baroreflex control and produces a pressor response, tachycardia, increased renal sympathetic nerve activity, and renal vasoconstriction. To test the hypothesis that increased central angiotensin activity would enhance the responses to peripheral thermal receptor stimulation, anesthetized normal rats in balance on low, normal, and high dietary sodium intake were subjected to acute peripheral thermal receptor stimulation. Low sodium rats had greater increases in renal sympathetic nerve activity, greater decreases in RBF, and greater increases in renal vascular resistance than high sodium rats. Responses of normal sodium rats were between those of low and high sodium rats. Arterial pressure and heart rate responses were not different among dietary groups. Spontaneously hypertensive rats, known to have increased central nervous system angiotensin activity, also had greater renal sympathoexcitatory and vasoconstrictor responses than normotensive Wistar-Kyoto rats. These results support the view that increased central nervous system angiotensin activity alters arterial baroreflex control of renal sympathetic nerve activity such that the renal sympathoexcitatory and vasoconstrictor responses to peripheral thermoreceptor stimulation are enhanced.

The influences of temperature and naloxone on the antinociceptive activity of Corchorus olitorius L. in mice.

PubMed

Zakaria, Z A; Safarul, M; Valsala, R; Sulaiman, M R; Fatimah, C A; Somchit, M N; Mat Jais, A M

2005-07-01

A series of preliminary studies was carried out to evaluate the antinociceptive (pain relief) activity of the aqueous extract of Corchorus olitorius L. leaves (COAE) and to determine the influence of temperature and opioid receptors on COAE activity using the abdominal constriction and hot plate tests in mice. COAE, at concentrations of 10, 25, 50, 75, and 100%, showed both peripheral and central antinociception that are non-concentration- and concentration-dependent respectively. The peripheral activity was clearly observed at a concentration of 25% and diminished at a concentration of 100%, while the central activity was observed at all the concentrations of COAE used. Furthermore, the insignificant results obtained indicated that this peripheral activity (at concentrations of 25 and 50%) was comparable to that of morphine (0.8 mg/kg). Pre-heating COAE at a temperature of 80 degrees C and 100 degrees C, or 60 degrees C and 80 degrees C was found to enhance its peripheral and central antinociception respectively. Pre-treatment with naloxone (10 mg/kg), a general opioid receptor antagonist, for 5 min, followed by COAE, was found to completely block its peripheral, but not central, antinociceptive activity. Based on this observation, we conclude that the antinociceptive activity exhibited by C. olitorius is enhanced by the increase in temperature and may be mediated peripherally, but not centrally, at least in part, via an opioid receptor.

CENTRAL PLATEAU REMEDIATION OPTIMIZATION STUDY

DOE Office of Scientific and Technical Information (OSTI.GOV)

BERGMAN, T. B.; STEFANSKI, L. D.; SEELEY, P. N.

2012-09-19

THE CENTRAL PLATEAU REMEDIATION OPTIMIZATION STUDY WAS CONDUCTED TO DEVELOP AN OPTIMAL SEQUENCE OF REMEDIATION ACTIVITIES IMPLEMENTING THE CERCLA DECISION ON THE CENTRAL PLATEAU. THE STUDY DEFINES A SEQUENCE OF ACTIVITIES THAT RESULT IN AN EFFECTIVE USE OF RESOURCES FROM A STRATEGIC PERSPECTIVE WHEN CONSIDERING EQUIPMENT PROCUREMENT AND STAGING, WORKFORCE MOBILIZATION/DEMOBILIZATION, WORKFORCE LEVELING, WORKFORCE SKILL-MIX, AND OTHER REMEDIATION/DISPOSITION PROJECT EXECUTION PARAMETERS.

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

PubMed

Matsukawa, Kanji

2012-01-01

Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

Effect of noxious electrical stimulation of the peroneal nerve on stretch reflex activity of the hamstring muscle in rats: possible implications of neuronal mechanisms in the development of tight hamstrings in lumbar disc herniation.

PubMed

Hirayama, Jiro; Yamagata, Masatsune; Takahashi, Kazuhisa; Moriya, Hideshige

2005-05-01

The effect of noxious electrical stimulation of the peroneal nerve on the stretch reflex electromyogram activity of the hamstring muscle (semitendinous) was studied. To verify the following hypothetical mechanisms underlying tight hamstrings in lumbar disc herniation: stretch reflex muscle activity of hamstrings is increased by painful inputs from an injured spinal nerve root and the increased stretch reflex muscle activity is maintained by central sensitization. It is reported that stretch reflex activity of the trunk muscles is induced by noxious stimulation of the sciatic nerve and maintained by central sensitization. In spinalized rats (transected spinal cord), the peroneal nerve was stimulated electrically as a conditioning stimulus. Stretch reflex electromyogram activity of the semitendinous muscle was recorded before and after the conditioning stimulus. Even after electrical stimulation was terminated, an increased stretch reflex activity of the hamstring muscle was observed. It is likely that a central sensitization mechanism at the spinal cord level was involved in the increased reflex activity. Central sensitization may play a part in the neuronal mechanisms of tight hamstrings in lumbar disc herniation.

Sustained reduction in blood pressure from electrical activation of the baroreflex is mediated via the central pathway of unmyelinated baroreceptors.

PubMed

Turner, Michael J; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

2014-06-13

This study aims to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Two binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fiber (3 V, 20-100 Hz) or C-fiber (20 V, 0-10 Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). The central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28 ± 0.04 vs. 4.01 ± 0.2%·Hz(-1), P<0.001) and coherence at 0.01 Hz (0.44 ± 0.05 vs. 0.81 ± 0.03, P<0.05) were significantly lower for A-fiber stimulation compared with C-fiber stimulation. The slope of the dynamic gain was higher for A-fiber stimulation (14.82 ± 1.02 vs. 7.21 ± 0.79 dB·decade(-1), P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fiber stimulation compared with C-fiber stimulation (0.23 ± 0.05 vs. 3.05 ± 0.31 mmHg·Hz(-1), P<0.001). These data indicate that the A-fiber central pathway contributes to high frequency arterial pressure regulation and the C-fiber central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fiber central pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of solar variability on the occurrence of central European weather types from 1763 to 2009

NASA Astrophysics Data System (ADS)

Schwander, Mikhaël; Rohrer, Marco; Brönnimann, Stefan; Malik, Abdul

2017-09-01

The impact of solar variability on weather and climate in central Europe is still not well understood. In this paper we use a new time series of daily weather types to analyse the influence of the 11-year solar cycle on the tropospheric weather of central Europe. We employ a novel, daily weather type classification over the period 1763-2009 and investigate the occurrence frequency of weather types under low, moderate, and high solar activity level. Results show a tendency towards fewer days with westerly and west-southwesterly flow over central Europe under low solar activity. In parallel, the occurrence of northerly and easterly types increases. For the 1958-2009 period, a more detailed view can be gained from reanalysis data. Mean sea level pressure composites under low solar activity also show a reduced zonal flow, with an increase of the mean blocking frequency between Iceland and Scandinavia. Weather types and reanalysis data show that the 11-year solar cycle influences the late winter atmospheric circulation over central Europe with colder (warmer) conditions under low (high) solar activity.

Wildfire atlas of the northeastern and north central states.

Treesearch

Donald A. Haines; Von J. Johnson; William A. Main

1975-01-01

Describes patterns of forest fire activity across the northeastern and north central United States. Gives average dates of greening ad curing of herbaceous plants, medium size of fires in various fuels, and annual profiles of peak fire activity. It also examines combinations of major fire cause and day-of-week activity.

The Central Sirtuin 1/p53 Pathway Is Essential for the Orexigenic Action of Ghrelin

PubMed Central

Velásquez, Douglas A.; Martínez, Gloria; Romero, Amparo; Vázquez, María J.; Boit, Katia D.; Dopeso-Reyes, Iria G.; López, Miguel; Vidal, Anxo; Nogueiras, Ruben; Diéguez, Carlos

2011-01-01

OBJECTIVE Ghrelin is a stomach-derived peptide that increases food intake through the activation of hypothalamic AMP-activated protein kinase (AMPK). However, the molecular mechanisms initiated by the activation of the ghrelin receptor, which in turn lead to AMPK activation, remain unclear. Sirtuin 1 (SIRT1) is a deacetylase activated in response to calorie restriction that acts through the tumor suppressor gene p53. We tested the hypothesis that the central SIRT1/p53 pathway might be mediating the orexigenic action of ghrelin. RESEARCH DESIGN AND METHODS SIRT1 inhibitors, such as Ex527 and sirtinol, and AMPK activators, such as AICAR, were administered alongside ghrelin in the brain of rats and mice (wild-type versus p53 knockout [KO]). Their hypothalamic effects on lipid metabolism and changes in transcription factors and neuropeptides were assessed by Western blot and in situ hybridization. RESULTS The central pretreatment with Ex527, a potent SIRT1 inhibitor, blunted the ghrelin-induced food intake in rats. Mice lacking p53, a target of SIRT1 action, failed to respond to ghrelin in feeding behavior. Ghrelin failed to phosphorylate hypothalamic AMPK when rats were pretreated with Ex527, as it did in p53 KO mice. It is noteworthy that the hypothalamic SIRT1/p53 pathway seems to be specific for mediating the orexigenic action of ghrelin, because central administration of AICAR, a potent AMPK activator, increased food intake in p53 KO mice. Finally, blockade of the central SIRT1 pathway did not modify ghrelin-induced growth hormone secretion. CONCLUSIONS Ghrelin specifically triggers a central SIRT1/p53 pathway that is essential for its orexigenic action, but not for the release of growth hormone. PMID:21386086

Relation between central adiposity and cognitive function in the Maine-Syracuse Study: attenuation by physical activity.

PubMed

Dore, Gregory A; Elias, Merrill F; Robbins, Michael A; Budge, Marc M; Elias, Penelope K

2008-06-01

Previous studies have demonstrated a relationship between central adiposity and cognitive function. However, only some of these studies have adjusted for cardiovascular risk factors and cardiovascular disease, and none have also adjusted for physical activity level. The purpose of the study was to examine the association between anthropometric measures of central adiposity (waist circumference and waist/hip ratio) and cognitive functioning with adjustment for cardiovascular disease risk factors and physical activity. Participants were 917 stroke- and dementia-free community-dwelling adults (59% women) in the Maine-Syracuse Study. The design was cross-sectional. Outcome measures included tests from the Wechsler Adult Intelligence Scale, the Halstead-Reitan Neuropsychological Battery, the Wechsler Memory Scale Revised, and the Mini-Mental State Examination. Waist circumference and waist/hip ratio were inversely related to multiple cognitive domains with adjustment for age, education, gender, and number of prior exams. For example, a 20-cm increment in waist circumference was associated with a 0.14 SD decrement in the Global Composite score. These relations were attenuated with adjustment for cardiovascular disease risk factors. However, with further adjustment for physical activity level, only waist circumference remained significantly associated with performance on the Similarities test. Waist circumference and waist/hip ratio are inversely related to cognitive function. Measures of central adiposity predict cognitive function independently of associated cardiovascular risk factors and events; however, the association between central adiposity and cognitive function is attenuated, to a large extent, by adjustment for physical activity level. Physical activity is an important covariate in studies relating measures of central adiposity to cognition.

Plasticity Beyond V1: Reinforcement of Motion Perception upon Binocular Central Retinal Lesions in Adulthood.

PubMed

Burnat, Kalina; Hu, Tjing-Tjing; Kossut, Małgorzata; Eysel, Ulf T; Arckens, Lutgarde

2017-09-13

Induction of a central retinal lesion in both eyes of adult mammals is a model for macular degeneration and leads to retinotopic map reorganization in the primary visual cortex (V1). Here we characterized the spatiotemporal dynamics of molecular activity levels in the central and peripheral representation of five higher-order visual areas, V2/18, V3/19, V4/21a,V5/PMLS, area 7, and V1/17, in adult cats with central 10° retinal lesions (both sexes), by means of real-time PCR for the neuronal activity reporter gene zif268. The lesions elicited a similar, permanent reduction in activity in the center of the lesion projection zone of area V1/17, V2/18, V3/19, and V4/21a, but not in the motion-driven V5/PMLS, which instead displayed an increase in molecular activity at 3 months postlesion, independent of visual field coordinates. Also area 7 only displayed decreased activity in its LPZ in the first weeks postlesion and increased activities in its periphery from 1 month onward. Therefore we examined the impact of central vision loss on motion perception using random dot kinematograms to test the capacity for form from motion detection based on direction and velocity cues. We revealed that the central retinal lesions either do not impair motion detection or even result in better performance, specifically when motion discrimination was based on velocity discrimination. In conclusion, we propose that central retinal damage leads to enhanced peripheral vision by sensitizing the visual system for motion processing relying on feedback from V5/PMLS and area 7. SIGNIFICANCE STATEMENT Central retinal lesions, a model for macular degeneration, result in functional reorganization of the primary visual cortex. Examining the level of cortical reactivation with the molecular activity marker zif268 revealed reorganization in visual areas outside V1. Retinotopic lesion projection zones typically display an initial depression in zif268 expression, followed by partial recovery with postlesion time. Only the motion-sensitive area V5/PMLS shows no decrease, and even a significant activity increase at 3 months post-retinal lesion. Behavioral tests of motion perception found no impairment and even better sensitivity to higher random dot stimulus velocities. We demonstrate that the loss of central vision induces functional mobilization of motion-sensitive visual cortex, resulting in enhanced perception of moving stimuli. Copyright © 2017 the authors 0270-6474/17/378989-11$15.00/0.

Channeling the Central Dogma

PubMed Central

Calabrese, Ronald L.

2014-01-01

How do neurons and networks achieve their characteristic electrical activity, regulate this activity homeostatically, and yet show population variability in expression? O'Leary et al. address some of these thorny questions in this theoretical analysis that starts with the Central Dogma. PMID:24853932

Regional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain.

PubMed

Fridman, Esteban A; Beattie, Bradley J; Broft, Allegra; Laureys, Steven; Schiff, Nicholas D

2014-04-29

Although disorders of consciousness (DOCs) demonstrate widely varying clinical presentations and patterns of structural injury, global down-regulation and bilateral reductions in metabolism of the thalamus and frontoparietal network are consistent findings. We test the hypothesis that global reductions of background synaptic activity in DOCs will associate with changes in the pattern of metabolic activity in the central thalamus and globus pallidus. We compared 32 [(18)F]fluorodeoxyglucose PETs obtained from severely brain-injured patients (BIs) and 10 normal volunteers (NVs). We defined components of the anterior forebrain mesocircuit on high-resolution T1-MRI (ventral, associative, and sensorimotor striatum; globus pallidus; central thalamus and noncentral thalamus). Metabolic profiles for BI and NV demonstrated distinct changes in the pattern of uptake: ventral and association striatum (but not sensorimotor) were significantly reduced relative to global mean uptake after BI; a relative increase in globus pallidus metabolism was evident in BI subjects who also showed a relative reduction of metabolism in the central thalamus. The reversal of globus pallidus and central thalamus profiles across BIs and NVs supports the mesocircuit hypothesis that broad functional (or anatomic) deafferentation may combine to reduce central thalamus activity and release globus pallidus activity in DOCs. In addition, BI subjects showed broad frontoparietal metabolic down-regulation consistent with prior studies supporting the link between central thalamic/pallidal metabolism and down-regulation of the frontoparietal network. Recovery of left hemisphere frontoparietal metabolic activity was further associated with command following.

Promoting Teacher Adoption of Physical Activity Breaks in the Classroom: Findings of the Central Texas Catch Middle School Project

ERIC Educational Resources Information Center

Delk, Joanne; Springer, Andrew E.; Kelder, Steven H.; Grayless, Megan

2014-01-01

Background: Research suggests that physical activity breaks (ABs) during class increase students' physical activity levels and provide an academic benefit. This study evaluates a 3-year intervention aimed at encouraging teacher AB use. Methods: Thirty central Texas middle schools were assigned to 1 of 3 conditions: training-only…

Central oxytocin receptors mediate mating-induced partner preferences and enhance correlated activation across forebrain nuclei in male prairie voles.

PubMed

Johnson, Zachary V; Walum, Hasse; Jamal, Yaseen A; Xiao, Yao; Keebaugh, Alaine C; Inoue, Kiyoshi; Young, Larry J

2016-03-01

Oxytocin (OT) is a deeply conserved nonapeptide that acts both peripherally and centrally to modulate reproductive physiology and sociosexual behavior across divergent taxa, including humans. In vertebrates, the distribution of the oxytocin receptor (OTR) in the brain is variable within and across species, and OTR signaling is critical for a variety of species-typical social and reproductive behaviors, including affiliative and pair bonding behaviors in multiple socially monogamous lineages of fishes, birds, and mammals. Early work in prairie voles suggested that the endogenous OT system modulates mating-induced partner preference formation in females but not males; however, there is significant evidence that central OTRs may modulate pair bonding behavior in both sexes. In addition, it remains unclear how transient windows of central OTR signaling during sociosexual interaction modulate neural activity to produce enduring shifts in sociobehavioral phenotypes, including the formation of selective social bonds. Here we re-examine the role of the central OT system in partner preference formation in male prairie voles using a selective OTR antagonist delivered intracranially. We then use the same antagonist to examine how central OTRs modulate behavior and immediate early gene (Fos) expression, a metric of neuronal activation, in males during brief sociosexual interaction with a female. Our results suggest that, as in females, OTR signaling is critical for partner preference formation in males and enhances correlated activation across sensory and reward processing brain areas during sociosexual interaction. These results are consistent with the hypothesis that central OTR signaling facilitates social bond formation by coordinating activity across a pair bonding neural network. Copyright © 2015 Elsevier Inc. All rights reserved.

Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase.

PubMed

Warren, Christopher M; van den Brink, Ruud L; Nieuwenhuis, Sander; Bosch, Jos A

2017-04-01

It has been suggested that central norepinephrine (NE) activity may be inferred from increases in salivary alpha-amylase (SAA), but data in favor of this proposition are limited. We administered 40mg of atomoxetine, a selective NE transporter blocker that increases central NE levels, to 24 healthy adult participants in a double-blind, placebo-controlled cross-over design. Atomoxetine administration significantly increased SAA secretion and concentrations at 75-180min after treatment (more than doubling baseline levels). Consistent with evidence that elevation in central NE is a co-determinant of hypothalamic-pituitary-adrenal axis activity, salivary cortisol also approximately doubled at the same time points. Moreover, changes in salivary cortisol positively correlated with SAA (0.44

The South Central Superpave Center: Report of Activities

DOT National Transportation Integrated Search

1998-12-01

The planning of the South Central Superpave Center (SCSC) began in mid-1994. The Center hired its first staff in early 1995 and was fully staffed by June 1995, at which point it became fully operational. This report describes SCSC activities that too...

CNS β3-adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight.

PubMed

Richard, Jennifer E; López-Ferreras, Lorena; Chanclón, Belén; Eerola, Kim; Micallef, Peter; Skibicka, Karolina P; Wernstedt Asterholm, Ingrid

2017-09-01

Pharmacological β 3 -adrenergic receptor (β 3 AR) activation leads to increased mitochondrial biogenesis and activity in white adipose tissue (WAT), a process commonly referred to as "browning", and transiently increased insulin release. These effects are associated with improved metabolic function and weight loss. It is assumed that this impact of β 3 AR agonists is mediated solely through activation of β 3 ARs in adipose tissue. However, β 3 ARs are also found in the brain, in areas such as the brain stem and the hypothalamus, which provide multisynaptic innervation to brown and white adipose depots. Thus, contrary to the current adipocentric view, the central nervous system (CNS) may also have the ability to regulate energy balance and metabolism through actions on central β 3 ARs. Therefore, this study aimed to elucidate whether CNS β 3 ARs can regulate browning of WAT and other aspects of metabolic regulation, such as food intake control and insulin release. We found that acute central injection of β 3 AR agonist potently reduced food intake, body weight, and increased hypothalamic neuronal activity in rats. Acute central β 3 AR stimulation was also accompanied by a transient increase in circulating insulin levels. Moreover, subchronic central β 3 AR agonist treatment led to a browning response in both inguinal (IWAT) and gonadal WAT (GWAT), along with reduced GWAT and increased BAT mass. In high-fat, high-sugar-fed rats, subchronic central β 3 AR stimulation reduced body weight, chow, lard, and sucrose water intake, in addition to increasing browning of IWAT and GWAT. Collectively, our results identify the brain as a new site of action for the anorexic and browning impact of β 3 AR activation. Copyright © 2017 the American Physiological Society.

Central Compact Objects in Kes 79 and RCW 103 as `Hidden' Magnetars with Crustal Activity

NASA Astrophysics Data System (ADS)

Popov, S. B.; Kaurov, A. A.; Kaminker, A. D.

2015-05-01

We propose that observations of `hidden' magnetars in central compact objects can be used to probe crustal activity of neutron stars with large internal magnetic fields. Estimates based on calculations by Perna & Pons, Pons & Rea and Kaminker et al. suggest that central compact objects, which are proposed to be `hidden' magnetars, must demonstrate flux variations on the time scale of months-years. However, the most prominent candidate for the `hidden' magnetars - CXO J1852.6+0040 in Kes 79 - shows constant (within error bars) flux. This can be interpreted by lower variable crustal activity than in typical magnetars. Alternatively, CXO J1852.6+0040 can be in a high state of variable activity during the whole period of observations. Then we consider the source 1E161348 - 5055 in RCW103 as another candidate. Employing a simple 2D-modelling we argue that properties of the source can be explained by the crustal activity of the magnetar type. Thus, this object may be supplemented for the three known candidates for the `hidden' magnetars among central compact objects discussed in literature.

Time perspective and the theory of planned behavior: moderate predictors of physical activity among central Appalachian adolescents.

PubMed

Gulley, Tauna; Boggs, Dusta

2014-01-01

The purpose of this study was to determine how well time perspective and the Theory of Planned Behavior (TPB) predicted physical activity among adolescents residing in the central Appalachian region of the United States. A descriptive, correlational design was used. The setting was a rural high school in central Appalachia. The sample included 185 students in grades 9 through 12. Data were collected in school. Variables included components of the TPB, time perspective, and various levels of exercise. Data were analyzed using Pearson's correlation coefficients and multiple regression analysis. The TPB was a moderate predictor of exercise frequency among central Appalachian adolescents, accounting for 42% of the variance. Time perspective did not add to the predictive ability of the TPB to predict exercise frequency in this sample. This study provides support for the TPB for predicting frequency of exercise among central Appalachian adolescents. By understanding the role of the TPB in predicting physical activity among adolescents, nurse practitioners will be able to adapt intervention strategies to improve the physical activity behaviors of this population. Copyright © 2014 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

Dependence of palmar sweating response and central nervous system activity on the frequency of whole-body vibration.

PubMed

Ando, Hideo; Noguchi, Ryo

2003-06-01

This study was carried out to determine the effects of the frequency of whole-body vibration on palmar sweating response and the activity of the central sympathetic nervous system. Palmar sweating volume was measured on the right palm of six healthy men before and during 3 minutes of exposure to sinusoidal whole-body vibration at three different frequencies (16, 31.5, and 63 Hz). The whole-body vibration had a frequency-weighted, root mean square (rms) acceleration magnitude of 2.0 m/s2. As the index of the activated central sympathetic nervous system, saliva level of 3-methoxy-4-hydroxyphenylglycol (MHPG) was analyzed before and immediately after each vibration exposure. Each vibration frequency induced a palmar sweating response, that of 31.5 Hz being the largest. However, no significant difference was found between the three vibration conditions. Saliva MHPG increased in all the vibration exposures, and the largest change was observed at 31.5 Hz, the difference being significant. Acute exposure to whole-body vibration induced a palmar sweating response and activated the central sympathetic nervous system. The effects on the central nervous system were found to be dependent on the frequency of the vibration.

28 CFR 524.70 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Office clearance for transfers, temporary releases, or community activities. This monitoring is not to... TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.70 Purpose and scope. The... activities of certain inmates who present special needs for management. Such inmates, known as central inmate...

28 CFR 524.70 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Office clearance for transfers, temporary releases, or community activities. This monitoring is not to... TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.70 Purpose and scope. The... activities of certain inmates who present special needs for management. Such inmates, known as central inmate...

28 CFR 524.70 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Office clearance for transfers, temporary releases, or community activities. This monitoring is not to... TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.70 Purpose and scope. The... activities of certain inmates who present special needs for management. Such inmates, known as central inmate...

28 CFR 524.70 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Office clearance for transfers, temporary releases, or community activities. This monitoring is not to... TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.70 Purpose and scope. The... activities of certain inmates who present special needs for management. Such inmates, known as central inmate...

28 CFR 524.70 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Office clearance for transfers, temporary releases, or community activities. This monitoring is not to... TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.70 Purpose and scope. The... activities of certain inmates who present special needs for management. Such inmates, known as central inmate...

Strategic planning for the activation and operation of the North Central Superpave Center (NCSC)

DOT National Transportation Integrated Search

1997-01-01

The North Central Superpave Center (NCSC) was established to serve the needs of the states and industry in ten states and two Canadian provinces as they implement the Superpave system. Accomplishing this goal requires the cooperation and active suppo...

Sex-specific respiratory effects of acute and chronic caffeine administration in newborn rats.

PubMed

Kouchi, Hayet; Uppari, NagaPraveena; Joseph, Vincent; Bairam, Aida

2017-06-01

Caffeine is widely used for the treatment of apnea of prematurity (AoP) but whether this effect varies with sex is unknown. To shed some light on this question, we present a summary of data obtained on the effects of caffeine on the respiratory chemoreflexes and apnea frequency in 1- and 12-days old male and female rats. Caffeine was either administered as a single acute injection (10mg/kg, i.p.) or for 10 consecutive days (7.5mg/kg/day between 3 and 12days of life by gavage, simulating its clinical use). Acute caffeine had little effects on breathing in 1-day old male and female rats. In 12-days old female rats caffeine reduced the response to hypercapnia (not hypoxia) compared to males. During the steady state of hypoxia females had a lower frequency of apneas than males, and acute injection of caffeine decreased the frequency of apnea, suppressing the differences between males and females. In 12-days old rats chronic administration of caffeine stimulated basal breathing and decreased the frequency of apnea similarly in males and females. In response to hypoxia, chronic caffeine administration also masked the difference in respiratory frequency between males and females observed in control rats. Female rats had lower frequency of apnea than males with or without caffeine treatment. These observations indicate that sex influences the respiratory responses to caffeine and this effect seems to depend on the modality of administration (acute vs chronic) and environmental oxygen (normoxia vs hypoxia). Copyright © 2017 Elsevier B.V. All rights reserved.

Carotid body potentiation during chronic intermittent hypoxia: implication for hypertension

PubMed Central

Del Rio, Rodrigo; Moya, Esteban A.; Iturriaga, Rodrigo

2014-01-01

Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH). It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB) chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14, and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS, and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function. PMID:25429271

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats.

PubMed

Del Rio, Rodrigo; Andrade, David C; Lucero, Claudia; Arias, Paulina; Iturriaga, Rodrigo

2016-08-01

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension. © 2016 American Heart Association, Inc.

Sedentary Behavior and Light Physical Activity Are Associated with Brachial and Central Blood Pressure in Hypertensive Patients

PubMed Central

Gerage, Aline M.; Benedetti, Tania R. B.; Farah, Breno Q.; Santana, Fábio da S.; Ohara, David; Andersen, Lars B.; Ritti-Dias, Raphael M.

2015-01-01

Background Physical activity is recommended as a part of a comprehensive lifestyle approach in the treatment of hypertension, but there is a lack of data about the relationship between different intensities of physical activity and cardiovascular parameters in hypertensive patients. The purpose of this study was to investigate the association between the time spent in physical activities of different intensities and blood pressure levels, arterial stiffness and autonomic modulation in hypertensive patients. Methods In this cross-sectional study, 87 hypertensive patients (57.5 ± 9.9 years of age) had their physical activity assessed over a 7 day period using an accelerometer and the time spent in sedentary activities, light physical activities, moderate physical activities and moderate-to-vigorous physical activities was obtained. The primary outcomes were brachial and central blood pressure. Arterial stiffness parameters (augmentation index and pulse wave velocity) and cardiac autonomic modulation (sympathetic and parasympathetic modulation in the heart) were also obtained as secondary outcomes. Results Sedentary activities and light physical activities were positively and inversely associated, respectively, with brachial systolic (r = 0.56; P < 0.01), central systolic (r = 0.51; P < 0.05), brachial diastolic (r = 0.45; P < 0.01) and central diastolic (r = 0.42; P < 0.05) blood pressures, after adjustment for sex, age, trunk fat, number of antihypertensive drugs, accelerometer wear time and moderate-to-vigorous physical activities. Arterial stiffness parameters and cardiac autonomic modulation were not associated with the time spent in sedentary activities and in light physical activities (P > 0.05). Conclusion Lower time spent in sedentary activities and higher time spent in light physical activities are associated with lower blood pressure, without affecting arterial stiffness and cardiac autonomic modulation in hypertensive patients. PMID:26717310

Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat.

PubMed

Matsukawa, Kanji; Ishii, Kei; Asahara, Ryota; Idesako, Mitsuhiro

2016-10-01

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade. Copyright © 2016 the American Physiological Society.

Mangiferin Upregulates Glyoxalase 1 Through Activation of Nrf2/ARE Signaling in Central Neurons Cultured with High Glucose.

PubMed

Liu, Yao-Wu; Cheng, Ya-Qin; Liu, Xiao-Li; Hao, Yun-Chao; Li, Yu; Zhu, Xia; Zhang, Fan; Yin, Xiao-Xing

2017-08-01

Mangiferin, a natural C-glucoside xanthone, has anti-inflammatory, anti-oxidative, neuroprotective actions. Our previous study showed that mangiferin could attenuate diabetes-associated cognitive impairment of rats by enhancing the function of glyoxalase 1 (Glo-1) in brain. The aim of this study was to investigate whether Glo-1 upregulation by mangiferin in central neurons exposed to chronic high glucose may be related to activation of Nrf2/ARE pathway. Compared with normal glucose (25 mmol/L) culture, Glo-1 protein, mRNA, and activity levels were markedly decreased in primary hippocampal and cerebral cortical neurons cultured with high glucose (50 mmol/L) for 72 h, accompanied by the declined Nrf2 nuclear translocation and protein expression of Nrf2 in cell nucleus, as well as protein expression and mRNA level of γ-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase activity, target genes of Nrf2/ARE signaling. Nonetheless, high glucose cotreating with mangiferin or sulforaphane, a typical inducer of Nrf2 activation, attenuated the above changes in both central neurons. In addition, mangiferin and sulforaphane significantly prevented the formation of advanced glycation end-products (AGEs) reflecting Glo-1 activity, while elevated the level of glutathione, a cofactor of Glo-1 activity and production of γ-GCS, in high glucose cultured central neurons. These findings demonstrated that Glo-1 was greatly downregulated in central neurons exposed to chronic high glucose, which is expected to lead the formation of AGEs and oxidative stress damages. We also proved that mangiferin enhanced the function of Glo-1 under high glucose condition by inducing activation of Nrf2/ARE signaling pathway.

Regional assessment of energy-producing metabolic activity in the endothelium of donor corneas.

PubMed

Greiner, Mark A; Burckart, Kimberlee A; Wagoner, Michael D; Schmidt, Gregory A; Reed, Cynthia R; Liaboe, Chase A; Flamme-Wiese, Miles J; Zimmerman, M Bridget; Mullins, Robert F; Kardon, Randy H; Goins, Kenneth M; Aldrich, Benjamin T

2015-05-01

We characterized mitochondrial respiration and glycolysis activity of human corneal endothelium, and compared metabolic activity between central and peripheral regions. Endothelial keratoplasty-suitable corneas were obtained from donors aged 50 to 75 years. The endothelium-Descemet membrane complex (EDM) was isolated, and 3-mm punches were obtained from central and peripheral regions. Endothelium-Descemet membrane punches were assayed for mitochondrial respiration (oxygen consumption) and glycolysis (extracellular acidification) using an extracellular flux analyzer. Enzymatic (citrate synthase, glucose hexokinase) and mitochondrial density (MitoTracker) assays also were performed. Ten corneas were analyzed per assay. Metabolic activity for mitochondrial respiration and glycolysis showed expected changes to assay compounds (P < 0.01, all pairwise comparisons). Basal mitochondrial respiration and glycolysis activity did not differ between regions (P > 0.99). Similarly, central versus peripheral activity after assay compound treatment showed no significant differences (P > 0.99, all time points). The intracorneal coefficient of variation for basal readings between two and four peripheral punches was 18.5% of the mean. Although peripheral samples displayed greater enzymatic activity than central samples (P < 0.05), similar to extracellular flux results, mitochondrial density did not differ between regions (P = 0.78). Extracellular flux analysis of oxygen and pH is a valid technique for characterizing metabolic activity of human corneal endothelium. This technique demonstrates high reproducibility, allows quantification of metabolic parameters using small quantities of live cells, and permits estimation of overall metabolic output. Neither oxygen consumption nor extracellular acidification differed between central and peripheral regions of transplant suitable corneas in this series. Our results show that endothelial cell health can be quantified biochemically in transplant suitable corneas.

Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions

PubMed Central

Eller-Smith, Olivia C.; Nicol, Andrea L.; Christianson, Julie A.

2018-01-01

Centralized pain syndromes are associated with changes within the central nervous system that amplify peripheral input and/or generate the perception of pain in the absence of a noxious stimulus. Examples of idiopathic functional disorders that are often categorized as centralized pain syndromes include fibromyalgia, chronic pelvic pain syndromes, migraine, and temporomandibular disorder. Patients often suffer from widespread pain, associated with more than one specific syndrome, and report fatigue, mood and sleep disturbances, and poor quality of life. The high degree of symptom comorbidity and a lack of definitive underlying etiology make these syndromes notoriously difficult to treat. The main purpose of this review article is to discuss potential mechanisms of centrally-driven pain amplification and how they may contribute to increased comorbidity, poorer pain outcomes, and decreased quality of life in patients diagnosed with centralized pain syndromes, as well as discuss emerging non-pharmacological therapies that improve symptomology associated with these syndromes. Abnormal regulation and output of the hypothalamic-pituitary-adrenal (HPA) axis is commonly associated with centralized pain disorders. The HPA axis is the primary stress response system and its activation results in downstream production of cortisol and a dampening of the immune response. Patients with centralized pain syndromes often present with hyper- or hypocortisolism and evidence of altered downstream signaling from the HPA axis including increased Mast cell (MC) infiltration and activation, which can lead to sensitization of nearby nociceptive afferents. Increased peripheral input via nociceptor activation can lead to “hyperalgesic priming” and/or “wind-up” and eventually to central sensitization through long term potentiation in the central nervous system. Other evidence of central modifications has been observed through brain imaging studies of functional connectivity and magnetic resonance spectroscopy and are shown to contribute to the widespreadness of pain and poor mood in patients with fibromyalgia and chronic urological pain. Non-pharmacological therapeutics, including exercise and cognitive behavioral therapy (CBT), have shown great promise in treating symptoms of centralized pain. PMID:29487504

Central noradrenergic mechanisms and the acute stress response during painful stimulation.

PubMed

Chapman, C Richard; Bradshaw, David H; Donaldson, Gary W; Jacobson, Robert C; Nakamura, Yoshio

2014-12-01

Events that threaten tissue integrity including noxious stimulation activate central noradrenergic circuits, particularly locus coeruleus and its projections. Recent advances in theory hold that an adaptive, defensive shift in brain activity takes place in response to threat. In principle, this shift may accentuate the autonomic and central biomarkers of the perception of painful events and the experience of pain itself. We have examined the effects of an alpha-2 agonist on pupil dilation responses, skin conductance responses, near field somatosensory evoked potentials and pain reports in normal volunteers undergoing repeated trials of painful fingertip stimulation delivered at low, medium and high intensities. In a double-blinded study, 114 healthy male and female volunteers underwent repeated noxious stimulation under baseline, placebo and active drug conditions where the active drug was the alpha-2 agonist tizanidine 4 mg. In contrast to baseline and placebo conditions, tizanidine 4 mg significantly reduced the magnitudes of the mean pupil dilation response, the mean skin conductance response, the mean near field somatosensory evoked potential peak-to-peak amplitude and the mean pain intensity rating. Stimulus intensity significantly altered all three biomarkers and the pain report in a graded fashion. There were no sex differences. These findings support the hypotheses that painful events activate central noradrenergic circuits, and that these circuits play a role in the autonomic and central arousal associated with pain. © The Author(s) 2014.

Optimization of the central linker of dicationic bis-benzimidazole anti-MRSA and anti-VRE agents.

PubMed

Hu, Laixing; Kully, Maureen L; Boykin, David W; Abood, Norman

2009-07-01

A series of bis-benzimidazole diamidine compounds containing different central linkers has been synthesized and evaluated for in vitro antibacterial activities, including drug-resistant bacterial strains. Seven compounds have shown potent antibacterial activities. The anti-MRSA and anti-VRE activities of compound 1h were more potent than that of the lead compound 1a and vancomycin.

Channeling the Central Dogma.

PubMed

Calabrese, Ronald L

2014-05-21

How do neurons and networks achieve their characteristic electrical activity, regulate this activity homeostatically, and yet show population variability in expression? In this issue of Neuron, O'Leary et al. (2014) address some of these thorny questions in this theoretical analysis that starts with the Central Dogma. Copyright © 2014 Elsevier Inc. All rights reserved.

32 CFR 1906.103 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY..., and other similar services and devices. The Central Intelligence Agency may prohibit from any of its...

32 CFR 1906.103 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY..., and other similar services and devices. The Central Intelligence Agency may prohibit from any of its...

32 CFR 1906.103 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY..., and other similar services and devices. The Central Intelligence Agency may prohibit from any of its...

32 CFR 1906.103 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY..., and other similar services and devices. The Central Intelligence Agency may prohibit from any of its...

Geomorphic indices indicated differential active tectonics of the Longmen Shan

NASA Astrophysics Data System (ADS)

Gao, M.; Xu, X.; Tan, X.

2012-12-01

The Longmen Shan thrust belt is located at the eastern margin of the Tibetan Plateau. It is a region of rapid active tectonics with high erosion rates and dense vegetation. The structure of the Longmen Shan region is dominated by northeast-trending thrusts and overturned folds that verge to the east and southeast (Burchfiel et al. 1995, Chen and Wilson 1996). The Longmen Shan thrust belt consists of three major faults from west to east: back-range fault, central fault, and frontal-range fault. The Mw 7.9 Wenchuan earthquake ruptured two large thrust faults along the Longmen Shan thrust belt (Xiwei et al., 2009). In this paper, we focus on investigating the spatial variance of tectonic activeness from the back-range fault to the frontal-range fault, particular emphasis on the differential recent tectonic activeness reflected by the hypsometry and the asymmetric factor of the drainage. Results from asymmetric factor indicate the back-rannge thrust fault on the south of the Maoxian caused drainage basins tilted on the hanging wall. For the north of the Maoxian, the strike-slip fault controlled the shapes of the drainage basins. Constantly river capture caused the expansion of the drainage basins which traversed by the fault. The drainages on the central fault and the frontal-range fault are also controlled by the fault slip. The drainage asymmetric factor suggested the central and southern segments of the Longmen Shan are more active than the northern segment, which is coherence with results of Huiping et al. (2010). The results from hypsometry show the back-range fault is the most active fault among the three major faults. Central fault is less active than the back-range fault but more active than the frontal-range fault. Beichuan is identified as the most active area along the central fault. Our geomorphic indices reflect an overall eastward decreasing of tectonic activeness of the Longmen Shan thrust belt.

Star Formation in the Central Regions of Galaxies

NASA Astrophysics Data System (ADS)

Tsai, Mengchun

2015-08-01

The galactic central region connects the galactic nucleus to the host galaxy. If the central black hole co-evolved with the host galaxies, there should be some evidence left in the central region. We use the environmental properties in the central regions such as star-forming activity, stellar population and molecular abundance to figure out a possible scenario of the evolution of galaxies. In this thesis at first we investigated the properties of the central regions in the host galaxies of active and normal galaxies. We used radio emission around the nuclei of the host galaxies to represent activity of active galactic nuclei (AGNs), and used infrared ray (IR) emission to represent the star-forming activity and stellar population of the host galaxies. We determined that active galaxies have higher stellar masses (SMs) within the central kiloparsec radius than normal galaxies do independent of the Hubble types of the host galaxies; but both active and normal galaxies exhibit similar specific star formation rates (SSFRs). We also discovered that certain AGNs exhibit substantial inner stellar structures in the IR images; most of the AGNs with inner structures are Seyferts, whereas only a few LINERs exhibit inner structures. We note that the AGNs with inner structures show a positive correlation between the radio activity of the AGNs and the SFRs of the host galaxies, but the sources without inner structures show a negative correlation between the radio power and the SFRs. These results might be explained with a scenario of starburst-AGN evolution. In this scenario, AGN activities are triggered following a nuclear starburst; during the evolution, AGN activities are accompanied by SF activity in the inner regions of the host galaxies; at the final stage of the evolution, the AGNs might transform into LINERs, exhibiting weak SF activity in the central regions of the host galaxies. For further investigation about the inner structure, we choose the most nearby and luminous Seyfert galaxy with inner structure as an example. In this thesis, we present CO(3-2) interferometric observations of the central region of the Seyfert 2 galaxy NGC1068 using the Submillimeter Array, together with CO(1-0) data taken with the Owens Valley Radio Observatory Millimeter Array. Both the CO(3-2) and CO(1-0) emission lines are mainly distributed within ~5 arcsec of the nucleus and along the spiral arms, but the intensity distributions show differences; the CO(3-2) map peaks in the nucleus, while the CO(1-0) emission is mainly located along the spiral arms. The CO(3-2)/CO(1-0) ratio is about 3.1 in the nucleus, which is four times as large as the average line ratio in the spiral arms, suggesting that the molecular gas there must be affected by the radiation arising from the AGN. On the other hand, the line ratios in the spiral arms vary over a wide range from 0.24 to 2.34 with a average value around 0.75, which is similar to the line ratios of star-formation regions, indicating that the molecular gas is affected by star formation. Besides, we see a tight correlation between CO(3-2)/(1-0) ratios in the spiral arms and star formation rate surface densities derived from Spitzer 8 micron dust flux densities. We also compare the CO(3-2)/(1-0) ratio and the star formation rate at different positions within the spiral arms; both are found to decrease as the radius from the nucleus increases.

