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Respiratory Control
Understanding of the respiratory control system has been greatly improved by technological and methodological advances. This volume integrates results from many perspectives, brings together diverse approaches to the investigations, and represents important additions to the field of neural control of breathing.
Topics include membrane properties of respiratory neurons, in vitro studies of respiratory control, chemical neuroanatomy, central integration of respiratory afferents, modulation of respiratory pattern by peripheral afferents, respiratory chemoreception, development of respiratory control, behavioral control of breathing, and human ventilatory control.
Forty-seven experts in the field report research and discuss novel issues facing future investigations in this collection of papers from an international conference of nearly two hundred leading scientists held in October 1990. This research is of vital importance to respiratory physiologists and those in neurosciences and neurobiology who work with integrative sensory and motor systems and is pertinent to both basic and clinical investigations.
Respiratory Controlis destined to be widely cited because of the strength of the contributors and the dearth of similar works.
eBook
Transcriptional regulation of fermentative and respiratory metabolism in Saccharomyces cerevisiae industrial bakers' strains
Abstract
Bakers' yeast-producing companies grow cells under respiratory conditions, at a very high growth rate. Some desirable properties of bakers' yeast may be altered if fermentation rather than respiration occurs during biomass production. That is why differences in gene expression patterns that take place when industrial bakers' yeasts are grown under fermentative, rather than respiratory conditions, were examined. Macroarray analysis of V1 strain indicated changes in gene expression similar to those already described in laboratory Saccharomyces cerevisiae strains: repression of most genes related to respiration and oxidative metabolism and derepression of genes related to ribosome biogenesis and stress resistance in fermentation. Under respiratory conditions, genes related to the glyoxylate and Krebs cycles, respiration, gluconeogenesis, and energy production are activated. DOG21 strain, a partly catabolite-derepressed mutant derived from V1, displayed gene expression patterns quite similar to those of V1, although lower levels of gene expression and changes in fewer number of genes as compared to V1 were both detected in all cases. However, under fermentative conditions, DOG21 mutant significantly increased the expression of SNF1-controlled genes and other genes involved in stress resistance, whereas the expression of the HXK2 gene, involved in catabolite repression, was considerably reduced, according to the pleiotropic stress-resistant phenotype of this mutant. These results also seemed to suggest that stress-resistant genes control desirable bakers' yeast qualities.
Journal Article
Evolution of Views on Physiology of Breathing in Microgravity
—
The author summarizes the results of own long-term investigations of the human respiratory system onboard space objects. These results were analyzed and compared to the data of other authors who also had studied the breathing system in microgravity. The paper describes the logic of space experiments arrangement, sequence, progressive accumulation of the knowledge about breathing physiology and microgravity. Microgravity alters the structure of pulmonary volumes and respiratory rate and volume; it disturbs biomechanics of the respiratory muscles contraction that may expedite muscular fatigue and weaken the proprioceptive inputs to the respiratory center. The thoracic-abdominal breathing ratio changes for abdominal. Microgravity affects the cosmonaut’s ability to control respiratory movements intentionally and reduces sensitivity of the central respiratory mechanism to endogenous hypoxia and hypercapnia. The magnitude of these deviations as compared to the ground measurements is not critical for cosmonaut’s health and performance. However, in complex they may aggravate the effect of hypoxemia in microgravity, as has been noted by several authors, and be the reason for degradation of physical performance in space mission and, particularly, after landing.
Journal Article
Metabolic control analysis of cellular respiration in situ in intraoperational samples of human breast cancer
The aim of this study was to analyze quantitatively cellular respiration in intraoperational tissue samples taken from human breast cancer (BC) patients. We used oxygraphy and the permeabilized cell techniques in combination with Metabolic Control Analysis (MCA) to measure a corresponding flux control coefficient (FCC). The activity of all components of ATP synthasome, and respiratory chain complexes was found to be significantly increased in human BC cells in situ as compared to the adjacent control tissue. FCC(s) were determined upon direct activation of respiration with exogenously-added ADP and by titrating the complexes with their specific inhibitors to stepwise decrease their activity. MCA showed very high sensitivity of all complexes and carriers studied in human BC cells to inhibition as compared to mitochondria in normal oxidative tissues. The sum of FCC(s) for all ATP synthasome and respiratory chain components was found to be around 4, and the value exceeded significantly that for normal tissue (close to 1). In BC cells, the key sites of the regulation of respiration are Complex IV (FCC = 0.74), ATP synthase (FCC = 0.61), and phosphate carrier (FCC = 0.60); these FCC(s) exceed considerably (~10-fold) those for normal oxidative tissues. In human BC cells, the outer mitochondrial membrane is characterized by an increased permeability towards adenine nucleotides, the mean value of the apparent K
m
for ADP being equal to 114.8 ± 13.6 μM. Our data support the two-compartment hypothesis of tumor metabolism, the high sum of FCC(s) showing structural and functional organization of mitochondrial respiratory chain and ATP synthasome as supercomplexes in human BC.