The importance of regulation of blood glucose levels through activation of peripheral 5'-AMP-activated protein kinase on ischemic neuronal damage.

PubMed

Harada, Shinichi; Fujita-Hamabe, Wakako; Tokuyama, Shogo

2010-09-10

5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in energy homeostasis. Recently, it was reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In addition, we have previously reported that the development of post-ischemic glucose intolerance could be one of the triggers for the aggravation of neuronal damage. In this study, we focused on effect of activation of peripheral or central AMPK on the development of ischemic neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histological and behavioral analysis after MCAO. In the liver and skeletal muscle, AMPK activity was not affected by MCAO. But, application of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly suppressed the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, application of intracerebroventricular metformin (25, 100 microg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO, in a dose-dependent manner. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK was activated by ischemic stress per se, however, peripheral AMPK was not altered. Furthermore, the regulation of post-ischemic glucose intolerance by activation of peripheral AMPK is of assistance for the suppression of cerebral ischemic neuronal damage. 2010 Elsevier B.V. All rights reserved.

Post-natal hypoxic activity of the central respiratory command is improved in transgenic mice overexpressing Epo in the brain.

PubMed

Caravagna, Céline; Kinkead, Richard; Soliz, Jorge

2014-08-15

Previous studies indicated that erythropoietin modulates central respiratory command in mice. Specifically, a one-hour incubation of the brainstems with erythropoietin attenuates hypoxia-induced central respiratory depression. Here, using transgenic mice constitutively overexpressing erythropoietin specifically in the brain (Tg21), we investigated the effect of chronic erythropoietin stimulation on central respiratory command activity during post-natal development. In vitro brainstem-spinal cord preparations from mice at 0 (P0) or 3 days of age (P3) were used to record the fictive inspiratory activity from the C4 ventral root. Our results show that erythropoietin already stimulates the hypoxic burst frequency at P0, and at P3, erythropoietin effectively stimulates the hypoxic burst frequency and amplitude. Because the maturation of the central respiratory command in mice is characterized by a decrease in the burst frequency with age, our results also suggest that erythropoietin accelerates the maturation of the newborn respiratory network and its response to hypoxia. Copyright © 2014 Elsevier B.V. All rights reserved.

Peripheral oxygen-sensing cells directly modulate the output of an identified respiratory central pattern generating neuron.

PubMed

Bell, Harold J; Inoue, Takuya; Shum, Kelly; Luk, Collin; Syed, Naweed I

2007-06-01

Breathing is an essential homeostatic behavior regulated by central neuronal networks, often called central pattern generators (CPGs). Despite ongoing advances in our understanding of the neural control of breathing, the basic mechanisms by which peripheral input modulates the activities of the central respiratory CPG remain elusive. This lack of fundamental knowledge vis-à-vis the role of peripheral influences in the control of the respiratory CPG is due in large part to the complexity of mammalian respiratory control centres. We have therefore developed a simpler invertebrate model to study the basic cellular and synaptic mechanisms by which a peripheral chemosensory input affects the central respiratory CPG. Here we report on the identification and characterization of peripheral chemoreceptor cells (PCRCs) that relay hypoxia-sensitive chemosensory information to the known respiratory CPG neuron right pedal dorsal 1 in the mollusk Lymnaea stagnalis. Selective perfusion of these PCRCs with hypoxic saline triggered bursting activity in these neurons and when isolated in cell culture these cells also demonstrated hypoxic sensitivity that resulted in membrane depolarization and spiking activity. When cocultured with right pedal dorsal 1, the PCRCs developed synapses that exhibited a form of short-term synaptic plasticity in response to hypoxia. Finally, osphradial denervation in intact animals significantly perturbed respiratory activity compared with their sham counterparts. This study provides evidence for direct synaptic connectivity between a peripheral regulatory element and a central respiratory CPG neuron, revealing a potential locus for hypoxia-induced synaptic plasticity underlying breathing behavior.

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

PubMed

Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

2017-08-01

The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes

PubMed Central

Esterson, Yonah B.; Carey, Michelle; Boucai, Laura; Goyal, Akankasha; Raghavan, Pooja; Zhang, Kehao; Mehta, Deeksha; Feng, Daorong; Wu, Licheng; Kehlenbrink, Sylvia; Koppaka, Sudha; Kishore, Preeti

2016-01-01

The challenges of achieving optimal glycemic control in type 2 diabetes highlight the need for new therapies. Inappropriately elevated endogenous glucose production (EGP) is the main source of hyperglycemia in type 2 diabetes. Because activation of central ATP-sensitive potassium (KATP) channels suppresses EGP in nondiabetic rodents and humans, this study examined whether type 2 diabetic humans and rodents retain central regulation of EGP. The KATP channel activator diazoxide was administered in a randomized, placebo-controlled crossover design to eight type 2 diabetic subjects and seven age- and BMI-matched healthy control subjects. Comprehensive measures of glucose turnover and insulin sensitivity were performed during euglycemic pancreatic clamp studies following diazoxide and placebo administration. Complementary rodent clamp studies were performed in Zucker Diabetic Fatty rats. In type 2 diabetic subjects, extrapancreatic KATP channel activation with diazoxide under fixed hormonal conditions failed to suppress EGP, whereas matched control subjects demonstrated a 27% reduction in EGP (P = 0.002) with diazoxide. Diazoxide also failed to suppress EGP in diabetic rats. These results suggest that suppression of EGP by central KATP channel activation may be lost in type 2 diabetes. Restoration of central regulation of glucose metabolism could be a promising therapeutic target to reduce hyperglycemia in type 2 diabetes. PMID:27207526

Central- and autonomic nervous system coupling in schizophrenia

PubMed Central

Schulz, Steffen; Bolz, Mathias; Bär, Karl-Jürgen

2016-01-01

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback–feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central–autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age–gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS–ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity. PMID:27044986

Central Nervous Activity upon Systemic Salicylate Application in Animals with Kanamycin-Induced Hearing Loss - A Manganese-Enhanced MRI (MEMRI) Study

PubMed Central

Gröschel, Moritz; Götze, Romy; Müller, Susanne; Ernst, Arne; Basta, Dietmar

2016-01-01

This study investigated the effect of systemic salicylate on central auditory and non-auditory structures in mice. Since cochlear hair cells are known to be one major target of salicylate, cochlear effects were reduced by using kanamycin to remove or impair hair cells. Neuronal brain activity was measured using the non-invasive manganese-enhanced magnetic resonance imaging technique. For all brain structures investigated, calcium-related neuronal activity was increased following systemic application of a sodium salicylate solution: probably due to neuronal hyperactivity. In addition, it was shown that the central effect of salicylate was not limited to the auditory system. A general alteration of calcium-related activity was indicated by an increase in manganese accumulation in the preoptic area of the anterior hypothalamus, as well as in the amygdala. The present data suggest that salicylate-induced activity changes in the auditory system differ from those shown in studies of noise trauma. Since salicylate action is reversible, central pharmacological effects of salicylate compared to those of (permanent) noise-induced hearing impairment and tinnitus might induce different pathophysiologies. These should therefore, be treated as different causes with the same symptoms. PMID:27078034

Muscle sympathetic nerve responses to passive and active one-legged cycling: insights into the contributions of central command.

PubMed

Doherty, Connor J; Incognito, Anthony V; Notay, Karambir; Burns, Matthew J; Slysz, Joshua T; Seed, Jeremy D; Nardone, Massimo; Burr, Jamie F; Millar, Philip J

2018-01-01

The contribution of central command to the peripheral vasoconstrictor response during exercise has been investigated using primarily handgrip exercise. The purpose of the present study was to compare muscle sympathetic nerve activity (MSNA) responses during passive (involuntary) and active (voluntary) zero-load cycling to gain insights into the effects of central command on sympathetic outflow during dynamic exercise. Hemodynamic measurements and contralateral leg MSNA (microneurography) data were collected in 18 young healthy participants at rest and during 2 min of passive and active zero-load one-legged cycling. Arterial baroreflex control of MSNA burst occurrence and burst area were calculated separately in the time domain. Blood pressure and stroke volume increased during exercise ( P < 0.0001) but were not different between passive and active cycling ( P > 0.05). In contrast, heart rate, cardiac output, and total vascular conductance were greater during the first and second minute of active cycling ( P < 0.001). MSNA burst frequency and incidence decreased during passive and active cycling ( P < 0.0001), but no differences were detected between exercise modes ( P > 0.05). Reductions in total MSNA were attenuated during the first ( P < 0.0001) and second ( P = 0.0004) minute of active compared with passive cycling, in concert with increased MSNA burst amplitude ( P = 0.02 and P = 0.005, respectively). The sensitivity of arterial baroreflex control of MSNA burst occurrence was lower during active than passive cycling ( P = 0.01), while control of MSNA burst strength was unchanged ( P > 0.05). These results suggest that central feedforward mechanisms are involved primarily in modulating the strength, but not the occurrence, of a sympathetic burst during low-intensity dynamic leg exercise. NEW & NOTEWORTHY Muscle sympathetic nerve activity burst frequency decreased equally during passive and active cycling, but reductions in total muscle sympathetic nerve activity were attenuated during active cycling. These results suggest that central command primarily regulates the strength, not the occurrence, of a muscle sympathetic burst during low-intensity dynamic leg exercise.

Central sensitization: Implications for the diagnosis and treatment of pain

PubMed Central

Woolf, Clifford J

2010-01-01

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and postsurgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk both of developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity. PMID:20961685

Multivariate assessment of the central-cardiorespiratory network structure in neuropathological disease.

PubMed

Schulz, Steffen; Haueisen, Jens; Bär, Karl-Juergen; Voss, Andreas

2018-06-22

The new interdisciplinary field of network physiology is getting more and more into the focus of interest in medicine. The autonomic nervous system (ANS) dysfunction is well described in schizophrenia (SZO). However, the linear and nonlinear coupling between the ANS and central nervous system (CNS) is only partly addressed until now. This coupling can be assumed as a feedback-feedforward network, reacting with flexible and adaptive responses to internal and external factors. Approach: For the first time, in this study, we investigated linear and nonlinear short-term central-cardiorespiratory couplings of 17 patients suffering from paranoid schizophrenia (SZO) in comparison to 17 age-gender matched healthy subjects (CON) analyzing heart rate (HR), respiration (RESP) and the power of frontal EEG activity (PEEG). The objective is to determine how the different regulatory aspects of the CNS-ANS compose the central-cardiorespiratory network (CCRN). To quantify these couplings within the CCRN the normalized short time partial directed coherence (NSTPDC) and the new multivariate high-resolution joint symbolic dynamics (mHRJSD) were applied. Main results: We found that the CCRN in SZO is characterized as a bidirectional one, with stronger central driving mechanisms (PEEG→HR) towards HR regulation than vice versa, and with stronger respiratory influence (RESP→PEEG) on central activity than vice versa. This suggests that the central-cardiorespiratory process (closed-loop) is mainly focusing on adapting the HR via the sinoatrial node than focusing on respiratory regulation. On the other side, the feedback-loop from ANS to CNS is strongly dominated via respiratory activity. Significance: We could demonstrate a considerably significantly different central-cardiorespiratory network structure in schizophrenia with strong central influence on the cardiac system and a strong respiratory influence on the central nervous system. Moreover, this study provides a more in-depth understanding of the interplay of the central and autonomic regulatory network in healthy subjects and schizophrenic patients. . © 2018 Institute of Physics and Engineering in Medicine.

32 CFR 1906.170 - Compliance procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... of this section. Complaints may be sent to Central Intelligence Agency, Director, Office of Equal...

32 CFR 1906.170 - Compliance procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... of this section. Complaints may be sent to Central Intelligence Agency, Director, Office of Equal...

32 CFR 1906.170 - Compliance procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... of this section. Complaints may be sent to Central Intelligence Agency, Director, Office of Equal...

32 CFR 1906.170 - Compliance procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... of this section. Complaints may be sent to Central Intelligence Agency, Director, Office of Equal...

32 CFR 1906.170 - Compliance procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... of this section. Complaints may be sent to Central Intelligence Agency, Director, Office of Equal...

Centrifugally activated bearing for high-speed rotating machinery

DOEpatents

Post, Richard F.

1994-01-01

A centrifugally activated bearing is disclosed. The bearing includes an annular member that extends laterally and radially from a central axis. A rotating member that rotates about the central axis relative to the annular member is also included. The rotating member has an interior chamber that surrounds the central axis and in which the annular member is suspended. Furthermore, the interior chamber has a concave shape for retaining a lubricant therein while the rotating member is at rest and for retaining a lubricant therein while the rotating member is rotating. The concave shape is such that while the rotating member is rotating a centrifugal force causes a lubricant to be forced away from the central axis to form a cylindrical surface having an axis collinear with the central axis. This centrifugally displaced lubricant provides restoring forces to counteract lateral displacement during operation.

Encoding of the cough reflex in anesthetized guinea pigs

PubMed Central

Mori, Nanako

2011-01-01

We have previously described the physiological and morphological properties of the cough receptors and their sites of termination in the airways and centrally in the nucleus tractus solitarius (nTS). In the present study, we have addressed the hypothesis that the primary central synapses of the cough receptors subserve an essential role in the encoding of cough. We found that cough requires sustained, high-frequency (≥8-Hz) afferent nerve activation. We also found evidence for processes that both facilitate (summation, sensitization) and inhibit the initiation of cough. Sensitization of cough occurs with repetitive subthreshold activation of the cough receptors or by coincident activation of C-fibers and/or nTS neurokinin receptor activation. Desensitization of cough evoked by repetitive and/or continuous afferent nerve activation has a rapid onset (<60 s) and does not differentiate between tussive stimuli, suggesting a central nervous system-dependent process. The cough reflex can also be actively inhibited upon activation of other airway afferent nerve subtypes, including slowly adapting receptors and pulmonary C-fibers. The sensitization and desensitization of cough are likely attributable to the prominent, primary, and unique role of N-methyl-d-aspartate receptor-dependent signaling at the central synapses of the cough receptors. These attributes may have direct relevance to the presentation of cough in disease and for the effectiveness of antitussive therapies. PMID:20926760

Integrating CSPAP into the PETE Programs at Southern Connecticut State University and Central Connecticut State University

ERIC Educational Resources Information Center

Ciotto, Carol M.; Fede, Marybeth H.

2017-01-01

Collaboration among state legislators, Central Connecticut State University (CCSU) and Southern Connecticut State University (SCSU) faculty, community leaders, teachers and school administrators is currently taking place in Connecticut to make it a physically active state through PASS (Physically Active Schools Systems). PASS is a comprehensive,…

Workload and time management in central cancer registries: baseline data and implication for registry staffing.

PubMed

Chapman, Susan A; Mulvihill, Linda; Herrera, Carolina

2012-01-01

The Workload and Time Management Survey of Central Cancer Registries was conducted in 2011 to assess the amount of time spent on work activities usually performed by cancer registrars. A survey including 39 multi-item questions,together with a work activities data collection log, was sent by email to the central cancer registry (CCR) manager in each of the 50 states and the District of Columbia. Twenty-four central cancer registries (47%) responded to the survey.Results indicate that registries faced reductions in budgeted staffing from 2008-2009. The number of source records and total cases were important indicators of workload. Four core activities, including abstracting at the registry, visual editing,case consolidation, and resolving edit reports, accounted for about half of registry workload. We estimate an average of 12.4 full-time equivalents (FTEs) are required to perform all cancer registration activities tracked by the survey; however,estimates vary widely by registry size. These findings may be useful for registries as a benchmark for their own registry workload and time-management data and to develop staffing guidelines.

Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors

PubMed Central

Fleming, Michael S; Vysochan, Anna; Paixão, Sόnia; Niu, Jingwen; Klein, Rüdiger; Savitt, Joseph M; Luo, Wenqin

2015-01-01

RET can be activated in cis or trans by its co-receptors and ligands in vitro, but the physiological roles of trans signaling are unclear. Rapidly adapting (RA) mechanoreceptors in dorsal root ganglia (DRGs) express Ret and the co-receptor Gfrα2 and depend on Ret for survival and central projection growth. Here, we show that Ret and Gfrα2 null mice display comparable early central projection deficits, but Gfrα2 null RA mechanoreceptors recover later. Loss of Gfrα1, the co-receptor implicated in activating RET in trans, causes no significant central projection or cell survival deficit, but Gfrα1;Gfrα2 double nulls phenocopy Ret nulls. Finally, we demonstrate that GFRα1 produced by neighboring DRG neurons activates RET in RA mechanoreceptors. Taken together, our results suggest that trans and cis RET signaling could function in the same developmental process and that the availability of both forms of activation likely enhances but not diversifies outcomes of RET signaling. DOI: http://dx.doi.org/10.7554/eLife.06828.001 PMID:25838128

Plants and the central nervous system.

PubMed

Carlini, E A

2003-06-01

This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaraná), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed.

Workload and Time Management in Central Cancer Registries: Baseline Data and Implication for Registry Staffing

PubMed Central

Chapman, Susan A.; Mulvihill, Linda; Herrera, Carolina

2015-01-01

The Workload and Time Management Survey of Central Cancer Registries was conducted in 2011 to assess the amount of time spent on work activities usually performed by cancer registrars. A survey including 39 multi-item questions, together with a work activities data collection log, was sent by email to the central cancer registry (CCR) manager in each of the 50 states and the District of Columbia. Twenty-four central cancer registries (47%) responded to the survey. Results indicate that registries faced reductions in budgeted staffing from 2008–2009. The number of source records and total cases were important indicators of workload. Four core activities, including abstracting at the registry, visual editing, case consolidation, and resolving edit reports, accounted for about half of registry workload. We estimate an average of 12.4 full-time equivalents (FTEs) are required to perform all cancer registration activities tracked by the survey; however, estimates vary widely by registry size. These findings may be useful for registries as a benchmark for their own registry workload and time-management data and to develop staffing guidelines. PMID:23493024

32 CFR 1906.102 - Application.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... National Security Act of 1947 (50 U.S.C. 402 et seq.), as amended; the Central Intelligence Agency Act of...

32 CFR 1906.102 - Application.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... National Security Act of 1947 (50 U.S.C. 402 et seq.), as amended; the Central Intelligence Agency Act of...

32 CFR 1906.102 - Application.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... National Security Act of 1947 (50 U.S.C. 402 et seq.), as amended; the Central Intelligence Agency Act of...

32 CFR 1906.102 - Application.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... National Security Act of 1947 (50 U.S.C. 402 et seq.), as amended; the Central Intelligence Agency Act of...

32 CFR 1906.102 - Application.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY... National Security Act of 1947 (50 U.S.C. 402 et seq.), as amended; the Central Intelligence Agency Act of...

Central sympathoexcitatory actions of angiotensin II: role of type 1 angiotensin II receptors.

PubMed

DiBona, G F

1999-01-01

The role of the renin-angiotensin system in the control of sympathetic nerve activity is reviewed. Two general mechanisms are considered, one that involves the effects of circulating angiotensin II (AngII) on the central nervous system and a second that involves the central nervous system effects of AngII that originates within the central nervous system. The role of type 1 AngII receptors in discrete brain sites that mediate the sympathoexcitatory actions of AngII of either circulating or central nervous system origin is examined. AngII of circulating origin has ready access to the subfornical organ and area postrema, where it can bind to type 1 AngII receptors on neurons whose connections to the nucleus tractus solitarius and rostral ventrolateral medulla result in sympathoexcitation. In the rostral ventrolateral medulla, angiotensin peptides of central nervous system origin, likely involving angiotensin species in addition to AngII and binding to receptors other than type 1 or 2 AngII receptors, tonically support sympathetic nerve activity.

The mechanics and three-dimensional internal structure of active magmatic systems: Kilauea volcano, Hawaii.

USGS Publications Warehouse

Ryan, M.P.

1988-01-01

Interpretation of abundant seismic data suggest that Kilauea's primary conduit within the upper mantle is concentrically zoned to about 34-km depth. This zoned structure is inferred to contain a central core region of relatively higher permeability, surrounded by numerous dikes that are in intermittent hydraulic communication with each other and with the central core. During periods of relatively high magma transport, the entire cross section of the conduit is utilized. During periods of relatively low to moderate transport, however, only the central core is active.-from Author

Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury

DTIC Science & Technology

2017-08-01

AWARD NUMBER: W81XWH-12-1-0051 TITLE: Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System ...Central Nervous System Following Neural Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0051 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Robert...induces re- growth of dopaminergic axons at 3 to 6 weeks after destruction by a neurotoxin. However, this approach cannot be used in humans because

Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity.

PubMed

Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Liang, Nan; Ishida, Tomoko

2012-08-15

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

[Central muscle relaxant activities of 2-methyl-3-aminopropiophenone derivatives].

PubMed

Kontani, H; Mano, A; Koshiura, R; Yamazaki, M; Shimada, Y; Oshita, M; Morikawa, K; Kato, H; Ito, Y

1987-02-01

In this experiment, we synthetized new 2-methyl-3-aminopropiophenone (MP) derivatives, whose structure is known to have central muscle relaxant activities, and quinolizidine and indan . tetralin derivatives derived from MP by cyclization, and we investigated the central muscle relaxant activity. Among the quinolizidine derivatives, there was a very strong central depressant agent, trans (3H, 9aH)-3-(p-chloro) benzoyl-quinolizidine (HSR-740), and among the indan . tetralin derivatives, there was an excitant agents, trans (1H, 2H)-5-methoxy-3, 3-dimethyl-2-piperidinomethyl indan-1-ol (HSR-719). From the results, these derivatives were not considered to be adequate for central muscle relaxant. Among the MP derivatives, (4'-chloro-2'-methoxy-3-piperidino) propiophenone HCl (HSR-733) and (4'-ethyl-2-methyl-3-pyrrolidino) propiophenone HCl (HSR-770) strongly inhibited the cooperative movement in the rotating rod method using mice, and it exerted almost the same depressant activity on the cross extensor reflex using alpha-chloralose anesthetized rats. However, the inhibitory effects of HSR-733 on the anemic decerebrate rigidity and the rigidity induced by intracollicular decerebration in rats were weaker than those of HSR-770 and eperisone. In spinal cats, at a low dose (5 mg/kg, i.v.), HSR-733 depressed monosynaptic and dorsal root reflex potentials as compared with polysynaptic reflex potentials, and inhibitory effects of HSR-733 on these three reflex potentials were more potent than those of eperisone and HSR-770. Although HSR-770 acts on the spinal cord and supraspinal level on which eperisone has been reported to act, HSR-733 may mainly act on the spinal cord. These results indicate that the MP derivative with a 2-methyl group may be suitable as a central muscle relaxant. HSR-770, which has equipotent muscle relaxant activity to eperisone, exerted strong inhibitory effects on oxotremorine-induced tremor and weak inhibitory effects on spontaneous motor activity in the Animex method using mice, as compared with eperisone.

School District Leadership: A Partnership between Central Office and School Leadership

ERIC Educational Resources Information Center

Snell, Jeff

2017-01-01

School reform efforts and accountability movements have shifted the responsibilities of central office leadership toward teaching and learning (Johnson & Chrispeels, 2010; Leithwood & Jantzi, 2012). Those responsibilities have encouraged central office leaders to take a more active role in ensuring improved outcomes for students (Center…

75 FR 41087 - Conforming Changes to Applicant Submission Requirements; Implementing Federal Financial Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

... Report and Central Contractor Registration Requirements AGENCY: Office of the Secretary, HUD. ACTION... codifies the requirement that applicants for HUD assistance possess an active Central Contractor... conform the reporting requirements to those provided for by the FFR. B. Requirement for Central Contractor...

Effects of Neuromuscular Fatigue on Quadriceps Strength and Activation and Knee Biomechanics in Individuals Post-Anterior Cruciate Ligament Reconstruction and Healthy Adults.

PubMed

Thomas, Abbey C; Lepley, Lindsey K; Wojtys, Edward M; McLean, Scott G; Palmieri-Smith, Riann M

2015-12-01

Laboratory-based experiment using a pretest/posttest design. To determine the effects of neuromuscular fatigue on quadriceps strength and activation and sagittal and frontal plane knee biomechanics during dynamic landing following anterior cruciate ligament reconstruction (ACLR). Impaired quadriceps central activation occurs post-ACLR, likely altering lower extremity biomechanics. Neuromuscular fatigue similarly reduces volitional muscle activation and impairs neuromuscular control. Upon return to full activity post-ACLR, individuals likely concurrently experience quadriceps central activation deficits and neuromuscular fatigue, though the effects of fatigue on muscle strength and activation and biomechanics post-ACLR are unknown. Seventeen individuals 7 to 10 months post-ACLR and 16 controls participated. Quadriceps strength and central activation ratio were recorded prefatigue and postfatigue, which was induced via sets of double-leg squats. Knee biomechanics were recorded during a dynamic landing activity prefatigue and postfatigue. Both groups demonstrated smaller knee flexion (initial contact, P = .017; peak, P = .004) and abduction (initial contact, P = .005; peak, P = .009) angles postfatigue. The ACLR group had smaller peak knee flexion angles (P<.001) prefatigue and postfatigue than controls. Knee flexion moment was smaller in those post-ACLR than controls prefatigue (P<.001), but not postfatigue (P = .103). Controls had smaller knee flexion moments postfatigue (P = .001). Knee abduction moment was smaller in both groups postfatigue (P = .003). All participants demonstrated significantly lower strength (P<.001) and activation (P = .003) postfatigue. Impaired strength, central activation, and biomechanics were present postfatigue in both groups, suggesting that neuromuscular fatigue may increase noncontact ACL injury risk. However, these changes were not exaggerated in those post-ACLR, likely because they already demonstrated a stiff-legged landing strategy prefatigue.

Centrifugally activated bearing for high-speed rotating machinery

DOEpatents

Post, R.F.

1994-02-15

A centrifugally activated bearing is disclosed. The bearing includes an annular member that extends laterally and radially from a central axis. A rotating member that rotates about the central axis relative to the annular member is also included. The rotating member has an interior chamber that surrounds the central axis and in which the annular member is suspended. Furthermore, the interior chamber has a concave shape for retaining a lubricant therein while the rotating member is at rest and for retaining a lubricant therein while the rotating member is rotating. The concave shape is such that while the rotating member is rotating a centrifugal force causes a lubricant to be forced away from the central axis to form a cylindrical surface having an axis collinear with the central axis. This centrifugally displaced lubricant provides restoring forces to counteract lateral displacement during operation. 4 figures.

Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

PubMed

Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C; Salgado, Humberto

2016-01-01

Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented-in order of decreasing affinity for the catecholamine-by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing-in turn-a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large number of experimental and clinical findings, a major challenge will be to adapt this hypothesis to integrate the role of other neurotransmitters released during stress in a centralized fashion, like serotonin, acetylcholine, and histamine, as well as those released in a non-centralized fashion, like purines and cytokines.

Recreation and tourism in south-central Alaska: patterns and prospects.

Treesearch

Steve Colt; Stephanie Martin; Jenna Mieren; Martha Tomeo

2002-01-01

Based on data from various sources, this report describes the extent and nature of recreation and tourism in south-central Alaska. Current activities, past trends, and prospective developments are presented. Particular attention is given to activities that occur on, or are directly affected by management of, the Chugach National Forest. Recreation and tourism in and...

Alcohol, Sex and Illegal Activities: An Analysis of Selected Facebook Central Photos in Fifty States

ERIC Educational Resources Information Center

Watson, Sandy White; Smith, Zachary; Driver, Jennifer

2006-01-01

The purpose of this research study was to evaluate the central photos of 150 students in 50 states participating in Facebook for evidence of alcohol consumption, illegal activities and portrayal of sexually inappropriate behaviors (including nudity or partial nudity). Because the media has frequently reported evidence of these behaviors in…

Calculation of regional geomorphic indices to constrain the mechanisms of tectonic uplift and active deformation of the Island of Puerto Rico

NASA Astrophysics Data System (ADS)

Martinez, S.

2016-12-01

The island of Puerto Rico in the northern Caribbean covers an area of about 14,000 km2 and is 180 km long and 65 km wide and is densely populated by 3.4 million persons. The island is mountainous with an east-west-trending, central mountain range with its highest point of 1338 m in the geographic center of the island. Previous workers have suggested that the origin of this east-west, Central Cordillera is active uplift and folding of a large, east-west-trending anticline whose fold axis is coincident with the topographic crest of the Cordillera Central. The folding mechanism has been attributed by previous workers to obliquely-subducting slabs of the North American and Caribbean plates beneath the island. To test the hypothesis that this topographic and structural axis is also the axis of active topographic uplift, I created a knickpoint density map for the island based on over 50 different river systems to reveal areas of active uplift. The knickpoint map shows an excellent correlation with the proposed arch both in width and trend of the axis and supports the conclusion that the arch is the main axis of active uplift on the Island. I also calculated geomorphic indices for 21 different watersheds of the island that include the Hypsometric Integral and a Stream Length Gradient Index that both assess tectonic activity based on stream and watershed behaviors. The Hack index and Hypsometric Integral show that the most active area of uplift is located in the central and north-central parts of the island that include about one half of the length of the proposed, east-west-trending arch. The two topographically-elevated ends of the arch in the western and eastern parts of the island are less active, according to the indices. Lower values in these areas may be influenced by higher amounts of precipitations in these areas.

Perceptual load-dependent neural correlates of distractor interference inhibition.

PubMed

Xu, Jiansong; Monterosso, John; Kober, Hedy; Balodis, Iris M; Potenza, Marc N

2011-01-18

The load theory of selective attention hypothesizes that distractor interference is suppressed after perceptual processing (i.e., in the later stage of central processing) at low perceptual load of the central task, but in the early stage of perceptual processing at high perceptual load. Consistently, studies on the neural correlates of attention have found a smaller distractor-related activation in the sensory cortex at high relative to low perceptual load. However, it is not clear whether the distractor-related activation in brain regions linked to later stages of central processing (e.g., in the frontostriatal circuits) is also smaller at high rather than low perceptual load, as might be predicted based on the load theory. We studied 24 healthy participants using functional magnetic resonance imaging (fMRI) during a visual target identification task with two perceptual loads (low vs. high). Participants showed distractor-related increases in activation in the midbrain, striatum, occipital and medial and lateral prefrontal cortices at low load, but distractor-related decreases in activation in the midbrain ventral tegmental area and substantia nigra (VTA/SN), striatum, thalamus, and extensive sensory cortices at high load. Multiple levels of central processing involving midbrain and frontostriatal circuits participate in suppressing distractor interference at either low or high perceptual load. For suppressing distractor interference, the processing of sensory inputs in both early and late stages of central processing are enhanced at low load but inhibited at high load.

Central insulin-mediated regulation of hepatic glucose production [Review].

PubMed

Inoue, Hiroshi

2016-01-01

Insulin controls hepatic glucose production (HGP) and maintains glucose homeostasis through the direct action of hepatic insulin receptors, as well as the indirect action of insulin receptors in the central nervous system. Insulin acts on insulin receptors in the hypothalamic arcuate nucleus, activates ATP-sensitive potassium channels in a phosphoinositide 3-kinase (PI3K)-dependent manner, induces hyperpolarization of the hypothalamic neurons, and regulates HGP via the vagus nerve. In the liver, central insulin action augments IL-6 expression in Kupffer cells and activates STAT3 transcription factors in hepatocytes. Activated STAT3 suppresses the gene expression of gluconeogenic enzymes, thereby reducing HGP. It has become evident that nutrients such as glucose, fatty acids, and amino acids act upon the hypothalamus together with insulin, affecting HGP. On the other hand, HGP control by central insulin action is impeded in obesity and impeded by insulin resistance due to disturbance of PI3K signaling and inflammation in the hypothalamus or inhibition of STAT3 signaling in the liver. Although the mechanism of control of hepatic gluconeogenic gene expression by central insulin action is conserved across species, its importance in human glucose metabolism has not been made entirely clear and its elucidation is anticipated in the future.

Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.

PubMed

Douris, Nicholas; Stevanovic, Darko M; Fisher, Ffolliott M; Cisu, Theodore I; Chee, Melissa J; Nguyen, Ngoc L; Zarebidaki, Eleen; Adams, Andrew C; Kharitonenkov, Alexei; Flier, Jeffrey S; Bartness, Timothy J; Maratos-Flier, Eleftheria

2015-07-01

Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis.

Activation-induced cytidine deaminase (AID) expression in human B-cell precursors is essential for central B-cell tolerance

PubMed Central

Cantaert, Tineke; Schickel, Jean-Nicolas; Bannock, Jason M.; Ng, Yen-Shing; Massad, Christopher; Oe, Tyler; Wu, Renee; Lavoie, Aubert; Walter, Jolan E.; Notarangelo, Luigi D.; Al-Herz, Waleed; Kilic, Sara Sebnem; Ochs, Hans D.; Nonoyama, Shigeaki; Durandy, Anne; Meffre, Eric

2015-01-01

SUMMARY Activation-induced cytidine deaminase (AID), the enzyme mediating class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B-cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID+ immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B-cell intrinsic AID expression mediates central B-cell tolerance potentially through its RAG-coupled genotoxic activity in self-reactive immature B cells. PMID:26546282

REMOVING COOL CORES AND CENTRAL METALLICITY PEAKS IN GALAXY CLUSTERS WITH POWERFUL ACTIVE GALACTIC NUCLEUS OUTBURSTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo Fulai; Mathews, William G., E-mail: fulai@ucolick.or

2010-07-10

Recent X-ray observations of galaxy clusters suggest that cluster populations are bimodally distributed according to central gas entropy and are separated into two distinct classes: cool core (CC) and non-cool core (NCC) clusters. While it is widely accepted that active galactic nucleus (AGN) feedback plays a key role in offsetting radiative losses and maintaining many clusters in the CC state, the origin of NCC clusters is much less clear. At the same time, a handful of extremely powerful AGN outbursts have recently been detected in clusters, with a total energy {approx}10{sup 61}-10{sup 62} erg. Using two-dimensional hydrodynamic simulations, we showmore » that if a large fraction of this energy is deposited near the centers of CC clusters, which is likely common due to dense cores, these AGN outbursts can completely remove CCs, transforming them to NCC clusters. Our model also has interesting implications for cluster abundance profiles, which usually show a central peak in CC systems. Our calculations indicate that during the CC to NCC transformation, AGN outbursts efficiently mix metals in cluster central regions and may even remove central abundance peaks if they are not broad enough. For CC clusters with broad central abundance peaks, AGN outbursts decrease peak abundances, but cannot effectively destroy the peaks. Our model may simultaneously explain the contradictory (possibly bimodal) results of abundance profiles in NCC clusters, some of which are nearly flat, while others have strong central peaks similar to those in CC clusters. A statistical analysis of the sizes of central abundance peaks and their redshift evolution may shed interesting insights on the origin of both types of NCC clusters and the evolution history of thermodynamics and AGN activity in clusters.« less

Seismic imaging of the geodynamic activity at the western Eger rift in central Europe

NASA Astrophysics Data System (ADS)

Mullick, N.; Buske, S.; Hrubcova, P.; Ruzek, B.; Shapiro, S.; Wigger, P.; Fischer, T.

2015-04-01

The western Eger rift at the Czech-German border in central Europe is an important geodynamically active area within the European Cenzoic rift system (ECRS) in the forelands of the Alps. Along with two other active areas of the ECRS, the French Massif Central and the east and west Eifel volcanic fields, it is characterized by numerous CO2-rich fluid emission points and frequent micro-seismicity. Existence of a plume(s) is indicated in the upper mantle which may be responsible for these observations. Here we reprocess a pre-existing deep seismic reflection profile '9HR' and interpret the subsurface structures as mapped by seismic reflectivity with previous findings, mainly from seismological and geochemical studies, to investigate the geodynamic activity in the subsurface. We find prominent hints of pathways which may allow magmatic fluids originating in the upper mantle to rise through the crust and cause the observed fluid emanations and earthquake activity.

IκB kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-κB in the central nervous system

PubMed Central

Raasch, Jenni; Zeller, Nicolas; van Loo, Geert; Merkler, Doron; Mildner, Alexander; Erny, Daniel; Knobeloch, Klaus-Peter; Bethea, John R.; Waisman, Ari; Knust, Markus; Del Turco, Domenico; Deller, Thomas; Blank, Thomas; Priller, Josef; Brück, Wolfgang

2011-01-01

The IκB kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, IκB kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific IκB kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by conditional ablation of IκB kinase 2 resulted in strong preservation of central nervous system myelin, reduced expression of proinflammatory mediators and a significantly attenuated glial response. Importantly, IκB kinase 2 depletion in astrocytes, but not in oligodendrocytes, was sufficient to protect mice from myelin loss. Our results reveal a crucial role of glial cell-specific IκB kinase 2/nuclear factor kappa B signalling for oligodendrocyte damage during toxic demyelination. Thus, therapies targeting IκB kinase 2 function in non-neuronal cells may represent a promising strategy for the treatment of distinct demyelinating central nervous system diseases. PMID:21310728

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism

PubMed Central

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Learning points: Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty. Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH. Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function. PMID:28721217

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism.

PubMed

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier; Mercado, Moisés

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.

Integrating natural disturbances and management activities to examine risks and opportunities in the central Oregon landscape analysis

Treesearch

Miles A. Hemstrom; James Merzenich; Theresa Burcsu; Janet Ohmann; Ryan Singleton

2010-01-01

We used state and transition models to integrate natural disturbances and management activities for a 275 000-ha landscape in the central Oregon Cascades. The landscape consists of a diverse mix of land ownerships, land use allocations, and environments. Three different management scenarios were developed from public input: (1) no management except wildfire suppression...

Augmented Central Pain Processing in Vulvodynia

PubMed Central

Hampson, Johnson P.; Reed, Barbara D.; Clauw, Daniel J.; Bhavsar, Rupal; Gracely, Richard H.; Haefner, Hope K.; Harris, Richard E.

2013-01-01

Vulvodynia (VVD) is a chronic pain disorder, wherein women display sensitivity to evoked stimuli at the vulva and/or spontaneous vulvar pain. Our previous work suggests generalized hyperalgesia in this population, however little is known about central neurobiological factors that may influence pain in VVD. Here we investigated local (vulvar) and remote (thumb) pressure evoked pain processing in 24 VVD patients compared to 13 age-matched, pain-free healthy controls (HC). As a positive control we also examined thumb pressure pain in 24 fibromyalgia (FM) patients. The VVD and FM patients displayed overlapping insular brain activations that were greater than HC, in response to thumb stimulation (P<0.005 corrected). Compared to HC, VVD participants displayed greater levels of activation during thumb stimulation within the insula, dorsal mid-cingulate, posterior cingulate and thalamus (P<0.005 corrected). Significant differences between VVD subgroups (primary versus secondary and provoked versus unprovoked) were seen within the posterior cingulate with thumb stimulation, and within the precuneus region with vulvar stimulation (provoked versus unprovoked only). The augmented brain activation in VVD patients in response to a stimulus remote from the vulva suggests central neural pathology in this disorder. Moreover, differing central activity between VVD subgroups suggests heterogeneous pathologies within this diagnosis. PMID:23578957

Cardiac Impairment Evaluated by Transesophageal Echocardiography and Invasive Measurements in Rats Undergoing Sinoaortic Denervation

PubMed Central

Sirvente, Raquel A.; Irigoyen, Maria C.; Souza, Leandro E.; Mostarda, Cristiano; La Fuente, Raquel N.; Candido, Georgia O.; Souza, Pamella R. M.; Medeiros, Alessandra; Mady, Charles; Salemi, Vera M. C.

2014-01-01

Background Sympathetic hyperactivity may be related to left ventricular (LV) dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE) using intracardiac echocardiographic catheter. Methods and Results We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD). The rats (n = 32) were divided into 4 groups: 16 Wistar (W) with (n = 8) or without SAD (n = 8) and 16 spontaneously hypertensive rats (SHR) with (n = 8) or without SAD (SHRSAD) (n = 8). Blood pressure (BP) and heart rate (HR) did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV) concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV) pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. Conclusions Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease. PMID:24828834

On the origins of sex-based differences in respiratory disorders: Lessons and hypotheses from stress neuroendocrinology in developing rats.

PubMed

Rousseau, Jean-Philippe; Tenorio-Lopes, Luana; Baldy, Cécile; Janes, Tara Adele; Fournier, Stéphanie; Kinkead, Richard

2017-11-01

The environment plays a critical role in shaping development and function of the brain. Stress, especially when experienced early in life, can interfere with these processes. In the context of respiratory control, perinatal stress can therefore alter the ability to achieve the "fine-tuning" necessary for proper detection of chemosensory stimuli and production of an adequate motor (respiratory) command. Depending on the timing, intensity, and duration, the detrimental consequences of perinatal exposure to adverse conditions on the respiratory network become manifest at various life stages and can persist into adulthood. During early life, respiratory diseases commonly associated with dysfunction of neural networks include apnea of prematurity (AOP) and cardio-respiratory failure leading to sudden infant death syndrome (SIDS). Sleep disordered breathing (SDB) can occur at various life stages, including adulthood. Regardless of age, a common element of these disorders is their greater prevalence in males. While this sexual dimorphism points to a potential role of sex hormones, our understanding of the neuroendocrine mechanisms remain poorly understood. In addition to their modulatory influence on breathing, gonadal hormones regulate sexual differentiation of the brain. Stress alters these effects, and over the years our laboratory has used various perinatal stress protocols to gain insight into the origins of sex-based differences in respiratory disorders. This review discusses our recent advances with a focus on the sex-specific impact of early life stress on O 2 -chemoreflex function both in newborn and adult rats. We conclude by discussing the basic principles emerging from this work, potential mechanisms, and clinical relevance. Copyright © 2017 Elsevier B.V. All rights reserved.

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

PubMed

Brutsaert, Tom D; Parra, Esteban J; Shriver, Mark D; Gamboa, Alfredo; Rivera-Ch, Maria; León-Velarde, Fabiola

2005-07-01

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

Time of day affects the frequency and duration of breathing events and the critical closing pressure during NREM sleep in participants with sleep apnea.

PubMed

El-Chami, Mohamad; Shaheen, David; Ivers, Blake; Syed, Ziauddin; Badr, M Safwan; Lin, Ho-Sheng; Mateika, Jason H

2015-09-15

We investigated if the number and duration of breathing events coupled to upper airway collapsibility were affected by the time of day. Male participants with obstructive sleep apnea completed a constant routine protocol that consisted of sleep sessions in the evening (10 PM to 1 AM), morning (6 AM to 9 AM), and afternoon (2 PM to 5 PM). On one occasion the number and duration of breathing events was ascertained for each sleep session. On a second occasion the critical closing pressure that demarcated upper airway collapsibility was determined. The duration of breathing events was consistently greater in the morning compared with the evening and afternoon during N1 and N2, while an increase in event frequency was evident during N1. The critical closing pressure was increased in the morning (2.68 ± 0.98 cmH2O) compared with the evening (1.29 ± 0.91 cmH2O; P ≤ 0.02) and afternoon (1.25 ± 0.79; P ≤ 0.01). The increase in the critical closing pressure was correlated to the decrease in the baseline partial pressure of carbon dioxide in the morning compared with the afternoon and evening (r = -0.73, P ≤ 0.005). Our findings indicate that time of day affects the duration and frequency of events, coupled with alterations in upper airway collapsibility. We propose that increases in airway collapsibility in the morning may be linked to an endogenous modulation of baseline carbon dioxide levels and chemoreflex sensitivity (12), which are independent of the consequences of sleep apnea.

Physical Activity is Related to Fatty Liver Marker in Obese Youth, Independently of Central Obesity or Cardiorespiratory Fitness

PubMed Central

Martins, Clarice; Aires, Luisa; Júnior, Ismael Freitas; Silva, Gustavo; Silva, Alexandre; Lemos, Luís; Mota, Jorge

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent complications associated with excess adiposity and has been identified as the leading cause of liver disease in pediatric populations worldwide. Because cardiorespiratory fitness (CRF) is related to physical activity (PA) levels, and increased PA plays a protective role against NAFLD risk factors, the aim of this study was to analyze the association between PA and a fatty liver marker (alanine aminotransferase - ALT) in obese children and adolescents, independently of central adiposity or CRF. 131 obese children (83 girls, 7-15 year-olds) involved in a PA promotion program comprised the sample. Measurements included anthropometric and body composition evaluations (DEXA), biological measurements (venipuncture), CRF (progressive treadmill test), PA (accelerometry), and maturational stage (Tanner criteria). The associations between ALT with PA intensities, central obesity, and CRF were calculated by three different models of linear regression, adjusted for potential confounders. Level of significance was set at 95%. RESULTS: ALT was negatively associated with MVPA (β = -0.305), and CRF (β = -0.426), and positively associated with central obesity (β=.468). After adjustment for central obesity the negative and statistically significant association between ALT with MVPA (β = -0.364) and CRF (β = -0.550) still persists while a positive and significantly correlation was shown between ALT and SB (β = 0.382). Additional adjustment for CRF (Model 3) showed significant associations for all the PA intensities analyzed including light activity. PA at different intensities is associated to a fatty liver marker in obese children and adolescents, independently of central adiposity or CRF. Key points In a previous study our group observed that there might be a potential protective effect of cardiorespiratory fitness (CRF) against abnormal ALT values; Considering that CRF is related to physical activity (PA), and increased PA plays a protective role against fatty liver, we hypothesized that it might be an association between PA and fatty liver in obese youth, independently of central adiposity or CRF; No other study has investigated these associations in obese youth; Our findings stresses the fact that moderate-to-vigorous and light physical activities, as well as lower sedentary behavior, is associated with lower fatty liver marker, independent of the effect of potential mediators, such as central obesity or CRF. PMID:25729297

Volcanoes in Central Java, Indonesia

NASA Technical Reports Server (NTRS)

1991-01-01

The Indonesian island of Java (8.0S, 112.0) has over 35 active volcanoes, some of which are the most explosive in the world, and form an east/west line of peaks the length of the island. Five are in this image and at least one is thought to be currently active. The plume flowing north from Welirang (just east of the central cloud mass) is believed to be steam emissions. Also, the lack of vegetation at the peak indicates volcanic activity.

Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury (Addendum)

DTIC Science & Technology

2016-03-01

AD_________________ Award Number: W81XWH-12-1-0051 TITLE: Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the...Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury 5a. CONTRACT NUMBER...incapable of axon regeneration . There are currently two principal concepts that form the basis of our understanding of the inability of the mature

Seattle Central Questions: Institutional and Educational Effectiveness, 2001.

ERIC Educational Resources Information Center

Bystrom, Valerie, Ed.; Kempen, Laurie, Ed.

2001-01-01

The aim of this newsletter, published twice a year by the office of Institutional Planning and Research at Seattle Central Community College (Washington), is to help Seattle Central faculty and staff gain access to the institutional data they need, and to help them link and integrate their various planning and assessment activities without…

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.

PubMed

Martínez-Sánchez, Noelia; Seoane-Collazo, Patricia; Contreras, Cristina; Varela, Luis; Villarroya, Joan; Rial-Pensado, Eva; Buqué, Xabier; Aurrekoetxea, Igor; Delgado, Teresa C; Vázquez-Martínez, Rafael; González-García, Ismael; Roa, Juan; Whittle, Andrew J; Gomez-Santos, Beatriz; Velagapudi, Vidya; Tung, Y C Loraine; Morgan, Donald A; Voshol, Peter J; Martínez de Morentin, Pablo B; López-González, Tania; Liñares-Pose, Laura; Gonzalez, Francisco; Chatterjee, Krishna; Sobrino, Tomás; Medina-Gómez, Gema; Davis, Roger J; Casals, Núria; Orešič, Matej; Coll, Anthony P; Vidal-Puig, Antonio; Mittag, Jens; Tena-Sempere, Manuel; Malagón, María M; Diéguez, Carlos; Martínez-Chantar, María Luz; Aspichueta, Patricia; Rahmouni, Kamal; Nogueiras, Rubén; Sabio, Guadalupe; Villarroya, Francesc; López, Miguel

2017-07-05

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Signal transduction of aortic and carotid sinus baroreceptors is not modified by central command during spontaneous motor activity in decerebrate cats.

PubMed

Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan

2014-05-15

Our laboratory has suggested that central command provides selective inhibition of the cardiomotor component of aortic baroreflex at the start of exercise, preserving carotid sinus baroreflex. It is postulated that central command may modify the signal transduction of aortic baroreceptors, so as to decrease aortic baroreceptor input to the cardiovascular centers, and, thereby, can cause the selective inhibition of aortic baroreflex. To test the hypothesis, we directly analyzed the responses in multifiber aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity in decerebrate, paralyzed cats. The increases of 62-104% in mean AoNA and CsNA were found during spontaneous motor activity, in proportion to a rise of 35 ± 3 mmHg (means ± SE) in mean arterial blood pressure (MAP), and had an attenuating tendency by restraining heart rate (HR) at the lower intrinsic frequency of 154 ± 6 beats/min. Brief occlusion of the abdominal aorta was conducted before and during spontaneous motor activity to produce a mechanically evoked increase in MAP and, thereby, to examine the stimulus-response relationship of arterial baroreceptors. Although the sensitivity of the MAP-HR baroreflex curve was markedly blunted during spontaneous motor activity, the stimulus-response relationships of AoNA and CsNA were not influenced by spontaneous motor activity, irrespective of the absence or presence of the HR restraint. Thus, it is concluded that aortic and carotid sinus baroreceptors can code beat-by-beat blood pressure during spontaneous motor activity in decerebrate cats and that central command is unlikely to modulate the signal transduction of arterial baroreceptors. Copyright © 2014 the American Physiological Society.

Central Plateau Cleanup at DOE's Hanford Site - 12504

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dowell, Jonathan

The discussion of Hanford's Central Plateau includes significant work in and around the center of the Hanford Site - located about 7 miles from the Columbia River. The Central Plateau is the area to which operations will be shrunk in 2015 when River Corridor cleanup is complete. This work includes retrieval and disposal of buried waste from miles of trenches; the cleanup and closure of massive processing canyons; the clean-out and demolition to 'slab on grade' of the high-hazard Plutonium Finishing Plant; installation of key groundwater treatment facilities to contain and shrink plumes of contaminated groundwater; demolition of all othermore » unneeded facilities; and the completion of decisions about remaining Central Plateau waste sites. A stated goal of EM has been to shrink the footprint of active cleanup to less than 10 square miles by 2020. By the end of FY2011, Hanford will have reduced the active footprint of cleanup by 64 percent exceeding the goal of 49 percent. By 2015, Hanford will reduce the active footprint of cleanup by more than 90 percent. The remaining footprint reduction will occur between 2015 and 2020. The Central Plateau is a 75-square-mile region near the center of the Hanford Site including the area designated in the Hanford Comprehensive Land Use Plan Environmental Impact Statement (DOE 1999) and Record of Decision (64 FR 61615) as the Industrial-Exclusive Area, a rectangular area of about 20 square miles in the center of the Central Plateau. The Industrial-Exclusive Area contains the 200 East and 200 West Areas that have been used primarily for Hanford's nuclear fuel processing and waste management and disposal activities. The Central Plateau also encompasses the 200 Area CERCLA National Priorities List site. The Central Plateau has a large physical inventory of chemical processing and support facilities, tank systems, liquid and solid waste disposal and storage facilities, utility systems, administrative facilities, and groundwater monitoring wells. As a companion to the Hanford Site Cleanup Completion Framework document, DOE issued its draft Central Plateau Cleanup Completion Strategy in September 2009 to provide an outline of DOE's vision for completion of cleanup activities across the Central Plateau. As major elements of the Hanford cleanup along the Columbia River Corridor near completion, DOE believed it appropriate to articulate the agency vision for the remainder of the cleanup mission. The Central Plateau Cleanup Completion Strategy and the Hanford Site Cleanup Completion Framework were provided to the regulatory community, the Tribal Nations, political leaders, the public, and Hanford stakeholders to promote dialogue on Hanford's future. The Central Plateau Cleanup Completion Strategy describes DOE's vision for completion of Central Plateau cleanup and outlines the decisions needed to achieve the vision. The Central Plateau strategy involves steps to: (1) contain and remediate contaminated groundwater, (2) implement a geographic cleanup approach that guides remedy selection from a plateau-wide perspective, (3) evaluate and deploy viable treatment methods for deep vadose contamination to provide long-term protection of the groundwater, and (4) conduct essential waste management operations in coordination with cleanup actions. The strategy will also help optimize Central Plateau readiness to use funding when it is available upon completion of River Corridor cleanup projects. One aspect of the Central Plateau strategy is to put in place the process to identify the final footprint for permanent waste management and containment of residual contamination within the 20-square-mile Industrial-Exclusive Area. The final footprint identified for permanent waste management and containment of residual contamination should be as small as practical and remain under federal ownership and control for as long as a potential hazard exists. Outside the final footprint, the remainder of the Central Plateau will be available for other uses consistent with the Hanford Comprehensive Land-Use Plan (DOE 1999), while maintained under federal ownership and control. (author)« less

Arterial Pulse Pressure and Its Association With Reduced Stroke Volume During Progressive Central Hypovolemia

DTIC Science & Technology

2006-09-01

NM, Joyner MJ. Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans. Am J Physiol Heart Circ Physiol...Arterial Pulse Pressure and Its Association With Reduced Stroke Volume During Progressive Central Hypovolemia Victor A. Convertino, PhD, William H...reduction of SV and change in MSNA during graded central hypovolemia in humans. Methods: After a 12-minute baseline data collection period, 13 men were

Sleepiness and activity in heart failure patients with reduced ejection fraction and central sleep-disordered breathing.

PubMed

Atalla, Angela; Carlisle, Thomas W; Simonds, Anita K; Cowie, Martin R; Morrell, Mary J

2017-06-01

Patients with heart failure (HF) and sleep disordered breathing (SDB) are typically not sleepy, unlike patients without heart failure. Previous work in HF patients with obstructive SDB suggested that sleepiness was associated with a reduction in daytime activity. The consequences of predominately central SDB on sleepiness in HF are less well understood. The aim of this study was to test the hypothesis that subjective sleepiness is associated with reduced daytime activity in HF patients with central SDB, compared to those without SDB. The Epworth Sleepiness Scale (ESS), nocturnal polysomnography, and 14 days of wrist watch actigraphy were used to assess subjective daytime sleepiness, nocturnal sleep and breathing, and 24-h activity levels, respectively. A total of 54 patients with HF were studied, nine had obstructive SDB and were removed from further analysis. Of the patients, 23 had HF with predominantly central SDB (HF-CSA; apnea-hypopnea index (AHI) median 20.6 (IQR 12.9-40.2)/h), and 22 had noSDB (HF-noSDB; AHI 3.7 (2.5-5.9)/h). The median patient age was 68 years (range 59-73 years). There were no significant differences either in ESS score (HF-CSA; 8 [4-10] vs. HF-noSDB; 8 (6-12); p = 0.49) or in duration of daytime activity (HF-CSA 14.5 (14.1-15.2) and HF-noSDB 15.1 (14.4-15.3) hours; p = 0.10) between the groups. HF patients with predominately central SDB are not subjectively sleepy compared to those without SDB, despite reduced sleep quality. We speculate that the lack of sleepiness (based on ESS score) may be due to increased sympathetic nerve activity, although further studies are needed due to the small number (n = 5) of sleepy HF-CSA patients. Daytime activity was not different between HF-noSDB and HF-CSA patients. Copyright © 2017. Published by Elsevier B.V.

Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity.

PubMed

Abid, Mohd; Hrishikeshavan, H J; Asad, Mohammed

2006-01-01

The research work deals with the screening of ethanol and chloroform extracts of Pachyrrhizus erosus seeds for central nervous system (CNS) depressant activity. The Pachyrrhizus erosus seed is known to contain rotinoids, flavonoids and phenylfuranocoumarin derivatives as chemical components and is reported to have antifungal, antisecretory, insecticides, antibacterial and spasmolytic activity. Since seeds of Pachyrrhizus erosus is used as folk medicine in treatment of insomnia, we made an attempt to study its CNS depressant effect. The different activities studied were potentiation of pentobarbitone-induced sleep, test for locomotor activity, effect on muscle co-ordination, antiaggressive and antianxiety activities. The result of the study reflected that ethanol extract of the seeds (150 mg/kg, p.o) decreased locomotor activity, produced muscle relaxation and showed antianxiety and antiaggressive activity.

Perceptual Load-Dependent Neural Correlates of Distractor Interference Inhibition

PubMed Central

Xu, Jiansong; Monterosso, John; Kober, Hedy; Balodis, Iris M.; Potenza, Marc N.

2011-01-01

Background The load theory of selective attention hypothesizes that distractor interference is suppressed after perceptual processing (i.e., in the later stage of central processing) at low perceptual load of the central task, but in the early stage of perceptual processing at high perceptual load. Consistently, studies on the neural correlates of attention have found a smaller distractor-related activation in the sensory cortex at high relative to low perceptual load. However, it is not clear whether the distractor-related activation in brain regions linked to later stages of central processing (e.g., in the frontostriatal circuits) is also smaller at high rather than low perceptual load, as might be predicted based on the load theory. Methodology/Principal Findings We studied 24 healthy participants using functional magnetic resonance imaging (fMRI) during a visual target identification task with two perceptual loads (low vs. high). Participants showed distractor-related increases in activation in the midbrain, striatum, occipital and medial and lateral prefrontal cortices at low load, but distractor-related decreases in activation in the midbrain ventral tegmental area and substantia nigra (VTA/SN), striatum, thalamus, and extensive sensory cortices at high load. Conclusions Multiple levels of central processing involving midbrain and frontostriatal circuits participate in suppressing distractor interference at either low or high perceptual load. For suppressing distractor interference, the processing of sensory inputs in both early and late stages of central processing are enhanced at low load but inhibited at high load. PMID:21267080

Influence of Human Activity Patterns, particle composition, and residential air exchange rates on modeled distributions of PM 2.5 exposure compared with central-site monitoring data

EPA Science Inventory

Central-site monitors do not account for factors such as outdoor-to-indoor transport and human activity patterns that influence personal exposures to ambient fine-particulate matter (PM_2.5). We describe and compare different ambient PM_2.5 exposure estimation...

Coordinated Inservice Activities for Health Occupations Teachers in Central Pennsylvania. Final Report. Health Occupations, Monograph Number 6. Vocational-Industrial Education Research Report. Volume 15, Number 16.

ERIC Educational Resources Information Center

Hole, F. Marvin

This report contains a twenty-one page narrative of a project which provided inservice education to health occupations teachers in Central Pennsylvania through four summer workshops as well as the workshop materials. The narrative describes the workshops, which focused on dental assisting activities for health assistant teachers, improvement of…

Landscape scale attributes of elk centers of activity in the central Black Hills of South Dakota

Treesearch

Cynthia H. Stubblefield; Kerri T. Vierling; Mark A. Rumble

2006-01-01

We researched the environmental attributes (n = 28) associated with elk (n = 50) summer range (1 May ­30 Sep) in the central Black Hills of South Dakota, USA, during 1998-­2001. We defined high-use areas or centers of activity as landscapes underlying large concentrations of elk locations resulting from the shared fidelity of...

Anticholinesterase Effects on Number and Function of Brain Muscarinic Receptors and Central Cholinergic Activity: Drug Intervention.

DTIC Science & Technology

1983-09-30

Pathways; GABAergic Pathway; Atropine; Reserpine; Alphamethylparatyrosine; Oxotremorine ; Feedback 20 ABSTRACT (Continue on reverse side It necessary and...see Preface). The purpose was the compare the regional distribution of the effect of anticholinesterases with oxotremorine ),a selective centrally...hippocampus, differently from oxotremorine which was ineffective. In the other two regions, physostigmine and oxotremorine were equally active. At the

Using analogy role-play activity in an undergraduate biology classroom to show central dogma revision.

PubMed

Takemura, Masaharu; Kurabayashi, Mario

2014-01-01

For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego® blocks (Lego System A/S, Denmark). Students were studying in the course of mathematics, physics, or chemistry, so biology was not among their usual studies. In this exercise, students perform the central dogma role-play and respectively act out nuclear matrix proteins, a transcription factor, an RNA polymerase II, an mRNA transport protein, nuclear pore proteins, a large ribosomal subunit, a small ribosomal subunit, and several amino-acyl tRNA synthetases. Questionnaire results obtained after the activity show that this central dogma role-play analogy holds student interest in the practical molecular biological processes of transcription and translation. © 2014 The International Union of Biochemistry and Molecular Biology.

Marriage Matters But How Much? Marital Centrality Among Young Adults.

PubMed

Willoughby, Brian J; Hall, Scott S; Goff, Saige

2015-01-01

Marriage, once a gateway to adulthood, is no longer as widely considered a requirement for achieving adult status. With declining marriage rates and delayed marital transitions, some have wondered whether current young adults have rejected the traditional notion of marriage. Utilizing a sample of 571 young adults, the present study explored how marital centrality (the expected importance to be placed on the marital role relative to other adult roles) functioned as a unique and previously unexplored marital belief among young adults. Results suggested that marriage remains an important role for many young adults. On average, young adults expected that marriage would be more important to their life than parenting, careers, or leisure activities. Marital centrality profiles were found to significantly differ based on both gender and religiosity. Marital centrality was also associated with various outcomes including binge-drinking and sexual activity. Specifically, the more central marriage was expected to be, the less young adults engaged in risk-taking or sexual behaviors.

Watershed Central: Harnessing a social media tool to organize local technical knowledge and find the right watershed resources for your watershed

EPA Science Inventory

Watershed Central was developed to be a bridge between sharing and searching for information relating to watershed issues. This is dependent upon active user support through additions and updates to the Watershed Central Wiki. Since the wiki is user driven, the content and applic...

Expenditure and Revenue Problems in Central-City School Districts: Problems for the 1980s.

ERIC Educational Resources Information Center

Murphy, Joseph F.; Hack, Walter G.

1983-01-01

Investigates the combination of expenditure and revenue problems facing central-city school districts. Examines educational overburden, related overburden, and cost differentials between central city and other types of districts. Also looks at tax capacity and efforts, and analyzes the effects of Federal and State activity on the problems of city…

Measurement and Analysis of Olfactory Responses with the Aim of Establishing an Objective Diagnostic Method for Central Olfactory Disorders

NASA Astrophysics Data System (ADS)

Uno, Tominori; Wang, Li-Qun; Miwakeichi, Fumikazu; Tonoike, Mitsuo; Kaneda, Teruo

In order to establish a new diagnostic method for central olfactory disorders and to identify objective indicators, we measured and analyzed brain activities in the parahippocampal gyrus and uncus, region of responsibility for central olfactory disorders. The relationship between olfactory stimulation and brain response at region of responsibility can be examined in terms of fitted responses (FR). FR in these regions may be individual indicators of changes in brain olfactory responses. In the present study, in order to non-invasively and objectively measure olfactory responses, an odor oddball task was conducted on four healthy volunteers using functional magnetic resonance imaging (fMRI) and a odorant stimulator with blast-method. The results showed favorable FR and activation in the parahippocampal gyrus or uncus in all subjects. In some subjects, both the parahippocampal gyrus and uncus were activated. Furthermore, activation was also confirmed in the cingulate gyrus, middle frontal gyrus, precentral gyrus, postcentral gyrus, superior temporal gyrus and insula. The hippocampus and uncus are known to be involved in the olfactory disorders associated with early-stage Alzheimer's disease and other olfactory disorders. In the future, it will be necessary to further develop the present measurement and analysis method to clarify the relationship between central olfactory disorders and brain activities and establish objective indicators that are useful for diagnosis.

Peripheral input and its importance for central sensitization.

PubMed

Baron, Ralf; Hans, Guy; Dickenson, Anthony H

2013-11-01

Many pain states begin with damage to tissue and/or nerves in the periphery, leading to enhanced transmitter release within the spinal cord and central sensitization. Manifestations of this central sensitization are windup and long-term potentiation. Hyperexcitable spinal neurons show reduced thresholds, greater evoked responses, increased receptive field sizes, and ongoing stimulus-independent activity; these changes probably underlie the allodynia, hyperalgesia, and spontaneous pain seen in patients. Central sensitization is maintained by continuing input from the periphery, but also modulated by descending controls, both inhibitory and facilitatory, from the midbrain and brainstem. The projections of sensitized spinal neurons to the brain, in turn, alter the processing of painful messages by higher centers. Several mechanisms contribute to central sensitization. Repetitive activation of primary afferent C fibers leads to a synaptic strengthening of nociceptive transmission. It may also induce facilitation of non-nociceptive Aβ fibers and nociceptive Aδ fibers, giving rise to dynamic mechanical allodynia and mechanical hyperalgesia. In postherpetic neuralgia and complex regional pain syndrome, for example, these symptoms are maintained and modulated by peripheral nociceptive input. Diagnosing central sensitization can be particularly difficult. In addition to the medical history, quantitative sensory testing and functional magnetic resonance imaging may be useful, but diagnostic criteria that include both subjective and objective measures of central augmentation are needed. Mounting evidence indicates that treatment strategies that desensitize the peripheral and central nervous systems are required. These should generally involve a multimodal approach, so that therapies may target the peripheral drivers of central sensitization and/or the central consequences. © 2013 American Neurological Association.

Low erythrocyte Na/K-pump activity and number in northeast Thailand adults: evidence suggesting an acquired disorder.

PubMed

Tosukhowong, P; Tungsanga, K; Kittinantavorakoon, C; Chaitachawong, C; Pansin, P; Sriboonlue, P; Sitprija, V

1996-07-01

Healthy northeastern Thais have a higher erythrocyte sodium concentration and a lower erythrocyte membrane Na,K-adenosine triphosphatase (ATPase) activity than central Thais. To elucidate whether the defect is hereditary or acquired, we studied plasma sodium and potassium and erythrocyte sodium, potassium, Na,K-ATPase activity, and ouabain-binding sites (OBS) in the following groups: healthy newborns of ethnic central Thais (group 1), healthy newborns of ethnic northeast Thais (group 2), healthy adults of central Thailand ethnicity who lived in the rural central region (group 3) or in Bangkok (group 4), healthy adults of northeast Thailand ethnicity who lived in the rural northeast region (group 5) or who migrated to work in Bangkok for at least 1 year (group 6). Erythrocyte Na was higher in group 2 than in group 1. Group 3 had lower erythrocyte Na,K-ATPase activity than group 4, and it was lower in group 5 than in group 6. Among all groups, group 5 had the highest erythrocyte Na (11.6 mmol/L,F < 0.0001) and the lowest Na,K-ATPase activity (63 mmol Pi/mg x h, F < 0.0001) and erythrocyte OBS (397 sites per cell, F < 0.05) than the other adult groups. There was a positive correlation between erythrocyte Na,K-ATPase and erythrocyte OBS (r = .416, P < .0001). Multiple regression analysis demonstrated a correlation between erythrocyte Na as a dependent variable and erythrocyte OBS, plasma potassium, erythrocyte potassium, and erythrocyte Na,K-ATPase (r = .517, P < .0001). The erythrocyte Na,K-ATPase/OBS ratio, an expression of Na,K-ATPase activity equalized for the number of Na,K-pump units, was lowest among rural adults of the central region (group 3) and the northeast region (group 5) (F < 0.0002). Our data suggest that rural dwellers in Thailand tend to have lower erythrocyte Na,K-ATPase activity than urban dwellers and that this is probably acquired after birth. It was more severe among those from the northeast versus the central region, and was less severe among those who migrated to an urban area. This defect in northeast rural dwellers was probably associated with low numbers of Na,K-pump units and a defect of the pump to express activity, whereas in central rural dwellers it was probably associated with the latter condition. We postulate that there might be circulating Na,K-pump inhibitors and metabolic disturbances that cause attenuation of Na,K-ATPase function and synthesis in the northeast Thailand rural population, and that such substances may have an environmental origin. There may be a relationship between these abnormalities and sudden unexpected deaths.

Coupling corticotropin-releasing-hormone and angiotensin converting enzyme 2 dampens stress responsiveness in male mice.

PubMed

Wang, Lei A; de Kloet, Annette D; Smeltzer, Michael D; Cahill, Karlena M; Hiller, Helmut; Bruce, Erin B; Pioquinto, David J; Ludin, Jacob A; Katovich, Michael J; Raizada, Mohan K; Krause, Eric G

2018-05-01

This study used mice to evaluate whether coupling expression of corticotropin-releasing hormone (CRH) and angiotensin converting enzyme 2 (ACE2) creates central interactions that blunt endocrine and behavioral responses to psychogenic stress. Central administration of diminazene aceturate, an ACE2 activator, had no effect on restraint-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis; however, mice that ubiquitously overexpress ACE2 had reduced plasma corticosterone (CORT) and pituitary expression of POMC mRNA. The Cre-LoxP system was used to restrict ACE2 overexpression to CRH synthesizing cells and probe whether HPA axis suppression was the result of central ACE2 and CRH interactions. Within the paraventricular nucleus of the hypothalamus (PVN), mice with ACE2 overexpression directed to CRH had a ≈2.5 fold increase in ACE2 mRNA, which co-localized with CRH mRNA. Relative to controls, mice overexpressing ACE2 in CRH cells had a decreased CORT response to restraint as well as decreased CRH mRNA in the PVN and CEA and POMC mRNA in the pituitary. Administration of ACTH similarly increased plasma CORT, indicating that the blunted HPA axis activation that accompanies ACE2 overexpression in CRH cells is centrally mediated. Anxiety-like behavior was assessed to determine whether the decreased HPA axis activation was predictive of anxiolysis. Mice with ACE2 overexpression directed to CRH cells displayed decreased anxiety-like behavior in the elevated plus maze and open field when compared to that of controls. Collectively, these results suggest that exogenous ACE2 suppresses CRH synthesis, which alters the central processing of psychogenic stress, thereby blunting HPA axis activation and attenuating anxiety-like behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fluctuations in central and peripheral temperatures induced by intravenous nicotine: central and peripheral contributions

PubMed Central

Tang, Jeremy; Kiyatkin, Eugene A.

2011-01-01

Nicotine (NIC) is a highly addictive substance that interacts with different subtypes of nicotinic acetylcholine receptors widely distributed in the central and peripheral nervous systems. While the direct action of NIC on central neurons appears to be essential for its reinforcing properties, the role of peripheral actions of this drug remains a matter of controversy. In this study, we examined changes in locomotor activity and temperature fluctuations in the brain (nucleus accumbens and ventral tegmental area), temporal muscle, and skin induced by intravenous (iv) NIC at low human-relevant doses (10 and 30 μg/kg) in freely moving rats. These effects were compared to those induced by social interaction, an arousing procedure that induces behavioral activation and temperature responses via pure neural mechanism procedure, and iv injections of a peripherally acting NIC analogue, NIC pyrrolidine methiodide (NIC-PM) used at equimolar doses. We found that NIC at 30 μg/kg induces a modest locomotor activation, rapid and strong decrease in skin temperature, and weak increases in brain and muscle temperature. While these effects were qualitatively similar to those induced by social interaction, they were much weaker and showed a tendency to increase with repeated drug administrations. In contrast, NIC-PM did not affect locomotion and induced much weaker than NIC increases in brain and muscle temperatures and decreases in skin temperature; these effects showed a tendency to be weaker with repeated drug administrations. Our data indicate that NIC's actions in the brain are essential to induce locomotor activation and brain and body hyperthermic responses. However, rapid peripheral action of NIC on sensory afferents could be an important factor in triggering its central effects, contributing to neural and physiological activation following repeated drug use. PMID:21295014

BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

PubMed Central

2012-01-01

Background As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Methods Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. Results The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. Conclusions The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells. PMID:23088614

Stress integration after acute and chronic predator stress: differential activation of central stress circuitry and sensitization of the hypothalamo-pituitary-adrenocortical axis.

PubMed

Figueiredo, Helmer F; Bodie, Bryan L; Tauchi, Miyuki; Dolgas, C Mark; Herman, James P

2003-12-01

Predator exposure is a naturalistic stressor of high ethological relevance. In the current study, our group examined central and peripheral integration of stress responses in rats after acute or repeated exposure to a natural predator (cat). Acute cat exposure rapidly induced hypothalamo-pituitary-adrenocortical (HPA) axis activation and paraventricular nucleus (PVN) CRH mRNA production. Repeated daily cat exposure (7 and 14 d) also up-regulated PVN mRNA CRH expression, but did not result in frank adrenocortical hyperactivity. Unlike other chronic homotypic stress regimens, repeated cat exposure facilitated corticosterone secretion after the 6th or 13th day of exposure. Notably, ACTH secretion and central amygdaloid nucleus CRH mRNA expression were enhanced in animals that were preexposed to the holding chamber relative to chamber-naive rats, suggesting that contextual cues can sensitize subsequent responses to a fearful stimulus. Analysis of c-fos activation was then used to identify brain circuits activated by acute predator stress. Cat exposure elicited a pattern of central c-fos activation that differed substantially from that after either restraint or hypoxia. Predator-specific c-fos mRNA induction was observed in several brain regions comprising the hypothetical brain defense circuit (bed nucleus of the stria terminalis, medial region of the ventromedial nucleus, and dorsal premammillary nucleus). Surprisingly, acute cat exposure did not induce c-fos expression in the PVN. In summary, the data indicate that 1) predation stress invokes a unique stress circuitry that promotes homotypic sensitization of the HPA axis, and 2) familiarization of animals to testing environments can prime central stress pathways to respond robustly to novel threats.

Colorful Central Peak in an Unnamed Crater

NASA Image and Video Library

2011-10-05

The colorful rocks exposed in the central peak visible in this image from NASA Mars Reconnaissance Orbiter probably reflect variations in mineral content that were caused by water activity early in Mars history.

75 FR 76260 - Conforming Changes to Applicant Submission Requirements; Implementing Federal Financial Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

... Report and Central Contractor Registration Requirements AGENCY: Office of the Secretary, HUD. ACTION... that applicants for HUD assistance possess an active Central Contractor Registration (CCR). HUD is...

Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats.

PubMed

Hegarty, Deborah M; Hermes, Sam M; Largent-Milnes, Tally M; Aicher, Sue A

2014-11-01

We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings. Copyright © 2014 Elsevier B.V. All rights reserved.

The increase in fiber size in male rat gastrocnemius after chronic central leptin infusion is related to activation of insulin signaling.

PubMed

Burgos-Ramos, Emma; Canelles, Sandra; Rodríguez, Amaia; Frago, Laura M; Gómez-Ambrosi, Javier; Chowen, Julie A; Frühbeck, Gema; Argente, Jesús; Barrios, Vicente

2018-07-15

Insulin potentiates leptin effects on muscle accrual and glucose homeostasis. However, the relationship between leptin's central effects on peripheral insulin sensitivity and the associated structural changes remain unclear. We hypothesized that central leptin infusion modifies muscle size through activation of insulin signaling. Muscle insulin signaling, enzymes of fatty acid metabolism, mitochondrial respiratory chain complexes, proliferating cell nuclear antigen (PCNA) and fiber area were analyzed in the gastrocnemius of chronic central infused (L), pair-fed (PF) and control rats. PCNA-positive nuclei, fiber area, GLUT4 and glycogen levels and activation of Akt and mechanistic target of rapamycin were increased in L, with no changes in PF. Acetyl-CoA carboxylase-β mRNA levels and non-esterified fatty acid and triglyceride content were reduced and carnitine palmitoyltransferase-1b expression and mitochondrial complexes augmented in L. These results suggest that leptin promotes an increase in muscle size associated with improved insulin signaling favored by lipid profile. Copyright © 2017 Elsevier B.V. All rights reserved.

Topographic mapping of electroencephalography coherence in hypnagogic state.

PubMed

Tanaka, H; Hayashi, M; Hori, T

1998-04-01

The present study examined the topographic characteristics of hypnagogic electroencephalography (EEG), using topographic mapping of EEG power and coherence corresponding to nine EEG stages (Hori's hypnagogic EEG stages). EEG stages 1 and 2, the EEG stages 3-8, and the EEG stage 9 each correspond with standard sleep stage W, 1 and 2, respectively. The dominant topographic components of delta and theta activities increased clearly from the vertex sharp-wave stage (the EEG stages 6 and 7) in the anterior-central areas. The dominant topographic component of alpha 3 activities increased clearly from the EEG stage 9 in the anterior-central areas. The dominant topographic component of sigma activities increased clearly from the EEG stage 8 in the central-parietal area. These results suggested basic sleep process might start before the onset of sleep stage 2 or of the manually scored spindles.

[Relationship between physical activity and hemodynamic parameters in adults].

PubMed

Gómez-Sánchez, L; García-Ortiz, L; Recio-Rodríguez, J I; Patino-Alonso, M C; Agudo-Conde, C; Gómez-Marcos, M A

2015-01-01

To analyze the relationship between physical activity, as assessed by accelerometer, with central and peripheral augmentation index and carotid intima media thickness (IMT) in adults. This study analyzed 263 subjects who were included in the EVIDENT study. Physical activity was assessed during 7 days using the ActigraphGT3X accelerometer (counts/min). Carotid ultrasound was used to measure carotid IMT. The Sphygmo Cor System was used to measure central and peripheral augmentation index (CAIx and PAIx). Mean age 55.85±12 years; 59.30% female; 26.7 body mass index and blood pressure 120/77mmHg. Mean physician activity counts/min was 244.37 and 2.63±10.26min/day of vigorous or very vigorous activity. Physical activity showed an inverse correlation with PAIx (r=-0.179; P<.01) and vigorous activity day time with IMT(r=-0.174; P<.01), CAIx (r=-0.217; P<.01) and PAIx (r=-0.324; P<.01). After adjusting for confounding factors in the multiple regression analysis, the inverse association of CAIx with counts/min and the time spent in vigorous/very vigorous activity was maintained. The results suggest that both physical activity and time spent in vigorous or vigorous activity are associated with the central augmentation index in adults. Copyright © 2015 SEHLELHA. Published by Elsevier Espana. All rights reserved.

Cognitive Activation by Central Thalamic Stimulation: The Yerkes-Dodson Law Revisited.

PubMed Central

Mair, Robert G.; Onos, Kristen D.; Hembrook, Jacqueline R.

2011-01-01

Central thalamus regulates forebrain arousal, influencing activity in distributed neural networks that give rise to organized actions during alert, wakeful states. Central thalamus has been implicated in working memory by the effects of lesions and microinjected drugs in this part of the brain. Lesions and drugs that inhibit neural activity have been found to impair working memory. Drugs that increase activity have been found to enhance and impair memory depending on the dose tested. Electrical deep brain stimulation (DBS) similarly enhances working memory at low stimulating currents and impairs it at higher currents. These effects are time dependent. They were observed when DBS was applied during the memory delay (retention) or choice response (retrieval) but not earlier in trials during the sample (acquisition) phase. The effects of microinjected drugs and DBS are consistent with the Yerkes-Dodson law, which describes an inverted-U relationship between arousal and behavioral performance. Alternatively these results may reflect desensitization associated with higher levels of stimulation, spread of drugs or current to adjacent structures, or activation of less sensitive neurons or receptors at higher DBS currents or drug doses. PMID:22013395

Central command dysfunction in rats with heart failure is mediated by brain oxidative stress and normalized by exercise training.

PubMed

Koba, Satoshi; Hisatome, Ichiro; Watanabe, Tatsuo

2014-09-01

Sympathoexcitation elicited by central command, a parallel activation of the motor and autonomic neural circuits in the brain, has been shown to become exaggerated in chronic heart failure (CHF). The present study tested the hypotheses that oxidative stress in the medulla in CHF plays a role in exaggerating central command-elicited sympathoexcitation, and that exercise training in CHF suppresses central command-elicited sympathoexcitation through its antioxidant effects in the medulla. In decerebrate rats, central command was activated by electrically stimulating the mesencephalic locomotor region (MLR) after neuromuscular blockade. The MLR stimulation at a current intensity greater than locomotion threshold in rats with CHF after myocardial infarction (MI) evoked larger (P < 0.05) increases in renal sympathetic nerve activity and arterial pressure than in sham-operated healthy rats (Sham) and rats with CHF that had completed longterm (8–12 weeks) exercise training (MI + TR). In the Sham and MI + TR rats, bilateral microinjection of a superoxide dismutase (SOD) mimetic Tempol into the rostral ventrolateral medulla (RVLM) had no effects on MLR stimulation-elicited responses. By contrast, in MI rats, Tempol treatment significantly reduced MLR stimulation-elicited responses. In a subset of MI rats, treatment with Tiron, another SOD mimetic, within the RVLM also reduced responses. Superoxide generation in the RVLM, as evaluated by dihydroethidium staining, was enhanced in MI rats compared with that in Sham and MI + TR rats. Collectively, these results support the study hypotheses. We suggest that oxidative stress in the medulla in CHF mediates central command dysfunction, and that exercise training in CHF is capable of normalizing central command dysfunction through its antioxidant effects in the medulla.

Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity.

PubMed

Verhagen, Linda A W; Egecioglu, Emil; Luijendijk, Mieneke C M; Hillebrand, Jacquelien J G; Adan, Roger A H; Dickson, Suzanne L

2011-05-01

Using the rodent activity-based anorexia (ABA) model that mimics clinical features of anorexia nervosa that include food restriction-induced hyperlocomotion, we found that plasma ghrelin levels are highly associated with food anticipatory behaviour, measured by running wheel activity in rats. Furthermore, we showed that ghrelin receptor (GHS-R1A) knockout mice do not anticipate food when exposed to the ABA model, unlike their wild type littermate controls. Likewise, food anticipatory activity in the ABA model was suppressed by a GHS-R1A antagonist administered either by acute central (ICV) injection to rats or by chronic peripheral treatment to mice. Interestingly, the GHS-R1A antagonist did not alter food intake in any of these models. Therefore, we hypothesize that suppression of the central ghrelin signaling system via GHS-R1A provides an interesting therapeutic target to treat hyperactivity in patients suffering from anorexia nervosa. Copyright © 2010. Published by Elsevier B.V.

Improved clinical, functional and work outcomes in spondyloarthritides during real-life adalimumab treatment in central-eastern Europe.

PubMed

Szántó, Sándor; Poór, Gyula; Opris, Daniela; Iaremenko, Oleg; Procházková, Leona; Kuuse, Reet; Nagy, Orsolya; Chernyshov, Valentyn; Géher, Pál

2016-08-01

Adalimumab effectiveness on clinical, functional and work-related outcomes was evaluated in patients with active ankylosing spondylitis or psoriatic arthritis treated in routine clinical practice in central-eastern Europe. Patients (n = 555) were followed for 12 months. Primary end point was percentage of patients with a treatment response (≥50% decrease from baseline in Bath Ankylosing Spondylitis Disease Activity Index or ≥1.2 point decrease from baseline in Disease Activity Index-28 joint for axial or peripheral symptoms, respectively). Functional status was evaluated by the Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire Disability Index. Working ability was evaluated by the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem. 76.1% of patients with axial symptoms and 83.5% with peripheral symptoms achieved a treatment response. Frequency of extra-articular manifestations decreased. Improvements were observed in functional status and workability. No new safety signals were observed. Adalimumab was effective and well tolerated during real-world use in central-eastern Europe.