Journal Article
Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism
The mitogen-induced D-type cyclins (D1, D2 and D3) are regulatory subunits of the cyclin-dependent kinases CDK4 and CDK6 that drive progression through the G1 phase of the cell cycle. In skeletal muscle, cyclin D3 plays a unique function in controlling the proliferation/differentiation balance of myogenic progenitor cells. Here, we show that cyclin D3 also performs a novel function, regulating muscle fiber type-specific gene expression. Mice lacking cyclin D3 display an increased number of myofibers with higher oxidative capacity in fast-twitch muscle groups, primarily composed of myofibers that utilize glycolytic metabolism. The remodeling of myofibers toward a slower, more oxidative phenotype is accompanied by enhanced running endurance and increased energy expenditure and fatty acid oxidation. In addition, gene expression profiling of cyclin D3−/− muscle reveals the upregulation of genes encoding proteins involved in the regulation of contractile function and metabolic markers specifically expressed in slow-twitch and fast-oxidative myofibers, many of which are targets of MEF2 and/or NFAT transcription factors. Furthermore, cyclin D3 can repress the calcineurin- or MEF2-dependent activation of a slow fiber-specific promoter in cultured muscle cells. These data suggest that cyclin D3 regulates muscle fiber type phenotype, and consequently whole body metabolism, by antagonizing the activity of MEF2 and/or NFAT.
Journal Article
Muscle fiber contractile type influences the regulation of mitochondrial function
Mitochondrial respiratory rates and regulation by phosphate acceptors were studied on permeabilized fiber bundles differing in their myosin heavy chain profiles. The acceptor control ratio, an indicator of oxidation to phosphorylation coupling, and mitochondrial K(m) for ADP were the highest in type I, intermediate in mixed IIa/IIx and the lowest in IIx and predominantly IIb fiber bundles. A functional coupling between mitochondrial creatine kinase and oxidative phosphorylation occurred in type I and IIa/IIx fiber bundles, exclusively. Our study suggests that mitochondrial functioning in fast IIa fibers is closer to that of the slow/I than fast IIx or IIb fibers.
Journal Article
Respiratory Reactions to Microinjections of Gastrin-Releasing Peptide into the Solitary Tract Nucleus
Acute experiments on urethane-anesthetized rats were performed to study the respiratory effects of administration of 10
–5
, 10
–8
, and 10
–10
M gastrin-releasing peptide into the solitary tract nucleus. Microinjections of this neuropeptide were found to lead to increases in respiratory volume and the amplitudes of volley activity in the diaphragm and external intercostal muscles, along with an increase in the duration of expiration. The most marked reactions were seen with 10
–8
M gastrin-releasing peptide, while a concentration of 10
–1
0 M was subthreshold and did not elicit changes in the pattern of respiration or the bioelectrical activity of the inspiratory muscles. Experiments in which the respiratory pattern was measured simultaneously with arterial blood pressure and heart rate showed that these parameters showed no reaction to microinjections of gastrin-releasing peptide into the study zone. These data, along with results on the distribution of specific gastrin-releasing peptide receptors in the brainstem, suggest that this peptide is involved in relating respiration at the level of the solitary tract nucleus.
Journal Article
Respiratory responses to microinjections of leptin into the solitary tract nucleus
The regulatory peptide leptin has a respiratory stimulating effect along with its well known hypothalamic effects. The present study, performed on anesthetized rats, addressed respiratory responses to microinjections of 10
−10
−10
−4
M leptin into the solitary tract nucleus, which contains a high concentration of leptin receptors. Injections of 10
−8
−10
−4
M leptin led to stimulation of respiration, inducing a dose-dependent increase in the level of pulmonary ventilation and an increase in respiratory volume, accompanied by an increase in bioelectrical activity in the inspiratory muscles; 10
−6
M leptin also induced a transient increase in respiratory rate due to shortening of inhalation and exhalation. A characteristic feature of the response was the appearance of “sighs” – deep, prolonged inhalations accompanied by increased volley activity on the electromyograms of the inspiratory muscles and lengthening of the subsequent intervolley interval. These leptin effects, along with data on the high concentrations of specific leptin receptors (ObRb) in the solitary tract nucleus, suggested that endogenous leptin has a role in controlling respiration at the level of the dorsal segment of the respiratory center.
Journal Article