A Preferentially Segregated Recycling Vesicle Pool of Limited Size Supports Neurotransmission in Native Central Synapses

PubMed Central

Marra, Vincenzo; Burden, Jemima J.; Thorpe, Julian R.; Smith, Ikuko T.; Smith, Spencer L.; Häusser, Michael; Branco, Tiago; Staras, Kevin

2012-01-01

Summary At small central synapses, efficient turnover of vesicles is crucial for stimulus-driven transmission, but how the structure of this recycling pool relates to its functional role remains unclear. Here we characterize the organizational principles of functional vesicles at native hippocampal synapses with nanoscale resolution using fluorescent dye labeling and electron microscopy. We show that the recycling pool broadly scales with the magnitude of the total vesicle pool, but its average size is small (∼45 vesicles), highly variable, and regulated by CDK5/calcineurin activity. Spatial analysis demonstrates that recycling vesicles are preferentially arranged near the active zone and this segregation is abolished by actin stabilization, slowing the rate of activity-driven exocytosis. Our approach reveals a similarly biased recycling pool distribution at synapses in visual cortex activated by sensory stimulation in vivo. We suggest that in small native central synapses, efficient release of a limited pool of vesicles relies on their favored spatial positioning within the terminal. PMID:23141069

Oxytocin receptor antagonist treatments alter levels of attachment to mothers and central dopamine activity in pre-weaning mandarin vole pups.

PubMed

He, Zhixiong; Hou, Wenjuan; Hao, Xin; Dong, Na; Du, Peirong; Yuan, Wei; Yang, Jinfeng; Jia, Rui; Tai, Fadao

2017-10-01

Oxytocin (OT) is known to be important in mother-infant bonding. Although the relationship between OT and filial attachment behavior has been studied in a few mammalian species, the effects on infant social behavior have received little attention in monogamous species. The present study examined the effects of OT receptor antagonist (OTA) treatment on attachment behavior and central dopamine (DA) activity in male and female pre-weaning mandarin voles (Microtus mandarinus). Our data showed that OTA treatments decreased the attachment behavior of pups to mothers, measured using preference tests at postnatal day 14, 16, 18 and 20. OTA treatments reduced serum OT concentration in pre-weaning pups and decreased tyrosine hydroxylase (TH) levels in the ventral tegmental area (VTA), indicating a decrease in central DA activity. In male and female pups, OTA reduced DA levels, DA 1-type receptor (D1R) and DA 2-type receptor (D2R) protein expression in the nucleus accumbens (NAcc). Our results indicate that OTA treatment inhibits the attachment of pre-weaning pups to mothers. This inhibition is possibly associated with central DA activity and levels of two types of dopamine receptor in the NAcc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Photoconductive switch package

DOEpatents

Ca[rasp, George J

2013-10-22

A photoconductive switch is formed of a substrate that has a central portion of SiC or other photoconductive material and an outer portion of cvd-diamond or other suitable material surrounding the central portion. Conducting electrodes are formed on opposed sides of the substrate, with the electrodes extending beyond the central portion and the edges of the electrodes lying over the outer portion. Thus any high electric fields produced at the edges of the electrodes lie outside of and do not affect the central portion, which is the active switching element. Light is transmitted through the outer portion to the central portion to actuate the switch.

Physical activity trends in Queensland (2002 to 2008): are women becoming more active than men?

PubMed

Vandelanotte, Corneel; Duncan, Mitch J; Caperchione, Cristina; Hanley, Christine; Mummery, W Kerry

2010-06-01

Regular monitoring of population levels of physical activity is an effective way to assess change over time towards meeting public health recommendations. The objective of this study was to determine physical activity trends in Central Queensland over the period 2002 to 2008. Data was obtained from the Central Queensland Social Survey (CQSS) conducted annually from 2002 to 2008. A total sample of 8,936 adults aged 18 and over participated in seven cross-sectional surveys. Physical activity was measured using the Active Australia Questionnaire. Binary logistic regression was used to examine trends in sufficient physical activity. Averaged over all survey years 46.5% of study participants met national physical activity guidelines. A small significant upward trend was found for meeting physical activity recommendations across all years (OR=1.03; 95%CI=1.01-1.05), indicating that the odds of meeting the guidelines increased by an average of 3% per year from 2002 to 2008. Slightly more men than women met the activity guidelines (ns); however a significant positive trend in achieving sufficient activity levels was present in women only (4%). Although an increasing trend for sufficient physical activity was observed, overall physical activity levels in Central Queensland remain suboptimal and more efforts to increase physical activity are needed. The gender differences in physical activity trends indicate that men and women might need to be targeted differently in health promotion messages. The continuous monitoring of population levels of physical activity in Australia, which allow both state specific and international comparisons, is needed.

Stagnation pressure activated fuel release mechanism for hypersonic projectiles

DOEpatents

Cartland, Harry E.; Hunter, John W.

2003-01-01

A propulsion-assisted projectile has a body, a cowl forming a combustion section and a nozzle section. The body has a fuel reservoir within a central portion of the body, and a fuel activation system located along the central axis of the body and having a portion of the fuel activation system within the fuel reservoir. The fuel activation system has a fuel release piston with a forward sealing member where the fuel release piston is adapted to be moved when the forward sealing member is impacted with an air flow, and an air-flow channel adapted to conduct ambient air during flight to the fuel release piston.

Maintenance of Mouse Gustatory Terminal Field Organization Is Disrupted following Selective Removal of Peripheral Sodium Salt Taste Activity at Adulthood

PubMed Central

Sun, Chengsan

2017-01-01

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience. SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits. PMID:28676575

Fiesta! Mexico and Central America: A Global Awareness Program for Children in Grades 2-5. Bridges between Nations Series.

ERIC Educational Resources Information Center

Linse, Barbara; Judd, Dick

Mexican and Central American cultures are a blend of Native American influences and Spanish traditions and religions. These are seen in aspects of Mexican and Central American celebrations. This book explores those celebrations through activities in art, folk and classical music, dances and fiestas. The book is organized into two sections to…

A Cooperative Career Education Project Involving the Fayette County Schools, Eastern Kentucky University, and Central Kentucky Vocational Region. Volume I. Final Report.

ERIC Educational Resources Information Center

Jenkins, John D.

The 3-year project was intended to provide for a systematic delivery of career development experiences within each of the three institutions involved--Fayette County Schools, Eastern Kentucky University, and the Central Kentucky Vocational Region--with central activity located in the Fayette County Schools. Major project themes centered on…

Central as well as Peripheral Attentional Bottlenecks in Dual-Task Performance Activate Lateral Prefrontal Cortices

PubMed Central

Szameitat, André J.; Vanloo, Azonya; Müller, Hermann J.

2016-01-01

Human information processing suffers from severe limitations in parallel processing. In particular, when required to respond to two stimuli in rapid succession, processing bottlenecks may appear at central and peripheral stages of task processing. Importantly, it has been suggested that executive functions are needed to resolve the interference arising at such bottlenecks. The aims of the present study were to test whether central attentional limitations (i.e., bottleneck at the decisional response selection stage) as well as peripheral limitations (i.e., bottleneck at response initiation) both demand executive functions located in the lateral prefrontal cortex. For this, we re-analyzed two previous studies, in which a total of 33 participants performed a dual-task according to the paradigm of the psychological refractory period (PRP) during functional magnetic resonance imaging (fMRI). In one study (N = 17), the PRP task consisted of two two-choice response tasks known to suffer from a central bottleneck (CB group). In the other study (N = 16), the PRP task consisted of two simple-response tasks known to suffer from a peripheral bottleneck (PB group). Both groups showed considerable dual-task costs in form of slowing of the second response in the dual-task (PRP effect). Imaging results are based on the subtraction of both single-tasks from the dual-task within each group. In the CB group, the bilateral middle frontal gyri and inferior frontal gyri were activated. Higher activation in these areas was associated with lower dual-task costs. In the PB group, the right middle frontal and inferior frontal gyrus (IFG) were activated. Here, higher activation was associated with higher dual-task costs. In conclusion we suggest that central and peripheral bottlenecks both demand executive functions located in lateral prefrontal cortices (LPFC). Differences between the CB and PB groups with respect to the exact prefrontal areas activated and the correlational patterns suggest that the executive functions resolving interference at least partially differ between the groups. PMID:27014044

Interaction between active tectonics, erosion and diapirism, a case study from Habble-Rud in Southern Central Alborz (Northern Iran)

NASA Astrophysics Data System (ADS)

Jaberi, Maryam; Ghassemi, Mohammad R.; Shayan, Siavosh; Yamani, Mojtaba; Zamanzadeh, Seyed Mohammad

2018-01-01

The Alborz mountain chain is a region of active deformation within the Arabia-Eurasia continental collision zone. The southern part of central Alborz Mountains, in the north of Iran, represents complex tectonics because it is located at the border of two developing continental sedimentary basins between southern central Alborz and Central Iran. An arid and semi-arid climate, a large extent of Quaternary sediments, rugged topography, salt domes and faults with historical seismicity influence the Habble-Rud River catchment. In the present research, a number of tectonic geomorphologic indices were extracted from satellite imagery and 10 m DEM (digital elevation model) data in order to identify relative tectonic activity within the basin. The indices include: stream length-gradient index (Sl), drainage basin asymmetry (Af), index of mountain front sinuosity (Smf), hypsometric integral (Hi), index of drainage basin shape (Bs), ratio of valley-floor width to valley height (Vf), and fault density (Fd). Due to the presence of heterogeneous indices for all sections of the catchment causing large extension of Habble-Rud (3260 km2), all of the variables such as extremely erodible formations, faults and folds and salt tectonics on the Southern part; were put into a matrix table. As a new approach, the variables were put into the SAW (simple additive model) model as one of MADM (multi-attribute decision-making models) techniques. The study area was divided into four regions according to the values of SAW. These classes include very high (%11), high (48.3%), moderate (34.7%), and low activity (3.4%). The result of the model suggests that the study area is located on a changing tectonic trend in central Alborz from NW-SE to NE-SW. The regions with high relative tectonic activity in HR catchment correspond to the active Garmsar and Sorkhe-Kalout faults and diapirs.

Taurine activates strychnine-sensitive glycine receptors in neurons of the rat inferior colliculus.

PubMed

Xu, Han; Zhou, Ke-Qing; Huang, Yi-Na; Chen, Lin; Xu, Tian-Le

2004-09-24

Taurine (Tau) is one of the most abundant free amino acids in the mammalian central nervous system. Whether the neurotransmission of the central auditory system is regulated or modulated by Tau is not clear. In the present study, we investigated the electrophysiological and pharmacological properties of Tau-activated currents in acutely dissociated neurons of the rat inferior colliculus (IC) using whole cell patch clamp recordings. At a holding potential of -60 mV and under a condition of chloride equilibrium potential near 0 mV, Tau activated an inward current and its half-maximal activation concentration was equal to 0.37 mM. The measured reversal potential of Tau-activated currents was close to theoretical chloride equilibrium potential. The currents evoked by Tau at both low (1 mM) and high (10 mM) concentrations were almost completely inhibited by strychnine, a glycine receptor antagonist. The Tau-activated current, however, was not affected by bicuculline, a GABA(A) receptor antagonist. Tau at increased concentrations progressively reduced the current response to subsequent glycine application. At saturated concentrations, Tau-activated current and glycine-activated current were mutually cross-desensitized by each other. These findings indicate that Tau activates glycine receptors in neurons of the rat IC and thus may have a functional role in regulating or modulating the neurotransmission of the central auditory system in mammals.

Central activation, metabolites, and calcium handling during fatigue with repeated maximal isometric contractions in human muscle.

PubMed

Cairns, Simeon P; Inman, Luke A G; MacManus, Caroline P; van de Port, Ingrid G L; Ruell, Patricia A; Thom, Jeanette M; Thompson, Martin W

2017-08-01

To determine the roles of calcium (Ca 2+ ) handling by sarcoplasmic reticulum (SR) and central activation impairment (i.e., central fatigue) during fatigue with repeated maximal voluntary isometric contractions (MVC) in human muscles. Contractile performance was assessed during 3 min of repeated MVCs (7-s contraction, 3-s rest, n = 17). In ten participants, in vitro SR Ca 2+ -handling, metabolites, and fibre-type composition were quantified in biopsy samples from quadriceps muscle, along with plasma venous [K + ]. In 11 participants, central fatigue was compared using tetanic stimulation superimposed on MVC in quadriceps and adductor pollicis muscles. The decline of peak MVC force with fatigue was similar for both muscles. Fatigue resistance correlated directly with % type I fibre area in quadriceps (r = 0.77, P = 0.009). The maximal rate of ryanodine-induced Ca 2+ -release and Ca 2+ -uptake fell by 31 ± 26 and 28 ± 13%, respectively. The tetanic force depression was correlated with the combined reduction of ATP and PCr, and increase of lactate (r = 0.77, P = 0.009). Plasma venous [K + ] increased from 4.0 ± 0.3 to 5.4 ± 0.8 mM over 1-3-min exercise. Central fatigue occurred during the early contractions in the quadriceps in 7 out of 17 participants (central activation ratio fell from 0.98 ± 0.05 to 0.86 ± 0.11 at 1 min), but dwindled at exercise cessation. Central fatigue was seldom apparent in adductor pollicis. Fatigue with repeated MVC in human limb muscles mainly involves peripheral aspects which include impaired SR Ca 2+ -handling and we speculate that anaerobic metabolite changes are involved. A faster early force loss in quadriceps muscle with some participants is attributed to central fatigue.

29 CFR 779.208 - Auxiliary activities which are “related activities.”

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Auxiliary activities which are ârelated activities.â 779...; Enterprise Coverage Related Activities § 779.208 Auxiliary activities which are “related activities.” As... activities, such as central office and warehousing activities and bookkeeping, auditing, purchasing...

Efficacy and mode of action of a noise-sensor light alarm to decrease noise in the pediatric intensive care unit: a prospective, randomized study.

PubMed

Jousselme, Chloé; Vialet, Renaud; Jouve, Elisabeth; Lagier, Pierre; Martin, Claude; Michel, Fabrice

2011-03-01

To determine whether a sound-activated light-alarm device could reduce the noise in the central area of our pediatric intensive care unit and to determine whether this reduction was significant enough to decrease the noise that could be perceived by a patient located in a nearby room. The secondary objective was to determine the mode of action of the device. In a 16-bed pediatric and neonatal intensive care unit, a large and clearly noticeable sound-activated light device was set in the noisiest part of the central area of our unit, and noise measurements were made in the central area and in a nearby room. In a prospective, quasi-experimental design, sound levels were compared across three different situations--no device present, device present and turned on, and device present but turned off--and noise level measurements were made over a total of 18 days. None. Setting a sound-activated light device on or off. When the device was present, the noise was about 2 dB lower in the central area and in a nearby room, but there was no difference in noise level with the device turned on vs. turned off. The noise decrease in the central area was of limited importance but was translated in a nearby room. The sound-activated light device did not directly decrease noise when turned on, but repetition of the visual signal throughout the day raised staff awareness of noise levels over time.

76 FR 75893 - Agency Information Collection Activities: Dominican Republic-Central America-United States Free...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-05

... Republic-Central America-United States Free Trade Agreement with Costa Rica, the Dominican Republic, El Salvador, Guatemala, Honduras, and Nicaragua (also known as CAFTA-DR). The Agreement was approved by...

Central command differentially affects aortic and carotid sinus baroreflexes at the onset of spontaneous motor activity.

PubMed

Matsukawa, Kanji; Ishii, Kei; Idesako, Mitsuhiro; Ishida, Tomoko; Endo, Kana; Liang, Nan

2013-12-01

Our laboratory has recently demonstrated that central command provides selective inhibition of the cardiomotor component of aortic (AOR) baroreflex during exercise, preserving carotid sinus (CS) baroreflex. To further explore the differential effects of central command on the arterial baroreflexes, we surgically separated the AOR and CS baroreflex systems, to identify the input-output relationship of each baroreflex system using brief occlusion of the abdominal aorta in decerebrate cats. Baroreflex sensitivity for heart rate (HR) was estimated from the baroreflex ratio between the pressor and bradycardia responses during aortic occlusion and from the slope of the baroreflex curve between the changes in mean arterial blood pressure (ΔMAP) and ΔHR. Spontaneous motor activity accompanied the abrupt increases in HR and MAP. When aortic occlusion was given at the onset of spontaneous motor activity, the baroreflex ratio was blunted to 11-25% of the preexercise value in either intact or AOR baroreflex. The slope of the ΔMAP-ΔHR curve was similarly attenuated at the onset of spontaneous motor activity to 11-18% of the slope during the preexercise period. In contrast, in the CS baroreflex, the baroreflex ratio and curve slope were not significantly (P>0.05) altered by spontaneous motor activity. An upward shift of the baroreflex curve appeared at the onset of spontaneous motor activity, irrespective of the intact, AOR, and CS baroreflex conditions. Taken together, it is concluded that central command provides selective inhibition for the cardiomotor limb of the aortic baroreflex at the onset of exercise, which in turn contributes to an instantaneous increase in HR. © 2013.

A Conformational Change of the γ Subunit Indirectly Regulates the Activity of Cyanobacterial F1-ATPase*

PubMed Central

Sunamura, Ei-Ichiro; Konno, Hiroki; Imashimizu, Mari; Mochimaru, Mari; Hisabori, Toru

2012-01-01

The central shaft of the catalytic core of ATP synthase, the γ subunit consists of a coiled-coil structure of N- and C-terminal α-helices, and a globular domain. The γ subunit of cyanobacterial and chloroplast ATP synthase has a unique 30–40-amino acid insertion within the globular domain. We recently prepared the insertion-removed α3β3γ complex of cyanobacterial ATP synthase (Sunamura, E., Konno, H., Imashimizu-Kobayashi, M., and Hisabori, T. (2010) Plant Cell Physiol. 51, 855–865). Although the insertion is thought to be located in the periphery of the complex and far from catalytic sites, the mutant complex shows a remarkable increase in ATP hydrolysis activity due to a reduced tendency to lapse into ADP inhibition. We postulated that removal of the insertion affects the activity via a conformational change of two central α-helices in γ. To examine this hypothesis, we prepared a mutant complex that can lock the relative position of two central α-helices to each other by way of a disulfide bond formation. The mutant obtained showed a significant change in ATP hydrolysis activity caused by this restriction. The highly active locked complex was insensitive to N-dimethyldodecylamine-N-oxide, suggesting that the complex is resistant to ADP inhibition. In addition, the lock affected ϵ inhibition. In contrast, the change in activity caused by removal of the γ insertion was independent from the conformational restriction of the central axis component. These results imply that the global conformational change of the γ subunit indirectly regulates complex activity by changing both ADP inhibition and ϵ inhibition. PMID:23012354

Sensitization of trigeminal brainstem pathways in a model for tear deficient dry eye

PubMed Central

Rahman, Mostafeezur; Okamoto, Keiichiro; Thompson, Randall; Katagiri, Ayano; Bereiter, David A.

2015-01-01

Abstract Chronic dry eye disease (DE) is associated with an unstable tear film and symptoms of ocular discomfort. The characteristics of symptoms suggest a key role for central neural processing; however, little is known about central neuroplasticity and DE. We used a model for tear deficient DE and assessed effects on eye blink behavior, orbicularis oculi muscle activity (OOemg), and trigeminal brainstem neural activity in male rats. Ocular-responsive neurons were recorded at the interpolaris/caudalis transition (Vi/Vc) and Vc/upper cervical cord (Vc/C1) regions under isoflurane, whereas OOemg activity was recorded under urethane. Spontaneous tear volume was reduced by ∼50% at 14 days after exorbital gland removal. Hypertonic saline–evoked eye blink behavior in awake rats was enhanced throughout the 14 days after surgery. Saline-evoked neural activity at the Vi/Vc transition and in superficial and deep laminae at the Vc/C1 region was greatly enhanced in DE rats. Neurons from DE rats classified as wide dynamic range displayed enlarged convergent periorbital receptive fields consistent with central sensitization. Saline-evoked OOemg activity was markedly enhanced in DE rats compared with controls. Synaptic blockade at the Vi/Vc transition or the Vc/C1 region greatly reduced hypertonic saline–evoked OOemg activity in DE and sham rats. These results indicated that persistent tear deficiency caused sensitization of ocular-responsive neurons at multiple regions of the caudal trigeminal brainstem and enhanced OOemg activity. Central sensitization of ocular-related brainstem circuits is a significant factor in DE and likely contributes to the apparent weak correlation between peripheral signs of tear dysfunction and symptoms of irritation. PMID:25734990

Active cycling of organic carbon in the central Arctic Ocean

NASA Astrophysics Data System (ADS)

Wheeler, Patricia A.; Gosselin, Michel; Sherr, Evelyn; Thibaultc, Delphine; Kirchman, David L.; Benner, Ronald; Whitledge, Terry E.

1996-04-01

THE notion of a barren central Arctic Ocean has been accepted since English's pioneering work1 on drifting ice-islands. The year-round presence of ice, a short photosynthetic season and low temperatures were thought to severely limit biological production1,2, although the paucity of data was often noted. Because primary production appeared to be low1,2, subsequent studies assumed that most organic carbon was either derived from river inputs or imported from adjacent continental-shelf regions3,4. Here we present shipboard measurements of biological produc-tion, biomass and organic carbon standing-stocks made during a cruise through the ice covering the central Arctic Ocean. Our results indicate that the central Arctic region is not a biological desert. Although it is less productive than oligotrophic ocean regions not covered by ice, it supports an active biological community which contributes to the cycling of organic carbon through dissolved and particulate pools.

Dry needling — peripheral and central considerations

PubMed Central

Dommerholt, Jan

2011-01-01

Dry needling is a common treatment technique in orthopedic manual physical therapy. Although various dry needling approaches exist, the more common and best supported approach targets myofascial trigger points. This article aims to place trigger point dry needling within the context of pain sciences. From a pain science perspective, trigger points are constant sources of peripheral nociceptive input leading to peripheral and central sensitization. Dry needling cannot only reverse some aspects of central sensitization, it reduces local and referred pain, improves range of motion and muscle activation pattern, and alters the chemical environment of trigger points. Trigger point dry needling should be based on a thorough understanding of the scientific background of trigger points, the differences and similarities between active and latent trigger points, motor adaptation, and central sensitize application. Several outcome studies are included, as well as comments on dry needling and acupuncture. PMID:23115475

The dynamics and fueling of active nuclei

NASA Technical Reports Server (NTRS)

Norman, C.; Silk, J.

1983-01-01

It is generally believed that quasars and active galactic nuclei produce their prodigious luminosities in connection with the release of gravitational energy associated with accretion and infall of matter onto a compact central object. In the present analysis, it is assumed that the central object is a massive black hole. The fact that a black hole provides the deepest possible central potential well does imply that it is the most natural candidate for the central engine. It is also assumed that the quasar is associated with the nucleus of a conventional galaxy. A number of difficulties arise in connection with finding a suitable stellar fueling model. A simple scheme is discussed for resolving these difficulties. Attention is given to fueling in a nonaxisymmetric potential, the effects of a massive accretion disk, and the variability in the disk luminosity caused by star-disk collisions assuming that the energy deposited in the disk is radiated.

Qualitative evaluation of the mineralogical and chemical composition of dry deposition in the central and southern highlands of Jordan.

PubMed

Jiries, Anwar; El-Hasan, Tayel; Manasrah, Walid

2002-09-01

The chemical and mineralogical composition of dry deposition in the western highlands of central and south Jordan at the end of the summer season 2000, reflect the composition of soils in addition to anthropogenic activities at these areas. Calcite predominated in the central region whereas calcite and quartz are the dominant minerals in south Jordan. The concentrations of Hg, Cr, Ni, Cu, Pb and Zn were higher in central Jordan, which might be attributed to higher anthropogenic activities than south. On the other hand, Fe, Mn, Ti, Ba, Sr, Y and Rb were higher in the south of Jordan reflecting the composition of soil at these sites. At Aqaba city, the only port of Jordan, where Cr, Cd, As and S were higher than other areas. This variation might be attributed to the contribution of phosphate dust in the atmosphere through handling processes.

The Role of the Central Noradrenergic System in Behavioral Inhibition

PubMed Central

Stone, Eric A.; Lin, Yan; Sarfraz, Yasmeen; Quartermain, David

2011-01-01

Although the central noradrenergic system has been shown to be involved in a number of behavioral and neurophysiological processes, the relation of these to its role in depressive illness has been difficult to define. The present review discusses the hypothesis that one of its chief functions that may be related to affective illness is the inhibition of behavioral activation, a prominent symptom of the disorder. This hypothesis is found to be consistent with most previous neuropsychopharmacological and immunohistochemical experiments on active behavior in rodents in a variety of experimental conditions using manipulation of neurotransmission at both locus coeruleus and forebrain adrenergic receptors. The findings support a mechanism in which high rates of noradrenergic neural activity suppress the neural activity of principal neurons in forebrain regions mediating active behavior. The suppression may be mediated through postsynaptic galaninergic and adrenergic receptors, and via the release of corticotrophin-releasing hormone. The hypothesis is consistent with clinical evidence for central noradrenergic system hyperactivity in depressives and with the view that this hyperactivity is a contributing etiological factor in the disorder. A similar mechanism may underlie the ability of the noradrenergic system to suppress seizure activity suggesting that inhibition of the spread of neural activation may be a unifying function. PMID:21315760

Administration of antioxidant vitamins does not alter plasma fibrinolytic activity in subjects with central obesity.

PubMed

Rifici, V A; Schneider, S H; Chen, Y; Khachadurian, A K

1997-09-01

In vitro studies suggest that oxidized low density lipoprotein inhibits fibrinolysis by stimulating the production of plasminogen activator inhibitor -1 (PAI). We assessed the effects of dietary antioxidant vitamins for four weeks on three indices of copper mediated oxidation of very low and low density lipoproteins (VLDL+LDL) and plasma fibrinolytic activities in 15 male subjects with central obesity, a condition associated with increased PAI activity. Vitamin administration resulted in a decrease in production of thiobarbituric acid reactive substances from 29.3 +/- 3.9 to 13.6 +/- 3.5 nmoles/mg VLDL + LDL protein (mean +/- SE, p <0.003), an increase in the lag phase of conjugated diene formation from 94.8 +/- 5.5 to 225.0 +/- 31.9 min (p <0.001) and an increase in reactivity of lysine residues from 73.6% +/- 4.8% to 86.8% +/- 3.6% (p <0.034) demonstrating a reduction in the susceptibility of the lipoproteins to oxidation. However, antioxidant vitamins had no effect on plasma PAI activity, PAI antigen, tissue-type plasminogen activator activity and antigen, fibrinogen and fibrin degradation products. These results do not support the hypothesis that lipoprotein oxidation is a significant cause of impaired fibrinolysis in men with central obesity.

Differences in meal patterns and timing with regard to central obesity in the ANIBES ('Anthropometric data, macronutrients and micronutrients intake, practice of physical activity, socioeconomic data and lifestyles in Spain') Study.

PubMed

Aparicio, Aránzazu; Rodríguez-Rodríguez, Elena E; Aranceta-Bartrina, Javier; Gil, Ángel; González-Gross, Marcela; Serra-Majem, Lluis; Varela-Moreiras, Gregorio; Ortega, Rosa Maria

2017-09-01

To study the association of meal patterns and timing with central obesity to identify the best dietary strategies to deal with the increasing obesity prevalence. A cross-sectional study performed on data from a representative sample of the Spanish population. Height and waist circumference were measured using standardized procedures and waist-to-height ratio (WHtR) was calculated. The sample was divided into those without central obesity (WHtR<0·5) and those with central obesity (WHtR≥0·5). ANIBES ('Anthropometric data, macronutrients and micronutrients intake, practice of physical activity, socioeconomic data and lifestyles in Spain') Study. Adults aged 18-64 years (n 1655; 798 men and 857 women). A higher percentage of people ate more than four meals daily in the group without central obesity and those with central obesity more frequently skipped the mid-afternoon snack than those without. Breakfasts containing >25 % of total energy intake and lunches containing >35 % of total energy intake were associated with increased likelihood of central obesity (OR=1·874, 95 % CI 1·019, 3·448; P15 % of total energy were associated with decreased likelihood of central obesity (OR=0·477, 95 % CI 0·313, 0·727; P<0·001 and OR=0·650, 95 % CI 0·453, 0·932; P<0·05, respectively). The variety of cereals, wholegrain cereals and dairy was higher in the population without central obesity. Our results suggest that 'what and when we eat' should be considered dietary strategies to reduce central obesity.

Very high energy observations of the Galactic Centre: recent results and perspectives with CTA

NASA Astrophysics Data System (ADS)

Terrier, Regis

2016-07-01

The central 300 pc of our Galaxy are a major laboratory for high energy astrophysics. They harbor the closest supermassive black hole (SMBH) and are the site of a sustained star formation activity. The energy released by the supernovae on the ambient medium must be very strong. Similarly, albeit extremely faint nowadays, the SMBH must have experienced episodes of intense activity in the past which can influence significantly the central regions and beyond, e.g. powering the Fermi bubbles. I review observational results at very high energies from the central region and discuss their implications and the questions they leave open. I discuss the perspectives CTA offers for Galactic Centre astrophysics.

Clusterin/ApoJ enhances central leptin signaling through Lrp2-mediated endocytosis.

PubMed

Byun, Kyunghee; Gil, So Young; Namkoong, Churl; Youn, Byung-Soo; Huang, Hu; Shin, Mi-Seon; Kang, Gil Myoung; Kim, Hyun-Kyong; Lee, Bonghee; Kim, Young-Bum; Kim, Min-Seon

2014-07-01

Hypothalamic leptin signaling plays a central role in maintaining body weight homeostasis. Here, we show that clusterin/ApoJ, recently identified as an anorexigenic neuropeptide, is an important regulator in the hypothalamic leptin signaling pathway. Coadministration of clusterin potentiates the anorexigenic effect of leptin and boosts leptin-induced hypothalamic Stat3 activation. In cultured neurons, clusterin enhances receptor binding and subsequent endocytosis of leptin. These effects are mainly mediated through the LDL receptor-related protein-2 (Lrp2). Notably, inhibition of hypothalamic clusterin, Lrp2 or endocytosis abrogates anorexia and hypothalamic Stat3 activation caused by leptin. These findings propose a novel regulatory mechanism in central leptin signaling pathways. © 2014 The Authors.

The central equipment pool, an opportunity for improved technology management.

PubMed

Gentles, W M

2000-01-01

A model for a central equipment pool managed by a clinical engineering department has been presented. The advantages to patient care and to the clinical engineering department are many. The distribution of portable technology that has been traditionally managed by the materials management function is a logical match to the expanding role of clinical engineering departments in technology management. Accurate asset management tools have allowed us to provide reliable measures of infusion pump utilization, permitting us to predict future needs as programs expand. Thus we are more actively involved in strategic technology planning. The central equipment pool is an excellent opportunity for the clinical engineering department to increase its technology management activities.

Neural Correlates of Central Inhibition during Physical Fatigue

PubMed Central

Tanaka, Masaaki; Ishii, Akira; Watanabe, Yasuyoshi

2013-01-01

Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG). Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs) in the posterior cingulated cortex (PCC), with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue. PMID:23923034

Role of Glutamate Release and Metabotropic Autoreceptors in Seizureogenic Actions of Cholinomimetic Agents

DTIC Science & Technology

2001-10-01

produced by centrally-active cholinomimetic agents and to evaluate possible palliative treatments for central cholinomimetic toxicity. The scope of...REPORT: 10/01/00-09/30/01 AWARD NUMBER: DAMD17-98-1-8617 evaluation of the effects by intracerebral infusion of the organophosphate agent paraoxon on EEG...agents. Previously, we had reported successful induction of seizure-like changes in EEG activity of anesthetized rats following intracerebral infusion

A brain-liver circuit regulates glucose homeostasis.

PubMed

Pocai, Alessandro; Obici, Silvana; Schwartz, Gary J; Rossetti, Luciano

2005-01-01

Increased glucose production (GP) is the major determinant of fasting hyperglycemia in diabetes mellitus. Previous studies suggested that lipid metabolism within specific hypothalamic nuclei is a biochemical sensor for nutrient availability that exerts negative feedback on GP. Here we show that central inhibition of fat oxidation leads to selective activation of brainstem neurons within the nucleus of the solitary tract and the dorsal motor nucleus of the vagus and markedly decreases liver gluconeogenesis, expression of gluconeogenic enzymes, and GP. These effects require central activation of ATP-dependent potassium channels (K(ATP)) and descending fibers within the hepatic branch of the vagus nerve. Thus, hypothalamic lipid sensing potently modulates glucose metabolism via neural circuitry that requires the activation of K(ATP) and selective brainstem neurons and intact vagal input to the liver. This crosstalk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to hyperglycemia.

Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity.

PubMed

Kim, Jongwan; Yun, Eun-Young; Quan, Fu-Shi; Park, Seung-Won; Goo, Tae-Won

2017-01-01

The α -glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV) administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS).

Heart Rate Variability in Nonlinear Rats with Different Orientation and Exploratory Activity in the Open Field.

PubMed

Kur'yanova, E V; Teplyi, D L; Zhukova, Yu D; Zhukovina, N V

2015-12-01

The basic behavioral activity of nonlinear rats was evaluated from the sum of crossed peripheral and central squares and peripheral and central rearing postures in the open fi eld test. This index was low (<20 episodes), intermediate (20-29 episodes), or high (>30 episodes). Male rats with high score of orientation and exploratory activity were characterized by higher indexes of total heart rate variability than rats with low or intermediate activity. Specimens with a greater contribution of VLF waves into the total power spectrum of heart rate variability were shown to dominate among the rats with high behavioral activity. Our results are consistent with the notions of a suprasegmental nature of VLF waves.

Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

PubMed

Zeng, Lingling; Yang, Yang; Hu, Yujuan; Sun, Yu; Du, Zhengde; Xie, Zhen; Zhou, Tao; Kong, Weijia

2014-01-01

Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

Serotonin and central nervous system fatigue: nutritional considerations.

PubMed

Davis, J M; Alderson, N L; Welsh, R S

2000-08-01

Fatigue from voluntary muscular effort is a complex phenomenon involving the central nervous system (CNS) and muscle. An understanding of the mechanisms within muscle that cause fatigue has led to the development of nutritional strategies to enhance performance. Until recently, little was known about CNS mechanisms of fatigue, even though the inability or unwillingness to generate and maintain central activation of muscle is the most likely explanation of fatigue for most people during normal daily activities. A possible role of nutrition in central fatigue is receiving more attention with the development of theories that provide a clue to its biological mechanisms. The focus is on the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] because of its role in depression, sensory perception, sleepiness, and mood. Nutritional strategies have been designed to alter the metabolism of brain 5-HT by affecting the availability of its amino acid precursor. Increases in brain 5-HT concentration and overall activity have been associated with increased physical and perhaps mental fatigue during endurance exercise. Carbohydrate (CHO) or branched-chain amino acid (BCAA) feedings may attenuate increases in 5-HT and improve performance. However, it is difficult to distinguish between the effects of CHO on the brain and those on the muscles themselves, and most studies involving BCAA show no performance benefits. It appears that important relations exist between brain 5-HT and central fatigue. Good theoretical rationale and data exist to support a beneficial role of CHO and BCAA on brain 5-HT and central fatigue, but the strength of evidence is presently weak.

Using Analogy Role-Play Activity in an Undergraduate Biology Classroom to Show Central Dogma Revision

ERIC Educational Resources Information Center

Takemura, Masaharu; Kurabayashi, Mario

2014-01-01

For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego®…

Histidine augments the suppression of hepatic glucose production by central insulin action.

PubMed

Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-Ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

2013-07-01

Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes.

Transcript abundance on its own cannot be used to infer fluxes in central metabolism

DOE PAGES

Schwender, Jorg; Konig, Christina; Klapperstuck, Matthias; ...

2014-11-28

An attempt has been made to define the extent to which metabolic flux in central plant metabolism is reflected by changes in the transcriptome and metabolome, based on an analysis of in vitro cultured immature embryos of two oilseed rape (Brassica napus) accessions which contrast for seed lipid accumulation. Metabolic flux analysis (MFA) was used to constrain a flux balance metabolic model which included 671 biochemical and transport reactions within the central metabolism. This highly confident flux information was eventually used for comparative analysis of flux vs. transcript (metabolite). Metabolite profiling succeeded in identifying 79 intermediates within the central metabolism,more » some of which differed quantitatively between the two accessions and displayed a significant shift corresponding to flux. An RNA-Seq based transcriptome analysis revealed a large number of genes which were differentially transcribed in the two accessions, including some enzymes/proteins active in major metabolic pathways. With a few exceptions, differential activity in the major pathways (glycolysis, TCA cycle, amino acid, and fatty acid synthesis) was not reflected in contrasting abundances of the relevant transcripts. The conclusion was that transcript abundance on its own cannot be used to infer metabolic activity/fluxes in central plant metabolism. Lastly, this limitation needs to be borne in mind in evaluating transcriptome data and designing metabolic engineering experiments.« less

Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action

PubMed Central

Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

2013-01-01

Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes. PMID:23474485

Task2 potassium channels set central respiratory CO2 and O2 sensitivity

PubMed Central

Gestreau, Christian; Heitzmann, Dirk; Thomas, Joerg; Dubreuil, Véronique; Bandulik, Sascha; Reichold, Markus; Bendahhou, Saïd; Pierson, Patricia; Sterner, Christina; Peyronnet-Roux, Julie; Benfriha, Chérif; Tegtmeier, Ines; Ehnes, Hannah; Georgieff, Michael; Lesage, Florian; Brunet, Jean-Francois; Goridis, Christo; Warth, Richard; Barhanin, Jacques

2010-01-01

Task2 K+ channel expression in the central nervous system is surprisingly restricted to a few brainstem nuclei, including the retrotrapezoid (RTN) region. All Task2-positive RTN neurons were lost in mice bearing a Phox2b mutation that causes the human congenital central hypoventilation syndrome. In plethysmography, Task2−/− mice showed disturbed chemosensory function with hypersensitivity to low CO2 concentrations, leading to hyperventilation. Task2 probably is needed to stabilize the membrane potential of chemoreceptive cells. In addition, Task2−/− mice lost the long-term hypoxia-induced respiratory decrease whereas the acute carotid-body-mediated increase was maintained. The lack of anoxia-induced respiratory depression in the isolated brainstem–spinal cord preparation suggested a central origin of the phenotype. Task2 activation by reactive oxygen species generated during hypoxia could silence RTN neurons, thus contributing to respiratory depression. These data identify Task2 as a determinant of central O2 chemoreception and demonstrate that this phenomenon is due to the activity of a small number of neurons located at the ventral medullary surface. PMID:20133877

[The role of recombinant activated factor VII in neuro- surgical and neurocritical patients].

PubMed

Rama-Maceiras, P; Ingelmo-Ingelmo, I; Fábregas-Juliá, N; Hernández-Palazón, J

2011-06-01

Central nervous system haemorrhage is a severe pathology, as a small amount of bleeding inside the brain can result in devastating consequences. Haemostatic agents might decrease the consequences of intra- cranial bleeding, whichever spontaneous, traumatic, or anticoagulation treatment etiology. Proacogulant recombinant activated factor VII (rFVIIa) has been given after central nervous system bleeding, with an off-label indication. In this update, we go over the drug mechanism of action, its role in the treatment of central nervous system haemorrhage and the published evidences regarding this subject. We carried out a literature review concerning the treatment with rFVIIa in central nervous system haemorrhage, neurocritical pathologies and neurosurgical procedures, searching in MEDLINE and in clinical trials registry: http://clinicaltrials.gov (last review September 2010), as well as performing a manual analysis of collected articles, looking for aditional references. The results of randomized clinical trials do not support the systematic administration of rFVIIa for spontaneous intracranial cerebral haemorrhage. In other central nervous system related haemorrhages, the current available data consist on retrospective studies, expert opinion or isolated case reports.

Influence of patterned electrical neuromuscular stimulation on quadriceps activation in individuals with knee joint injury.

PubMed

Glaviano, Neal R; Langston, William T; Hart, Joseph M; Saliba, Susan

2014-12-01

Neuromuscular Electrical Stimulation is a common intervention to address muscle weakness, however presents with many limitations such as fatigue, muscle damage, and patient discomfort that may influence its effectiveness. One novel form of electrical stimulation purported to improve neuromuscular re-education is Patterned Electrical Neuromuscular Stimulation (PENS), which is proposed to mimic muscle-firing patterns of healthy individuals. PENS provides patterned stimulating to the agonist muscle, antagonist muscle and then agonist muscle again in an effort to replicate firing patterns. The purpose of this study was to determine the effect of a single PENS treatment on knee extension torque and quadriceps activation in individuals with quadriceps inhibition. 18 subjects (10 males and 8 females: 24.2±3.4 years, 175.3±11.8cm, 81.8±12.4kg) with a history of knee injury/pain participated in this double-blinded randomized controlled laboratory trial. Participants demonstrated quadriceps inhibition with a central activation ratio of ≤90%. Maximal voluntary isometric contraction of the quadriceps and central activation ratio were measured before and after treatment. The treatment intervention was a 15-minute patterned electrical stimulation applied to the quadriceps and hamstring muscles with a strong motor contraction or a sham group, who received an identical set up as the PENS group, but received a 1mA subsensory stimulation. A 2×2 (group × time) ANCOVA was used to determine differences in maximal voluntary isometric contraction and central activation ratio between groups. The maximal voluntary isometric contraction was selected as a covariate due to baseline differences. There were no differences in change scores between pre- and post-intervention for maximal voluntary isometric contraction: (PENS: 0.09±0.32Nm/kg and Sham 0.15±0.18Nm/kg, p=0.713), or central activation ratio:(PENS: -1.22±6.06 and Sham: 1.48±3.7, p=0.270). A single Patterned Electrical Neuromuscular Stimulation treatment did not alter quadriceps central activation ratio or maximal voluntary isometric contraction. Unlike other types of muscle stimulation, PENS did not result in a reduction of quadriceps torque. Level III.

Contraindications to Athletic Participation. Cardiac, Respiratory, and Central Nervous System Conditions.

ERIC Educational Resources Information Center

Moeller, James L.

1996-01-01

Discusses contraindications to athletic participation, examining the cardiac, respiratory, and central nervous system conditions that warrant activity disqualification. Provides guidelines about when it is safe for individuals to participate, and discusses the physician's responsibility. (SM)

The dependency on central government funding of decentralised health systems: experiences of the challenges and coping strategies in the Kongwa District, Tanzania.

PubMed

Frumence, Gasto; Nyamhanga, Tumaini; Mwangu, Mughwira; Hurtig, Anna-Karin

2014-01-25

Decentralised health systems in Tanzania depend largely on funding from the central government to run health services. Experience has shown that central funding in a decentralised system is not an appropriate approach to ensure the effective and efficient performance of local authorities due to several limitations. One of the limitations is that funds from the central government are not disbursed on a timely basis, which in turn, leads to the serious problem of shortage of financial resources for Council Health Management Teams (CHMT). This paper examines how dependency on central government funding in Tanzania affects health activities in Kongwa district council and the strategies used by the CHMT cope with the situation. The study adopted a qualitative approach and data were collected using semi-structured interviews and focus group discussions. One district in the central region of Tanzania was strategically selected. Ten key informants involved in the management of health service delivery at the district level were interviewed and one focus group discussion was held, which consisted of members of the council health management team. The data generated were analysed for themes and patterns. The results showed that late disbursement of funds interrupts the implementation of health activities in the district health system. This situation delays the implementation of some activities, while a few activities may not be implemented at all. However, based on their prior knowledge of the anticipated delays in financial disbursements, the council health management team has adopted three main strategies to cope with this situation. These include obtaining supplies and other services on credit, borrowing money from other projects in the council, and using money generated from cost sharing. Local government authorities (LGAs) face delays in the disbursement of funds from the central government. This has necessitated introduction of informal coping strategies to deal with the situation. National-level policy and decision makers should minimise the bureaucracy involved in allocating funds to the district health systems to reduce delays.

The dependency on central government funding of decentralised health systems: experiences of the challenges and coping strategies in the Kongwa District, Tanzania

PubMed Central

2014-01-01

Background Decentralised health systems in Tanzania depend largely on funding from the central government to run health services. Experience has shown that central funding in a decentralised system is not an appropriate approach to ensure the effective and efficient performance of local authorities due to several limitations. One of the limitations is that funds from the central government are not disbursed on a timely basis, which in turn, leads to the serious problem of shortage of financial resources for Council Health Management Teams (CHMT). This paper examines how dependency on central government funding in Tanzania affects health activities in Kongwa district council and the strategies used by the CHMT cope with the situation. Methods The study adopted a qualitative approach and data were collected using semi-structured interviews and focus group discussions. One district in the central region of Tanzania was strategically selected. Ten key informants involved in the management of health service delivery at the district level were interviewed and one focus group discussion was held, which consisted of members of the council health management team. The data generated were analysed for themes and patterns. Results The results showed that late disbursement of funds interrupts the implementation of health activities in the district health system. This situation delays the implementation of some activities, while a few activities may not be implemented at all. However, based on their prior knowledge of the anticipated delays in financial disbursements, the council health management team has adopted three main strategies to cope with this situation. These include obtaining supplies and other services on credit, borrowing money from other projects in the council, and using money generated from cost sharing. Conclusion Local government authorities (LGAs) face delays in the disbursement of funds from the central government. This has necessitated introduction of informal coping strategies to deal with the situation. National-level policy and decision makers should minimise the bureaucracy involved in allocating funds to the district health systems to reduce delays. PMID:24460781

The crystal structure of the D-alanine-D-alanine ligase from Acinetobacter baumannii suggests a flexible conformational change in the central domain before nucleotide binding.

PubMed

Huynh, Kim-Hung; Hong, Myoung-ki; Lee, Clarice; Tran, Huyen-Thi; Lee, Sang Hee; Ahn, Yeh-Jin; Cha, Sun-Shin; Kang, Lin-Woo

2015-11-01

Acinetobacter baumannii, which is emerging as a multidrug-resistant nosocomial pathogen, causes a number of diseases, including pneumonia, bacteremia, meningitis, and skin infections. With ATP hydrolysis, the D-alanine-D-alanine ligase (DDL) catalyzes the synthesis of D-alanyl-D-alanine, which is an essential component of bacterial peptidoglycan. In this study, we determined the crystal structure of DDL from A. baumannii (AbDDL) at a resolution of 2.2 Å. The asymmetric unit contained six protomers of AbDDL. Five protomers had a closed conformation in the central domain, while one protomer had an open conformation in the central domain. The central domain with an open conformation did not interact with crystallographic symmetry-related protomers and the conformational change of the central domain was not due to crystal packing. The central domain of AbDDL can have an ensemble of the open and closed conformations before the binding of substrate ATP. The conformational change of the central domain is important for the catalytic activity and the detail information will be useful for the development of inhibitors against AbDDL and putative antibacterial agents against A. baumannii. The AbDDL structure was compared with that of other DDLs that were in complex with potent inhibitors and the catalytic activity of AbDDL was confirmed using enzyme kinetics assays.

Late Pleistocene-Holocene Activity of the Strike-slip Xianshuihe Fault Zone, Tibetan Plateau, Inferred from Tectonic Landforms

NASA Astrophysics Data System (ADS)

Lin, A.; Yan, B.

2017-12-01

Knowledges on the activity of the strike-slip fault zones on the Tibetan Plateau have been promoted greatly by the interpretation of remote sensing images (Molnar and Tapponnier, 1975; Tapponnier and Molnar, 1977). The active strike-slip Xianshuihe-Xiaojiang Fault System (XXFS), with the geometry of an arc projecting northeastwards, plays an important role in the crustal deformation of the Tibetan Plateau caused by the continental collision between the Indian and Eurasian plates. The Xianshuihe Fault Zone (XFZ) is located in the central segment of the XXFS and extends for 370 km, with a maximum sinistral offset of 60 km since 13‒5 Ma. In this study, we investigated the tectonic landforms and slip rate along the central segment of the left-lateral strike-slip XFZ. Field investigations and analysis of ttectonic landforms show that horizontal offset has been accumulated on the topographical markers of different scales that developed since the Last Glacial Maximum (LGM). The central segment of the XFZ is composed of three major faults: Yalahe, Selaha, and Zheduotang faults showing a right-stepping echelon pattern, that is characterized by systematical offset of drainages, alluvial fans and terrace risers with typical scissoring structures, indicating a structural feature of left-lateral strike-slip fault. Based on the offset glacial morphology and radiocarbon dating ages, we estimate the Late Pleistocene-Holocene slip rate to be 10 mm/yr for the central segment of the XFZ, which is consistent with that estimated from the GPS observations and geological evidence as reported previously. Across the central segment of the XFZ, the major Selaha and Zheduotang faults participate a slip rate of 5.8 mm/yr and 3.4 mm/yr, respectively. Detailed investigations of tectonic landforms are essential for the understanding the activity of active faults. Our findings suggest that the left-lateral slipping of the XFZ partitions the deformation of eastward extrusion and northeastward shortening of the central Tibetan Plateau to accommodate the continuing penetration of the Indian plate into the Eurasian plate.

Central core disease. A correlated genetic, histochemical, ultramicroscopic, and biochemical study.

PubMed Central

Isaacs, H; Heffron, J J; Badenhorst, M

1975-01-01

Two patients suffering from central core disease are presented. The condition is associated with musculoskeletal abnormalities which have been traced back over five generations. In addition to the typical histochemical findings, electronmicroscopic study has revealed the presence of both structured and non-structured cores in adjacent areas. The calcium uptake by the sarcoplasmic reticulum was reduced to one-third of normal. Phosphorylase activity was normal in the one case and reduced to 63% in the other. Actomyosin Mg2+-activated ATPase activity was decreased, as was the Ca2+-dependent ATPase of the sarcoplasmic reticulum. Images PMID:130467

The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia

PubMed Central

2011-01-01

Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids). PMID:21542893

Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

PubMed

Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

2017-06-01

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

Comprehending expository texts: the dynamic neurobiological correlates of building a coherent text representation

PubMed Central

Swett, Katherine; Miller, Amanda C.; Burns, Scott; Hoeft, Fumiko; Davis, Nicole; Petrill, Stephen A.; Cutting, Laurie E.

2013-01-01

Little is known about the neural correlates of expository text comprehension. In this study, we sought to identify neural networks underlying expository text comprehension, how those networks change over the course of comprehension, and whether information central to the overall meaning of the text is functionally distinct from peripheral information. Seventeen adult subjects read expository passages while being scanned using functional magnetic resonance imaging (fMRI). By convolving phrase onsets with the hemodynamic response function (HRF), we were able to identify regions that increase and decrease in activation over the course of passage comprehension. We found that expository text comprehension relies on the co-activation of the semantic control network and regions in the posterior midline previously associated with mental model updating and integration [posterior cingulate cortex (PCC) and precuneus (PCU)]. When compared to single word comprehension, left PCC and left Angular Gyrus (AG) were activated only for discourse-level comprehension. Over the course of comprehension, reliance on the same regions in the semantic control network increased, while a parietal region associated with attention [intraparietal sulcus (IPS)] decreased. These results parallel previous findings in narrative comprehension that the initial stages of mental model building require greater visuospatial attention processes, while maintenance of the model increasingly relies on semantic integration regions. Additionally, we used an event-related analysis to examine phrases central to the text's overall meaning vs. peripheral phrases. It was found that central ideas are functionally distinct from peripheral ideas, showing greater activation in the PCC and PCU, while over the course of passage comprehension, central and peripheral ideas increasingly recruit different parts of the semantic control network. The finding that central information elicits greater response in mental model updating regions than peripheral ideas supports previous behavioral models on the cognitive importance of distinguishing textual centrality. PMID:24376411

Application of the Landsat Thematic Mapper to the identification of potentially active volcanoes in the Central Andes

NASA Technical Reports Server (NTRS)

Francis, P. W.; De Silva, S. L.

1989-01-01

A systematic study of the potentially active volcanoes in the Central Andes (14 deg S to 28 deg S) was carried out on the basis of Landsat Thematic Mapper images which provided consistent coverage of the area. More than 60 major volcanoes were identified as potentially active, as compared to 16 that are listed in the Catalog of Active Volcanoes of the World (Casertano, 1963; Hantke and Parodi, 1966). Most of these volcanoes are large (up to 6000 m in height) composite cones. Some of them could threaten nearby settlements, especially those in southern Peru, where the volcanoes rise above deep canyons with settlements along them.

Slack, Slick, and Sodium-Activated Potassium Channels

PubMed Central

Kaczmarek, Leonard K.

2013-01-01

The Slack and Slick genes encode potassium channels that are very widely expressed in the central nervous system. These channels are activated by elevations in intracellular sodium, such as those that occur during trains of one or more action potentials, or following activation of nonselective cationic neurotransmitter receptors such as AMPA receptors. This review covers the cellular and molecular properties of Slack and Slick channels and compares them with findings on the properties of sodium-activated potassium currents (termed KNa currents) in native neurons. Human mutations in Slack channels produce extremely severe defects in learning and development, suggesting that KNa channels play a central role in neuronal plasticity and intellectual function. PMID:24319675

Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats

NASA Technical Reports Server (NTRS)

Moffitt, J. A.; Schadt, J. C.; Hasser, E. M.

1999-01-01

The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

Gut commensalism, cytokines, and central nervous system demyelination.

PubMed

Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

2014-08-01

There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination.

Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

PubMed

Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

2016-11-01

Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Central control of cardiorespiratory interactions in fish.

PubMed

Taylor, Edwin W; Leite, Cleo A C; Levings, Jennifer J

2009-01-01

Fish control the relative flow rates of water and blood over the gills in order to optimise respiratory gas exchange. As both flows are markedly pulsatile, close beat-to-beat relationships can be predicted. Cardiorespiratory interactions in fish are controlled primarily by activity in the parasympathetic nervous system that has its origin in cardiac vagal preganglionic neurons. Recordings of efferent activity in the cardiac vagus include units firing in respiration-related bursts. Bursts of electrical stimuli delivered peripherally to the cardiac vagus or centrally to respiratory branches of cranial nerves can recruit the heart over a range of frequencies. So, phasic, efferent activity in cardiac vagi, that in the intact fish are respiration-related, can cause heart rate to be modulated by the respiratory rhythm. In elasmobranch fishes this phasic activity seems to arise primarily from central feed-forward interactions with respiratory motor neurones that have overlapping distributions with cardiac neurons in the brainstem. In teleost fish, they arise from increased levels of efferent vagal activity arising from reflex stimulation of chemoreceptors and mechanoreceptors in the orobranchial cavity. However, these differences are largely a matter of emphasis as both groups show elements of feed-forward and feed-back control of cardiorespiratory interactions.

Thermostable 𝜶-Amylase Activity from Thermophilic Bacteria Isolated from Bora Hot Spring, Central Sulawesi

NASA Astrophysics Data System (ADS)

Gazali, F. M.; Suwastika, I. N.

2018-03-01

α-Amylase is one of the most important enzyme in biotechnology field, especially in industrial application. Thermostability of α-Amylase produced by thermophilic bacteria improves industrial process of starch degradation in starch industry. The present study were concerned to the characterization of α-Amylase activity from indigenous thermophilic bacteria isolated from Bora hot spring, Central Sulawesi. There were 18 isolates which had successfully isolated from 90°C sediment samples of Bora hot spring and 13 of them showed amylolytic activity. The α-Amylase activity was measured qualitatively at starch agar and quantitatively based on DNS (3,5-Dinitrosalicylic acid) methods, using maltose as standard solution. Two isolates (out of 13 amylolytic bacteria), BR 002 and BR 015 showed amylolytic index of 0.8 mm and 0.5 mm respectively, after being incubated at 55°C in the 0.002% Starch Agar Medium. The α-Amylase activity was further characterized quantitatively which includes the optimum condition of pH and temperature of α-Amylase crude enzyme from each isolate. To our knowledge, this is the first report on isolation and characterization of a thermostable α-Amylase from thermophilic bacteria isolated from Central Sulawesi particularly from Bora hot spring.

Mechanisms of insulin action on sympathetic nerve activity

NASA Technical Reports Server (NTRS)

Muntzel, Martin S.; Anderson, Erling A.; Johnson, Alan Kim; Mark, Allyn L.

1996-01-01

Insulin resistance and hyperinsulinemia may contribute to the development of arterial hypertension. Although insulin may elevate arterial pressure, in part, through activation of the sympathetic nervous system, the sites and mechanisms of insulin-induced sympathetic excitation remain uncertain. While sympathoexcitation during insulin may be mediated by the baroreflex, or by modulation of norepinephrine release from sympathetic nerve endings, it has been shown repeatedly that insulin increases sympathetic outflow by actions on the central nervous system. Previous studies employing norepinephrine turnover have suggested that insulin causes sympathoexcitation by acting in the hypothalamus. Recent experiments from our laboratory involving direct measurements of regional sympathetic nerve activity have provided further evidence that insulin acts in the central nervous system. For example, administration of insulin into the third cerebralventricle increased lumbar but not renal or adrenal sympathetic nerve activity in normotensive rats. Interestingly, this pattern of regional sympathetic nerve responses to central neural administration of insulin is similar to that seen with systemic administration of insulin. Further, lesions of the anteroventral third ventricle hypothalamic (AV3V) region abolished increases in sympathetic activity to systemic administration of insulin with euglycemic clamp, suggesting that AV3V-related structures are critical for insulin-induced elevations in sympathetic outflow.

Plasticity and Activation of Spared Intraspinal Respiratory Circuits Following Spinal Cord Injury

DTIC Science & Technology

2016-10-01

fluorescent immunohistochemistry (IHC) procedures. Accordingly, we performed IHC with two markers commonly used in the central nervous system (GFAP and...immunohistochemistry (IHC) procedures. Accordingly, we performed IHC with two 365 markers commonly used in the central nervous system (GFAP and NeuN) either...905 mammalian central nervous system . J Neurosci Methods 1: 107-132, 1979. 906 Kirkwood PA, Munson JB, Sears TA, and Westgaard RH. Respiratory

Raising the Curtain. A Report with Recommendations on Academic Exchanges with East Central Europe and the USSR. East Central Europe Information Exchange Report 1.

ERIC Educational Resources Information Center

Burn, Barbara B.

This report provides an overview of the changes in the development of academic exchange activity between the United States, the Soviet Union, and East Central Europe in the context of far-reaching reforms throughout the region. It also explores the factors which may facilitate or inhibit further growth in academic exchanges. The report begins with…

Nucleosome exclusion from the interspecies-conserved central AT-rich region of the Ars insulator.

PubMed

Takagi, Haruna; Inai, Yuta; Watanabe, Shun-ichiro; Tatemoto, Sayuri; Yajima, Mamiko; Akasaka, Koji; Yamamoto, Takashi; Sakamoto, Naoaki

2012-01-01

The Ars insulator is a boundary element identified in the upstream region of the arylsulfatase (HpArs) gene in the sea urchin, Hemicentrotus pulcherrimus, and possesses the ability to both block enhancer-promoter communications and protect transgenes from silent chromatin. To understand the molecular mechanism of the Ars insulator, we investigated the correlation between chromatin structure, DNA structure and insulator activity. Nuclease digestion of nuclei isolated from sea urchin embryos revealed the presence of a nuclease-hypersensitive site within the Ars insulator. Analysis of micrococcal nuclease-sensitive sites in the Ars insulator, reconstituted with nucleosomes, showed the exclusion of nucleosomes from the central AT-rich region. Furthermore, the central AT-rich region in naked DNA was sensitive to nucleotide base modification by diethylpyrocarbonate (DEPC). These observations suggest that non-B-DNA structures in the central AT-rich region may inhibit nucleosomal formation, which leads to nuclease hypersensitivity. Furthermore, comparison of nucleotide sequences between the HpArs gene and its ortholog in Strongylocentrotus purpuratus revealed that the central AT-rich region of the Ars insulator is conserved, and this conserved region showed significant enhancer blocking activity. These results suggest that the central AT-rich nucleosome-free region plays an important role in the function of the Ars insulator.

STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.

PubMed

Mizowaki, Takashi; Sasayama, Takashi; Tanaka, Kazuhiro; Mizukawa, Katsu; Takata, Kumi; Nakamizo, Satoshi; Tanaka, Hirotomo; Nagashima, Hiroaki; Nishihara, Masamitsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

2015-09-01

Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.

Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

PubMed Central

Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

2016-01-01

Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867

Variation in diel activity of ground beetles (Coleoptera: Carabidae) associated with a soybean field and coal mine remnant

USGS Publications Warehouse

Willand, J.E.; McCravy, K.W.

2006-01-01

Diel activities of carabids (Coleoptera: Carabidae) associated with a coal mine remnant and surrounding soybean field were studied in west-central Illinois from June through October 2002. A total of 1,402 carabids, representing 29 species and 17 genera, were collected using pitfall traps. Poecilus chalcites (Say) demonstrated roughly equal diurnal and nocturnal activity in June, but greater diurnal activity thereafter. Pterostichus permundus (Say), Cyclotrachelus seximpressus (LeConte), Amara obesa (Say), and Scarites quadriceps Chaudoir showed significant nocturnal activity. Associations between habitat and diel activity were found for three species: P. chalcites associated with the remnant and edge habitats showed greater diurnal activity than those associated with the soybean field; C. seximpressus was most active diurnally in the remnant, and Harpalus pensylvanicus (DeGeer) showed the greatest nocturnal activity in the remnant and edge habitats. We found significant temporal and habitat-related variation in diel activity among carabid species inhabiting agricultural areas in west-central Illinois.

A study of Quaternary structures in the Qom region, West Central Iran

NASA Astrophysics Data System (ADS)

Babaahmadi, A.; Safaei, H.; Yassaghi, A.; Vafa, H.; Naeimi, A.; Madanipour, S.; Ahmadi, M.

2010-12-01

West Central Iran comprises numerous Quaternary faults. Having either strike-slip or thrust mechanisms, these faults are potentially active and therefore capable of creating destructive earthquakes. In this paper, we use satellite images as well as field trips to identify these active faults in the Qom region. The Qom and Indes faults are the main NW-trending faults along which a Quaternary restraining step-over zone has formed. Kamarkuh, Mohsen Abad, and Ferdows anticlines are potentially active structures that formed in this restraining step-over zone. There are some thrusts and anticlines, such as the Alborz anticline and Alborz fault, which are parallel to strike-slip faults such as the Qom fault, indicating deformation partitioning in the area. In addition to NW-trending structures, there is an important NE-trending fault known as the Qomrud fault that has deformed Quaternary deposits and affected Kushk-e-Nosrat fault, Alborz anticline, and Qomrud River. The results of this study imply that the major Quaternary faults of West Central Iran and their restraining step-over zones are potentially active.

Time perspective and physical activity among central Appalachian adolescents.

PubMed

Gulley, Tauna

2013-04-01

Time perspective is a cultural behavioral concept that reflects individuals' orientations or attitudes toward the past, present, or future. Individuals' time perspectives influence their choices regarding daily activities. Time perspective is an important consideration when teaching adolescents about the importance of being physically active. However, little is known about the relationship between time perspective and physical activity among adolescents. The purpose of this study was to determine the time perspective of central Appalachian adolescents and explore the relationship between time perspective and physical activity. This study was guided by The theory of planned behavior (TPB). One hundred and ninety-three students completed surveys to examine time perspective and physical activity behaviors. Data were collected in one school. Results of this study can inform school nurses and high school guidance counselors about the importance of promoting a future-oriented time perspective to improve physical activity and educational outcomes.

Protection against high-fat diet-induced obesity in Helz2-deficient male mice due to enhanced expression of hepatic leptin receptor.

PubMed

Yoshino, Satoshi; Satoh, Tetsurou; Yamada, Masanobu; Hashimoto, Koshi; Tomaru, Takuya; Katano-Toki, Akiko; Kakizaki, Satoru; Okada, Shuichi; Shimizu, Hiroyuki; Ozawa, Atsushi; Tuchiya, Takafumi; Ikota, Hayato; Nakazato, Yoichi; Mori, Munemasa; Matozaki, Takashi; Sasaki, Tsutomu; Kitamura, Tadahiro; Mori, Masatomo

2014-09-01

Obesity arises from impaired energy balance, which is centrally coordinated by leptin through activation of the long form of leptin receptor (Leprb). Obesity causes central leptin resistance. However, whether enhanced peripheral leptin sensitivity could overcome central leptin resistance remains obscure. A peripheral metabolic organ targeted by leptin is the liver, with low Leprb expression. We here show that mice fed a high-fat diet (HFD) and obese patients with hepatosteatosis exhibit increased expression of hepatic helicase with zinc finger 2, a transcriptional coactivator (Helz2), which functions as a transcriptional coregulator of several nuclear receptors, including peroxisome proliferator-activated receptor γ in vitro. To explore the physiological importance of Helz2, we generated Helz2-deficient mice and analyzed their metabolic phenotypes. Helz2-deficient mice showing hyperleptinemia associated with central leptin resistance were protected against HFD-induced obesity and had significantly up-regulated hepatic Leprb expression. Helz2 deficiency and adenovirus-mediated liver-specific exogenous Leprb overexpression in wild-type mice significantly stimulated hepatic AMP-activated protein kinase on HFD, whereas Helz2-deficient db/db mice lacking functional Leprb did not. Fatty acid-β oxidation was increased in Helz2-deficeint hepatocytes, and Helz2-deficient mice revealed increased oxygen consumption and decreased respiratory quotient in calorimetry analyses. The enhanced hepatic AMP-activated protein kinase energy-sensing pathway in Helz2-deficient mice ameliorated hyperlipidemia, hepatosteatosis, and insulin resistance by reducing lipogenic gene expression and stimulating lipid-burning gene expression in the liver. These findings together demonstrate that Helz2 deficiency ameliorates HFD-induced metabolic abnormalities by stimulating endogenous hepatic Leprb expression, despite central leptin resistance. Hepatic HELZ2 might be a novel target molecule for the treatment of obesity with hepatosteatosis.

The prefrontal oxygenation and ventilatory responses at start of one-legged cycling exercise have relation to central command.

PubMed

Asahara, Ryota; Matsukawa, Kanji; Ishii, Kei; Liang, Nan; Endo, Kana

2016-11-01

When performing exercise arbitrarily, activation of central command should start before the onset of exercise, but when exercise is forced to start with cue, activation of central command should be delayed. We examined whether the in-advance activation of central command influenced the ventilatory response and reflected in the prefrontal oxygenation, by comparing the responses during exercise with arbitrary and cued start. The breath-by-breath respiratory variables and the prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) were measured during one-legged cycling. Minute ventilation (V̇e) at the onset of arbitrary one-legged cycling was augmented to a greater extent than cued cycling, while end-tidal carbon dioxide tension (ETco 2 ) decreased irrespective of arbitrary or cued start. Symmetric increase in the bilateral prefrontal Oxy-Hb occurred before and at the onset of arbitrary one-legged cycling, whereas such an increase was absent with cued start. The time course and magnitude of the increased prefrontal oxygenation were not influenced by the extent of subjective rating of perceived exertion and were the same as those of the prefrontal oxygenation during two-legged cycling previously reported. Mental imagery or passive performance of the one-legged cycling increased V̇e and decreased ETco 2 Neither intervention, however, augmented the prefrontal Oxy-Hb. The changes in ETco 2 could not explain the prefrontal oxygenation response during voluntary or passive one-legged cycling. Taken together, it is likely that the in-advance activation of central command influenced the ventilatory response by enhancing minute ventilation at the onset of one-legged cycling exercise and reflected in the preexercise increase in the prefrontal oxygenation. Copyright © 2016 the American Physiological Society.

c-Fos and pERK, which is a better marker for neuronal activation and central sensitization after noxious stimulation and tissue injury?

PubMed Central

Gao, Yong-Jing; Ji, Ru-Rong

2009-01-01

c-Fos, the protein of the protooncogene c-fos, has been extensively used as a marker for the activation of nociceptive neurons in the spinal cord for more than twenty years since Hunt et al. first reported that peripheral noxious stimulation to a hind paw of rats leads to a marked induction of c-Fos in superficial and deep dorsal horn neurons in 1987. In 1999, Ji et al. reported that phosphorylated extracellular signal-regulated kinase (pERK) is specifically induced by noxious stimulation in superficial dorsal horn neurons. Accumulating evidence indicates that pERK induction or ERK activation in dorsal horn neurons is essential for the development of central sensitization, increased sensitivity of dorsal horn neurons that is responsible for the generation of persistent pain. Further, molecular mechanisms underlying ERK-mediated central sensitization have been revealed. In contrast, direct evidence for c-Fos-mediated central sensitization is not sufficient. After a noxious stimulus (e.g., capsaicin injection) or tissue injury, c-Fos begins to be induced after 30-60 minutes, whereas pERK can be induced within a minute, which can correlate well with the development of pain hypersensitivity. While c-Fos is often induced in the nuclei of neurons, pERK can be induced in different subcellular structures of neurons such as nuclei, cytoplasma, axons, and dendrites. pERK can even be induced in spinal cord microglia and astrocytes after nerve injury. In summary, both c-Fos and pERK can be used as markers for neuronal activation following noxious stimulation and tissue injury, but pERK is much more dynamic and appears to be a better marker for central sensitization. PMID:19898681

Effects of Gentiana lutea ssp. symphyandra on the central nervous system in mice.

PubMed

Oztürk, Nilgün; Başer, K Hüsnü Can; Aydin, Süleyman; Oztürk, Yusuf; Caliş, Ihsan

2002-11-01

A methanolic extact of Gentiana lutea ssp. symphyandra roots has been investigated for its possible effects on the central nervous system of mice. At doses of 250 and 500 mg/kg (i.p.), the methanol extract of Gentiana roots caused a significant increase in the swimming endurance test and exhibited slight analgesic activity, but no lethality in mice suggesting some activity on the central nervous system. However, there was no indication of sedation or muscular fatigue at the doses employed. HPLC analysis showed that three secoiridoid compounds, gentiopicroside, swertiamarine and sweroside were present and may have been responsible for the CNS effects of the methanol extract of Gentiana lutea ssp. symphyandra roots. Copyright 2002 John Wiley & Sons, Ltd.

Proceedings of the Galactic Center Workshop 2002: The Central 300 Parsecs of the Milky Way. Astronomische Nachrichten Supplementary Issue 1/2003

NASA Astrophysics Data System (ADS)

Cotera, Angela; Markoff, Sera; Geballe, T. R.; Falcke, Heino

2004-03-01

Our knowledge of the environment of the nucleus of our galaxy has been greatly enhanced, by more extensive and sensitive observations at radio and infrared wavelengths, the advent of high resolution x-ray imaging and spectroscopy, and considerable theoretical activity to understand the nucleus and its components, and their activity. The Galactic Center Workshop 2002 was organized to review recent research on the galactic center, including the latest state-of-the-art observations and important theoretical developments. The workshop covered phenomena on scales ranging from the central several hundred parsecs to the central parsec and within. Each topic was approached from both multi-wavelength observational and theoretical perspectives.

Glucagon-Like Peptide 1 and Its Analogs Act in the Dorsal Raphe and Modulate Central Serotonin to Reduce Appetite and Body Weight.

PubMed

Anderberg, Rozita H; Richard, Jennifer E; Eerola, Kim; López-Ferreras, Lorena; Banke, Elin; Hansson, Caroline; Nissbrandt, Hans; Berqquist, Filip; Gribble, Fiona M; Reimann, Frank; Wernstedt Asterholm, Ingrid; Lamy, Christophe M; Skibicka, Karolina P

2017-04-01

Glucagon-like peptide 1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as antiobesity strategies. Surprisingly, whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the central nervous system. Serotonin depletion impaired the ability of exendin-4, a clinically used GLP-1 analog, to reduce body weight in rats, suggesting that serotonin is a critical mediator of the energy balance impact of GLP-1 receptor (GLP-1R) activation. Serotonin turnover and expression of 5-hydroxytryptamine (5-HT) 2A (5-HT 2A ) and 5-HT 2C serotonin receptors in the hypothalamus were altered by GLP-1R activation. We demonstrate that the 5-HT 2A , but surprisingly not the 5-HT 2C , receptor is critical for weight loss, anorexia, and fat mass reduction induced by central GLP-1R activation. Importantly, central 5-HT 2A receptors are also required for peripherally injected liraglutide to reduce feeding and weight. Dorsal raphe (DR) harbors cell bodies of serotonin-producing neurons that supply serotonin to the hypothalamic nuclei. We show that GLP-1R stimulation in DR is sufficient to induce hypophagia and increase the electrical activity of the DR serotonin neurons. Finally, our results disassociate brain metabolic and emotionality pathways impacted by GLP-1R activation. This study identifies serotonin as a new critical neural substrate for GLP-1 impact on energy homeostasis and expands the current map of brain areas impacted by GLP-1R activation. © 2017 by the American Diabetes Association.

Neuronal Activation in the Central Nervous System of Rats in the Initial Stage of Chronic Kidney Disease-Modulatory Effects of Losartan and Moxonidine

PubMed Central

Palkovits, Miklós; Šebeková, Katarína; Klenovics, Kristina Simon; Kebis, Anton; Fazeli, Gholamreza; Bahner, Udo; Heidland, August

2013-01-01

The effect of mild chronic renal failure (CRF) induced by 4/6-nephrectomy (4/6NX) on central neuronal activations was investigated by c-Fos immunohistochemistry staining and compared to sham-operated rats. In the 4/6 NX rats also the effect of the angiotensin receptor blocker, losartan, and the central sympatholyticum moxonidine was studied for two months. In serial brain sections Fos-immunoreactive neurons were localized and classified semiquantitatively. In 37 brain areas/nuclei several neurons with different functional properties were strongly affected in 4/6NX. It elicited a moderate to high Fos-activity in areas responsible for the monoaminergic innervation of the cerebral cortex, the limbic system, the thalamus and hypothalamus (e.g. noradrenergic neurons of the locus coeruleus, serotonergic neurons in dorsal raphe, histaminergic neurons in the tuberomamillary nucleus). Other monoaminergic cell groups (A5 noradrenaline, C1 adrenaline, medullary raphe serotonin neurons) and neurons in the hypothalamic paraventricular nucleus (innervating the sympathetic preganglionic neurons and affecting the peripheral sympathetic outflow) did not show Fos-activity. Stress- and pain-sensitive cortical/subcortical areas, neurons in the limbic system, the hypothalamus and the circumventricular organs were also affected by 4/6NX. Administration of losartan and more strongly moxonidine modulated most effects and particularly inhibited Fos-activity in locus coeruleus neurons. In conclusion, 4/6NX elicits high activity in central sympathetic, stress- and pain-related brain areas as well as in the limbic system, which can be ameliorated by losartan and particularly by moxonidine. These changes indicate a high sensitivity of CNS in initial stages of CKD which could be causative in clinical disturbances. PMID:23818940

[Neural control of somatic muscle function in the earthworm, Allobophora longa, and in the leech, Hirudo medicinalis].

PubMed

David, O F

1978-01-01

Studies have been made on the electrical activity of the segmentary nerves and connectives of the abdominal nervous chain in the earthworm and leech. It was shown that the electrical activity of the isolated piece of the abdominal chain of the leech is manifested of periodic outbursts of impulsation. Presumably this central periodicity accounts for the discharge-like pattern of muscle rhythmic activity which was revealed in our earlier investigations. The electrical activity in the central nervous system of the earthworm depends on afferent influences which pass to the ganglia from the peripheral sensory nervous cells. Stimulation of the abdominal nervous chain did not result in extra discharges of muscle activity, but only affected some of the parameters of the latter.

Organization of the central control of muscles of facial expression in man

PubMed Central

Root, A A; Stephens, J A

2003-01-01

Surface EMGs were recorded simultaneously from ipsilateral pairs of facial muscles while subjects made three different common facial expressions: the smile, a sad expression and an expression of horror, and three contrived facial expressions. Central peaks were found in the cross-correlograms of EMG activity recorded from the orbicularis oculi and zygomaticus major during smiling, the corrugator and depressor anguli oris during the sad look and the frontalis and mentalis during the horror look. The size of the central peak was significantly greater between the orbicularis oculi and zygomaticus major during smiling. It is concluded that co-contraction of facial muscles during some facial expressions are accompanied by the presence of common synaptic drive to the motoneurones supplying the muscles involved. Central peaks were found in the cross-correlograms of EMG activity recorded from the frontalis and depressor anguli oris during a contrived expression. However, no central peaks were found in the cross-correlograms of EMG activity recorded from the frontalis and orbicularis oculi or from the frontalis and zygomaticus major during the other two contrived expressions. It is concluded that a common synaptic drive is not present between all possible facial muscle pairs and suggests a functional role for the synergy. The origin of the common drive is discussed. It is concluded that activity in branches of common stem last-order presynaptic input fibres to motoneurones innervating the different facial muscles and presynaptic synchronization of input activity to the different motoneurone pools is involved. The former probably contributes more to the drive to the orbicularis oculi and zygomaticus major during smiling, while the latter is probably more prevalent in the corrugator and depressor anguli oris during the sad look, the frontalis and mentalis during the horror look and the frontalis and depressor anguli oris during one of the contrived expressions. The strength of common synaptic drive is inversely related to the degree of separate control that can be exhibited by the facial muscles involved. PMID:12692176

32 CFR 1906.160 - Communications.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Communications. 1906.160 Section 1906.160 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.140 - Employment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Employment. 1906.140 Section 1906.140 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.101 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Purpose. 1906.101 Section 1906.101 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.111 - Notice.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Notice. 1906.111 Section 1906.111 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.111 - Notice.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Notice. 1906.111 Section 1906.111 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.111 - Notice.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Notice. 1906.111 Section 1906.111 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.160 - Communications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Communications. 1906.160 Section 1906.160 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.140 - Employment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Employment. 1906.140 Section 1906.140 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.101 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Purpose. 1906.101 Section 1906.101 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.140 - Employment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Employment. 1906.140 Section 1906.140 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.111 - Notice.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Notice. 1906.111 Section 1906.111 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.111 - Notice.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Notice. 1906.111 Section 1906.111 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.160 - Communications.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Communications. 1906.160 Section 1906.160 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.101 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Purpose. 1906.101 Section 1906.101 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.140 - Employment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Employment. 1906.140 Section 1906.140 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.101 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Purpose. 1906.101 Section 1906.101 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.140 - Employment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Employment. 1906.140 Section 1906.140 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.101 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Purpose. 1906.101 Section 1906.101 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.160 - Communications.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Communications. 1906.160 Section 1906.160 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.160 - Communications.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Communications. 1906.160 Section 1906.160 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

40 CFR 437.1 - General applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... centralized silver recovery from used photographic or x-ray materials activities. The discharge resulting from centralized silver recovery from used photographic or x-ray materials that is treated at a CWT facility along... Nickel Subcategory), Subpart X (Secondary Precious Metals Subcategory), Subpart Z (Secondary Tantalum...

40 CFR 437.1 - General applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... centralized silver recovery from used photographic or x-ray materials activities. The discharge resulting from centralized silver recovery from used photographic or x-ray materials that is treated at a CWT facility along... Nickel Subcategory), subpart X (Secondary Precious Metals Subcategory), subpart Z (Secondary Tantalum...

A study of reconstruction accuracy for a cardiac SPECT system with multi-segmental collimation

NASA Astrophysics Data System (ADS)

Yu, D.-C.; Chang, W.; Pan, T.-S.

1997-06-01

To improve the geometric efficiency of cardiac SPECT imaging, the authors previously proposed to use a multi-segmental collimation with a cylindrical geometry. The proposed collimator consists of multiple parallel-hole collimators with most of the segments directed toward a small central region, where the patient's heart should be positioned. This technique provides a significantly increased detection efficiency for the central region, but at the expense of reduced efficiency for the surrounding region. The authors have used computer simulations to evaluate the implication of this technique on the accuracy of the reconstructed cardiac images. Two imaging situations were simulated: 1) the heart well placed inside the central region, and 2) the heart shifted and partially outside the central region. A neighboring high-uptake liver was simulated for both imaging situations. The images were reconstructed and corrected for attenuation with ML-EM and OS-FM methods using a complete attenuation map. The results indicate that errors caused by projection truncation are not significant and are not strongly dependent on the activity of the liver when the heart is well positioned within the central region. When the heart is partially outside the central region, hybrid emission data (a combination of high-count projections from the central region and low-count projections from the background region) can be used to restore the activity of the truncated section of the myocardium. However, the variance of the image in the section of the myocardium outside the central region is increased by 2-3 times when 10% of the collimator segments are used to image the background region.

A review of bioinformatics training applied to research in molecular medicine, agriculture and biodiversity in Costa Rica and Central America.

PubMed

Orozco, Allan; Morera, Jessica; Jiménez, Sergio; Boza, Ricardo

2013-09-01

Today, Bioinformatics has become a scientific discipline with great relevance for the Molecular Biosciences and for the Omics sciences in general. Although developed countries have progressed with large strides in Bioinformatics education and research, in other regions, such as Central America, the advances have occurred in a gradual way and with little support from the Academia, either at the undergraduate or graduate level. To address this problem, the University of Costa Rica's Medical School, a regional leader in Bioinformatics in Central America, has been conducting a series of Bioinformatics workshops, seminars and courses, leading to the creation of the region's first Bioinformatics Master's Degree. The recent creation of the Central American Bioinformatics Network (BioCANET), associated to the deployment of a supporting computational infrastructure (HPC Cluster) devoted to provide computing support for Molecular Biology in the region, is providing a foundational stone for the development of Bioinformatics in the area. Central American bioinformaticians have participated in the creation of as well as co-founded the Iberoamerican Bioinformatics Society (SOIBIO). In this article, we review the most recent activities in education and research in Bioinformatics from several regional institutions. These activities have resulted in further advances for Molecular Medicine, Agriculture and Biodiversity research in Costa Rica and the rest of the Central American countries. Finally, we provide summary information on the first Central America Bioinformatics International Congress, as well as the creation of the first Bioinformatics company (Indromics Bioinformatics), spin-off the Academy in Central America and the Caribbean.

Maintenance of Mouse Gustatory Terminal Field Organization Is Disrupted following Selective Removal of Peripheral Sodium Salt Taste Activity at Adulthood.

PubMed

Skyberg, Rolf; Sun, Chengsan; Hill, David L

2017-08-09

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience. SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits. Copyright © 2017 the authors 0270-6474/17/377619-12$15.00/0.

Active Site Gate Dynamics Modulate the Catalytic Activity of the Ubiquitination Enzyme E2-25K.

PubMed

Rout, Manoj K; Lee, Brian L; Lin, Aiyang; Xiao, Wei; Spyracopoulos, Leo

2018-05-03

The ubiquitin proteasome system (UPS) signals for degradation of proteins through attachment of K48-linked polyubiquitin chains, or alterations in protein-protein recognition through attachment of K63-linked chains. Target proteins are ubiquitinated in three sequential chemical steps by a three-component enzyme system. Ubiquitination, or E2 enzymes, catalyze the central step by facilitating reaction of a target protein lysine with the C-terminus of Ub that is attached to the active site cysteine of the E2 through a thioester bond. E2 reactivity is modulated by dynamics of an active site gate, whose central residue packs against the active site cysteine in a closed conformation. Interestingly, for the E2 Ubc13, which specifically catalyzes K63-linked ubiquitination, the central gate residue adopts an open conformation. We set out to determine if active site gate dynamics play a role in catalysis for E2-25K, which adopts the canonical, closed gate conformation, and which selectively synthesizes K48-linked ubiquitin chains. Gate dynamics were characterized using mutagenesis of key residues, combined with enzyme kinetics measurements, and main chain NMR relaxation. The experimental data were interpreted with all atom MD simulations. The data indicate that active site gate opening and closing rates for E2-25K are precisely balanced.

Central Limit Theorem: New SOCR Applet and Demonstration Activity

PubMed Central

Dinov, Ivo D.; Christou, Nicolas; Sanchez, Juana

2011-01-01

Modern approaches for information technology based blended education utilize a variety of novel instructional, computational and network resources. Such attempts employ technology to deliver integrated, dynamically linked, interactive content and multifaceted learning environments, which may facilitate student comprehension and information retention. In this manuscript, we describe one such innovative effort of using technological tools for improving student motivation and learning of the theory, practice and usability of the Central Limit Theorem (CLT) in probability and statistics courses. Our approach is based on harnessing the computational libraries developed by the Statistics Online Computational Resource (SOCR) to design a new interactive Java applet and a corresponding demonstration activity that illustrate the meaning and the power of the CLT. The CLT applet and activity have clear common goals; to provide graphical representation of the CLT, to improve student intuition, and to empirically validate and establish the limits of the CLT. The SOCR CLT activity consists of four experiments that demonstrate the assumptions, meaning and implications of the CLT and ties these to specific hands-on simulations. We include a number of examples illustrating the theory and applications of the CLT. Both the SOCR CLT applet and activity are freely available online to the community to test, validate and extend (Applet: http://www.socr.ucla.edu/htmls/SOCR_Experiments.html and Activity: http://wiki.stat.ucla.edu/socr/index.php/SOCR_EduMaterials_Activities_GeneralCentralLimitTheorem). PMID:21833159

Central Limit Theorem: New SOCR Applet and Demonstration Activity.

PubMed

Dinov, Ivo D; Christou, Nicolas; Sanchez, Juana

2008-07-01

Modern approaches for information technology based blended education utilize a variety of novel instructional, computational and network resources. Such attempts employ technology to deliver integrated, dynamically linked, interactive content and multifaceted learning environments, which may facilitate student comprehension and information retention. In this manuscript, we describe one such innovative effort of using technological tools for improving student motivation and learning of the theory, practice and usability of the Central Limit Theorem (CLT) in probability and statistics courses. Our approach is based on harnessing the computational libraries developed by the Statistics Online Computational Resource (SOCR) to design a new interactive Java applet and a corresponding demonstration activity that illustrate the meaning and the power of the CLT. The CLT applet and activity have clear common goals; to provide graphical representation of the CLT, to improve student intuition, and to empirically validate and establish the limits of the CLT. The SOCR CLT activity consists of four experiments that demonstrate the assumptions, meaning and implications of the CLT and ties these to specific hands-on simulations. We include a number of examples illustrating the theory and applications of the CLT. Both the SOCR CLT applet and activity are freely available online to the community to test, validate and extend (Applet: http://www.socr.ucla.edu/htmls/SOCR_Experiments.html and Activity: http://wiki.stat.ucla.edu/socr/index.php/SOCR_EduMaterials_Activities_GeneralCentralLimitTheorem).

Central and peripheral components of short latency vestibular responses in the chicken

NASA Technical Reports Server (NTRS)

Nazareth, A. M.; Jones, T. A.

1998-01-01

Far-field recordings of short latency vestibular responses to pulsed cranial translation are composed of a series of positive and negative peaks occurring within 10 ms following stimulus onset. In the bird, these vestibular evoked potentials (VsEPs) can be recorded noninvasively and have been shown in the chicken and quail to depend strictly upon the activation of the vestibular component of the eighth nerve. The utility of the VsEP in the study of vestibular systems is dependent upon a clear understanding of the neural sources of response components. The primary aim of the current research in the chicken was to critically test the hypotheses that 1) responses are generated by both peripheral and central neurons and 2) peaks P1 and N1 originate from first order vestibular neurons, whereas later waves primarily depend on activity in higher order neurons. The principal strategy used here was to surgically isolate the eighth nerve as it enters the brainstem. Interruption of primary afferents of the eighth nerve in the brainstem substantially reduced or eliminated peaks beyond P2, whereas P1 and N1 were generally spared. Surgical sections that spared vestibular pathways had little effect on responses. The degree of change in response components beyond N1 was correlated with the extent of damage to central vestibular relays. These findings support the conclusion that responses are produced by both peripheral and central elements of the vestibular system. Further, response peaks later than N1 appear to be dependent upon central relays, whereas P1 and N1 reflect activity of the peripheral nerve. These findings clarify the roles of peripheral and central neurons in the generation of vestibular evoked potentials and provide the basis for a more useful and detailed interpretation of data from vestibular response testing.

Attentional load and sensory competition in human vision: modulation of fMRI responses by load at fixation during task-irrelevant stimulation in the peripheral visual field.

PubMed

Schwartz, Sophie; Vuilleumier, Patrik; Hutton, Chloe; Maravita, Angelo; Dolan, Raymond J; Driver, Jon

2005-06-01

Perceptual suppression of distractors may depend on both endogenous and exogenous factors, such as attentional load of the current task and sensory competition among simultaneous stimuli, respectively. We used functional magnetic resonance imaging (fMRI) to compare these two types of attentional effects and examine how they may interact in the human brain. We varied the attentional load of a visual monitoring task performed on a rapid stream at central fixation without altering the central stimuli themselves, while measuring the impact on fMRI responses to task-irrelevant peripheral checkerboards presented either unilaterally or bilaterally. Activations in visual cortex for irrelevant peripheral stimulation decreased with increasing attentional load at fixation. This relative decrease was present even in V1, but became larger for successive visual areas through to V4. Decreases in activation for contralateral peripheral checkerboards due to higher central load were more pronounced within retinotopic cortex corresponding to 'inner' peripheral locations relatively near the central targets than for more eccentric 'outer' locations, demonstrating a predominant suppression of nearby surround rather than strict 'tunnel vision' during higher task load at central fixation. Contralateral activations for peripheral stimulation in one hemifield were reduced by competition with concurrent stimulation in the other hemifield only in inferior parietal cortex, not in retinotopic areas of occipital visual cortex. In addition, central attentional load interacted with competition due to bilateral versus unilateral peripheral stimuli specifically in posterior parietal and fusiform regions. These results reveal that task-dependent attentional load, and interhemifield stimulus-competition, can produce distinct influences on the neural responses to peripheral visual stimuli within the human visual system. These distinct mechanisms in selective visual processing may be integrated within posterior parietal areas, rather than earlier occipital cortex.

Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

PubMed Central

Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

2014-01-01

Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS, no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and movement, pressure pain thresholds (PPTs), 6 minute walk test (6MWT), range of motion (ROM), five time sit to stand test (FTSTS), and single leg stance (SLS). Conditioned pain modulation (CPM) was completed at end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. PPTs increased at site of TENS (spine) and outside site of TENS (leg) when compared to placebo TENS or no TENS. During Active TENS CPM was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to how TENS is used clinically, on pain, fatigue, function and quality of life in individuals with fibromyalgia. PMID:23900134

Role of central command in carotid baroreflex resetting in humans during static exercise

NASA Technical Reports Server (NTRS)

Ogoh, S.; Wasmund, W. L.; Keller, D. M.; O-Yurvati, A.; Gallagher, K. M.; Mitchell, J. H.; Raven, P. B.

2002-01-01

The purpose of the experiments was to examine the role of central command in the exercise-induced resetting of the carotid baroreflex. Eight subjects performed 30 % maximal voluntary contraction (MVC) static knee extension and flexion with manipulation of central command (CC) by patellar tendon vibration (PTV). The same subjects also performed static knee extension and flexion exercise without PTV at a force development that elicited the same ratings of perceived exertion (RPE) as those observed during exercise with PTV in order to assess involvement of the exercise pressor reflex. Carotid baroreflex (CBR) function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid changes in neck pressure and suction during steady state static exercise. Knee extension exercise with PTV (decreased CC activation) reset the CBR-HR and CBR-MAP to a lower operating pressure (P < 0.05) and knee flexion exercise with PTV (increased CC activation) reset the CBR-HR and CBR-MAP to a higher operating pressure (P < 0.05). Comparison between knee extension and flexion exercise at the same RPE with and without PTV found no difference in the resetting of the CBR-HR function curves (P > 0.05) suggesting the response was determined primarily by CC activation. However, the CBR-MAP function curves were reset to operating pressures determined by both exercise pressor reflex (EPR) and central command activation. Thus the physiological response to exercise requires CC activation to reset the carotid-cardiac reflex but requires either CC or EPR to reset the carotid-vasomotor reflex.

Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology

PubMed Central

Browning, Kirsteen N.

2015-01-01

Vagal neurocircuits are vitally important in the co-ordination and modulation of GI reflexes and homeostatic functions. 5-hydroxytryptamine (5-HT; serotonin) is critically important in the regulation of several of these autonomic gastrointestinal (GI) functions including motility, secretion and visceral sensitivity. While several 5-HT receptors are involved in these physiological responses, the ligand-gated 5-HT3 receptor appears intimately involved in gut-brain signaling, particularly via the afferent (sensory) vagus nerve. 5-HT is released from enterochromaffin cells in response to mechanical or chemical stimulation of the GI tract which leads to activation of 5-HT3 receptors on the terminals of vagal afferents. 5-HT3 receptors are also present on the soma of vagal afferent neurons, including GI vagal afferent neurons, where they can be activated by circulating 5-HT. The central terminals of vagal afferents also exhibit 5-HT3 receptors that function to increase glutamatergic synaptic transmission to second order neurons of the nucleus tractus solitarius within the brainstem. While activation of central brainstem 5-HT3 receptors modulates visceral functions, it is still unclear whether central vagal neurons, i.e., nucleus of the tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) neurons themselves also display functional 5-HT3 receptors. Thus, activation of 5-HT3 receptors may modulate the excitability and activity of gastrointestinal vagal afferents at multiple sites and may be involved in several physiological and pathophysiological conditions, including distention- and chemical-evoked vagal reflexes, nausea, and vomiting, as well as visceral hypersensitivity. PMID:26578870

Epigenetic role for the conserved Fe-S cluster biogenesis protein AtDRE2 in Arabidopsis thaliana.

PubMed

Buzas, Diana Mihaela; Nakamura, Miyuki; Kinoshita, Tetsu

2014-09-16

On fertilization in Arabidopsis thaliana, one maternal gamete, the central cell, forms a placenta-like tissue, the endosperm. The DNA glycosylase DEMETER (DME) excises 5-methylcytosine via the base excision repair pathway in the central cell before fertilization, creating patterns of asymmetric DNA methylation and maternal gene expression across DNA replications in the endosperm lineage (EDL). Active DNA demethylation in the central cell is essential for transcriptional activity in the EDL of a set of genes, including FLOWERING WAGENINGEN (FWA). A DME-binding motif for iron-sulfur (Fe-S) cluster cofactors is indispensable for its catalytic activity. We used an FWA-GFP reporter to find mutants defective in maternal activation of FWA-GFP in the EDL, and isolated an allele of the yeast Dre2/human antiapoptotic factor CIAPIN1 homolog, encoding an enzyme previously implicated in the cytosolic Fe-S biogenesis pathway (CIA), which we named atdre2-2. We found that AtDRE2 acts in the central cell to regulate genes maternally activated in the EDL by DME. Furthermore, the FWA-GFP expression defect in atdre2-2 was partially suppressed genetically by a mutation in the maintenance DNA methyltransferase MET1; the DNA methylation levels at four DME targets increased in atdre2-2 seeds relative to WT. Although atdre2-2 shares zygotic seed defects with CIA mutants, it also uniquely manifests dme phenotypic hallmarks. These results demonstrate a previously unidentified epigenetic function of AtDRE2 that may be separate from the CIA pathway.

Autonomic responses to exercise: where is central command?

PubMed

Williamson, J W

2015-03-01

A central command is thought to involve a signal arising in a central area of the brain eliciting a parallel activation of the autonomic nervous system and skeletal muscle contraction during exercise. Although much of the neural circuitry involved in autonomic control has been identified, defining the specific higher brain region(s) serving in a central command capacity has proven more challenging. Investigators have been faced with redundancies in regulatory systems, feedback mechanisms and the complexities ofhuman neural connectivity. Several studies have attempted to address these issues and provide more definitive neuroanatomical information. However, none have clearly answered the question, "where is central command?" Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis of Nonpoint-Source Ground-Water Contamination in Relation to Land Use: Assessment of Nonpoint-Source Contamination in Central Florida

USGS Publications Warehouse

German, Edward R.

1996-01-01

In central Florida, activities that might affect the quality of ground water include disposal of stormwater through drainage wells, citrus cultivation, and mining and processing of phosphate ore. Possible effects of these and other land-use activities include high concentrations of nitrogen compounds and the pesticide bromacil in the citrus area, and high concentrations of most of the major-dissolved constituents and some organic compounds in the mining area.

The effects of Dalmane /flurazepam hydrochloride/ on human EEG characteristics.

NASA Technical Reports Server (NTRS)

Frost, J. D., Jr.; Carrie, J. R. G.; Borda, R. P.; Kellaway, P.

1973-01-01

Evaluation of the changes in the waking EEGs of six healthy male subjects who received 30 mg daily oral doses of flurazepam hydrochloride for two weeks. A placebo was then substituted for flurazepam for another two weeks. An increase in beta activity with a maximum in fronto-central leads was observed during the test period. A small increase in the mean wavelength of the alpha and theta activities in the central-occipital derivations was also apparent in the subjects during the period.

[Role of central alpha-adrenoreceptors in the mechanism of the hyperthermic action of prostaglandin E2].

PubMed

Gurin, V N; Vismont, F I; Tsariuk, V V

1984-01-01

It has been demonstrated in rat experiments that the central action of PGE2 results in body temperature rise associated with a reduction in the functional activity of hypothalamic adrenergic systems. In contrast to PGE2 and the beta-adrenomimetic isoproterenol, the alpha-adrenomimetics noradrenaline, mezaton and clonidine were shown to lower body temperature. In the rabbit, clonidine and PGE2 were found to have opposing effects on the neuronal activity of the anterior hypothalamus.

The Redox Proteome*

PubMed Central

Go, Young-Mi; Jones, Dean P.

2013-01-01

The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges. PMID:23861437

Map showing seismicity and sandblows in the vicinity of New Madrid, Missouri

USGS Publications Warehouse

Rhea, B. Susan; Tarr, Arthur C.; Wheeler, Russell L.

1994-01-01

This is one of a series of five seismotectic maps of the seismically active New Madrid, Missouri, area (table 1; Wheeler and others, 1992). The map area centers near the sites of three great earthquakes that struck during the winter of 1811-12 (Fuller, 1912; Nuttli, 1973). These earthquakes and continuing subsequent seismicity rank the New Madrid area with Cherlevoix, Quebec, as the two most seismically active areas in North America east of the Rocky Mountains. The threat posed by New Madrid seismicity to the central United States makes the area the focus of many investigations (for examples, Heyl and McKeown, 1978; McKeown and Pakiser, 1982; Algemissen and Hopper, 1984; Hamilton and Johnston, 1990; Applied Technology Council, 1991; Johnston and others, 1992). The map area includes the most intense seismic activity in the New Madrid region. A seismotectic map shows some of the geologic and geophysical information needed to assess seismic hazard (Hadley and Devine, 1974; Pavoni, 1985). A previous seismotectonic map of the central Mississippi River valley (Heyl and McKeown, 1978) has had wide use for planning field surveys, as a base map for plotting data collected during single investigations, and for compiling a range of information. Since 1978 numcrous researchers have greatly advanced our knowledge of the geology and geophysics of the central Mississippi Valley. The New Madrid seismotectonic map folio updates approximately the south-central sixth of the central Mississippi Valley seismotectonic map of Heyl and McKeown (1978).

The effects of central pro-and anti-inflammatory immune challenges on depressive-like behavior induced by chronic forced swim stress in rats.

PubMed

Pan, Yuqin; Lin, Wenjuan; Wang, Weiwen; Qi, Xiaoli; Wang, Donglin; Tang, Mingming

2013-06-15

Although increasing evidence demonstrates that both chronic stressors and inflammatory immune activation contribute to pathophysiology and behavioral alterations associated with major depression, little is known about the interaction effect of central inflammatory immune activation and stress on depressive-like behavior. Our previous work has shown that 14-day chronic forced swim stress induces significant depressive-like behavior. The present investigation assessed whether pro-inflammatory cytokine and anti-inflammatory cytokine challenges have differential interaction effect on depressive-like behavior induced by chronic forced swim stress in rats. The pro-inflammatory and anti-inflammatory immune challenges were achieved respectively by central administration of lipopolysaccharide (LPS), a pro-inflammatory cytokine inducer, and interleukin-10 (IL-10), an anti-inflammatory cytokine. It was found that either central LPS treatment alone or chronic forced swim stress alone significantly induced depressive-like behavior, including reduced body weight gain, reduced saccharin preference and reduced locomotor activity. However, there was no significant synergistic or additive effect of central LPS treatment and stress on depressive-like behavior. LPS treatment did not exacerbate the depressive-like behavior induced by forced swim stress. Nevertheless, IL-10 reversed depressive-like behavior induced by forced swim stress, a finding indicating that IL-10 has antidepressant effect on behavioral depression induced by stress. The present findings provide new insight into the complexity of the immunity-inflammation hypothesis of depression. Copyright © 2013 Elsevier B.V. All rights reserved.

Gullies in a Central Pit Crater

NASA Image and Video Library

2015-10-14

Sometimes a central pit forms inside some Martian craters, especially when there substantial ground ice. Such is the case in this observation from NASA Mars Reconnaissance Orbiter spacecraft. Sometimes what we call "mass wasting" processes (think small avalanches or landslides) occur on the slopes of the central pit. We took this image to search for any recent activity that would add to or modify previously identified gullies. http://photojournal.jpl.nasa.gov/catalog/PIA20005

Combating Gangs: Federal Agencies Have Implemented a Central American Gang Strategy, but Could Strengthen Oversight and Measurement of Efforts. Report to Congressional Requesters. GAO-10-395

ERIC Educational Resources Information Center

Larence, Eileen R.

2010-01-01

Thousands of gang members in the United States belong to gangs such as MS-13 and 18th Street that are also active in Central American countries. Federal entities with responsibilities for addressing Central American gangs include the National Security Council (NSC); the Departments of Homeland Security (DHS), Justice (DOJ), and State; and the U.S.…

[Individual Types Reactivity of EEG Oscillations in Effective Heart Rhythm Biofeedback Parameters in Adolescents and Young People in the North].

PubMed

Krivonogova, E V; Poskotinova, L V; Demin, D B

2015-01-01

A single session of heart rate variability (HRV) biofeedback in apparently healthy young people and adolescents aged 14-17 years in order to increase vagal effects on heart rhythm and also electroencephalograms were carried out. Different variants of EEG spectral power during the successful HRV biofeedback session were identified. In the case of I variant of EEG activity the increase of power spectrum of alpha-, betal-, theta-components takes place in all parts of the brain. In the case of II variant of EEG activity the reduction of power spectrum of alpha-, betal-, theta-activity in all parts of the brain was observed. I and II variants of EEG activity cause more intensive regime of cortical-subcortical interactions. During the III variant of EEG activity the successful biofeedback is accompanied by increase of alpha activity in the central, front and anteriofrontal brain parts and so indicates the formation of thalamocortical relations of neural network in order to optimize the vegetal regulation of heart function. There was an increase in alpha- and beta1-activity in the parietal, central, frontal and temporal brain parts during the IV variant of EEG activity and so that it provides the relief of neural networks communication for information processing. As a result of V variance of EEG activity there was the increase of power spectrum of theta activity in the central and frontal parts of both cerebral hemispheres, so it was associated with the cortical-hippocampal interactions to achieve a successful biofeedback.

28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

Acute and prolonged complement activation in the central nervous system during herpes simplex encephalitis.

PubMed

Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas

2016-06-15

Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

Control of Vertebrate Respiration and Locomotion: A Brief Account.

ERIC Educational Resources Information Center

Feldman, Jack L.; Grillner, Sten

1983-01-01

Areas considered in this discussion include: activation/modulation of movement; control of motoneuronal discharge by excitation/inhibition; neural generation of movement synergies (considering interaction of central/peripheral elements, phasic gating of reflex effects, and neuronal organization of central pattern generators); protean nature of…

32 CFR 1906.110 - Self-evaluation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Self-evaluation. 1906.110 Section 1906.110 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.110 - Self-evaluation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Self-evaluation. 1906.110 Section 1906.110 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.110 - Self-evaluation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Self-evaluation. 1906.110 Section 1906.110 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.110 - Self-evaluation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Self-evaluation. 1906.110 Section 1906.110 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

32 CFR 1906.110 - Self-evaluation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Self-evaluation. 1906.110 Section 1906.110 National Defense Other Regulations Relating to National Defense CENTRAL INTELLIGENCE AGENCY ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE CENTRAL INTELLIGENCE AGENCY...

RELATIONSHIPS BETWEEN ENVIRONMENTAL VARIABLES AND BENTHIC DIATOM ASSEMBLAGES IN CALIFORNIA CENTRAL VALLEY STREAMS (USA)

EPA Science Inventory

Streams and rivers in the California Central Valley Ecoregion have been substantially modified by human activities. This study examines distributional patterns of benthic diatom assemblages in relation to environmental characteristics in streams and rivers of this region. Benthic...

Increased urinary excretion rates of serotonin and metabolites during bedrest

NASA Astrophysics Data System (ADS)

Platen, Petra; Lebenstedt, Marion; Schneider, Myriam; Boese, Andrea; Heer, Martina

2005-05-01

Astronauts are often on a voluntarily reduced energy intake during space missions, possibly caused by a metabolic or emotional stress response with involvement of the central serotonergic system (SES). We investigated 24 h urinary excretion (24 h-E) of serotonin (5-HT) and 5-hydroxyindol acidic acid as indicators of the SES in healthy males under two different normocaloric conditions: normal physical activity (NPA) and -6∘ head-down-tilt (HDT). HDT or NPA were randomly arranged with a recovery period of 6 months in between. 24 h-E of hormones varied widely among individuals. Values were higher in HDT compared to NPA. Assuming that the 24 h-E values are, beside being indicators for alterations in the number and metabolism of platelets, Also indicators of central SES, HDT condition seems to activate central SES in a higher degree compared to NPA. Therefore, changes in central SES might be involved in the mechanisms associated with space flight or microgravity, including possible maladaptations such as voluntary undernutrition.

The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation.

PubMed

Rocha, Ana Sofia; Vidal, Valerie; Mertz, Marjolijn; Kendall, Timothy J; Charlet, Aurelie; Okamoto, Hitoshi; Schedl, Andreas

2015-12-01

Liver zonation, the spatial separation of different metabolic pathways along the liver sinusoids, is fundamental for proper functioning of this organ, and its disruption can lead to the development of metabolic disorders such as hyperammonemia. Metabolic zonation involves the induction of β-catenin signaling around the central veins, but how this patterned activity is established and maintained is unclear. Here, we show that the signaling molecule Rspondin3 is specifically expressed within the endothelial compartment of the central vein. Conditional deletion of Rspo3 in mice disrupts activation of central fate, demonstrating its crucial role in determining and maintaining β-catenin-dependent zonation. Moreover, ectopic expression of Rspo1, a close family member of Rspo3, induces the expression of pericentral markers, demonstrating Rspondins to be sufficient to imprint a more central fate. Thus, Rspo3 is a key angiocrine factor that controls metabolic zonation of liver hepatocytes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Interactive effects of mechano- and chemo-receptor inputs on cardiorespiratory outputs in the toad.

PubMed

Wang, T; Taylor, E W; Reid, S G; Milsom, W K

2004-04-20

Arterial blood pressure (P(b)), pulmocutaneous blood flow (Q(pc)), heart rate (f(H)), and fictive ventilation (motor activity in the Vth cranial nerve, V(int)), were recorded from decerebrated, paralysed toads receiving unidirectional ventilation with experimental gas mixtures over a range of lung inflation. At the onset of spontaneous bouts of fictive ventilation, (Q(pc)) and P(b) increased immediately, often with changes in heart rate, implying central cardiorespiratory interactions. Inflation of the lungs with different gas mixtures revealed that the effect of hypercarbia on V(int) was reduced by lung inflation and that feedback from pulmonary stretch receptors may summate with central feedforward control of f(H) and (Q(pc)) in an interactive fashion. The results of bolus injections of cyanide into the carotid or the pulmonary circulations suggest there are oxygen sensitive receptors in both circuits that affect the cardiovascular system directly and respiratory activity by complex central interactions with inputs from central chemoreceptors and pulmonary stretch receptors.

The p38α mitogen-activated protein kinase as a central nervous system drug discovery target

PubMed Central

Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

2008-01-01

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38α mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38α MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38α MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38α MAPK in neurodegenerative disorders. PMID:19090985

The p38alpha mitogen-activated protein kinase as a central nervous system drug discovery target.

PubMed

Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

2008-12-03

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38alpha mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38alpha MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38alpha MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38alpha MAPK in neurodegenerative disorders.

Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense Physical Activity.

PubMed

Coca, Mircea; Tecle, Nahom; Amde, Wendewessen; Mehta, Ankur

2017-08-23

We report a case of combined central retinal vein occlusion and branch retinal artery occlusion. A previously healthy 47-year-old male presented with decreased vision in the right eye after completing a half marathon. A fundus exam and retinal imaging revealed a combined central retinal vein and branch retinal artery occlusion. In the present report, we review the literature and discuss the possible mechanisms behind combined retinal vessel occlusions. To our knowledge, this is the first reported case of combined central retinal vein occlusion and branch retinal artery occlusion following intense exercise.

Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense Physical Activity

PubMed Central

Tecle, Nahom; Amde, Wendewessen; Mehta, Ankur

2017-01-01

We report a case of combined central retinal vein occlusion and branch retinal artery occlusion. A previously healthy 47-year-old male presented with decreased vision in the right eye after completing a half marathon. A fundus exam and retinal imaging revealed a combined central retinal vein and branch retinal artery occlusion. In the present report, we review the literature and discuss the possible mechanisms behind combined retinal vessel occlusions. To our knowledge, this is the first reported case of combined central retinal vein occlusion and branch retinal artery occlusion following intense exercise. PMID:29067224

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases.

PubMed

Yarandi, Shadi S; Peterson, Daniel A; Treisman, Glen J; Moran, Timothy H; Pasricha, Pankaj J

2016-04-30

Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

Expression, purification, and DNA-binding activity of the solubilized NtrC protein of Herbaspirillum seropedicae.

PubMed

Twerdochlib, Adriana L; Chubatsu, Leda S; Souza, Emanuel M; Pedrosa, Fábio O; Steffens, M Berenice R; Yates, M Geoffrey; Rigo, Liu U

2003-07-01

NtrC is a bacterial enhancer-binding protein (EBP) that activates transcription by the sigma54 RNA polymerase holoenzyme. NtrC has a three domain structure typical of EBP family. In Herbaspirillum seropedicae, an endophytic diazotroph, NtrC regulates several operons involved in nitrogen assimilation, including glnAntrBC. In order to over-express and purify the NtrC protein, DNA fragments containing the complete structural gene for the whole protein, and for the N-terminal+Central and Central+C-terminal domains were cloned into expression vectors. The NtrC and NtrC(N-terminal+Central) proteins were over-expressed as His-tag fusion proteins upon IPTG addition, solubilized using N-lauryl-sarcosyl and purified by metal affinity chromatography. The over-expressed His-tag-NtrC(Central+C-terminal) fusion protein was partially soluble and was also purified by affinity chromatography. DNA band-shift assays showed that the NtrC protein and the Central+C-terminal domains bound specifically to the H. seropedicae glnA promoter region. The C-terminal domain is presumably necessary for DNA-protein interaction and DNA-binding does not require a phosphorylated protein.

Effects of acute handling stress on short-term central expression of orexigenic/anorexigenic genes in zebrafish.

PubMed

Cortés, Raul; Teles, Mariana; Oliveira, Miguel; Fierro-Castro, Camino; Tort, Lluis; Cerdá-Reverter, José Miguel

2018-02-01

Physiological mechanisms driving stress response in vertebrates are evolutionarily conserved. These mechanisms involve the activation of both the hypothalamic-sympathetic-chromaffin cell (HSC) and the hypothalamic-pituitary-adrenal (HPA) axes. In fish, the reduction of food intake levels is a common feature of the behavioral response to stress but the central mechanisms coordinating the energetic response are not well understood yet. In this work, we explore the effects of acute stress on key central systems regulating food intake in fish as well as on total body cortisol and glucose levels. We show that acute stress induced a rapid increase in total body cortisol with no changes in body glucose, at the same time promoting a prompt central response by activating neuronal pathways. All three orexigenic peptides examined, i.e., neuropeptide y (npy), agouti-related protein (agrp), and ghrelin, increased their central expression level suggesting that these neuronal systems are not involved in the short-term feeding inhibitory effects of acute stress. By contrast, the anorexigenic precursors tested, i.e., cart peptides and pomc, exhibited increased expression after acute stress, suggesting their involvement in the anorexigenic effects.

The Influence of Closeness Centrality on Lexical Processing

PubMed Central

Goldstein, Rutherford; Vitevitch, Michael S.

2017-01-01

The present study examined how the network science measure known as closeness centrality (which measures the average distance between a node and all other nodes in the network) influences lexical processing. In the mental lexicon, a word such as CAN has high closeness centrality, because it is close to many other words in the lexicon. Whereas, a word such as CURE has low closeness centrality because it is far from other words in the lexicon. In an auditory lexical decision task (Experiment 1) participants responded more quickly to words with high closeness centrality. In Experiment 2 an auditory lexical decision task was again used, but with a wider range of stimulus characteristics. Although, there was no main effect of closeness centrality in Experiment 2, an interaction between closeness centrality and frequency of occurrence was observed on reaction times. The results are explained in terms of partial activation gradually strengthening over time word-forms that are centrally located in the phonological network. PMID:29018396

Bat activity following restoration prescribed burning in the central Appalachian Upland and riparian habitats

USGS Publications Warehouse

Austin, Lauren V.; Silvis, Alexander; Ford, W. Mark; Muthersbaugh, Michael; Powers, Karen E.

2018-01-01

After decades of fire suppression in eastern North America, land managers now are prioritizing prescribed fire as a management tool to restore or maintain fire-adapted vegetation communities. However, in long—fire-suppressed landscapes, such as the central and southern Appalachians, it is unknown how bats will respond to prescribed fire in both riparian and upland forest habitats. To address these concerns, we conducted zero-crossing acoustic surveys of bat activity in burned, unburned, riparian, and non-riparian areas in the central Appalachians, Virginia, USA. Burn and riparian variables had model support (ΔAICc < 4) to explain activity of all bat species. Nonetheless, parameter estimates for these conditions were small and confidence intervals overlapped zero for all species, indicating effect sizes were marginal. Our results suggest that bats respond to fire differently between upland and riparian forest habitats, but overall, large landscape-level prescribed fire has a slightly positive to neutral impact on all bats species identified at our study site post—fire application.

Thermal activation energy for bidirectional movement of actin along bipolar tracks of myosin filaments.

PubMed

Okubo, Hiroyuki; Iwai, Masanori; Iwai, Sosuke; Chaen, Shigeru

2010-05-28

Previous in vitro motility assays using bipolar myosin thick filaments demonstrated that actin filaments were capable of moving in both directions along the myosin filament tracks. The movements; however, were slower in the direction leading away from the central bare zone than towards it. To understand the mechanism underlying these different direction-dependent motilities, we have examined the effects of temperature on the velocities of the bidirectional movements along reconstituted myosin filaments. Activation energies of the movements were determined by Arrhenius plots at high and low concentrations of ATP. As a result, the thermal activation energy of the movement away from the central bare zone was significantly higher than that of the movement toward the zone. Given that the backward movement away from the central bare zone would cause the myosin heads to be constrained and the stiffness of the cross-bridges to increase, these results suggest that elastic energy required for the cross-bridge transition is supplied by thermal fluctuations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

PubMed

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-05-01

Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks

PubMed Central

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-01-01

Abstract Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic–pituitary–adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases. PMID:29713692

AGN ACTIVITY AND IGM HEATING IN THE FOSSIL CLUSTER RX J1416.4+2315

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miraghaei, H.; Khosroshahi, H. G.; Abbassi, S.

2015-12-15

We study active galactic nucleus (AGN) activity in the fossil galaxy cluster RX J1416.4+2315. Radio observations were carried out using the Giant Metrewave Radio Telescope at two frequencies, 1420 and 610 MHz. A weak radio lobe that extends from the central nucleus is detected in the 610 MHz map. Assuming the radio lobe originated from the central AGN, we show that the energy injection into the intergalactic medium is only sufficient to heat up the central 50 kpc within the cluster core, while the cooling radius is larger (∼130 kpc). In the hardness ratio map, three low energy cavities havemore » been identified. No radio emission is detected for these regions. We evaluated the power required to inflate the cavities and showed that the total energy budget is sufficient to offset the radiative cooling. We showed that the initial conditions would change the results remarkably. Furthermore, the efficiency of the Bondi accretion in powering the AGN has been estimated.« less

Pharmacogenetic research activity in Central America and the Caribbean: a systematic review

PubMed Central

Céspedes-Garro, Carolina; Naranjo, María-Eugenia G; Rodrigues-Soares, Fernanda; LLerena, Adrián; Duconge, Jorge; Montané-Jaime, Lazara K; Roblejo, Hilda; Fariñas, Humberto; Campos, María de los A; Ramírez, Ronald; Serrano, Víctor; Villagrán, Carmen I; Peñas-LLedó, Eva M

2016-01-01

Aim: The present review was aimed at analyzing the pharmacogenetic scientific activity in Central America and the Caribbean. Materials & methods: A literature search for pharmacogenetic studies in each country of the region was conducted on three databases using a list of the most relevant pharmacogenetic biomarkers including ‘phenotyping probe drugs’ for major drug metabolizing enzymes. The review included 132 papers involving 47 biomarkers and 35,079 subjects (11,129 healthy volunteers and 23,950 patients). Results: The country with the most intensive pharmacogenetic research was Costa Rica. The most studied medical therapeutic area was oncology, and the most investigated biomarkers were CYP2D6 and HLA-A/B. Conclusion: Research activity on pharmacogenetics in Central American and the Caribbean populations is limited or absent. Therefore, strategies to promote effective collaborations, and foster interregional initiatives and research efforts among countries from the region could help for the rational clinical implementation of pharmacogenetics and personalized medicine. PMID:27633613

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petty, C. C., E-mail: petty@fusion.gat.com; Van Zeeland, M. A.; Pace, D. C.

“Steady-state” hybrid plasmas in DIII-D with zero surface loop voltage have been maintained for up to two current relaxation times using 3.4 MW of central electron cyclotron current drive (ECCD). In addition to driving ≈0.2 MA of plasma current, central ECCD leads to significant changes in Alfvén eigenmode (AE) activity and thermal transport. For neutral-beam-only heating, strong AE activity is observed that causes a ∼35% degradation in the neutron rate. With central ECCD this AE activity is suppressed, replaced by a bursty energetic particle mode that appears more benign as the neutron rate is closer to the classical value. Themore » electron thermal diffusivity increases by ≈50% for 2.4 MW of ECCD compared to neutral-beam-only cases. Fortunately, the global thermal confinement factor remains the same (H{sub 98y2}=1.4) as the higher thermal transport for P{sub EC}=2.4 MW hybrids is offset by the decreased fast ion transport resulting from AE suppression.« less

Prevalence of central obesity in a large sample of adolescents from public schools in Recife, Brazil.

PubMed

Griz, Luiz H M; Viégas, Maíra; Barros, Mauro; Griz, Adriana L; Freese, Eduardo; Bandeira, Francisco

2010-10-01

To determine the prevalence and association of central obesity (CO) and hypertension and its associations with alcohol intake, smoking and physical activity in adolescents. Cross sectional study in 1,824 students from 29 public schools in Recife. 89.6% were normal weight, 6.7% overweight and 3.7% obese; 77.2% were normotensive, 5.9% prehypertensive and 16.9% hypertensive; CO was 10.2% when the 90th percentile was used as cutoff and 25.2% when the 75th percentile was used. There was a higher likelihood of central obesity among students aged 18 to 20 years, smoking and alcohol intake. The probability of hypertension increases if the subject is male, has a waist circumference (WC) ≥ 90, WC ≥ 75 and does not practice physical activity. A high prevalence of CO and hypertension was found in adolescents. CO was more frequent in students aged 18 to 20 years, smokers and with alcohol intake and hypertension was associated with male, CO and no physical activity.

Cooperation with Central and Eastern Europe in Language Engineering.

ERIC Educational Resources Information Center

Andersen, Poul

This paper outlines trends and activities in Central and Eastern European language research and language-related software development (language engineering) and briefly describes some specific projects. The language engineering segment of the European Union's Fourth Framework Programme, intended to facilitate use of telematics applications and…

Characterizing the subsurface geology in and around the U.S. Army Camp Stanley Storage Activity, south-central Texas

USGS Publications Warehouse

Blome, Charles D.; Clark, Allan K.

2018-02-15

Several U.S. Geological Survey projects, supported by the National Cooperative Geologic Mapping Program, have used multi-disciplinary approaches over a 14-year period to reveal the surface and subsurface geologic frameworks of the Edwards and Trinity aquifers of central Texas and the Arbuckle-Simpson aquifer of south-central Oklahoma. Some of the project achievements include advancements in hydrostratigraphic mapping, three-dimensional subsurface framework modeling, and airborne geophysical surveys as well as new methodologies that link geologic and groundwater flow models. One area where some of these milestones were achieved was in and around the U.S. Army Camp Stanley Storage Activity, located in north­western Bexar County, Texas, about 19 miles north­west of downtown San Antonio.

The role of the GAF and central domains of the transcriptional activator VnfA in Azotobacter vinelandii.

PubMed

Yoshimitsu, Kyohei; Takatani, Nobuyuki; Miura, Yukio; Watanabe, Yoshihito; Nakajima, Hiroshi

2011-09-01

VnfA is a transcriptional activator that is required for the expression of the structural genes encoding nitrogenase-2 in Azotobacter vinelandii. VnfA consists of three domains: an N-terminal regulatory domain termed GAF, including a Cys-rich motif; a central domain from the AAA+ family; and a C-terminal domain for DNA binding. Previously, we reported that transcriptionally active VnfA harboring an Fe-S cluster (presumably of the 3Fe-4S type) as a prosthetic group and the Cys-rich motif were possibly associated with coordination of the Fe-S cluster. In the present study, we have investigated the roles of the GAF and central domains in the regulatory function of VnfA using truncated variants: ΔN15(VnfA) and ΔGAF(VnfA) that lack the N-terminal 15 residues and whole GAF domain, respectively, and GAF(VnfA) consisting of only the GAF domain. ΔN15(VnfA) and ΔGAF(VnfA) lost the ability to bind the Fe-S cluster, whereas GAF(VnfA) was still able to bind to the cluster, consistent with the hypothesis that the Cys-rich motif is essential for Fe-S cluster binding. The GAF domain showed an inhibitory effect on the transcriptional activity of VnfA, which was reversed in the presence of the Fe-S cluster, and reactivated upon disassembly of the cluster. The inhibitory activity of the GAF domain acts on the NTPase activity of the central domain, whereas the binding ability of VnfA to DNA was not significantly affected, when VnfA retains its tetrameric conformation. The results imply that a major pathway, by which VnfA function is regulated, operates via the control of NTPase activity by the GAF domain. © 2011 The Authors Journal compilation © 2011 FEBS.

Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

PubMed

Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

2016-01-28

In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

[Spatial organization of bioelectrical brain activity in epilepsy and amenorrhea of central genesis].

PubMed

Avakian, G N; Oleĭnikova, O M; Nerobkova, L N; Dovletkhanova, E R; Mitrofanov, A A; Gusev, E I

2002-01-01

The study aimed at modification of co-herent analysis (CA), as a mathematical method for EEG data processing for objective evaluation of bioelectric brain activity spatial organization in women with epilepsy and secondary amenorrhea of central genesis. One hundred sixty one women (30 with epilepsy, 116 with amenorrhea and 115 controls aged 15 to 41 years) have been examined. Characteristic changes of cortico-cortical inter- and intra-hemisphere relations for patients with catamenial (CTM) and noncatamenial (NCTM) epilepsy in different menstrual cycle terms were found. The most distinct changes were detected in theta-activity analysis. In the beginning of menstrual cycle, the patients with CTM epilepsy exhibited higher CA indices in theta-rhythm range in all right hemisphere pairs studied. On the contrary, patients with NCTM epilepsy exhibited lower CA indices mainly in the right brain hemisphere. alpha-rhythm spatial organization analysis in the same patients showed similar correlations, but they were better expressed in alpha-rhythm generation zone: in the beginning of menstrual cycle CA indices were high in patients with CTM epilepsy and low in those with NCTM epilepsy. Comparing to controls, patients with secondary amenorrhea of central genesis showed most distinct changes in theta-activity towards the CA indices increase in the majority of the leads. In patients with epilepsy and amenorrhea, CA indices of right brain hemisphere and intra-central temporal lead pairs were lower than in patients with amenorrhea without epilepsy by both alpha- and theta-rhythms.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwender, Jorg; Konig, Christina; Klapperstuck, Matthias

An attempt has been made to define the extent to which metabolic flux in central plant metabolism is reflected by changes in the transcriptome and metabolome, based on an analysis of in vitro cultured immature embryos of two oilseed rape (Brassica napus) accessions which contrast for seed lipid accumulation. Metabolic flux analysis (MFA) was used to constrain a flux balance metabolic model which included 671 biochemical and transport reactions within the central metabolism. This highly confident flux information was eventually used for comparative analysis of flux vs. transcript (metabolite). Metabolite profiling succeeded in identifying 79 intermediates within the central metabolism,more » some of which differed quantitatively between the two accessions and displayed a significant shift corresponding to flux. An RNA-Seq based transcriptome analysis revealed a large number of genes which were differentially transcribed in the two accessions, including some enzymes/proteins active in major metabolic pathways. With a few exceptions, differential activity in the major pathways (glycolysis, TCA cycle, amino acid, and fatty acid synthesis) was not reflected in contrasting abundances of the relevant transcripts. The conclusion was that transcript abundance on its own cannot be used to infer metabolic activity/fluxes in central plant metabolism. Lastly, this limitation needs to be borne in mind in evaluating transcriptome data and designing metabolic engineering experiments.« less

Thyroid hormones induce browning of white fat

PubMed Central

Martínez-Sánchez, Noelia; Moreno-Navarrete, José M; Contreras, Cristina; Rial-Pensado, Eva; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos

2016-01-01

The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3′,5,5′ tetraiodothyroxyne (T4)-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3′,5-triiodothyronine (T3) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T3 on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T4. Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance. PMID:27913573

Joint association of birth weight and physical activity/sedentary behavior with obesity in children ages 9-11 years from 12 countries.

PubMed

Qiao, Yijuan; Zhang, Tao; Liu, Hongyan; Katzmarzyk, Peter T; Chaput, Jean-Philippe; Fogelholm, Mikael; Johnson, William D; Kuriyan, Rebecca; Kurpad, Anura; Lambert, Estelle V; Maher, Carol; Maia, José A R; Matsudo, Victor; Olds, Timothy; Onywera, Vincent; Sarmiento, Olga L; Standage, Martyn; Tremblay, Mark S; Tudor-Locke, Catrine; Zhao, Pei; Hu, Gang

2017-06-01

To examine the joint association of birth weight and physical activity/sedentary time with childhood obesity in 12 countries. A cross-sectional study of 5,088 children aged 9 to 11 years was conducted. Birth weight was recalled by parents or guardians. Moderate-to-vigorous physical activity (MVPA) and sedentary behavior were objectively measured using accelerometry. The association of birth weight with the odds of obesity, central obesity, and high body fat was significant among children with either low MVPA or high sedentary time but not among children with either high MVPA or low sedentary time. In comparison with children with normal birth weight and high MVPA, children with high birth weight and low MVPA showed 4.48- to 5.18-fold higher odds of obesity, central obesity, and high body fat; children with normal birth weight and low MVPA showed 3.00- to 3.30-fold higher odds of obesity, central obesity, and high body fat, and children with high birth weight and high MVPA showed 1.16- to 1.68-fold higher odds of obesity, central obesity, and high body fat. High MVPA is more important than high birth weight as a correlate of obesity in children. © 2017 The Obesity Society.

Thyroid hormones induce browning of white fat.

PubMed

Martínez-Sánchez, Noelia; Moreno-Navarrete, José M; Contreras, Cristina; Rial-Pensado, Eva; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos; Fernández-Real, José-Manuel; López, Miguel

2017-02-01

The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3',5,5' tetraiodothyroxyne (T 4 )-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3',5-triiodothyronine (T 3 ) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T 3 on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T 4 Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance. © 2017 The authors.

Responses to increasing exercise upon reaching the anaerobic threshold, and their control by the central nervous system.

PubMed

Peinado, Ana B; Rojo, Jesús J; Calderón, Francisco J; Maffulli, Nicola

2014-01-01

The anaerobic threshold (AT) has been one of the most studied of all physiological variables. Many authors have proposed the use of several markers to determine the moment at with the AT is reached. The present work discusses the physiological responses made to exercise - the measurement of which indicates the point at which the AT is reached - and how these responses might be controlled by the central nervous system. The detection of the AT having been reached is a sign for the central nervous system (CNS) to respond via an increase in efferent activity via the peripheral nervous system (PNS). An increase in CNS and PNS activities are related to changes in ventilation, cardiovascular function, and gland and muscle function. The directing action of the central command (CC) allows for the coordination of the autonomous and motor systems, suggesting that the AT can be identified in the many ways: changes in lactate, ventilation, plasma catecholamines, heart rate (HR), salivary amylase and muscular electrical activity. This change in response could be indicative that the organism would face failure if the exercise load continued to increase. To avoid this, the CC manages the efferent signals that show the organism that it is running out of homeostatic potential.

Responses to increasing exercise upon reaching the anaerobic threshold, and their control by the central nervous system

PubMed Central

2014-01-01

The anaerobic threshold (AT) has been one of the most studied of all physiological variables. Many authors have proposed the use of several markers to determine the moment at with the AT is reached. The present work discusses the physiological responses made to exercise - the measurement of which indicates the point at which the AT is reached - and how these responses might be controlled by the central nervous system. The detection of the AT having been reached is a sign for the central nervous system (CNS) to respond via an increase in efferent activity via the peripheral nervous system (PNS). An increase in CNS and PNS activities are related to changes in ventilation, cardiovascular function, and gland and muscle function. The directing action of the central command (CC) allows for the coordination of the autonomous and motor systems, suggesting that the AT can be identified in the many ways: changes in lactate, ventilation, plasma catecholamines, heart rate (HR), salivary amylase and muscular electrical activity. This change in response could be indicative that the organism would face failure if the exercise load continued to increase. To avoid this, the CC manages the efferent signals that show the organism that it is running out of homeostatic potential. PMID:24818009

Joint association of birth weight and physical/sedentary activity with obesity at children ages 9–11 years in 12 countries

PubMed Central

Qiao, Yijuan; Zhang, Tao; Liu, Hongyan; Katzmarzyk, Peter T.; Chaput, Jean-Philippe; Fogelholm, Mikael; Johnson, William D.; Kuriyan, Rebecca; Kurpad, Anura; Lambert, Estelle V.; Maher, Carol; Maia, José A.R.; Matsudo, Victor; Olds, Timothy; Onywera, Vincent; Sarmiento, Olga L.; Standage, Martyn; Tremblay, Mark S.; Tudor-Locke, Catrine; Zhao, Pei; Hu, Gang

2017-01-01

Objective To examine the joint association of birth weight and physical/sedentary activity time with obesity in 12 countries. Methods A cross-sectional study of 5,088 children aged 9–11 years was conducted. Birth weight was recalled by parents or guardians. Moderate-to-vigorous physical activity (MVPA) and sedentary behavior were objectively measured using accelerometry. Results The association of birth weight with the odds of obesity, central obesity and high body fat was significant among children with either low MVPA or high sedentary time but not among children with either high MVPA or low sedentary time. In comparison with children with normal birth weight and high MVPA, children with high birth weight and low MVPA showed 4.48–5.18 fold higher odds of obesity, central obesity, and high body fat; children with normal birth weight and low MVPA showed 3.00–3.30 fold higher odds of obesity, central obesity, and high body fat, and children with high birth weight and high MVPA showed 1.16–1.68 fold higher odds of obesity, central obesity, and high body fat. Conclusions High MVPA is more important than high birth weight as a correlate of obesity in children. PMID:28544795

Radio afterglow rebrightening: evidence for multiple active phases in gamma-ray burst central engines

NASA Astrophysics Data System (ADS)

Li, Long-Biao; Zhang, Zhi-Bin; Rice, Jared

2015-09-01

The rebrightening phenomenon is an interesting feature in some X-ray, optical, and radio afterglows of gamma-ray bursts (GRBs). Here, we propose a possible energy-supply assumption to explain the rebrightenings of radio afterglows, in which the central engine with multiple active phases can supply at least two GRB pulses in a typical GRB duration time. Considering the case of double pulses supplied by the central engine, the double pulses have separate physical parameters, except for the number density of the surrounding interstellar medium (ISM). Their independent radio afterglows are integrated by the ground detectors to form the rebrightening phenomenon. In this Letter, we firstly simulate diverse rebrightening light curves under consideration of different and independent physical parameters. Using this assumption, we also give our best fit to the radio afterglow of GRB 970508 at three frequencies of 1.43, 4.86, and 8.46 GHz. We suggest that the central engine may be active continuously at a timescale longer than that of a typical GRB duration time as many authors have suggested (e.g., Zhang et al., Astrophys. J. 787:66, 2014; Gao and Mészáros, Astrophys. J. 802:90, 2015), and that it may supply enough energy to cause the long-lasting rebrightenings observed in some GRB afterglows.

The interaction of psychological and physiological homeostatic drives and role of general control principles in the regulation of physiological systems, exercise and the fatigue process - The Integrative Governor theory.

PubMed

St Clair Gibson, A; Swart, J; Tucker, R

2018-02-01

Either central (brain) or peripheral (body physiological system) control mechanisms, or a combination of these, have been championed in the last few decades in the field of Exercise Sciences as how physiological activity and fatigue processes are regulated. In this review, we suggest that the concept of 'central' or 'peripheral' mechanisms are both artificial constructs that have 'straight-jacketed' research in the field, and rather that competition between psychological and physiological homeostatic drives is central to the regulation of both, and that governing principles, rather than distinct physical processes, underpin all physical system and exercise regulation. As part of the Integrative Governor theory we develop in this review, we suggest that both psychological and physiological drives and requirements are underpinned by homeostatic principles, and that regulation of the relative activity of each is by dynamic negative feedback activity, as the fundamental general operational controller. Because of this competitive, dynamic interplay, we propose that the activity in all systems will oscillate, that these oscillations create information, and comparison of this oscillatory information with either prior information, current activity, or activity templates create efferent responses that change the activity in the different systems in a similarly dynamic manner. Changes in a particular system are always the result of perturbations occurring outside the system itself, the behavioural causative 'history' of this external activity will be evident in the pattern of the oscillations, and awareness of change occurs as a result of unexpected rather than planned change in physiological activity or psychological state.

Honduras’ National Security Strategy To Combat Terrorism

DTIC Science & Technology

2006-12-01

ENVIRONMENT Culture in “ancient” America was based in two major locations. In Mexico and Central America were the Aztecs and the Mayas, and in Peru were the...Colombia), the drugs transit via the West Indies, Central America and Mexico (fig. 2), which are the trafficking centers of the international mafia...by migrants.42 Some of the factors that contribute to the increase of gang activities in Central America, Mexico , and the U.S. are: income

Possible inhibitory role of endogenous 2-arachidonoylglycerol as an endocannabinoid in (±)-epibatidine-induced activation of central adrenomedullary outflow in the rat.

PubMed

Shimizu, Takahiro; Tanaka, Kenjiro; Shimizu, Shogo; Higashi, Youichirou; Yawata, Toshio; Nakamura, Kumiko; Taniuchi, Keisuke; Ueba, Tetsuya; Yuri, Kazunari; Saito, Motoaki

2015-08-01

We previously reported that intracerebroventricularly (i.c.v.) administered (±)-epibatidine (1, 5 or 10 nmol/animal), a nicotinic acetylcholine receptor agonist, dose-dependently induced secretion of noradrenaline and adrenaline (catecholamines) from the rat adrenal medulla by brain diacylglycerol lipase- (DGL), monoacylglycerol lipase- (MGL) and cyclooxygenase-mediated mechanisms. Diacylglycerol is hydrolyzed by DGL into 2-arachidonoylglycerol (2-AG), which is further hydrolyzed by MGL to arachidonic acid (AA), a cyclooxygenase substrate. These findings suggest that brain 2-AG-derived AA is involved in the (±)-epibatidine-induced response. This AA precursor 2-AG is also a major brain endocannabinoid, which inhibits synaptic transmission through presynaptic cannabinoid CB1 receptors. Released 2-AG into the synaptic cleft is rapidly inactivated by cellular uptake. Here, we examined a role of brain 2-AG as an endocannabinoid in the (±)-epibatidine-induced activation of central adrenomedullary outflow using anesthetized male Wistar rats. In central presence of AM251 (CB1 antagonist) (90 and 180 nmol/animal, i.c.v.), (±)-epibatidine elevated plasma catecholamines even at an ineffective dose (1 nmol/animal, i.c.v.). Central pretreatment with ACEA (CB1 agonist) (0.7 and 1.4 μmol/animal, i.c.v.), 2-AG ether (stable 2-AG analog for MGL) (0.5 and 1.0 μmol/animal, i.c.v.) or AM404 (endocannabinoid uptake inhibitor) (80 and 250 nmol/animal, i.c.v.) significantly reduced an effective dose of (±)-epibatidine- (5 nmol/animal, i.c.v.) induced elevation of plasma catecholamines, and AM251 (90 and 180 nmol/animal, i.c.v.) centrally abolished the reduction induced by 2-AG ether (1.0 μmol/animal, i.c.v.) or AM404 (250 nmol/animal, i.c.v.). Immunohistochemical studies demonstrated that (±)-epibatidine (10 nmol/animal, i.c.v.) activated DGLα-positive spinally projecting neurons in the hypothalamic paraventricular nucleus, a control center of central adrenomedullary system. These results suggest a possibility that a brain endocannabinoid, probably 2-AG, plays an inhibitory role in (±)-epibatidine-induced activation of central adrenomedullary outflow through brain CB1 receptors in the rat. Copyright © 2015 Elsevier Ltd. All rights reserved.

Geographic Variation in Daily Temporal Activity Patterns of a Neotropical Marsupial (Gracilinanus agilis)

PubMed Central

Vieira, Emerson M.; de Camargo, Nícholas F.; Colas, Paul F.; Ribeiro, Juliana F.; Cruz-Neto, Ariovaldo P.

2017-01-01

The temporal activity of animals is an outcome of both biotic and abiotic factors, which may vary along the geographic range of the species. Therefore, studies conducted with a species in different localities with distinct features could elucidate how animals deal with such factors. In this study, we used live traps equipped with timing devices to investigate the temporal activity patterns of the didelphid Gracilinanus agilis in two dry-woodland areas of the Brazilian savanna (Cerrado). These areas were located about 660 km apart, one in Central Brazil and the other in Southeastern Brazil. We compared such patterns considering both reproductive and non-reproductive periods, and how it varies as a function of temperature on a seasonal basis. In Central Brazil, we found a constant, and temperature-independent activity during the night in both reproductive and non-reproductive periods. On the other hand, in Southeastern Brazil, we detected a constant activity during the reproductive period, but in the non-reproductive period G. agilis presented a peak of activity between two and four hours after sunset. Moreover, in this latter we found a relation between temporal activity and temperature during the autumn and spring. These differences in temporal activity between areas, observed during the non-reproductive period, might be associated with the higher seasonal variability in temperature, and lower mean temperatures in the Southeastern site in comparison to the Central one. In Southeastern Brazil, the decrease in temperature during the non-reproductive season possibly forced G. agilis to be active only at certain hours of the night. However, likely due to the reproductive activities (intensive foraging and searching for mates) this marsupial showed constant, temperature-independent activity during the night in the reproductive period at both sites. PMID:28052077

Autonomic nervous system balance in children and adolescents with craniopharyngioma and hypothalamic obesity.

PubMed

Cohen, Michal; Syme, Catriona; McCrindle, Brian W; Hamilton, Jill

2013-06-01

Dysregulation of the autonomic nervous system is thought to be involved in craniopharyngioma-related hypothalamic obesity (CRHO). Increased parasympathetic activity and decreased sympathetic activity have been suggested. We aimed to study autonomic activity using heart rate variability (HRV) and biochemical measures in youth with CRHO compared with controls and to explore relationships between obesity and autonomic indices. A cross-sectional study of 16 youth with CRHO and 16 controls matched for sex, age, and BMI. Anthropometrics, fasting blood-work, resting energy expenditure (REE), 24-h HRV, and 24-h urine catecholamines were assessed. Quality of life, sleepiness, and autonomic symptoms were evaluated. Power spectral analysis of the HRV was performed. HRV power spectral analysis parameters of both parasympathetic activity (mean high frequency (HF (ms(2))) 611±504 vs 459±336, P=0.325) and sympathetic activity (median low frequency/HF 1.62 (1.37, 2.41) vs 1.89 (1.44, 2.99), P=0.650) did not differ between the groups. Parasympathetic activity negatively correlated with central adiposity in both groups (r=-0.53, P=0.034 and r=-0.54, P=0.029) and sympathetic activity positively correlated with central adiposity in CRHO (r=0.51, P=0.043). Youth with CRHO had significantly lower REE; lower health and activity scores in the quality of life questionnaires, and higher sleepiness scores. Autonomic activity was similar in CRHO and control subjects. The degree of central adiposity correlated negatively with parasympathetic activity and positively with sympathetic activity in children with CRHO. These results provide a new perspective regarding autonomic balance in this unique patient population.

PLUS highway network analysis: Case of in-coming traffic burden in 2013

NASA Astrophysics Data System (ADS)

Asrah, Norhaidah Mohd; Djauhari, Maman Abdurachman; Mohamad, Ismail

2017-05-01

PLUS highway is the largest concessionary in Malaysia. The study on PLUS highway development, in order to overcome the demand for efficient road transportation, is crucial. If the highways have better interconnected network, it will help the economic activities such as trade to increase. If economic activities are increasing, the benefit will come to the people and state. In its turn, it will help the leaders to plan and conduct national development program. In this paper, network analysis approach will be used to study the in-coming traffic burden during the year of 2013. The highway network linking all the toll plazas is a dynamic network. The objective of this study is to learn and understand about highway network in terms of the in-coming traffic burden entering to each toll plazas along PLUS highway. For this purpose, the filtered network topology based on the forest of all possible minimum spanning trees is used. The in-coming traffic burden of a city is represented by the number of cars passing through the corresponding toll plaza. To interpret the filtered network, centrality measures such as degree centrality, betweenness centrality, closeness centrality, eigenvector centrality are used. An overall centrality will be proposed if those four measures are assumed to have the same role. Based on the results, some suggestions and recommendations for PLUS highway network development will be delivered to PLUS highway management.

Central control of body temperature

PubMed Central

Morrison, Shaun F.

2016-01-01

Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis. PMID:27239289

Central control of body temperature.

PubMed

Morrison, Shaun F

2016-01-01

Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis.

Current deformation in Central Afar and triple junction kinematics deduced from GPS and InSAR measurements

NASA Astrophysics Data System (ADS)

Doubre, Cécile; Déprez, Aline; Masson, Frédéric; Socquet, Anne; Lewi, Elias; Grandin, Raphaël; Nercessian, Alexandre; Ulrich, Patrice; De Chabalier, Jean-Bernard; Saad, Ibrahim; Abayazid, Ahmadine; Peltzer, Gilles; Delorme, Arthur; Calais, Eric; Wright, Tim

2017-02-01

Kinematics of divergent boundaries and Rift-Rift-Rift junctions are classically studied using long-term geodetic observations. Since significant magma-related displacements are expected, short-term deformation provides important constraints on the crustal mechanisms involved both in active rifting and in transfer of extensional deformation between spreading axes. Using InSAR and GPS data, we analyse the surface deformation in the whole Central Afar region in detail, focusing on both the extensional deformation across the Quaternary magmato-tectonic rift segments, and on the zones of deformation transfer between active segments and spreading axes. The largest deformation occurs across the two recently activated Asal-Ghoubbet (AG) and Manda Hararo-Dabbahu (MH-D) magmato-tectonic segments with very high strain rates, whereas the other Quaternary active segments do not concentrate any large strain, suggesting that these rifts are either sealed during interdyking periods or not mature enough to remain a plate boundary. Outside of these segments, the GPS horizontal velocity field shows a regular gradient following a clockwise rotation of the displacements from the Southeast to the East of Afar, with respect to Nubia. Very few shallow creeping structures can be identified as well in the InSAR data. However, using these data together with the strain rate tensor and the rotations rates deduced from GPS baselines, the present-day strain field over Central Afar is consistent with the main tectonic structures, and therefore with the long-term deformation. We investigate the current kinematics of the triple junction included in our GPS data set by building simple block models. The deformation in Central Afar can be described by adding a central microblock evolving separately from the three surrounding plates. In this model, the northern block boundary corresponds to a deep EW-trending trans-tensional dislocation, locked from the surface to 10-13 km and joining at depth the active spreading axes of the Red Sea and the Aden Ridge, from AG to MH-D rift segments. Over the long-term, this plate configuration could explain the presence of the en-échelon magmatic basins and subrifts. However, the transient behaviour of the spreading axes implies that the deformation in Central Afar evolves depending on the availability of magma supply within the well-established segments.

Micro-opioid receptor agonist diminishes POMC gene expression and anorexia by central insulin in neonatal chicks.

PubMed

Shiraishi, Jun-Ichi; Yanagita, Kouchi; Fujita, Masanori; Bungo, Takashi

2008-07-18

Pro-opiomelanocortin (POMC) neurons in the hypothalamus are direct targets of peripheral satiety signals, such as leptin and insulin in mammals. The stimulation of these signals activates hypothalamic POMC neurons and elevates POMC-derived melanocortin peptides that inhibit food intake in mammals. On the other hand, it has been recognized that beta-endorphin, a post-translational processing of POMC, acts in an autoreceptor manner to the micro-opioid receptor (MOR) on POMC neurons, diminishing POMC neuronal activity in mammals. Recently, we found that central insulin functions as an anorexic peptide in chicks. Thus, the present study was done to elucidate whether beta-endorphin affects the activation of POMC neurons by insulin in neonatal chicks. Consequently, quantitative real-time PCR analysis shows that intracerebroventricular (ICV) injection of insulin with beta-endorphin significantly decreases brain POMC mRNA expression when compared with insulin alone. In addition, co-injection of MOR agonist (beta-endorphin or [d-Ala2, N-MePhe4, Gly5-ol]-enkephalin (DAMGO)) significantly attenuates insulin-induced hypophagia in chicks. These data suggest that beta-endorphin regulates the activity of the central melanocortin system, and its activation may provide an inhibitory feedback mechanism in the brain of neonatal chicks.

Identification of catalytic residues of a very large NAD-glutamate dehydrogenase from Janthinobacterium lividum by site-directed mutagenesis.

PubMed

Kawakami, Ryushi; Sakuraba, Haruhiko; Ohshima, Toshihisa

2014-01-01

We previously found a very large NAD-dependent glutamate dehydrogenase with approximately 170 kDa subunit from Janthinobacterium lividum (Jl-GDH) and predicted that GDH reaction occurred in the central domain of the subunit. To gain further insights into the role of the central domain, several single point mutations were introduced. The enzyme activity was completely lost in all single mutants of R784A, K810A, K820A, D885A, and S1142A. Because, in sequence alignment analysis, these residues corresponded to the residues responsible for glutamate binding in well-known small GDH with approximately 50 kDa subunit, very large GDH and well-known small GDH may share the same catalytic mechanism. In addition, we demonstrated that C1141, one of the three cysteine residues in the central domain, was responsible for the inhibition of enzyme activity by HgCl2, and HgCl2 functioned as an activating compound for a C1141T mutant. At low concentrations, moreover, HgCl2 was found to function as an activating compound for a wild-type Jl-GDH. This suggests that the mechanism for the activation is entirely different from that for the inhibition.

Centrality dependence of particle production in p - Pb collisions at s NN = 5.02 TeV

DOE PAGES

Adam, J.; Adamová, D.; Aggarwal, M. M.; ...

2015-06-08

Here, we report measurements of the primary charged-particle pseudorapidity density and transverse momentum distributions in p–Pb collisions at √s NN = 5.02TeV and investigate their correlation with experimental observables sensitive to the centrality of the collision. Centrality classes are defined by using different event-activity estimators, i.e., charged-particle multiplicities measured in three different pseudorapidity regions as well as the energy measured at beam rapidity (zero degree). The procedures to determine the centrality, quantified by the number of participants (N part) or the number of nucleon-nucleon binary collisions (N coll) are described. We show that, in contrast to Pb-Pb collisions, in p–Pbmore » collisions large multiplicity fluctuations together with the small range of participants available generate a dynamical bias in centrality classes based on particle multiplicity. We propose to use the zero-degree energy, which we expect not to introduce a dynamical bias, as an alternative event-centrality estimator. Based on zero-degree energy-centrality classes, the N part dependence of particle production is studied. Under the assumption that the multiplicity measured in the Pb-going rapidity region scales with the number of Pb participants, an approximate independence of the multiplicity per participating nucleon measured at mid-rapidity of the number of participating nucleons is observed. Furthermore, at high-p T the p–Pb spectra are found to be consistent with the pp spectra scaled by N coll for all centrality classes. Our results represent valuable input for the study of the event-activity dependence of hard probes in p–Pb collisions and, hence, help to establish baselines for the interpretation of the Pb-Pb data.« less

Gender-specific association of the plasminogen activator inhibitor-1 4G/5G polymorphism with central arterial blood pressure.

PubMed

Björck, Hanna M; Eriksson, Per; Alehagen, Urban; De Basso, Rachel; Ljungberg, Liza U; Persson, Karin; Dahlström, Ulf; Länne, Toste

2011-07-01

The functional plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism has previously been associated with hypertension. In recent years, central blood pressure, rather than brachial has been argued a better measure of cardiovascular damage and clinical outcome. The aim of this study was to investigate the possible influence of the 4G/5G polymorphism on central arterial blood pressure in a cohort of elderly individuals. We studied 410 individuals, 216 men and 194 women, aged 70-88. Central pressures and pulse waveforms were calculated from the radial artery pressure waveform by the use of the SphygmoCor system and a generalized transfer function. Brachial pressure was recorded using oscillometric technique (Dinamap, Critikon, Tampa, FL). PAI-1 antigen was determined in plasma. The results showed that central pressures were higher in women carrying the PAI-1 4G/4G genotype compared to female carriers of the 5G/5G genotype, (P = 0.025, P = 0.002, and P = 0.002 for central systolic-, diastolic-, and mean arterial pressure, respectively). The association remained after adjustment for potentially confounding factors related to hypertension. No association of the PAI-1 genotype with blood pressure was found in men. Multiple regression analysis revealed an association between PAI-1 genotype and plasma PAI-1 levels (P = 0.048). Our findings show a gender-specific association of the PAI-1 4G/5G polymorphism with central arterial blood pressure. The genotype effect was independent of other risk factors related to hypertension, suggesting that impaired fibrinolytic potential may play an important role in the development of central hypertension in women.

Changes in force associated with the amount of aligner activation and lingual bodily movement of the maxillary central incisor

PubMed Central

Li, Xiaowei; Ren, Chaochao; Wang, Zheyao; Zhao, Pai; Wang, Hongmei

2016-01-01

Objective The purposes of this study were to measure the orthodontic forces generated by thermoplastic aligners and investigate the possible influences of different activations for lingual bodily movements on orthodontic forces, and their attenuation. Methods Thermoplastic material of 1.0-mm in thickness was used to manufacture aligners for 0.2, 0.3, 0.4, 0.5, and 0.6 mm activations for lingual bodily movements of the maxillary central incisor. The orthodontic force in the lingual direction delivered by the thermoplastic aligners was measured using a micro-stress sensor system for the invisible orthodontic technique, and was monitored for 2 weeks. Results Orthodontic force increased with the amount of activation of the aligner in the initial measurements. The attenuation speed in the 0.6 mm group was faster than that of the other groups (p < 0.05). All aligners demonstrated rapid relaxation in the first 8 hours, which then decreased slowly and plateaued on day 4 or 5. Conclusions The amount of activation had a substantial influence on the orthodontic force imparted by the aligners. The results suggest that the activation of lingual bodily movement of the maxillary central incisor should not exceed 0.5 mm. The initial 4 or 5 days is important with respect to orthodontic treatment incorporating an aligner. PMID:27019820

Late Neogene and Active Tectonics along the Northern Margin of the Central Anatolian Plateau,TURKEY

NASA Astrophysics Data System (ADS)

Yildirim, C.; Schildgen, T. F.; Melnick, D.; Echtler, H. P.; Strecker, M. R.

2009-12-01

Margins of orogenic plateaus are conspicuous geomorphic provinces that archive tectonic and climatic variations related to surface uplift. Their growth is associated with spatial and temporal variations of mode and rate of tectonics and surface processes. Those processes can be strongly linked to the evolution of margins and plateaus thorough time. As one of the major morpho-tectonic provinces of Turkey, the Central Pontides (coinciding with the northern margin of the Central Anatolian Plateau (CAP)) display a remarkable topography and present valuable geologic and geomorphic indicators to identify active tectonics. Morpho-tectonic analysis, geological cross-sections, seismic profiles, and geodetic analysis reveal continuous deformation characterized by brittle faults from Late Miocene to recent across the northern margin of the CAP. In the Sinop Peninsula and offshore in the southern Black Sea, pervasive faulting and folding and uplift of Late Miocene to Quaternary marine deposits is related to active margin tectonics of the offshore southern Black Sea thrust and the onshore Balifaki and Erikli faults. In the Kastamonu-Boyabat sedimentary basin, the Late Miocene to Quaternary continental equivalents are strongly deformed by the Ekinveren Fault. This vergent inverse and thrust fault with overstepping en echelon segments deforms not only Quaternary travertines and conglomerates, but also patterns of the Pleistocene to Holocene drainage systems. In the southern Kastamonu-Boyabat basin, an antithetic thrust fault of the Ekinveren Fault system deformed also Quaternary fluviatile terrace deposits. Farther south, a dextral transpressive splay of the North Anatolian Fault (NAF) deforms pediment surfaces and forms the northern flank of the Ilgaz active mountain range. The Ilgaz Range rises up to 2587 m.a.s.l and is delimited by active segments of the NAF.The Central Pontides are located at the apex of northward convex arc of the NAF. Geodetic analysis indicate a deviation of the slip vectors and strain partitioning in the Central Pontides due to the large restraining bend geometry of the NAF. DEM analysis and field observations reveal that the Central Pontides integrate an active bivergent wedge, indicating out-of sequence thrusting and topographical asymmetry, with a gentle pro-wedge northern slope and a steep retro-wedge southern slopes, and regional surface tilting from south to north. Uplifted presumably Late Pleistocene to Holocene marine terraces 4 to 40 m.a.s.l. along the coast and well developed pediment and fill and strath terrace surfaces ranging from 10 to 300 m above along the Gokirmak and Kizilirmak rivers will provide chronological constraints on the uplift and incision rates of the study area.

Activities of the ILO.

ERIC Educational Resources Information Center

Labour Education, 1984

1984-01-01

Seven articles on International Labour Organization (ILO) activities cover study groups at ILO headquarters, a Philippine rural workers seminar, women's participation in Central American union activities, worksite courses in India, and seminars and symposia in Cape Verde, Mauritius, and Sierra Leone. (SK)

Tanks have left, Gazprom is back: Russian energy companies' expansion towards Poland, Slovakia and Hungary between 1991 and 2004

NASA Astrophysics Data System (ADS)

Orban, Anita

A casual observant of post-Soviet Russian corporate activity in Central Europe finds a hectic behavior of Russian companies in the Polish, Hungarian and Slovakian economies. There were times when these companies showed great interest toward the region, followed by periods of non-activity. To solve the puzzle, the study tests neoclassical realist theory in explaining Russian corporate propensity to expand into Central Europe. Neoclassical realist theory argues that the relative distribution of power in the international system (independent variable) through the perception of state leaders (intervening variable) together with state power, to be defined as power to mobilize the necessary resources (intervening variable), explain foreign political outcomes (dependent variable). The dissertation draws the following hypothesis from neorealist theory: When the Russian leadership perceives that Russia's relative influence vis-a-vis the West is low and Russia possesses enough state power to mobilize the necessary resources, Russian energy companies will manifest expansionary moves into Central Europe. When Russia does not perceive its influence low and/or does not possess enough state power, Russian companies will not manifest any expansionary moves into Central Europe. To test the hypotheses the study uses the case study methodology. There is one case examined: Russian energy companies' activity in Central Europe between 1991 and 2004. The study splits this period into five sub-periods which correspond with the widely accepted milestones of post-Soviet Russian foreign policy: 1991-1993 Early Atlanticism, 1994-1996 Facing Nato Enlargement, 1996-1998 Against a Unipolar World, 1998-2000 Instability and Uncertainty, and 2000-2004 The First Putin Presidency. Russian energy companies were very active in two sub-periods: between 1994 and 1996, and between 2000 and 2004. However, they showed little to no interest for expansion in the other three sub-periods: 1991-1993, 1996-1998 and 1998-2000. In Chapters Four and Five the study examines in detail Russian perceptions about Russia's place in the world, changes in its state power and the Russian energy companies' activity in Central Europe where it is applicable. It finds that in the "active periods" (between 1994 and 1996 as well as between 2000 and 2004) Russian leadership assessed the relative power distribution in the international system to be disadvantageous for Russia and at the same time had considerable state power to mobilize. These two variables were not present together in the three "inactive periods". That is to say, the energy companies' Central European activities were consistent with what the hypothesis drawn from neoclassical realist theory would predict. The study proves the validity of neoclassical realist theory in explaining post-Soviet Russian foreign policy. Additionally, in the Russian studies today it is conventional wisdom that Vladimir Putin turned Russian energy companies into tools of his country's foreign policy vis-a-vis its neighbors. However, this study shows that the phenomenon is neither new, nor dependent on the current Russian president; moreover, it has never been limited to the countries of the former Soviet Union. In fact, ever since 1991, Russian corporate expansion in Central Europe has been driven by the highs and lows of Russian state power and its key decision makers' perceptions about their country's relative power vis-a-vis the West.

Protecting and managing traditional Allagash Wilderness Waterway recreation activities

Treesearch

Thomas J. Cieslinski

1998-01-01

The statute creating the Allagash Wilderness Waterway in 1966 specified several outdoor activities traditionally participated in along the watercourse. Additionally, there are other outdoor activities traditional to the watercourse. The identification and provision of opportunities for these activities, consistent with maintaining wilderness character, is central to...

THE EXTENT OF MINE DRAINAGE INTO STREAMS OF THE CENTRAL APPALACHIAN AND ROCKY MOUNTAIN REGIONS

EPA Science Inventory

Runoff and drainage from active and inactive mines are contaminating streams throughout the United States with acidic and metal contaminated waters and sediments. The extent of mining impacts on streams of the coal bearing region of the Central Appalachians and the metal bearing...

75 FR 16544 - Bureau of Educational and Cultural Affairs (ECA) Request for Grant Proposals: Youth Leadership...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

... for Grant Proposals: Youth Leadership Program With Central Europe Announcement Type: New Grant... Leadership Program with Central Europe. Public and private non-profit organizations meeting the provisions... exchange activities will focus broadly on the themes of civic rights and responsibilities, leadership, and...

Central America: A Regional Study.

ERIC Educational Resources Information Center

Mowry, George; Lacy, Ann

This lesson is a series of activities and multi-media presentations designed to enable students to understand the historic and geographic roots of some of the problems that Central American nations have faced. Geography, history, writing, and storytelling are used as ways of understanding a multicultural world. Creative thinking and participation…

Habitat improvement for wildlife in North-Central Sonora, Mexico

Treesearch

Martha Martin-Rivera; Fernando Ibarra-Flores; Fred S. Guthery; William P. Kublesky; Gustavo Camou-Luders; Jesus Fimbres-Preciado; Donald Johnson-Gordon

2001-01-01

Native vegetation of semiarid grasslands and desert ecosystems that comprise the Arbosufrutescent Desert scrub vegetation in north-central Sonora has been degraded by overgrazing, drought, farming, woodcutting, and a host of other activities over the past century. Several studies were conducted at "Rancho Grande" and at "Rancho El Carrizo," Sonora...

78 FR 3381 - Endangered and Threatened Species: Designation of a Nonessential Experimental Population of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... Experimental Population of Central Valley Spring-Run Chinook Salmon Below Friant Dam in the San Joaquin River... Fisheries Service (NMFS), propose a rule to designate a nonessential experimental population of Central... nonessential experimental population for particular activities inside the experimental population's geographic...

Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia.

PubMed

Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Liebano, Richard E; Amrit, Anand S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

2013-11-01

Because transcutaneous electrical nerve stimulation (TENS) works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo-controlled cross-over design to test the effects of a single treatment of TENS with people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS and no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and in movement; pressure pain thresholds, 6-m walk test, range of motion; 5-time sit-to-stand test, and single-leg stance. Conditioned pain modulation was completed at the end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. Pressure pain thresholds increased at the site of TENS (spine) and outside the site of TENS (leg) when compared to placebo TENS or no TENS. During active TENS, conditioned pain modulation was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to the way in which TENS is used clinically on pain, fatigue, function, and quality of life in individuals with fibromyalgia. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Menin: A Tumor Suppressor That Mediates Postsynaptic Receptor Expression and Synaptogenesis between Central Neurons of Lymnaea stagnalis

PubMed Central

Flynn, Nichole; Getz, Angela; Visser, Frank; Janes, Tara A.; Syed, Naweed I.

2014-01-01

Neurotrophic factors (NTFs) support neuronal survival, differentiation, and even synaptic plasticity both during development and throughout the life of an organism. However, their precise roles in central synapse formation remain unknown. Previously, we demonstrated that excitatory synapse formation in Lymnaea stagnalis requires a source of extrinsic NTFs and receptor tyrosine kinase (RTK) activation. Here we show that NTFs such as Lymnaea epidermal growth factor (L-EGF) act through RTKs to trigger a specific subset of intracellular signalling events in the postsynaptic neuron, which lead to the activation of the tumor suppressor menin, encoded by Lymnaea MEN1 (L-MEN1) and the expression of excitatory nicotinic acetylcholine receptors (nAChRs). We provide direct evidence that the activation of the MAPK/ERK cascade is required for the expression of nAChRs, and subsequent synapse formation between pairs of neurons in vitro. Furthermore, we show that L-menin activation is sufficient for the expression of postsynaptic excitatory nAChRs and subsequent synapse formation in media devoid of NTFs. By extending our findings in situ, we reveal the necessity of EGFRs in mediating synapse formation between a single transplanted neuron and its intact presynaptic partner. Moreover, deficits in excitatory synapse formation following EGFR knock-down can be rescued by injecting synthetic L-MEN1 mRNA in the intact central nervous system. Taken together, this study provides the first direct evidence that NTFs functioning via RTKs activate the MEN1 gene, which appears sufficient to regulate synapse formation between central neurons. Our study also offers a novel developmental role for menin beyond tumour suppression in adult humans. PMID:25347295

Neuroinflammatory contributions to pain after SCI: roles for central glial mechanisms and nociceptor-mediated host defense.

PubMed

Walters, Edgar T

2014-08-01

Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI. Interventions that reduce neuroinflammation have been found to ameliorate pain-related behavior, such as treatment with agents that inhibit the activation states of microglia and/or astroglia (including IL-10, minocycline, etanercept, propentofylline, ibudilast, licofelone, SP600125, carbenoxolone). Reversal of pain-related behavior has also been shown with disruption by an inhibitor (CR8) and/or genetic deletion of cell cycle-related proteins, deletion of a truncated receptor (trkB.T1) for brain-derived neurotrophic factor (BDNF), or reduction by antisense knockdown or an inhibitor (AMG9810) of the activity of channels (TRPV1 or Nav1.8) important for electrical activity in primary nociceptors. Nociceptor activity is known to drive central neuroinflammation in peripheral injury models, and nociceptors appear to be an integral component of host defense. Thus, emerging results suggest that spinal and systemic effects of SCI can activate nociceptor-mediated host defense responses that interact via neuroinflammatory signaling with complex central consequences of SCI to drive chronic pain. This broader view of SCI-induced neuroinflammation suggests new targets, and additional complications, for efforts to develop effective treatments for neuropathic SCI pain. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain RVD-haemopressin, a haemoglobin-derived peptide, inhibits bombesin-induced central activation of adrenomedullary outflow in the rat.

PubMed

Tanaka, Kenjiro; Shimizu, Takahiro; Yanagita, Toshihiko; Nemoto, Takayuki; Nakamura, Kumiko; Taniuchi, Keisuke; Dimitriadis, Fotios; Yokotani, Kunihiko; Saito, Motoaki

2014-01-01

Haemopressin and RVD-haemopressin, derived from the haemoglobin α-chain, are bioactive peptides found in brain and are ligands for cannabinoid CB1 receptors. Activation of brain CB1 receptors inhibited the secretion of adrenal catecholamines (noradrenaline and adrenaline) induced by i.c.v. bombesin in the rat. Here, we investigated the effects of two haemoglobin-derived peptides on this bombesin-induced response Anaesthetised male Wistar rats were pretreated with either haemoglobin-derived peptide, given i.c.v., 30 min before i.c.v. bombesin and plasma catecholamines were subsequently measured electrochemically after HPLC. Direct effects of bombesin on secretion of adrenal catecholamines were examined using bovine adrenal chromaffin cells. Furthermore, activation of haemoglobin α-positive spinally projecting neurons in the rat hypothalamic paraventricular nucleus (PVN, a regulatory centre of central adrenomedullary outflow) after i.c.v. bombesin was assessed by immunohistochemical techniques. Bombesin given i.c.v. dose-dependently elevated plasma catecholamines whereas incubation with bombesin had no effect on spontaneous and nicotine-induced secretion of catecholamines from chromaffin cells. The bombesin-induced increase in catecholamines was inhibited by pretreatment with i.c.v. RVD-haemopressin (CB1 receptor agonist) but not after pretreatment with haemopressin (CB1 receptor inverse agonist). Bombesin activated haemoglobin α-positive spinally projecting neurons in the PVN. The haemoglobin-derived peptide RVD-haemopressin in the brain plays an inhibitory role in bombesin-induced activation of central adrenomedullary outflow via brain CB1 receptors in the rat. These findings provide basic information for the therapeutic use of haemoglobin-derived peptides in the modulation of central adrenomedullary outflow. © 2013 The British Pharmacological Society.

Central analgesic activity of the aqueous and ethanolic extracts of the leaves of Albizia lebbeck: role of the GABAergic and serotonergic pathways.

PubMed

Meshram, Girish G; Kumar, Anil; Rizvi, Waseem; Tripathi, C D; Khan, R A

2015-01-01

Albizia lebbeck Benth. is extensively used in Indian traditional medicine for treating several painful and inflammatory disorders. The possible central analgesic activity and the underlying mechanism of action of the aqueous (AE) and ethanolic extracts (EE) of the leaves of A. lebbeck were investigated in Wistar rats using Eddy's hot plate and the tail flick tests. In order to investigate the underlying mechanism of action, rats were pretreated with naloxone, bicuculline or methysergide and then were administered a per os (p.o.) dose of AE or EE. AE and EE caused a significant (p<0.05) elevation in the mean basal reaction time in the hot plate method and an increase in the latency time in the tail flick method. In rats pretreated with bicuculline and methysergide, a significant (p<0.05) reduction in the analgesic activity was observed in comparison to AE and EE. Thus, AE and EE exhibited significant central analgesic activity and act possibly via the GABAergic and serotonergic pathways. The flavonoids and saponins found in the leaves could be responsible for the observed effect.

System Controls on the South Texas Sand Sheet

NASA Astrophysics Data System (ADS)

Barrineau, Clifton Patrick

Semi-stabilized dune systems are important indicators of Quaternary drought variability across central North America. The South Texas sand sheet (STSS) is the southernmost relict dune system in central North America and is exposed to higher evapotranspiration and moisture variability than similar landscapes farther north. This study uses multi-scale analysis of LiDAR data, geophysical surveys, optically stimulated luminescence dates of core samples, and X-ray fluorescence analysis to identify historical periods of desertification across the STSS. These data suggest long-term relationships between climate, ecological disturbances, geological framework, and desertification. Aeolian activations dated at ca. 75, 230, 2000, 4100, and 6600 yr bp correspond to periods of persistent regional drought, changes in sediment supply, and anthropogenic disturbances of native ecology. From these results it appears that regionalized activation in semi-stabilized dune systems is controlled primarily by climatic variations that reduce the overall moisture available for maintaining vigorous vegetation growth, while localized activation patterns depend more on stresses related to site-specific morphodynamics as well as human activity. With enhanced aridity forecast for much of central North America through the 21 st century, understanding the specific thresholds of desertification is an important step towards building a conceptual model of desertification in semi-stabilized dune landscapes.

The contribution of the Global Change Observatory Central Asia to seismic hazard and risk assessment in the Central Asian region

NASA Astrophysics Data System (ADS)

Parolai, S.; Bindi, D.; Haberland, C. A.; Pittore, M.; Pilz, M.; Rosenau, M.; Schurr, B.; Wieland, M.; Yuan, X.

2012-12-01

Central Asia has one of the world's highest levels of earthquake hazard, owing to its exceptionally high deformation rates. Moreover, vulnerability to natural disasters in general is increasing, due to rising populations and a growing dependence on complex lifelines and technology. Therefore, there is an urgent need to undertake seismic hazard and risk assessment in this region, while at the same time improving upon existing methodologies, including the consideration of temporal variability in the seismic hazard, and in structural and social vulnerability. Over the last few years, the German Research Center for Geosciences (GFZ), in collaboration with local partners, has initiated a number of scientific activities within the framework of the Global Change Observatory Central Asia (GCO-CA). The work is divided into projects with specific concerns: - The installation and maintenance of the Central-Asian Real-time Earthquake MOnitoring Network (CAREMON) and the setup of a permanent wireless mesh network for structural health monitoring in Bishkek. - The TIPAGE and TIPTIMON projects focus on the geodynamics of the Tien-Shan, Pamir and Hindu Kush region, the deepest and most active intra-continental subduction zone in the world. The work covers time scales from millions of years to short-term snapshots based on geophysical measurements of seismotectonic activity and of the physical properties of the crust and upper mantle, as well as their coupling with other surface processes (e.g., landslides). - Existing risk analysis methods assume time-independent earthquake hazard and risk, although temporal changes are likely to occur due to, for example, co- and post-seismic changes in the regional stress field. We therefore aim to develop systematic time-dependent hazard and risk analysis methods in order to undertake the temporal quantification of earthquake activity (PROGRESS). - To improve seismic hazard assessment for better loss estimation, detailed site effects studies are necessary. Temporary seismic networks have been installed in several Central Asian cities (Bishkek and Karakol, Kyrgyzstan; Dushanbe, Tajikistan; Tashkent, Uzbekistan) within the framework of the Earthquake Model Central Asia (EMCA), a regional program of the Global Earthquake Model (GEM). The empirically estimated site effects have already helped to improve real-time risk scenarios for Bishkek and will be applied to other major cities. - A crucial requirement for disaster risk reduction involves the analysis of the vulnerability of existing building inventories. Whereas traditional approaches are very time- and cost-consuming, and even impossible given the high rate of urbanization in Central Asian capitals, our integrated approach is based on satellite remote sensing and ground-based omni-directional imaging, providing building inventories and thus structural vulnerability over large areas (EMCA, GEM-IDCT). All mentioned activities are carried out within the framework of cooperation between GFZ and regional national institutes, in particular the Central Asian Institute for Applied Geosciences. Altogether, this comprehensive and long-term risk analyses and research program will lead to a better understanding of the coupling of endogene and exogene processes and the identification of their impact on society.

Advances in Distributed Operations and Mission Activity Planning for Mars Surface Exploration

NASA Technical Reports Server (NTRS)

Fox, Jason M.; Norris, Jeffrey S.; Powell, Mark W.; Rabe, Kenneth J.; Shams, Khawaja

2006-01-01

A centralized mission activity planning system for any long-term mission, such as the Mars Exploration Rover Mission (MER), is completely infeasible due to budget and geographic constraints. A distributed operations system is key to addressing these constraints; therefore, future system and software engineers must focus on the problem of how to provide a secure, reliable, and distributed mission activity planning system. We will explain how Maestro, the next generation mission activity planning system, with its heavy emphasis on portability and distributed operations has been able to meet these design challenges. MER has been an excellent proving ground for Maestro's new approach to distributed operations. The backend that has been developed for Maestro could benefit many future missions by reducing the cost of centralized operations system architecture.

Anti-babesial activity of some central kalimantan plant extracts and active oligostilbenoids from Shorea balangeran.

PubMed

Subeki; Nomura, Shinkichi; Matsuura, Hideyuki; Yamasaki, Masahiro; Yamato, Osamu; Maede, Yoshimitsu; Katakura, Ken; Suzuki, Mamoru; Trimurningsih; Chairul; Yoshihara, Teruhiko

2005-05-01

Bark extracts from a total of 22 species of Central Kalimantan plants were evaluated for their anti-babesial activity against Babesia gibsoni in vitro. Of these plant species, extracts of Calophyllum tetrapterum, Garcinia rigida, Lithocarpus sp., Sandoricum emarginatum, and Shorea balangeran showed more than 90% inhibition of the parasite growth at a test concentration of 1000 microg/mL. Activity-guided fractionation of the bark of S. balangeran (Dipterocarpaceae) led to the reisolation of oligostilbenoids, vaticanol A(1), B(2), and G(3). The structures were determined on the basis of spectral evidence. Compounds 1 and 3 showed complete inhibition on the growth of Babesia gibsoni in vitro at a concentration of 25 microg/mL, and compound 2 at concentration of 50 microg/mL.

Optimization of banana trunk-activated carbon production for methylene blue-contaminated water treatment

NASA Astrophysics Data System (ADS)

Danish, Mohammed; Ahmad, Tanweer; Nadhari, W. N. A. W.; Ahmad, Mehraj; Khanday, Waheed Ahmad; Ziyang, Lou; Pin, Zhou

2018-03-01

This experiment was run to characterize the banana trunk-activated carbon through methylene blue dye adsorption property. The H3PO4 chemical activating agent was used to produce activated carbons from the banana trunk. A small rotatable central composite design of response surface methodology was adopted to prepare chemically (H3PO4) activated carbon from banana trunk. Three operating variables such as activation time (50-120 min), activation temperature (450-850 °C), and activating agent concentration (1.5-7.0 mol/L) play a significant role in the adsorption capacities ( q) of activated carbons against methylene blue dye. The results implied that the maximum adsorption capacity of fixed dosage (4.0 g/L) banana trunk-activated carbon was achieved at the activation time of 51 min, the activation temperature of 774 °C, and H3PO4 concentration of 5.09 mol/L. At optimum conditions of preparation, the obtained banana trunk-activated carbon has adsorption capacity 64.66 mg/g against methylene blue. Among the prepared activated carbons run number 3 (prepared with central values of the operating variables) was characterized through Fourier transform infrared spectroscopy, field emission scanning microscopy, and powder X-ray diffraction.

Unretrieved shooting loss of mourning doves in north-central South Carolina

USGS Publications Warehouse

Haas, G.H.

1977-01-01

Unretrieved loss for mourning doves (Zenaida macroura) in north-central South Carolina was between 27 and 41 percent of the retrieved kill for the 1973 through 1975 hunting seasons based on 1,396 doves shot by 281 hunters. Dove hunters hunted in groups, fired 8.6 shots per retrieved dove, and engaged in a substantial number of illegal activities. Increased dove populations and hunter bag resulted in increased unretrieved loss, numbers of shots per bagged bird, and illegal activities. Retriever dogs increased the efficiency of dove hunters.

July 1973 ground survey of active Central American volcanoes

NASA Technical Reports Server (NTRS)

Stoiber, R. E. (Principal Investigator); Rose, W. I., Jr.

1973-01-01

The author has identified the following significant results. Ground survey has shown that thermal anomalies of various sizes associated with volcanic activity at several Central American volcanoes should be detectable from Skylab. Anomalously hot areas of especially large size (greater than 500 m in diameter) are now found at Santiaguito and Pacaya volcanoes in Guatemala and San Cristobal in Nicaragua. Smaller anomalous areas are to be found at least seven other volcanoes. This report is completed after ground survey of eleven volcanoes and ground-based radiation thermometry mapping at these same points.

Comparison of telavancin and vancomycin lock solutions in eradication of biofilm-producing staphylococci and enterococci from central venous catheters.

PubMed

Luther, Megan K; Mermel, Leonard A; LaPlante, Kerry L

2016-03-01

Results of a study of the activity of antibiotic lock solutions of vancomycin and telavancin against biofilm-forming strains of Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus are reported. An established in vitro central venous catheter model was used to evaluate lock solutions containing vancomycin (5 mg/mL) or telavancin (5 mg/mL), with and without preservative-containing heparin sodium (with 0.45% benzyl alcohol) 2500 units/mL, heparin, and 0.9% sodium chloride solution. Lock solutions were introduced after 24-hour bacterial growth in catheters incubated at 35 °C. After 72 hours of exposure to the lock solutions, catheters were drained, flushed, and cut into segments for quantification of colony-forming units. Against S. epidermidis, vancomycin and telavancin (with or without heparin) had similar activity. Against E. faecalis, vancomycin alone was more active than telavancin alone (p < 0.01). Against S. aureus, vancomycin plus heparin had activity similar to that of vancomycin alone; both lock agents had greater activity than telavancin (p < 0.02). The addition of heparin was associated with reduced activity of the vancomycin lock solution against S. epidermidis and E. faecalis (p < 0.01). Telavancin activity was not significantly changed with the addition of heparin. In a central venous catheter model, vancomycin and telavancin activity was similar in reducing biofilm-producing S. epidermidis. However, vancomycin was more active than telavancin against E. faecalis and S. aureus. None of the tested agents eradicated biofilm-forming strains. The addition of preservative-containing heparin sodium 2500 units/mL to vancomycin was associated with reduced activity against S. epidermidis and E. faecalis. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

The (pro)renin receptor and body fluid homeostasis

PubMed Central

Cao, Theresa

2013-01-01

The renin-angiotensin system (RAS) has long been established as one of the major mechanisms of hypertension through the increased levels of angiotensin (ANG) II and its resulting effect on the sympathetic nerve activity, arterial vasoconstriction, water reabsorption, and retention, etc. In the central nervous system, RAS activation affects body fluid homeostasis through increases in sympathetic nerve activity, water intake, food intake, and arginine vasopressin secretion. Previous studies, however, have shown that ANG II can be made in the brain, and it could possibly be through a new component called the (pro)renin receptor. This review intends to summarize the central and peripheral effects of the PRR on body fluid homeostasis. PMID:23678024

An overview of current activities at the National Solar Thermal Test Facility

NASA Astrophysics Data System (ADS)

Cameron, C. P.; Klimas, P. C.

This paper is a description of the United States Department of Energy's National Solar Thermal Test Facility, highlighting current test programs. In the central receiver area, research underway supports commercialization of molten nitrate salt technology, including receivers, thermal energy transport, and corrosion experiments. Concentrator research includes large-area, glass-metal heliostats and stretched-membrane heliostats and dishes. Test activities in support of dish-Stirling systems with reflux receivers are described. Research on parabolic troughs includes characterization of several receiver configurations. Other test facility activities include solar detoxification experiments, design assistance testing of commercially-available solar hardware, and non-DOE-funded work, including thermal exposure tests and testing of volumetric and PV central receiver concepts.

Stereochemical requirements for central and peripheral muscarinic and antimuscarinic activity of some acetylenic compounds related to oxotremorine.

PubMed Central

Dahlbom, R.; Jenden, D. J.; Resul, B.; Ringdahl, B.

1982-01-01

1 The enantiomers of some analogues of the central muscarinic agent, oxotremorine, were prepared and investigated for tremorogenic and tremorolytic activity in intact mice and for muscarinic and antimuscarinic activity on the isolated ileum of the guinea-pig. 2 The R-isomers were more potent than the S-isomers both in vivo and in vitro regardless of whether the compounds are agonists, partial agonists or competitive antagonists. 3 It is suggested that in the oxotremorine series, agonists and antagonists interact with a common receptor site, in contrast to classical muscarinic antagonists which are believed to bind also to accessory receptor areas, located close to the agonist binding site. PMID:7093587

Space-Based Detection of Sinkhole Activity in Central Florida

NASA Astrophysics Data System (ADS)

Oliver-Cabrera, T.; Kruse, S.; Wdowinski, S.

2015-12-01

Central Florida's thick carbonate deposits and hydrological conditions have made the area prone to sinkhole development. Sinkhole collapse is a major geologic hazard in central Florida threatening human life and causing substantial damage to property. According to the Florida Senate report in 2010, between 2006-2010 total insurance claims due to sinkhole activity were around $200 million per year. Detecting sinkhole deformation before a collapse is a very difficult task, due to small or sometimes unnoticeable surface changes. Most techniques used to monitor sinkholes provide very localized information and cannot be implemented to study broad areas. This is the case of central Florida, where the active zone spans over hundreds of square-kilometers. In this study we use Interferometric Synthetic Aperture Radar (InSAR) observations acquired over several locations in central Florida to detect possible pre-collapse deformation. The study areas were selected because they have shown suspicious sinkhole behavior. One of the sites collapsed on March 2013 destroying a property and killing a man. To generate the InSAR results we use six datasets acquired by the TerraSAR-X and Cosmo-SkyMed satellites with various acquisition modes reflecting pixel resolutions between 25cm and 2m. Preliminary InSAR results show good coherence over constructed areas and low coherence in vegetated zones, justifying our analysis that focuses on the man-made structures. After full datasets will be acquired, a Persistent Scatterer Interferometry (PSI) time series analysis will be performed for detecting localized deformation at spatial scale of 1-5 meters. The project results will be verified using Ground Penetrating Radar.

Central electrical utility power for a satellite ring city in low earth orbit space

NASA Technical Reports Server (NTRS)

Myers, Ira T.; Faymon, Karl A.; Patton, A. D.

1989-01-01

Information is given in viewgraph form on central electrical power for a satellite ring city, defined as a group of large free flyers of 10 to 20 units with perhaps 100 people in each unit, and organized in a circle so that power can be fed from a central location. The free flyers would be located at 300 to 700 miles in altitude, and spaced about a kilometer apart. Potential activities of a ring city are listed as well as the electrical power needs. Information is given on costs and individual and centralized solar arrays and nuclear reactor systems.

Photoconductive switch package

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caporaso, George J.

2015-10-27

A photoconductive switch is formed of a substrate that has a central portion of SiC or other photoconductive material and an outer portion of cvd-diamond or other suitable material surrounding the central portion. Conducting electrodes are formed on opposed sides of the substrate, with the electrodes extending beyond the central portion and the edges of the electrodes lying over the outer portion. Thus any high electric fields produced at the edges of the electrodes lie outside of and do not affect the central portion, which is the active switching element. Light is transmitted through the outer portion to the centralmore » portion to actuate the switch.« less

Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients.

PubMed

Davidson, M; Losonczy, M F; Mohs, R C; Lesser, J C; Powchik, P; Freed, L B; Davis, B M; Mykytyn, V V; Davis, K L

1987-12-01

Plasma levels of the dopamine metabolite homovanillic acid (pHVA) may potentially reflect upon central dopamine activity. This study examines the effects of debrisoquin, haloperidol, and the two drugs combined on pHVA concentrations of schizophrenic patients. Debrisoquin is a drug that suppresses the peripheral formation of homovanillic acid without affecting the central formation. Acute haloperidol administration consistently increased pHVA concentrations in patients pretreated or not pretreated with debrisoquin, suggesting that this increment reflects haloperidol's central and not peripheral effects.

The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss

PubMed Central

Qu, Pei; Gao, Wei; Chen, Huixian; Li, Dan; Yang, Na; Zhu, Jian; Li, Zhongqiu

2016-01-01

Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15-20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N- nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-20-27) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(1-15-20-27) could be a promising antimicrobial agent for clinical application. PMID:26902768

Morphological study of the prostate gland in viscacha (Lagostomus maximus maximus) during periods of maximal and minimal reproductive activity.

PubMed

Chaves, Maximiliano; Aguilera-Merlo, Claudia; Cruceño, Albana; Fogal, Teresa; Mohamed, Fabian

2015-11-01

The viscacha (Lagostomus maximus maximus) is a rodent with photoperiod-dependent seasonal reproduction. The aim of this work was to study the morphological variations of the prostate during periods of maximal (summer, long photoperiod) and minimal (winter, short photoperiod) reproductive activity. Prostates of adult male viscachas were studied by light and electron microscopy, immunohistochemistry for androgen receptor, and morphometric analysis. The prostate consisted of two regions: peripheral and central. The peripheral zone exhibited large adenomeres with a small number of folds and lined with a pseudostratified epithelium. The central zone had small adenomeres with pseudostratified epithelium and the mucosa showed numerous folds. The morphology of both zones showed variations during periods of maximal and minimal reproductive activity. The prostate weight, prostate-somatic index, luminal diameter of adenomeres, epithelial height and major nuclear diameter decreased during the period of minimal reproductive activity. Principal cells showed variations in their shape, size and ultrastructural characteristics during the period of minimal reproductive activity in comparison with the active period. The androgen receptor expression in epithelial and fibromuscular stromal cells was different between the studied periods. Our results suggest a reduced secretory activity of viscacha prostate during the period of minimal reproductive activity. Thus, the morphological variations observed in both the central and peripheral zones of the viscacha prostate agree with the results previously obtained in the gonads of this rodent of photoperiod-dependent reproduction. Additionally, the variations observed in the androgen receptors suggest a direct effect of the circulating testosterone on the gland. © 2015 Wiley Periodicals, Inc.

Radiocaesium derived from the TEPCO Fukushima accident in the North Pacific Ocean: Surface transport processes until 2017.

PubMed

Aoyama, Michio; Hamajima, Yasunori; Inomata, Yayoi; Kumamoto, Yuichiro; Oka, Eitarou; Tsubono, Takaki; Tsumune, Daisuke

2018-04-04

We report temporal variations of 137 Cs activity concentrations in surface waters of six regions of the western and central North Pacific Ocean during 2011-2017 using a combination of 1264 previously published data and 42 new data. In the western and central North Pacific Ocean at latitudes of 30-42°N and longitudes of 140°E to 160°W, eastward transport of radiocaesium was clearly apparent. 137 Cs activity concentrations in surface water decreased rapidly to ∼2-3 Bq m -3 in 2015/2016, still a bit higher than 137 Cs activity concentrations before the FNPP1 accident (1.5-2 Bq m -3 ). 134 Cs/ 137 Cs activity ratios decay-corrected to 11 March 2011 were ∼0.5-0.8. To the south of 30°N and between 130°E and 160°W in the western and central Pacific Ocean, 137 Cs activity concentrations were around 1-7 Bq m -3 in 2011/2012 but then stabilized at a few Bq m -3 up to 2017. 134 Cs activity concentrations were detected at levels of 0.1-0.9 Bq m -3 , and 134 Cs/ 137 Cs activity ratios decay-corrected to 11 March 2011 were ∼0.3-0.5. Temporal variations of model-simulated 137 Cs activity concentrations in surface water in the region of interest showed good agreement with observations, except in the southwestern North Pacific Ocean. Copyright © 2018 Elsevier Ltd. All rights reserved.

Raindrops of synaptic noise on dual excitability landscape: an approach to astrocyte network modelling

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Yu.; Postnov, Dmitry E.; Verveyko, Darya V.; Brazhe, Alexey R.

2018-04-01

The most abundant non-neuronal cells in the brain, astrocytes, populate all parts of the central nervous system (CNS). Astrocytic calcium activity ranging from subcellular sparkles to intercellular waves is believed to be the key to a plethora of regulatory pathways in the central nervous system from synaptic plasticity to blood flow regulation. Modeling of the calcium wave initiation and transmission and their spatiotemporal dynamics is therefore an important step stone in understanding the crucial cogs of cognition. Astrocytes are active sensors of ongoing neuronal and synaptic activity, and neurotransmitters diffusing from the synaptic cleft make a strong impact on the astrocytic activity. Here we propose a model describing the patterns of calcium wave formation at a single cell level and discuss the interplay between astrocyte shape the calcium waves dynamics driven by local stochastic surges of glutamate simulating synaptic activity.

Risk factors associated with PICC-related upper extremity venous thrombosis in cancer patients.

PubMed

Yi, Xiao-lei; Chen, Jie; Li, Jia; Feng, Liang; Wang, Yan; Zhu, Jia-An; Shen, E; Hu, Bing

2014-03-01

To investigate the incidence and risk factors for peripherally inserted central venous catheters-related upper extremity venous thrombosis in patients with cancer. With the widespread use of peripherally inserted central venous catheters, peripherally inserted central venous catheters-related upper extremity venous thrombosis in patients with cancer leads to increasing morbidity and mortality. It is very important to further explore the incidence and risk factors for peripherally inserted central venous catheters-related venous thrombosis. Consecutive patients with cancer who were scheduled to receive peripherally inserted central venous catheters, between September 2009 and May 2012, were prospectively studied in our centre. They were investigated for venous thrombosis by Doppler sonography three times a day within 30 days after catheter insertion. Univariable and multivariable logistic regressions' analyses were performed to identify the risk factors for peripherally inserted central venous catheters-related thrombosis. A total of 89 patients with cancer were studied in our research. Of these, 81 patients were followed up within one month. The mean interval between catheter insertion and the onset of thrombosis was 12.45 ± 6.17 days. The multivariable analyses showed that chemotherapy history, less activities and diabetes were the key risk factors for thrombosis. Peripherally inserted central venous catheters-related upper extremity venous thrombosis had high incidence rate, and most cases had no significant symptoms. The history of chemotherapy, less activities and diabetes were found to be the key risk factors. It should be routinely scanned in high-risk patients every 3-5 days after catheter insertion, which would then find blood clots in time and reduce the incidence of pulmonary embolism. Risk factors associated with peripherally inserted central venous catheters-related upper extremity venous thrombosis are of critical importance in improving the quality of patients' life. It is very important to grasp the indications to reduce the incidence rate of peripherally inserted central venous catheters-related upper extremity venous thrombosis. © 2013 John Wiley & Sons Ltd.

Estimation of proliferative potentiality of central neurocytoma: correlational analysis of minimum ADC and maximum SUV with MIB-1 labeling index.

PubMed

Sakamoto, Ryo; Okada, Tomohisa; Kanagaki, Mitsunori; Yamamoto, Akira; Fushimi, Yasutaka; Kakigi, Takahide; Arakawa, Yoshiki; Takahashi, Jun C; Mikami, Yoshiki; Togashi, Kaori

2015-01-01

Central neurocytoma was initially believed to be benign tumor type, although atypical cases with more aggressive behavior have been reported. Preoperative estimation for proliferating activity of central neurocytoma is one of the most important considerations for determining tumor management. To investigate predictive values of image characteristics and quantitative measurements of minimum apparent diffusion coefficient (ADCmin) and maximum standardized uptake value (SUVmax) for proliferative activity of central neurocytoma measured by MIB-1 labeling index (LI). Twelve cases of central neurocytoma including one recurrence from January 2001 to December 2011 were included. Preoperative scans were conducted in 11, nine, and five patients for computed tomography (CT), diffusion-weighted imaging (DWI), and fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET), respectively, and ADCmin and SUVmax of the tumors were measured. Image characteristics were investigated using CT, T2-weighted (T2W) imaging and contrast-enhanced T1-weighted (T1W) imaging, and their differences were examined using the Fisher's exact test between cases with MIB-1 LI below and above 2%, which is recognized as typical and atypical central neurocytoma, respectively. Correlational analysis was conducted for ADCmin and SUVmax with MIB-1 LI. A P value <0.05 was considered significant. Morphological appearances had large variety, and there was no significant correlation with MIB-1 LI except a tendency that strong enhancement was observed in central neurocytomas with higher MIB-1 LI (P = 0.061). High linearity with MIB-1 LI was observed in ADCmin and SUVmax (r = -0.91 and 0.74, respectively), but only ADCmin was statistically significant (P = 0.0006). Central neurocytoma had a wide variety of image appearance, and assessment of proliferative potential was considered difficult only by morphological aspects. ADCmin was recognized as a potential marker for differentiation of atypical central neurocytomas from the typical ones. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Nonthermal electron-positron pairs and cold matter in the central engines of active galactic nuclei

NASA Technical Reports Server (NTRS)

Zdziarski, Andrzej A.

1992-01-01

The nonthermal e(+/-) pair model of the central engine of active galactic nuclei (AGNs) is discussed. The model assumes that nonthermal e(+/-) pairs are accelerated to highly relativistic energies in a compact region close to the central black hole and in the vicinity of some cold matter. The model has a small number of free parameters and explains a large body of AGN observations from EUV to soft gamma-rays. In particular, the model explains the existence of the UV bump, the soft X-rays excess, the canonical hard X-ray power law, the spectral hardening above about 10 keV, and some of the variability patterns in the soft and hard X-rays. In addition, the model explains the spectral steepening above about 50 keV seen in NGC 4151.

Final Report for UW-Madison Portion of DE-SC0005301, "Collaborative Project: Pacific Decadal Variability and Central Pacific Warming El Niño in a Changing Climate"

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vimont, Daniel

This project funded two efforts at understanding the interactions between Central Pacific ENSO events, the mid-latitude atmosphere, and decadal variability in the Pacific. The first was an investigation of conditions that lead to Central Pacific (CP) and East Pacific (EP) ENSO events through the use of linear inverse modeling with defined norms. The second effort was a modeling study that combined output from the National Center for Atmospheric Research (NCAR) Community Atmospheric Model (CAM4) with the Battisti (1988) intermediate coupled model. The intent of the second activity was to investigate the relationship between the atmospheric North Pacific Oscillation (NPO), themore » Pacific Meridional Mode (PMM), and ENSO. These two activities are described herein.« less

Centrality in earthquake multiplex networks

NASA Astrophysics Data System (ADS)

Lotfi, Nastaran; Darooneh, Amir Hossein; Rodrigues, Francisco A.

2018-06-01

Seismic time series has been mapped as a complex network, where a geographical region is divided into square cells that represent the nodes and connections are defined according to the sequence of earthquakes. In this paper, we map a seismic time series to a temporal network, described by a multiplex network, and characterize the evolution of the network structure in terms of the eigenvector centrality measure. We generalize previous works that considered the single layer representation of earthquake networks. Our results suggest that the multiplex representation captures better earthquake activity than methods based on single layer networks. We also verify that the regions with highest seismological activities in Iran and California can be identified from the network centrality analysis. The temporal modeling of seismic data provided here may open new possibilities for a better comprehension of the physics of earthquakes.

Central nervous system complications and neuroradiological findings in children with chronic active Epstein-Barr virus infection.

PubMed

Ishikawa, Nobutsune; Kawaguchi, Hiroshi; Nakamura, Kazuhiro; Kobayashi, Masao

2013-02-01

Although many neurological complications have been described in acute Epstein-Barr virus infection, few reports have discussed the central nervous system complications in chronic active Epstein-Barr virus (CAEBV) infection. We retrospectively surveyed the medical records of 14 patients with CAEBV infection in our institute. Neuroradiological studies were performed in 10 of these patients. Five had no neurological symptoms, whereas two presented with posterior reversible encephalopathy syndrome, one presented with basal ganglia calcification, and one presented with falx cerebri hemorrhage. Although both of the posterior reversible encephalopathy syndrome cases developed epilepsy several years after recovering from prolonged neurological deterioration, the others had no neurological sequelae. This study revealed that various central nervous system complications may occur during the clinical course in pediatric CAEBV patients. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

Active balance system and vibration balanced machine

NASA Technical Reports Server (NTRS)

White, Maurice A. (Inventor); Qiu, Songgang (Inventor); Augenblick, John E. (Inventor); Peterson, Allen A. (Inventor)

2005-01-01

An active balance system is provided for counterbalancing vibrations of an axially reciprocating machine. The balance system includes a support member, a flexure assembly, a counterbalance mass, and a linear motor or an actuator. The support member is configured for attachment to the machine. The flexure assembly includes at least one flat spring having connections along a central portion and an outer peripheral portion. One of the central portion and the outer peripheral portion is fixedly mounted to the support member. The counterbalance mass is fixedly carried by the flexure assembly along another of the central portion and the outer peripheral portion. The linear motor has one of a stator and a mover fixedly mounted to the support member and another of the stator and the mover fixedly mounted to the counterbalance mass. The linear motor is operative to axially reciprocate the counterbalance mass.

Relationship between auditory thresholds, central spontaneous activity and hair cell loss after acoustic trauma

PubMed Central

Mulders, W.H.A.M.; Ding, D.; Salvi, R.; Robertson, D.

2011-01-01

Acoustic trauma caused by exposure to a very loud sound increases spontaneous activity in central auditory structures such as the inferior colliculus. This hyperactivity has been suggested as a neural substrate for tinnitus, a phantom hearing sensation. In previous studies we have described a tentative link between the frequency region of hearing impairment and the corresponding tonotopic regions in the inferior colliculus showing hyperactivity. In this study we further investigated the relationship between cochlear compound action potential threshold loss, cochlear outer and inner hair cell loss and central hyperactivity in inferior colliculus of guinea pigs. Two weeks after a 10 kHz pure tone acoustic trauma, a tight relationship was demonstrated between the frequency region of compound action potential threshold loss and frequency regions in the inferior colliculus showing hyperactivity. Extending the duration of the acoustic trauma from 1 to 2 h did not result in significant increases in final cochlear threshold loss, but did result in a further increase of spontaneous firing rates in the inferior colliculus. Interestingly, hair cell loss was not present in the frequency regions where elevated cochlear thresholds and central hyperactivity were measured, suggesting that subtle changes in hair cell or primary afferent neural function are sufficient for central hyperactivity to be triggered and maintained. PMID:21491427

Holocene forest dynamics in central and western Mediterranean: periodicity, spatio-temporal patterns and climate influence.

PubMed

Di Rita, Federico; Fletcher, William J; Aranbarri, Josu; Margaritelli, Giulia; Lirer, Fabrizio; Magri, Donatella

2018-06-12

It is well-known that the Holocene exhibits a millennial-scale climate variability. However, its periodicity, spatio-temporal patterns and underlying processes are not fully deciphered yet. Here we focus on the central and western Mediterranean. We show that recurrent forest declines from the Gulf of Gaeta (central Tyrrhenian Sea) reveal a 1860-yr periodicity, consistent with a ca. 1800-yr climate fluctuation induced by large-scale changes in climate modes, linked to solar activity and/or AMOC intensity. We show that recurrent forest declines and dry events are also recorded in several pollen and palaeohydrological proxy-records in the south-central Mediterranean. We found coeval events also in several palaeohydrological records from the south-western Mediterranean, which however show generally wet climate conditions, indicating a spatio-temporal hydrological pattern opposite to the south-central Mediterranean and suggesting that different expressions of climate modes occurred in the two regions at the same time. We propose that these opposite hydroclimate regimes point to a complex interplay of the prevailing or predominant phases of NAO-like circulation, East Atlantic pattern, and extension and location of the North African anticyclone. At a larger geographical scale, displacements of the ITCZ, modulated by solar activity and/or AMOC intensity, may have also indirectly influenced the observed pattern.

Diminished metabolic responses to centrally-administered apelin-13 in diet-induced obese rats fed a high-fat diet.

PubMed

Clarke, K J; Whitaker, K W; Reyes, T M

2009-02-01

The central administration of apelin, a recently identified adipokine, has been shown to affect food and water intake. The present study investigated whether body weight could affect an animal's response to apelin. The effects of centrally-administered apelin-13 on food and water intake, activity and metabolic rate were investigated in adult male diet-induced obese (DIO) rats fed either a high fat (32%) or control diet. Rats were administered i.c.v. apelin-13, 15-30 min prior to lights out, and food and water intake, activity and metabolic rate were assessed. Intracerebroventricular administration of apelin-13 decreased food and water intake and respiratory exchange ratio in DIO rats on the control diet, but had no effect in DIO rats on the high-fat diet. In an effort to identify potential central mechanisms explaining the observed physiological responses, the mRNA level of the apelin receptor, APJ, was examined in the hypothalamus. A high-fat diet induced an up-regulation of the expression of the receptor. Apelin induced a down-regulation of the receptor, but only in the DIO animals on the high-fat diet. In conclusion, we have demonstrated a diminished central nervous system response to apelin that is coincident with obesity.

BADERI: an online database to coordinate handsearching activities of controlled clinical trials for their potential inclusion in systematic reviews.

PubMed

Pardo-Hernandez, Hector; Urrútia, Gerard; Barajas-Nava, Leticia A; Buitrago-Garcia, Diana; Garzón, Julieth Vanessa; Martínez-Zapata, María José; Bonfill, Xavier

2017-06-13

Systematic reviews provide the best evidence on the effect of health care interventions. They rely on comprehensive access to the available scientific literature. Electronic search strategies alone may not suffice, requiring the implementation of a handsearching approach. We have developed a database to provide an Internet-based platform from which handsearching activities can be coordinated, including a procedure to streamline the submission of these references into CENTRAL, the Cochrane Collaboration Central Register of Controlled Trials. We developed a database and a descriptive analysis. Through brainstorming and discussion among stakeholders involved in handsearching projects, we designed a database that met identified needs that had to be addressed in order to ensure the viability of handsearching activities. Three handsearching teams pilot tested the proposed database. Once the final version of the database was approved, we proceeded to train the staff involved in handsearching. The proposed database is called BADERI (Database of Iberoamerican Clinical Trials and Journals, by its initials in Spanish). BADERI was officially launched in October 2015, and it can be accessed at www.baderi.com/login.php free of cost. BADERI has an administration subsection, from which the roles of users are managed; a references subsection, where information associated to identified controlled clinical trials (CCTs) can be entered; a reports subsection, from which reports can be generated to track and analyse the results of handsearching activities; and a built-in free text search engine. BADERI allows all references to be exported in ProCite files that can be directly uploaded into CENTRAL. To date, 6284 references to CCTs have been uploaded to BADERI and sent to CENTRAL. The identified CCTs were published in a total of 420 journals related to 46 medical specialties. The year of publication ranged between 1957 and 2016. BADERI allows the efficient management of handsearching activities across different countries and institutions. References to all CCTs available in BADERI can be readily submitted to CENTRAL for their potential inclusion in systematic reviews.

Pyloric motor response to central and peripheral nitric oxide in the ferret.

PubMed

Lingenfelser, T; Blackshaw, L A; Sun, W M; Dent, J

1997-09-01

This study has investigated the relative importance of central nervous and peripheral nitroxidergic mechanisms in the control of pyloric motility. In 10 urethane-anaesthetized ferrets, drugs were administered directly to the CNS via a 0.5-mm-diameter cannula inserted into the 4th ventricle, approximately at the obex. Drugs were also given directly to the upper GI tract by close intra-arterial (i.a.) injection at the coeliac axis. Antropyloroduodenal pressures were recorded with a five-channel sleeve/sidehole micromanometric assembly (1.35 x 1.75 mm o.d.), which was introduced via the duodenum. Pyloric motility was stimulated throughout the main part of each study with a continuous i.v. infusion of CCK-8 (30 pmol min-1). This infusion produced an immediate and sustained increase in tonic and phasic pyloric activity, and sustained abolition of antral pressure waves. CCK-8 also induced a duodenal motor response, but this was short-lived (11.4 +/- 7.9 min). Coeliac axis injection of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) decreased phasic pyloric activity (from 330 +/- 35 to 148 +/- 21 mmHg min-1 after SNAP 5 micrograms, P < 0.01). By comparison central SNAP administration over the same dose range had no effect on CCK-stimulated pyloric motlity. Inhibition of endogenous NO synthase with L-Nitro Arginine Methyl Ester (L-NAME, 100 mg kg-1 close i.a.) caused a marked increase of phase pyloric motor activity from 349 +/- 59 to 1044 +/- 140 mmHg min-1 (P < 0.01). In addition, SNAP caused marked stimulation of pyloric tone from 2.6 +/- 0.5 to 13.1 +/- 2.8 mmHg (P < 0.01). Central nervous administration of L-NAME caused modest enhancement of phasic pyloric activity (248 +/- 31 to 283 +/- 32 mmHg min-1 P < 0.05) and pyloric tone (2.6 +/- 0.5 to 3.7 +/- 0.7 mmHg, P < 0.05). Our data indicate that motor activity of the ferret pylorus is potently modulated by NO released within the upper gut. Additionally, there is potential for modulation of pyloric motility by central nervous system production of NO.

A survey of cyclic replacements for the central diamide moiety of inhibitors of inosine monophosphate dehydrogenase.

PubMed

Dhar, T G Murali; Liu, Chunjian; Pitts, William J; Guo, Junquing; Watterson, Scott H; Gu, Henry; Fleener, Catherine A; Rouleau, Katherine; Sherbina, N Z; Barrish, Joel C; Hollenbaugh, Diane; Iwanowicz, Edwin J

2002-11-04

A series of heterocyclic replacements for the central diamide moiety of 1, a potent small molecule inhibitor of inosine monophosphate dehydrogenase (IMPDH) were explored The synthesis and the structure-activity relationships (SARs), derived from in vitro studies, for these new series of inhibitors is given.

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

ERIC Educational Resources Information Center

Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

2011-01-01

Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

38 CFR 4.88b - Schedule of ratings-infectious diseases, immune disorders and nutritional deficiencies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... disease 100 Thereafter rate residuals such as liver or spleen damage or central nervous system involvement... complications of nervous system, vascular system, eyes or ears. (See DC 7004, syphilitic heart disease, DC 8013... associated with central nervous system syphilis) 6311Tuberculosis, miliary: As active disease 100 Inactive...

Piece by Piece: The Story of the Central Bands Commissioning Project

ERIC Educational Resources Information Center

Sindberg, Laura K.

2005-01-01

The Central Bands Commissioning Project was a multidimensional endeavor. One dimension included organizational details, such as selecting a composer, negotiating a contract, and securing funds. A second dimension was made up of teaching and learning activities related to the commission, such as meeting local composers, writing letters to composers…

Landscape features and characteristics of Great Gray Owl (Strix nebulosa) nests in fragmented landscapes of central Alberta

Treesearch

D. P. Stepnisky

1997-01-01

Forest fragmentation through timber harvesting, agricultural clearing, and other industrial activities is increasing on the Canadian landscape. This study was conducted in order to gain an understanding of habitat requirements for breeding Great Gray Owls (Strix nebulosa) in the forest fragments of central Alberta.

Essential oil composition of five collections of Achillea biebersteinii from central Turkey and their antifungal and insecticidal activity

USDA-ARS?s Scientific Manuscript database

The composition of the essential oils hydrodistilled from the aerial parts of five Achillea biebersteinii Afan samples, collected in central Turkey from Konya, Isparta and Ankara, were analyzed both by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Eighty-four componen...

Introduction: seismology and earthquake engineering in Central and South America.

USGS Publications Warehouse

Espinosa, A.F.

1983-01-01

Reports the state-of-the-art in seismology and earthquake engineering that is being advanced in Central and South America. Provides basic information on seismological station locations in Latin America and some of the programmes in strong-motion seismology, as well as some of the organizations involved in these activities.-from Author

Bovine central memory T cells are highly proliferative in response to bovine tuberculosis infection

USDA-ARS?s Scientific Manuscript database

Long-term (i.e., 14 days) cultured IFN-gamma ELISPOT assays measure central memory T cell (Tcm) responses in both humans and cattle. With bovine tuberculosis, vaccine-elicited long-term IFN-gamma ELISPOT responses correlate with protection. In other species, Tcm’s pose low activation threshold and a...

Towards an Integrated Model of Individual, Psychosocial, and Organizational Predictors of Retirement Adjustment

ERIC Educational Resources Information Center

Wong, Jessica Y.; Earl, Joanne K.

2009-01-01

This cross-sectional study examines three predictors of retirement adjustment: individual (demographic and health), psychosocial (work centrality), and organizational (conditions of workforce exit). It also examines the effect of work centrality on post-retirement activity levels. Survey data was collected from 394 retirees (aged 45-93 years).…

Evaluation of minerals, phytochemical compounds and antioxidant activity of Mexican, Central American, and African green leafy vegetables

USDA-ARS?s Scientific Manuscript database

The green leafy vegetables Cnidoscolus aconitifolius and Crotalaria longirostrata are native to Mexico and Central America, while Solanum scabrum and Gynandropsis gynandra are native to Africa. They are consumed in both rural and urban areas in those places as a main food, food ingredient or traditi...

The Interaction between Sytactic and Semantic Modules in Chinese Learners' English Spotaneous Speech

ERIC Educational Resources Information Center

Gang, Xu

2014-01-01

According to modular theory, there are interactive effects between the central modules and language modules. The central cognition may deploy and redeploy resources from language modules. Moreover, the language modules can activate the cognitive ability. So this paper studies the spontaneous speech of students who learn English as a foreign…